Stuff about stuffers: the effectiveness of public utilities bill inserts

Thesis (M.S.)--Boston Universit

Higher derivative terms and their influence on N=2 supersymmetric systems

This thesis is concerned with so-called higher derivative terms which arise in low energy approximations to certain physical models. In particular, the aim is to investigate the role that such terms play in low energy N=2 supersymmetric gauge theories in 4 dimensions, with gauge group SU(2).Chapter one serves as an introduction to the notions of supersymmetry and superfields. The problem of constructing an effective action which describes the low energy dynamics is introduced, and the construction of the Wilsonian action in terms of light and heavy modes is developed. The concept on a derivative expansion is also described. Chapter two introduces N=2 supersymmetric gauge theories with spontaneous symmetry breaking. It is observed that such systems always have a Bogomolnyi bound, and the consequences are discussed. We then develop a derivative expansion of this system in terms of N=2 superfields, drawing particular attention to the next-to- leading order derivative term (that is, those with 4 derivatives/8 fermions). The duality properties of such a term are reviewed, and their impact on the mass formula discussed. Conclusions are drawn as to their influence on the results of Seiberg and Witten. Chapter three deals with a non-renormalisation theorem for the next-to-leading order higher derivative term proposed by Dine and Seiberg. This states that instanton contributions to such a term in massless N=2 SU(N(_c)) gauge theories vanish when the number of flavours N(_f) = 2N(_c). We prove this result using the ADHM formalism for multi-instantons in the case N(_c) = 2

A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome

<i>Trypanosoma brucei</i> is the causative agent of African sleeping sickness in humans and one of several pathogens that cause the related veterinary disease Nagana. A complex co-evolution has occurred between these parasites and primates that led to the emergence of trypanosome-specific defences and counter-measures. The first line of defence in humans and several other <i>catarrhine</i> primates is the trypanolytic protein apolipoprotein-L1 (APOL1) found within two serum protein complexes, trypanosome lytic factor 1 and 2 (TLF-1 and TLF-2). Two sub-species of <i>T. Brucei</i> have evolved specific mechanisms to overcome this innate resistance, <i>Trypanosoma brucei gambiense</i> and <i>Trypanosoma brucei rhodesiense</i>. In <i>T. b. Rhodesiense</i>, the presence of the serum resistance associated (SRA) gene, a truncated variable surface glycoprotein (VSG), is sufficient to confer resistance to lysis. The resistance mechanism of <i>T. b. Gambiense</i> is more complex, involving multiple components: reduction in binding affinity of a receptor for TLF, increased cysteine protease activity and the presence of the truncated VSG, <i>T. b. Gambiense</i>-specific glycoprotein <i>(TgsGP)</i>. In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by <i>T. b. Gambiense</i> and <i>T. b. Rhodesiense</i>, with several populations of humans and primates displaying resistance to infection by these two sub-species

Post-processing partitions to identify domains of modularity optimization

We introduce the Convex Hull of Admissible Modularity Partitions (CHAMP) algorithm to prune and prioritize different network community structures identified across multiple runs of possibly various computational heuristics. Given a set of partitions, CHAMP identifies the domain of modularity optimization for each partition ---i.e., the parameter-space domain where it has the largest modularity relative to the input set---discarding partitions with empty domains to obtain the subset of partitions that are "admissible" candidate community structures that remain potentially optimal over indicated parameter domains. Importantly, CHAMP can be used for multi-dimensional parameter spaces, such as those for multilayer networks where one includes a resolution parameter and interlayer coupling. Using the results from CHAMP, a user can more appropriately select robust community structures by observing the sizes of domains of optimization and the pairwise comparisons between partitions in the admissible subset. We demonstrate the utility of CHAMP with several example networks. In these examples, CHAMP focuses attention onto pruned subsets of admissible partitions that are 20-to-1785 times smaller than the sets of unique partitions obtained by community detection heuristics that were input into CHAMP.Comment: http://www.mdpi.com/1999-4893/10/3/9

Use of hyaluronidase in the comparison between manual and automated hematology analysis with the ADVIA 120 to improve analysis of feline body cavity effusions

Classification of body cavity effusions is an important step in the investigation and diagnosis of disease in cats. Feline inflammatory effusions are often highly proteinaceous and viscous, which can cause clumping of white cells and subsequently inaccurate nucleated cell counts (NCCs) using automated and manual methods. Microscopic assessment of cellularity can also be difficult given the variable thickness of smears and cell clumping, which skews white cell distribution. The ADVIA 120 uses 2 white cell–counting channels, the basophil/lobularity (WBC/baso) and differential/peroxidase channels, which can provide quite different results in highly viscous feline samples and often disagree with smear assessment of cellularity. We investigated the effects of pre-incubation of feline effusion samples with hyaluronidase and its effects on NCCs and cellularity assessment. NCCs were obtained by automated analysis using the ADVIA 120 and by manual counting methods. Agreement was assessed using a Bland–Altman chart. Pretreatment of samples with hyaluronidase resulted in good agreement between the ADVIA basophil channel and manual counting methods in all samples in the study. However, improvements in NCCs after hyaluronidase treatment were significantly greater in clumped samples, and cell distribution of these samples on direct smears was also improved. Therefore, when nucleated cell clumping is observed on a direct smear, pretreatment of the sample with hyaluronidase prior to analysis on an automated analyzer is advised, with the WBC/baso channel displaying the most accurate NCC

Molecular confirmation of Sarcocystis fayeri in a donkey

Sarcocystis fayeri is a canine protozoan parasite with an equine intermediate host. Historically classified as an incidental pathogen, recent literature has described the toxic effects of Sarcocystis fayeri in human food poisoning, and highlighted potential involvement in equine neuromuscular disease. Until now, horses were believed to be the exclusive intermediate host. This study reports the first molecular confirmation of S. fayeri in a donkey, and gives rise to the consideration of donkeys being a potential reservoir for the parasite. This finding is of particular importance in understanding the epidemiology of this disease

Cysteine proteinase C1A paralog profiles correspond with phylogenetic lineages of pathogenic piroplasmids

Piroplasmid parasites comprising of Babesia, Theileria, and Cytauxzoon are transmitted by ticks to farm and pet animals and have a significant impact on livestock industries and animal health in tropical and subtropical regions worldwide. In addition, diverse Babesia spp. infect humans as opportunistic hosts. Molecular phylogeny has demonstrated at least six piroplasmid lineages exemplified by B. microti, B. duncani, C. felis, T. equi, Theileria sensu stricto (T. annulata, T. parva, and T. orientalis) and Babesia sensu stricto (B. bovis, B. bigemina, and B. ovis). C1A cysteine-proteinases (C1A-Cp) are papain-like enzymes implicated in pathogenic and vital steps of the parasite life cycle such as nutrition and host cell egress. An expansion of C1A-Cp of T. annulata and T. parva with respect to B. bovis and B. ovis was previously described. In the present work, C1A-Cp paralogs were identified in available genomes of species pertaining to each piroplasmid lineage. Phylogenetic analysis revealed eight C1A-Cp groups. The profile of C1A-Cp paralogs across these groups corroborates and defines the existence of six piroplasmid lineages. C. felis, T. equi and Theileria s.s. each showed characteristic expansions into extensive families of C1A-Cp paralogs in two of the eight groups. Underlying gene duplications have occurred as independent unique evolutionary events that allow distinguishing these three piroplasmid lineages. We hypothesize that C1A-Cp paralog families may be associated with the advent of the schizont stage. Differences in the invertebrate tick host specificity and/or mode of transmission in piroplasmid lineages might also be associated with the observed C1A-Cp paralog profiles

Genomic and population genetic studies on Theileria annulata

Tropical theileriosis, caused by the tick-transmitted protozoan Theileria annulata, is a major disease of cattle in many regions of the developing world. Current research is directed towards developing a sub-unit vaccine, and it is therefore important that genetic diversity in field populations of the parasite is investigated and quantified. The recently completed genome sequence provided an opportunity to develop a panel of genetic markers for population studies and also enabled the identification of novel antigen genes. The genome was bioinformatically screened to identify micro- and mini-satellite loci, several of which were PCR amplified from a series of diverse parasite stocks in order to characterise their polymorphism and to determine their species-specificity. A panel of ten markers were selected for population genetic studies and were used to genotype laboratorymaintained cell lines and clonal stocks of T. annulata isolated from different countries. Cell lines comprised a multiplicity of genotypes, while clonal stocks showed evidence of a single haploid genome. Preliminary population genetic analysis revealed a large amount of genotypic diversity both between and within countries and indicated that the parasite population is geographically sub-structured. Comparison of a limited number of stocks isolated in different countries demonstrated that genetic differentiation between populations positively correlates with intervening physical distance. A low standard index of association (IS A) suggested that the population in Tunisia is in linkage equilibrium, indicating that the parasite possesses a panmictic (randomly mating) population structure. To confirm these findings, a large number of field isolates from Tunisia and Turkey were analysed (n = 305). This supported the earlier finding that geographical sub-structuring separates panmictic populations and an almost identical amount of genetic differentiation between countries was evident (FST = 0.05). Limited linkage disequilibrium was observed in some populations and this was attributed to several factors including inbreeding and the Wahlund effect, caused by putatively immigrant sub-populations. A similar multiplicity of infection was demonstrated in vaccinated and unvaccinated animals and the immunising genotype did not appear to establish in the field population. Multiplicity of infection was instead shown to positively correlate with the host age in several sampling locations. The genome of T. annulata was compared with that of T. parva to identify gene families under the influence of positive selection using mean family inter-genomic nonsynonymous to synonymous substitution rates (dNdS). Codon usage between the species and between several life-cycle stages within T. annulata was shown to be virtually invariant and independent of the dNdS distribution. In addition to a subset of merozoite genes, which were predicted to be antigens on the basis of their motif signature, a subtelomeric gene family (SVSP) and a family of parasite-encoded host nuclear genes (TashATs) showed evidence of positive selection between the species. An allelesequencing approach was taken to verify these predictions which indicated that, in general, the TashAT genes are under the effect of purifying selection while two SVSP genes were shown to be highly variable, however there was no firm evidence of positive selection. One of the merozoite antigen candidates showed evidence of both positive immune selection and balancing selection. Consequently, further studies are indicated to assess whether this gene has value as a vaccine candidate

Prevalence of tick-borne haemoparasites in small ruminants in Turkey and diagnostic sensitivity of single-PCR and RLB

Background: Tick-borne haemoparasitic diseases (TBHDs), caused by Theileria, Babesia, Anaplasma and Ehrlichia, are common in regions of the world where the distributions of host, pathogen and vector overlap. Many of these diseases threaten livestock production and some also represent a concern to human public health. The primary aim of this study was to determine the prevalence of the above-mentioned pathogens in a large number of blood samples (n = 1979) collected from sheep (n = 1727) and goats (n = 252) in Turkey. A secondary aim was to assess the diagnostic sensitivity of a number of species-specific polymerase chain reaction (PCR) tests and the reverse line blotting (RLB) assay. DNA samples were screened using species-specific PCR for the presence of Theileria ovis, Theileria sp. MK, T. lestoquardi, T. uilenbergi, T. luwenshuni, Babesia ovis, Anaplasma ovis and A. phagocytophilum while RLB was undertaken to test for the presence of all known Theileria, Babesia, Anaplasma and Ehrlichia species. The diagnostic sensitivity of these two approaches was then compared in terms of their ability to detect single species and mixed infections. Results: Overall, 84 and 74.43% of the small ruminants sampled were identified as hosting one or more pathogen(s) by species-specific PCR and RLB respectively. The presence of Theileria sp. OT1, T. luwenshuni and T. uilenbergi in Turkey was revealed for the first time while the presence of Babesia motasi, B. crassa and T. separata in Turkish small ruminants was confirmed using molecular methods. A high prevalence of mixed infection was evident, with PCR and RLB approaches indicating that 52.24 and 35.42% of animals were co-infected with multiple species, respectively. More than 80% of the mixed infections contained T. ovis and/or A. ovis. The RLB approach was found to be capable of detecting mixed infections with species such as Theileria sp. OT1, Theileria sp. OT3, T. separata, B. crassa and Babesia spp. Conclusion: The results indicated that pathogens causing TBHDs are highly prevalent in sheep and goats in Turkey. The diagnostic sensitivity of species-specific single PCR was generally higher than that of RLB. However, the latter approach was still capable of identifying a high proportion of individuals containing mixed-species infections. The use of species-specific single PCR is recommended to accurately estimate pathogen prevalence and to identify co-infected hosts