Effector function of leucocytes from susceptible and resistant mice against distinct isolates of Candida albicans

Neutrophils and macrophages were generated in vitro from mice that display either high or low tissue susceptibilities to Candida albicans infection and their ability to phagocytose and kill three isolates of the yeast with different virulence characteristics was evaluated. In the absence of opsonization, phagocytosis by BALB/c and CBA/CaH neutrophils was comparable, but the killing was very poor. Opsonization with normal serum slightly decreased phagocytosis, but it had markedly different effects on killing, either enhancing or inhibiting candidacidal activity, depending on the combination of yeast isolate and mouse strain. In contrast, BALB/c macrophages showed high levels of phagocytosis and killing of both unopsonized yeasts and opsonized yeasts; whereas killing of unopsonized yeasts by CBA/CaH macrophages was poor, it was markedly enhanced by opsonization.

Influence of iron deprivation and sub-inhibitory concentrations of antifungal antibiotics on surface antigens of candida albicans yeast cells

This study examined the effect of iron deprivation and sub-inhibitory concentrations of antifungal agents on yeast cell surface antigen recognition by antibodies from patients with Candida infections. Separation of cell wall surface proteins by sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE) and immunological detection by immunoblotting, revealed that antigenic profiles of yeasts were profoundly influenced by the growth environment. Cells grown under iron-depleted conditions expressed several iron-regulated proteins that were recognized by antibodies from patient sera. An attempt to characterize these proteins by lectin blotting with concanavalin A revealed that some could be glycoprotein in nature. Furthermore, these proteins which were located within cell walls and on yeast surfaces, were barely or not expressed in yeasts cultivated under iron-sufficient conditions. The magnitude and heterogeneity of human antibody responses to these iron-regulated proteins were dependent on the type of Candida infection, serum antibody class and yeast strain. Hydroxamate-type siderophores were also detected in supernatants of iron depleted yeast cultures. This evidence suggests that Candida albicans expresses iron-regulated proteins/glycoproteins in vitro which may play a role in siderophore-mediated iron uptake in Candida albicans. Sequential monitoring of IgG antibodies directed against yeast surface antigens during immunization of rabbits revealed that different antigens were recognized particularly during early and later stages of immunization in iron-depleted cells compared to iron-sufficient cells. In vitro and in vivo adherence studies demonstrated that growth phase, yeast strain and growth conditions affect adhesion mechanisms. In particular, growth under iron-depletion in the presence of sub-inhibitory concentrations of polyene and azole antifungals enhanced the hydrophobicity of C.albicans. Growth conditions also influenced MICs of antifungals, notably that of ketoconazole. Sub-inhibitory concentrations of amphotericin B and fluconazole had little effect on surface antigens, whereas nystatin induced profound changes in surface antigens of yeast cells. The effects of such drug concentrations on yeast cells coupled with host defence mechanisms may have a significant affect on the course of Candida infections.

New horizons in mouse immunoinformatics:reliable in silico prediction of mouse class I histocompatibility major complex peptide binding affinity

Quantitative structure–activity relationship (QSAR) analysis is a main cornerstone of modern informatic disciplines. Predictive computational models, based on QSAR technology, of peptide-major histocompatibility complex (MHC) binding affinity have now become a vital component of modern day computational immunovaccinology. Historically, such approaches have been built around semi-qualitative, classification methods, but these are now giving way to quantitative regression methods. The additive method, an established immunoinformatics technique for the quantitative prediction of peptide–protein affinity, was used here to identify the sequence dependence of peptide binding specificity for three mouse class I MHC alleles: H2–Db, H2–Kb and H2–Kk. As we show, in terms of reliability the resulting models represent a significant advance on existing methods. They can be used for the accurate prediction of T-cell epitopes and are freely available online (http://www.jenner.ac.uk/MHCPred).

Structural Analysis of Contours as the Sequences of the Digital Straight Segments and of the Digital Curve Arcs

Recognition of the object contours in the image as sequences of digital straight segments and/or digital curve arcs is considered in this article. The definitions of digital straight segments and of digital curve arcs are proposed. The methods and programs to recognize the object contours are represented. The algorithm to recognize the digital straight segments is formulated in terms of the growing pyramidal networks taking into account the conceptual model of memory and identification (Rabinovich [4]).

Familial amyloid polyneuropathy: TTR sequencing and "in silico" analysis

Familial amyloid polyneuropathy (FAP) or paramiloidosis is an autosomal dominant neurodegenerative disease with onset on adult age that is characterized by mutated protein deposition in the form of amyloid substance. FAP is due to a point alteration in the transthyretin (TTR) gene and until now more than 100 amyloidogenic mutations have been described in TTR gene. FAP shows a wide variation in age-at-onset (AO) (19-82 years, in Portuguese cases) and the V30M mutation often runs through several generation of asymptomatic carriers, before expressing in a proband, but the protective effect disappear in a single generation, with offspring of late-onset cases having early onset. V30M mutation does not explain alone the symptoms and AO variability of the disease observed in the same family. Our aim in this study was to identify genetic factors associated with AO variability and reduced penetrance which can have important clinical implications. To accomplish this we genotyped 230 individuals, using a directautomated sequencing approach in order to identify possible genetic modifiers within the TTR locus. After genotyping, we assessed a putative association of the SNPs found with AO and an intensive in silico analysis was performed in order to understand a possible regulation of gene expression. Although we did not find any significant association between SNPs and AO, we found very interesting and unreported results in the in silico analysis since we observed some alterations in the mechanism of splicing, transcription factors binding and miRNAs binding. All of these mechanisms when altered can lead to dysregulation of gene expression, which can have an impact in AO and phenotypic variability. These putative mechanisms of regulation of gene expression within the TTR gene could be used in the future as potential therapeutical targets, and could improve genetic counselling and follow-up of mutation carriers.

Improvements in sustainable energy and water practice in the food processing industry : an in depth analysis of the manufacture of Ghee at the Butter Producers' Cooperative Federation Limited, Brisbane

This thesis is a documented energy audit and long term study of energy and water reduction in a ghee factory. Global production of ghee exceeds 4 million tonnes annually. The factory in this study refines dairy products by non-traditional centrifugal separation and produces 99.9% pure, canned, crystallised Anhydrous Milk Fat (Ghee). Ghee is traditionally made by batch processing methods. The traditional method is less efficient, than centrifugal separation. An in depth systematic investigation was conducted of each item of major equipment including; ammonia refrigeration, a steam boiler, canning equipment, pumps, heat exchangers and compressed air were all fine-tuned. Continuous monitoring of electrical usage showed that not every initiative worked, others had pay back periods of less than a year. In 1994-95 energy consumption was 6,582GJ and in 2003-04 it was 5,552GJ down 16% for a similar output. A significant reduction in water usage was achieved by reducing the airflow in the refrigeration evaporative condensers to match the refrigeration load. Water usage has fallen 68% from18ML in 1994-95 to 5.78ML in 2003-04. The methods reported in this thesis could be applied to other industries, which have similar equipment, and other ghee manufacturers.

In vitro and in vivo analysis of co-electrospun scaffolds made of medical grade poly(epsilon-caprolactone) and porcine collagen

In this study, a nanofiber mesh made by co-electrospinning medical grade poly(epsilon-caprolactone) and collagen (mPCL/Col) was fabricated and studied. Its mechanical properties and characteristics were analyzed and compared to mPCL meshes. mPCL/Col meshes showed a reduction in strength but an increase in ductility when compared to PCL meshes. In vitro assays revealed that mPCL/Col supported the attachment and proliferation of smooth muscle cells on both sides of the mesh. In vivo studies in the corpus cavernosa of rabbits revealed that the mPCL/Col scaffold used in conjunction with autologous smooth muscle cells resulted in better integration with host tissue when compared to cell free scaffolds. On a cellular level preseeded scaffolds showed a minimized foreign body reaction.

In-depth analysis of the J.A.C.K. model

The Texas Transportation Commission (“the Commission”) is responsible for planning and making policies for the location, construction, and maintenance of a comprehensive system of highways and public roads in Texas. In order for the Commission to carry out its legislative mandate, the Texas Constitution requires that most revenue generated by motor vehicle registration fees and motor fuel taxes be used for constructing and maintaining public roadways and other designated purposes. The Texas Department of Transportation (TxDOT) assists the Commission in executing state transportation policy. It is the responsibility of the legislature to appropriate money for TxDOT’s operation and maintenance expenses. All money authorized to be appropriated for TxDOT’s operations must come from the State Highway Fund (also known as Fund 6, Fund 006, or Fund 0006). The Commission can then use the balance in the fund to fulfill its responsibilities. However, the value of the revenue received in Fund 6 is not keeping pace with growing demand for transportation infrastructure in Texas. Additionally, diversion of revenue to nontransportation uses now exceeds $600 million per year. As shown in Figure 1.1, revenues and expenditures of the State Highway Fund per vehicle mile traveled (VMT) in Texas have remained almost flat since 1993. In the meantime, construction cost inflation has gone up more than 100%, effectively halving the value of expenditure.

Talking it through : the case for the use of conversation analytic approaches in the analysis of news journalism

This study makes out the case for the use of the Conversational Analytic method as a research approach that might both extricate and chronicle the features of the journalism interview. It seeks to encourage such research to help inform understanding of this form and to provide further lessons as to the nature of journalism practice. Such studies might follow many paths but this paper focuses more particularly on the outcomes for the debate as to the continued relevance of "objectivity" in informing journalism professional practice. To make out the case for the veracity of CA as a means through which the conduct of journalism practice might be explored the paper examines: the theories of the interaction order that gave rise to the CA method; outlines the key features of the journalism interview as explicated through the CA approach; outlines the implications of such research for the establishment of the standing of "objectivity". It concludes as to the wider relevance of such studies of journalism practice for a fracturing journalism field, which suffers from a lack of benchmarks to measure the public benefit of the range of forms that now proliferate on the internet.

Secondary prevention of osteoporosis in Australia: Analysis of government-dispensed prescription data

Background Osteoporosis is a common cause of disability and death in elderly men and women. Until 2007, Australian Government-subsidized use of oral bisphosphonates, raloxifene and calcitriol (1α,25-dihydroxycholecalciferol) was limited to secondary prevention (requiring x-ray evidence of previous low-trauma fracture). The cost to the Pharmaceutical Benefits Scheme was substantial (164 million Australian dollars in 2005/6). Objective To examine the dispensed prescriptions for oral bisphosphonates, raloxifene, calcitriol and two calcium products for the secondary prevention of osteoporosis (after previous low-trauma fracture) in the Australian population. Methods We analysed government data on prescriptions for oral bisphosphonates, raloxifene, calcitriol and two calcium products from 1995 to 2006, and by sex and age from 2002 to 2006. Prescription counts were converted to defined daily doses (DDD)/1000 population/day. This standardized drug utilization method used census population data, and adjusts for the effects of aging in the Australian population. Results Total bisphosphonate use increased 460% from 2.19 to 12.26 DDD/1000 population/day between June 2000 and June 2006. The proportion of total bisphosphonate use in June 2006 was 75.1% alendronate, 24.6% risedronate and 0.3% etidronate. Raloxifene use in June 2006 was 1.32 DDD/1000 population/day. The weekly forms of alendronate and risedronate, introduced in 2001 and 2003, respectively, were quickly adopted. Bisphosphonate use peaked at age 80–89 years in females and 85–94 years in males, with 3-fold higher use in females than in males. Conclusions Pharmaceutical intervention for osteoporosis in Australia is increasing with most use in the elderly, the population at greatest risk of fracture. However, fracture prevalence in this population is considerably higher than prescribing of effective anti-osteoporosis medications, representing a missed opportunity for the quality use of medicines.

Correcting flaws in Mitchell’s analysis of EPBC

Efficient error-Propagating Block Chaining (EPBC) is a block cipher mode intended to simultaneously provide both confidentiality and integrity protection for messages. Mitchell’s analysis pointed out a weakness in the EPBC integrity mechanism that can be used in a forgery attack. This paper identifies and corrects a flaw in Mitchell’s analysis of EPBC, and presents other attacks on the EPBC integrity mechanism.

Missing in space: An evaluation of imputation methods for missing data in spatial analysis of risk factors for type II diabetes

Background Spatial analysis is increasingly important for identifying modifiable geographic risk factors for disease. However, spatial health data from surveys are often incomplete, ranging from missing data for only a few variables, to missing data for many variables. For spatial analyses of health outcomes, selection of an appropriate imputation method is critical in order to produce the most accurate inferences. Methods We present a cross-validation approach to select between three imputation methods for health survey data with correlated lifestyle covariates, using as a case study, type II diabetes mellitus (DM II) risk across 71 Queensland Local Government Areas (LGAs). We compare the accuracy of mean imputation to imputation using multivariate normal and conditional autoregressive prior distributions. Results Choice of imputation method depends upon the application and is not necessarily the most complex method. Mean imputation was selected as the most accurate method in this application. Conclusions Selecting an appropriate imputation method for health survey data, after accounting for spatial correlation and correlation between covariates, allows more complete analysis of geographic risk factors for disease with more confidence in the results to inform public policy decision-making.