Utilizing Structure Property Correlations to Predict and Analyze Two Derivatives of an Ampicillin Homologous Series

Structure Property Correlation methods such as regression analysis and pattern recognition are applied to predict the molecular properties of two members of an ampicillin homologous series. The pentyl and hexyl esters of ampicillin are also evaluated for their similarity to other penicillins by use of multiple regression, contingency tables, cluster analysis, correspondence analysis, self organizing tree algorithms, factor analysis, principal component analysis, box plots, and other graphing methods. Other members of the homologous series include methyl, ethyl, propyl, and butyl esters of ampicillin which have been previously synthesized and tested in tissue culture against Escherichia coli. All of the tested esters of ampicillin significantly inhibited penicillin susceptible and ampicillin resistant bacteria, as well as streptomycin resistant bacteria. Drug homologous series has been observed with other antibiotics and medicinal compounds. Homologous series activity is a trend observed for ampicillin by graphing the reciprocal equi-effective concentrations versus the number of carbons comprising the ester group. Regression analysis and contingency tables predict the molecular properties of the hexyl and pentyl esters, while cluster analysis, factor analysis, correspondence analysis, principal component analysis, and tree algorithms correlate them to the parent ampicillin and other members of the ß - lactam class of antibiotics. This work demonstrates the effectiveness of applying numerical analysis methods to drug design and development

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Contains reports on three research projects

Loss of monomorphic and polymorphic HLA antigens in metastatic breast and colon carcinoma.

MHC class I antigens are intimately involved in intercellular communication, and recognition by cytotoxic T cells. Thus tumour cells that fail to express them may be at a growth or metastatic advantage. A series of ten colorectal and ten breast carcinomas, and their respective lymph node metastases, were examined immunohistologically using monoclonal antibodies (mAb) against both monomorphic and A2 polymorphic determinants, and beta-2-microglobulin (beta 2m). Four colon polypoid adenomas stained positively throughout, but 6/10 primary tumours had partial or complete loss of expression of monomorphic determinants using mAb W6/32: two node and the liver metastasis showed less, four more expression. Similar results were seen for beta 2m. HLA-A2 expression was absent or reduced in 4/4 colon tumours and all their metastases. Among the breast tumours, W6/32 staining was absent or reduced in 2/10, and node deposits showed two with less reactivity than their primary. Beta 2m staining was reduced or absent in 8/10 primaries and all the node metastases; in every case in which beta 2m was detected in the primary tumour their corresponding lymph node metastasis showed a decreased expression. HLA-A2 expression was absent or reduced in 3/4 primary breast carcinomas, and all their metastases. These results show that individual human colon and breast carcinomas often have a reduced HLA class I antigen expression, which apparently confers a metastatic advantage

ADAPT: a price-stabilizing compliance policy for renewable energy certificates: the case of SREC markets

Currently most Renewable Energy Certificate (REC) markets are defined based on targets which create an artificial step demand function resembling a cliff. This target policy produces volatile prices which can make investing in renewables a risky proposition. In this paper, we propose an alternative policy called Adjustable Dynamic Assignment of Penalties and Targets (ADAPT) which uses a sloped compliance penalty and a self-regulating requirement schedule, both designed to stabilize REC prices, helping to alleviate a common weakness of environmental markets. To capture market behavior, we model the market as a stochastic dynamic programming problem to understand how the market might balance the decision to use a REC now versus holding it for future periods (in the face of uncertain new supply). Then, we present and prove some of the properties of this market, and finally we show that this mechanism reduces the volatility of REC prices which should stabilize the market and encourage long-term investment in renewables

Energy Impacts of Water Based Recreation

The overall objective of the study reported here was to determine to what extent energy accounting could supplement and/or complement economic benfit/cost analyses of water management projects and to specifically examine the energy impacts of water based recreation. The energy accounting literature was carefully reviewed and an energy accounting methodology applicable to water management was devised. Data pertaining to receation at five reservoirs in Utah were assembled from visitation recoreds and on-site surveys. Energy requirements for site construction, travel to and from the recreation site, and recreation at the site were estimated. It was determined that energy devoted to water based recreation is not inconsequential. As much energy is devoted to recreation at Lake Powell alone as is required for all of production agriculture in Utah. It is suggested that while the models developed in this study could be used with confidence in the preparation of energy impact statements the authors are not persuaded energy accounting provides additional information to water use planners beyong that obtainable from traditional economic analysis

Epidemiology of influenza-like illness in the Amazon Basin of Peru, 2008-2009.

BackgroundData addressing the incidence and epidemiology of influenza and influenza-like illness (ILI) in tropical regions of the world is scarce, particularly for the neotropics of South America.MethodsWe conducted active, population-based surveillance for ILI across 45 city blocks within the Amazon Basin city of Iquitos, Peru. Demographic data and household characteristics were collected for all participants, and participating households were visited three times weekly to inquire about ILI (fever plus cough or sore throat) among household residents. Nasal and oropharyngeal swabs were collected from participants with ILI and tested for influenza virus infection.ResultsBetween May 1, 2008 and July 8, 2009, we monitored 10,341 participants for ILI for a total of 11,569.5 person-years. We detected 459 ILI episodes, with 252 (54.9%) of the participants providing specimens. Age-adjusted incidence of ILI was estimated to be 46.7 episodes/1000 person-years. Influenza A and B viruses were detected in 25 (9.9%) and 62 (24.6%) specimens of ILI patients, respectively, for an estimated age-adjusted incidence rate of 16.5 symptomatic influenza virus infections/1000 person-years. Risk factors for ILI included age, household crowding, and use of wood as cooking fuel. For influenza virus infection specifically, age and use of wood as a cooking fuel were also identified as risk factors, but no effect of household crowding was observed.ConclusionsOur results represent the initial population-based description of the epidemiology of ILI in the Amazon region of Peru, which will be useful for developing region-specific strategies for reducing the burden of respiratory disease

Estimating the impact of city-wide Aedes aegypti population control: An observational study in Iquitos, Peru.

During the last 50 years, the geographic range of the mosquito Aedes aegypti has increased dramatically, in parallel with a sharp increase in the disease burden from the viruses it transmits, including Zika, chikungunya, and dengue. There is a growing consensus that vector control is essential to prevent Aedes-borne diseases, even as effective vaccines become available. What remains unclear is how effective vector control is across broad operational scales because the data and the analytical tools necessary to isolate the effect of vector-oriented interventions have not been available. We developed a statistical framework to model Ae. aegypti abundance over space and time and applied it to explore the impact of citywide vector control conducted by the Ministry of Health (MoH) in Iquitos, Peru, over a 12-year period. Citywide interventions involved multiple rounds of intradomicile insecticide space spray over large portions of urban Iquitos (up to 40% of all residences) in response to dengue outbreaks. Our model captured significant levels of spatial, temporal, and spatio-temporal variation in Ae. aegypti abundance within and between years and across the city. We estimated the shape of the relationship between the coverage of neighborhood-level vector control and reductions in female Ae. aegypti abundance; i.e., the dose-response curve. The dose-response curve, with its associated uncertainties, can be used to gauge the necessary spraying effort required to achieve a desired effect and is a critical tool currently absent from vector control programs. We found that with complete neighborhood coverage MoH intra-domicile space spray would decrease Ae. aegypti abundance on average by 67% in the treated neighborhood. Our framework can be directly translated to other interventions in other locations with geolocated mosquito abundance data. Results from our analysis can be used to inform future vector-control applications in Ae. aegypti endemic areas globally

The genetic structure of Aedes aegypti populations is driven by boat traffic in the Peruvian Amazon.

In the Americas, as in much of the rest of the world, the dengue virus vector Aedes aegypti is found in close association with human habitations, often leading to high population densities of mosquitoes in urban settings. In the Peruvian Amazon, this vector has been expanding to rural communities over the last 10-15 years, but to date, the population genetic structure of Ae. aegypti in this region has not been characterized. To investigate the relationship between Ae. aegypti gene flow and human transportation networks, we characterized mosquito population structure using a panel of 8 microsatellite markers and linked results to various potential mechanisms for long-distance dispersal. Adult and immature Ae. aegypti (>20 individuals per site) were collected from Iquitos city and from six neighboring riverine communities, i.e., Nauta, Indiana, Mazan, Barrio Florida, Tamshiaco, and Aucayo. FST statistics indicate significant, but low to moderate differentiation for the majority of study site pairs. Population structure of Ae. aegypti is not correlated with the geographic distance between towns, suggesting that human transportation networks provide a reasonable explanation for the high levels of population mixing. Our results indicate that Ae. aegypti gene flow among sub-populations is greatest between locations with heavy boat traffic, such as Iquitos-Tamshiaco and Iquitos-Indiana-Mazan, and lowest between locations with little or no boat/road traffic between them such as Barrio Florida-Iquitos. Bayesian clustering analysis showed ancestral admixture among three genetic clusters; no single cluster was exclusive to any site. Our results are consistent with the hypothesis that human transportation networks, particularly riverways, are responsible for the geographic spread of Ae. aegypti in the Peruvian Amazon. Our findings are applicable to other regions of the world characterized by networks of urban islands connected by fluvial transport routes