Rapid Detection of Botulinum Neurotoxins—A Review

A toxin is a poisonous substance produced within living cells or organisms. One of the most potent groups of toxins currently known are the Botulinum Neurotoxins (BoNTs). These are so deadly that as little as 62 ng could kill an average human; to put this into context that is approximately 200,000 × less than the weight of a grain of sand. The extreme toxicity of BoNTs leads to the need for methods of determining their concentration at very low levels of sensitivity. Currently the mouse bioassay is the most widely used detection method monitoring the activity of the toxin; however, this assay is not only lengthy, it also has both cost and ethical issues due to the use of live animals. This review focuses on detection methods both existing and emerging that remove the need for the use of animals and will look at three areas; speed of detection, sensitivity of detection and finally cost. The assays will have wide reaching interest, ranging from the pharmaceutical/clinical industry for production quality management or as a point of care sensor in suspected cases of botulism, the food industry as a quality control measure, to the military, detecting BoNT that has been potentially used as a bio warfare agent

St. Michaels association for special education new facility and master plan: final report

St. Michael's Association for Special Education, located near Window Rock, AZ, is an institution that has been established for the schooling and therapy of approximately 100 mentally and physically challenged Navajo children and adults. The existing school buildings are located on a 20 acre site are structurally unsound, crowded and poorly equipped to handle the daily functions of the school. FBM has outlined criteria by which the ideal solution to the problems at St. Michael's maybe resolved. The selected design alternative is a single, one story, 70,600 square foot multipurpose building that addresses site, structural, electrical, HVAC, plumbing, fire protection, and other concerns of the students, faculty, and staff of St. Michael's. The building is located on the previously developed portion of St. Michael's site. The site is regraded in order to accommodate the building materials and methods chosen and to add to the long term stability of the structure. Architectural features of the building fall in line with the client's preferences. Masonry bearing walls and steel KCS joists make up the superstructure of the building and are supported by continuous footings. Pilasters are employed for lateral support. A ground source heat pump is employed for HVAC. Solar power supplements 509,000 kWh per year of electricity supplied to the building. Our design brings about a safe, efficient building that promotes a healing and nurturing school environment at a cost of about $7 million

St. Michaels association for special education new facility and master plan: final report

St. Michael's Association for Special Education, located near Window Rock, AZ, is an institution that has been established for the schooling and therapy of approximately 100 mentally and physically challenged Navajo children and adults. The existing school buildings are located on a 20 acre site are structurally unsound, crowded and poorly equipped to handle the daily functions of the school. FBM has outlined criteria by which the ideal solution to the problems at St. Michael's maybe resolved. The selected design alternative is a single, one story, 70,600 square foot multipurpose building that addresses site, structural, electrical, HVAC, plumbing, fire protection, and other concerns of the students, faculty, and staff of St. Michael's. The building is located on the previously developed portion of St. Michael's site. The site is regraded in order to accommodate the building materials and methods chosen and to add to the long term stability of the structure. Architectural features of the building fall in line with the client's preferences. Masonry bearing walls and steel KCS joists make up the superstructure of the building and are supported by continuous footings. Pilasters are employed for lateral support. A ground source heat pump is employed for HVAC. Solar power supplements 509,000 kWh per year of electricity supplied to the building. Our design brings about a safe, efficient building that promotes a healing and nurturing school environment at a cost of about $7 million

Why Does Inflation Start at the Top of the Hill?

We show why the universe started in an unstable de Sitter state. The quantum origin of our universe implies one must take a `top down' approach to the problem of initial conditions in cosmology, in which the histories that contribute to the path integral, depend on the observable being measured. Using the no boundary proposal to specify the class of histories, we study the quantum cosmological origin of an inflationary universe in theories like trace anomaly driven inflation in which the effective potential has a local maximum. We find that an expanding universe is most likely to emerge in an unstable de Sitter state, by semiclassical tunneling via a Hawking-Moss instanton. Since the top down view is forced upon us by the quantum nature of the universe, we argue that the approach developed here should still apply when the framework of quantum cosmology will be based on M-Theory.Comment: 21 pages, 1 figur

Analysis of plasma indices of redox homeostasis in dairy cows reared in polluted areas of Piedmont (northern Italy)

Steel manufacturing is responsible for the emission of pollutants, including dioxins and transition metals, inducing reactive oxygen species generation and DNA damage. Dioxin pollution represents the major cause of milk and dairy product contamination, in Italy, and is associated with oxidative stress-related processes, that may impair health and performance of cows.We evaluated the effect of exposure to different concentrations of pollutants derived from steel manufacturing on blood redox homeostasis of bovine cows. We analyzed two groups of dairy cows (A, B), reared in two different polluted areas, and a control group of cows bred in an industry free area. The extent of exposure to contaminants was defined by measuring dioxin level in bulk milk samples collected from animals of each farm. This level was lower in milk of group A than in group B. Plasma concentrations of retinol, alpha-tocopherol and ascorbate, the total antioxidant capacity, and the activities of superoxide dismutase and glutathione peroxidase were higher in control group than in exposed groups. In particular, retinol and tocopherol levelswere higher in the groupwith lower milk dioxin level. Plasma titers of protein-bound carbonyls (PC), nitro-tyrosine, and hydroperoxideswere lower in control group than in A or B. Hydroperoxides and PC plasmaconcentrationswere increased in the groupwith higher milk concentration of dioxin. Our results demonstrate that, irrespective of the nature of chemicals inducing oxidativemodifications, the extent of damage to plasmaprotein and lipid, is correlatedwith the concentration of dioxin in milk. So, the characterization of blood redox status might be a useful tool for identifying animals exposed to environmental pollutants. Plasma concentrations of retinol, alpha-tocopherol, PC and hydroperoxides could therefore represent good indices of the extent of animal exposure, as they significantly change in groups with different milk concentrations of dioxi