Heart rate and rhythm patterns in the fetus, neonate and child

Imperial Users onl

Feasibility study of an Integrated Program for Aerospace vehicle Design (IPAD). Volume 2: The design process

The extent to which IPAD is to support the design process is identified. Case studies of representative aerospace products were developed as models to characterize the design process and to provide design requirements for the IPAD computing system

Experimental field studies to measure behavioral responses of cetaceans to sonar

Funding was provided by a variety of military and governmental funding sources from several nations acknowledged within referenced publications, notably the US Office of Naval Research, US Navy Living Marine Resources Program, and the navies of the USA, Norway, and the Netherlands. P.L.T. acknowledges the support of the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland) in the completion of this study. MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions.Substantial recent progress has been made in directly measuring behavioral responses of free-ranging marine mammals to sound using controlled exposure experiments. Many studies were motivated by concerns about observed and potential negative effects of military sonar, including stranding events. Well-established experimental methods and increasingly sophisticated technologies have enabled fine-resolution measurement of many aspects of baseline behavior and responses to sonar. Studies have considered increasingly diverse taxa, but primarily odontocete and mysticete cetaceans that are endangered, particularly sensitive, or frequently exposed to sonar. This review focuses on recent field experiments studying cetacean responses to simulated or actual active military sonars in the 1 to 8 kHz band. Overall results demonstrate that some individuals of different species display clear yet varied responses, some of which have negative implications, while others appear to tolerate relatively high levels, although such exposures may have other consequences not measured. Responses were highly variable and may not be fully predictable with simple acoustic exposure metrics (e.g. received sound level). Rather, differences among species and individuals along with contextual aspects of exposure (e.g. behavioral state) appear to affect response probability. These controlled experiments provide critically needed documentation of identified behavioral responses occurring upon known sonar exposures, and they directly inform regulatory assessments of potential effects. They also inform more targeted opportunistic monitoring of potential responses of animals during sonar operations and have stimulated adaptations of field methods to consider increasingly realistic exposure scenarios and how contextual factors such as behavioral state and source proximity influence response type and probability.Publisher PDFPeer reviewe

Comparison on Functional Assays for Gq-Coupled GPCRs by Measuring Inositol Monophospate-1 and Intracellular Calcium in 1536-Well Plate Format

Cell-based functional assays used for compound screening and lead optimization play an important role in drug discovery for G-protein coupled receptors (GPCRs). Cell-based assays can define the role of a compound as an agonist, antagonist or inverse agonist and can provide detailed information about the potency and efficacy of a compound. In addition, cell-based screens can be used to identify allosteric modulators that interact with sites other than the binding site of the endogenous ligand. Intracellular calcium assays which use a fluorescent calcium binding dye (such as Fluo-3, Fluo-4 or Fura-2) have been used in compound screening campaigns to measure the activity of Gq-coupled GPCRs. However, such screening methodologies require a special instrumentation to record the rapid change in intracellular free calcium concentration over time. The radioactive inositol 1,4,5- triphosphate (IP3) assay measures 3H-inositol incorporation and is another traditional assay for the assessment of Gq-coupled GPCR activity, but it is not suitable for screening of large size compound collections because it requires a cell wash step and generates radioactive waste. To avoid these limitations, we have optimized and miniaturized a TR-FRET based IP-One assay that measures inositol monophosphate in a 1536-well plate format. This assay is homogenous, non-radioactive and does not require a kinetic readout. It has been tested with the cell lines expressing M1 acetylcholine, FFAR1, vasopressin V1b, or Neuropeptide S receptors. The activities of antagonists determined in the IP-One assay correlated well with these measured in the intracellular calcium assay while the correlation of agonist activities might vary from cell line to cell line. This IP-One assay offers an alternative method for high throughput screening of Gq-coupled GPCRs without using costly kinetic plate readers