Taking advantage of an old concept, "illegitimate transcription", for a proposed novel method of genetic diagnosis of McArdle disease

McArdle disease is a metabolic disorder caused by pathogenic mutations in the PYGM gene. Timely diagnosis can sometimes be difficult with direct genomic analysis, which requires additional studies of cDNA from muscle transcripts. Although the "nonsense-mediated mRNA decay" (NMD) eliminates tissue-specific aberrant transcripts, there is some residual transcription of tissue-specific genes in virtually all cells, such as peripheral blood mononuclear cells (PBMCs).We studied a subset of the main types of PYGM mutations (deletions, missense, nonsense, silent, or splicing mutations) in cDNA from easily accessible cells (PBMCs) in 12 McArdle patients.Analysis of cDNA from PBMCs allowed detection of all mutations. Importantly, the effects of mutations with unknown pathogenicity (silent and splicing mutations) were characterized in PBMCs. Because the NMD mechanism does not seem to operate in nonspecific cells, PBMCs were more suitable than muscle biopsies for detecting the pathogenicity of some PYGM mutations, notably the silent mutation c.645G>A (p.K215=), whose effect in the splicing of intron 6 was unnoticed in previous muscle transcriptomic studies.We propose considering the use of PBMCs for detecting mutations that are thought to cause McArdle disease, particularly for studying their actual pathogenicity.

Statistical method of modeling and optimization for wireless sensor nodes with different interconnect technologies and substrates

A comparison study was carried out between a wireless sensor node with a bare die flip-chip mounted and its reference board with a BGA packaged transceiver chip. The main focus is the return loss (S parameter S11) at the antenna connector, which was highly depended on the impedance mismatch. Modeling including the different interconnect technologies, substrate properties and passive components, was performed to simulate the system in Ansoft Designer software. Statistical methods, such as the use of standard derivation and regression, were applied to the RF performance analysis, to see the impacts of the different parameters on the return loss. Extreme value search, following on the previous analysis, can provide the parameters' values for the minimum return loss. Measurements fit the analysis and simulation well and showed a great improvement of the return loss from -5dB to -25dB for the target wireless sensor node.

A method of assessing air toxics concentrations in urban areas using mobile platform measurements.

The objective of this paper is to demonstrate an approach to characterize the spatial variability in ambient air concentrations using mobile platform measurements. This approach may be useful for air toxics assessments in Environmental Justice applications, epidemiological studies, and environmental health risk assessments. In this study, we developed and applied a method to characterize air toxics concentrations in urban areas using results of the recently conducted field study in Wilmington, DE. Mobile measurements were collected over a 4- x 4-km area of downtown Wilmington for three components: formaldehyde (representative of volatile organic compounds and also photochemically reactive pollutants), aerosol size distribution (representing fine particulate matter), and water-soluble hexavalent chromium (representative of toxic metals). These measurements were,used to construct spatial and temporal distributions of air toxics in the area that show a very strong temporal variability, both diurnally and seasonally. An analysis of spatial variability indicates that all pollutants varied significantly by location, which suggests potential impact of local sources. From the comparison with measurements at the central monitoring site, we conclude that formaldehyde and fine particulates show a positive correlation with temperature, which could also be the reason that photochemically generated formaldehyde and fine particulates over the study area correlate well with the fine particulate matter measured at the central site.

A method of false coincidence removal from measurements of quadruple coincidences between two photoelectrons and two photoions generated in molecular double photoionization

The removal of false coincidences from measurements of coincidences between two photoelectrons and one or two ions formed in molecular double photoionization is described. False coincidences arise by several mechanisms; experimental procedures and mathematical formulae required to remove all the different false coincidence contributions are described. Sample spectra taken of the double photoionization of carbon dioxide are presented to illustrate the method of false coincidence subtraction.