The Global Networked Value Circle: A new model for best-in-class manufacturing

As companies face deflation, slowing production and declining prices, they will need to assess their entire value chain as they look for ways to keep costs low and improve efficiencies while continuing to innovate. To help address this challenge, this report reflects fresh research undertaken by Capgemini in collaboration with the University of Edinburgh into the ?Best-in-Class Global Manufacturing Value Chain?

Hot Topic: State-Shared Taxes and Appropriations (2012-2013) (Revised)

Based on economic projections for FY 2013, municipalities are expected to receive approximately $106.30 per capita for the fiscal year beginning July 1, 2012

Hot Topic: Changes in Federal and State Reimbursement Rates for Travel

Summary of changes in the federal and state lodging and meals reimbursement rates for travel

Boomerang employees: should you welcome them back?

Former employees who want to come back to an old job form an increasingly common pool of job applicants, write Brad Harris and Richard Gardne

Quantitative Real-time PCR (qPCR) for the Determination of Salmonella Levels in Lairage

The sensitivity of the quantitative polymerase chain reaction assay (qPCR) was shown to be 10,000 Salmonella colony forming units (cfu) of bacteria per gram of fecal matter; this means that this rapid and specific test is a useful tool for the industry. The study found a trend toward a reduced, but not statistically significant, amount of Salmonella in lairage pens from standard hygiene practices of washing pens between groups of swine. This reduction of Salmonella in lairage pens may result in decrease transmission between groups, and, ultimately, in fewer numbers of contaminated carcasses at slaughter. It might also allow one to determine if on farm and transport methods are reducing Salmonella fecal incidence in lairage pens. The lack of significance is partially due to the low number of positive pens in this study before washing. Due to the low numbers found in pens in this study, samples were not collected from transport as they would have not lead to significant differences between various treatments

Endosomal Escape of Antisense Oligonucleotides Internalized by Stabilin Receptors Is Regulated by Rab5C and EEA1 During Endosomal Maturation

Second-generation (Gen 2) Antisense oligonucleotides (ASOs) show increased nuclease stability and affinity for their RNA targets, which has translated to improved potency and therapeutic index in the clinic. Gen 2 ASOs are typically modified using the phosphorothioate (PS) backbone modification, which enhances ASO interactions with plasma, cell surface, and intracellular proteins. This facilitates ASO distribution to peripheral tissues and also promotes cellular uptake after injection into animals. Previous work identified that Stabilin receptors specifically internalize PS-ASOs in the sinusoidal endothelial cells of the liver and the spleen. By modulating expression of specific proteins involved in the trafficking and maturation of the endolysosomal compartments, we show that Rab5C and EEA1 in the early endosomal pathway, and Rab7A and lysobisphosphatidic acid in the late endosomal pathway, are important for trafficking of PS-ASOs and facilitate their escape from endolysosomal compartments after Stabilin-mediated internalization. In conclusion, this work identifies key ratelimiting proteins in the pathway for PS-ASO translocation and escape from the endosome

An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction channels.

Gap junction channels mediate intercellular signalling that is crucial in tissue development, homeostasis and pathologic states such as cardiac arrhythmias, cancer and trauma. To explore the mechanism by which Ca(2+) blocks intercellular communication during tissue injury, we determined the X-ray crystal structures of the human Cx26 gap junction channel with and without bound Ca(2+). The two structures were nearly identical, ruling out both a large-scale structural change and a local steric constriction of the pore. Ca(2+) coordination sites reside at the interfaces between adjacent subunits, near the entrance to the extracellular gap, where local, side chain conformational rearrangements enable Ca(2+)chelation. Computational analysis revealed that Ca(2+)-binding generates a positive electrostatic barrier that substantially inhibits permeation of cations such as K(+) into the pore. Our results provide structural evidence for a unique mechanism of channel regulation: ionic conduction block via an electrostatic barrier rather than steric occlusion of the channel pore