Quantitative analysis of directional strengths in jointly stationary linear multivariate processes

Identification and analysis of directed influences in multivariate systems is an important problem in many scientific areas. Recent studies in neuroscience have provided measures to determine the network structure of the process and to quantify the total effect in terms of energy transfer. These measures are based on joint stationary representations of a multivariate process using vector auto-regressive (VAR) models. A few important issues remain unaddressed though. The primary outcomes of this study are (i) a theoretical proof that the total coupling strength consists of three components, namely, the direct, indirect, and the interference produced by the direct and indirect effects, (ii) expressions to estimate/calculate these effects, and (iii) a result which shows that the well-known directed measure for linear systems, partial directed coherence (PDC) only aids in structure determination but does not provide a normalized measure of the direct energy transfer. Simulation case studies are shown to illustrate the theoretical results.     

Opiates do not violate the viability and proliferative activity of human articular chondrocytes

Articular cartilage injuries present a challenge for the clinician. Autologous chondrocyte implantation embedded in scaffolds are used to treat cartilage defects with favorable outcomes. Autologous serum is often used as a medium for chondrocyte cell culture during the proliferation phase of the process of such products. A previous report showed that opiate analgesics (fentanyl, alfentanil and diamorphine) in the sera have a significant inhibitory effect on chondrocyte proliferation. In order to determine if opiates in serum inhibit chondrocyte proliferation, twenty two patients who underwent knee arthroscopy and were anesthetized with either fentanyl or remifentanil were studied. Blood was drawn before and during opiate administration and up to 2 h after its discontinuation. The sera were used as medium for in vitro proliferation of both cryopreserved and freshly isolated chondrocytes, and the number and viability of cells were measured. There was no difference in the yield or cell viability between the serum samples of patients anesthetized with fentanyl when either fresh or cryopreserved human articular chondrocytes (hACs) were used. Some non-significant reduction in the yield of cells was observed in the serum samples of patients anesthetized with remifentanil when fresh hAC were used. We conclude that Fentanyl in human autologous serum does not inhibit in vitro hAC proliferation. Remifentanil may show minimal inhibitory effect on in vitro fresh hAC proliferation.     

Dynamic Mechanical Responses of Arabidopsis Thylakoid Membranes during PSII-Specific Illumination

Remodeling of thylakoid membranes in response to illumination is an important process for the regulation of photosynthesis. We investigated the thylakoid network from Arabidopsis thaliana using atomic force microscopy to capture dynamic changes in height, elasticity, and viscosity of isolated thylakoid membranes caused by changes in illumination. We also correlated the mechanical response of the thylakoid network with membrane ultrastructure using electron microscopy. We find that the elasticity of the thylakoid membranes increases immediately upon PSII-specific illumination, followed by a delayed height change. Direct visualization by electron microscopy confirms that there is a significant change in the packing repeat distance of the membrane stacks in response to illumination. Although experiments with Gramicidin show that the change in elasticity depends primarily on the transmembrane pH gradient, the height change requires both the pH gradient and STN7-kinase-dependent phosphorylation of LHCII. Our studies indicate that lumen expansion in response to illumination is not simply a result of the influx of water, and we propose a dynamic model in which protein interactions within the lumen drive these changes.     

Clustering class I MHC modulates sensitivity of T cell recognition

T cell recognition of peptide-MHC is highly specific and is sensitive to very low levels of agonist peptide; however, it is unclear how this effect is achieved or regulated. In this study we show that clustering class I MHC molecules on the cell surface of B lymphoblasts enhances their recognition by mouse and human T cells. We increased clustering of MHC I molecules by two methods, cholesterol depletion and direct cross-linking of a dimerizable MHC construct. Imaging showed that both treatments increased the size and intensity of MHC clusters on the cell surface. Enlarged clusters correlated with enhanced lysis and T cell effector function. Enhancements were peptide-specific and greatest at low concentrations of peptide. Clustering MHC class I enhanced recognition of both strong and weak agonists but not null peptide. Our results indicate that the lateral organization of MHC class I on the cell surface can modulate the sensitivity of T cell recognition of agonist peptide.     

Getting medicine to millions: New strategies for mass distribution

This article examines the feasibility of allowing private industries such as grocery stores, wholesale clubs, and community immunizers to partner with public health authorities for the mass distribution of vaccines or antibiotics. Retail grocery and wholesale stores already have experience with annual influenza vaccination and may be a resource in a public health emergency, including a bioterrorist attack. This analysis suggests that retail store executives are willing to work with public health authorities to plan for and respond to public health emergencies.     

HHS guidance on synthetic DNA is the right step

Synthetic biology has advanced to the point where some pathogens can be manufactured from scratch. This technical leap has beneficent implications for medical research and vaccine design, but it also raises concerns that the technology could be used to produce a deadly pathogen for nefarious use. Addressing these concerns, the Department of Health and Human Services (HHS) released their Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA on October 13, 2010. They took the right approach: The oversight framework for gene synthesis companies included in this guidance is adaptable to new technical developments and changing risks, it can be implemented immediately, it can be readily adopted by other countries, and it will cost little. Though there have been some calls to increase the regulatory controls on synthetic biology, these should be resisted. For now, at least, the oversight is appropriate to the risks.     

Anthrax countermeasures: current status and future needs

The U.S. government does not yet have the range of medical countermeasures needed to protect its citizens from anthrax and other potential bioweapons. In the event of an anthrax attack, treatment interventions in addition to antibiotics would be needed so that very ill patients can be treated and clean-up crews can be better protected, especially if an engineered strain is used. This article describes specific anthrax countermeasures that are in development, barriers to development, and potential mechanisms the government could use to accelerate the movement of these countermeasures through the pipeline. A key challenge will be to encourage the transition of promising leads from basic research to the product development stage, when they may qualify for BioShield funds.