In-Band Asymmetry Compensation for Accurate Time/Phase Transport over Optical Transport Network

The demands of precise time/phase synchronization have been increasing recently due to the next generation of telecommunication synchronization. This paper studies the issues that are relevant to distributing accurate time/phase over optical transport network (OTN). Each node and link can introduce asymmetry, which affects the adequate time/phase accuracy over the networks. In order to achieve better accuracy, protocol level full timing support is used (e.g., Telecom-Boundary clock). Due to chromatic dispersion, the use of different wavelengths consequently causes fiber link delay asymmetry. The analytical result indicates that it introduces significant time error (i.e., phase offset) within 0.3397 ns/km in C-band or 0.3943 ns/km in L-band depending on the wavelength spacing. With the proposed scheme in this paper, the fiber link delay asymmetry can be compensated relying on the estimated mean fiber link delay by the Telecom-Boundary clock, while the OTN control plane is responsible for processing the fiber link delay asymmetry to determine the asymmetry compensation in the timing chain

Application of Rat In Situ Single-pass Intestinal Perfusion in the Evaluation of Presystemic Extraction of Indinavir Under Different Perfusion Rates

Background/PurposeFirst-pass effect has been an important concern for oral pharmaceuticals. An in vivo system was developed for measuring different concentrations of pharmaceuticals in the portal vein and hepatic vein (via the inferior vena cava) for delineating presystemic metabolism under different perfusion rates by using indinavir as an exemplary agent.MethodsAn in situ single-pass intestinal perfusion technique was modified from previous studies to concomitantly obtain portal and hepatic venous bloods. Portal and hepatic venous samples were simultaneously taken from rats at appropriate time points using the perfusion model of 1 mg/mL indinavir at flow rates of 0.05, 0.1, 0.5 and 1.0 mL/min. The indinavir concentrations were assayed by binary-gradient high-pressure liquid chromatography with UV detection.ResultsThe mean indinavir concentrations in portal vein concentration−time profiles at different perfusion times under various flow rates were all higher than those obtained for hepatic veins. At flow rates of 0.5 and 1.0 mL/min, in particular, the area under the curve (AUC) and maximal concentration (C max) of indinavir absorption were significantly different between portal veins and hepatic veins (p < 0.05), indicating considerable hepatic involvement in the presystemic extraction of indinavir. The system also has potential for use when estimating the hepatic extraction ratio (E H) and hepatic clearance (Cl H).ConclusionThis in vivo approach could provide another useful tool for improving our basic understanding of the absorption kinetics and hepatic metabolism of pharmaceuticals under development and facilitating the clinical application of such

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Identification of differentially expressed genes induced by <it>Bamboo mosaic virus </it>infection in <it>Nicotiana benthamiana </it>by cDNA-amplified fragment length polymorphism

Abstract Background The genes of plants can be up- or down-regulated during viral infection to influence the replication of viruses. Identification of these differentially expressed genes could shed light on the defense systems employed by plants and the mechanisms involved in the adaption of viruses to plant cells. Differential gene expression in Nicotiana benthamiana plants in response to infection with Bamboo mosaic virus (BaMV) was revealed using cDNA-amplified fragment length polymorphism (AFLP). Results Following inoculation with BaMV, N. benthamiana displayed differential gene expression in response to the infection. Isolation, cloning, and sequencing analysis using cDNA-AFLP furnished 90 cDNA fragments with eight pairs of selective primers. Fifteen randomly selected genes were used for a combined virus-induced gene silencing (VIGS) knockdown experiment, using BaMV infection to investigate the roles played by these genes during viral infection, specifically addressing the means by which these genes influence the accumulation of BaMV protein. Nine of the 15 genes showed either a positive or a negative influence on the accumulation of BaMV protein. Six knockdown plants showed an increase in the accumulation of BaMV, suggesting that they played a role in the resistance to viral infection, while three plants showed a reduction in coat protein, indicating a positive influence on the accumulation of BaMV in plants. An interesting observation was that eight of the nine plants showing an increase in BaMV coat protein were associated with cell rescue, defense, death, aging, signal transduction, and energy production. Conclusions This study reports an efficient and straightforward method for the identification of host genes involved in viral infection. We succeeded in establishing a cDNA-AFLP system to help track changes in gene expression patterns in N. benthamiana plants when infected with BaMV. The combination of both DNA-AFLP and VIGS methodologies made it possible to screen a large number of genes and identify those associated with infections of plant viruses. In this report, 9 of the 15 analyzed genes exhibited either a positive or a negative influence on the accumulation of BaMV in N. benthamiana plants.</p

Application of Rat In Situ Single-pass Intestinal Perfusion in the Evaluation of Presystemic Extraction of Indinavir Under Different Perfusion Rates

First-pass effect has been an important concern for oral pharmaceuticals. An in vivo system was developed for measuring different concentrations of pharmaceuticals in the portal vein and hepatic vein (via the inferior vena cava) for delineating presystemic metabolism under different perfusion rates by using indinavir as an exemplary agent. Methods: An in situ single-pass intestinal perfusion technique was modified from previous studies to concomitantly obtain portal and hepatic venous bloods. Portal and hepatic venous samples were simultaneously taken from rats at appropriate time points using the perfusion model of 1 mg/mL indinavir at flow rates of 0.05, 0.1, 0.5 and 1.0 mL/min. The indinavir concentrations were assayed by binary-gradient high-pressure liquid chromatography with UV detection. Results: The mean indinavir concentrations in portal vein concentration−time profiles at different perfusion times under various flow rates were all higher than those obtained for hepatic veins. At flow rates of 0.5 and 1.0 mL/min, in particular, the area under the curve (AUC) and maximal concentration (C max) of indinavir absorption were significantly different between portal veins and hepatic veins (p < 0.05), indicating considerable hepatic involvement in the presystemic extraction of indinavir. The system also has potential for use when estimating the hepatic extraction ratio (E H) and hepatic clearance (Cl H). Conclusion: This in vivo approach could provide another useful tool for improving our basic understanding of the absorption kinetics and hepatic metabolism of pharmaceuticals under development and facilitating the clinical application of such

Injectable DNA-architected nanoraspberry depot-mediated on-demand programmable refilling and release drug delivery

Drug delivery depots boosting a local concentration of therapeutic agents have received great attention in clinical applications due to their low occurrence of side effects and high therapeutic efficacy. However, once the payload is exhausted, the local drug concentration will be lower than the therapeutic window. To address this issue, an injectable double-strand deoxyribonucleic acid (DNA)-architected nanoraspberry depot (DNR-depot) was developed that can refill doxorubicin (Dox, an anticancer drug) from the blood and remotely control drug release on demand. The large porous surface on a uniform nanoraspberry (NR) filled covalently with DNA serves as a Dox sponge-like refilling reservoir, and the NR serves as a magnetic electrical absorber. Via the strong affinity between Dox and DNA molecules, the refilling process of Dox can be achieved on DNR-depot both in vitro and in vivo. Upon high-frequency magnetic field (HFMF) treatment, the remotely triggered release of Dox is actuated by the dissociation of Dox and DNA molecules, facilitating an approximately 800% improvement in drug concentration at the tumor site compared to free Dox injection alone. Furthermore, the cycles of refilling and release can be carried out more than 3 times in vivo within 21 days. The combination of refilling and HFMF-programmable Dox release in tumors via DNR-depot can effectively inhibit tumor growth for 30 days

Early Detection of Glutaric Aciduria Type I by Newborn Screening in Taiwan

Glutaric aciduria type 1 (GA1) is an inborn error of lysine and tryptophan metabolism. There is a lack of initial diagnostic signs of the disease, but late treatment often results in severe neurologic impairment. In this study, we analyzed the results of screening for GA1 in a Chinese population. Methods: Dry blood spots were obtained at about 3 days of age from 357,307 newborns and tested for elevation of glutaryl (C5DC)-carnitine by tandem mass spectroscopy. A second sample of blood spots was required from those cases with abnormal elevation of C5DC-carnitine (higher than the cut-off value) (recall). If the results remained abnormal, those cases were referred for confirmation of the diagnosis and treatment. Results: Between August 2001 and February 2005, there were 40 cases with C5DC-carnitine more than 0.13 μM (the cut-off value), from whom a second sample of blood spots was obtained (recall rate, 0.02%); two cases were confirmed to be affected by GA1. Because of the low positive prediction rate using this cut-off value, we elevated the cut-off value slightly. Between February 2005 and August 2006, there were eight cases with C5DC-carnitine more than 0.22 μM from whom a second sample of blood spots was obtained (recall rate, 0.01%); three cases were confirmed to be affected by GA1. All five cases with persistent elevation of C5DC-carnitine were referred and diagnosis was confirmed in each, giving an incidence of 1 in 71,461 newborns. There were no false negatives. Magnetic resonance imaging studies obtained from four cases showed frontotemporal atrophy at the time of diagnosis. Two cases were followed for over 1 year, and under treatment with dietary control and carnitine supplementation, both had normal development and neither exhibited a frank episode of encephalopathic crisis. Conclusion: With properly established cut-offs, GA1 can be successfully screened for in populations with a low incidence of the disease. Early treatment is likely to improve the outcome of cases discovered by screening