A microchip optomechanical accelerometer

The monitoring of accelerations is essential for a variety of applications ranging from inertial navigation to consumer electronics. The basic operation principle of an accelerometer is to measure the displacement of a flexibly mounted test mass; sensitive displacement measurement can be realized using capacitive, piezo-electric, tunnel-current, or optical methods. While optical readout provides superior displacement resolution and resilience to electromagnetic interference, current optical accelerometers either do not allow for chip-scale integration or require bulky test masses. Here we demonstrate an optomechanical accelerometer that employs ultra-sensitive all-optical displacement read-out using a planar photonic crystal cavity monolithically integrated with a nano-tethered test mass of high mechanical Q-factor. This device architecture allows for full on-chip integration and achieves a broadband acceleration resolution of 10 \mu g/rt-Hz, a bandwidth greater than 20 kHz, and a dynamic range of 50 dB with sub-milliwatt optical power requirements. Moreover, the nano-gram test masses used here allow for optomechanical back-action in the form of cooling or the optical spring effect, setting the stage for a new class of motional sensors.Comment: 16 pages, 9 figure

A mathematical model for the onset of avascular tumor growth in response to the loss of p53 function

We present a mathematical model for the formation of an avascular tumor based on the loss by gene mutation of the tumor suppressor function of p53. The wild type p53 protein regulates apoptosis, cell expression of growth factor and matrix metalloproteinase, which are regulatory functions that many mutant p53 proteins do not possess. The focus is on a description of cell movement as the transport of cell population density rather than as the movement of individual cells. In contrast to earlier works on solid tumor growth, a model is proposed for the initiation of tumor growth. The central idea, taken from the mathematical theory of dynamical systems, is to view the loss of p53 function in a few cells as a small instability in a rest state for an appropriate system of differential equations describing cell movement. This instability is shown (numerically) to lead to a second, spatially inhomogeneous, solution that can be thought of as a solid tumor whose growth is nutrient diffusion limited. In this formulation, one is led to a system of nine partial differential equations. We show computationally that there can be tumor states that coexist with benign states and that are highly unstable in the sense that a slight increase in tumor size results in the tumor occupying the sample region while a slight decrease in tumor size results in its ultimate disappearance

Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia

Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (ISC) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A2B adenosine receptor (A2BAR), largely abolished the adenosine-stimulated chloride transport, suggesting that A2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Transplacental Passage of Interleukins 4 and 13?

The mechanisms by which prenatal events affect development of adult disease are incompletely characterized. Based on findings in a murine model of maternal transmission of asthma risk, we sought to test the role of the pro-asthmatic cytokines interleukin IL-4 and -13. To assess transplacental passage of functional cytokines, we assayed phosphorylation of STAT-6, a marker of IL-4 and -13 signaling via heterodimeric receptor complexes which require an IL-4 receptor alpha subunit. IL-4 receptor alpha−/− females were mated to wild-type males, and pregnant females were injected with supraphysiologic doses of IL-4 or 13. One hour after injection, the receptor heterozygotic embryos were harvested and tissue nuclear proteins extracts assayed for phosphorylation of STAT-6 by Western blot. While direct injection of embryos produced a robust positive control, no phosphorylation was seen after maternal injection with either IL-4 or -13, indicating that neither crossed the placenta in detectable amounts. The data demonstrate a useful approach to assay for transplacental passage of functional maternal molecules, and indicate that molecules other than IL-4 and IL-13 may mediate transplacental effects in maternal transmission of asthma risk

Comparison between the HCV IRES domain IV RNA structure and the Iron Responsive Element

Background: Serum ferritin and hepatic iron concentrations are frequently elevated in patients who are chronically infected with the hepatitis C virus (HCV), and hepatic iron concentration has been used to predict response to interferon therapy, but these correlations are not well understood. The HCV genome contains an RNA structure resembling an iron responsive element (IRE) in its internal ribosome entry site (IRES) structural domain IV (dIV). An IRE is a stem loop structure used to control the expression of eukaryotic proteins involved in iron homeostasis by either inhibiting ribosomal binding or protecting the mRNA from nuclease degradation. The HCV structure, located within the binding site of the 40S ribosomal subunit, might function as an authentic IRE or by an IRE-like mechanism.----- Results: Electrophoretic mobility shift assays showed that the HCV IRES domain IV structure does not interact with the iron regulatory protein 1 (IRP1) in vitro. Systematic HCV IRES RNA mutagenesis suggested that IRP1 cannot accommodate the shape of the wild type HCV IRES dIV RNA structure.----- Conclusion The HCV IRES dIV RNA structure is not an authentic IRE. The possibility that this RNA structure is responsible for the observed correlations between intracellular iron concentration and HCV infection parameters through an IRE-like mechanism in response to some other cellular signal remains to be tested

Proteinuria Is Associated with Quality of Life and Depression in Adults with Primary Glomerulopathy and Preserved Renal Function

BACKGROUND: There is no information about HRQoL, depression and associated factors in adult with nephrotic syndrome-associated glomerulopathy. METHODOLOGY/PRINCIPAL FINDINGS: Patients with primary glomerulopathy where compared with age and sex-matched hemodialysis patients and healthy subjects. Laboratory data, medical history, comorbid conditions were collected to evaluate factors associated with HRQoL (SF-36) and Depression (Hamilton Depression Rating Scale-HAMD). Glomerulopathy patients had low HRQoL in all eight SF-36 domains and two composite scores (physical and mental) in comparison with healthy subjects. HAMD score also was elevated and there was high depression prevalence. Overall, these data were comparable between glomerulopathy and hemodialysis patients. Using multiple regression analysis, factors associated with low HRQoL physical composite score were: last 24 h-urine protein excretion (-0.183, 95%CI -0.223 to -0.710 for each gram of proteinuria, p = 0.01) and cyclosporine use (-15.315, 95%CI -25.913 to -2.717, p = 0.03). Low HRQoL mental composite score was associated with last 24 h-urine protein excretion (-0.157, 95%CI -0.278 to -0.310 for each gram of proteinuria, p = 0.03) and HMAD score was independently associated with age (0.155, 95%CI 0.318 to 0.988 for each year, p = 0.04), female sex (4.788, 95%CI 1.005 to 8.620, 0 = 0.03), disease duration (0.074, 95%CI 0.021 to 0.128 for each month, p = 0.01) and last 24 h-urine protein excretion (0.050, 95%CI 0.018 to 0.085 for each gram of proteinuria, p = 0.02). CONCLUSIONS/SIGNIFICANCE: Nephrotic-syndrome associated glomerulopathy patients have low HRQoL and high prevalence of depression symptoms, comparable with those of hemodialysis patients. Last 24 h-protein excretion rate is independently associated with physical and mental HRQoL domains in addition to depression

Burnout among chiropractic practitioners: real or imagined an exploratory study protocol

Burnout is a psychological syndrome of emotional exhaustion, depersonalization and reduced personal accomplishment that has been found to exist in a significant number of healthcare and helping professionals. It imposes a significant societal burden by shortened practitioner lifespan, decreased efficiency, negative health outcomes and poorer levels of patient care. Theoretical models suggest that it appears to be the result of a complex interaction between job resources and job demands. It may be reasonable to conclude that Chiropractic professionals experience similar vocational demands and thus experience significant levels of occupational stress and subsequent burnout. However the data on burnout within the chiropractic profession is limited. It is possible that this results in significant negative outcomes on chiropractors and their patients. Therefore, the objective of this paper is to demonstrate the need to explore burnout in chiropractic practice and offer a research protocol for a potential study

Intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder characterized by (i) pruritus with onset in the second or third trimester of pregnancy, (ii) elevated serum aminotransferases and bile acid levels, and (iii) spontaneous relief of signs and symptoms within two to three weeks after delivery. ICP is observed in 0.4–1% of pregnancies in most areas of Central and Western Europe and North America, while in Chile and Bolivia as well as Scandinavia and the Baltic states roughly 5–15% and 1–2%, respectively, of pregnancies are associated with ICP. Genetic and hormonal factors, but also environmental factors may contribute to the pathogenesis of ICP. Intrahepatic cholestasis of pregnancy increases the risk of preterm delivery (19–60%), meconium staining of amniotic fluid (27%), fetal bradycardia (14%), fetal distress (22–41%), and fetal loss (0.4–4.1%), particularly when associated with fasting serum bile acid levels > 40 μmol/L. The hydrophilic bile acid ursodeoxycholic acid (10–20 mg/kg/d) is today regarded as the first line treatment for intrahepatic cholestasis of pregnancy. Delivery has been recommended in the 38th week when lung maturity has been established