Precision surveying using very long baseline interferometry

Radio interferometry measurements were used to measure the vector baselines between large microwave radio antennas. A 1.24 km baseline in Massachusetts between the 36 meter Haystack Observatory antenna and the 18 meter Westford antenna of Lincoln Laboratory was measured with 5 mm repeatability in 12 separate experiments. Preliminary results from measurements of the 3,928 km baseline between the Haystack antenna and the 40 meter antenna at the Owens Valley Radio Observatory in California are presented

Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during chemotherapy of acute myeloid leukemia

<p>Abstract</p> <p>Background</p> <p>The molecular changes <it>in vivo </it>in acute myeloid leukemia cells early after start of conventional genotoxic chemotherapy are incompletely understood, and it is not known if early molecular modulations reflect clinical response.</p> <p>Methods</p> <p>The gene expression was examined by whole genome 44 k oligo microarrays and 12 k cDNA microarrays in peripheral blood leukocytes collected from seven leukemia patients before treatment, 2–4 h and 18–24 h after start of chemotherapy and validated by real-time quantitative PCR. Statistically significantly upregulated genes were classified using gene ontology (GO) terms. Parallel samples were examined by flow cytometry for apoptosis by annexin V-binding and the expression of selected proteins were confirmed by immunoblotting.</p> <p>Results</p> <p>Significant differential modulation of 151 genes were found at 4 h after start of induction therapy with cytarabine and anthracycline, including significant overexpression of 31 genes associated with p53 regulation. Within 4 h of chemotherapy the BCL2/BAX and BCL2/PUMA ratio were attenuated in proapoptotic direction. FLT3 mutations indicated that non-responders (5/7 patients, 8 versus 49 months survival) are characterized by a unique gene response profile before and at 4 h. At 18–24 h after chemotherapy, the gene expression of p53 target genes was attenuated, while genes involved in chemoresistance, cytarabine detoxification, chemokine networks and T cell receptor were prominent. No signs of apoptosis were observed in the collected cells, suggesting the treated patients as a physiological source of pre-apoptotic cells.</p> <p>Conclusion</p> <p>Pre-apoptotic gene expression can be monitored within hours after start of chemotherapy in patients with acute myeloid leukemia, and may be useful in future determination of therapy responders. The low number of patients and the heterogeneity of acute myeloid leukemia limited the identification of gene expression predictive of therapy response. Therapy-induced gene expression reflects the complex biological processes involved in clinical cancer cell eradication and should be explored for future enhancement of therapy.</p

The Actin Cytoskeleton as a Barrier to Virus Infection of Polarized Epithelial Cells

Many diverse viruses target a polarized epithelial monolayer during host invasion. The polarized epithelium is adept at restricting the movement of solutes, ions, macromolecules, and pathogens across the mucosa. This regulation can be attributed to the presence of a junctional complex between adjacent cells and to an intricate network of actin filaments that provides support to the subapical membrane and stabilizes intercellular junctions. It is therefore not surprising that many viruses have evolved highly varied strategies to dissolve or modulate the cortical actin meshwork to promote infection of polarized cells. In this review, we will discuss the cell biological properties of the actin cytoskeleton in polarized epithelial cells and review the known mechanisms utilized by viral pathogens to manipulate this system in order to facilitate their infection

Cost-Effectiveness of New Cardiac and Vascular Rehabilitation Strategies for Patients with Coronary Artery Disease

Objective: Peripheral arterial disease (PAD) often hinders the cardiac rehabilitation program. The aim of this study was evaluating the relative cost-effectiveness of new rehabilitation strategies which include the diagnosis and treatment of PAD in patients with coronary artery disease (CAD) undergoing cardiac rehabilitation. Data Sources: Best-available evidence was retrieved from literature and combined with primary data from 231 patients. Methods: We developed a Markov decision model to compare the following treatment strategies: 1. cardiac rehabilitation only; 2. ankle-brachial index (ABI) if cardiac rehabilitation fails followed by diagnostic work-up and revascularization for PAD if needed; 3. ABI prior to cardiac rehabilitation followed by diagnostic work-up and revascularization for PAD if needed. Quality-adjusted-life years (QALYs), life-time costs (US $), incremental cost-effectiveness ratios (ICER), and gain in net health benefits (NHB) in QALY equivalents were calculated. A threshold willingness-to-pay of$75 000 was used. Results: ABI if cardiac rehabilitation fails was the most favorable strategy with an ICER of $44 251 per QALY gained and an incremental NHB compared to cardiac rehabilitation only of 0.03 QALYs (95$75 000/QALY. After sensitivity analysis, a combined cardiac and vascular rehabilitation program increased the success rate and would dominate the other two strategies with total lifetime costs of $30 246 a quality-adjusted life expectancy of 3.84 years, and an incremental NHB of 0.06 QALYs (95%CI:−0.24, 0.46) compared to current practice. The results were robust for other different input parameters. Conclusion: ABI measurement if cardiac rehabilitation fails followed by a diagnostic work-up and revascularization for PAD if needed are potentially cost-effective compared to cardiac rehabilitation only

Models of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major global health problem and is predicted to become the third most common cause of death by 2020. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition, and therefore there is a need to understand the pathophysiological mechanisms that could lead to new therapeutic strategies. The development of experimental models will help to dissect these mechanisms at the cellular and molecular level. COPD is a disease characterized by progressive airflow obstruction of the peripheral airways, associated with lung inflammation, emphysema and mucus hypersecretion. Different approaches to mimic COPD have been developed but are limited in comparison to models of allergic asthma. COPD models usually do not mimic the major features of human COPD and are commonly based on the induction of COPD-like lesions in the lungs and airways using noxious inhalants such as tobacco smoke, nitrogen dioxide, or sulfur dioxide. Depending on the duration and intensity of exposure, these noxious stimuli induce signs of chronic inflammation and airway remodelling. Emphysema can be achieved by combining such exposure with instillation of tissue-degrading enzymes. Other approaches are based on genetically-targeted mice which develop COPD-like lesions with emphysema, and such mice provide deep insights into pathophysiological mechanisms. Future approaches should aim to mimic irreversible airflow obstruction, associated with cough and sputum production, with the possibility of inducing exacerbations

Lipid metabolism in the newborn heart.

In recent years long chain fatty acids have been shown to be the principal metabolic fuel of the adult heart (1-3). For the tissues of the mam-malian fetus, however, carbohydrates rather than lipids appear to serve as the primary source of energy (4, 5). This difference in energy metabo-lism related to maturation suggested that the heart of the newborn, in contrast to that of the adult, might be unable to utilize long chain fatty acids and perforce must rely on glucose as the major substrate for energy production. After the observation that the rate of long chain fatty acid oxidation in tissues was enhanced by carnitine (y-trimethyl ammonium 18-hydroxy-butyrate) (6), intensive investigation was under-taken to elucidate the mechanism of action of this compound. Carnitine, a normal constituent of many tissues, is especially abundant in myocardium (7, 8). From the evidence obtained in several laboratories (9, 10), it has been proposed that carnitine effects a stimulation of long chain fatty acid oxidation by functioning as a carrier of acti-vated long chain fatty acyl groups from the extra-mitochondrial cytoplasm to the intramitochondrial sites of fatty acid oxidation. In this operation, a reversible transesterification between long chain fatty acyl CoA and carnitine has been demon-strated whereby long chain fatty acylcarnitine is formed. As acylcarnitine esters, the long chain fatty acids can be translocated across the mito-chondrial membrane, which is relatively imperme-able to acyl CoA molecules. The transesterifica-tion reaction is catalyzed by a long chain fatty acyl CoA-carnitine transferase, which has bee