A multi-dimensional view of transport-related social exclusion: A comparative study of Greater Perth and Sydney

Transport-related social exclusion is a complex issue. It can be studied from a variety of angles, be influenced by a number of factors, and affect diverse population groups. This study investigates transport-related social exclusion from a multi-dimensional view. Transport inequity was measured based on different development stages of a region using the Lorenz Curve and Gini index, and compared socio-economic characteristics, such as housing affordability, employment self-sufficiency, urban sprawl, and transport-mode share at different degrees of spatial aggregation. Two hierarchical spatial aggregation levels are used: (1) Sydney – Perth; (2) Inner – Middle – Outer sectors. Spatial gaps of transport-related social exclusion are identified for both cities and a number of policy implications are considered to provide suggestions to improve transport-related social inclusion in both cities

A DNA barcode reference library for Swiss butterflies and forester moths as a tool for species identification, systematics and conservation.

Butterfly monitoring and Red List programs in Switzerland rely on a combination of observations and collection records to document changes in species distributions through time. While most butterflies can be identified using morphology, some taxa remain challenging, making it difficult to accurately map their distributions and develop appropriate conservation measures. In this paper, we explore the use of the DNA barcode (a fragment of the mitochondrial gene COI) as a tool for the identification of Swiss butterflies and forester moths (Rhopalocera and Zygaenidae). We present a national DNA barcode reference library including 868 sequences representing 217 out of 224 resident species, or 96.9% of Swiss fauna. DNA barcodes were diagnostic for nearly 90% of Swiss species. The remaining 10% represent cases of para- and polyphyly likely involving introgression or incomplete lineage sorting among closely related taxa. We demonstrate that integrative taxonomic methods incorporating a combination of morphological and genetic techniques result in a rate of species identification of over 96% in females and over 98% in males, higher than either morphology or DNA barcodes alone. We explore the use of the DNA barcode for exploring boundaries among taxa, understanding the geographical distribution of cryptic diversity and evaluating the status of purportedly endemic taxa. Finally, we discuss how DNA barcodes may be used to improve field practices and ultimately enhance conservation strategies

Sensitive and Specific Fluorescent Probes for Functional Analysis of the Three Major Types of Mammalian ABC Transporters

An underlying mechanism for multi drug resistance (MDR) is up-regulation of the transmembrane ATP-binding cassette (ABC) transporter proteins. ABC transporters also determine the general fate and effect of pharmaceutical agents in the body. The three major types of ABC transporters are MDR1 (P-gp, P-glycoprotein, ABCB1), MRP1/2 (ABCC1/2) and BCRP/MXR (ABCG2) proteins. Flow cytometry (FCM) allows determination of the functional expression levels of ABC transporters in live cells, but most dyes used as indicators (rhodamine 123, DiOC2(3), calcein-AM) have limited applicability as they do not detect all three major types of ABC transporters. Dyes with broad coverage (such as doxorubicin, daunorubicin and mitoxantrone) lack sensitivity due to overall dimness and thus may yield a significant percentage of false negative results. We describe two novel fluorescent probes that are substrates for all three common types of ABC transporters and can serve as indicators of MDR in flow cytometry assays using live cells. The probes exhibit fast internalization, favorable uptake/efflux kinetics and high sensitivity of MDR detection, as established by multidrug resistance activity factor (MAF) values and Kolmogorov-Smirnov statistical analysis. Used in combination with general or specific inhibitors of ABC transporters, both dyes readily identify functional efflux and are capable of detecting small levels of efflux as well as defining the type of multidrug resistance. The assay can be applied to the screening of putative modulators of ABC transporters, facilitating rapid, reproducible, specific and relatively simple functional detection of ABC transporter activity, and ready implementation on widely available instruments

ZD6474 reverses multidrug resistance by directly inhibiting the function of P-glycoprotein

P-glycoprotein (P-gp) pumps multiple types of drugs out of the cell, using energy generated from ATP, and confers multidrug resistance (MDR) on cancer cells. ZD6474 is an orally active, selective inhibitor of the vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection tyrosine kinases. This study was designed to examine whether ZD6474 reverses P-gp-mediated MDR in cancer cells. Here, we show that clinically achievable levels of ZD6474 reverse P-gp-mediated MDR of the P-gp-overexpressing cell lines derived from breast cancer, MCF-7/adriamycin (ADR), and human oral epidermoid carcinoma, KBV200 to ADR, docetaxel, and vinorelbine. This ability to reverse the P-gp-mediated resistance is comparable to that of another frequently used reversal agent known as verapamil. ZD6474 itself moderately inhibits the proliferation of both MCF-7 and MCF-7/ADR cells with almost equal activity, but its inhibitory effect is not altered by co-incubation with verapamil, suggesting that ZD6474 may not be a substrate of P-gp. In addition, ZD6474 increases the intracellular accumulation of the P-gp substrate, rhodamine-123, and ADR, by enhancing the uptake and/or decreasing the efflux of these compounds in resistant cells. Further studies show that ZD6474 stimulates ATPase activity in a dose-dependent manner, which is required for the proper function of P-gp. In contrast, ZD6474 does not inhibit the expression level of P-gp. Our results suggest that ZD6474 is capable of reversing MDR in cancer cells by directly inhibiting the function of P-gp, a finding that may have clinical implications for ZD6474

Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey

Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans ( jawless fish) and of immunoglobulin gene segments in gnathostomes ( jawed vertebrates).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62870/1/nature02740.pd

Analyzing collaborative learning processes automatically

In this article we describe the emerging area of text classification research focused on the problem of collaborative learning process analysis both from a broad perspective and more specifically in terms of a publicly available tool set called TagHelper tools. Analyzing the variety of pedagogically valuable facets of learners’ interactions is a time consuming and effortful process. Improving automated analyses of such highly valued processes of collaborative learning by adapting and applying recent text classification technologies would make it a less arduous task to obtain insights from corpus data. This endeavor also holds the potential for enabling substantially improved on-line instruction both by providing teachers and facilitators with reports about the groups they are moderating and by triggering context sensitive collaborative learning support on an as-needed basis. In this article, we report on an interdisciplinary research project, which has been investigating the effectiveness of applying text classification technology to a large CSCL corpus that has been analyzed by human coders using a theory-based multidimensional coding scheme. We report promising results and include an in-depth discussion of important issues such as reliability, validity, and efficiency that should be considered when deciding on the appropriateness of adopting a new technology such as TagHelper tools. One major technical contribution of this work is a demonstration that an important piece of the work towards making text classification technology effective for this purpose is designing and building linguistic pattern detectors, otherwise known as features, that can be extracted reliably from texts and that have high predictive power for the categories of discourse actions that the CSCL community is interested in

Fitting the Elementary Rate Constants of the P-gp Transporter Network in the hMDR1-MDCK Confluent Cell Monolayer Using a Particle Swarm Algorithm

P-glycoprotein, a human multidrug resistance transporter, has been extensively studied due to its importance to human health and disease. In order to understand transport kinetics via P-gp, confluent cell monolayers overexpressing P-gp are widely used. The purpose of this study is to obtain the mass action elementary rate constants for P-gp's transport and to functionally characterize members of P-gp's network, i.e., other transporters that transport P-gp substrates in hMDR1-MDCKII confluent cell monolayers and are essential to the net substrate flux. Transport of a range of concentrations of amprenavir, loperamide, quinidine and digoxin across the confluent monolayer of cells was measured in both directions, apical to basolateral and basolateral to apical. We developed a global optimization algorithm using the Particle Swarm method that can simultaneously fit all datasets to yield accurate and exhaustive fits of these elementary rate constants. The statistical sensitivity of the fitted values was determined by using 24 identical replicate fits, yielding simple averages and standard deviations for all of the kinetic parameters, including the efflux active P-gp surface density. Digoxin required additional basolateral and apical transporters, while loperamide required just a basolateral tranporter. The data were better fit by assuming bidirectional transporters, rather than active importers, suggesting that they are not MRP or active OATP transporters. The P-gp efflux rate constants for quinidine and digoxin were about 3-fold smaller than reported ATP hydrolysis rate constants from P-gp proteoliposomes. This suggests a roughly 3∶1 stoichiometry between ATP hydrolysis and P-gp transport for these two drugs. The fitted values of the elementary rate constants for these P-gp substrates support the hypotheses that the selective pressures on P-gp are to maintain a broad substrate range and to keep xenobiotics out of the cytosol, but not out of the apical membrane

Subcutaneous dissociative conscious sedation (sDCS) an alternative method for airway regional blocks: a new approach

<p>Abstract</p> <p>Background</p> <p>Predicted difficult airway is a definite indication for awake intubation and spontaneous ventilation. Airway regional blocks which are commonly used to facilitate awake intubation are sometimes impossible or forbidden. On the other hand deep sedation could be life threatening in the case of compromised airway.</p> <p>The aim of this study is evaluating "Subcutaneous Dissociative Conscious Sedation" (sDCS) as an alternative method to airway regional blocks for awake intubation.</p> <p>Methods</p> <p>In this prospective, non-randomized study, 30 patients with predicted difficult airway (laryngeal tumors), who were scheduled for direct laryngoscopic biopsy (DLB), underwent "Subcutaneous Dissociative Conscious Sedation" (sDCS) exerted by intravenous fentanyl 3-4ug/kg and subcutaneous ketamine 0.6-0.7 mg/kg. The tongue and pharynx were anesthetized with lidocaine spray (4%<b>)</b>. 10 minutes after a subcutaneous injection of ketamine direct laryngoscopy was performed. Extra doses of fentanyl 50-100 ug were administered if the patient wasn't cooperative enough for laryngoscopy.</p> <p>Patients were evaluated for hemodynamic stability (heart rate and blood pressure), oxygen saturation (Spo₂), patient cooperation (obedient to open the mouth for laryngoscopy and the number of tries for laryngoscopy), patient comfort (remaining moveless), hallucination, nystagmus and salivation (need for aspiration before laryngoscopy).</p> <p>Results</p> <p>Direct laryngoscopy was performed successfully in all patients. One patient needed extra fentanyl and then laryngoscopy was performed successfully on the second try. All patients were cooperative enough during laryngoscopy. Hemodynamic changes more than 20% occurred in just one patient. Oxygen desaturation (spo₂< 90%) didn't occur in any patient.</p> <p>Conclusions</p> <p>Subcutaneous Dissociative Conscious Sedation (sDCS) as a new approach to airway is an acceptable and safe method for awake intubation and it can be suggested as a noninvasive substitute of low complication rate for regional airway blocks.</p> <p>Registration ID in IRCT</p> <p>IRCT201012075333N1</p

Evaluating the transport, health and economic impacts of new urban cycling infrastructure in Sydney, Australia – protocol paper

BACKGROUND: There are repeated calls to build better cycling paths in Australian cities if the proportion of people cycling is to increase. Yet the full range of transport, health, environmental and economic impacts of new cycling infrastructure and the extent to which observed changes are sustained is not well understood. The City of Sydney is currently building a new bicycle network, which includes a new bicycle path separated from road traffic in the south Sydney area. This protocol paper describes a comprehensive method to evaluate this new cycling infrastructure. METHOD: A cohort of residents within two kilometres of the new bicycle path will be surveyed at baseline before a new section of bicycle path is built, and again 12 and 24 months later to assess changes in travel behaviour, sense of community, quality of life and health behaviours. Residents in a comparable area of Sydney that will not get a new separated bike path will act as a comparison group. At baseline a sub-set of residents who volunteer will also take a small GPS device with them for one week to assess travel behaviour. DISCUSSION: This research should contribute to the advancement in evaluation and appraisal methods for cycling projects