An apoptosis targeted stimulus with nanosecond pulsed electric fields (nsPEFs) in E4 squamous cell carcinoma

Stimuli directed towards activation of apoptosis mechanisms are an attractive approach to eliminate evasion of apoptosis, a ubiquitous cancer hallmark. In these in vitro studies, kinetics and electric field thresholds for several apoptosis characteristics are defined in E4 squamous carcinoma cells (SCC) exposed to ten 300 ns pulses with increasing electric fields. Cell death was >95% at the highest electric field and coincident with phosphatidylserine externalization, caspase and calpain activation in the presence and absence of cytochrome c release, decreases in Bid and mitochondria membrane potential (Δψm) without apparent changes reactive oxygen species levels or in Bcl2 and Bclxl levels. Bid cleavage was caspase-dependent (55–60%) and calcium-dependent (40–45%). Intracellular calcium as an intrinsic mechanism and extracellular calcium as an extrinsic mechanism were responsible for about 30 and 70% of calcium dependence for Bid cleavage, respectively. The results reveal electric field-mediated cell death induction and progression, activating pro-apoptotic-like mechanisms and affecting plasma membrane and intracellular functions, primarily through extrinsic-like pathways with smaller contributions from intrinsic-like pathways. Nanosecond second pulsed electric fields trigger heterogeneous cell death mechanisms in E4 SCC populations to delete them, with caspase-associated cell death as a predominant, but not an unaccompanied event

Malaria vectors of Timor-Leste

Background: The island of Timor lies at the south-eastern edge of Indonesia on the boundary of the Oriental and Australian faunal regions. The country of Timor-Leste, which occupies the eastern part of the island, is malarious but anopheline faunal surveys and malaria vector incrimination date back to the 1960 s. Over the last decade the malaria vectors of south-east Asia and the south-west Pacific have been intensely studied using molecular techniques that can confirm identification within complexes of isomorphic species. The aim of this study is to accurately identify the Anopheles fauna of Timor-Leste using these techniques

Two-dimensional nanosecond electric field mapping based on cell electropermeabilization

Nanosecond, megavolt-per-meter electric pulses cause permeabilization of cells to small molecules, programmed cell death (apoptosis) in tumor cells, and are under evaluation as a treatment for skin cancer. We use nanoelectroporation and fluorescence imaging to construct two-dimensional maps of the electric field associated with delivery of 15 ns, 10 kV pulses to monolayers of the human prostate cancer cell line PC3 from three different electrode configurations: single-needle, five-needle, and flat-cut coaxial cable. Influx of the normally impermeant fluorescent dye YO-PRO-1 serves as a sensitive indicator of membrane permeabilization. The level of fluorescence emission after pulse exposure is proportional to the applied electric field strength. Spatial electric field distributions were compared in a plane normal to the center axis and 15-20 μm from the tip of the center electrode. Measurement results agree well with models for the three electrode arrangements evaluated in this study. This live-cell method for measuring a nanosecond pulsed electric field distribution provides an operationally meaningful calibration of electrode designs for biological applications and permits visualization of the relative sensitivities of different cell types to nanoelectropulse stimulation. PACS Codes: 87.85.M

Water Use, Leaf Cooling and Carbon Assimilation Efficiency of Heat Resistant Common Beans Evaluated in Western Amazonia

In our study, we analyzed 30years of climatological data revealing the bean production risks for Western Amazonia. Climatological profiling showed high daytime and nighttime temperatures combined with high relative humidity and low vapor pressure deficit. Our understanding of the target environment allows us to select trait combinations for reaching higher yields in Amazonian acid soils. Our research was conducted using 64 bean lines with different genetic backgrounds. In high temperatures, we identified three water use efficiency typologies in beans based on detailed data analysis on gasometric exchange. Profligate water spenders and not water conservative accessions showed leaf cooling, and effective photosynthate partitioning to seeds, and these attributes were found to be related to higher photosynthetic efficiency. Thus, water spenders and not savers were recognized as heat resistant in acid soil conditions in Western Amazonia. Genotypes such as BFS 10, SEN 52, SER 323, different SEFs (SEF 73, SEF 10, SEF 40, SEF 70), SCR 56, SMR 173, and SMN 99 presented less negative effects of heat stress on yield. These genotypes could be suitable as parental lines for improving dry seed production. The improved knowledge on water-use efficiency typologies can be used for bean crop improvement efforts as well as further studies aimed at a better understanding of the intrinsic mechanisms of heat resistance in legumes

Development of a Mesoamerican intra-genepool genetic map for quantitative trait loci detection in a drought tolerant × susceptible common bean (Phaseolus vulgaris L.) cross

Drought is a major constraint to common bean (Phaseolus vulgaris L.) production, especially in developing countries where irrigation for the crop is infrequent. The Mesoamerican genepool is the most widely grown subdivision of common beans that include small red, small cream and black seeded varieties. The objective of this study was to develop a reliable genetic map for a Mesoamerican × Mesoamerican drought tolerant × susceptible cross and to use this map to analyze the inheritance of yield traits under drought and fully irrigated conditions over 3 years of experiments. The source of drought tolerance used in the cross was the cream-seeded advanced line BAT477 crossed with the small red variety DOR364 and the population was made up of recombinant inbred lines in the F5 generation. Quantitative trait loci were detected by composite interval mapping for the traits of overall seed yield, yield per day, 100 seed weight, days to flowering and days to maturity for each field environment consisting of two treatments (irrigated and rainfed) and lattice design experiments with three repetitions for a total of six environments. The genetic map based on amplified fragment length polymorphism and random amplified polymorphic DNA markers was anchored with 60 simple sequence repeat (SSR) markers and had a total map length of 1,087.5 cM across 11 linkage groups covering the whole common bean genome with saturation of one marker every 5.9 cM. Gaps for the genetic map existed on linkage groups b03, b09 and b11 but overall there were only nine gaps larger than 15 cM. All traits were inherited quantitatively, with the greatest number for seed weight followed by yield per day, yield per se, days to flowering and days to maturity. The relevance of these results for breeding common beans is discussed in particular in the light of crop improvement for drought tolerance in the Mesoamerican genepool

Controls on gut phosphatisation : the trilobites from the Weeks Formation Lagerstätte (Cambrian; Utah)

Despite being internal organs, digestive structures are frequently preserved in Cambrian Lagerstätten. However, the reasons for their fossilisation and their biological implications remain to be thoroughly explored. This is particularly true with arthropods--typically the most diverse fossilised organisms in Cambrian ecosystems--where digestive structures represent an as-yet underexploited alternative to appendage morphology for inferences on their biology. Here we describe the phosphatised digestive structures of three trilobite species from the Cambrian Weeks Formation Lagerstätte (Utah). Their exquisite, three-dimensional preservation reveals unique details on trilobite internal anatomy, such as the position of the mouth and the absence of a differentiated crop. In addition, the presence of paired pygidial organs of an unknown function is reported for the first time. This exceptional material enables exploration of the relationships between gut phosphatisation and the biology of organisms. Indeed, soft-tissue preservation is unusual in these fossils as it is restricted to the digestive structures, which indicates that the gut played a central role in its own phosphatisation. We hypothesize that the gut provided a microenvironment where special conditions could develop and harboured a source of phosphorus. The fact that gut phosphatization has almost exclusively been observed in arthropods could be explained by their uncommon ability to store ions (including phosphorous) in their digestive tissues. However, in some specimens from the Weeks Formation, the phosphatisation extends to the entire digestive system, suggesting that trilobites might have had some biological particularities not observed in modern arthropods. We speculate that one of them might have been an increased capacity for ion storage in the gut tissues, related to the moulting of their heavily-mineralised carapace

Design and test of an automated version of the modified Jebsen test of hand function using Microsoft Kinect

Abstract Background The present paper describes the design and evaluation of an automated version of the Modified Jebsen Test of Hand Function (MJT) based on the Microsoft Kinect sensor. Methods The MJT was administered twice to 11 chronic stroke subjects with varying degrees of hand function deficits. The test times of the MJT were evaluated manually by a therapist using a stopwatch, and automatically using the Microsoft Kinect sensor. The ground truth times were assessed based on inspection of the video-recordings. The agreement between the methods was evaluated along with the test-retest performance. Results The results from Bland-Altman analysis showed better agreement between the ground truth times and the automatic MJT time evaluations compared to the agreement between the ground truth times and the times estimated by the therapist. The results from the test-retest performance showed that the subjects significantly improved their performance in several subtests of the MJT, indicating a practice effect. Conclusions The results from the test showed that the Kinect can be used for automating the MJT

A randomised trial and economic evaluation of the effect of response mode on response rate, response bias, and item non-response in a survey of doctors

<p>Abstract</p> <p>Background</p> <p>Surveys of doctors are an important data collection method in health services research. Ways to improve response rates, minimise survey response bias and item non-response, within a given budget, have not previously been addressed in the same study. The aim of this paper is to compare the effects and costs of three different modes of survey administration in a national survey of doctors.</p> <p>Methods</p> <p>A stratified random sample of 4.9% (2,702/54,160) of doctors undertaking clinical practice was drawn from a national directory of all doctors in Australia. Stratification was by four doctor types: general practitioners, specialists, specialists-in-training, and hospital non-specialists, and by six rural/remote categories. A three-arm parallel trial design with equal randomisation across arms was used. Doctors were randomly allocated to: online questionnaire (902); simultaneous mixed mode (a paper questionnaire and login details sent together) (900); or, sequential mixed mode (online followed by a paper questionnaire with the reminder) (900). Analysis was by intention to treat, as within each primary mode, doctors could choose either paper or online. Primary outcome measures were response rate, survey response bias, item non-response, and cost.</p> <p>Results</p> <p>The online mode had a response rate 12.95%, followed by the simultaneous mixed mode with 19.7%, and the sequential mixed mode with 20.7%. After adjusting for observed differences between the groups, the online mode had a 7 percentage point lower response rate compared to the simultaneous mixed mode, and a 7.7 percentage point lower response rate compared to sequential mixed mode. The difference in response rate between the sequential and simultaneous modes was not statistically significant. Both mixed modes showed evidence of response bias, whilst the characteristics of online respondents were similar to the population. However, the online mode had a higher rate of item non-response compared to both mixed modes. The total cost of the online survey was 38% lower than simultaneous mixed mode and 22% lower than sequential mixed mode. The cost of the sequential mixed mode was 14% lower than simultaneous mixed mode. Compared to the online mode, the sequential mixed mode was the most cost-effective, although exhibiting some evidence of response bias.</p> <p>Conclusions</p> <p>Decisions on which survey mode to use depend on response rates, response bias, item non-response and costs. The sequential mixed mode appears to be the most cost-effective mode of survey administration for surveys of the population of doctors, if one is prepared to accept a degree of response bias. Online surveys are not yet suitable to be used exclusively for surveys of the doctor population.</p

Riding on the Coat-Tails of Traditional Cultural Expressions

Matters related to the protection of traditional cultural expressions (‘TCEs’) or expressions of folklore (‘EoFs’) are sensitive and intricate as a blend of legal, economic, philosophical and anthropological considerations jostle to capture their core features. This results in disparate views surrounding what should qualify as TCEs or EoFs, who should be considered their ‘owner’ (assuming that ownership per se is conceptually compatible with these items), which is the most appropriate legal protection regime and how broad their scope of protection should be. Drawing from these various accounts on TCEs, this article focuses on the interaction between TCEs and EoFs originating on the European continent and the European Union (‘EU’) trade mark legislation. Specifically, this article examines whether the limitations of the effects of trade mark rights and of the absolute grounds of refusal, as developed by the case law of the Court of Justice of the European Union, are effective in preserving the cohesion of TCEs. This article advances the thesis that registration of TCEs and EoFs as trade marks generates an imbalance between the rights of the trade mark owner and the defences available to others under the EU trade mark law framework. Furthermore, such an imbalance is likely to hinder the unfettered circulation of TCEs and undermine their original meaning. Lastly, in some cases, trade mark registration of TCEs contributes to their appropriation and misappropriation. The article concludes that, de lege ferenda, the direct exclusion of TCEs as eligible subject matter for trade mark registration is preferable to seeking a post factum remedy