bluuebunny/crossref_metadata_2025 huggingface dataset:
Compact DEMO, SlimCS: design progress and issues
Authors: Tobita K. , Nishio S. , Enoeda M. , Kawashima H. , Kurita G. , Tanigawa H. , Nakamura H. , Honda M. , Saito A. , Sato S. , Hayashi T. , Asakura N. , Sakurai S. , Nishitani T. , Ozeki T. , Ando M. , Ezato K. , Hamamatsu K. , Hirose T. , Hoshino T. , Ide S. , Inoue T. , Isono T. , Liu C. , Kakudate S. , Kawamura Y. , Mori S. , Nakamichi M. , Nishi H. , Nozawa T. , Ochiai K. , Ogiwara H. , Oyama N. , Sakamoto K. , Sakamoto Y. , Seki Y. , Shibama Y. , Shimizu K. , Suzuki S. , Takahashi K. , Tanigawa H. , Tsuru D. , Yamanishi T. , Yoshida T.
Published: July 2009

The design progress in a compact low aspect ratio (low A) DEMO reactor, ‘SlimCS’, and its design issues are reported. The design study focused mainly on the torus configuration including the blanket, divertor, materials and maintenance scheme. For continuity with the Japanese ITER-TBM, the blanket is based on a water-cooled solid breeder blanket. For vertical stability of the elongated plasma and high beta access, the blanket is segmented into replaceable and permanent blankets and a sector-wide conducting shell is arranged inbetween these blankets. A numerical calculation indicates that fuel self-sufficiency can be satisfied when the blanket interior is ideally fabricated. An allowable heat load to the divertor plate should be 8 MW m−2 or lower, which can be a critical constraint for determining a handling power of DEMO.
V3FIT: a code for three-dimensional equilibrium reconstruction
Authors: Hanson James D. , Hirshman Steven P. , Knowlton Stephen F. , Lao Lang L. , Lazarus Edward A. , Shields John M.
Published: July 2009

The V3FIT code for performing equilibrium reconstruction in three-dimensional plasmas is described. It is a modular code that has the potential to be coupled with a variety of equilibrium solvers to compute the externally measured response to an arbitrary internal state of the plasma. Singular-value decomposition is used to identify the dominant components of the plasma state that can be accurately determined by the reconstruction process and to guide the minimization of the χ2 variance-normalized mismatch between the measured and computed signals. Comparison of a tokamak plasma equilibrium computed by V3FIT and by the axisymmetric equilibrium reconstruction code EFIT is presented. V3FIT is used to reconstruct an axisymmetric DIII-D equilibrium using experimentally observed magnetic diagnostic signals. Three-dimensional reconstructions of stellarator plasma equilibria in the CTH device show the code behaves as expected in the presence of experimental noise, appropriately ignores near-singular directions in parameter space and robustly reconstructs equilibria starting from substantially different initial parameter values.
DrosophilaGoLoco-Protein Pins Is a Target of Gαo-mediated G Protein–coupled Receptor Signaling
Authors: Kopein Damir , Katanaev Vladimir L.
Published: July 2009

G protein–coupled receptors (GPCRs) transduce their signals through trimeric G proteins, inducing guanine nucleotide exchange on their Gα-subunits; the resulting Gα-GTP transmits the signal further inside the cell. GoLoco domains present in many proteins play important roles in multiple trimeric G protein–dependent activities, physically binding Gα-subunits of the Gαi/oclass. In most cases GoLoco binds exclusively to the GDP-loaded form of the Gα-subunits. Here we demonstrate that the poly-GoLoco–containing protein Pins of Drosophila can bind to both GDP- and GTP-forms of Drosophila Gαo. We identify Pins GoLoco domain 1 as necessary and sufficient for this unusual interaction with Gαo-GTP. We further pinpoint a lysine residue located centrally in this domain as necessary for the interaction. Our studies thus identify Drosophila Pins as a target of Gαo-mediated GPCR receptor signaling, e.g., in the context of the nervous system development, where Gαoacts downstream from Frizzled and redundantly with Gαito control the asymmetry of cell divisions.
REDOX Reaction at ASK1-Cys250 Is Essential for Activation of JNK and Induction of Apoptosis
Authors: Nadeau Philippe J. , Charette Steve J. , Landry Jacques
Published: July 2009

ASK1 cysteine oxidation allows JNK activation upon oxidative stress. Trx1 negatively regulates this pathway by reducing the oxidized cysteines of ASK1. However, precisely how oxidized ASK1 is involved in JNK activation and how Trx1 regulates ASK1 oxidoreduction remains elusive. Here, we describe two different thiol reductase activities of Trx1 on ASK1. First, in H2O2-treated cells, Trx1 reduces the various disulfide bonds generated between cysteines of ASK1 by a rapid and transient action. Second, in untreated cells, Trx1 shows a more stable thiol reductase activity on cysteine 250 (Cys250) of ASK1. After H2O2treatment, Trx1 dissociates from Cys250, which is not sufficient to activate the ASK1-JNK pathway. Indeed, in untreated cells, a Cys250 to alanine mutant of ASK1 (C250A), which cannot bind Trx1, does not constitutively activate JNK. On the other hand, in H2O2-treated cells, this mutant (C250A) fails to activate JNK and does not induce apoptosis, although it remains fully phosphorylated on Threonine 838 (Thr838) in its activation loop. Overall, our data show that Cys250 is essential for H2O2-dependent signaling downstream from ASK1 but at a step subsequent to the phosphorylation of ASK1 Thr838. They also clarify the thiol reductase function of Trx1 on ASK1 activity.
A Link between Aurora Kinase and Clp1/Cdc14 Regulation Uncovered by the Identification of a Fission Yeast Borealin-Like Protein
Authors: Bohnert K. Adam , Chen Jun-Song , Clifford Dawn M. , Vander Kooi Craig W. , Gould Kathleen L.
Published: July 2009

The chromosomal passenger complex (CPC) regulates various events in cell division. This complex is composed of a catalytic subunit, Aurora B kinase, and three nonenzymatic subunits, INCENP, Survivin, and Borealin. Together, these four subunits interdependently regulate CPC function, and they are highly conserved among eukaryotes. However, a Borealin homologue has never been characterized in the fission yeast, Schizosaccharomyces pombe . Here, we isolate a previously uncharacterized S. pombe protein through association with the Cdc14 phosphatase homologue, Clp1/Flp1, and identify it as a Borealin-like member of the CPC. Nbl1 (novel Borealin-like 1) physically associates with known CPC components, affects the kinase activity and stability of the S. pombe Aurora B homologue, Ark1, colocalizes with known CPC subunits during mitosis, and shows sequence similarity to human Borealin. Further analysis of the Clp1–Nbl1 interaction indicates that Clp1 requires CPC activity for proper accumulation at the contractile ring (CR). Consistent with this, we describe negative genetic interactions between mutant alleles of CPC and CR components. Thus, this study characterizes a fission yeast Borealin homologue and reveals a previously unrecognized connection between the CPC and the process of cytokinesis in S. pombe .
Reduced ATR or Chk1 Expression Leads to Chromosome Instability and Chemosensitization of Mismatch Repair–deficient Colorectal Cancer Cells
Authors: Jardim Melanie J. , Wang Qinhong , Furumai Ryohei , Wakeman Timothy , Goodman Barbara K. , Wang Xiao-Fan
Published: July 2009

Genomic instability in colorectal cancer is categorized into two distinct classes: chromosome instability (CIN) and microsatellite instability (MSI). MSI is the result of mutations in the mismatch repair (MMR) machinery, whereas CIN is often thought to be associated with a disruption in the APC gene. Clinical data has recently shown the presence of heterozygous mutations in ATR and Chk1 in human cancers that exhibit MSI, suggesting that those mutations may contribute to tumorigenesis. To determine whether reduced activity in the DNA damage checkpoint pathway would cooperate with MMR deficiency to induce CIN, we used siRNA strategies to partially decrease the expression of ATR or Chk1 in MMR-deficient colorectal cancer cells. The resultant cancer cells display a typical CIN phenotype, as characterized by an increase in the number of chromosomal abnormalities. Importantly, restoration of MMR proficiency completely inhibited induction of the CIN phenotype, indicating that the combination of partial checkpoint blockage and MMR deficiency is necessary to trigger CIN. Moreover, disruption of ATR and Chk1 in MMR-deficient cells enhanced the sensitivity to treatment with the commonly used colorectal chemotherapeutic compound, 5-fluorouracil. These results provide a basis for the development of a combination therapy for those cancer patients.
Regulation of Fission Yeast Myosin-II Function and Contractile Ring Dynamics by Regulatory Light-Chain and Heavy-Chain Phosphorylation
Authors: Sladewski Thomas E. , Previs Michael J. , Lord Matthew
Published: July 2009

We investigated the role of regulatory light-chain (Rlc1p) and heavy-chain phosphorylation in controlling fission yeast myosin-II (Myo2p) motor activity and function during cytokinesis. Phosphorylation of Rlc1p leads to a fourfold increase in Myo2p's in vitro motility rate, which ensures effective contractile ring constriction and function. Surprisingly, unlike with smooth muscle and nonmuscle myosin-II, RLC phosphorylation does not influence the actin-activated ATPase activity of Myo2p. A truncated form of Rlc1p lacking its extended N-terminal regulatory region (including phosphorylation sites) supported maximal Myo2p in vitro motility rates and normal contractile ring function. Thus, the unphosphorylated N-terminal extension of Rlc1p can uncouple the ATPase and motility activities of Myo2p. We confirmed the identity of one out of two putative heavy-chain phosphorylation sites previously reported to control Myo2p function and cytokinesis. Although in vitro studies indicated that phosphorylation at Ser-1444 is not needed for Myo2p motor activity, phosphorylation at this site promotes the initiation of contractile ring constriction.
Budding YeastSSD1-VRegulates Transcript Levels of Many Longevity Genes and Extends Chronological Life Span in Purified Quiescent Cells
Authors: Li Lihong , Lu Yong , Qin Li-Xuan , Bar-Joseph Ziv , Werner-Washburne Margaret , Breeden Linda L.
Published: July 2009

Ssd1 is an RNA-binding protein that affects literally hundreds of different processes and is polymorphic in both wild and lab yeast strains. We have used transcript microarrays to compare mRNA levels in an isogenic pair of mutant (ssd1-d) and wild-type (SSD1-V) cells across the cell cycle. We find that 15% of transcripts are differentially expressed, but there is no correlation with those mRNAs bound by Ssd1. About 20% of cell cycle regulated transcripts are affected, and most show sharper amplitudes of oscillation in SSD1-V cells. Many transcripts whose gene products influence longevity are also affected, the largest class of which is involved in translation. Ribosomal protein mRNAs are globally down-regulated by SSD1-V. SSD1-V has been shown to increase replicative life span¤ and we show that SSD1-V also dramatically increases chronological life span (CLS). Using a new assay of CLS in pure populations of quiescent prototrophs, we find that the CLS for SSD1-V cells is twice that of ssd1-d cells.
High-throughput minor histocompatibility antigen prediction
Authors: DeLuca David S. , Eiz-Vesper Britta , Ladas Nektarios , Khattab Barbara Anna-Maria , Blasczyk Rainer
Published: July 2009

Motivation: Minor histocompatibility antigens (mHags) are a diverse collection of MHC-bound peptides that have immunological implications in the context of allogeneic transplantation because of their differential presence in donor and host, and thus play a critical role in the induction of the detrimental graft-versus-host disease (GvHD) or in the development of the beneficial graft-versus-leukemia (GvL) effect. Therefore, the search for mHags has implications not only for preventing GvHD, but also for therapeutic applications involving leukemia-specific T cells. We have created a web-based system, named PeptideCheck, which aims to augment the experimental discovery of mHags using bioinformatic means. Analyzing peptide elution data to search for mHags and predicting mHags from polymorphism and protein databases are the core features.

Results: Comparison with known mHag data reveals that some but not all of the previously known mHags can be reproduced. By applying a system of filtering and ranking, we were able to produce an ordered list of potential mHag candidates in which HA-1, HA-3 and HA-8 occur in the best 0.25%. By combining single nucleotide polymorphism, protein, tissue expression and genotypic frequency data, together with antigen presentation prediction algorithms, we propose a list of the best peptide candidates which could potentially induce the GvL effect without causing GvFD.

Availability:  http://www.peptidecheck.org

Contact:  blasczyk.rainer@mh-hannover.de
Robustness considerations in selecting efficient two-color microarray designs
Authors: Latif A. H. M. Mahbub , Bretz Frank , Brunner Edgar
Published: July 2009

The main goal of microarray experiments is to select a small subset of genes that are differentially expressed among competing mRNA samples. For a given set of such mRNA samples, it is possible to consider a number of two-color cDNA microarray designs with a fixed number of arrays. Appropriate criteria can be used to select an efficient design from such a set of alternative experimental designs. In practice, however, microarray expression data often contain missing observations and the most efficient design (with complete observations) for a specific setup may not be efficient in the presence of missing observations. In this article, we propose two criteria to address the robustness of microarray designs against missing observations. We demonstrate the simultaneous use of efficiency and robustness criteria to select good microarray designs for both one-factor and multi-factor experiments.

Contact:  mlatif@isrt.ac.bd
Determining noisy attractors of delayed stochastic gene regulatory networks from multiple data sources
Authors: Dai Xiaofeng , Yli-Harja Olli , Ribeiro Andre S.
Published: July 2009

Motivation: Gene regulatory networks (GRNs) are stochastic, thus, do not have attractors, but can remain in confined regions of the state space, i.e. the ‘noisy attractors’, which define the cell type and phenotype.

Results: We propose a gamma-Bernoulli mixture model clustering algorithm (ΓBMM), tailored for quantizing states from gamma and Bernoulli distributed data, to determine the noisy attractors of stochastic GRN. ΓBMM uses multiple data sources, naturally selects the number of states and can be extended to other parametric distributions according to the number and type of data sources available. We apply it to protein and RNA levels, and promoter occupancy state of a toggle switch and show that it can be bistable, tristable or monostable depending on its internal noise level. We show that these results are in agreement with the patterns of differentiation of model cells whose pathway choice is driven by the switch. We further apply ΓBMM to a model of the MeKS module of Bacillus subtilis, and the results match experimental data, demonstrating the usability of ΓBMM.

Availability: Implementation software is available upon request.

Contact:  andre.sanchesribeiro@tut.fi; xiaofeng.dai@tut.fi

Supplementary information:  Supplementary data are available at Bioinformatics online.
HI: haplotype improver using paired-end short reads
Authors: Long Quan , MacArthur Daniel , Ning Zemin , Tyler-Smith Chris
Published: July 2009

Summary: We present a program to improve haplotype reconstruction by incorporating information from paired-end reads, and demonstrate its utility on simulated data. We find that given a fixed coverage, longer reads (implying fewer of them) are preferable.

Availability: The executable and user manual can be freely downloaded from ftp://ftp.sanger.ac.uk/pub/zn1/HI.

Contact:  ql2@sanger.ac.uk
Affy exon tissues: exon levels in normal tissues in human, mouse and rat
Authors: Pohl Andrew A. , Sugnet Charles W. , Clark Tyson A. , Smith Kayla , Fujita Pauline A. , Cline Melissa S.
Published: July 2009

Summary: Most genes in human, mouse and rat produce more than one transcript isoform. The Affymetrix Exon Array is a tool for studying the many processes that regulate RNA production, with separate probesets measuring RNA levels at known and putative exons. For insights on how exons levels vary between normal tissues, we constructed the Affy Exon Tissues track from tissue data published by Affymetrix. This track reports exon probeset intensities as log ratios relative to median values across the dataset and renders them as colored heat maps, to yield quick visual identification of exons with intensities that vary between normal tissues.

Availability: Affy Exon Tissues track is freely available under the UCSC Genome Browser (http://genome.ucsc.edu/) for human (hg18), mouse (mm8 and mm9), and rat (rn4).

Contact:  cline@soe.ucsc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
The fat years: the structure and profitability of the US banking sector in the pre-crisis period
Authors: Tregenna Fiona
Published: July 2009

Bank profitability in the USA was extremely high in the pre-crisis period, yet this did not prevent the current crisis. It has become clear that these profits were on shaky grounds and also that bank profits were not used to buttress banks’ capital bases. This paper analyses the effects of structure on profitability from 1994 to 2005. Bank-level panel data are used to test the effects of concentration, market power, bank size and operational efficiency on profitability. Efficiency is not found to be a strong determinant of profitability, suggesting that banks’ high profits during this period were not ‘earned’ through efficient performance. Robust evidence is found that concentration increases bank profitability. This holds even when the largest banks are excluded from the sample, suggesting that the relationship between concentration and profitability acts in a generalised structural way and that the higher profits arising from concentration are at the expense of the rest of the economy. The analysis points to various policy implications relevant to the current crisis, in particular in terms of the legitimacy of expectations of the restoration of pre-crisis profit rates and the need for much stronger regulation of the banking sector, especially in terms of the structure of the sector, pricing behaviour and use of profits.
Altruists are trusted based on non-verbal cues
Authors: Oda Ryo , Naganawa Takuya , Yamauchi Shinsaku , Yamagata Noriko , Matsumoto-Oda Akiko
Published: July 2009

The identification of altruists based on non-verbal cues might offer a solution to the problem of subtle cheating. Previous studies have indicated that the ability to discriminate altruists from non-altruists emerges during evolution. However, behavioural differences with regard to social exchanges involving altruists and non-altruists have not been studied. We investigated differences in responses to videotaped altruists and non-altruists with the Faith Game. Participants tended to entrust real money to altruists more than to non-altruists, providing strong evidence that cognitive adaptations evolve as counter-strategies to subtle cheating.
Aggressive use of Batesian mimicry by an ant-like jumping spider
Authors: Nelson Ximena J. , Jackson Robert R.
Published: July 2009

Batesian and aggressive mimicry are united by deceit: Batesian mimics deceive predators and aggressive mimics deceive prey. This distinction is blurred by
Myrmarachne melanotarsa
, an ant-like jumping spider (Salticidae). Besides often preying on salticids, ants are well defended against most salticids that might target them as potential prey. Earlier studies have shown that salticids identify ants by their distinctive appearance and avoid them. They also avoid ant-like salticids from the genus
Myrmarachne. Myrmarachne melanotarsa
is an unusual species from this genus because it typically preys on the eggs and juveniles of ant-averse salticid species. The hypothesis considered here is that, for
M. melanotarsa
, the distinction between Batesian and aggressive mimicry is blurred. We tested this by placing female
Menemerus
sp. and their associated hatchling within visual range of
M. melanotarsa
, its model, and various non-ant-like arthropods.
Menemerus
is an ant-averse salticid species. When seeing ants or ant mimics,
Menemerus
females abandoned their broods more frequently than when seeing non-ant-like arthropods or in control tests (no arthropods visible), as predicted by our hypothesis that resembling ants functions as a predatory ploy.
Atomic force microscopy of the morphology and mechanical behaviour of barnacle cyprid footprint proteins at the nanoscale
Authors: Phang In Yee , Aldred Nick , Ling Xing Yi , Huskens Jurriaan , Clare Anthony S. , Vancso G. Julius
Published: July 2009

Barnacles are a major biofouler of man-made underwater structures. Prior to settlement, cypris larvae explore surfaces by reversible attachment effected by a ‘temporary adhesive’. During this exploratory behaviour, cyprids deposit proteinaceous ‘footprints’ of a putatively adhesive material. In this study, footprints deposited by
Balanus amphitrite
cyprids were probed by atomic force microscopy (AFM) in artificial sea water (ASW) on silane-modified glass surfaces. AFM images obtained in air yielded better resolution than in ASW and revealed the fibrillar nature of the secretion, suggesting that the deposits were composed of single proteinaceous nanofibrils, or bundles of fibrils. The force curves generated in pull-off force experiments in sea water consisted of regions of gradually increasing force, separated by sharp drops in extension force manifesting a characteristic saw-tooth appearance. Following the relaxation of fibrils stretched to high strains, force–distance curves in reverse stretching experiments could be described by the entropic elasticity model of a polymer chain. When subjected to relaxation exceeding 500 ms, extended footprint proteins refolded, and again showed saw-tooth unfolding peaks in subsequent force cycles. Observed rupture and hysteresis behaviour were explained by the ‘sacrificial bond’ model. Longer durations of relaxation (>5 s) allowed more sacrificial bond reformation and contributed to enhanced energy dissipation (higher toughness). The persistence length for the protein chains (
L
P
) was obtained. At high elongation, following repeated stretching up to increasing upper strain limits, footprint proteins detached at total stretched length of 10 µm.
The ideal reporting interval for an epidemic to objectively interpret the epidemiological time course
Authors: Nishiura Hiroshi , Chowell Gerardo , Heesterbeek Hans , Wallinga Jacco
Published: July 2009

The reporting interval of infectious diseases is often determined as a time unit in the calendar regardless of the epidemiological characteristics of the disease. No guidelines have been proposed to choose the reporting interval of infectious diseases. The present study aims at translating coarsely reported epidemic data into the reproduction number and clarifying the ideal reporting interval to offer detailed insights into the time course of an epidemic. We briefly revisit the dispersibility ratio, i.e. ratio of cases in successive reporting intervals, proposed by Clare Oswald Stallybrass, detecting technical flaws in the historical studies. We derive a corrected expression for this quantity and propose simple algorithms to estimate the effective reproduction number as a function of time, adjusting the reporting interval to the generation time of a disease and demonstrating a clear relationship among the generation-time distribution, reporting interval and growth rate of an epidemic. Our exercise suggests that an ideal reporting interval is the mean generation time, so that the ratio of cases in successive intervals can yield the reproduction number. When it is impractical to report observations every mean generation time, we also present an alternative method that enables us to obtain straightforward estimates of the reproduction number for any reporting interval that suits the practical purpose of infection control.
Low-energy X-ray fluorescence microscopy opening new opportunities for bio-related research
Authors: Kaulich Burkhard , Gianoncelli Alessandra , Beran Alfred , Eichert Diane , Kreft Ivan , Pongrac Paula , Regvar Marjana , Vogel-Mikuš Katarina , Kiskinova Maya
Published: July 2009

Biological systems are unique matter with very complex morphology and highly heterogeneous chemical composition dominated by light elements. Discriminating qualitatively at the sub-micrometer level the lateral distribution of constituent elements, and correlating it to the sub-cellular biological structure, continues to be a challenge. The low-energy X-ray fluorescence microspectroscopy, recently implemented in TwinMic scanning transmission mode, has opened up new opportunities for mapping the distribution of the light elements, complemented by morphology information provided by simultaneous acquisition of absorption and phase contrast images. The important new information that can be obtained in bio-related research domains is demonstrated by two pilot experiments with specimens of interest for marine biology and food science. They demonstrate the potential to yield important insights into the structural and compositional enrichment, distribution and correlation of essential trace elements in the lorica of
Tintinnopsis radix
, and the lateral distribution of trace nutrients in the seeds of wheat
Triticum aestivum
.
The interaction of seasonal forcing and immunity and the resonance dynamics of malaria
Authors: Childs Dylan Z. , Boots Michael
Published: July 2009

Theory has emphasized the importance of both intrinsic factors such as host immunity and extrinsic drivers such as climate in determining disease dynamics. In particular, seasonality may lead to multi-annual cycles in prevalence, but the likelihood of this depends on the role of acquired immunity. Some diseases including malaria have immunity that falls between the classic susceptible–infectious–removed and susceptible–infectious–susceptible models. Here, we investigate the general conditions promoting the subharmonic resonance behaviour that may lead to multi-annual cycles in a general malaria dynamical model. Utilizing two complementary approaches to bifurcation analyses, we show that resonance is promoted by processes shortening the length of the infectious period and that subharmonic cycles are favoured in situations with strong seasonality in transmission but at intermediate levels of endemicity. We discuss the implications of our results for understanding prevalence patterns in long-term malaria datasets from Kenya that show multi-annual cycles and one from Thailand that does not and discuss the possible implications of treatment.
Hygromorphs: from pine cones to biomimetic bilayers
Authors: Reyssat E. , Mahadevan L.
Published: July 2009

We consider natural and artificial hygromorphs, objects that respond to environmental humidity by changing their shape. Using the pine cone as an example that opens when dried and closes when wet, we quantify the geometry, mechanics and dynamics of closure and opening at the cell, tissue and organ levels, building on our prior structural knowledge. A simple scaling theory allows us to quantify the hysteretic dynamics of opening and closing. We also show how simple bilayer hygromorphs of paper and polymer show similar behaviour that can be quantified via a theory which couples fluid transport in a porous medium and evaporative flux to mechanics and geometry. Our work unifies varied observations of natural hygromorphs and suggests interesting biomimetic analogues, which we illustrate using an artificial flower with a controllable blooming and closing response.
The atmosphere of heaven: the 1799 nitrous oxide researches reconsidered
Authors: Jay Mike
Published: July 2009

Thomas Beddoes's and Humphry Davy's accounts of the nitrous oxide experiments carried out at the Pneumatic Institution in 1799 include extravagant descriptions of its mind-altering effects. Many people, both at the time and subsequently, have considered these descriptions to be the product not of the gas but of its subjects’ overheated imaginations. To what extent were these effects ‘all in the mind’ of the experimenters? Modern understandings of nitrous oxide throw new light on this question; but it was also considered, and resolved in different ways, by Beddoes and Davy themselves.
Radicals, romantics and electrical showmen: placing galvanism at the end of the english enlightenment
Authors: Morus Iwan Rhys
Published: July 2009

This paper examines the shifting cultural place of galvanic experiments at the beginning of the nineteenth century. It surveys the ways in which political readings of galvanism by radicals and Tories during this period had an important role in determining the ways in which these kinds of experiment, and galvanism in general, were understood later in the century. The paper examines the attitudes of Humphry Davy, Thomas Beddoes and Giovanni Aldini to galvanism and suggests that there was a good deal of contemporary interpretative flexibility about the ways in which galvanic experimentation might be understood. It argues in particular that Humphry Davy's rejection of his earlier views on galvanism after his arrival at the Royal Institution can be regarded as emblematic of a broader shift in the culture of experimental natural philosophy at the end of the English Enlightenment.
Dr Thomas Beddoes: chemistry, medicine, and the perils of democracy
Authors: Levere Trevor H.
Published: July 2009

Beddoes lectured on chemistry at Oxford in the years that included the French Revolution, the Terror, and the outbreak of war with France, as well as the success in France of the chemical revolution. The very public dispute between Edmund Burke and Joseph Priestley meant that the latter's study of different kinds of air was politically tainted. Beddoes's democratic beliefs and his support for the new chemistry of Lavoisier meant that as chemist and physician he had to deal with complaints that he was potentially seditious and pro-French. His medical theories, allied to pneumatic chemistry and building on the work of Priestley, were accordingly suspect. In spite of that, he became the physician and friend to several members of the Lunar Society of Birmingham and to members of their family, and they in return became his patrons. His collaboration with James Watt was crucial for his development of pneumatic medicine. The full extent of Lunar patronage, and especially that of James Keir and Thomas Wedgwood, has hitherto not been recognized, but it was the concealed scale of that patronage that made possible the execution of Beddoes's ambitious programme of treatment and research.
Synthetic aperture diffraction tomography for three-dimensional imaging
Authors: Simonetti Francesco , Huang Lianjie
Published: July 2009

Tomography of complex three-dimensional objects with ultrasound or microwave has been a long-standing goal since the introduction of these technologies after World War II. While current state-of-the-art systems can provide high-resolution images of cylindrical objects characterized by a two-dimensional structure, the three-dimensional case remains an open challenge owing to current limitations of sensor technology and computer power. Here, this problem is addressed by means of a synthetic aperture technique that, while using hardware technology developed for two-dimensional problems, accounts for the complexity of three-dimensional scattering and leads to high-resolution three-dimensional reconstructions. In this paper, we present the theoretical formulation of this new approach and illustrate it by means of a numerical example.
DNA content and distribution in ancient feathers and potential to reconstruct the plumage of extinct avian taxa
Authors: Rawlence Nicolas J. , Wood Jamie R. , Armstrong Kyle N. , Cooper Alan
Published: July 2009

Feathers are known to contain amplifiable DNA at their base (calamus) and have provided an important genetic source from museum specimens. However, feathers in subfossil deposits generally only preserve the upper shaft and feather ‘vane’ which are thought to be unsuitable for DNA analysis. We analyse subfossil moa feathers from Holocene New Zealand rockshelter sites and demonstrate that both ancient DNA and plumage information can be recovered from their upper portion, allowing species identification and a means to reconstruct the appearance of extinct taxa. These ancient DNA sequences indicate that the distal portions of feathers are an untapped resource for studies of museum, palaeontological and modern specimens. We investigate the potential to reconstruct the plumage of pre-historically extinct avian taxa using subfossil remains, rather than assuming morphological uniformity with closely related extant taxa. To test the notion of colour persistence in subfossil feathers, we perform digital comparisons of feathers of the red-crowned parakeet (
Cyanoramphus novaezelandiae novaezelandiae
) excavated from the same horizons as the moa feathers, with modern samples. The results suggest that the coloration of the moa feathers is authentic, and computer software is used to perform plumage reconstructions of moa based on subfossil remains.
An improved rapid quantitative detection and identification method for a wide range of fungi
Authors: Soeta Nobutoshi , Terashima Masanori , Gotoh Mitsukazu , Mori Shuichi , Nishiyama Kyoko , Ishioka Ken , Kaneko Hisatoshi , Suzutani Tatsuo
Published: July 2009

To develop a rapid and quantitative diagnostic technique for the detection and identification of a wide range of fungi, an improved molecular method based on real-time PCR and the analysis of its products that targets the internal transcribed spacer (ITS) 2 region was established. The real-time PCR could quantitatively and specifically detect the ITS2 region from all 24 tested pathogenic fungal species at between 101 and 107 copies per test without amplification of bacterial or human DNA. The sequences of the primer-binding sites are conserved in the registered sequences of 34 other pathogenic fungal species, suggesting that the PCR would also detect these species. The hyperpolymorphic nature of the ITS2 region between fungal species in terms of length and nucleotide sequence provided valuable information for the determination of species. By labelling the 5′ end of the reverse primer with NED fluorescent dye, the fragment lengths of the real-time PCR products and their 3′-terminal fragments, derived using restriction enzyme ScrFI digestion, were easily evaluated by capillary electrophoresis. Using this analysis, the number and species of fungi present in samples could be estimated. Moreover, sequence analysis of the real-time PCR products could accurately determine species in samples containing a single species. This diagnostic technique can estimate a wide range of fungi from various clinical samples within 1 day and accurately identify them in 2 days. Quantitative results for fungal titre in samples can also provide useful information for understanding the progression of disease and the efficacy of antifungal chemotherapy.
Rapid diagnosis of candidaemia by real-time PCR detection of Candida DNA in blood samples
Authors: Wellinghausen Nele , Siegel Dunja , Winter Juliane , Gebert Susanne
Published: July 2009

This study prospectively evaluated an 18S rRNA gene-targeted real-time PCR approach in comparison with standard blood culture (BC) diagnostics for rapid diagnosis of candidaemia in a large study population of 384 patients, including 902 whole blood samples from 468 infectious episodes (IEs) of 329 adults and 55 children with haematological malignancies and various forms of immunodeficiency, and intensive care unit patients. Seven out of eight BC-proven cases (87.5 %) of candidaemia and seven out of twelve BC-positive samples (58.3 %) were positive by the Candida-specific PCR. A positive PCR result was also obtained for 28/460 BC-negative samples from IEs, including 8 patients with culture-confirmed Candida infection at primary sterile body sites. Of the PCR-positive, culture-negative patients, more than 50 % received systemic antifungal therapy. In 432/460 BC-negative IEs, the Candida specific-PCR was negative, resulting in a negative predictive value of 99.8 %. In conclusion, the Candida specific-PCR approach facilitates rapid detection of Candida DNA in blood samples of patients at risk of candidaemia within a few hours. Although standard BC diagnostics appear to remain indispensable for the detection of all cases of candidaemia, this PCR assay allowed the detection of candidaemia at a mean of 3 days earlier than BC diagnostics. Thus, it enables earlier antifungal therapy for patients with suspected candidaemia and may prevent further complications.
Guidelines for interpretation of 16S rRNA gene sequence-based results for identification of medically important aerobic Gram-positive bacteria
Authors: Woo Patrick C. Y. , Teng Jade L. L. , Wu Jeff K. L. , Leung Fion P. S. , Tse Herman , Fung Ami M. Y. , Lau Susanna K. P. , Yuen Kwok-yung
Published: July 2009

This study is believed to be the first to provide guidelines for facilitating interpretation of results based on full and 527 bp 16S rRNA gene sequencing and MicroSeq databases used for identifying medically important aerobic Gram-positive bacteria. Overall, full and 527 bp 16S rRNA gene sequencing can identify 24 and 40 % of medically important Gram-positive cocci (GPC), and 21 and 34 % of medically important Gram-positive rods (GPR) confidently to the species level, whereas the full-MicroSeq and 500-MicroSeq databases can identify 15 and 34 % of medically important GPC and 14 and 25 % of medically important GPR confidently to the species level. Among staphylococci, streptococci, enterococci, mycobacteria, corynebacteria, nocardia and members ofBacillusand related taxa (Paenibacillus,Brevibacillus,GeobacillusandVirgibacillus), the methods and databases are least useful for identification of staphylococci and nocardia. Only 0–2 and 2–13 % of staphylococci, and 0 and 0–10 % of nocardia, can be confidently and doubtfully identified, respectively. However, these methods and databases are most useful for identification ofBacillusand related taxa, with 36–56 and 11–14 % ofBacillusand related taxa confidently and doubtfully identified, respectively. A total of 15 medically important GPC and 18 medically important GPR that should be confidently identified by full 16S rRNA gene sequencing are not included in the full-MicroSeq database. A total of 9 medically important GPC and 21 medically important GPR that should be confidently identified by 527 bp 16S rRNA gene sequencing are not included in the 500-MicroSeq database. 16S rRNA gene sequence results of Gram-positive bacteria should be interpreted with basic phenotypic tests results. Additional biochemical tests or sequencing of additional gene loci are often required for definitive identification. To improve the usefulness of the MicroSeq databases, bacterial species that can be confidently identified by 16S rRNA gene sequencing but are not found in the MicroSeq databases should be included.
Pro-apoptotic effect of the landrace Bangla Mahoba of Piper betle on Leishmania donovani may be due to the high content of eugenol
Authors: Misra Pragya , Kumar Awanish , Khare Prashant , Gupta Swati , Kumar Nikhil , Dube Anuradha
Published: July 2009

In the absence of effective and safe treatment for visceral leishmaniasis or Kala-azar – a devastating parasitic disease caused byLeishmania donovani– the search for anti-leishmanial agents from natural resources in common use is imperative. Recently, the comparativein vitroanti-leishmanial activity of methanolic extracts from two landraces ofPiper betle–P. betlelandrace Bangla Mahoba (PB-BM) andP. betlelandrace Kapoori Vellaikodi (PB-KV) – has been reported. Here, the putative pathway responsible for death induced by the effective extract of PB-BM methanolic extract in promastigotes, as well as the intracellular amastigote form ofL. donovani, was assessed using various biochemical approaches. It was found that PB-BM was capable of selectively inhibiting both stages ofLeishmaniaparasites by accelerating apoptotic events by generation of reactive oxygen species targeting the mitochondria without any cytotoxicity towards macrophages. The study was extended to determine the presence or absence of activity of the methanolic extract of PB-BM and PB-KV on the basis of differences in essential oil composition present in the extract assessed by GC and MS. The essential oil from PB-BM was found to be rich in eugenol compared with that from PB-KV. The anti-leishmanial efficacy of PB-BM methanolic extract mediated through apoptosis is probably due to the higher content of eugenol in the active landrace. This observation emphasizes the need to extend studies related to traditional medicines from bioactive plants below the species level to the gender/landrace level for better efficacy and reproducibility.
Role of persisters and small-colony variants in antibiotic resistance of planktonic and biofilm-associated Staphylococcus aureus: an in vitro study
Authors: Singh Rachna , Ray Pallab , Das Anindita , Sharma Meera
Published: July 2009

The presence of persister cells and small-colony variants (SCVs) has been associated with enhanced antibiotic resistance of many organisms in biofilms. This study investigated whether persisters and/or SCVs contribute to the antibiotic resistance ofStaphylococcus aureusbiofilms. A detailed dose-dependent killing of biofilms and planktonic cells with five antibiotics (oxacillin, cefotaxime, amikacin, ciprofloxacin and vancomycin) was analysed by treating them with each antibiotic at a concentration of 0–100 μg ml−1at 37 °C for 48 h. The killing of biofilm cells by all of the antibiotics showed the presence of persister cells – most cells in the population died, leaving a fraction that persisted, even at higher concentrations of the antibiotics. These persisters represented a transient resistant phenotype and reverted to a killing curve resembling that of the wild-type parent upon re-exposure to the antibiotics. SCVs were observed in biofilms only after treatment with ciprofloxacin, and these SCVs were of a transient nature. The treatment of planktonic cells with oxacillin, cefotaxime, ciprofloxacin and vancomycin killed the entire population and no persisters were detected. Transient SCVs, observed in planktonic cells following exposure to these antibiotics, were killed at higher antibiotic concentrations. The treatment of planktonic cells with amikacin yielded a small subpopulation of survivors that included persisters (at numbers significantly lower than for the biofilms) and highly resistant, stable SCVs with an increased biofilm-forming capacity in comparison with the wild-type parent. Thus the high resistance ofS. aureusbiofilms to multiple unrelated antibiotics is largely dependent on the presence of persister cells. Biofilms harbour a large number of persisters in comparison with planktonic cultures, which either do not harbour persisters or harbour only a small number. SCVs, although not specifically associated withS. aureusbiofilms, have an increased biofilm-forming capacity and this may explain the frequent isolation of SCVs from biofilm-associated infections. The intrinsic resistance of these variants may in turn contribute to the enhanced antibiotic resistance of the biofilms thus formed.
Reduced susceptibility to amoxicillin of oral streptococci following amoxicillin exposure
Authors: Chardin H. , Yasukawa K. , Nouacer N. , Plainvert C. , Aucouturier P. , Ergani A. , Descroix V. , Toledo-Arenas R. , Azerad J. , Bouvet A.
Published: July 2009

As antibiotic pressure often triggers bacterial resistance, the use of short-duration therapies is increasingly recommended. The objective of the present study was to evaluate both the clinical efficiency and the impact on oral streptococci of a 3 day versus a 7 day amoxicillin therapy for odontogenic infection requiring tooth extraction. On day 0, patients were randomly assigned to a 3 day or 7 day amoxicillin treatment. The tooth was extracted on day 2 and the post-operative follow-up was carried out on day 9. Oral flora was collected on days 0, 9 and 30, and the susceptibility of the streptococci to amoxicillin was determined. The results showed that treatment with amoxicillin for 3 or 7 days had a similar clinical efficiency, and also induced similar selection of oral streptococci with reduced susceptibility to amoxicillin, suggesting that the selection of strains with reduced susceptibility to amoxicillin is a rapid phenomenon, appearing even with short-duration therapies.
Novel peptide therapeutics for treatment of infections
Authors: Oyston P. C. F. , Fox M. A. , Richards S. J. , Clark G. C.
Published: July 2009

As antibiotic resistance increases worldwide, there is an increasing pressure to develop novel classes of antimicrobial compounds to fight infectious disease. Peptide therapeutics represent a novel class of therapeutic agents. Some, such as cationic antimicrobial peptides and peptidoglycan recognition proteins, have been identified from studies of innate immune effector mechanisms, while others are completely novel compounds generated in biological systems. Currently, only selected cationic antimicrobial peptides have been licensed, and only for topical applications. However, research using new approaches to identify novel antimicrobial peptide therapeutics, and new approaches to delivery and improving stability, will result in an increased range of peptide therapeutics available in the clinic for broader applications.
JBrowse: A next-generation genome browser
Authors: Skinner Mitchell E. , Uzilov Andrew V. , Stein Lincoln D. , Mungall Christopher J. , Holmes Ian H.
Published: July 2009

We describe an open source, portable, JavaScript-based genome browser, JBrowse, that can be used to navigate genome annotations over the web. JBrowse helps preserve the user's sense of location by avoiding discontinuous transitions, instead offering smoothly animated panning, zooming, navigation, and track selection. Unlike most existing genome browsers, where the genome is rendered into images on the webserver and the role of the client is restricted to displaying those images, JBrowse distributes work between the server and client and therefore uses significantly less server overhead than previous genome browsers. We report benchmark results empirically comparing server- and client-side rendering strategies, review the architecture and design considerations of JBrowse, and describe a simple wiki plug-in that allows users to upload and share annotation tracks.