bluuebunny/crossref_metadata_2025 huggingface dataset:
Milking efficiency of swingover herringbone parlours in pasture-based dairy systems
Authors: Edwards J Paul , O'Brien Bernadette , Lopez-Villalobos Nicolas , Jago Jenny G
Published: September 2013

The objective of this study was to collect and analyse milking data from a sample of commercial farms with swingover herringbone parlours to evaluate milking efficiency over a range of parlour sizes (12–32 milking units). Data were collected from 19 farms around the Republic of Ireland equipped with electronic milk metres and herd management software that recorded data at individual milking sessions. The herd management software on each farm was programmed to record similar data for each milking plant type. Variables recorded included cow identification, milking date, identification time, cluster-attachment time, cluster/unit number, milk yield, milking duration, and average milk flow rate. Calculations were performed to identify efficiency benchmarks such as cow throughput (cows milked per h), milk harvesting efficiency (kg of milk harvested per h) and operator efficiency (cows milked per operator per h). Additionally, the work routine was investigated and used to explain differences in the benchmark values. Data were analysed using a linear mixed model that included the fixed effects of season-session (e.g. spring-AM), parlour size and their interaction, and the random effect of farm. Additionally, a mathematical model was developed to illustrate the potential efficiency gains that could be achieved by implementing a maximum milking time (i.e. removing the clusters at a pre-set time regardless of whether the cow had finished milking or not). Cow throughput and milk harvesting efficiency increased with increasing parlour size (12 to 32 units), with throughput ranging from 42 to 129 cows/h and milk harvesting efficiency from 497 to 1430 kg/h (1–2 operators). Greater throughput in larger parlours was associated with a decrease in operator idle time. Operator efficiency was variable across farms and probably dependent on milking routines in use. Both of these require consideration when sizing parlours so high levels of operator efficiency as well as cow throughput can be achieved simultaneously. The mathematical model indicated that application of a maximum milking time within the milking process could improve cow throughput (66% increase in an 18-unit parlour when truncating the milking time of 20% of cows). This could allow current herd milking durations to be maintained as herd size increases.
Ultraviolet emission from high-quality crystalline ultra-long AlN whiskers
Authors: Zuo Sibin , Zhang Haiyun , Wang Jun , Wang Wenjun
Published: September 2013

We report here the fabrication and characterization of ultra-long AlN whiskers by physical vapor transport method. The obtained whiskers are 1–3 µm in diameter and up to millimeters in length. The whiskers grow along the [0001] crystallographic direction and are well crystallized. They exhibit a strong ultraviolet emission at 345 nm, the shortest wavelength reported in AlN whiskers or nanowires. Our results indicate that these large scales of AlN whiskers are less contaminated by oxygen and other impurities compared with the previously reported ones, which may find wide applications in fabricating ultraviolet optoelectronic devices.
Synchrotron X-Ray Microanalysis and Imaging of Synthetic Biological Calcium Carbonate in Comparison With Archaeological Samples Originating from the Large Cave of Arcy-sur-Cure (28000-24500 BP, Yonne, France)
Authors: Chalmin Emilie , Reiche Ina
Published: September 2013

Biosynthetic calcite samples were investigated using combined synchrotron X-ray microspectroscopy mapping. These samples were prepared with bacteria isolated from the Large cave of Arcy-sur-Cure in which prehistoric figures are masked by an opaque calcite layer. The biotic or abiotic origin of this layer is the issue of the present work. As previously known, a large community of bacteria may be involved in the CaCO3 formation in caves. A mixture of calcite/vaterite was obtained from bacteria isolated from the cave. Therefore, we can offer conclusions on their calcifying capability. The rare presence of vaterite in cave environments may be treated as a marker of biotic carbonate formations. Moreover, an amorphous calcium phosphate phase was present in the form of a calcite/vaterite mixture in the biotic model samples. This mixture of phases could be used as a tracer of the biotic process of CaCO3 formation. These biotic tracer phases were not identified using the applied analytical methods in the natural samples taken from the opaque calcite layers that covered the prehistoric figures of the Large cave. In this case, based on the obtained results, the biotic calcite formation process is likely to be considered as an undetectable effect at minimum.
Introduction: Portuguese Society for Microscopy
Authors: Alves de Matos A.P.
Published: September 2013

SPMicros was founded in 1966 as Sociedade Portuguesa de Microscopia and since then has promoted Congresses dedicated to microscopy each year. For many of us this was the place where we delivered our first communications and received feedback by a panel of senior scientists devoted to the promotion of scientific quality; the Society was thus crucial to the rise of more than one generation of microscopists. In 2005 the Society's designation was changed to the “Portuguese Society for Microscopy” aka SPMicros, and incorporated a strong and growing group dedicated to materials science as well as to the life sciences.
APPROXIMATING THE KOHLRAUSCH FUNCTION BY SUMS OF EXPONENTIALS
Authors: ZHONG MIN , LOY R. J. , ANDERSSEN R. S.
Published: September 2013

The Kohlrausch functions $\exp (- {t}^{\beta } )$, with $\beta \in (0, 1)$, which are important in a wide range of physical, chemical and biological applications, correspond to specific realizations of completely monotone functions. In this paper, using nonuniform grids and midpoint estimates, constructive procedures are formulated and analysed for the Kohlrausch functions. Sharper estimates are discussed to improve the approximation results. Numerical results and representative approximations are presented to illustrate the effectiveness of the proposed method.
A EUROPEAN OPTION GENERAL FIRST-ORDER ERROR FORMULA
Authors: LEDUC GUILLAUME
Published: September 2013

We study the value of European security derivatives in the Black–Scholes model when the underlying asset $\xi $ is approximated by random walks ${\xi }^{(n)} $. We obtain an explicit error formula, up to a term of order $ \mathcal{O} ({n}^{- 3/ 2} )$, which is valid for general approximating schemes and general payoff functions. We show how this error formula can be used to find random walks ${\xi }^{(n)} $ for which option values converge at a speed of $ \mathcal{O} ({n}^{- 3/ 2} )$.
Pioneers in Optics: James Bradley and August Köhler
Authors: Davidson Michael W.
Published: September 2013

James Bradley was an English astronomer most famous for his discovery of the aberration of starlight. The finding was an important piece of evidence supporting Copernicus's theory that the Earth moved around the sun and also provided an alternative way to estimate the velocity of light.
Certified Electron Microscopy Technologist
Authors: Kysar Patricia , Cohen-Gould Leona
Published: September 2013

The acronym for “certified electron microscopy technologist” is CEMT, and these letters designate the bearer as having passed the written and practical exams necessary to become “certified”! The acronym was approved by the MSA Council to more firmly provide a professional identification of certification in the area of transmission electron microscopy (TEM) of biological tissue. A CEMT may use these initials after his or her name for as long as the certification remains valid (for example, Jane Doe, AA, BS, CEMT).
Electronic density response to molecular geometric changes from explicit electronic susceptibility calculations
Authors: Ihrig Arvid Conrad , Scherrer Arne , Sebastiani Daniel
Published: September 2013

We present a first principles approach to compute the response of the molecular electronic charge distribution to a geometric distortion. The scheme is based on an explicit representation of the linear electronic susceptibility. The linear electronic susceptibility is a tensor quantity which directly links the first-order electronic response density to the perturbation potential, without requiring self-consistency. We first show that the electronic susceptibility is almost invariant to small changes in the molecular geometry. We then compute the dipole moments from the response density induced by the geometrical changes. We verify the accuracy by comparing the results to the corresponding values obtained from the self-consistent calculations of the ground-state densities in both geometries.
Strain engineering of magnetic states of vacancy-decorated hexagonal boron nitride
Authors: Ouyang Bin , Song Jun
Published: September 2013

Nanomaterials with tunable magnetic states play a significant role in the development of next-generation spintronic devices. In this paper, we examine the role of biaxial strain on the electronic properties of vacancy-decorated hexagonal boron nitride (h-BN) monolayers using density functional theory calculations. We found that the strain can lead to switching of the magnetic state for h-BN monolayers with boron vacancy or divacancy. Our findings promise an effective route for the operation of low-dimensional spintronic devices.
Molecular dynamics study of CO2 hydrate dissociation: Fluctuation-dissipation and non-equilibrium analysis
Authors: English Niall J. , Clarke Elaine T.
Published: September 2013

Equilibrium and non-equilibrium molecular dynamics (MD) simulations have been performed to investigate thermal-driven break-up of planar CO2 hydrate interfaces in liquid water at 300–320 K. Different guest compositions, at 85%, 95%, and 100% of maximum theoretical occupation, led to statistically-significant differences in the observed initial dissociation rates. The melting temperatures of each interface were estimated, and dissociation rates were observed to be strongly dependent on temperature, with higher dissociation rates at larger over-temperatures vis-à-vis melting. A simple coupled mass and heat transfer model developed previously was applied to fit the observed dissociation profiles, and this helps to identify clearly two distinct régimes of break-up; a second well-defined region is essentially independent of composition and temperature, in which the remaining nanoscale, de facto two-dimensional system's lattice framework is intrinsically unstable. From equilibrium MD of the two-phase systems at their melting point, the relaxation times of the auto-correlation functions of fluctuations in number of enclathrated guest molecules were used as a basis for comparison of the variation in the underlying, non-equilibrium, thermal-driven dissociation rates via Onsager's hypothesis, and statistically significant differences were found, confirming the value of a fluctuation-dissipation approach in this case.
Nanoparticle size and morphology control using ultrafast laser induced forward transfer of Ni thin films
Authors: Murphy Ryan D. , Abere Michael J. , Schrider Keegan J. , Torralva Ben , Yalisove Steven M.
Published: September 2013

We have developed a nanoparticle (NP) printing technique using Ni thin film lift-off from glass substrates after ultrafast irradiation in air. Unique interactions of ultrafast laser pulses with thin films allow for control over NP faceting and size distributions. Control is achieved by changing the laser fluence, film thickness, and film-substrate distance. We demonstrate 20 nm Ni film removal from substrates and rapid NP printing, with size distributions centered at a 6 nm diameter. When the Ni film thickness is lowered to 10 nm, NPs are printed with distributions peaked at a 2 nm diameter.
Propagation of shear Alvén waves in two-ion species plasmas confined by a nonuniform magnetic field
Authors: Farmer W. A. , Morales G. J.
Published: September 2013

Ray tracing calculations are performed for shear Alfvén waves in two-ion species plasmas in which the magnetic field varies with position. Three different magnetic topologies of contemporary interest are explored: a linear magnetic mirror, a pure toroidal field, and a tokamak field. The wave frequency is chosen to lie in the upper propagation band, so that reflection at the ion-ion hybrid frequency can occur for waves originally propagating along the magnetic field direction. Calculations are performed for a magnetic well configuration used in recent experiments [S. T. Vincena et al., Geophys. Res. Lett. 38, L11101 (2011) and S. T. Vincena et al., Phys. Plasmas 20, 012111 (2013)] in the Large Plasma Device (LAPD) related to the ion-ion hybrid resonator. It is found that radial spreading cannot explain the relatively low values of the resonator quality factor (Q) measured in those experiments, even when finite ion temperature is considered. This identifies that a damping mechanism is present that is at least an order of magnitude larger than dissipation due to radial energy loss. Calculations are also performed for a magnetic field with pure toroidal geometry, without a poloidal field, as in experiments being planned for the Enormous Toroidal Plasma Device. In this case, the effects of field-line curvature cause radial reflections. A poloidal field is included to explore a tokamak geometry with plasma parameters expected in ITER. When ion temperature is ignored, it is found that the ion-ion hybrid resonator can exist and trap waves for multiples bounces. The effects of finite ion temperature combine with field line curvature to cause the reflection point to move towards the tritium cyclotron frequency when electron temperature is negligible. However, for ITER parameters, it is shown that the electrons must be treated in the adiabatic limit to properly describe resonator phenomena.
Electrical potentials in bone induced by ultrasound irradiation in the megahertz range
Authors: Okino M. , Coutelou S. , Mizuno K. , Yanagitani T. , Matsukawa M.
Published: September 2013

Low frequency mechanical studies have reported the contribution of stress-induced electrical potentials to bone metabolism. However, the healing mechanism of bone fractures by low intensity ultrasound is not yet clear. We demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. Electrical potentials were obtained from the output of bovine cortical bone transducers. In the range of 0.7–2.5 MHz, sensitivities of bone transducers were around 1/1000 of a poly (vinylidene fluoride) ultrasonic transducer and did not depend on magnitude and alignment of hydroxyapatite crystallites in bone.
Fabrication and optical properties of controlled Ag nanostructures for plasmonic applications
Authors: Mei Fei , Xiao Xiangheng , Dai Zhigao , Xu Jinxia , Zhou Yuanming , Zhong Cai , Wu Linzhang
Published: September 2013

Noble metal nanoparticles exhibit unique plasmon resonances compared to bulk metal that depends on the nanoparticle size, shape, and interparticle distance. Towards this goal, the paper describes a simple and low-cost method for producing large area arrays of ordered silver nanoparticles with morphologies such as dots, rings, and bowls, based on the nanosphere lithography by combining evaporation and sputtering techniques. Pronounced, we demonstrate here a facile fabrication strategy that nanosphere monolayer could serve as a sacrificial mask access to generate silver nanobowl arrays. The experimental and simulated results show that the Ag nanodot arrays exhibit a satisfactory surface-enhanced Raman spectroscopy effect and adjustable frequency. These approaches will surely facilitate further exploration of metal nanostructures for applications in nanoscale optical sensors.
WSe2 field effect transistors with enhanced ambipolar characteristics
Authors: Das Saptarshi , Appenzeller Joerg
Published: September 2013

One of the most relevant features that a semiconducting channel material can offer when used in a field-effect transistor (FET) layout is its capability to enable both electron transport in the conduction band and hole transport in the valence band. In this way, complementary metal-oxide-semiconductor type applications become feasible once similar electron and hole drive current densities are achieved, and the threshold voltages are properly adjusted. In this article, we demonstrate pronounced ambipolar device characteristics of multilayer WSe2 FETs using different contact electrodes. Our study reveals that nickel electrodes facilitate electron injection while palladium electrodes are more efficient for hole injection. We also show, as an interesting demonstration, that by using nickel as the source contact electrode and palladium as the drain contact electrode, ambipolar device characteristics with similar on-state performance for both the electron and the hole branch can be achieved in WSe2 FETs. Finally, we discuss a unique technique based on the asymmetry in the ambipolar device characteristics to extract the Schottky barrier heights for such metal to WSe2 contacts.
Detection and Prevention of Aggregation-based False Positives in STD-NMR-based Fragment Screening
Authors: Vom Amelia , Headey Stephen , Wang Geqing , Capuano Ben , Yuriev Elizabeth , Scanlon Martin J. , Simpson Jamie S.
Published: September 2013

Aggregation of small organic compounds is a problem encountered in a variety of assay screening formats where it often results in detection of false positives. A saturation transfer difference-NMR-detected screen of a commercially available fragment library, followed by biochemical assay, identified several inhibitors of the enzyme ketopantoate reductase. These inhibitors were subsequently revealed to be aggregation-based false positives. Modification of the fragment screen by addition of detergent in the saturation transfer difference-NMR experiments allowed an assay format to be developed that resulted in the identification of genuine hit molecules suitable for further development.
A critical discussion of the benefits of e-health in population-level dental research
Authors: Lam Raymond , Kruger Estie , Tennant Marc
Published: September 2013

Population-level research is an essential area of health with the potential to affect quality of life and the broader economy. There are excellent epidemiological studies that have improved health services, but traditional research requires a considerable investment. Although electronic technology has changed the practice of many industries with improved efficiency, its application to health is relatively new. Termed ‘e-health’, this emerging area has been defined by the World Health Organization as the use of information technology to support many aspects of health such as in administration and scientific information. However, not all professionals are convinced of its use. This paper presents a novel application of this emerging area to describe the benefit in data collation and research to support one of the most pressing issues in public health: oral health and policy. Using the Chronic Disease Dental Scheme as an example, a critical discussion of its benefit to population-level research is presented. The Chronic Disease Dental Scheme method of electronic administration has been shown to enhance research and to complement existing progress in health data linkage. e-Health is an invaluable tool for population-level dental research.
Octave effect in auditory attention
Authors: Borra Tobias , Versnel Huib , Kemner Chantal , van Opstal A. John , van Ee Raymond
Published: September 2013

Significance

The human auditory system can filter sounds to select specific information. For example, when attention is “drawn” toward a tone of 1,000 Hz, the ear becomes more sensitive to that tone than to other tones. Here, we report that attention is drawn not only toward one specific frequency, as previously was assumed, but to octave-related frequencies as well. We show that this “octave effect” does not require the physical presence of the attended tone, as it persists for imagined tones: thinking of a tone increases sensitivity for the imagined tone and its octave-related frequencies. We speculate that the octave effect evolved from exposure to natural vibrations containing octave-related spectral peaks, e.g., as produced by the human vocal cords.
Macroevolutionary speciation rates are decoupled from the evolution of intrinsic reproductive isolation in
Drosophila
and birds
Authors: Rabosky Daniel L. , Matute Daniel R.
Published: September 2013

Significance

Rates of species diversification vary widely in the natural world, leading to profound differences in species richness among different kinds of organisms. Variation in the rate at which new species arise is frequently assumed to result from factors that influence the rate at which populations become reproductively isolated from each other. We tested this assumption in
Drosophila
flies and birds. Surprisingly, we find no evidence that the propensity of organisms to evolve reproductive isolation predicts the rate at which they form new species over geological timescales. These results suggest that factors that cause intrinsic reproductive isolation may play less of a role in explaining biological diversity than generally assumed.
Priming of jasmonate-mediated antiherbivore defense responses in rice by silicon
Authors: Ye Mao , Song Yuanyuan , Long Jun , Wang Ruilong , Baerson Scott R. , Pan Zhiqiang , Zhu-Salzman Keyan , Xie Jiefen , Cai Kunzheng , Luo Shiming , Zeng Rensen
Published: September 2013

Significance

Silicon (Si) is the second most abundant element in soil, and it can increase plant resistance against many abiotic and biotic stresses. The jasmonate (JA) signaling pathway plays a crucial role in mediating antiherbivore defense responses in plants. Our work shows that Si primes JA-mediated antiherbivore defense responses and increases rice resistance to the leaffolder caterpillar and that Si accumulation in rice leaves is mediated by the JA pathway, suggesting a strong interaction between Si and JA in rice defense against insect herbivores. This interaction may represent a widespread mechanism by which Si enhances plant resistance against biotic stresses in Si-accumulating plants.
Manipulating L-type calcium channels in cardiomyocytes using split-intein protein transsplicing
Authors: Subramanyam Prakash , Chang Donald D. , Fang Kun , Xie Wenjun , Marks Andrew R. , Colecraft Henry M.
Published: September 2013

Significance

Manipulating expression of proteins directly in isolated heart cells is an important method to study cardiac biology and disease. However, this approach is challenging for large genes (>6 kb) because these exceed the packaging capacity of commonly used viral vectors used to deliver genes into heart cells. Here, we used a split-intein–mediated protein transsplicing strategy to reconstitute the large pore-forming subunit of L-type calcium channels from two separate fragments in heart cells. This approach provides a general method to express different large proteins in heart cells and will help advance new insights into basic mechanisms underlying cardiac function and disease.
Divergence of the mock and scrambled Fourier series on fractal measures
Authors: Dutkay Dorin , Han Deguang , Sun Qiyu
Published: September 2013

We study divergence properties of the Fourier series on Cantor-type fractal measures, also called the mock Fourier series. We show that in some cases the

L
1

L^1

-norm of the corresponding Dirichlet kernel grows exponentially fast, and therefore the Fourier series are not even pointwise convergent. We apply these results to the Lebesgue measure to show that a certain rearrangement of the exponential functions, with affine structure, which we call a scrambled Fourier series, have a corresponding Dirichlet kernel whose

L
1

L^1

-norm grows exponentially fast, which is much worse than the known logarithmic bound. The divergence properties are related to the Mahler measure of certain polynomials and to spectral properties of Ruelle operators.
srGAP1 regulates lamellipodial dynamics and cell migratory behavior by modulating Rac1 activity
Authors: Yamazaki Daisuke , Itoh Toshiki , Miki Hiroaki , Takenawa Tadaomi
Published: September 2013

The distinct levels of Rac activity differentially regulate the pattern of intrinsic cell migration. However, it remains unknown how Rac activity is modulated and how the level of Rac activity controls cell migratory behavior. Here we show that Slit-Robo GAP 1 (srGAP1) is a modulator of Rac activity in locomotive cells. srGAP1 possesses a GAP activity specific to Rac1 and is recruited to lamellipodia in a Rac1-dependent manner. srGAP1 limits Rac1 activity and allows concomitant activation of Rac1 and RhoA, which are mutually inhibitory. When both GTPases are activated, the protrusive structures caused by Rac1-dependent actin reorganization are spatially restricted and periodically destabilized, causing ruffling by RhoA-induced actomyosin contractility. Depletion of srGAP1 overactivates Rac1 and inactivates RhoA, resulting in continuous spatiotemporal spreading of lamellipodia and a modal shift of intrinsic cell motility from random to directionally persistent. Thus srGAP1 is a key determinant of lamellipodial dynamics and cell migratory behavior.
Variance in mating success does not produce strong sexual selection in a polygynous songbird
Authors: Sousa Bridget F. , Westneat David F.
Published: September 2013

The sexually dimorphic ornaments and songs of birds are generally thought to be the result of sexual selection. For some time, variation in dimorphism among taxa was attributed to differences in social mating patterns. However, extrapair mating provides an alternative mechanism for sexual selection in both monogamous and polygynous birds. In monogamous systems, extrapair mating typically increases variance in mating success and hence sexual selection. However, it is less clear how extrapair mating influences sexual selection in polygynous species. We measured sexual selection acting on 6 sexually dimorphic male traits in a polygynous songbird, the dickcissel (Spiza americana). We also examined patterns of association between social and extrapair mating success, between male traits and reproductive success within each mating context, and the contribution of each type of mating to overall reproductive success. Despite high variance in both mating success and male traits, we found no evidence for current sexual selection in dickcissels. Indeed, variance among males in dimorphic traits did not significantly contribute to male success in any mating context. These results add to an array of studies uncovering relatively weak sexual selection in polygynous species. It is possible that, in contrast to monogamous systems, extrapair paternity weakens sexual selection in polygynous systems. In addition, natural selection arising from high predation and interspecific brood parasitism, stochastic processes, or annual variation in selective pressures may also weaken sexual selection in this species.
Quantifying the complexity of medical research
Authors: Rodriguez-Esteban Raul , Loging William T.
Published: September 2013

Motivation: A crucial phenomenon of our times is the diminishing marginal returns of investments in pharmaceutical research and development. A potential reason is that research into diseases is becoming increasingly complex, and thus more burdensome, for humans to handle. We sought to investigate whether we could measure research complexity by analyzing the published literature.

Results: Through the text mining of the publication record of multiple diseases, we have found that the complexity and novelty of disease research has been increasing over the years. Surprisingly, we have also found that research on diseases with higher publication rate does not possess greater complexity or novelty than that on less-studied diseases. We have also shown that the research produced about a disease can be seen as a differentiated area of knowledge within the wider biomedical research. For our analysis, we have conceptualized disease research as a parallel multi-agent search in which each scientific agent (a scientist) follows a search path based on a model of a disease. We have looked at trends in facts published for diseases, measured their diversity and turnover using the entropy measure and found similar patterns across disease areas.

Contact:  raul.rodriguez-esteban@roche.com
M2SG: mapping human disease-related genetic variants to protein sequences and genomic loci
Authors: Ji Renkai , Cong Qian , Li Wenlin , Grishin Nick V.
Published: September 2013

Summary: Online Mendelian Inheritance in Man (OMIM) is a manually curated compendium of human genetic variants and the corresponding phenotypes, mostly human diseases. Instead of directly documenting the native sequences for gene entries, OMIM links its entries to protein and DNA sequences in other databases. However, because of the existence of gene isoforms and errors in OMIM records, mapping a specific OMIM mutation to its corresponding protein sequence is not trivial. Combining computer programs and extensive manual curation of OMIM full-text descriptions and original literature, we mapped 98% of OMIM amino acid substitutions (AASs) and all SwissProt Variant (SwissVar) disease-related AASs to reference sequences and confidently mapped 99.96% of all AASs to the genomic loci. Based on the results, we developed an online database and interactive web server (M2SG) to (i) retrieve the mapped OMIM and SwissVar variants for a given protein sequence; and (ii) obtain related proteins and mutations for an input disease phenotype. This database will be useful for analyzing sequences, understanding the effect of mutations, identifying important genetic variations and designing experiments on a protein of interest.

Availability and implementation: The database and web server are freely available at http://prodata.swmed.edu/M2S/mut2seq.cgi.

Contact:  grishin@chop.swmed.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
SAMstrt: statistical test for differential expression in single-cell transcriptome with spike-in normalization
Authors: Katayama Shintaro , Töhönen Virpi , Linnarsson Sten , Kere Juha
Published: September 2013

Motivation: Recent transcriptome studies have revealed that total transcript numbers vary by cell type and condition; therefore, the statistical assumptions for single-cell transcriptome studies must be revisited. SAMstrt is an extension code for SAMseq, which is a statistical method for differential expression, to enable spike-in normalization and statistical testing based on the estimated absolute number of transcripts per cell for single-cell RNA-seq methods.

Availability and Implementation: SAMstrt is implemented on R and available in github (https://github.com/shka/R-SAMstrt).

Contact:  shintaro.katayama@ki.se

Supplementary Information:  Supplementary data are available at Bioinformatics online.
PyroHMMvar: a sensitive and accurate method to call short indels and SNPs for Ion Torrent and 454 data
Authors: Zeng Feng , Jiang Rui , Chen Ting
Published: September 2013

Motivation: The identification of short insertions and deletions (indels) and single nucleotide polymorphisms (SNPs) from Ion Torrent and 454 reads is a challenging problem, essentially because these techniques are prone to sequence erroneously at homopolymers and can, therefore, raise indels in reads. Most of the existing mapping programs do not model homopolymer errors when aligning reads against the reference. The resulting alignments will then contain various kinds of mismatches and indels that confound the accurate determination of variant loci and alleles.

Results: To address these challenges, we realign reads against the reference using our previously proposed hidden Markov model that models homopolymer errors and then merges these pairwise alignments into a weighted alignment graph. Based on our weighted alignment graph and hidden Markov model, we develop a method called PyroHMMvar, which can simultaneously detect short indels and SNPs, as demonstrated in human resequencing data. Specifically, by applying our methods to simulated diploid datasets, we demonstrate that PyroHMMvar produces more accurate results than state-of-the-art methods, such as Samtools and GATK, and is less sensitive to mapping parameter settings than the other methods. We also apply PyroHMMvar to analyze one human whole genome resequencing dataset, and the results confirm that PyroHMMvar predicts SNPs and indels accurately.

Availability and implementation: Source code freely available at the following URL: https://code.google.com/p/pyrohmmvar/, implemented in C++ and supported on Linux.

Contact:  ruijiang@tsinghua.edu.cn or cengf08@mails.thu.edu.cn
Consed: a graphical editor for next-generation sequencing
Authors: Gordon David , Green Phil
Published: September 2013

Summary: The rapid growth of DNA sequencing throughput in recent years implies that graphical interfaces for viewing and correcting errors must now handle large numbers of reads, efficiently pinpoint regions of interest and automate as many tasks as possible. We have adapted consed to reflect this. To allow full-feature editing of large datasets while keeping memory requirements low, we developed a viewer, bamScape, that reads billion-read BAM files, identifies and displays problem areas for user review and launches the consed graphical editor on user-selected regions, allowing, in addition to longstanding consed capabilities such as assembly editing, a variety of new features including direct editing of the reference sequence, variant and error detection, display of annotation tracks and the ability to simultaneously process a group of reads. Many batch processing capabilities have been added.

Availability: The consed package is free to academic, government and non-profit users, and licensed to others for a fee by the University of Washington. The current version (26.0) is available for linux, macosx and solaris systems or as C++ source code. It includes a user’s manual (with exercises) and example datasets. http://www.phrap.org/consed/consed.html

Contact:  dgordon@uw.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Adjusting scoring matrices to correct overextended alignments
Authors: Mills Lauren J. , Pearson William R.
Published: September 2013

Motivation: Sequence similarity searches performed with BLAST, SSEARCH and FASTA achieve high sensitivity by using scoring matrices (e.g. BLOSUM62) that target low identity (<33%) alignments. Although such scoring matrices can effectively identify distant homologs, they can also produce local alignments that extend beyond the homologous regions.

Results: We measured local alignment start/stop boundary accuracy using a set of queries where the correct alignment boundaries were known, and found that 7% of BLASTP and 8% of SSEARCH alignment boundaries were overextended. Overextended alignments include non-homologous sequences; they occur most frequently between sequences that are more closely related (>33% identity). Adjusting the scoring matrix to reflect the identity of the homologous sequence can correct higher identity overextended alignment boundaries. In addition, the scoring matrix that produced a correct alignment could be reliably predicted based on the sequence identity seen in the original BLOSUM62 alignment. Realigning with the predicted scoring matrix corrected 37% of all overextended alignments, resulting in more correct alignments than using BLOSUM62 alone.

Availability: RefProtDom2 (RPD2) sequences and the FASTA software are available from http://faculty.virginia.edu/wrpearson/fasta.

Contact:  wrp@virginia.edu
Phosphorylated (pT371)TRF1 is recruited to sites of DNA damage to facilitate homologous recombination and checkpoint activation
Authors: McKerlie Megan , Walker John R. , Mitchell Taylor R. H. , Wilson Florence R. , Zhu Xu-Dong
Published: September 2013

TRF1, a duplex telomeric DNA-binding protein, plays an important role in telomere metabolism. We have previously reported that a fraction of endogenous TRF1 can stably exist free of telomere chromatin when it is phosphorylated at T371 by Cdk1; however, the role of this telomere-free (pT371)TRF1 has yet to be fully characterized. Here we show that phosphorylated (pT371)TRF1 is recruited to sites of DNA damage, forming damage-induced foci in response to ionizing radiation (IR), etoposide and camptothecin. We find that IR-induced (pT371)TRF1 foci formation is dependent on the ATM- and Mre11/Rad50/Nbs1-mediated DNA damage response. While loss of functional BRCA1 impairs the formation of IR-induced (pT371)TRF1 foci, depletion of either 53BP1 or Rif1 stimulates IR-induced (pT371)TRF1 foci formation. In addition, we show that TRF1 depletion or the lack of its phosphorylation at T371 impairs DNA end resection and repair of nontelomeric DNA double-strand breaks by homologous recombination. The lack of TRF1 phosphorylation at T371 also hampers the activation of the G2/M checkpoint and sensitizes cells to PARP inhibition, IR and camptothecin. Collectively, these results reveal a novel but important function of phosphorylated (pT371)TRF1 in facilitating DNA double-strand break repair and the maintenance of genome integrity.
Role of the protein in the DNA sequence specificity of the cleavage site stabilized by the camptothecin topoisomerase IB inhibitor: a metadynamics study
Authors: Coletta Andrea , Desideri Alessandro
Published: September 2013

Camptothecin (CPT) is a topoisomerase IB (TopIB) selective inhibitor whose derivatives are currently used in cancer therapy. TopIB cleaves DNA at any sequence, but in the presence of CPT the only stabilized protein–DNA covalent complex is the one having a thymine in position −1 with respect to the cleavage site. A metadynamics simulation of two TopIB–DNA–CPT ternary complexes differing for the presence of a thymine or a cytosine in position −1 indicates the occurrence of two different drug’s unbinding pathways. The free-energy difference between the bound state and the transition state is large when a thymine is present in position −1 and is strongly reduced in presence of a cytosine, in line with the different drug stabilization properties of the two systems. Such a difference is strictly related to the changes in the hydrogen bond network between the protein, the DNA and the drug in the two systems, indicating a direct role of the protein in determining the specificity of the cleavage site sequence stabilized by the CPT. Calculations carried out in presence of one compound of the indenoisoquinoline family (NSC314622) indicate a comparable energy difference between the bound and the transition state independently of the presence of a thymine or a cytosine in position −1, in line with the experimental results.
Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synuclein
Authors: Zanzoni Andreas , Marchese Domenica , Agostini Federico , Bolognesi Benedetta , Cirillo Davide , Botta-Orfila Maria , Livi Carmen Maria , Rodriguez-Mulero Silvia , Tartaglia Gian Gaetano
Published: September 2013

Previous evidence indicates that a number of proteins are able to interact with cognate mRNAs. These autogenous associations represent important regulatory mechanisms that control gene expression at the translational level. Using the catRAPID approach to predict the propensity of proteins to bind to RNA, we investigated the occurrence of autogenous associations in the human proteome. Our algorithm correctly identified binding sites in well-known cases such as thymidylate synthase, tumor suppressor P53, synaptotagmin-1, serine/ariginine-rich splicing factor 2, heat shock 70 kDa, ribonucleic particle-specific U1A and ribosomal protein S13. In addition, we found that several other proteins are able to bind to their own mRNAs. A large-scale analysis of biological pathways revealed that aggregation-prone and structurally disordered proteins have the highest propensity to interact with cognate RNAs. These findings are substantiated by experimental evidence on amyloidogenic proteins such as TAR DNA-binding protein 43 and fragile X mental retardation protein. Among the amyloidogenic proteins, we predicted that Parkinson’s disease-related α-synuclein is highly prone to interact with cognate transcripts, which suggests the existence of RNA-dependent factors in its function and dysfunction. Indeed, as aggregation is intrinsically concentration dependent, it is possible that autogenous interactions play a crucial role in controlling protein homeostasis.
Nano-/microstructure improved photocatalytic activities of semiconductors
Authors: Zhao Tianyi , Zhao Yong , Jiang Lei
Published: September 2013

Photocatalysis has emerged as a promising technique owing to its valuable applications in environmental purification. With the demand of building effective photocatalyst materials, semiconductor investigation experienced a developing process from simple chemical modification to complicated morphology design. In this review, the general relationship between morphology structures and photocatalytic properties is mainly discussed. Various nano-/microsized structures from zero- to three-dimensional are discussed, and the photocatalytic efficiency correspon- ding to the structures is analysed. The results showed that simple structures can be easily obtained and can facilitate chemical modification, whereas one- or three-dimensional structures can provide structure-enhanced properties such as surface area increase, multiple reflections of UV light, etc. Those principles of structure-related photocatalytic properties will afford basic ideology in designing new photocatalytic materials with more effective catalytic properties.
RNA nanotechnology for computer design and
in vivo
computation
Authors: Qiu Meikang , Khisamutdinov Emil , Zhao Zhengyi , Pan Cheryl , Choi Jeong-Woo , Leontis Neocles B. , Guo Peixuan
Published: September 2013

Molecular-scale computing has been explored since 1989 owing to the foreseeable limitation of Moore's law for silicon-based computation devices. With the potential of massive parallelism, low energy consumption and capability of working
in vivo
, molecular-scale computing promises a new computational paradigm. Inspired by the concepts from the electronic computer, DNA computing has realized basic Boolean functions and has progressed into multi-layered circuits. Recently, RNA nanotechnology has emerged as an alternative approach. Owing to the newly discovered thermodynamic stability of a special RNA motif (Shu
et al.
2011
Nat. Nanotechnol.
6
, 658–667 (
doi:10.1038/nnano.2011.105
)), RNA nanoparticles are emerging as another promising medium for nanodevice and nanomedicine as well as molecular-scale computing. Like DNA, RNA sequences can be designed to form desired secondary structures in a straightforward manner, but RNA is structurally more versatile and more thermodynamically stable owing to its non-canonical base-pairing, tertiary interactions and base-stacking property. A 90-nucleotide RNA can exhibit 4
90
nanostructures, and its loops and tertiary architecture can serve as a mounting dovetail that eliminates the need for external linking dowels. Its enzymatic and fluorogenic activity creates diversity in computational design. Varieties of small RNA can work cooperatively, synergistically or antagonistically to carry out computational logic circuits. The riboswitch and enzymatic ribozyme activities and its special
in vivo
attributes offer a great potential for
in vivo
computation. Unique features in transcription, termination, self-assembly, self-processing and acid resistance enable
in vivo
production of RNA nanoparticles that harbour various regulators for intracellular manipulation. With all these advantages, RNA computation is promising, but it is still in its infancy. Many challenges still exist. Collaborations between RNA nanotechnologists and computer scientists are necessary to advance this nascent technology.
Organic dye-sensitized sponge-like TiO
2
photoanode for dye-sensitized solar cells
Authors: Liu Jian , Yang Qiang , Li Mingzhu , Zhu Weihong , Tian He , Song Yanlin
Published: September 2013

Light harvesting inside a solar cell is crucial for overall performance. Increasing the optical path of a photon through the delicate design of photoanode morphology can increase the light absorbance. The marine sponge-like photoanode is facilely constructed and assembled into a solar cell, using an organic D−A−
π
−A-type dye with wide-spectrum response as the sensitizer. The light scattering derived from the large porous cavities in the photoanode enhances the improved light absorbance of the dye molecules, especially in the long-wavelength region, and therefore improves the cell efficiency. Synergistically engineering the photoanode morphology and adopting matchable dye maximized the light energy conversion efficiency in this study, and a maximal conversion efficiency of 5.02% was achieved.
Enhancement of the immune response against Salmonella infection of mice by heat-killed multispecies combinations of lactic acid bacteria
Authors: Chen Chih-Yuan , Tsen Hau-Yang , Lin Chun-Li , Lin Chien-Ku , Chuang Li-Tsen , Chen Chin-Shuh , Chiang Yu-Cheng
Published: September 2013

Heat-killed lactic acid bacteria (LAB) has advantages over live LAB in that it has a long shelf‐life and is therefore easy to store and transport. From four LAB strains selected by immunomodulatory activity and adherent properties, we prepared the heat-killed multispecies combination of LAB (MLAB) and the cell walls from MLAB under two conditions (100 °C for 30 min and 121 °C for 15 min). Different effects on the adherent properties of these four LAB strains were observed, depending on the heating conditions. With mouse macrophage cells, the two heat-killed MLABs (HMLABs) showed significantly higher induction activities on the production of interleukin 12 (IL-12) than their individual strains did. Heat-killed MLABs and cell‐wall preparations were able to reduce theSalmonellainvasion of Caco-2 and mouse macrophage cells. Feeding mice with HMLAB could inhibit theSalmonellainvasion of mice significantly. For these mice, the expression level of pro-inflammatory cytokines, such as TNF-α and IL-6, in mouse serum was reduced while that of the anti-inflammatory cytokine, i.e. IL-10, was enhanced. The HMLABs developed in this study showed higher protective effect againstSalmonellainvasion either of Caco-2 cells or of mice, relative to the heat-killed lactobacilli, which consisted ofLactobacillusacidophilusstrains selected at random. In conclusion, the HMLABs were potentially useful for the protection of mice againstSalmonellainfection and the induced inflammation.
In Vivo Time-Lapse Imaging of Neuronal Development in Xenopus
Authors: Ruthazer Edward S. , Schohl Anne , Schwartz Neil , Tavakoli Aydin , Tremblay Marc , Cline Hollis T.
Published: September 2013

In vivo fluorescence imaging of cells in the developing nervous system is greatly facilitated in specimens in which cells are brightly but sparsely labeled. In this article, we describe a number of techniques that can be used for delivering fluorophore to neurons in the albino Xenopus laevis tadpole. Fluorescent dye or DNA that encodes a fluorescent protein can be delivered to single cells by electroporation. Alternatively, multiple cells can be labeled with fluorescent dye introduced by local iontophoresis or with plasmid DNA introduced by bulk electroporation. Technical considerations and analysis methods for time-lapse imaging in living tissue are also discussed.