bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of novel arylimidamides against Trypanosoma cruzi in vitro
Authors: DA SILVA CRISTIANE FRANÇA , DALIRY ANISSA , DA SILVA PATRÍCIA BERNARDINO , AKAY SENOL , BANERJEE MOLOY , FARAHAT ABDELBASSET A. , FISHER MARY K. , HU LAIXING , KUMAR ARVIND , LIU ZONGYING , STEPHENS CHAD E. , BOYKIN DAVID W. , CORREIA SOEIRO MARIA DE NAZARÉ
Published: September 2011

The present study aimed to determine the in vitro biological efficacy and selectivity of 7 novel AIAs upon bloodstream trypomastigotes and intracellular amastigotes of Trypanosoma cruzi. The biological activity of these aromatic compounds was assayed for 48 and 24 h against intracellular parasites and bloodstream forms of T. cruzi (Y strain), respectively. Additional assays were also performed to determine their potential use in blood banks by treating the bloodstream parasites with the compounds diluted in mouse blood for 24 h at 4°C. Toxicity against mammalian cells was evaluated using primary cultures of cardiac cells incubated for 24 and 48 h with the AIAs and then cellular death rates were determined by MTT colorimetric assays. Our data demonstrated the outstanding trypanocidal effect of AIAs against T. cruzi, especially DB1853, DB1862, DB1867 and DB1868, giving IC50 values ranging between 16 and 70 nanomolar against both parasite forms. All AIAs presented superior efficacy to benznidazole and some, such as DB1868, also demonstrated promising activity as a candidate agent for blood prophylaxis. The excellent anti-trypanosomal efficacy of these novel AIAs against T. cruzi stimulates further in vivo studies and justifies the screening of new analogues with the goal of establishing a useful alternative therapy for Chagas disease.
The Hybrid II assay: a sensitive and specific real-time hybridization assay for the diagnosis ofTheileria parvainfection in Cape buffalo (Syncerus caffer) and cattle
Authors: PIENAAR RONEL , POTGIETER FRED T. , LATIF ABDALLA A. , THEKISOE ORIEL M. M. , MANS BEN J.
Published: September 2011

Corridor disease is an acute, fatal disease of cattle caused by buffalo-adaptedTheileria parva. This is a nationally controlled disease in South Africa and strict control measures apply for the movement of buffalo, which includes mandatory testing for the presence ofT. parvaand other controlled diseases. Accurate diagnosis of theT. parvacarrier state in buffalo using the official real-time hybridization PCR assay (Sibekoet al.2008), has been shown to be affected by concurrent infection withT.sp. (buffalo)-like parasites. We describe the Hybrid II assay, a real-time hybridization PCR method, which compares well with the official hybridization assay in terms of specificity and sensitivity. It is, however, not influenced by mixed infections ofT.sp. (buffalo)-like parasites and is as such a significant improvement on the current hybridization assay.
Toxoplasma gondii: the changing paradigm of congenital toxoplasmosis
Authors: LINDSAY D. S. , DUBEY J. P.
Published: September 2011

Researchers have learned much concerning the population biology ofToxoplasma gondiiover the past 2 decades. It is now apparent that many atypical genotypes exist besides the typical 3 genotypes (type I, type II and type III) first described from samples from Europe and the United States. These genotypes can differ in pathogenicity and transmissibility from the typical genotypes that have been used in the majority of scientific research over the past 70 years. These differences impact much of what we used to believe as facts about congenital toxoplasmosis (CT) and will be important in developing new recommendations for prevention of CT and the monitoring of women at risk for developing CT. The present review highlights new information onT. gondiigenotypes and how this information will change the way we convey information about CT to pregnant women, physicians and students.
Involvement of sulfated glycosaminoglycans on the development and attachment of Trypanosoma cruzi to the luminal midgut surface in the vector, Rhodnius prolixus
Authors: GONZALEZ MARCELO S. , SILVA LUIZ-CLAUDIO F. , ALBUQUERQUE-CUNHA J. M. , NOGUEIRA NADIR F. S. , MATTOS DÉBORA P. , CASTRO DANIELE P. , AZAMBUJA PATRICIA , GARCIA ELOI S.
Published: September 2011

In the present study, we investigated the involvement of sulfated glycosaminoglycans in both the in vivo development and adhesion of T. cruzi epimastigotes to the luminal surface of the digestive tract of the insect vector, Rhodnius prolixus. Pre-incubation of T. cruzi, Dm 28c epimastigotes with heparin, chondroitin 4-sulfate, chondroitin 6-sulfate or protamine chloridrate inhibited in vitro attachment of parasites to the insect midgut. Enzymatic removal of heparan sulfate moieties by heparinase I or of chondroitin sulfate moieties by chondroitinase AC from the insect posterior midgut abolished epimastigote attachment in vitro. These treatments also reduced the labelling of anionic sites exposed at the luminal surface of the perimicrovillar membranes in the triatomine midgut epithelial cells. Inclusion of chondroitin 4-sulfate or chondroitin 6-sulfate and to a lesser extent, heparin, in the T. cruzi-infected bloodmeal inhibited the establishment of parasites in R. prolixus. These observations indicate that sulfated glycosaminoglycans are one of the determinants for both adhesion of the T. cruzi epimastigotes to the posterior midgut epithelial cells of the triatomine and the parasite infection in the insect vector, R. prolixus.
Translating CBT for Voices into a Program for Carers: A Pilot Study
Authors: Maxwell Janet , Farhall John , Matyas Thomas
Published: September 2011

Background: The treatment of persisting psychotic symptoms with cognitive behavioural therapy (CBTp) is now established as an evidence-based treatment; however its availability remains limited. We piloted a novel CBTp skills-based group training program for carers. The aim was to reduce service users’ auditory hallucinations severity through carers’ use of basic CBTp methods in their regular interactions. Method: Eight carer-service user dyads and one carer-carer-service user triad participated. Carers attended the 10-week (25-hour) program, and completed measures of subjective burden and expressed emotion (EE) over a 30-week period that included a baseline phase prior to the training and implementation phase. Service users completed weekly interviews assessing voice symptomatology. Analyses were conducted for each dyad using time-series methods. Results: The training program was rated highly. Improvements in symptoms and carer burden ranged from none to clinically significant across different dyads. Carer implementation of strategies was related to reduced symptoms in one dyad; reductions in EE were related to symptom improvements in two dyads. Conclusions: There may be benefits in training carers in behavioural and cognitive management of persisting hallucinations. Possible mechanisms for improvements in voice symptomatology include reduction in carers’ EE, and carer implementation of strategies taught.
Planning a deep drilling project in the Koyna region of India
Authors: Gupta Harsh , Nayak Shailesh , Bhaskar Rao Y. J.
Published: September 2011

Workshop on Deep Scientific Drilling to Study Reservoir Triggered Earthquakes; Koyna, India, 21–25 March 2011; The Koyna region in western India is a classical site of reservoir‐triggered seismicity in an intraplate setting. Triggered earthquakes have been occurring in a restricted area of 20 × 30 square kilometers since the impoundment of Shivajisagar Lake in 1962; these include the largest triggered earthquake of M ∼ 6.3 on 10 December 1967, 21 earthquakes of M ≥ 5, about 200 earthquakes of M ∼ 4, and several thousand smaller earthquakes. There is no other source of seismic activity within a radius of 50 kilometers from the Koyna region. The shallow (4‐ to 6‐kilometer) occurrence of moderate size earthquakes in this region makes it an ideal site for deep drilling to study earthquake processes and the mechanics of faulting in an intraplate zone.
Mixing along continental slopes affects North Atlantic Deep Water
Authors: Kumar Mohi
Published: September 2011

In the northern Atlantic Ocean, cold salty water from the Arctic Ocean sinks to form North Atlantic Deep Water, a current that hugs the bottom of the ocean as it travels south toward Antarctica. The formation of this water mass is vital to large‐scale global ocean circulation and the spread of heat and nutrients across the planet's waters—when deep waters surface, they form warm surface currents such as the Gulf Stream, which are swept by wind back to the North Atlantic, where they cool and sink, beginning the cycle anew. In the Faroe‐Shetland Channel, so named because it lies between Scotland's Shetland Islands and Denmark's Faroe Islands, deep water masses that are tributaries to North Atlantic Deep Water abut the steep continental slopes that bracket the channel. The ebb and flow of ocean tides there produce horizontal and vertical waves that travel long distances and may break on the slopes like waves on a beach. These waves, called internal tides, were monitored and modeled by Hall et al., who sought to understand how they affect the mixing of different water masses that pass through the channel. They found that strong mixing due to internal tides on the slopes that bound the Faroe‐Shetland Channel may be an important mechanism by which North Atlantic Deep Water acquires the physical and chemical properties that it carries across the globe. (Journal of Geophysical Research‐Oceans, doi:10.1029/2010JC006213, 2011)
Two millennia of sea level data: The key to predicting change
Authors: Gehrels W. Roland , Horton Benjamin P. , Kemp Andrew C. , Sivan Dorit
Published: September 2011

Sea level reconstructions spanning the late Holocene (the past 2000 years) provide a preindustrial context for understanding the patterns and causes of contemporary and future change. The Intergovernmental Panel on Climate Change (IPCC) assumed that global sea level change during the past two millennia (prior to the middle of the nineteenth century) was close to zero [Bindoff et al., 2007], but understanding of late Holocene sea level variability is limited. Glaciers and ice sheets changed significantly in size during this period, and therefore sea level likely oscillated on the order of several decimeters. In addition, ocean dynamics, solid Earth movements, steric (density) changes, and gravitational effects contributed to complex regional patterns of sea level change.
Cocos plate gravity lineaments due to thermal contraction cracks
Authors: Balcerak Ernie
Published: September 2011

Gravity lineaments, narrow strips of stronger gravity, were first observed on the ocean floor in the south central Pacific several decades ago, but scientists still debate their origin. Because the south central Pacific gravity lineaments align with the tectonic plate motion, some scientists have suggested that they were created through small‐scale convection cells below the lithosphere that become elongated as the plate moved. Other proposed explanations have included flow of low‐viscosity material along the base of the the lithosphere and cracking of the lithosphere due to thermal contraction. Newly recognized gravity lineaments on the Cocos plate, which lies beneath the Pacific Ocean off the coast of Central America, could help scientists figure out how such lineaments form. Cormier et al. identified the lineaments using satellite altimetry data. They used gravity, bathymetric, and magnetic data to investigate the physical characteristics of the lineaments and how they changed over time. (Geochemistry, Geophysics, Geosystems, doi:10.1029/2011GC003573, 2011)
One‐sided transform basins and “inverted curtains”: Implications for releasing bends along strike‐slip faults
Authors: Choi Eunseo , Seeber Leonardo , Steckler Michael S. , Buck Roger
Published: September 2011

Some basins associated with bends along strike‐slip faults grow only on one side of the fault. We ascribe this asymmetry to a characteristic 3D geometry. The strike‐slip fault is planar and vertical, except at the “inverted curtain” where the fault has a sinusoidal bend that decreases linearly downward and vanishes below a prescribed depth. We model numerically the deformation around inverted curtains with different dips. We consider a crustal block traversed by a fault with lower cohesion than the surrounding rock and subject it to strike‐slip motion, first with purely elastic models and then with Mohr‐Coulomb elasto‐plastic ones. We found that when a curtain is vertical, both sides of the bend subside forming a symmetrical basin. In contrast, basins are formed only on the hanging wall side of a releasing bend of a non‐vertical curtain, in agreement with field examples. For the same curtain geometries, the basins are broader and shallower in an elastic crust than in an elastic‐plastic one. While releasing bends are stable over a range of dips, restraining bends are “shunted” by new straight faults except in shallow‐dipping curtains. These model results show that bends on transcurrent faults with inverted curtain geometries lead to asymmetric ridges and basins. Conversely, such a characteristically asymmetric basin (ridge) is symptomatic of a transform bend with oblique slip that attenuates with depth and is rooted below the subsided (uplifted) area. One implication is that master transcurrent faults may remain primarily or solely responsible for earthquake hazard along segments with anomalous vertical deformation.
Dismay with GM maize
Authors: Ryffel Gerhart U
Published: September 2011

New discoveries often raise new problems or meet with public resistance. Rather than giving up on technologies such as genetically modified organisms, we should use science to develop them further and make them safer.
Measure it to better manage it: a biodiversity monitoring framework for the Australian rangelands
Authors: Eyre Teresa J. , Fisher Alaric , Hunt Leigh P. , Kutt Alex S.
Published: September 2011

The need for broad-scale, long-term biodiversity monitoring to support evidence-based policy and management in the Australian rangelands is clear and pressing but, despite protracted discussion of this need, there has been little progress towards implementation. To prompt real progress, we propose a framework of spatially hierarchical and complementary components that together use a combination of direct and indirect measures of biodiversity and drivers: • Targeted monitoring; involving localised field-based monitoring of target species, addressing specific management questions. • Surveillance monitoring; involving broad-scale, field-based sampling of multi-taxa and a set of habitat and condition attributes. • Landscape-scale monitoring; providing regional to national-scale intelligence on habitat quality and trends in threats to or drivers of biodiversity, with data obtained using systematic ground-based and remote methods. The framework aims to provide information on the response of biodiversity to rangeland management that is relevant to regional, state and national jurisdictions. We believe the characteristics of the proposed framework address many of the pitfalls that often stall biodiversity monitoring in Australia. These characteristics include: clarification of the desired outcomes and management requirements; a strong collaborative partnership that oversees the administration of the framework and ensures long-term commitment; a conceptual model that guides clear and relevant question-setting; careful design and analysis aimed at addressing the set questions; timely and relevant communication and reporting; and, regular data analysis and review, providing an adaptive mechanism for the framework to evolve and remain relevant. The proposed framework can be incrementally implemented at a moderate cost, relative to current total expenditure in natural resource management in the Australian rangelands.
Reinforcing alternative economies: self-motivated work by central Anmatyerr people to sell Katyerr (Desert raisin, Bush tomato) in central Australia
Authors: Holcombe Sarah , Yates Peter , Walsh Fiona
Published: September 2011

This paper examines an alternative economy in the Anmatyerr region of central Australia, with reference to the ‘hybrid economy’ concept. We argue that this concept has application in recognising emerging Aboriginal economies surrounding the utilisation and management of natural resources. In particular, we examine the ‘bush harvest’ of one species – where Aboriginal people sell Desert raisin (Katyerr or Bush tomato) to traders who then on-sell to manufacturers and retailers. This seasonal economy intermittently injects relatively significant amounts of cash into households (but unaccounted for in census figures). Although some groups have been selling bush harvest produce for up to 30 years, it is increasingly gaining momentum with a larger market developing. Yet, there is a risk that this burgeoning market and the mainstream interest in horticulture will fail to recognise the value of local Aboriginal motivations that drive the customary harvest activity. Nevertheless, there is increased federal government recognition, via the Central Land Council, of the value of Aboriginal people as local land managers; as rangers. This in turn has provided resources to promote and encourage this harvest through the recognition of Aboriginal land management practices, such as seasonal burning to encourage the crop’s growth.
Periodic rest from grazing provided no control of an invasive perennial forb
Authors: Price J. N. , Whalley R. D. B. , van Klinken R. D. , Duggin J. A. , Gross C. L.
Published: September 2011

This study examined if one grazing strategy (namely seasonal rest) was effective in the control of the invasive forb Phyla canescens (Kunth) Greene (hereafter lippia). We examined if rest from grazing could increase the competitiveness of native palatable species by allowing time to recover from defoliation, thereby altering competitive interactions between native species and lippia. In a field trial, we manipulated cattle grazing to determine its effects on the biomass of lippia and native species. We compared rest from grazing at different times of the year with year-long grazing (low intensity continuous and high intensity short duration) and no grazing (permanently excluding large grazing animals). Experimental plots were stratified into different hydrological areas (approximately annual flooding and flooded less than once every 5 years) to include flood dynamics in the management scenarios. We detected no negative impacts of seasonal rest on lippia, but some positive effects on native species. We found that complete exclusion from grazing in areas that already have substantial lippia invasion (and no flooding) may actually favour the expansion of lippia (at certain times). This study does not suggest that grazing management cannot be used as a tool for lippia control – simply that seasonal resting had no effect over a 3-year period. This is likely due to the dynamics of a boom-and-bust landscape in which if the abiotic conditions are not suitable for growth, then native species will not grow whether grazed or rested.
Evaluating the efficacy of the EZ-Ject herbicide system in Queensland, Australia
Authors: Vitelli Joseph , Madigan Barbara
Published: September 2011

The EZ-Ject herbicide system was evaluated as a stem injection method for controlling woody weeds in a range of situations where traditional chemical application methods have limited scope. The equipment was trialled on three Queensland weed species; pond apple (Annona glabra), velvety tree pear (Opuntia tomentosa) and yellow oleander (Cascabela thevetia); at five different cartridge densities (0, 1, 2, 3 and 4) and with two herbicides (glyphosate and imazapyr). Cartridges filled with imazapyr were significantly more effective at controlling the three woody weed species than those filled with glyphosate. Injecting plants with three imazapyr cartridges resulted in plant kills ranging from 93 to 100%, compared with glyphosate kills of 17 to 100%. Pond apple was the most susceptible species, requiring one imazapyr cartridge or two glyphosate cartridges to kill 97 and 92% of the treated plants. Plant mortality increased as the number of cartridges injected increased. Mortality did not differ significantly for treatments receiving three and four imazapyr cartridges, as these cartridge densities met the criterion of injecting one cartridge per 10-cm basal circumference, a criterion recommended by the manufacturers for treating large plants (>6.35 cm in diameter at breast height). The cost of treating a weed infestation of 1500 plants ha–1 with three cartridges per tree is $1070 ha–1, with labour costs accounting for 16% of the total. The high chemical costs would preclude this technique from broad-scale use, but the method could have application for treating woody weeds in sensitive, high conservation areas.
Delivery of siRNA and other macromolecules into skin and cells using a peptide enhancer
Authors: Hsu Tracy , Mitragotri Samir
Published: September 2011

Delivery of macromolecules into cells and tissues such as skin is a major challenge. This obstacle poses a particular challenge for the delivery of siRNA where cellular and tissue level transport barriers need to be overcome. siRNAs are potential therapeutics for various dermatological diseases including psoriasis, atopic dermatitis, and cancer; however, their utility is limited by their low absorption across the stratum corneum (SC) and into viable cells of skin. Here, we address this challenge using a peptide identified by phage display termed skin penetrating and cell entering (SPACE) peptide. In vitro studies indicated that the SPACE peptide, when conjugated to cargoes such as small molecules and proteins, was able to facilitate their penetration across the SC into epidermis and dermis. The peptide also exhibited increased penetration into various cells including keratinocytes, fibroblasts, and endothelial cells, likely through a macropinocytosis pathway. The ability of SPACE peptide to deliver siRNA was tested in vivo using two targets, interleukin-10 and GAPDH. Conjugation of the peptide to siRNA led to their enhanced absorption into skin and knockdown of corresponding protein targets.
The bacterial actin MreB rotates, and rotation depends on cell-wall assembly
Authors: van Teeffelen Sven , Wang Siyuan , Furchtgott Leon , Huang Kerwyn Casey , Wingreen Ned S. , Shaevitz Joshua W. , Gitai Zemer
Published: September 2011

Bacterial cells possess multiple cytoskeletal proteins involved in a wide range of cellular processes. These cytoskeletal proteins are dynamic, but the driving forces and cellular functions of these dynamics remain poorly understood. Eukaryotic cytoskeletal dynamics are often driven by motor proteins, but in bacteria no motors that drive cytoskeletal motion have been identified to date. Here, we quantitatively study the dynamics of the
Escherichia coli
actin homolog MreB, which is essential for the maintenance of rod-like cell shape in bacteria. We find that MreB rotates around the long axis of the cell in a persistent manner. Whereas previous studies have suggested that MreB dynamics are driven by its own polymerization, we show that MreB rotation does not depend on its own polymerization but rather requires the assembly of the peptidoglycan cell wall. The cell-wall synthesis machinery thus either constitutes a novel type of extracellular motor that exerts force on cytoplasmic MreB, or is indirectly required for an as-yet-unidentified motor. Biophysical simulations suggest that one function of MreB rotation is to ensure a uniform distribution of new peptidoglycan insertion sites, a necessary condition to maintain rod shape during growth. These findings both broaden the view of cytoskeletal motors and deepen our understanding of the physical basis of bacterial morphogenesis.
Using speech and gesture to introduce new objects to young children
Authors: Clark Eve V. , Estigarribia Bruno
Published: September 2011

Adults rely on both speech and gesture to provide children with information pertinent to new word meanings. Parents were videotaped introducing new objects to their children (aged 1;6 and 3;0). They introduce these objects in three phases: (1) they establish joint attention on an object; (2) they introduce a label for it; (3) they situate the object conceptually. Parents used labels and gestures to maintain attention on the object; with one-year-olds, they led with gestures to capture the children’s attention. They added supplementary information about objects only after labeling them, again with speech and gesture. They used indicating gestures (point, touch, tap) to identify the objects labeled, their parts, and their properties. They used demonstrating gestures (turning a truck wheel, opening salad tongs) to depict actions and functions they were describing in words. These procedures support children in their construction of meanings for new words.
Adapting to the reader during writing
Authors: Lindgren Eva , Leijten Mariëlle , Van Waes Luuk
Published: September 2011

Awareness of the reader and ability to adapt the text to the reader are assumed to be important aspects of successful writing. Models of writing development include the aspect of reader awareness, as a rhetorical goal, that writers develop gradually and that eventually distinguishes expert writers from novice writers. However, developing writers can present an awareness of writing aspects without being able to apply them successfully on task. The role of maturation on the one hand and instruction and training on the other have been put forward as crucial aspects of writing development. Against this background, six writers, representing different levels of expertise in writing, undertook the same writing tasks. Eighteen texts, interviews and stimulated recall protocols are analysed, compared and contrasted with a particular focus on writers’ awareness of and adaptation to the intended reader. Keystroke logs provide a solid and complementary base for detailed analysis of the writing processes, in which revisions relating to a reader perspective are of particular importance. Findings provide support for the theoretical framework, but they also raise questions about the role of knowledge about genre and writing strategies in relation to maturation for successful writing development. Keywords: writing development; reader awareness; reader adaptation; keystroke logging; knowledge crafting; cognitive processes; revision; stimulated recall
The cognitive and linguistic demands of everyday, functional literacy tasks
Authors: White Sheida
Published: September 2011

After examining seminal research related to functional literacy and the national assessments of adult literacy, seven key cognitive and linguistic demands are proposed that everyday literacy tasks (e.g. reading a drug label) make: read words, comprehend sentences, search text, identify computations, perform computations, infer meaning, and apply information. The distinctiveness of the five non-quantitative task demands and their progression in difficulty were subjected to verification via independent psychometric analyses using 252 functional literacy tasks and responses of 46,000 adults aged 16 and older residing in households and prisons in the United States. The results of multidimensional item respond theory (MIRT) modeling indicate delineation among three sets of task demands. Findings are illustrated through application to a common task involving an over-the-counter drug label. Keywords: adult literacy; cognitive demand; functional literacy; linguistic demand; health literacy; over-the-counter drug labels
Local dialects, supralocal writing systems
Authors: Rutten Gijsbert , van der Wal Marijke J.
Published: September 2011

In historical sociolinguistics, it is often assumed that ego-documents such as private letters represent the spoken language of the past as closely as possible. In this paper, we will try to determine the degree of orality of seventeenth-century Dutch private letters: the degree to which the spoken local dialect is represented in these texts, and at the same time, the extent to which scribes possibly converged towards supralocal writing systems. We study the orthographical representation of four phonemes in a corpus of letters from the provinces of Holland and Zeeland. Clear cases of local writing practices are revealed, contributing to our knowledge of the spoken language in the past, as well as to the different ways in which it was represented in written language. However, the degree to which local features appear in the corpus is remarkably low. Only a minority of the letters contains localizable features, and if a letter contains these, it is usually only in a minority of the positions which, historically, were phonologically possible. We conclude that, in general, scribes did not aim to write their local dialect, but employed an intended supraregional variety instead. Keywords: Historical sociolinguistics; Dutch, seventeenth century; ego-documents; letters; writing systems; historical phonology; language from below; orality
Micromagnetic modelling on magnetization dynamics in nanopillars driven by spin-transfer torque
Authors: Kim Woojin , Lee Seo-Won , Lee Kyung-Jin
Published: September 2011

An overview on the current-induced magnetization dynamics in spin-valve nanopillars using micromagnetic modelling is presented in this paper. We first review briefly the terms of spin-transfer torque (STT) added to the conventional Landau–Lifshitz–Gilbert equation. Then, the effects of STT on the magnetization dynamics are discussed in the framework of micromagnetic modelling. The discussion mainly concerns the angular dependence of the STT, the pinned-layer dynamics and the non-uniform magnetization distribution along the thickness direction. At the end of the paper, we introduce some emerging issues which will be feasible for micromagnetic modelling such as the spin-motive force, the non-local spin torque and the Rashba effect.
Spin-transfer magnetization switching in ordered alloy-based nanopillar devices
Authors: Mitani S
Published: September 2011

This paper reviews spin-transfer magnetization switching in ordered alloy-based nanopillar devices. L10-ordered FePt was used for one of the earliest demonstrations of spin-transfer switching in perpendicularly magnetized systems. The behaviour of magnetization switching deviates from the predictions based on a macro-spin model, suggesting incoherent magnetization switching in the system with a large perpendicular magnetic anisotropy. The effect of a 90° spin injector on spin-transfer switching was also examined using L10-ordered FePt. Full-Heusler alloys are in another fascinating material class for spin-transfer switching because of their high-spin polarization of conduction electrons and possible small magnetization damping. A B2-ordered Co2FeAl0.5Si0.5-based device showed a low intrinsic critical current density of 9.3 × 106 A cm−2 for spin-transfer switching as well as a relatively large current-perpendicular-to-plane giant-magnetoresistance (CPP-GMR) up to ∼9%. The specific physical properties of ordered alloys may be useful for fundamental studies and applications in spin-transfer switching.
A brief review of field- and current-driven domain-wall motion
Authors: Shibata Junya , Tatara Gen , Kohno Hiroshi
Published: September 2011

A brief review of field- and recently developed current-driven domain-wall motion in a ferromagnetic nanowire is presented from a theoretical point of view. In the first part, the wall motion driven by an external magnetic field is studied on the basis of the Landau–Lifshitz–Gilbert equation and the collective coordinate method. The domain wall is treated as planar and rigid, called a one-dimensional model, and the wall motion is described by the relevant collective coordinates, centre position X and the polarization angle ϕ0 of the wall. We also consider the interaction between the collective coordinates and spin waves excited around the wall and provide applicable criteria for the collective coordinate method in the domain-wall system. In the second part, we devote ourselves to studying the effect of conduction electrons on the domain-wall dynamics in a ferromagnetic metal. Microscopic calculations of the spin-transfer torque, dissipative spin torque (β-term), non-adiabatic force and Gilbert damping are presented on the basis of the linear response theory and its extension. In the third part, the current-driven domain-wall motion described by the collective coordinates is studied. The effect of external pinning is also examined. There are several depinning mechanisms and threshold currents in different pinning regimes.
Current-induced domain wall motion in nanoscale ferromagnetic elements
Authors: Malinowski G , Boulle O , Kläui M
Published: September 2011

We review the details of domain wall (DW) propagation due to spin-polarized currents that could potentially be used in magnetic data storage devices based on domains and DWs. We discuss briefly the basics of the underlying spin torque effect and show how the two torques arising from the interaction between the spin-polarized charge carriers and the magnetization lead to complex dynamics of a spin texture such as a DW. By direct imaging we show how confined DWs in nanowires can be displaced using currents in in-plane soft-magnetic materials, and that when using short pulses, fast velocities can be attained. For high-anisotropy out-of-plane magnetized wires with narrow DWs we present approaches to deducing the torque terms and show that in these materials potentially more efficient domain wall motion could be achieved.
FLASH: fast length adjustment of short reads to improve genome assemblies
Authors: Magoč Tanja , Salzberg Steven L.
Published: September 2011

Motivation: Next-generation sequencing technologies generate very large numbers of short reads. Even with very deep genome coverage, short read lengths cause problems in de novo assemblies. The use of paired-end libraries with a fragment size shorter than twice the read length provides an opportunity to generate much longer reads by overlapping and merging read pairs before assembling a genome.

Results: We present FLASH, a fast computational tool to extend the length of short reads by overlapping paired-end reads from fragment libraries that are sufficiently short. We tested the correctness of the tool on one million simulated read pairs, and we then applied it as a pre-processor for genome assemblies of Illumina reads from the bacterium Staphylococcus aureus and human chromosome 14. FLASH correctly extended and merged reads >99% of the time on simulated reads with an error rate of <1%. With adequately set parameters, FLASH correctly merged reads over 90% of the time even when the reads contained up to 5% errors. When FLASH was used to extend reads prior to assembly, the resulting assemblies had substantially greater N50 lengths for both contigs and scaffolds.

Availability and Implementation: The FLASH system is implemented in C and is freely available as open-source code at http://www.cbcb.umd.edu/software/flash.

Contact:  t.magoc@gmail.com
survcomp: an R/Bioconductor package for performance assessment and comparison of survival models
Authors: Schröder Markus S. , Culhane Aedín C. , Quackenbush John , Haibe-Kains Benjamin
Published: September 2011

Summary: The survcomp package provides functions to assess and statistically compare the performance of survival/risk prediction models. It implements state-of-the-art statistics to (i) measure the performance of risk prediction models; (ii) combine these statistical estimates from multiple datasets using a meta-analytical framework; and (iii) statistically compare the performance of competitive models.

Availability: The R/Bioconductor package survcomp is provided open source under the Artistic-2.0 License with a user manual containing installation, operating instructions and use case scenarios on real datasets. survcomp requires R version 2.13.0 or higher. http://bioconductor.org/packages/release/bioc/html/survcomp.html

Contact:  bhaibeka@jimmy.harvard.edu; mschroed@jimmy.harvard.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Protein–protein binding affinity prediction on a diverse set of structures
Authors: Moal Iain H. , Agius Rudi , Bates Paul A.
Published: September 2011

Motivation: Accurate binding free energy functions for protein–protein interactions are imperative for a wide range of purposes. Their construction is predicated upon ascertaining the factors that influence binding and their relative importance. A recent benchmark of binding affinities has allowed, for the first time, the evaluation and construction of binding free energy models using a diverse set of complexes, and a systematic assessment of our ability to model the energetics of conformational changes.

Results: We construct a large set of molecular descriptors using commonly available tools, introducing the use of energetic factors associated with conformational changes and disorder to order transitions, as well as features calculated on structural ensembles. The descriptors are used to train and test a binding free energy model using a consensus of four machine learning algorithms, whose performance constitutes a significant improvement over the other state of the art empirical free energy functions tested. The internal workings of the learners show how the descriptors are used, illuminating the determinants of protein–protein binding.

Availability: The molecular descriptor set and descriptor values for all complexes are available in the Supplementary Material. A web server for the learners and coordinates for the bound and unbound structures can be accessed from the website: http://bmm.cancerresearchuk.org/~Affinity

Contact:  paul.bates@cancer.org.uk

Supplementary Information:  Supplementary data are available at Bioinformatics online.
First Report of Squash Mosaic Virus in Ornamental Pumpkin in the Czech Republic
Authors: Svoboda J. , Leisova-Svobodova L.
Published: September 2011

In August 2010, yellow mosaic and leaf deformation were observed on leaves of field planted ornamental pumpkin (Cucurbita pepo L. convar. microcarpina Grebenščikov) plants near Tasovice Village in the Znojmo District of the Czech Republic. These symptoms were typical of a virus infection. Nine leaf samples were collected and examined for the presence of commonly occurring cucurbit viruses by double-antibody sandwich (DAS)-ELISA. Eight samples were infected with Zucchini yellow mosaic virus (ZYMV), seven with Watermelon mosaic virus-2 (WMV-2), five with Cucumber mosaic virus (CMV), and two with Squash mosaic virus (SqMV). Some aphid species were observed on inspected plants but we did not carried out a search for vectors. SqMV isolates, Tas-1 and Tas-5, were also infected with ZYMV and WMV-2. SqMV was separated from the other viruses by mechanical inoculation onto the resistant plant species Cucumis sativus L. ‘Taichung Mou Gua-1’, which is resistant to ZYMV and WMV-2 (3). The virus was transmitted back to C. pepo plants, and DAS-ELISA used for testing for multiple viruses proved the presence of SqMV alone. A C. pepo leaf sample was examined by electron microscopy to validate the presence of the virus. Isometric particles of approximately 30 nm in diameter, corresponding in size and shape to the described particles of SqMV (2), were observed. The presence of SqMV was verified by reverse transcription (RT)-PCR using specific primers designed on the sequence for coat proteins of SqMV found in NCBI and EMBL databases (SqMV-F: TGTGTACAAGATTGGTGGAGATGC; SqMV-R: AGGCTTCTAAAGCGAACTGGG). The obtained amplicons of approximately 1,900 bp were sequenced (GenBank Accession No. JF922966), and by using nucleotide blast analysis (4), identified as a part of RNA-2 genome. Blast analysis showed that the Czech SqMV isolates, Tas-1 and Tas-5, were identical and similar to published SqMV sequences from the United States, Japan, and China. The highest similarity was found between the Czech isolates and one isolate from the United States (Accession No. M96148; E = 0, nucleotide sequence identity = 90%) and one from China (Accession No. AF059533; E = 0, nucleotide sequence identity = 90%). To our knowledge, this is the first report of a natural occurrence of SqMV in the Czech Republic. SqMV can be transmitted via infected seeds by as much as 35% (1); therefore, protection against epidemics should be based on clean seed programs.

References: (1) M. Alvarez et al. Phytopathology 68:257, 1978. (2) H. M. Mazzone et al. Biochim. Biophys. Acta 55:164, 1962. (3) T. Wai et al. J. Hered. 88:454, 1997. (4) Z. Zhang et al. J. Comput. Biol. 7:203, 2000.
Differential expression in RNA-seq: A matter of depth
Authors: Tarazona Sonia , García-Alcalde Fernando , Dopazo Joaquín , Ferrer Alberto , Conesa Ana
Published: September 2011

Next-generation sequencing (NGS) technologies are revolutionizing genome research, and in particular, their application to transcriptomics (RNA-seq) is increasingly being used for gene expression profiling as a replacement for microarrays. However, the properties of RNA-seq data have not been yet fully established, and additional research is needed for understanding how these data respond to differential expression analysis. In this work, we set out to gain insights into the characteristics of RNA-seq data analysis by studying an important parameter of this technology: the sequencing depth. We have analyzed how sequencing depth affects the detection of transcripts and their identification as differentially expressed, looking at aspects such as transcript biotype, length, expression level, and fold-change. We have evaluated different algorithms available for the analysis of RNA-seq and proposed a novel approach—NOISeq—that differs from existing methods in that it is data-adaptive and nonparametric. Our results reveal that most existing methodologies suffer from a strong dependency on sequencing depth for their differential expression calls and that this results in a considerable number of false positives that increases as the number of reads grows. In contrast, our proposed method models the noise distribution from the actual data, can therefore better adapt to the size of the data set, and is more effective in controlling the rate of false discoveries. This work discusses the true potential of RNA-seq for studying regulation at low expression ranges, the noise within RNA-seq data, and the issue of replication.
Paediatric B‐cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13): clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols
Authors: Andersen Mette K. , Autio Kirsi , Barbany Gisela , Borgström Georg , Cavelier Lucia , Golovleva Irina , Heim Sverre , Heinonen Kristina , Hovland Randi , Johannsson Johann H. , Johansson Bertil , Kjeldsen Eigil , Nordgren Ann , Palmqvist Lars , Forestier Erik
Published: September 2011

The translocation t(1;19)(q23;p13)/der(19)t(1;19) is a risk stratifying aberration in childhood B‐cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19)t(1;19)‐positive BCP ALL treated on two successive Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007 and have reviewed the clinical and cytogenetic characteristics of these cases, comprising 1·8% of all cases. The translocation was balanced in 15 cases (32%) and unbalanced in 29 cases (62%). The most common additional chromosome abnormalities were del(9p), i(9q), del(6q), and del(13q). The median age was 7 years, the median white blood cell (WBC) count was 16 × 109/l, and the female/male ratio was 1·2. The predicted event‐free survival (EFS) at 5 and 10 years was 0·79, whereas the predicted overall survival (OS) at 5 and 10 years was 0·85 and 0·82, respectively. Nine patients had a bone marrow relapse after a median of 23 months; no patient had a central nervous system relapse. Additional cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was balanced or unbalanced did not influence EFS or OS. Compared to cases with t(12,21) and high hyperdiploidy, EFS was similar, but overall survival was worse in patients with t(1;19)/der(19)t(1;19) (P = 0·004).
KRN5500, a spicamycin derivative, exerts anti‐myeloma effects through impairing both myeloma cells and osteoclasts
Authors: Miki Hirokazu , Ozaki Shuji , Nakamura Shingen , Oda Asuka , Amou Hiroe , Ikegame Akishige , Watanabe Keiichiro , Hiasa Masahiro , Cui Qu , Harada Takeshi , Fujii Shiro , Nakano Ayako , Kagawa Kumiko , Takeuchi Kyoko , Yata Ken‐ichiro , Sakai Akira , Abe Masahiro , Matsumoto Toshio
Published: September 2011

The spicamycin analogue KRN5500 alters glycoprotein processing and induces damage in the endoplasmic reticulum (ER)‐Golgi apparatus in cancer cells. In the present study, we explored the cytotoxic effects of KRN5500 on multiple myeloma (MM) cells and the bone marrow microenvironment with special reference to ER stress. Cell proliferation assay showed that KRN5500 induced G1 arrest and apoptosis in MM cells in a time‐ and dose‐dependent manner. KRN5500 enhanced ER stress independently of caspase activation in MM cells. This cell death was observed even in the presence of bone marrow stroma cells or osteoclasts. Notably, KRN5500 induced cell death also in osteoclasts. In vivo effects of KRN5500 were evaluated using two xenograft models established in severe combined immunodeficient (SCID) mice by either subcutaneous injection of RPMI 8226 cells or intra‐bone injection of INA‐6 cells to subcutaneously implanted rabbit bones (SCID‐rab model). KRN5500 significantly inhibited tumour growth in both animal models, and decreased the number of osteoclasts, which resulted in prevention of bone destruction in the SCID‐rab model. These results suggest that KRN5500 exerts anti‐MM effects through impairing both MM cells and osteoclasts. Therefore, this unique mechanism of KRN5500 might be a useful therapeutic option in patients with MM.
Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents
Authors: Ghanima Waleed , Junker Peter , Hasselbalch Hans Carl , Boiocchi Leonardo , Geyer Julia T. , Feng Xingmin , Gudbrandsdottir Sif , Orazi Attilio , Bussel James B.
Published: September 2011

This study assessed the grade of bone marrow (BM) fibrosis and its association with a seromarker for collagen‐III formation and fibrosis‐related cytokines in 25 immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists (Tpo‐RA) who had at least one BM biopsy. Assessment of 8 pre‐ and on‐treatment BM biopsies revealed statistically significant increases in reticulin. Reticulin in biopsies performed after a median of 1·4 years of treatment was graded: MF‐0 in 3 (12%), MF‐1 in 19 (76%), MF‐2 in 2 (8%) and MF‐3 in 1 (4%). No cytogenetic or flow‐cytometric abnormalities were detected. Median pretreatment Procollagen III N‐propeptide (PIIINP) (6·6 μg/l) was significantly higher than on‐treatment levels (5·6 μg/l); both were higher than controls (3·4 μg/l; P < 0·001). PIIINP was negatively correlated with treatment duration (r = −0·49) suggesting a decelerated reticulin production over time. There was a trend towards an association between grade of reticulin and PIIINP. Transforming growth factor (GF)‐beta and basic‐Fibroblast GF were not different between patients and controls but Hepatocyte GF (HGF), an anti‐fibrotic cytokine, was significantly elevated in patients. In conclusion, low‐grade BM reticulin fibrosis is seen in most ITP patients on Tpo‐RA. The novel findings of decreasing PIIINP and elevated HGF need further investigation to explore their significance in BM fibrogenesis.