bluuebunny/crossref_metadata_2025 huggingface dataset:
Staining of Mitochondria with Cy5-Labeled Oligonucleotides for Long-Term Microscopy Studies
Authors: Lorenz Steffen , Tomcin Stephanie , Mailänder Volker
Published: May 2011

Labeling of organelles for microscopy is achieved generally by specific dyes that either accumulate in a cellular compartment such as cyanine dyes in mitochondria or are only fluorescent under specific conditions such as the low pH in the lysosome. Here we demonstrate that Cy5—a fluorescent molecule that does not enter cells by itself—can be loaded into cells by attaching a short oligonucleotide. This very inexpensive labeling procedure can be done in the presence of serum. Therefore, very sensitive cell types should also be amenable to this procedure, and longer observations can be achieved compared to other commercially available dyes as the labeling reagent does not need to be washed out. This also points to the pitfall of using fluorescently labeled oligonucleotides for live cell imaging where the oligonucleotide is supposed to detect a specific target sequence in its subcellular distribution.
G-Spirantization and Lateral Ambivalence in Northern German Dialects
Authors: Glover Justin
Published: May 2011

In the Kiel German regional variety (KG), /ɡ/ undergoes spirantization after vowels and /ʀ/ but not after /l/. KG contrasts with data provided by Wiese (1996) for a dialect that he calls Northern Colloquial Speech (NCS), in which /ɡ/ spirantizes not only after vowels and /ʀ/, but also after /l/. I argue that G-Spirantization in both regional varieties is an example of an assimilation which spreads [+continuant] from a vowel or /ʀ/ in KG (and /l/ in NCS) to a following coda /ɡ/. The difference between the /…lɡ/ environment in the two dialects can be explained by lateral ambivalence, as described in detail by Mielke (2005).*
Extrasolar asteroid mining as forensic evidence for extraterrestrial intelligence
Authors: Forgan Duncan H. , Elvis Martin
Published: May 2011

The development of civilizations such as ours into spacefaring, multi-planet entities requires significant raw materials to construct vehicles and habitats. Interplanetary debris, including asteroids and comets, may provide such a source of raw materials. In this article, we present the hypothesis that extraterrestrial intelligences (ETIs) engaged in asteroid mining may be detectable from Earth. Considering the detected disc of debris around Vega as a template, we explore the observational signatures of targeted asteroid mining (TAM), such as unexplained deficits in chemical species, changes in the size distribution of debris and other thermal signatures that may be detectable in the spectral energy distribution (SED) of a debris disc. We find that individual observational signatures of asteroid mining can be explained by natural phenomena, and as such they cannot provide conclusive detections of ETIs. But, it may be the case that several signatures appearing in the same system will prove harder to model without extraterrestrial involvement. Therefore, signatures of TAM are not detections of ETI in their own right, but as part of ‘piggy-back’ studies carried out in tandem with conventional debris disc research, they could provide a means of identifying unusual candidate systems for further study using other search for extra terrestrial intelligence (SETI) techniques.
Informal payments for health care – the phenomenon and its context
Authors: Cohen Nissim
Published: May 2011

This paper reviews current research and literature on the issue of informal payments for health care and its context and suggests a new perspective for a better understanding of this phenomenon. This perspective, based on political culture and behavior and on wider social processes, is already used to explain various phenomena from different fields of public policy. The paper explains the impact of a specific type of political culture, called ‘alternative politics’ (AP) in the Israeli literature, on healthcare policy and institutional healthcare settings. AP is based on a ‘do-it-yourself’ approach adopted by citizens to address their dissatisfaction with governmental services. When such a mode of political culture is diffused to all sectors and levels of society, all players, including bureaucrats and politicians, are guided by short-term considerations and apply unilateral strategies that bypass formal rules either through illegal activity or by marginalizing formal rules. Explaining informal payments by analyzing social processes and political culture and behavior has some disadvantages, but it provides us with a better understanding of the phenomenon while covering most of its characteristics and configurations.
The Layha for the Mujahideen: an analysis of the code of conduct for the Taliban fighters under Islamic law
Authors: Munir Muhammad
Published: May 2011

The following article focuses on the Islamic Emirate of Afghanistan Rules for the Mujahideen** to determine their conformity with the Islamic jus in bello. This code of conduct, or Layha, for Taliban fighters highlights limiting suicide attacks, avoiding civilian casualties, and winning the battle for the hearts and minds of the local civilian population. However, it has altered rules or created new ones for punishing captives that have not previously been used in Islamic military and legal history. Other rules disregard the principle of distinction between combatants and civilians and even allow perfidy, which is strictly prohibited in both Islamic law and international humanitarian law. The author argues that many of the Taliban rules have only a limited basis in, or are wrongly attributed to, Islamic law.
The protective scope of Common Article 3: more than meets the eye
Authors: Pejic Jelena
Published: May 2011

Non-international armed conflicts are not only prevalent today, but are also evolving in terms of the types that have been observed in practice. The article sets out a possible typology and argues that Common Article 3 to the Geneva Conventions may be given an expanded geographical reading as a matter of treaty law. It also suggests that there is a far wider range of rules – primarily of a binding nature, but also policy-based – that apply in Common Article 3 armed conflicts with regard to the treatment of persons in enemy hands and the conduct of hostilities.
Polyamorphism and the universal liquid–liquid critical point in the supercooled state
Authors: Greaves G.N.
Published: May 2011

The physics of critical phenomena is well established in systems as diverse as molecular fluids, crystalline alloys and magnetic materials. As the critical point is approached, the susceptibility increases anomalously and fluctuations give rise to dramatic opalescence. Evidence has recently emerged for the existence of a second critical point in the liquid state at supercooled temperatures, below which polyamorphic phases coexist differing in density but sharing the same composition. Whilst much attention has been paid to supercooled water, polyamorphic phases have been observed in many elemental and oxide liquids potentially offering routes to low-entropy glasses. Our recent direct observation of a polyamorphic phase transition in levitated molten yttria–alumina offers the first opportunity to study the associated critical point in a real supercooled system.In situsmall-angle X-ray scattering records sharp rises in the average correlation length of density fluctuations and in the compressibility as the transition is approached. Both increases approximate to the universal power-law relations predicted by the three-dimensional Ising model in common with all critical point phenomena. The observation brings the second critical point predicted in liquids into line with other critical phenomena.
A divide and conquer approach to cope with uncertainty, human health risk, and decision making in contaminant hydrology
Authors: de Barros Felipe P. J. , Bolster Diogo , Sanchez‐Vila Xavier , Nowak Wolfgang
Published: May 2011

Assessing health risk in hydrological systems is an interdisciplinary field. It relies on the expertise in the fields of hydrology and public health and needs powerful translation concepts to provide decision support and policy making. Reliable health risk estimates need to account for the uncertainties and variabilities present in hydrological, physiological, and human behavioral parameters. Despite significant theoretical advancements in stochastic hydrology, there is still a dire need to further propagate these concepts to practical problems and to society in general. Following a recent line of work, we use fault trees to address the task of probabilistic risk analysis and to support related decision and management problems. Fault trees allow us to decompose the assessment of health risk into individual manageable modules, thus tackling a complex system by a structural divide and conquer approach. The complexity within each module can be chosen individually according to data availability, parsimony, relative importance, and stage of analysis. Three differences are highlighted in this paper when compared to previous works: (1) The fault tree proposed here accounts for the uncertainty in both hydrological and health components, (2) system failure within the fault tree is defined in terms of risk being above a threshold value, whereas previous studies that used fault trees used auxiliary events such as exceedance of critical concentration levels, and (3) we introduce a new form of stochastic fault tree that allows us to weaken the assumption of independent subsystems that is required by a classical fault tree approach. We illustrate our concept in a simple groundwater‐related setting.
Deterministic nanoassembly of a coupled quantum emitter–photonic crystal cavity system
Authors: van der Sar T. , Hagemeier J. , Pfaff W. , Heeres E. C. , Thon S. M. , Kim H. , Petroff P. M. , Oosterkamp T. H. , Bouwmeester D. , Hanson R.
Published: May 2011

Controlling the interaction of a single quantum emitter with its environment is a key challenge in quantum optics. Here, we demonstrate deterministic coupling of single nitrogen-vacancy (NV) centers to high-quality photonic crystal cavities. We preselect single NV centers and position their 50-nm-sized host nanocrystals into the mode maximum of photonic crystal S1 cavities with few-nanometer accuracy. The coupling results in a strong enhancement of NV center emission at the cavity wavelength.
Nonlinear simulation of toroidal Alfvén eigenmode with microturbulence-induced radial diffusion
Authors: Lang Jianying , Fu Guo-Yong
Published: May 2011

It is shown analytically and numerically that microturbulence-induced diffusivity can affect nonlinear saturation of energetic particle driven modes in the similar way as collisional pitch angle scattering does. Introducing a simple diffusion operator to the code, our numerical results have shown that a single toroidal Alfvén eigenmode (TAE) can saturate at a steady state with sufficiently high diffusion rate. The calculated saturation level scales with the radial diffusion rate by the same scaling of pitch angle scattering. A criterion is derived to judge the importance of microturbulence-induced radial diffusion effect comparing to the collisional pitch angle scattering effect. According to the criterion, we find that the microturbulence-induced diffusion has a stronger effect than the Coulomb collision on the TAE saturation in present tokamak devices and future burning plasmas [International Thermonuclear Experimental Reactor (ITER)].
Self-catalyzed GaAs nanowire growth on Si-treated GaAs(100) substrates
Authors: Ambrosini S. , Fanetti M. , Grillo V. , Franciosi A. , Rubini S.
Published: May 2011

Self-catalyzed GaAs nanowire growth was obtained by molecular beam epitaxy on GaAs(001) substrates after predeposition of subnanometer-thick Si layers. Two substrate preparation methods are presented, the first based on the epitaxial growth of Si on GaAs and subsequent exposure to atmosphere, and the second on the direct deposition of Si on epiready GaAs substrates. X-ray photoemission spectroscopy shows that both methods result in a thin Si oxide layer that promotes the growth of GaAs nanowires aligned along the 〈111〉 direction. High densities of nanowires were obtained at substrate temperatures between 620 and 680 °C. Systematic electron microscopy studies indicate that nanowire growth is associated with the formation of Ga nanoparticles on the substrate surface, which act as a catalyst in the vapor-liquid-solid growth mechanism frame. The majority of the nanowires have a pure zinc-blende structure, and their photoluminescence is dominated by a photoluminescence peak 3 to 5 meV in width and centered at 1.516 to 1517 eV.
Dependence of crystal orientation and bandgap on substrate temperature of molecular-beam epitaxy grown InN on bare Al2O3 (0001)
Authors: Kuyyalil Jithesh , Tangi Malleswararao , Shivaprasad S. M.
Published: May 2011

The issue of variable bandgap values for InN films grown on c-sapphire has been addressed in this work. α-InN films have been deposited in nitrogen rich condition at different substrate temperatures on bare Al2O3 (0001) by plasma assisted molecular beam epitaxy (PA-MBE). The results of several complementary characterization techniques show that single crystalline wurtzite InN is formed, but their orientation depends on the substrate temperature. The bandgap measured on these samples (1.78 eV) is explained by Moss-Burstein shift on these degenerately n-doped samples. Our results discount effects of crystal orientation, presence of oxygen at grain boundaries and In/N stoichiometry as factors that influence the measured band-gap values.
Interaction of two solitary waves in quantum electron-positron-ion plasma
Authors: Xu Yan-Xia , Liu Zong-Ming , Lin Mai-Mai , Shi Yu-Ren , Chen Jian-Min , Duan Wen-Shan
Published: May 2011

The collision between two ion-acoustic solitary waves with arbitrary colliding angle θ in an unmagnetized, ultracold quantum three-component e-p-i plasma has been investigated. By using the extended Poincaré-Lighthill-Kuo (PLK) perturbation method, we obtain the KdV equations and the analytical phase shifts after the collision of two solitary waves in this three-component plasma. The effects of the quantum parameter H, the ratio of Fermi positron temperature to Fermi electron temperature σ, the ratio of Fermi positron number density to Fermi electron number density μ, and the ratio of Fermi ion temperature to Fermi electron temperature ρ on the phase shifts are studied. It is found that these parameters can significantly influence the phase shifts of the solitons.
A dynamic punch method to quantify the dynamic shear strength of brittle solids
Authors: Huang S. , Feng X. T. , Xia K.
Published: May 2011

Shear strength is an important material parameter for brittle solids. This parameter has been extensively used in material failure models. Although a few methods have been proposed to quantify this parameter under the static loading condition, there is no such a method available to measure it under dynamic loading conditions. This paper presents a punch shear device to measure the dynamic shear strength of brittle solids. In this method, a split Hopkinson pressure bar system (SHPB) is used to exert the dynamic load to a thin disc sample, which is placed in a specially designed holder to minimize the bending stress induced by punching. The sample holder also allows the punch head to load the sample directly and in combination with momentum-trap technique in SHPB, it enables soft recovery of the rock plug and rock ring produced by the punching test. The flexibility and applicability of this method is demonstrated by the application of an isotropic and fine-grained sandstone. Within the theoretical framework of the classical Mohr-Coulomb failure model, the obtained dynamic shear strengths are consistent with the dynamic tensile strengths for the same rock from the literature.
Impact of dispersion, free carriers, and two-photon absorption on the generation of intense terahertz pulses in ZnTe crystals
Authors: Vidal S. , Degert J. , Tondusson M. , Oberlé J. , Freysz E.
Published: May 2011

We study the evolution of the energy and the spectrum of a terahertz wave generated by optical rectification of an ultrashort laser pulse in ZnTe crystals with different thicknesses. As the pump intensity increases, we observe a shift in the terahertz spectrum toward lower frequencies. Moreover, at high pump intensities, in disagreement with common sense, thin crystals have a better conversion efficiency than thicker ones. These phenomena are accounted for by the pump depletion induced by two-photon absorption, pulse broadening and the impact of the photoinduced free carriers on the complex refractive index of the crystal in the terahertz range.
Demographic structure, genetic diversity and habitat distribution of the endangered, Australian rainforest tree Macadamia jansenii help facilitate an introduction program
Authors: Shapcott Alison , Powell Michael
Published: May 2011

Macadamia jansenii is endemic to south-east Queensland, Australia, and is currently known from a single population 180 km north of the nearest wild population of its congener, the edible Macadamia integrifolia. A recently developed Macadamia recovery plan identified that this population was under significant threat and recommended a reintroduction program to safeguard against chance extinction of the single wild population. This study undertook demographic population census surveys, genetic analysis, habitat analysis and niche modelling to determine the potential long-term viability for the species, and to guide search and reintroduction programs. We expanded the known population size of the species to ~60 individuals (1 m and taller) spread over a 900-m distance along a single creek clumped into three subpopulations. There was moderate genetic diversity in the species and the subpopulations showed little genetic differentiation. We developed a potential habitat model combining abiotic variables and vegetation associations, and mapped areas of potentially suitable habitat for M. jansenii within its local area. These maps are being used to target searches for other populations and to guide the location of introduction populations.
Origins of a morphological cline between Eucalyptus melanophloia and Eucalyptus whitei
Authors: Holman James E. , Hughes Jane M. , Fensham Roderick J.
Published: May 2011

Most theories to explain the origin and maintenance of clines in Eucalyptus are based on a morphological classification system. The true relationships between putative species along clines require detailed investigation of phylogenetic relationships. A cline between Eucalyptus melanophloia and E. whitei was examined using morphological and molecular analyses to determine whether genetic structuring in nuclear and chloroplast DNA along the cline could be explained by secondary contact between independent evolutionary lineages, or whether the cline represents a single species that has undergone primary differentiation. Morphological analysis showed phenotypic variation distributed continuously across the cline and that seedlings bred true to parental type. Microsatellite analysis indicated that there was little genetic structuring across the cline, and low levels of population differentiation. This result was further reinforced by analysis of the cpDNA. The phylogeographic distribution of cpDNA haplotypes is likely to have resulted from restricted seed-mediated gene flow with isolation by distance. A cogent explanation for the cline is that it has arisen by selection on leaf types promoted by a gradient in precipitation with the short-broad, subsessile leaves of E. melanophloia favoured under higher rainfall and the long, narrow, petiolate leaves of E. whitei favoured in arid environments.
Ophiostoma species (Ophiostomatales, Ascomycota), including two new taxa on eucalypts in Australia
Authors: Nkuekam G. Kamgan , Wilhelm de Beer Z. , Wingfield Michael J. , Mohammed Caroline , Carnegie Angus J. , Pegg Geoff S. , Roux Jolanda
Published: May 2011

The genus Ophiostoma accommodates ascomycetes in the order Ophiostomatales, some of which are important pathogens of trees. Although these fungi are well known in the northern hemisphere, very little is known regarding their occurrence or importance in Australia. The aim of the present study was to collect Ophiostoma spp. infecting wounds on Eucalyptus spp. in Australia, where most of these trees are native. Collections were made in three states of Australia and the isolates were identified using morphological and multigene-sequence comparisons. Of the 76 isolates collected, two previously unknown species of Ophiostoma were found and these are described here as O. tasmaniense sp. nov. and O. undulatum sp. nov. In addition, O. quercus (Georgev.) Nannf. and O. tsotsi Grobbelaar, Z.W.de Beer & M.J.Wingf. are reported for the first time from eucalypts in Australia and the distribution of Pesotum australiae Kamgan Nkuekam, Jacobs & Wingfield is expanded to include eucalypts in Tasmania. In pathogenicity tests, very small lesions were observed in both the bark and xylem of E. grandis (Hill) Maiden trees, suggesting that none of the collected species is a pathogen of Eucalyptus spp.
Triploidy causes sexual infertility in Cyrtanthus breviflorus (Amaryllidaceae)
Authors: Ramsey Mike , Vaughton Glenda , Ascough Glendon D. , Johnson Steven D.
Published: May 2011

The balance between sexual and asexual reproduction can vary markedly in clonal plants. At one extreme, plants are sexually infertile and reproduction is solely clonal. Infertility can be caused by environmental and/or genetic factors, but the role of each is often unknown. Here we determine variation in sexual reproduction and explore the underlying factors causing sexual infertility in Cyrtanthus breviflorus Harv. We examined open- and cross-pollinated fruit set, ploidy using flow cytometry, pollen viability, pollinator visits to flowers and pollen deposition onto stigmas. One population was sexually infertile; no plants produced fruit. Three populations were sexually fertile; >98% of plants produced fruit. Percent pollen viability differed between infertile (18%) and fertile (97%) populations. The most likely cause of infertility was unequal ploidy. Plants in the infertile population were triploid, whereas those in fertile populations were diploid. Pollination factors were not related to infertility. In infertile and fertile populations, pollen-collecting insects visited flowers frequently, depositing 4-fold more pollen grains onto stigmas than the number of ovules per flower. Our study is the first to demonstrate infertility and triploidy in C. breviflorus. How triploidy became established despite high levels of pollinator activity remains a challenging question.
Nitrous oxide and methane emissions from soil are reduced following afforestation of pasture lands in three contrasting climatic zones
Authors: Allen D. E. , Mendham D. S. , Bhupinderpal-Singh  , Cowie A. , Wang W. , Dalal R. C. , Raison R. J.
Published: May 2011

Land use change from agriculture to forestry offers potential opportunities for carbon (C) sequestration and thus partial mitigation of increasing levels of carbon dioxide (CO2) in the atmosphere. The effects of land use change of grazed pastures on in situ fluxes of nitrous oxide (N2O) and methane (CH4) from soil were examined across 3 forest types in Australian temperate, Mediterranean, and subtropical regions, using a network of paired pasture−forest sites, representing 3 key stages of forest stand development: establishment, canopy-closure, and mid to late rotation. During the 12-month study, soil temperature ranged from –6° to 40°C and total rainfall from 487 to 676 mm. Rates of N2O flux ranged between 1 and 100 μg/m2.h in pasture soils and from –5 to 50 μg/m2.h in forest soils; magnitudes were generally similar across the 3 climate zones. Rates of CH4 flux varied from –1 to –50 μg/m2.h in forest soil and from +10 to –30 μg/m2.h in pasture soils; CH4 flux was highest at the subtropics sites and lowest at the Mediterranean sites. In general, N2O emissions were lower, and CH4 consumption was higher, under forest than pasture soils, suggesting that land use change from pasture to forest can have a positive effect on mitigation of non-CO2 greenhouse gas (GHG) emissions from soil as stands become established. The information derived from this study can be used to improve the capacity of models for GHG accounting (e.g. FullCAM, which underpins Australia’s National Carbon Accounting System) to estimate N2O and CH4 fluxes resulting from land use change from pasture to forest in Australia. There is still, however, a need to test model outputs against continuous N2O and CH4 measurements over extended periods of time and across a range of sites with similar land use, to increase confidence in spatial and temporal estimates at regional levels.
Soil nematode community succession in stabilised sand dunes in the Tengger Desert, China
Authors: Zhi Dejuan , Nan Wenbin , Ding Xiaoxia , Xie Qinjian , Li Hongyu
Published: May 2011

In order to examine how nematodes respond to sand dune succession after stabilisation and reclamation techniques, nematode communities were investigated in sand dunes stabilised for 0, 16, 26, 43, and 51 years in the Tengger Desert, China. Our results revealed that the abundance of nematodes; the proportion of fungivores, omnivores, and predators; maturity index (MI); Shannon index; evenness; and structure index (SI) were affected significantly by the age of stabilised sand dunes, and were correlated with soil physical and chemical properties to different degrees. There were differences in nematode abundance, the proportion of fungivores, Shannon index, and evenness between the shifting dunes and the stabilised dunes, but not within the different succession stages of the stabilised dunes. MI showed a tendency to increase with dune age and SI increased significantly with dune age. MI, and especially SI, could act as robust indicators of stabilised sand dune succession. Redundancy analysis using data on nematode community composition showed that shifting sand dunes were clearly separated from stabilised sand dunes, and younger sand dunes stabilised for 16 and 26 years were also separated from older dunes stabilised for 43 and 51 years to a lesser degree. The results indicated that changes in nematode communities could predict initial sand dune stabilisation due to the planting of artificial vegetation, and clearly differentiate sand dune succession accompanied by vegetation succession and variation of soil properties.
Soil quality and plant yield under dryland and irrigated winter forage crops grazed by sheep or cattle
Authors: Houlbrooke D. J. , Paton R. J. , Morton J. D. , Littlejohn R. P.
Published: May 2011

In New Zealand, the winter grazing of standing forage crops combines high animal stocking densities with soil water and climatic conditions conducive to soil compaction and pugging deformation. The extent of soil damage under winter forage cropping practices and impact of management factors such as stock type and irrigation on soil quality is relatively unknown. A research trial was established, on a Pallic soil type (Aeric Fragiaquept) in the North Otago Rolling Downlands of New Zealand, to compare cattle v. sheep and dryland v. irrigation management. Kale, Swedes, and triticale were direct-drilled in 3 consecutive years and soil physical (macroporosity, bulk density, structural condition score), chemical (total C, total N, C : N ratio), and biological (mineralisable N, mineralisable C, and earth worm mass and numbers) properties were assessed annually post grazing in midwinter. Increased soil compaction was evident following grazing of winter forage crops, with lower macroporosity (P < 0.01) measured at 0–50 mm under cattle grazing compared with sheep grazing for 2 of 3 years and greater bulk density (P < 0.05) measured under cattle grazing for all years. However, there was no affect of stock type on crop yield for all 3 forage crops as a result of the measured differences in soil compaction. There were few differences between treatments or through time in soil chemical or biological properties following 3 years of continuous winter forage cropping as pools of C and N are slow to change under a no-tillage cropping regime and not necessarily measurable over a relatively short time frame.
Generating protein interaction maps from incomplete data:
application to fold assignment
Authors: Lappe Michael , Park Jong , Niggemann Oliver , Holm Liisa
Published: May 2011

Motivation: We present a framework to generate comprehensive overviews of protein-protein interactions. In the post-genomic view of cellular function, each biological entity is seen in the context of a complex network of interactions. Accordingly, we model functional space by representing protein-protein-interaction data as undirected graphs. We suggest a general approach to generate interaction maps of cellular networks in the presence of huge amounts of fragmented and incomplete data, and to derive representations of large networks which hide clutter while keeping the essential architecture of the interaction space. This is achieved by contracting the graphs according to domain-specific hierarchical classifications. The key concept here is the notion of induced interaction, which allows the integration, comparison and analysis of interaction data from different sources and different organisms at a given level of abstraction.

Results: We apply this approach to compute the overlap between the DIP compendium of interaction data and a dataset of yeast two-hybrid experiments. The architecture of this network is scale-free, as frequently seen in biological networks, and this property persists through many levels of abstraction. Connections in the network can be projected downwards from higher levels of abstraction down to the level of individual proteins. As an example, we describe an algorithm for fold assignment by network context. This method currently predicts protein folds at 30% accuracy without any requirement of detectable sequence similarity of the query protein to a protein of known structure. We used this algorithm to compile a list of structural assignments for previously unassigned genes from yeast. Finally we discuss ways forward to use interaction networks for the prediction of novel protein-protein interactions.

Availability: http://www.ebi.ac.uk/~lappe/FoldPred/

Contact: lappe@ebi.ac.uk

*To whom correspondence should be addressed.
Fragment assembly with double-barreled data
Authors: Pevzner Pavel A. , Tang Haixu
Published: May 2011

For the last twenty years fragment assembly was dominated by the “overlap - layout - consensus” algorithms that are used in all currently available assembly tools. However, the limits of these algorithms are being tested in the era of genomic sequencing and it is not clear whether they are the best choice for large-scale assemblies. Although the “overlap - layout - consensus” approach proved to be useful in assembling clones, it faces difficulties in genomic assemblies: the existing algorithms make assembly errors even in bacterial genomes. We abandoned the “overlap - layout - consensus” approach in favour of a new Eulerian Superpath approach that outperforms the existing algorithms for genomic fragment assembly (Pevzner et al. 2001 InProceedings of the Fifth Annual International Conference on Computational Molecular Biology (RECOMB-01), 256–26). In this paper we describe our new EULER-DB algorithm that, similarly to the Celera assembler takes advantage of clone-end sequencing by using the double-barreled data. However, in contrast to the Celera assembler, EULER-DB does not mask repeats but uses them instead as a powerful tool for contig ordering. We also describe a new approach for the Copy Number Problem: “How many times a given repeat is present in the genome?”. For long nearly-perfect repeats this question is notoriously difficult and some copies of such repeats may be “lost” in genomic assemblies. We describe our EULER-CN algorithm for the Copy Number Problem that proved to be successful in difficult sequencing projects.

Contact: ppevzner@ucsd.edu
Probabilistic approaches to the use of higher order clone

relationships in physical map assembly
Authors: States David J. , Nowotny Volker , Blackwell Thomas W.
Published: May 2011

Physical map assembly is the inference of genome structure from experimental data. Map assembly depends on the integration of diverse data including sequence tagged site (STS) marker content, clone sizing, and restriction digest fingerprints (RDF). As experimentally measured data, these are uncertain and error prone. Physical map assembly from error free data is straightforward and can be accomplished in linear time in the number of clones, but the assembly of an optimal map from error prone data is an NP-hard problem. We present an alternative approach to physical map assembly that is based on a probabilistic view of the data and seeks to identify those features of the map that can be reliably inferred from the available data. With this approach, we achieve a number of goals. These include the use of multiple data sources, appropriate representation of uncertainties in the underlying data, the use of clone length information in fingerprint map assembly, and the use of higher order information in map assembly. By higher order information, we mean relationships that are not expressible in terms of neighbouring clone relationships. These include triplet and multiple clone overlaps, the uniqueness of STS position, and fingerprint marker locations. In a probabilistic view of physical mapping, we assert that all of the many possible map assemblies are equally likely a priori. Given experimental data, we can only state which assemblies are more likely than others given the experimental observations. Parameters of interest are then derived as likelihood weighted averages over map assemblies. Ideally these averages should be sums or integrals over all possible map assemblies, but computationally this is not feasible for real-world map assembly problems. Instead, sampling is used to asymptotically approach the desired parameters. Software implementing our probabilistic approach to mapping has been written. Assembly of mixed RDF and STS maps containing up to 60 clones can be accomplished on a desktop PC with run times under an hour.

Availability: http://stl.wustl.edu/software/gibbsmap/

Contact: states@ccb.wustl.edu
Computational expansion of genetic networks
Authors: Tanay Amos , Shamir Ron
Published: May 2011

We present a new methodology for computational analysis of gene and protein networks. The aim is to generate new educated hypotheses on gene functions and on the logic of the biological network circuitry, based on gene expression profiles. The framework supports the incorporation of biologically motivated network constraints and rules to improve specificity. Since current data is insufficient for de-novo reconstruction, the method receives as input a known pathway core and suggests likely expansions to it. Network modeling is combinatorial, yet data can be probabilistic. At the heart of the approach are a fitness function which estimates the quality of suggested network expansions given the core and the data, and a specificity measure of the expansions. The approach has been implemented in an interactive software tool called GENESYS. We report encouraging results in preliminary analysis of yeast ergosterol pathway based on transcription profiles. In particular, the analysis suggests a novel ergosterol transcription factor.

Contact: rshamir@tau.ac.il
Centralization: a new method for the normalization of gene

expression data
Authors: Zien Alexander , Aigner Thomas , Zimmer Ralf , Lengauer Thomas
Published: May 2011

Microarrays measure values that are approximately proportional to the numbers of copies of different mRNA molecules in samples. Due to technical difficulties, the constant of proportionality between the measured intensities and the numbers of mRNA copies per cell is unknown and may vary for different arrays. Usually, the data are normalized (i.e., array-wise multiplied by appropriate factors) in order to compensate for this effect and to enable informative comparisons between different experiments. Centralization is a new two-step method for the computation of such normalization factors that is both biologically better motivated and more robust than standard approaches. First, for each pair of arrays the quotient of the constants of proportionality is estimated. Second, from the resulting matrix of pairwise quotients an optimally consistent scaling of the samples is computed.

Contact: Alexander.Zien@gmd.de
Gene recognition based on DAG shortest paths
Authors: Chuang John S. , Roth Dan
Published: May 2011

We describe Dagger, an ab initio gene recognition program which combines the output of high dimensional signal sensors in an intuitive gene model based on directed acyclic graphs. In the first stage, candidate start, donor, acceptor, and stop sites are scored using the SNoW learning architecture. These sites are then used to generate a directed acyclic graph in which each source-sink path represents a possible gene structure. Training sequences are used to optimize an edge weighting function so that the shortest source-sink path maximizes exon-level prediction accuracy. Experimental evaluation of prediction accuracy on two benchmark data sets demonstrates that Daggeris competitive with ab initio gene finding programs based on Hidden Markov Models.

Contact: jsc@ocf.berkeley.edu, danr@cs.uiuc.edu
Binary tree-structured vector quantization approach to
clustering and visualizing microarray data
Authors: Sultan M. , Wigle D.A. , Cumbaa C.A. , Maziarz M. , Glasgow J. , Tsao M.S. , Jurisica I.
Published: May 2011

Motivation: With the increasing number of gene expression databases, the need for more powerful analysis and visualization tools is growing. Many techniques have successfully been applied to unravel latent similarities among genes and/or experiments. Most of the current systems for microarray data analysis use statistical methods, hierarchical clustering, self-organizing maps, support vector machines, or k-means clustering to organize genes or experiments into ‘meaningful’ groups. Without prior explicit bias almost all of these clustering methods applied to gene expression data not only produce different results, but may also produce clusters with little or no biological relevance. Of these methods, agglomerative hierarchical clustering has been the most widely applied, although many limitations have been identified.

Results: Starting with a systematic comparison of the underlying theories behind clustering approaches, we have devised a technique that combines tree-structured vector quantization and partitive k-means clustering (BTSVQ). This hybrid technique has revealed clinically relevant clusters in three large publicly available data sets. In contrast to existing systems, our approach is less sensitive to data preprocessing and data normalization. In addition, the clustering results produced by the technique have strong similarities to those of self-organizing maps (SOMs). We discuss the advantages and the mathematical reasoning behind our approach.

Availability: The BTSVQ system is implemented in Matlab R12 using the SOM toolbox for the visualization and preprocessing of the data http://www.cis.hut.fi/projects/somtoolbox/ BTSVQ is available for non-commercial use http://www.uhnres.utoronto.ca/ta3/BTSVQ

Contact: ij@uhnres.utoronto.ca

Keywords: microarray data clustering and visulization; self-organizing maps, partitive k-means clustering; lung cancer.
Linking gene expression data with patient survival times using partial least squares
Authors: Park Peter J. , Tian Lu , Kohane Isaac S.
Published: May 2011

There is an increasing need to link the large amount of genotypic data, gathered using microarrays for example, with various phenotypic data from patients. The classification problem in which gene expression data serve as predictors and a class label phenotype as the binary outcome variable has been examined extensively, but there has been less emphasis in dealing with other types of phenotypic data. In particular, patient survival times with censoring are often not used directly as a response variable due to the complications that arise from censoring.

We show that the issues involving censored data can be circumvented by reformulating the problem as a standard Poisson regression problem. The procedure for solving the transformed problem is a combination of two approaches: partial least squares, a regression technique that is especially effective when there is severe collinearity due to a large number of predictors, and generalized linear regression, which extends standard linear regression to deal with various types of response variables. The linear combinations of the original variables identified by the method are highly correlated with the patient survival times and at the same time account for the variability in the covariates. The algorithm is fast, as it does not involve any matrix decompositions in the iterations. We apply our method to data sets from lung carcinoma and diffuse large B-cell lymphoma studies to verify its effectiveness.

Contact: peter_park@harvard.edu

Keywords: microarrays; generalized linear models; survivial analysis; Poisson regression; principal components analysis.
Statistical process control for large scale microarray experiments
Authors: Model Fabian , König Thomas , Piepenbrock Christian , Adorján Péter
Published: May 2011

Motivation: Maintaining and controlling data quality is a key problem in large scale microarray studies. In particular systematic changes in experimental conditions across multiple chips can seriously affect quality and even lead to false biological conclusions. Traditionally the influence of these effects can be minimized only by expensive repeated measurements, because a detailed understanding of all process relevant parameters seems impossible.

Results: We introduce a novel method for microarray process control that estimates quality based solely on the distribution of the actual measurements without requiring repeated experiments. A robust version of principle component analysis detects single outlier microarrays and thereby enables the use of techniques from multivariate statistical process control. In particular, the T2 control chart reliably tracks undesired changes in process relevant parameters. This can be used to improve the microarray process itself, limits necessary repetitions to only affected samples and therefore maintains quality in a cost effective way. We prove the power of the approach on 3 large sets of DNA methylation microarray data.

Contact: Fabian.Model@epigenomics.com

Keywords: DNA methylation; robust PCA; micorarray; statistical process control; quality control.
Assigning probes into a small number of pools separable by electrophoresis
Authors: Kivioja Teemu , Arvas Mikko , Kataja Kari , Penttilä Merja , Söderlund Hans , Ukkonen Esko
Published: May 2011

Motivation: Measuring transcriptional expression levels (transcriptional profiling) has become one of the most important methods in functional genomics. Still, new measuring methods are needed to obtain more reliable, quantitative data about transcription on a genomic scale. In this paper we concentrate on certain computational optimization problems arising in the design of one such novel method. From a computational point of view the key feature of the new method is that the hybridized probes are distinguished from each other based on their different size. Therefore the probes have to be assigned into pools such that the probes in the same pool have unique sizes different enough from each other. Identification of expressed RNA is given by probe pool and probe size while quantification is given by the label of the probe, e.g. fluorescence intensity.

Results: We show how to computationally find the probes and assign them into pools for a whole genome such that (i) each gene has a specific probe suitable for amplification and hybridization, and (ii) the expression level measurement can be done in a minimal number of pools separable by electrophoresis in order to minimize the total experiment cost of the measurement. Our main result is a polynomial-time approximation algorithm for assigning the probes into pools. We demonstrate the feasibility of the procedure by selecting probes for the yeast genome and assigning them into less than 100 pools. The probe sequences and their assignment into pools are available for academic research on request from the authors.

Contact: Teemu.Kivioja@cs.Helsinki.FI

Keywords: transciptional profiling; hybridization probe selection; graph algorithms; degree-contrained subgraph.
Of truth and pathways: chasing bits of information through myriads of articles
Authors: Krauthammer Michael , Kra Pauline , Iossifov Ivan , Gomez Shawn M. , Hripcsak George , Hatzivassiloglou Vasileios , Friedman Carol , Rzhetsky Andrey
Published: May 2011

Motivation: Knowledge on interactions between molecules in living cells is indispensable for theoretical analysis and practical applications in modern genomics and molecular biology. Building such networks relies on the assumption that the correct molecular interactions are known or can be identified by reading a few research articles. However, this assumption does not necessarly hold, as truth is rather an emerging property based on many potentially conflicting facts. This paper explores the processes of knowledge generation and publishing in the molecular biology literature using modelling and analysis of real molecular interaction data. The data analysed in this article were automatically extracted from 50000 research articles in molecular biology using a computer system called GeneWays containing a natural language processing module. The paper indicates that truthfulness of statements is associated in the minds of scientists with the relative importance (connectedness) of substances under study, revealing a potential selection bias in the reporting of research results. Aiming at understanding the statistical properties of the life cycle of biological facts reported in research articles, we formulate a stochastic model describing generation and propagation of knowledge about molecular interactions through scientific publications. We hope that in the future such a model can be useful for automatically producing consensus views of molecular interaction data.

Contact: ar345@columbia.edu

Keywords: statistical modelling; scientometric analysis; molecular interaction data; natural language processing
Statistically based postprocessing of phylogenetic
analysis by clustering
Authors: Stockham Cara , Wang Li-San , Warnow Tandy
Published: May 2011

Motivation: Phylogenetic analyses often produce thousands of candidate trees. Biologists resolve the conflict by computing the consensus of these trees. Single-tree consensus as postprocessing methods can be unsatisfactory due to their inherent limitations.

Results: In this paper we present an alternative approach by using clustering algorithms on the set of candidate trees. We propose bicriterion problems, in particular using the concept of information loss, and new consensus trees called characteristic trees that minimize the information loss. Our empirical study using four biological datasets shows that our approach provides a significant improvement in the information content, while adding only a small amount of complexity. Furthermore, the consensus trees we obtain for each of our large clusters are more resolved than the single-tree consensus trees. We also provide some initial progress on theoretical questions that arise in this context.

Availability: Software available upon request from the authors. The agglomerative clustering is implemented using Matlab (MathWorks, 2000) with the Statistics Toolbox. The Robinson-Foulds distance matrices and the strict consensus trees are computed using PAUP (Swofford, 2001) and the Daniel Huson's tree library on Intel Pentium workstations running Debian Linux.

Contact: lisan@cs.utexas.edu

Supplementary Information: http://www.cs.utexas.edu/users/lisan/ismb02/

Keywords: consensus methods; clustering; phylogenetics; information theory; maximum parsimony.

*To whom correspondence should be addressed.