bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of micronuclei and superoxide production in neuroblastoma and glioma cell lines exposed to weak 50 Hz magnetic fields
Authors: Kesari Kavindra Kumar , Juutilainen Jukka , Luukkonen Jukka , Naarala Jonne
Published: January 2016

Extremely low-frequency (ELF) magnetic fields (MF) have been associated with adverse health effects in epidemiological studies. However, there is no known mechanism for biological effects of weak environmental MFs. Previous studies indicate MF effects on DNA integrity and reactive oxygen species, but such evidence is limited to MFs higher (greater than or equal to 100 µT) than those generally found in the environment. Effects of 10 and 30 µT fields were studied in SH-SY5Y and C6 cells exposed to 50-Hz MFs for 24 h. Based on earlier findings, menadione (MQ) was used as a cofactor. Responses to MF were observed in both cell lines, but the effects differed between the cell lines. Micronuclei were significantly increased in SH-SY5Y cells at 30 µT. This effect was largest at the highest MQ dose used. Increased cytosolic and mitochondrial superoxide levels were observed in C6 cells. The effects on superoxide levels were independent of MQ, enabling further mechanistic studies without co-exposure to MQ. The micronucleus and mitochondrial superoxide data were consistent with a conventional rising exposure–response relationship. For cytosolic superoxide, the effect size was unexpectedly large at 10 µT. The results indicate that the threshold for biological effects of ELF MFs is 10 µT or less.
Keeping a lid on nodal: transcriptional and translational repression of nodal signalling
Authors: Sampath Karuna , Robertson Elizabeth J.
Published: January 2016

Nodal is an evolutionarily conserved member of the transforming growth factor-β(TGF-β) superfamily of secreted signalling factors. Nodal factors are known to play key roles in embryonic development and asymmetry in a variety of organisms ranging from hydra and sea urchins to fish, mice and humans. In addition to embryonic patterning, Nodal signalling is required for maintenance of human embryonic stem cell pluripotency and mis-regulated Nodal signalling has been found associated with tumour metastases. Therefore, precise and timely regulation of this pathway is essential. Here, we discuss recent evidence from sea urchins, frogs, fish, mice and humans that show a role for transcriptional and translational repression of Nodal signalling during early development.
Improved community detection in weighted bipartite networks
Authors: Beckett Stephen J.
Published: January 2016

Real-world complex networks are composed of non-random quantitative interactions. Identifying communities of nodes that tend to interact more with each other than the network as a whole is a key research focus across multiple disciplines, yet many community detection algorithms only use information about the presence or absence of interactions between nodes. Weighted modularity is a potential method for evaluating the quality of community partitions in quantitative networks. In this framework, the optimal community partition of a network can be found by searching for the partition that maximizes modularity. Attempting to find the partition that maximizes modularity is a computationally hard problem requiring the use of algorithms. QuanBiMo is an algorithm that has been proposed to maximize weighted modularity in bipartite networks. This paper introduces two new algorithms, LPAwb+ and DIRTLPAwb+, for maximizing weighted modularity in bipartite networks. LPAwb+ and DIRTLPAwb+ robustly identify partitions with high modularity scores. DIRTLPAwb+ consistently matched or outperformed QuanBiMo, while the speed of LPAwb+ makes it an attractive choice for detecting the modularity of larger networks. Searching for modules using weighted data (rather than binary data) provides a different and potentially insightful method for evaluating network partitions.
Diversification rates and phenotypic evolution in venomous snakes (Elapidae)
Authors: Lee Michael S. Y. , Sanders Kate L. , King Benedict , Palci Alessandro
Published: January 2016

The relationship between rates of diversification and of body size change (a common proxy for phenotypic evolution) was investigated across Elapidae, the largest radiation of highly venomous snakes. Time-calibrated phylogenetic trees for 175 species of elapids (more than 50% of known taxa) were constructed using seven mitochondrial and nuclear genes. Analyses using these trees revealed no evidence for a link between speciation rates and changes in body size. Two clades (Hydrophis,Micrurus) show anomalously high rates of diversification within Elapidae, yet exhibit rates of body size evolution almost identical to the general elapid ‘background’ rate. Although correlations between speciation rates and rates of body size change exist in certain groups (e.g. ray-finned fishes, passerine birds), the two processes appear to be uncoupled in elapid snakes. There is also no detectable shift in diversification dynamics associated with the colonization of Australasia, which is surprising given that elapids appear to be the first clade of venomous snakes to reach the continent.
Individual, unit and vocal clan level identity cues in sperm whale codas
Authors: Gero Shane , Whitehead Hal , Rendell Luke
Published: January 2016

The ‘social complexity hypothesis’ suggests that complex social structure is a driver of diversity in animal communication systems. Sperm whales have a hierarchically structured society in which the largest affiliative structures, the vocal clans, are marked on ocean-basin scales by culturally transmitted dialects of acoustic signals known as ‘codas’. We examined variation in coda repertoires among both individual whales and social units—the basic element of sperm whale society—using data from nine Caribbean social units across six years. Codas were assigned to individuals using photo-identification and acoustic size measurement, and we calculated similarity between repertoires using both continuous and categorical methods. We identified 21 coda types. Two of those (‘1+1+3’ and ‘5R1’) made up 65% of the codas recorded, were shared across all units and have dominated repertoires in this population for at least 30 years. Individuals appear to differ in the way they produce ‘5R1’ but not ‘1+1+3’ coda. Units use distinct 4-click coda types which contribute to making unit repertoires distinctive. Our results support the social complexity hypothesis in a marine species as different patterns of variation between coda types suggest divergent functions, perhaps representing selection for identity signals at several levels of social structure.
Adjustment errors of sunstones in the first step of sky-polarimetric Viking navigation: studies with dichroic cordierite/ tourmaline and birefringent calcite crystals
Authors: Száz Dénes , Farkas Alexandra , Blahó Miklós , Barta András , Egri Ádám , Kretzer Balázs , Hegedüs Tibor , Jäger Zoltán , Horváth Gábor
Published: January 2016

According to an old but still unproven theory, Viking navigators analysed the skylight polarization with dichroic cordierite or tourmaline, or birefringent calcite sunstones in cloudy/foggy weather. Combining these sunstones with their sun-dial, they could determine the position of the occluded sun, from which the geographical northern direction could be guessed. In psychophysical laboratory experiments, we studied the accuracy of the first step of this sky-polarimetric Viking navigation. We measured the adjustment erroreof rotatable cordierite, tourmaline and calcite crystals when the task was to determine the direction of polarization of white light as a function of the degree of linear polarizationp. From the obtained error functionse(p), the thresholdsp* above which the first step can still function (i.e. when the intensity change seen through the rotating analyser can be sensed) were derived. Cordierite is about twice as reliable as tourmaline. Calcite sunstones have smaller adjustment errors if the navigator looks for that orientation of the crystal where the intensity difference between the two spots seen in the crystal is maximal, rather than minimal. For higherp(greater thanpcrit) of incident light, the adjustment errors of calcite are larger than those of the dichroic cordierite (pcrit=20%) and tourmaline (pcrit=45%), while for lowerp(less thanpcrit) calcite usually has lower adjustment errors than dichroic sunstones. We showed that real calcite crystals are not as ideal sunstones as it was believed earlier, because they usually contain scratches, impurities and crystal defects which increase considerably their adjustment errors. Thus, cordierite and tourmaline can also be at least as good sunstones as calcite. Using the psychophysicale(p) functions and the patterns of the degree of skylight polarization measured by full-sky imaging polarimetry, we computed how accurately the northern direction can be determined with the use of the Viking sun-dial under 10 different sky conditions at 61° latitude, which was one of the main Viking sailing routes. According to our expermiments, under clear skies, using calcite or cordierite or tourmaline sunstones, Viking sailors could navigate with net orientation errors|Σmax|≤3∘. Under overcast conditions, their net navigation error depends on the sunstone type:|Σmax(calcite)|≤6∘,|Σmax(cordierite)|≤10∘and|Σmax(tourmaline)|≤17∘.
Coupled mode theory of scattering by a cylindrically symmetric seamount
Authors: Pannatoni Ronald F.
Published: January 2016

The coupled-mode equations of Shevchenko are extended to three-dimensional irregular acoustic waveguides. These equations are solved for a model of a cylindrically symmetric seamount and a time-harmonic point source in a horizontally stratified ocean. An algebraic formula for the scattered field beyond the seamount is obtained from this solution. The formula is characterized by a set of infinite-dimensional matrices that are independent of the source. A stable numerical procedure is developed to compute finite-dimensional approximations to these matrices for use in truncated versions of the formula.
Performances and robustness of quantum teleportation with identical particles
Authors: Marzolino Ugo , Buchleitner Andreas
Published: January 2016

When quantum teleportation is performed with truly identical massive particles, indistinguishability allows us to teleport addressable degrees of freedom which do not identify particles, but, for example, orthogonal modes. The key resource of the protocol is a state of entangled modes, but the conservation of the total number of particles does not allow for perfect deterministic teleportation unless the number of particles in the resource state goes to infinity. Here, we study the convergence of teleportation performances in the above limit and provide sufficient conditions for asymptotic perfect teleportation. We also apply these conditions to the case of resource states affected by noise.
Are some people suffering as a result of increasing mass exposure of the public to ultrasound in air?
Authors: Leighton T. G.
Published: January 2016

New measurements indicate that the public are being exposed, without their knowledge, to airborne ultrasound. Existing guidelines are insufficient for such exposures; the vast majority refers to occupational exposure only (where workers are aware of the exposure, can be monitored and can wear protection). Existing guidelines are based on an insufficient evidence base, most of which was collected over 40 years ago by researchers who themselves considered it insufficient to finalize guidelines, but which produced preliminary guidelines. This warning of inadequacy was lost as nations and organizations issued ‘new’ guidelines based on these early guidelines, and through such repetition generated a false impression of consensus. The evidence base is so slim that few reports have progressed far along the sequence from anecdote to case study, to formal scientific controlled trials and epidemiological studies. Early studies reported hearing threshold shifts, nausea, headache, fatigue, migraine and tinnitus, but there is insufficient research on human subjects, and insufficient measurement of fields, to assess what health risk current occupational and public exposures might produce. Furthermore, the assumptions underpinning audiology and physical measurements at high frequencies must be questioned: simple extrapolation of approaches used at lower frequencies does not address current unknowns. Recommendations are provided.
Quantum asymmetry between time and space
Authors: Vaccaro Joan A.
Published: January 2016

An asymmetry exists between time and space in the sense that physical systems inevitably evolve over time, whereas there is no corresponding ubiquitous translation over space. The asymmetry, which is presumed to be
elemental
, is represented by equations of motion and conservation laws that operate differently over time and space. If, however, the asymmetry was found to be due to deeper causes, this conventional view of time evolution would need reworking. Here we show, using a sum-over-paths formalism, that a violation of time reversal (T) symmetry might be such a cause. If T symmetry is obeyed, then the formalism treats time and space symmetrically such that states of matter are localized both in space and in time. In this case, equations of motion and conservation laws are undefined or inapplicable. However, if T symmetry is violated, then the same sum over paths formalism yields states that are localized in space and distributed without bound over time, creating an asymmetry between time and space. Moreover, the states satisfy an equation of motion (the Schrödinger equation) and conservation laws apply. This suggests that the time–space asymmetry is
not elemental
as currently presumed, and that T violation may have a deep connection with time evolution.
Large deformations of planar extensible beams and pantographic lattices: heuristic homogenization, experimental and numerical examples of equilibrium
Authors: dell’Isola F. , Giorgio I. , Pawlikowski M. , Rizzi N. L.
Published: January 2016

The aim of this paper is to find a computationally efficient and predictive model for the class of systems that we call ‘pantographic structures’. The interest in these materials was increased by the possibilities opened by the diffusion of technology of three-dimensional printing. They can be regarded, once choosing a suitable length scale, as families of beams (also called fibres) interconnected to each other by pivots and undergoing large displacements and large deformations. There are, however, relatively few ‘ready-to-use’ results in the literature of nonlinear beam theory. In this paper, we consider a discrete spring model for extensible beams and propose a heuristic homogenization technique of the kind first used by Piola to formulate a continuum fully nonlinear beam model. The homogenized energy which we obtain has some peculiar and interesting features which we start to describe by solving numerically some exemplary deformation problems. Furthermore, we consider pantographic structures, find the corresponding homogenized second gradient deformation energies and study some planar problems. Numerical solutions for these two-dimensional problems are obtained via minimization of energy and are compared with some experimental measurements, in which elongation phenomena cannot be neglected.
Energetic and ecological constraints on population density of reef fishes
Authors: Barneche D. R. , Kulbicki M. , Floeter S. R. , Friedlander A. M. , Allen A. P.
Published: January 2016

Population ecology has classically focused on pairwise species interactions, hindering the description of general patterns and processes of population abundance at large spatial scales. Here we use the metabolic theory of ecology as a framework to formulate and test a model that yields predictions linking population density to the physiological constraints of body size and temperature on individual metabolism, and the ecological constraints of trophic structure and species richness on energy partitioning among species. Our model was tested by applying Bayesian quantile regression to a comprehensive reef-fish community database, from which we extracted density data for 5609 populations spread across 49 sites around the world. Our results indicate that population density declines markedly with increases in community species richness and that, after accounting for richness, energetic constraints are manifested most strongly for the most abundant species, which generally are of small body size and occupy lower trophic groups. Overall, our findings suggest that, at the global scale, factors associated with community species richness are the major drivers of variation in population density. Given that populations of species-rich tropical systems exhibit markedly lower maximum densities, they may be particularly susceptible to stochastic extinction.
Stimulation of dopamine D
1
receptor improves learning capacity in cooperating cleaner fish
Authors: Messias João P. M. , Santos Teresa P. , Pinto Maria , Soares Marta C.
Published: January 2016

Accurate contextual decision-making strategies are important in social environments. Specific areas in the brain are tasked to process these complex interactions and generate correct follow-up responses. The dorsolateral and dorsomedial parts of the telencephalon in the teleost fish brain are neural substrates modulated by the neurotransmitter dopamine (DA), and are part of an important neural circuitry that drives animal behaviour from the most basic actions such as learning to search for food, to properly choosing partners and managing decisions based on context. The Indo-Pacific cleaner wrasse
Labroides dimidiatus
is a highly social teleost fish species with a complex network of interactions with its ‘client’ reef fish. We asked if changes in DA signalling would affect individual learning ability by presenting cleaner fish two ecologically different tasks that simulated a natural situation requiring accurate decision-making. We demonstrate that there is an involvement of the DA system and D
1
receptor pathways on cleaners' natural abilities to learn both tasks. Our results add significantly to the growing literature on the physiological mechanisms that underlie and facilitate the expression of cooperative abilities.
Projecting effects of climate change on marine systems: is the mean all that matters?
Authors: Boersma Maarten , Grüner Nico , Tasso Signorelli Natália , Montoro González Pedro E. , Peck Myron A. , Wiltshire Karen H.
Published: January 2016

Studies dealing with the effects of changing global temperatures on living organisms typically concentrate on annual mean temperatures. This, however, might not be the best approach in temperate systems with large seasonality where the mean annual temperature is actually not experienced very frequently. The mean annual temperature across a 50-year, daily time series of measurements at Helgoland Roads (54.2° N, 7.9° E) is 10.1°C while seasonal data are characterized by a clear, bimodal distribution; temperatures are around 6°C in winter and 15°C in summer with rapid transitions in spring and autumn. Across those 50 years, the temperature at which growth is maximal for each single bloom event for 115 phytoplankton species (more than 6000 estimates of optimal temperature) mirrors the bimodal distribution of the
in situ
temperatures. Moreover, independent laboratory data on temperature optima for growth of North Sea organisms yielded similar results: a deviance from the normal distribution, with a gap close to the mean annual temperature, and more optima either above or below this temperature. We conclude that organisms, particularly those that are short-lived, are either adapted to the prevailing winter or summer temperatures in temperate areas and that few species exist with thermal optima within the periods characterized by rapid spring warming and autumn cooling.
Climate, demography and lek stability in an Amazonian bird
Authors: Ryder Thomas B. , Sillett T. Scott
Published: January 2016

Lekking is a rare, but iconic mating system where polygynous males aggregate and perform group displays to attract females. Existing theory postulates that demographic and environmental stability are required for lekking to be an evolutionarily viable reproductive strategy. However, we lack empirical tests for the hypotheses that lek stability is facilitated by age-specific variation in demographic rates, and by predictable, abundant resources. To address this knowledge gap, we use multistate models to examine how two demographic elements of lek stability—male survival and recruitment—vary with age, social status and phase of the El Niño Southern Oscillation (ENSO) in a Neotropical frugivorous bird, the wire-tailed manakin (Pipra filicauda).Our results show that demographic and environmental conditions were related to lek stability in the Ecuadorean Amazon. Apparent annual survival probability of territorial males was higher than that of non-territorial floaters, and recruitment probability increased as males progressed in an age-graded queue. Moreover, annual survival of territorial males and body condition of both floaters and territory holders were higher following years with El Niño conditions, associated with reduced rainfall and probably higher fruit production in the northern Neotropics, and lower after years with wet, La Niña conditions that predominated our study. Recruitment probabilities varied annually, independent of ENSO phase, and increased over our study period, but the annual mean number of territorial males per lek declined. Our results provide empirical support for hypothesized demographic and environmental drivers of lek dynamics. This study also suggests that climate-mediated changes in resource availability can affect demography and subsequent lek stability in a relatively buffered, lowland rainforest.
Reproductive costs in terrestrial male vertebrates: insights from bird studies
Authors: Bleu Josefa , Gamelon Marlène , Sæther Bernt-Erik
Published: January 2016

Reproduction requires resources that cannot be allocated to other functions resulting in direct reproductive costs (i.e. trade-offs between current reproduction and subsequent survival/reproduction). In wild vertebrates, direct reproductive costs have been widely described in females, but their occurrence in males remains to be explored. To fill this gap, we gathered 53 studies on 48 species testing direct reproductive costs in male vertebrates. We found a trade-off between current reproduction and subsequent performances in 29% of the species and in every clade. As 73% of the studied species are birds, we focused on that clade to investigate whether such trade-offs are associated with (i) levels of paternal care, (ii) polygyny or (iii) pace of life. More precisely for this third question, it is expected that fast species (i.e. short lifespan, early maturity, high fecundity) pay a cost in terms of survival, whereas slow species (with opposite characteristics) do so in terms of fecundity. Our findings tend to support this hypothesis. Finally, we pointed out the potential confounding effects that should be accounted for when investigating reproductive costs in males and strongly encourage the investigation of such costs in more clades to understand to what extent our results are relevant for other vertebrates.
Efficient Correction of the Sickle Mutation in Human Hematopoietic Stem Cells Using a Cas9 Ribonucleoprotein Complex
Authors: DeWitt Mark A. , Magis Wendy , Bray Nicolas L. , Wang Tianjiao , Berman Jennifer R. , Urbinati Fabrizia , Muñoz Denise P. , Kohn Donald B. , Walters Mark C. , Carroll Dana , Martin David K. , Corn Jacob E.
Published: January 2016

Sickle Cell Disease (SCD) is a serious recessive genetic disorder caused by a single nucleotide polymorphism (SNP) in the ß-globin gene (HBB). Sickle hemoglobin polymerizes within red blood cells (RBCs), causing them to adopt an elongated “sickle” shape. Sickle RBCs damage vasculature, leading to severe symptoms, ultimately diminishing patient quality of life and reducing lifespan. Here, we use codelivery of a pre-formed Cas9 ribonucleoprotein complex (RNP) and a singlestranded DNA (ssDNA) oligonucleotide donor to drive sequence replacement at the SCD SNP in human CD34+ hematopoietic stem/progenitor cells (HSPCs). Corrected HSPCs from SCD patients produce less sickle hemoglobin protein and correspondingly increased wild-type hemoglobin when differentiated into erythroblasts. When injected into immunocompromised mice, treated HSPCs maintain editing long-term at therapeutically relevant levels. These results demonstrate that the Cas9 RNP/ssDNA donor approach can mediate efficient HSPC gene editing and could form the basis for treatment of SCD by autologous hematopoietic cell transplantation.
Population-Scale Sequencing Data Enables Precise Estimates of Y-STR Mutation Rates
Authors: Willems Thomas , Gymrek Melissa , Poznik G. David , Tyler-Smith Chris ,   The 1000 Genomes Project Chromosome Y Group, Erlich Yaniv
Published: January 2016

Short Tandem Repeats (STRs) are mutation-prone loci that span nearly 1% of the human genome. Previous studies have estimated the mutation rates of highly polymorphic STRs using capillary electrophoresis and pedigree-based designs. While this work has provided insights into the mutational dynamics of highly mutable STRs, the mutation rates of most others remain unknown. Here, we harnessed whole-genome sequencing data to estimate the mutation rates of Y-chromosome STRs (Y-STRs) with 2-6 base pair repeat units that are accessible to Illumina sequencing. We genotyped 4,500 Y-STRs using data from the 1000 Genomes Project and the Simons Genome Diversity Project. Next, we developed MUTEA, an algorithm that infers STR mutation rates from population-scale data using a high-resolution SNP-based phylogeny. After extensive intrinsic and extrinsic validations, we harnessed MUTEA to derive mutation rate estimates for 702 polymorphic STRs by tracing each locus over 222,000 meioses, resulting in the largest collection of Y-STR mutation rates to date. Using our estimates, we identified determinants of STR mutation rates and built a model to predict rates for STRs across the genome. These predictions indicate that the load of de novo STR mutations is at least 75 mutations per generation, rivaling the load of all other known variant types. Finally, we identified Y-STRs with potential applications in forensics and genetic genealogy, assessed the ability to differentiate between the Y-chromosomes of father-son pairs, and imputed Y-STR genotypes.
Transethnic genetic correlation estimates from summary statistics
Authors: Brown Brielin C. ,   Asian Genetic Epidemiology Network-Type 2 Diabetes (AGEN-T2G) Consortium, Ye Chun Jimmie , Price Alkes L. , Zaitlen Noah
Published: January 2016

abstract

The increasing number of genetic association studies conducted in multiple populations provides unprecedented opportunity to study how the genetic architecture of complex phenotypes varies between populations, a problem important for both medical and population genetics. Here we develop a method for estimating thetransethnic genetic correlation: the correlation of causal variant effect sizes at SNPs common in populations. We take advantage of the entire spectrum of SNP associations and use only summary-level GWAS data. This avoids the computational costs and privacy concerns associated with genotype-level information while remaining scalable to hundreds of thousands of individuals and millions of SNPs. We apply our method to gene expression, rheumatoid arthritis, and type-two diabetes data and overwhelmingly find that the genetic correlation is significantly less than 1. Our method is implemented in a python package calledpopcorn.
Invasion fitness, inclusive fitness, and reproductive numbers in heterogeneous populations
Authors: Lehmann Laurent , Mullon Charles , Akcay Erol , Van Cleve Jeremy
Published: January 2016

How should fitness be measured to determine which phenotype or "strategy" is uninvadable when evolution occurs in subdivided populations subject to local demographic and environmental heterogeneity? Several invasion fitness measures, such as basic reproductive number, lifetime dispersal success of a local lineage, or inclusive fitness have been proposed to address this question, but the relationships between them and their generality remains unclear. Here, we ascertain uninvadability (all mutant strategies always go extinct) in terms of the growth rate of a mutant allele arising as a single copy in a population. We show from this growth rate that uninvadability is equivalently characterized by at least three conceptually distinct invasion fitness measures: (i) lineage fitness, giving the average personal fitness of a randomly sampled mutant lineage member; (ii) inclusive fitness, giving a reproductive value weighted average of the direct fitness cost and relatedness weighted indirect fitness benefits accruing to a randomly sampled mutant lineage member; and (iii) three types of reproductive numbers, giving lifetime success of a local lineage. Our analysis connects approaches that have been deemed different, generalizes the exact version of inclusive fitness to class-structured populations, and provides a biological interpretation of selection on a mutant allele under arbitrary strength of selection.
Open Hardware: Towards a Fully-Wireless Sub-Cranial Neuro-Implant for Measuring Electrocorticography Signals
Authors: Rotermund David , Pistor Jonas , Hoeffmann Janpeter , Schellenberg Tim , Boll Dmitriy , Tolstosheeva Elena , Gauck Dieter , Stemmann Heiko , Peters-Drolshagen Dagmar , Kreiter Andreas K. , Schneider Martin , Paul Steffen , Lang Walter , Pawelzik Klaus R.
Published: January 2016

Implantable neuronal interfaces to the brain are an important keystone for future medical applications. However, entering this field of research is difficult since such an implant requires components from many different areas of technology. Since the complete avoidance of wires is important due to the risk of infections and other long-term problems, means for wireless transmitting data and energy are a necessity which adds to the requirements. In recent literature many high-tech components for such implants are presented with remarkable properties. However, these components are typically not freely available for your system. Every group needs to re-develop their own solution. This raises the question if it is possible to create a reusable design for an implant and its external base-station, such that it allows other groups to use it as a starting point. In this article we try to answer this question by presenting a design based exclusively on commercial off-the-shelf components and studying the properties of the resulting system. Following this idea, we present a fully wireless neuronal implant for simultaneously measuring electrocorticography signals at 128 locations from the surface of the brain. All design files are available as open source.
pileup.js: a JavaScript library for interactive and in-browser visualization of genomic data
Authors: Vanderkam Dan , Aksoy B. Arman , Hodes Isaac , Perrone Jaclyn , Hammerbacher Jeffrey
Published: January 2016

pileup.js is a new browser-based genome viewer. It is designed to facilitate the investigation of evidence for genomic variants within larger web applications. It takes advantage of recent developments in the JavaScript ecosystem to provide a modular, reliable and easily embedded library.
Logic models to predict continuous outputs based on binary inputs with an application to personalized cancer therapy
Authors: Knijnenburg Theo , Klau Gunnar , Iorio Francesco , Garnett Mathew , McDermott Ultan , Shmulevich Ilya , Wessels Lodewyk
Published: January 2016

Mining large datasets using machine learning approaches often leads to models that are hard to interpret and not amenable to the generation of hypotheses that can be experimentally tested. Finding ‘actionable knowledge’ is becoming more important, but also more challenging as datasets grow in size and complexity. We present ‘Logic Optimization for Binary Input to Continuous Output’ (LOBICO), a computational approach that infers small and easily interpretable logic models of binary input features that explain a binarized continuous output variable. Although the continuous output variable is binarized prior to optimization, the continuous information is retained to find the optimal logic model. Applying LOBICO to a large cancer cell line panel, we find that logic combinations of multiple mutations are more predictive of drug response than single gene predictors. Importantly, we show that the use of the continuous information leads to robust and more accurate logic models. LOBICO is formulated as an integer programming problem, which enables rapid computation on large datasets. Moreover, LOBICO implements the ability to uncover logic models around predefined operating points in terms of sensitivity and specificity. As such, it represents an important step towards practical application of interpretable logic models.
Read-Based Phasing of Related Individuals
Authors: Garg Shilpa , Martin Marcel , Marschall Tobias
Published: January 2016

Motivation

Read-based phasing deduces the haplotypes of an individual from sequencing reads that cover multiple variants, while genetic phasing takes only genotypes as input and applies the rules of Mendelian inheritance to infer haplotypes within a pedigree of individuals. Combining both into an approach that uses these two independent sources of information - reads and pedigree - has the potential to deliver results better than each individually.

Results

We provide a theoretical framework combining read-based phasing with genetic haplotyping, and describe a fixed-parameter algorithm and its implementation for finding an optimal solution. We show that leveraging reads of related individuals jointly in this way yields more phased variants and at a higher accuracy than when phased separately, both in simulated and real data. Coverages as low as 2× for each member of a trio yield haplotypes that are as accurate as when analyzed separately at 15× coverage per individual.

Availability

https://bitbucket.org/whatshap/whatshap(branch pedmec)

Contact

t.marschall@mpi-inf.mpg.de
Expanding perspectives on cognition in humans, animals, and machines
Authors: Gomez-Marin Alex , Mainen Zachary F
Published: January 2016

Over the past decade neuroscience has been attacking the problem of cognition with increasing vigor. Yet, what exactlyiscognition, beyond a general signifier of anything seemingly complex the brain does? Here, we briefly review attempts to define, describe, explain, build, enhance and experience cognition. We highlight perspectives including psychology, molecular biology, computation, dynamical systems, machine learning, behavior and phenomenology. This survey of the landscape reveals not a clear target for explanation but a pluralistic and evolving scene with diverse opportunities for grounding future research. We argue that rather than getting to the bottom of it, over the next century, by deconstructing and redefining cognition, neuroscience will and should expand rather than merely reduce our concept of the mind.
Bayesian Inference of Natural Selection from Allele Frequency Time Series
Authors: Schraiber Joshua G. , Evans Steven N. , Slatkin Montgomery
Published: January 2016

The advent of accessible ancient DNA technology now allows the direct ascertainment of allele frequencies in ancestral populations, thereby enabling the use of allele frequency time series to detect and estimate natural selection. Such direct observations of allele frequency dynamics are expected to be more powerful than inferences made using patterns of linked neutral variation obtained from modern individuals. We developed a Bayesian method to make use of allele frequency time series data and infer the parameters of general diploid selection, along with allele age, in non-equilibrium populations. We introduce a novel path augmentation approach, in which we use Markov chain Monte Carlo to integrate over the space of allele frequency trajectories consistent with the observed data. Using simulations, we show that this approach has good power to estimate selection coefficients and allele age. Moreover, when applying our approach to data on horse coat color, we find that ignoring a relevant demographic history can significantly bias the results of inference. Our approach is made available in a C++ software package.
Automated Discrimination of Dicentric and Monocentric Chromosomes by Machine Learning-based Image Processing
Authors: Li Yanxin , Knoll Joan H. , Wilkins Ruth , Flegal Farrah N. , Rogan Peter K.
Published: January 2016

Dose from radiation exposure can be estimated from dicentric chromosome (DC) frequencies in metaphase cells of peripheral blood lymphocytes. We automated DC detection by extracting features in Giemsa-stained metaphase chromosome images and classifying objects by machine learning (ML). DC detection involves i) intensity thresholded segmentation of metaphase objects, ii) chromosome separation by watershed transformation and elimination of inseparable chromosome clusters, fragments and staining debris using a morphological decision tree filter, iii) determination of chromosome width and centreline, iv) derivation of centromere candidates and v) distinction of DCs from monocentric chromosomes (MC) by ML. Centromere candidates are inferred from 14 image features input to a Support Vector Machine (SVM). 16 features derived from these candidates are then supplied to a Boosting classifier and a second SVM which determines whether a chromosome is either a DC or MC. The SVM was trained with 292 DCs and 3135 MCs, and then tested with cells exposed to either low (1 Gy) or high (2-4 Gy) radiation dose. Results were then compared with those of 3 experts. True positive rates (TPR) and positive predictive values (PPV) were determined for the tuning parameter, σ. At larger σ, PPV decreases and TPR increases. At high dose, for σ= 1.3, TPR = 0.52 and PPV = 0.83, while at σ= 1.6, the TPR = 0.65 and PPV = 0.72. At low dose and σ = 1.3, TPR = 0.67 and PPV = 0.26. The algorithm differentiates DCs from MCs, overlapped chromosomes and other objects with acceptable accuracy over a wide range of radiation exposures.
Divorcing Strain Classification From Species Names
Authors: Baltrus David A.
Published: January 2016

Confusion about strain classification and nomenclature permeates modern microbiology. Although taxonomists have traditionally acted as gatekeepers of order, the numbers of and speed at which new strains are identified has outpaced the opportunity for professional classification for many lineages. Furthermore, the growth of bioinformatics and database fueled investigations have placed metadata curation in the hands of researchers with little taxonomic experience. Here I describe practical challenges facing modern microbial taxonomy, provide an overview of complexities of classification for environmentally ubiquitous taxa likePseudomonas syringae, and emphasize that classification and nomenclature need not be the one in the same. A move toward implementation of relational classification schemes based on inherent properties of whole genomes could provide sorely needed continuity in how strains are referenced across manuscripts and data sets.
A Bayesian framework for comparing the structure of spontaneous correlated activity recorded under different conditions
Authors: Cutts Catherine S , Eglen Stephen J
Published: January 2016

Distant-dependent correlations in spontaneous retinal activity are thought to be instructive in the development of the retinotopic map and eye-specific segregation maps. Many studies which seek to investigate these correlations and their role in map formation record spontaneous retinal activity from different pheno-types or experimental conditions and compare the distance-dependence of the correlations between different conditions. They seek to demonstrate that these correlations differ significantly, and this analysis is often key to the study’s conclusions. In this work, we assess the methods of inference which have been previously used to investigate this problem and conclude that they are inadequate. We propose a hierarchical Bayesian framework to model distant-dependent correlations in spontaneous retinal activity data and specify a method which uses the data to specify the form of the model. This model allows us to assess the evidence for/against differences in correlations between experimental conditions in a more robust and credible way. We demonstrate the use of this method by applying it to data from two studies of spontaneous retinal activity. We believe however the framework to be rather more general and that it can be used in a wide range of datasets where distance and correlation are substitute for other independent and dependent variables from experiments.
Dendritic trafficking faces physiologically critical speed-precision tradeoffs
Authors: Williams Alex H. , O’Donnell Cian , Sejnowski Terrence , O’Leary Timothy
Published: January 2016

Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the “sushi-belt model” (Doyle and Kiebler, 2011). Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, showing how it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimates of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. These findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons.
Genome-wide target specificities of CRISPR-Cas9 nucleases revealed by multiplex Digenome-seq
Authors: Kim Daesik , Kim Sojung , Kim Sunghyun , Park Jeongbin , Kim Jin-Soo
Published: January 2016

We present multiplex Digenome-seq to profile genome-wide specificities of up to 11 CRISPR-Cas9 nucleases simultaneously, saving time and reducing cost. Cell-free human genomic DNA was digested using multiple sgRNAs combined with the Cas9 protein and then subjected to whole-genome sequencing. In vitro cleavage patterns, characteristic of on- and off-target sites, were computationally identified across the genome using a new DNA cleavage scoring system. We found that many false-positive, bulge-type off-target sites were cleaved by sgRNAs transcribed from an oligonucleotide duplex but not by those transcribed from a plasmid template. Multiplex Digenome-seq captured many bona fide off-target sites, missed by other genome-wide methods, at which indels were induced at frequencies <0.1%. After analyzing 964 sites cleaved in vitro by these sgRNAs and measuring indel frequencies at hundreds of off-target sites in cells, we propose a guideline for the choice of target sites for minimizing CRISPR-Cas9 off-target effects in the human genome.
Relationship between the volume of the unit cell of hexagonal-close-packed Ti, hardness and oxygen content after α-case formation in Ti–6Al–2Sn–4Zr–2Mo–0.1Si alloy
Authors: Baillieux J. , Poquillon D. , Malard B.
Published: January 2016

In this study, the influence of oxygen diffusion on the physical properties of Ti–6Al–2Sn–4Zr–2Mo–0.1Si was examined. Measurements were carried out directly on sample cross sections which were preoxidized at high temperature. The lattice parameter evolution was measured using synchrotron X-ray diffraction and was coupled with microhardness and electron probe microanalyzer results with the aim of highlighting their relationships. The results show that the hardness and oxygen gradients along the oxygen diffusion zone in the alloy are similar to the evolution of the α-phase unit-cell volume quantified by X-ray diffraction. Linear relationships were found between these three parameters.
X-ray nanodiffraction analysis of stress oscillations in a W thin film on through-silicon via
Authors: Todt J. , Hammer H. , Sartory B. , Burghammer M. , Kraft J. , Daniel R. , Keckes J. , Defregger S.
Published: January 2016

Synchrotron X-ray nanodiffraction is used to analyse residual stress distributions in a 200 nm-thick W film deposited on the scalloped inner wall of a through-silicon via. The diffraction data are evaluated using a novel dedicated methodology which allows the quantification of axial and tangential stress components under the condition that radial stresses are negligible. The results reveal oscillatory axial stresses in the range of ∼445–885 MPa, with a distribution that correlates well with the scallop wavelength and morphology, as well as nearly constant tangential stresses of ∼800 MPa. The discrepancy with larger stress values obtained from a finite-element model, as well as from a blanket W film, is attributed to the morphology and microstructural nature of the W film in the via.
Monte Carlo X-ray transport simulation of small-angle X-ray scattering instruments using measured sample cross sections
Authors: Choi Mina , Ghammraoui Bahaa , Badal Andreu , Badano Aldo
Published: January 2016

Small-angle X-ray scattering (SAXS) has recently been proposed as a novel noninvasivein vivomolecular imaging technique to characterize molecular interactions deep within the body using high-contrast probes. This article describes a detailed Monte Carlo X-ray transport simulation technique that utilizes user-provided cross sections to describe X-ray interaction in virtual samples and explore SAXS instrument design choices. The accuracy of the simulation code is validated with sample material cross sections derived from analytical models and empirical measurements of a homogeneous spherical gold nanoparticle (GNP) monomer, a dimer and heterogeneous mixtures of the two in aqueous solution. Analytical and measured scattering profiles from these samples were converted to cross sections using an absolute water standard. Our Monte Carlo estimates of the fraction of dimers from analytically derived and empirically derived cross sections are strongly correlated, with less than 1.5 and 16% error, respectively, to the expected concentration of monomer and dimer species. In addition, a variety of monoenergetic X-ray beams were simulated to investigate coherent scatteringversusradiation dose for a range of sample sizes. For GNP spheres in aqueous solution, the energy range that produces the most coherent scattering at the detector per deposited energy was between 31 and 49 keV for a sample thickness of 1 mm to 10 cm. The method described here for the detailed simulation of SAXS using measured and modeled cross sections will enable instrumentation optimization forin vivomolecular imaging applications.