Connecting the dots between PubMed abstracts

Background: There are now a multitude of articles published in a diversity of journals providing information about genes, proteins, pathways, and diseases. Each article investigates subsets of a biological process, but to gain insight into the functioning of a system as a whole, we must integrate information from multiple publications. Particularly, unraveling relationships between extra-cellular inputs and downstream molecular response mechanisms requires integrating conclusions from diverse publications. Methodology: We present an automated approach to biological knowledge discovery from PubMed abstracts, suitable for "connecting the dots" across the literature. We describe a storytelling algorithm that, given a start and end publication, typically with little or no overlap in content, identifies a chain of intermediate publications from one to the other, such that neighboring publications have significant content similarity. The quality of discovered stories is measured using local criteria such as the size of supporting neighborhoods for each link and the strength of individual links connecting publications, as well as global metrics of dispersion. To ensure that the story stays coherent as it meanders from one publication to another, we demonstrate the design of novel coherence and overlap filters for use as post-processing steps. Conclusions: We demonstrate the application of our storytelling algorithm to three case studies: i) a many-one study exploring relationships between multiple cellular inputs and a molecule responsible for cell-fate decisions, ii) a many-many study exploring the relationships between multiple cytokines and multiple downstream transcription factors, and iii) a one-to-one study to showcase the ability to recover a cancer related association, viz. the Warburg effect, from past literature. The storytelling pipeline helps narrow down a scientist's focus from several hundreds of thousands of relevant documents to only around a hundred stories. We argue that our approach can serve as a valuable discovery aid for hypothesis generation and connection exploration in large unstructured biological knowledge bases.Institute for Critical Technology and Applied Science, Virginia Tech, and the US National Science Foundation through grant CCF-0937133.Scopu

Advances in single crystal growth and annealing treatment of electron-doped HTSC

High quality electron-doped HTSC single crystals of $\rm Pr_{2-x}Ce_{x}CuO_{4+\delta}$ and $\rm Nd_{2-x}Ce_{x}CuO_{4+\delta}$ have been successfully grown by the container-free traveling solvent floating zone technique. The optimally doped $\rm Pr_{2-x}Ce_{x}CuO_{4+\delta}$ and $\rm Nd_{2-x}Ce_{x}CuO_{4+\delta}$ crystals have transition temperatures $T_{\rm c}$ of $25$\,K and $23.5$\,K, respectively, with a transition width of less than $1$\,K. We found a strong dependence of the optimal growth parameters on the Ce content $x$. We discuss the optimization of the post-growth annealing treatment of the samples, the doping extension of the superconducting dome for both compounds as well as the role of excess oxygen. The absolute oxygen content of the as-grown crystals is determined from thermogravimetric experiments and is found to be $\ge 4.0$. This oxygen surplus is nearly completely removed by a post-growth annealing treatment. The reduction process is reversible as demonstrated by magnetization measurements. In as-grown samples the excess oxygen resides on the apical site O(3). This apical oxygen has nearly no doping effect, but rather influences the evolution of superconductivity by inducing additional disorder in the CuO$_{2}$ layers. The very high crystal quality of $\rm Nd_{2-x}Ce_{x}CuO_{4+\delta}$ is particularly manifest in magnetic quantum oscillations observed on several samples at different doping levels. They provide a unique opportunity of studying the Fermi surface and its dependence on the carrier concentration in the bulk of the crystals.Comment: 19 pages, 7 figures, submitted to Eur. Phys. J.

Late Pleistocene vertebrate trace fossils in the Goukamma Nature Reserve, Cape South Coast, South Africa

More than 100 Late Pleistocene trace fossil sites have been identified in aeolianites along a 275 kilometer stretch of the Cape south coast. A zone of concentration of such sites exists within the Goukamma Nature Reserve, both along the coast and along the Goukamma River. These sites provide insight into the Pleistocene fauna along the Cape south coast. Features include lion trackways, multiple elephant tracksites, a long trackway most likely attributable to Long-horned Buffalo, medium-sized carnivore tracks, avian tracks, equid tracks attributable to the giant Cape horse, numerous artiodactyl tracks, and burrow traces. The ephemeral nature of the tracksites makes regular surveys of these areas desirable, along with site documentation and trackway replication and preservation initiatives. The protected status of the area offers opportunities for geoheritage appreciation.JN

Sequences outside recognition sets are not neutral for tRNA aminoacylation. Evidence for nonpermissive combinations of nucleotides in the acceptor stem of yeast tRNAPhe.

Phenylalanine identity of yeast tRNAPhe is governed by five nucleotides including residues A73, G20, and the three anticodon nucleotides (Sampson et al., 1989, Science 243, 1363-1366). Analysis of in vitro transcripts derived from yeast tRNAPhe and Escherichia coli tRNAAla bearing these recognition elements shows that phenylalanyl-tRNA synthetase is sensitive to additional nucleotides within the acceptor stem. Insertion of G2-C71 has dramatic negative effects in both tRNA frameworks. These effects become compensated by a second-site mutation, the insertion of the wobble G3-U70 pair, which by itself has no effect on phenylalanylation. From a mechanistic point of view, the G2-C71/G3-U70 combination is not a "classical" recognition element since its antideterminant effect is compensated for by a second-site mutation. This enlarges our understanding of tRNA identity that appears not only to be the outcome of a combination of positive and negative signals forming the so-called recognition/identity set but that is also based on the presence of nonrandom combinations of sequences elsewhere in tRNA. These sequences, we name "permissive elements," are retained by evolution so that they do not hinder aminoacylation. Likely, no nucleotide within a tRNA is of random nature but has been selected so that a tRNA can fulfill all its functions efficiently.journal articleresearch support, non-u.s. gov't1998 May 08importe

Search for characteristic structural features of mammalian mitochondrial tRNAs.

A number of mitochondrial (mt) tRNAs have strong structural deviations from the classical tRNA cloverleaf secondary structure and from the conventional L-shaped tertiary structure. As a consequence, there is a general trend to consider all mitochondrial tRNAs as "bizarre" tRNAs. Here, a large sequence comparison of the 22 tRNA genes within 31 fully sequenced mammalian mt genomes has been performed to define the structural characteristics of this specific group of tRNAs. Vertical alignments define the degree of conservation/variability of primary sequences and secondary structures and search for potential tertiary interactions within each of the 22 families. Further horizontal alignments ascertain that, with the exception of serine-specific tRNAs, mammalian mt tRNAs do fold into cloverleaf structures with mostly classical features. However, deviations exist and concern large variations in size of the D- and T-loops. The predominant absence of the conserved nucleotides G18G19 and T54T55C56, respectively in these loops, suggests that classical tertiary interactions between both domains do not take place. Classification of the tRNA sequences according to their genomic origin (G-rich or G-poor DNA strand) highlight specific features such as richness/poorness in mismatches or G-T pairs in stems and extremely low G-content or C-content in the D- and T-loops. The resulting 22 "typical" mammalian mitochondrial sequences built up a phylogenetic basis for experimental structural and functional investigations. Moreover, they are expected to help in the evaluation of the possible impacts of those point mutations detected in human mitochondrial tRNA genes and correlated with pathologies.journal articleresearch support, non-u.s. gov't2000 Octimporte

Innovation Contests with Entry Auction

We consider procurement of an innovation from heterogeneous sellers. Innovations are random but depend on unobservable effort and private information. We compare two procurement mechanisms where potential sellers first bid in an auction for admission to an innovation contest. After the contest, an innovation is procured employing either a fixed prize or a first-price auction. We characterize Bayesian Nash equilibria such that both mechanisms are payoff-equivalent and induce the same efforts and innovations. In these equilibria, signaling in the entry auction does not occur since contestants play a simple strategy that does not depend on rivals' private information

Metagenomic analysis of planktonic riverine microbial consortia using nanopore sequencing reveals insight into river microbe taxonomy and function

Background Riverine ecosystems are biogeochemical powerhouses driven largely by microbial communities that inhabit water columns and sediments. Because rivers are used extensively for anthropogenic purposes (drinking water, recreation, agriculture, and industry), it is essential to understand how these activities affect the composition of river microbial consortia. Recent studies have shown that river metagenomes vary considerably, suggesting that microbial community data should be included in broad-scale river ecosystem models. But such ecogenomic studies have not been applied on a broad “aquascape” scale, and few if any have applied the newest nanopore technology. Results We investigated the metagenomes of 11 rivers across 3 continents using MinION nanopore sequencing, a portable platform that could be useful for future global river monitoring. Up to 10 Gb of data per run were generated with average read lengths of 3.4 kb. Diversity and diagnosis of river function potential was accomplished with 0.5–1.0 ⋅ 106 long reads. Our observations for 7 of the 11 rivers conformed to other river-omic findings, and we exposed previously unrecognized microbial biodiversity in the other 4 rivers. Conclusions Deeper understanding that emerged is that river microbial consortia and the ecological functions they fulfil did not align with geographic location but instead implicated ecological responses of microbes to urban and other anthropogenic effects, and that changes in taxa manifested over a very short geographic space

Antiskyrmions and their electrical footprint in crystalline mesoscale structures of Mn1.4PtSn

Skyrmionic materials hold the potential for future information technologies, such as racetrack memories. Key to that advancement are systems that exhibit high tunability and scalability, with stored information being easy to read and write by means of all-electrical techniques. Topological magnetic excitations such as skyrmions and antiskyrmions, give rise to a characteristic topological Hall effect. However, the electrical detection of antiskyrmions, in both thin films and bulk samples has been challenging to date. Here, we apply magneto-optical microscopy combined with electrical transport to explore the antiskyrmion phase as it emerges in crystalline mesoscale structures of the Heusler magnet Mn1.4PtSn. We reveal the Hall signature of antiskyrmions in line with our theoretical model, comprising anomalous and topological components. We examine its dependence on the vertical device thickness, field orientation, and temperature. Our atomistic simulations and experimental anisotropy studies demonstrate the link between antiskyrmions and a complex magnetism that consists of competing ferromagnetic, antiferromagnetic, and chiral exchange interactions, not captured by micromagnetic simulations