Identification of single nucleotides in MoS2 nanopores

Ultrathin membranes have drawn much attention due to their unprecedented spatial resolution for DNA nanopore sequencing. However, the high translocation velocity (3000-50000 nt/ms) of DNA molecules moving across such membranes limits their usability. To this end, we have introduced a viscosity gradient system based on room-temperature ionic liquids (RTILs) to control the dynamics of DNA translocation through a nanometer-size pore fabricated in an atomically thin MoS2 membrane. This allows us for the first time to statistically identify all four types of nucleotides with solid state nanopores. Nucleotides are identified according to the current signatures recorded during their transient residence in the narrow orifice of the atomically thin MoS2 nanopore. In this novel architecture that exploits high viscosity of RTIL, we demonstrate single-nucleotide translocation velocity that is an optimal speed (1-50 nt/ms) for DNA sequencing, while keeping the signal to noise ratio (SNR) higher than 10. Our findings pave the way for future low-cost and rapid DNA sequencing using solid-state nanopores.Comment: Manuscript 24 pages, 4 Figures Supporting Information 24 pages, 12 Figures, 2 Tables Manuscript in review Nature Nanotechnology since May 27th 201

Direct Determination of Electron-Phonon Coupling Matrix Element in a Correlated System

High-resolution electron energy loss spectroscopy measurements have been carried out on an optimally doped cuprate Bi2Sr2CaCu2O8+{\delta}. The momentum-dependent linewidth and the dispersion of an A1 optical phonon are obtained. Based on these data as well as the detailed knowledge of the electronic structure from angle-resolved photoemission spectroscopy, we develop a scheme to determine the full structure of electron-phonon coupling for a specific phonon mode, thus providing a general method for directly resolving the EPC matrix element in systems with anisotropic electronic structures

GAGrank: Software for Glycosaminoglycan Sequence Ranking using a Bipartite Graph Model

The Sulfated Glycosaminoglycans (GAGs) Are Long, Linear Polysaccharide Chains that Are Typically Found as the Glycan Portion of Proteoglycans. These GAGs Are Characterized by Repeating Disaccharide Units with Variable Sulfation and Acetylation Patterns Along the Chain. GAG Length and Modification Patterns Have Profound Impacts on Growth Factor Signaling Mechanisms Central to Numerous Physiological Processes. Electron Activated Dissociation Tandem Mass Spectrometry is a Very Effective Technique for Assigning the Structures of GAG Saccharides; However, Manual Interpretation of the Resulting Complex Tandem Mass Spectra is a Difficult and Time-Consuming Process that Drives the Development of Computational Methods for Accurate and Efficient Sequencing. We Have Recently Published GAGfinder, the First Peak Picking and Elemental Composition Assignment Algorithm Specifically Designed for GAG Tandem Mass Spectra. Here, We Present GAGrank, a Novel Network-Based Method for Determining GAG Structure using Information Extracted from Tandem Mass Spectra using GAGfinder. GAGrank is based on Google\u27s PageRank Algorithm for Ranking Websites for Search Engine Output. in Particular, It is an Implementation of BiRank, an Extension of PageRank for Bipartite Networks. in Our Implementation, the Two Partitions Comprise Every Possible Sequence for a Given GAG Composition and the Tandem MS Fragments Found using GAGfinder. Sequences Are Given a Higher Ranking If They Link to Many Important Fragments. using the Simulated Annealing Probabilistic Optimization Technique, We Optimized GAGrank\u27s Parameters on Ten Training Sequences. We Then Validated GAGrank\u27s Performance on Three Validation Sequences. We Also Demonstrated GAGrank\u27s Ability to Sequence Isomeric Mixtures using Two Mixtures at Five Different Ratios

Ultrafast femtosecond relaxation processes in luminescent and nonluminescent conducting polymers

Optical Science, Engineering and Instrumentation '97, 1997, San Diego, CA, United StatesJiandong D. Huang, Sergey V. Frolov, Z. Valy Vardeny, W. Chen, Thomas J. Barton, R. Sugimoto, Masanori Ozaki, and Katsumi Yoshino "Ultrafast femtosecond relaxation processes in luminescent and nonluminescent conducting polymers", Proc. SPIE 3145, Optical Probes of Conjugated Polymers, (1 December 1997). DOI: https://doi.org/10.1117/12.28415

Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in DICER1 syndrome: a unique variant of the two-hit tumor suppression model [v1; ref status: approved with reservations 1, http://f1000r.es/5l9]

Pleuropulmonary blastoma (PPB) is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition, DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific “hotspot” codons within the RNase IIIb domain of DICER 1, combined with complete loss of function (LOF) in the other allele. We analyzed a cohort of 124 PPB children for predisposing DICER1 mutations and sought correlations with clinical phenotypes. Over 70% have inherited or de novo germline LOF mutations, most of which truncate the DICER1 open reading frame. We identified a minority of patients who have no germline mutation, but are instead mosaic for predisposing DICER1 mutations. Mosaicism for RNase IIIb domain hotspot mutations defines a special category of DICER1 syndrome patients, clinically distinguished from those with germline or mosaic LOF mutations by earlier onsets and numerous discrete foci of neoplastic disease involving multiple syndromic organ sites. A final category of patients lack predisposing germline or mosaic mutations and have disease limited to a single PPB tumor bearing tumor-specific RNase IIIb and LOF mutations. We propose that acquisition of a neomorphic RNase IIIb domain mutation is the rate limiting event in DICER1-associated tumorigenesis, and that distinct clinical phenotypes associated with mutational categories reflect the temporal order in which LOF and RNase IIIb domain mutations are acquired during development

Extreme Food-Plant Specialisation in Megabombus Bumblebees as a Product of Long Tongues Combined with Short Nesting Seasons

© 2015 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. http://creativecommons.org/licenses/by/4.0/ The attached file is the published version of the article

DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma

The pathogenesis of cystic nephroma of the kidney has interested pathologists for over 50 years. Emerging from its initial designation as a type of unilateral multilocular cyst, cystic nephroma has been considered as either a developmental abnormality or a neoplasm or both. Many have viewed cystic nephroma as the benign end of the pathologic spectrum with cystic partially differentiated nephroblastoma and Wilms tumor, whereas others have considered it a mixed epithelial and stromal tumor. We hypothesize that cystic nephroma, like the pleuropulmonary blastoma in the lung, represents a spectrum of abnormal renal organogenesis with risk for malignant transformation. Here we studied DICER1 mutations in a cohort of 20 cystic nephromas and 6 cystic partially differentiated nephroblastomas, selected independently of a familial association with pleuropulmonary blastoma and describe four cases of sarcoma arising in cystic nephroma, which have a similarity to the solid areas of type II or III pleuropulmonary blastoma. The genetic analyses presented here confirm that DICER1 mutations are the major genetic event in the development of cystic nephroma. Further, cystic nephroma and pleuropulmonary blastoma have similar DICER1 loss of function and ‘hotspot' missense mutation rates, which involve specific amino acids in the RNase IIIb domain. We propose an alternative pathway with the genetic pathogenesis of cystic nephroma and DICER1-renal sarcoma paralleling that of type I to type II/III malignant progression of pleuropulmonary blastoma

A global-scale expert assessment of drivers and risks associated with pollinator decline.

Pollinator decline has attracted global attention and substantial efforts are underway to respond through national pollinator strategies and action plans. These policy responses require clarity on what is driving pollinator decline and what risks it generates for society in different parts of the world. Using a formal expert elicitation process, we evaluated the relative regional and global importance of eight drivers of pollinator decline and ten consequent risks to human well-being. Our results indicate that global policy responses should focus on reducing pressure from changes in land cover and configuration, land management and pesticides, as these were considered very important drivers in most regions. We quantify how the importance of drivers and risks from pollinator decline, differ among regions. For example, losing access to managed pollinators was considered a serious risk only for people in North America, whereas yield instability in pollinator-dependent crops was classed as a serious or high risk in four regions but only a moderate risk in Europe and North America. Overall, perceived risks were substantially higher in the Global South. Despite extensive research on pollinator decline, our analysis reveals considerable scientific uncertainty about what this means for human society.University of Reading’s Building Outstanding Impact Support Programm