Analysis of nanopore detector measurements using Machine-Learning methods, with application to single-molecule kinetic analysis

<p>Abstract</p> <p>Background</p> <p>A nanopore detector has a nanometer-scale trans-membrane channel across which a potential difference is established, resulting in an ionic current through the channel in the pA-nA range. A distinctive channel current blockade signal is created as individually "captured" DNA molecules interact with the channel and modulate the channel's ionic current. The nanopore detector is sensitive enough that nearly identical DNA molecules can be classified with very high accuracy using machine learning techniques such as Hidden Markov Models (HMMs) and Support Vector Machines (SVMs).</p> <p>Results</p> <p>A non-standard implementation of an HMM, emission inversion, is used for improved classification. Additional features are considered for the feature vector employed by the SVM for classification as well: The addition of a single feature representing spike density is shown to notably improve classification results. Another, much larger, feature set expansion was studied (2500 additional features instead of 1), deriving from including all the HMM's transition probabilities. The expanded features can introduce redundant, noisy information (as well as diagnostic information) into the current feature set, and thus degrade classification performance. A hybrid Adaptive Boosting approach was used for feature selection to alleviate this problem.</p> <p>Conclusion</p> <p>The methods shown here, for more informed feature extraction, improve both classification and provide biologists and chemists with tools for obtaining a better understanding of the kinetic properties of molecules of interest.</p

Local Television Journalism: Developing Ethics through Discussion

The purpose of this paper is to examine the views of local television news producers about ethical policies and situations they face. A majority of respondents agreed that it was important for a television newsroom to have a code of ethics or discussion of ethics in the newsroom. Most often producers perceived that their newsrooms were involved in discussions of fairness, balance, and objectivity; allocating air-time to opposing interest groups or political candidates; and, providing right of reply to criticism. Producers support a written code of ethics, or occasional discussion of ethics in the television newsroom, but see the competitive nature of local news and the current philosophy of the newsroom as a profit center as eroding ethical standards. Political orientation did not appear to make a difference. This study found that television news producers, who are often the final gatekeepers of the newscasts, want to maintain fairness, balance, and objectivity in the station\u27s reporting of events. The producers feel the competitive pressures to relax ethical news standards, want to resist it, and see newsroom discussions as one means of defense

The NTD Nanoscope: potential applications and implementations

<p>Abstract</p> <p>Background</p> <p>Nanopore transduction detection (NTD) offers prospects for a number of highly sensitive and discriminative applications, including: (i) single nucleotide polymorphism (SNP) detection; (ii) targeted DNA re-sequencing; (iii) protein isoform assaying; and (iv) biosensing via antibody or aptamer coupled molecules. Nanopore event transduction involves single-molecule biophysics, engineered information flows, and nanopore cheminformatics. The NTD Nanoscope has seen limited use in the scientific community, however, due to lack of information about potential applications, and lack of availability for the device itself. Meta Logos Inc. is developing both pre-packaged device platforms and component-level (unassembled) kit platforms (the latter described here). In both cases a lipid bi-layer workstation is first established, then augmentations and operational protocols are provided to have a nanopore transduction detector. In this paper we provide an overview of the NTD Nanoscope applications and implementations. The NTD Nanoscope Kit, in particular, is a component-level reproduction of the standard NTD device used in previous research papers.</p> <p>Results</p> <p>The NTD Nanoscope method is shown to functionalize a single nanopore with a channel current modulator that is designed to transduce events, such as binding to a specific target. To expedite set-up in new lab settings, the calibration and troubleshooting for the NTD Nanoscope kit components and signal processing software, the NTD Nanoscope Kit, is designed to include a set of test buffers and control molecules based on experiments described in previous NTD papers (the model systems briefly described in what follows). The description of the Server-interfacing for advanced signal processing support is also briefly mentioned.</p> <p>Conclusions</p> <p>SNP assaying, SNP discovery, DNA sequencing and RNA-seq methods are typically limited by the accuracy of the error rate of the enzymes involved, such as methods involving the polymerase chain reaction (PCR) enzyme. The NTD Nanoscope offers a means to obtain higher accuracy as it is a single-molecule method that does not inherently involve use of enzymes, using a functionalized nanopore instead.</p

Ethics in Local Television Newsrooms: A Comparison of Assignment Editors and Producers

This paper examines the attitudes of local television news assignment editors toward ethics in the newsroom. A large majority of producers say newsrooms should have a code of ethics or discussions of ethics, that ethics should not change with the story and that newsroom ethics are being eroded by pressure to get ratings. It goes on to compare these attitudes with those of news producers from an earlier survey. Assignment editors also ranked how often discussion of certain ethical situations take place in the newsroom

Mechanism Design in Social Networks

This paper studies an auction design problem for a seller to sell a commodity in a social network, where each individual (the seller or a buyer) can only communicate with her neighbors. The challenge to the seller is to design a mechanism to incentivize the buyers, who are aware of the auction, to further propagate the information to their neighbors so that more buyers will participate in the auction and hence, the seller will be able to make a higher revenue. We propose a novel auction mechanism, called information diffusion mechanism (IDM), which incentivizes the buyers to not only truthfully report their valuations on the commodity to the seller, but also further propagate the auction information to all their neighbors. In comparison, the direct extension of the well-known Vickrey-Clarke-Groves (VCG) mechanism in social networks can also incentivize the information diffusion, but it will decrease the seller's revenue or even lead to a deficit sometimes. The formalization of the problem has not yet been addressed in the literature of mechanism design and our solution is very significant in the presence of large-scale online social networks.Comment: In The Thirty-First AAAI Conference on Artificial Intelligence, San Francisco, US, 04-09 Feb 201

Recombination in Avian Gamma-Coronavirus Infectious Bronchitis Virus

Recombination in the family Coronaviridae has been well documented and is thought to be a contributing factor in the emergence and evolution of different coronaviral genotypes as well as different species of coronavirus. However, there are limited data available on the frequency and extent of recombination in coronaviruses in nature and particularly for the avian gamma-coronaviruses where only recently the emergence of a turkey coronavirus has been attributed solely to recombination. In this study, the full-length genomes of eight avian gamma-coronavirus infectious bronchitis virus (IBV) isolates were sequenced and along with other full-length IBV genomes available from GenBank were analyzed for recombination. Evidence of recombination was found in every sequence analyzed and was distributed throughout the entire genome. Areas that have the highest occurrence of recombination are located in regions of the genome that code for nonstructural proteins 2, 3 and 16, and the structural spike glycoprotein. The extent of the recombination observed, suggests that this may be one of the principal mechanisms for generating genetic and antigenic diversity within IBV. These data indicate that reticulate evolutionary change due to recombination in IBV, likely plays a major role in the origin and adaptation of the virus leading to new genetic types and strains of the virus

Synthesis and Characterization of CREKA-Conjugated Iron Oxide Nanoparticles for Hyperthermia Applications

One of the current challenges in the systemic delivery of nanoparticles in cancer therapy applications is the lack of effective tumor localization. Iron oxide nanoparticles coated with crosslinked dextran were functionalized with the tumor homing peptide CREKA, which binds to fibrinogen complexes in the extracellular matrix of tumors. This allows for the homing of these nanoparticles to tumor tissue. The iron oxide nanoparticle core allows for particle heating upon exposure to an alternating magnetic field (AMF) while the dextran coating stabilizes the particles in suspension and decreases the cytotoxicity of the system. Magnetically mediated hyperthermia (MMH) allows for the heating of tumor tissue to increase the efficacy of traditional cancer treatments using the iron oxide nanoparticles. While MMH provides the opportunity for localized heating, this method is currently limited by the lack of particle penetration into tumor tissue, even after effective targeted delivery to the tumor site. The CREKA-conjugated nanoparticles presented were characterized for their size, stability, biocompatibility, and heating capabilities. The particles were stable in PBS and media over at least twelve hours, had a hydrated diameter of 52 nm, and generated enough heat to raise solution temperatures well into the hyperthermia range (41 – 45 °C) when exposed to an AMF. Biocompatibility studies demonstrated that the particles have low cytotoxicity over long exposure times at low concentrations. A fibrinogen clotting assay was used to determine the binding affinity of CREKA-conjugated particles, which was significantly greater than the binding affinity of dextran, only coated iron oxide nanoparticles demonstrating the potential for this particle system to effectively home to a variety of tumor locations. Finally, it was shown that in vitro MMH increased the effects of cisplatin compared to cisplatin or MMH treatments alone

Stripe-hexagon competition in forced pattern forming systems with broken up-down symmetry

We investigate the response of two-dimensional pattern forming systems with a broken up-down symmetry, such as chemical reactions, to spatially resonant forcing and propose related experiments. The nonlinear behavior immediately above threshold is analyzed in terms of amplitude equations suggested for a $1:2$ and $1:1$ ratio between the wavelength of the spatial periodic forcing and the wavelength of the pattern of the respective system. Both sets of coupled amplitude equations are derived by a perturbative method from the Lengyel-Epstein model describing a chemical reaction showing Turing patterns, which gives us the opportunity to relate the generic response scenarios to a specific pattern forming system. The nonlinear competition between stripe patterns and distorted hexagons is explored and their range of existence, stability and coexistence is determined. Whereas without modulations hexagonal patterns are always preferred near onset of pattern formation, single mode solutions (stripes) are favored close to threshold for modulation amplitudes beyond some critical value. Hence distorted hexagons only occur in a finite range of the control parameter and their interval of existence shrinks to zero with increasing values of the modulation amplitude. Furthermore depending on the modulation amplitude the transition between stripes and distorted hexagons is either sub- or supercritical.Comment: 10 pages, 12 figures, submitted to Physical Review