Computational analysis of stochastic heterogeneity in PCR amplification efficiency revealed by single molecule barcoding

The polymerase chain reaction (PCR) is one of the most widely used techniques in molecular biology. In combination with High Throughput Sequencing (HTS), PCR is widely used to quantify transcript abundance for RNA-seq, and in the context of analysis of T and B cell receptor repertoires. In this study, we combine DNA barcoding with HTS to quantify PCR output from individual target molecules. We develop computational tools that simulate both the PCR branching process itself, and the subsequent subsampling which typically occurs during HTS sequencing. We explore the influence of different types of heterogeneity on sequencing output, and compare them to experimental results where the efficiency of amplification is measured by barcodes uniquely identifying each molecule of starting template. Our results demonstrate that the PCR process introduces substantial amplification heterogeneity, independent of primer sequence and bulk experimental conditions. This heterogeneity can be attributed both to inherited differences between different template DNA molecules, and the inherent stochasticity of the PCR process. The results demonstrate that PCR heterogeneity arises even when reaction and substrate conditions are kept as constant as possible, and therefore single molecule barcoding is essential in order to derive reproducible quantitative results from any protocol combining PCR with HTS

Energy transfer in nonlinear network models of proteins

We investigate how nonlinearity and topological disorder affect the energy relaxation of local kicks in coarse-grained network models of proteins. We find that nonlinearity promotes long-range, coherent transfer of substantial energy to specific, functional sites, while depressing transfer to generic locations. Remarkably, transfer can be mediated by the self-localization of discrete breathers at distant locations from the kick, acting as efficient energy-accumulating centers.Comment: 4 pages, 3 figure

Perception of nonnative tonal contrasts by Mandarin-English and English-Mandarin sequential bilinguals

This study examined the role of acquisition order and crosslinguistic similarity in influencing transfer at the initial stage of perceptually acquiring a tonal third language (L3). Perception of tones in Yoruba and Thai was tested in adult sequential bilinguals representing three different first (L1) and second language (L2) backgrounds: L1 Mandarin-L2 English (MEBs), L1 English-L2 Mandarin (EMBs), and L1 English-L2 intonational/non-tonal (EIBs). MEBs outperformed EMBs and EIBs in discriminating L3 tonal contrasts in both languages, while EMBs showed a small advantage over EIBs on Yoruba. All groups showed better overall discrimination in Thai than Yoruba, but group differences were more robust in Yoruba. MEBs’ and EMBs’ poor discrimination of certain L3 contrasts was further reflected in the L3 tones being perceived as similar to the same Mandarin tone; however, EIBs, with no knowledge of Mandarin, showed many of the same similarity judgments. These findings thus suggest that L1 tonal experience has a particularly facilitative effect in L3 tone perception, but there is also a facilitative effect of L2 tonal experience. Further, crosslinguistic perceptual similarity between L1/L2 and L3 tones, as well as acoustic similarity between different L3 tones, play a significant role at this early stage of L3 tone acquisition.Published versio

An Information Theoretic perspective on perceptual structure: cross-accent vowel perception

Analytical tools from Information Theory were used to quantify behaviour in cross-accent vowel perception by Australian, London, New Zealand, Yorkshire and Newcastle UK listeners. Results show that Australian listeners impose expected patterns of perceptual similarity from their own accent experience on unfamiliar accents, regardless of the actual phonetic distance between accents

Multiple electromagnetic electron positron pair production in relativistic heavy ion collisions

We calculate the cross sections for the production of one and more electron-positron pairs due to the strong electromagnetic fields in relativistic heavy ion collisions. Using the generating functional of fermions in an external field we derive the N-pair amplitude. Neglecting the antisymmetrisation in the final state we find that the total probability to produce N pairs is a Poisson distribution. We calculate total cross sections for the production of one pair in lowest order and also include higher-order corrections from the Poisson distribution up to third order. Furthermore we calculate cross sections for the production of up to five pairs including corrections from the Poisson distribution.Comment: 13 pages REVTeX, 4 Postscript figures, This and related papers may also be obtained from http://www.phys.washington.edu/~hencken

Empirical Evidence on the Use of Credit Scoring for Predicting Insurance Losses with Psycho-social and Biochemical Explanations

An important development in personal lines of insurance in the United States is the use of credit history data for insurance risk classification to predict losses. This research presents the results of collaboration with industry conducted by a university at the request of its state legislature. The purpose was to see the viability and validity of the use of credit scoring to predict insurance losses given its controversial nature and criticism as redundant of other predictive variables currently used. Working with industry and government, this study analyzed more than 175,000 policyholders’ information for the relationship between credit score and claims. Credit scores were significantly related to incurred losses, evidencing both statistical and practical significance. We investigate whether the revealed relationship between credit score and incurred losses was explainable by overlap with existing underwriting variables or whether the credit score adds new information about losses not contained in existing underwriting variables. The results show that credit scores contain significant information not already incorporated into other traditional rating variables (e.g., age, sex, driving history). We discuss how sensation seeking and self-control theory provide a partial explanation of why credit scoring works (the psycho-social perspective). This article also presents an overview of biological and chemical correlates of risk taking that helps explain why knowing risk-taking behavior in one realm (e.g., risky financial behavior and poor credit history) transits to predicting risk-taking behavior in other realms (e.g., automobile insurance incurred losses). Additional research is needed to advance new nontraditional loss prediction variables from social media consumer information to using information provided by technological advances. The evolving and dynamic nature of the insurance marketplace makes it imperative that professionals continue to evolve predictive variables and for academics to assist with understanding the whys of the relationships through theory development.IC2 Institut

AGN-Induced Cavities in NGC 1399 and NGC 4649

We present an analysis of archival Chandra and VLA observations of the E0 galaxy NGC 1399 and the E2 galaxy NGC 4649 in which we investigate cavities in the surrounding X-ray emitting medium caused by the central AGN. We calculate the jet power required for the AGN to evacuate these cavities and find values of ~8x10^{41} erg/s and ~14x10^{41} erg/s for the lobes of NGC 1399 and ~7x10^{41} erg/s and ~6x10^{41} erg/s for those of NGC 4649. We also calculate the k/f values for each cavity, where k is the ratio of the total particle energy to that of electrons radiating in the range of 10 MHz to 10 GHz, and f is the volume filling factor of the plasma in the cavity. We find that the values of k/f for the lobes of NGC 1399 are ~93 and ~190, and those of the lobes of NGC 4649 are ~15000 and ~12000. We conclude that the assumed spectrum describes the electron distribution in the lobes of NGC 1399 reasonably well, and that there are few entrained particles. For NGC 4649, either there are many entrained particles or the model spectrum does not accurately describe the population of electrons.Comment: 8 pages, 2 figures, accepted for publication in MNRA

QSO Absorbing Galaxies at z<~1: Deep Imaging and Spectroscopy in the Field of 3C 336

We present very deep WFPC2 images and FOS spectroscopy from the Hubble Space Telescope (HST) together with numerous supporting ground-based observations of the field of the quasar 3C 336 ($z_{em}=0.927$). The observations are designed to investigate the nature of galaxies producing metal line absorption systems in the spectrum of the QSO. Along a single line of sight, we find at least 6 metal line absorption systems (of which 3 are newly discovered) ranging in redshift from 0.317 to 0.892. Through an extensive program of optical and IR imaging, QSO spectroscopy, and faint galaxy spectroscopy, we have identified 5 of the 6 metal line absorption systems with luminous (L_K > 0.1 L*_K) galaxies. These have morphologies ranging from very late-type spiral to S0, and exhibit a wide range of inclination and position angles with respect to the QSO sightline. The only unidentified absorber, despite our intensive search, is a damped Lyman $\alpha$ system at $z_{abs}=0.656$. Analysis of the absorption spectrum suggests that the metal abundances ([Fe/H]$=-1.2$) in this system are similar to those in damped systems at $z \sim 2$, and to the two other damped systems for which abundances have been determined at $z <1$. We have found no examples of intrinsically faint galaxies ($L < 0.1 L^{\ast}$) at small impact parameters that might have been missed as absorber candidates in our previous ground-based imaging and spectroscopic programs on MgII absorbing galaxies. There are no bright galaxies (L > 0.1 L_K) within 50h^{-1} kpc which do not produce detectable metal lines (of Mg II 2796, 2803 and/or C IV 1548, 1550) in the QSO spectrum. All of these results generally support the inferences which we have previously reached from a larger survey for absorption-selected galaxies at z\simlt 1.Comment: 32 pages latex (AAS v4.0 style). 8 Postscript figures (including HST plate) available at ftp://astro.caltech.edu/users/ccs/3c336_figs.ps.gz . Submitted to Ap

Double Lobed Radio Quasars from the Sloan Digital Sky Survey

We have combined a sample of 44984 quasars, selected from the Sloan Digital Sky Survey (SDSS) Data Release 3, with the FIRST radio survey. Using a novel technique where the optical quasar position is matched to the complete radio environment within 450", we are able to characterize the radio morphological make-up of what is essentially an optically selected quasar sample, regardless of whether the quasar (nucleus) itself has been detected in the radio. About 10% of the quasar population have radio cores brighter than 0.75 mJy at 1.4 GHz, and 1.7% have double lobed FR2-like radio morphologies. About 75% of the FR2 sources have a radio core (> 0.75 mJy). A significant fraction (~40%) of the FR2 quasars are bent by more than 10 degrees, indicating either interactions of the radio plasma with the ICM or IGM. We found no evidence for correlations with redshift among our FR2 quasars: radio lobe flux densities and radio source diameters of the quasars have similar distributions at low (mean 0.77) and high (mean 2.09) redshifts. Using a smaller high reliability FR2 sample of 422 quasars and two comparison samples of radio-quiet and non-FR2 radio-loud quasars, matched in their redshift distributions, we constructed composite optical spectra from the SDSS spectroscopic data. Based on these spectra we can conclude that the FR2 quasars have stronger high-ionization emission lines compared to both the radio quiet and non-FR2 radio loud sources. This is consistent with the notion that the emission lines are brightened by ongoing shock ionization of ambient gas in the quasar host as the radio source expands.Comment: 20 pages, 10 figures - some of which have been reduced in quality / size. Accepted for publication in the Astronomical Journa

Mechanical response of random heteropolymers

We present an analytical theory for heteropolymer deformation, as exemplified experimentally by stretching of single protein molecules. Using a mean-field replica theory, we determine phase diagrams for stress-induced unfolding of typical random sequences. This transition is sharp in the limit of infinitely long chain molecules. But for chain lengths relevant to biological macromolecules, partially unfolded conformations prevail over an intermediate range of stress. These necklace-like structures, comprised of alternating compact and extended subunits, are stabilized by quenched variations in the composition of finite chain segments. The most stable arrangements of these subunits are largely determined by preferential extension of segments rich in solvophilic monomers. This predicted significance of necklace structures explains recent observations in protein stretching experiments. We examine the statistical features of select sequences that give rise to mechanical strength and may thus have guided the evolution of proteins that carry out mechanical functions in living cells.Comment: 10 pages, 6 figure