bluuebunny/crossref_metadata_2025 huggingface dataset:
A direct-compatible formulation of the coupled perturbed complete active space self-consistent field equations on graphical processing units
Authors: Snyder James W. , Fales B. Scott , Hohenstein Edward G. , Levine Benjamin G. , Martínez Todd J.
Published: May 2017

We recently developed an algorithm to compute response properties for the state-averaged complete active space self-consistent field method (SA-CASSCF) that capitalized on sparsity in the atomic orbital basis. Our original algorithm was limited to treating small to moderate sized active spaces, but the recent development of graphical processing unit (GPU) based direct-configuration interaction algorithms provides an opportunity to extend this to large active spaces. We present here a direct-compatible version of the coupled perturbed equations, enabling us to compute response properties for systems treated with arbitrary active spaces (subject to available memory and computation time). This work demonstrates that the computationally demanding portions of the SA-CASSCF method can be formulated in terms of seven fundamental operations, including Coulomb and exchange matrix builds and their derivatives, as well as, generalized one- and two-particle density matrix and σ vector constructions. As in our previous work, this algorithm exhibits low computational scaling and is accelerated by the use of GPUs, making possible optimizations and nonadiabatic dynamics on systems with O(1000) basis functions and O(100) atoms, respectively.
Assigning the low lying vibronic states of CH3O and CD3O
Authors: Johnson Britta A. , Sibert Edwin L.
Published: May 2017

The assignment of lines in vibrational spectra in strongly mixing systems is considered. Several low lying vibrational states of the ground electronic X∼2E state of the CH3O and CD3O radicals are assigned. Jahn-Teller, spin-orbit, and Fermi couplings mix the normal mode states. The mixing complicates the assignment of the infrared spectra using a zero-order normal mode representation. Alternative zero-order representations, which include specific Jahn-Teller couplings, are explored. These representations allow for definitive assignments. In many instances it is possible to plot the wavefunctions on which the assignments are based. The plots, which are shown in the adiabatic representation, allow one to visualize the effects of various higher order couplings. The plots also enable one to visualize the conical seam and its effect on the wavefunctions. The first and the second order Jahn-Teller couplings in the rocking motion dominate the spectral features in CH3O, while first order and modulated first order couplings dominate the spectral features in CD3O. The methods described here are general and can be applied to other Jahn-Teller systems.
Effect of n-propyl substituents on the emission properties of blue phosphorescent iridium(iii) complexes
Authors: Zhou Xiuwen , Burn Paul L. , Powell Benjamin J.
Published: May 2017

Ligand substitution is often used for tuning the emission color of phosphorescent iridium(iii) complexes that are used in organic light-emitting diodes. However, in addition to tuning the emission color, the substituents can also affect the radiative and non-radiative decay rates of the excited state and hence the photoluminescence quantum yield. Understanding the substituent effect is therefore important for the design of new iridium(iii) complexes with specific emission properties. Using (time dependent) density functional methods, we investigate the substituent effect of n-propyl groups on the structure, emission color, and emission efficiency of fac-tris(1-methyl-5-phenyl-[1,2,4]triazolyl)iridium(iii) based phosphorescent complexes by comparing the calculated results for structural models with and without the n-propyl substituents. We find that attachment of the n-propyl groups increases the length of three Ir–N bonds, and although the emission color does not change significantly, the radiative and non-radiative rates do, leading to a prediction of enhanced blue phosphorescence emission efficiency. Furthermore, the calculations show that the attachment of the n-propyl groups leads to a larger activation energy to degradation and the formation of dark states.
Apparatus for the investigation of high-temperature, high-pressure gas-phase heterogeneous catalytic and photo-catalytic materials
Authors: Alvino Jason F. , Bennett Trystan , Kler Rantej , Hudson Rohan J. , Aupoil Julien , Nann Thomas , Golovko Vladimir B. , Andersson Gunther G. , Metha Gregory F.
Published: May 2017

A high-temperature, high-pressure, pulsed-gas sampling and detection system has been developed for testing new catalytic and photocatalytic materials for the production of solar fuels. The reactor is fitted with a sapphire window to allow the irradiation of photocatalytic samples from a lamp or solar simulator light source. The reactor has a volume of only 3.80 ml allowing for the investigation of very small quantities of a catalytic material, down to 1 mg. The stainless steel construction allows the cell to be heated to 350 °C and can withstand pressures up to 27 bar, limited only by the sapphire window. High-pressure sampling is made possible by a computer controlled pulsed valve that delivers precise gas flow, enabling catalytic reactions to be monitored across a wide range of pressures. A residual gas analyser mass spectrometer forms a part of the detection system, which is able to provide a rapid, real-time analysis of the gas composition within the photocatalytic reaction chamber. This apparatus is ideal for investigating a number of industrially relevant reactions including photocatalytic water splitting and CO2 reduction. Initial catalytic results using Pt-doped and Ru nanoparticle-doped TiO2 as benchmark experiments are presented.
Influence of interfacial viscosity on the dielectrophoresis of drops
Authors: Mandal Shubhadeep , Chakraborty Suman
Published: May 2017

The dielectrophoresis of a Newtonian uncharged drop in the presence of an axisymmetric nonuniform DC electric field is studied analytically. The present study is focused on the effects of interfacial viscosities on the dielectrophoretic motion and shape deformation of an isolated suspended drop. The interfacial viscosities generate surface-excess viscous stress which is modeled as a two-dimensional Newtonian fluid which obeys the Boussinesq-Scriven constitutive law with constant values of interfacial tension, interfacial shear, and dilatational viscosities. In the regime of small drop deformation, we have obtained analytical solution for the drop velocity and deformed shape by neglecting surface charge convection and fluid inertia. Our study demonstrates that the drop velocity is independent of the interfacial shear viscosity, while the interfacial dilatational viscosity strongly affects the drop velocity. The interfacial viscous effects always retard the dielectrophoretic motion of a perfectly conducting/dielectric drop. Notably, the interfacial viscous effects can retard or augment the dielectrophoretic motion of a leaky dielectric drop depending on the electrohydrodynamic properties. The shape deformation of a leaky dielectric drop is found to decrease (or increase) due to interfacial shear (or dilatational) viscosity.
Development of a linear-type double reflectron for focused imaging of photofragment ions from mass-selected complex ions
Authors: Okutsu Kenichi , Nakashima Yuji , Yamazaki Kenichiro , Fujimoto Keita , Nakano Motoyoshi , Ohshimo Keijiro , Misaizu Fuminori
Published: May 2017

An ion imaging apparatus with a double linear reflectron mass spectrometer has been developed, in order to measure velocity and angular distributions of mass-analyzed fragment ions produced by photodissociation of mass-selected gas phase complex ions. The 1st and the 2nd linear reflectrons were placed facing each other and controlled by high-voltage pulses in order to perform the mass-separation of precursor ions in the 1st reflectron and to observe the focused image of the photofragment ions in the 2nd reflectron. For this purpose, metal meshes were attached on all electrodes in the 1st reflectron, whereas the mesh was attached only on the last electrode in the 2nd reflectron. The performance of this apparatus was evaluated using imaging measurement of Ca+ photofragment ions from photodissociation reaction of Ca+Ar complex ions at 355 nm photoexcitation. The focused ion images were obtained experimentally with the double linear reflectron at the voltages of the reflection electrodes close to the predictions by ion trajectory simulations. The velocity and angular distributions of the produced Ca+ ([Ar] 4p1, 2P3/2) ion were analyzed from the observed images. The binding energy D0 of Ca+Ar in the ground state deduced in the present measurement was consistent with those determined theoretically and by spectroscopic measurements. The anisotropy parameter β of the transition was evaluated for the first time by this instrument.
Explicit symplectic methods for solving charged particle trajectories
Authors: Zhou Zhaoqi , He Yang , Sun Yajuan , Liu Jian , Qin Hong
Published: May 2017

In this paper, we consider the Lorentz force system based on its Hamiltonian formulation. We decompose the Lorentz force system into four subsystems which can be solved with the help of coordinate transformations. Via the coordinate transformations, three kinds of explicit symplectic numerical methods have been established for simulating the motion of charged particles under the time-independent electromagnetic field. We generalize our methods to solve the system with time-dependent external electromagnetic fields, and also the system with a relativistic effect. In numerical experiments, the computing efficiency and accuracy over a long time for the newly derived methods are demonstrated. Also, the long-term simulation for the dynamics of runaway electrons is performed.
Thermal annealing behavior of nano-size metal-oxide particles synthesized by ion implantation in Fe-Cr alloy
Authors: Zheng C. , Gentils A. , Ribis J. , Borodin V. A. , Descoins M. , Mangelinck D. , Dalle F. , Arnal B. , Delauche L.
Published: May 2017

Oxide dispersion strengthened (ODS) steels are promising structural materials for the next generation nuclear reactors, as well as fusion facilities. The detailed understanding of the mechanisms involved in the precipitation of nano-oxides during ODS steel production would strongly contribute to the improvement of the mechanical properties and the optimization of manufacturing of ODS steels, with a potentially strong economic impact for their industrialization. A useful tool for the experimental study of nano-oxide precipitation is ion implantation, a technique that is widely used to synthesize precipitate nanostructures in well-controlled conditions. Earlier, we have demonstrated the feasibility of synthesizing aluminum-oxide particles in the high purity Fe-10Cr alloy by consecutive implantation with Al and O ions at room temperature. This paper describes the effects of high-temperature annealing after the ion implantation stage on the development of the aluminum based oxide nanoparticle system. Using transmission electron microscopy and atom probe tomography experiments, we demonstrate that post-implantation heat treatment induces the growth of the nano-sized oxides in the implanted region and nucleation of new oxide precipitates behind the implantation zone as a result of the diffusion driven broadening of implant profiles. A tentative scenario for the development of metal-oxide nano-particles at both ion implantation and heat treatment stages is suggested based on the experimental observations.
Thermal switching probability distribution of L10 FePt for heat assisted magnetic recording
Authors: Liu Zengyuan , Huang Pin-Wei , Ju Ganping , Victora R. H.
Published: May 2017

Transition jitter is one of the most important parameters for evaluating the potential areal density of Heat Assisted Magnetic Recording. However, obtaining this either experimentally or through micro-magnetic simulation is time consuming. Here, we show that the more easily calculated thermal switching probability distribution (SPD) can serve as a substitute. In particular, we provide an equation relating the standard deviation of write temperature to the jitter. The equation is verified for three critical noise sources: Tc variance, HK variance, and grain size distribution. In addition, the SPD subject to cooling at various cross-track positions is investigated. A method to determine the magnetic grain size is proposed.
Genetic rescue models refute nonautonomous rod cell death in retinitis pigmentosa
Authors: Koch Susanne F. , Duong Jimmy K. , Hsu Chun-Wei , Tsai Yi-Ting , Lin Chyuan-Sheng , Wahl-Schott Christian A. , Tsang Stephen H.
Published: May 2017

Significance

Retinitis pigmentosa is the leading cause of inherited blindness. Although gene therapy has the capacity to rescue diseased cells (usually rods), current methods generate retinas that are a mix of treated, rescued and untreated, dying rods. To determine whether the dying rods negatively impact rescue, we developed mouse models that allowed us to treat defined fractions of diseased rods. We found that dying rods did not trigger the death of rescued photoreceptors, even when the rescued cells are greatly outnumbered. On the other hand, the rescued photoreceptors did exhibit long-term defects, which were less severe when more rods were treated. Thus, although genetic rescue leads to survival of treated rods, it does not prevent other aspects of the retinitis pigmentosa pathology.
Substrate recognition of the catalytic α-subunit of glucosidase II from Schizosaccharomyces pombe
Authors: Okuyama Masayuki , Miyamoto Masashi , Matsuo Ichiro , Iwamoto Shogo , Serizawa Ryo , Tanuma Masanari , Ma Min , Klahan Patcharapa , Kumagai Yuya , Tagami Takayoshi , Kimura Atsuo
Published: May 2017

The recombinant catalytic α-subunit of N-glycan processing glucosidase II from Schizosaccharomyces pombe (SpGIIα) was produced in Escherichia coli. The recombinant SpGIIα exhibited quite low stability, with a reduction in activity to <40% after 2-days preservation at 4 °C, but the presence of 10% (v/v) glycerol prevented this loss of activity. SpGIIα, a member of the glycoside hydrolase family 31 (GH31), displayed the typical substrate specificity of GH31 α-glucosidases. The enzyme hydrolyzed not only α-(1→3)- but also α-(1→2)-, α-(1→4)-, and α-(1→6)-glucosidic linkages, and p-nitrophenyl α-glucoside. SpGIIα displayed most catalytic properties of glucosidase II. Hydrolytic activity of the terminal α-glucosidic residue of Glc2Man3-Dansyl was faster than that of Glc1Man3-Dansyl. This catalytic α-subunit also removed terminal glucose residues from native N-glycans (Glc2Man9GlcNAc2 and Glc1Man9GlcNAc2) although the activity was low.
Enhancements in sucrose biosynthesis capacity affect shoot branching in Arabidopsis
Authors: Otori Kumi , Tamoi Masahiro , Tanabe Noriaki , Shigeoka Shigeru
Published: May 2017

We previously demonstrated that transgenic tobacco plants expressing cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase in the cytosol increased the number of lateral shoots and leaves at elevated CO2 levels. These findings suggest that alterations in carbon partitioning affect the development of shoot branching. In order to elucidate the underlying mechanisms at the molecular level, we generated transgenic Arabidopsis plants overexpressing cyanobacterial fructose-1,6-bisphosphatase-II in the cytosol (AcF). At elevated CO2 levels, the number of lateral shoots was significantly increased in AcF plants. Sucrose and hexose levels were also higher in AcF plants than in wild-type plants. The expression levels of MAX1, MAX4, YUCCA8, YUCCA9, and BRC1, which are involved in auxin or strigolactone biosynthesis and responses, were lower in AcF plants than in wild-type plants. These results suggest that alterations in sugar partitioning affect hormone metabolism and responses, resulting in enhanced shoot branching.
Map learning and working memory: Multimodal learning strategies
Authors: Knight Matthew James , Tlauka Michael
Published: May 2017

The current research investigated whether learning spatial information from a map involves different modalities, which are managed by discrete components in working memory. In four experiments, participants studied a map either while performing a simultaneous interference task (high cognitive load) or without interference (low cognitive load). The modality of interference varied between experiments. Experiment 1 used a tapping task (visuospatial), Experiment 2 a backward counting task (verbal), Experiment 3 an articulatory suppression task (verbal) and Experiment 4 an n-back task (central executive). Spatial recall was assessed in two tests: directional judgements and map drawing. Cognitive load was found to affect spatial recall detrimentally regardless of interference modality. The findings suggest that when learning maps, people use a multimodal learning strategy, utilising resources from all components of working memory.
EURAMET key comparison no. EURAMET.T-K1: realisations of the ITS-90 from 2.6 K to 24.5561 K, using rhodium-iron resistance thermometers
Authors: Gaiser Christof , Fellmuth Bernd , Steur Peter , Szmyrka-Grzebyk Anna , Manuszkiewicz Henryk , Lipinski Leszek , Peruzzi Andrea , Rusby Richard , Head David
Published: May 2017

In the temperature range from 0.65 K to 24.5561 K, the ITS-90 is defined by specified vapour-pressure equations for 3He and 4He and interpolation equations for a constant-volume gas thermometer using 3He or 4He. The definitions are given in sections 3.1 and 3.2 of the ITS-90 text, and methods for realising the scale in this range are outlined in chapters 4 and 5 of the Guide to the Realization of the ITS-90 (formerly Supplementary Information for the ITS-90). Direct realisations of the ITS-90 by these methods require relatively sophisticated apparatus and time-consuming experiments, and consequently they are rarely carried out. The situation is acceptable in practice only because rhodium-iron resistance thermometers (RIRTs) are available that, once calibrated, are able to maintain their calibrations reliably for long periods of time. They are the practical thermometers on which realisations of the ITS-90 are most accurately maintained, disseminated and compared. The key comparison EURAMET.T-K1 is therefore a comparison of calibrated RIRTs.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCT, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Shakespeare's Tragedies: A Very Short Introduction
Authors: Wells Stanley
Published: May 2017

Tragedy, including grief, pain, and suffering, is a common theme in Shakespeare’s plays, often leading to the death of at least one character. Yet such themes can also be found in Shakespearian plays which are classed as comedies or histories. What is it that makes a Shakespearian tragedy, and what dramatic themes and conventions did the bard draw upon when writing them? Shakespeare’s Tragedies: A Very Short Introduction considers what is meant by the word ‘tragedy’, offering a critical analysis of nine of Shakespeare’s iconic tragic plays. It concludes by discussing why tragedy is regarded as a fit subject for entertainment, and why audiences find tragic plays so enjoyable.
Romeo and Juliet
Authors: Wells Stanley
Published: May 2017

The story of the ‘star-crossed lovers’ was already popular when Shakespeare wrote his play, around 1595, basing its narrative fairly closely on a long poem by Arthur Brooke. The difference between Titus Andronicus and Romeo and Juliet, written only a few years apart, is a measure of the speed of Shakespeare’s development as both a dramatist and a poet, and of the openness of his concept of tragedy, which in this play permits the inclusion of romance and of many comic elements. ‘Romeo and Juliet’ outlines the play’s plot and structure, and explains how the play’s scenario is cunningly devised so that it incorporates a variety of theatrical entertainment.
Julius Caesar
Authors: Wells Stanley
Published: May 2017

Many tragedies of Shakespeare’s time are concerned with the fall from power, and eventual death, of great men of the past. In writing about the assassination of Julius Caesar, perhaps the greatest ruler who had ever lived, Shakespeare was dramatizing one of the most famous events in world history. ‘Julius Caesar’ explains how Shakespeare based his play quite closely on Plutarch’s description of Caesar’s life. Shakespeare wrote a study of the uses and abuses of political power, the morality of rebellion, and of assassination, applicable to the state of the nation when the play was first performed, at the Globe in 1599, towards the end of Queen Elizabeth I’s reign.
Othello
Authors: Wells Stanley
Published: May 2017

Like Romeo and Juliet, Othello is a fictional love tragedy focusing on two private individuals whose lives are not bound up with the fate of nations. The play is based on an Italian tale—a prosaic story of love and jealousy—by Giraldi Cinthio, which Shakespeare romanticizes and dignifies. Compact, fast-moving, tensely dramatic, emotionally compelling, and rising to a riveting tragic conclusion with the murder of Desdemona by Othello followed by his suicide, it is an immensely effective piece of theatre written in dialogue, sometimes racy and conversational, which rises to great heights of eloquence. ‘Othello’ describes the key characters Othello, Iago, and Desdemona, and the plot of the play.
Antony and Cleopatra
Authors: Wells Stanley
Published: May 2017

Antony and Cleopatra is a great sprawling masterpiece of a play, rich in poetry, vast in imaginative power, in depth of characterization, in psychological penetration, in ironical comedy, and ultimately in tragic grandeur. Its irony results partly from the fact that its central characters invite us not so much to identify with them, but rather to wonder at them with awe and amazement. ‘Antony and Cleopatra’ explains that the play draws heavily on Plutarch’s Lives of the Noble Grecians and Romans and describes two worlds—Cleopatra’s Egypt and Mark Antony’s Rome—and of the links, but also of the contrasts and tensions, between them.
FlashPCA2: principal component analysis of Biobank-scale genotype datasets
Authors: Abraham Gad , Qiu Yixuan , Inouye Michael
Published: May 2017

Motivation

Principal component analysis (PCA) is a crucial step in quality control of genomic data and a common approach for understanding population genetic structure. With the advent of large genotyping studies involving hundreds of thousands of individuals, standard approaches are no longer feasible. However, when the full decomposition is not required, substantial computational savings can be made.

Results

We present FlashPCA2, a tool that can perform partial PCA on 1 million individuals faster than competing approaches, while requiring substantially less memory.

Availability and implementation

https://github.com/gabraham/flashpca.

Supplementary information

Supplementary data are available at Bioinformatics online.
Implications of electronic health record downtime: an analysis of patient safety event reports
Authors: Larsen Ethan , Fong Allan , Wernz Christian , Ratwani Raj M
Published: May 2017

Objective

We sought to understand the types of clinical processes, such as image and medication ordering, that are disrupted during electronic health record (EHR) downtime periods by analyzing the narratives of patient safety event report data.

Materials and Methods

From a database of 80 381 event reports, 76 reports were identified as explicitly describing a safety event associated with an EHR downtime period. These reports were analyzed and categorized based on a developed code book to identify the clinical processes that were impacted by downtime. We also examined whether downtime procedures were in place and followed.

Results

The reports were coded into categories related to their reported clinical process: Laboratory, Medication, Imaging, Registration, Patient Handoff, Documentation, History Viewing, Delay of Procedure, and General. A majority of reports (48.7%, n = 37) were associated with lab orders and results, followed by medication ordering and administration (14.5%, n = 11). Incidents commonly involved patient identification and communication of clinical information. A majority of reports (46%, n = 35) indicated that downtime procedures either were not followed or were not in place. Only 27.6% of incidents (n = 21) indicated that downtime procedures were successfully executed.

Discussion

Patient safety report data offer a lens into EHR downtime–related safety hazards. Important areas of risk during EHR downtime periods were patient identification and communication of clinical information; these should be a focus of downtime procedure planning to reduce safety hazards.

Conclusion

EHR downtime events pose patient safety hazards, and we highlight critical areas for downtime procedure improvement.
Impact of Young Age on the Presentation of Saccular Intracranial Aneurysms: Population-Based Analysis of 4082 Patients
Authors: Räisänen Sari , Frösen Juhana , Kurki Mitja I , Huttunen Terhi , Huttunen Jukka , Koivisto Timo , Helin Katariina , von und zu Fraunberg Mikael , Jääskeläinen Juha E , Lindgren Antti E
Published: May 2017

BACKGROUND

Formation and rupture of saccular intracranial aneurysms (sIAs) may have different pathobiologies in patients with younger age at first diagnosis of sIA disease.

OBJECTIVE

To study the phenotype of sIA disease and formation of new (de novo) sIAs in patients below 40 yr.

METHODS

A population-based cohort study was conducted in 613 young (<40 yr) sIA patients with first diagnosis between 1980 and 2014 and total angiographic follow-up of 3768 yr.

RESULTS

Of the 613 sIA patients <40 yr, 508 had aneurysmal subarachnoid hemorrhage (sIA-SAH) and 105 unruptured sIA(s) at first sIA diagnosis. Hypertension was 2 times less common among <40 than >40-yr-old patients (unruptured and ruptured). Smoking was very prevalent in <40-yr-old patients (33% in SAH, 68% unruptured). SAH patients <40 yr more often had family history of sIA, and lower PHASES scores (age omitted, P < .001). Ruptured sIAs were small (<7 mm) in 33% of 39 to 30 yr patients, in 44% of 29 to 20 yr patients, and 57% of <19 yr patients. Their shape was irregular in 90%, 94%, and 95%, respectively. Smoking history (hazard ratio [HR] 2.8, 95% confidence interval [CI] 1.2-7.0), family history for sIAs (HR 3.1, 95% CI 1.3-7.7), and age at presentation (HR .91 per year, 95% CI .85-.98) were risk factors for de novo sIA formation, diagnosed in 4% even after 20 yr (median 11.8 yr).

CONCLUSION

Smoking and family history are risk factors for sIA formation and aneurysmal SAH at young age. Young aneurysmal SAH patients had lower PHASES scores and often rupture from a small sIA, suggesting need for more aggressive management.
Endoscopic Transcranial Duraplasty for Rhinoliquorrhea: A Cadaveric Study
Authors: Bartoli Andrea , Fasel Jean H , Schaller Karl , Jägersberg Max
Published: May 2017

BACKGROUND

Repair of the anterior skull base for cerebrospinal fluid leak requires either endoscopic endonasal approach or open transcranial approach.

OBJECTIVE

To present a less invasive surgical procedure for sealing of the entire anterior fossa floor for traumatic rhinoliquorrhea.

METHODS

Cadaver study in 3 head specimens. Endoscopic placement of a furled bovine pericardial patch bilaterally along the sphenoid ridge and planum in guidewire technique. Unfurling and spreading of the patch under endoscope assistance.

RESULTS

Patch placement was feasible in all 3 specimens without visible injuries to the frontal lobes. Dissection and preservation of the olfactory tracts was only possible for 50% of olfactory tracts.

CONCLUSION

Endoscopic transcranial keyhole duraplasty is a promising concept for traumatic rhinoliquorrhea.
Newborn Congenital Cytomegalovirus Screening Based on Clinical Manifestations and Evaluation of DNA-based Assays for In Vitro Diagnostics
Authors: Fujii Tomoyuki , Oka Akira , Morioka Ichiro , Moriuchi Hiroyuki , Koyano Shin , Yamada Hideto , Saito Shigeru , Sameshima Hiroshi , Nagamatsu Takeshi , Tsuchida Shinya , Inoue Naoki
Published: May 2017

Objectives:

To establish a strategy for congenital cytomegalovirus (cCMV) screening and to establish confirmatory assays approved as in vitro diagnostics by the regulatory authorities, we evaluated the clinical risks and performance of diagnostic assays developed by commercial companies, since cCMV infection has significant clinical consequences.

Study Design:

Newborns with clinical manifestations considered to be consequences of cCMV infection (n = 575) were screened for the presence of cytomegalovirus (CMV) DNA in urine specimens collected onto filter paper placed in their diapers using the polymerase chain reaction–based assay reported previously. Liquid urine specimens were obtained from all of 20 CMV-positive newborns and 107 of the CMV-negative newborns identified in the screening. We used these 127 specimens, as well as 12 from cCMV cases identified in a previous study and 41 from healthy newborns, to compare the performance of 2 commercial assays and 1 in-house assay.

Results:

The risk-based screening allowed the identification of cCMV cases at least 10-fold more efficiently than our previous universal screening, although there appears to be a limit to the identification of asymptomatically infected newborns. Although CMV-specific IgM during pregnancy was found frequently in mothers of cCMV newborns, CMV-IgM alone is not an effective diagnostic marker. The urine-filter–based assay and the 3 diagnostic assays yielded identical results.

Conclusions:

Although risk-based and universal newborn screening strategies for cCMV infection each have their respective advantages and disadvantages, urine-filter–based assay followed by confirmatory in vitro diagnostics assays is able to identify cCMV cases efficiently.
Long-term Survival After Surgery Compared With Concurrent Chemoradiation for Node-negative Small Cell Lung Cancer
Authors: Yang Chi-Fu Jeffrey , Chan Derek Y. , Shah Shivani A. , Yerokun Babatunde A. , Wang Xiaofei F. , D’Amico Thomas A. , Berry Mark F. , Jr David H. Harpole
Published: May 2017

Objective:

To determine whether surgery with adjuvant chemotherapy offers a survival advantage over concurrent chemoradiation for patients with cT1-2N0M0 small cell lung cancer (SCLC).

Background:

Although surgery with adjuvant chemotherapy is the recommended treatment for patients with cT1-2N0M0 SCLC per international guidelines, there have been no prospective or retrospective studies evaluating the impact of surgery versus optimal medical management for cT1-2N0M0 SCLC.

Methods:

Outcomes of patients with cT1-2N0M0 SCLC who underwent surgery with adjuvant chemotherapy or concurrent chemoradiation in the National Cancer Data Base (2003–2011) were evaluated using Cox proportional hazards analyses and propensity-score-matched analyses.

Results:

During the study period, 681 (30%) patients underwent surgery with adjuvant chemotherapy and 1620 (70%) underwent concurrent chemoradiation. After propensity-score matching, all 14 covariates were well balanced between the surgery (n = 501) and concurrent chemoradiation (n = 501) groups. Surgery was associated with a higher overall survival (OS) than concurrent chemoradiation (5-year OS 47.6% vs 29.8%, P < 0.01). To minimize selection bias due to comorbidities, we limited the propensity-matched analysis to 492 patients with no comorbidities; surgery remained associated with a higher OS than concurrent chemoradiation (5-year OS 49.2% vs 32.5%, P < 0.01).

Conclusions:

In a national analysis, surgery with adjuvant chemotherapy was used in the minority of patients for early stage SCLC. Surgery with adjuvant chemotherapy for node-negative SCLC was associated with improved long-term survival when compared to concurrent chemoradiation. These results suggest a significant underuse of surgery among patients with early stage SCLC and support an increased role of surgery in multimodality therapy for cT1-2N0M0 SCLC.
Aeromonas species endogenous endophthalmitis
Authors: Ryan Laura , Higgins Gareth , Doyle Maeve
Published: May 2017

Introduction.
Aeromonas spp. are Gram-negative bacteria classically associated with water sources and a variety of clinical infections in humans.

Case presentation. A 79-year-old female patient presented with gastroenteritis with associated Aeromonas spp. bloodstream infection. Two days after admission she developed eye symptoms and was diagnosed with endophthalmitis and underwent emergency evisceration and implant. Aeromonas spp. was also recovered from intra-ocular samples.

Conclusion. In this case gastroenteritis caused by Aeromonas spp. was complicated by bloodstream infection which seeded to the eye, resulting in rapidly progressive endogenous endophthalmitis.
Diagnostic, Infection Timing and Incidence Surveillance Applications of High Dynamic Range Chemiluminescent HIV Immuno-Assay Platforms
Authors: Grebe Eduard , Welte Alex , Hall Jake , Keating Sheila M. , Facente Shelley N. , Marson Kara , Martin Jeffrey N. , Little Susan J. , Price Matthew A. , Kallas Esper G. , Busch Michael P. , Pilcher Christopher D. , Murphy Gary ,   on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA)
Published: May 2017

Background

Custom staging assays, including the Sedia HIV-1 Limiting Antigen Avidity EIA (LAg) and avidity modifications of the Ortho VITROS anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify ‘recent’ infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and longstanding infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications.

Methods

We tested a panel of 2,500 well-characterised specimens with estimable duration of HIV infection with the three assays and the unmodified ARCHITECT. Regression models were used to estimate mean durations of recent infection (MDRI), context-specific false-recent rates (FRR) and correlation between signal intensity and LAg measurements. A hypothetical epidemiological scenario was constructed to evaluate utility in surveillance applications.

Results

Over a range of MDRIs (reflecting recency discrimination thresholds), a diluted ARCHITECT-based RITA produced lower FRRs than the VITROS platform (FRR ≈ 0.5% and 1.5% respectively at MDRI of 200 days) and the unmodified diagnostic ARCHITECT produces incidence estimates with comparable precision to LAg (RSE ≈ 17.5% and 15% respectively at MDRI of 200 days). ARCHITECT S/CO measurements were highly correlated with LAg ODn measurements (r = 0.80) and values below 200 are strongly predictive of LAg recency and duration of infection less than one year.

Conclusions

Low quantitative measurements from the unmodified ARCHITECT obviate the need for additional recency testing and its use is feasible in clinical staging and incidence surveillance applications.
Testing an alternative explanation for relatively greater base-sharing between Neanderthals and non-African humans
Authors: Amos William
Published: May 2017

Most accept that non-African humans share ∼2% of their genome with Neanderthals (1) and that inter-breeding occurred between several archaic lineages (2-4). However, most evidence assumes that mutation rate is constant. It has been suggested that heterozygosity is mutagenic (5-8). If so, an alternative explanation of the data becomes possible. Instead of non-Africans sharing relatively more bases with Neanderthals due to interbreeding, Africans could appear unexpectedly divergent due to their mutation rate not having been lowered when diversity was lost during the out of Africa bottleneck. I therefore tested a series of predictions aimed at distinguishing mutation slowdown from inter-breeding. Predictions from mutation slowdown are generally better supported. For example, the signal used to infer inter-breeding remains even when Neanderthal sequences are excluded. I conclude that, while some inter-breeding probably did occur, an appreciable component of the signal seems better explained by mutation slowdown.
Experimental evidence that thermal selection shapes mitochondrial genome evolution
Authors: Lajbner Zdeněk , Pnini Reuven , Camus M. Florencia , Miller Jonathan , Dowling Damian K.
Published: May 2017

Mitochondria are essential organelles, found within eukaryotic cells, which contain their own DNA. Mitochondrial DNA (mtDNA) has traditionally been used in population genetic and biogeographic studies as a maternally-inherited and evolutionary-neutral genetic marker. However, it is now clear that polymorphisms within the mtDNA sequence are routinely non-neutral, and furthermore several studies have suggested that such mtDNA polymorphisms are also sensitive to thermal selection. These observations led to the formulation of the “mitochondrial climatic adaptation” hypothesis, for which all published evidence to date is correlational. Here, we use laboratory-based experimental evolution in the fruit fly,Drosophila melanogaster,to test whether thermal selection can shift population frequencies of two mtDNA haplogroups whose natural frequencies exhibit clinal associations with latitude along the Australian east-coast. We present experimental evidence that the thermal regime in which the laboratory populations were maintained, drove changes in haplogroup frequencies across generations. Our results strengthen the emerging view that intra-specific mtDNA variants are sensitive to selection, and suggest spatial distributions of mtDNA variants in natural populations of metazoans might reflect adaptation to climatic environments rather than within-population coalescence and diffusion of selectively-neutral haplotypes across populations.

Impact Summary

We applied experimental laboratory evolution to provide the first direct test of the “mitochondrial climatic hypothesis,” which predicts that the variation of mitochondrial genomes across natural distributions of metazoans can be shaped by thermal selection. Our design is the first of its kind when it comes to inferring the role of thermal selection in shaping mtDNA frequencies in nature. We harness two naturally occurring mtDNA haplotypes ofDrosophila melanogasterthat segregate along the east coast of Australia. One of these haplotypes predominates at sub-tropical northern latitudes and the other in the temperate and cooler south of the country. We then compete these haplotypes against each other in replicated experimental fly populations submitted to one of four different thermal regimes, in either the presence or absence of infection byWolbachia, a coevolved endosymbiont that also exhibits maternal transmission.

We confirm that when evolving in the laboratory under warmer conditions, a haplotype naturally predominating in subtropical conditions outcompetes a haplotype that predominates at cooler Australian latitudes in the wild. We see this effect on haplotype frequencies in females in populations where latentWolbachiainfections had been purged.

Our results also suggest that sex-specificity of mtDNA effects, and co-occurrence of other maternally-inherited microbiotic entities - of whichWolbachiais just one example - are likely to shape the trajectories of mitochondrial genome evolution in the wild.
Stimulus dependent diversity and stereotypy in the output of an olfactory functional unit
Authors: Arneodo Ezequiel M. , Penikis Kristina B. , Rabinowitz Neil , Cichy Annika , Zhang Jingji , Bozza Thomas , Rinberg Dmitry
Published: May 2017

Olfactory inputs are organized in an array of parallel functional units (glomeruli), each relaying information from sensory neurons that express a given odorant receptor to a small population of output neurons, mitral/tufted (MT) cells. MT cells have complex temporal responses to odorants, but how these diverse responses relate to stimulus features is not known. We recorded in awake mice responses from “sister” MT cells that receive input from a functionally-characterized, genetically identified glomerulus, corresponding to a specific receptor (M72). Despite receiving similar inputs, sister MT cells exhibited temporally diverse, concentration variant, excitatory and inhibitory responses to most M72 ligands. In contrast, the strongest known ligand for M72 elicited temporally-stereotyped, early excitatory responses in all sister MT cells that persisted across all odor concentrations. Our data demonstrate that information about ligand affinity is encoded in the collective stereotypy or diversity of activity among sister MT cells within a glomerular functional unit in concentration-independent manner.
In-silico read normalization using set multi-cover optimization
Authors: Durai Dilip A , Schulz Marcel H
Published: May 2017

DeBruijn graphs are a common assembly data structure for large sequencing datasets. But with the advances in sequencing technologies, assembling high coverage datasets has become a computational challenge. Read normalization, which removes redundancy in large datasets, is widely applied to reduce resource requirements. Current normalization algorithms, though efficient, provide no guarantee to preserve importantk-mers that form connections between regions in the graph. Here, normalization is phrased as aset multi-cover problemon reads and a heuristic algorithm, ORNA, is proposed. ORNA normalizes to the minimum number of reads required to retain allk-mers and their relativekmer abundances from the original dataset. Hence, all connections and coverage information from the original graph are preserved. ORNA was tested on various RNA-seq datasets with different coverage values. It was compared to the current normalization algorithms and was found to be performing better. It is shown that combining read error correction and normalization allows more accurate and resource efficient RNA assemblies compared to the original dataset. Further, an application was proposed in which multiple datasets were combined and normalized to predict novel transcripts that would have been missed otherwise. Finally, ORNA is a general purpose normalization algorithm that is fast and significantly reduces datasets with little loss of assembly quality.

ORNA can be found underhttps://github.com/SchulzLab/ORNA
Self-organisation and positioning of bacterial protein clusters
Authors: Murray Seán M. , Sourjik Victor
Published: May 2017

Many cellular processes require sub-cellular positioning of proteins. This can be due to passive mechanisms such as recruitment by existing landmarks or curvature sensing. However, in bacteria active self-positioning is likely to play a role in multiple processes, including the positioning of the future division site and cytoplasmic protein clusters. How can such dynamic clusters be formed and positioned? Here, we present a model for the self-organization and positioning of dynamic protein clusters into regularly repeating patterns based on a phase-locked Turing pattern. A single peak in the concentration is always positioned at mid-domain (mid-cell) while two peaks are positioned one at each quarter-position etc. Furthermore, domain growth results in peak-splitting and pattern doubling. We argue that the model may explain the regular positioning of the highly conserved Structural Maintenance of Chromosomes (SMC) complexes on the bacterial nucleoid and provides an attractive mechanism for the self-positioning of dynamic protein clusters in other systems.
Activations of Deep Convolutional Neural Network are Aligned with Gamma Band Activity of Human Visual Cortex
Authors: Kuzovkin Ilya , Vicente Raul , Petton Mathilde , Lachaux Jean-Philippe , Baciu Monica , Kahane Philippe , Rheims Sylvain , Vidal Juan R. , Aru Jaan
Published: May 2017

Previous work demonstrated a direct correspondence between the hierarchy of the human visual areas and layers of deep convolutional neural networks (DCNN) trained on visual object recognition. We used DCNNs to investigate which frequency bands correlate with feature transformations of increasing complexity along the ventral visual pathway. By capitalizing on intracranial depth recordings from 100 patients and 11293 electrodes we assessed the alignment between the DCNN and signals at different frequency bands in different time windows. We found that gamma activity, especially in the low gamma-band (30 – 70 Hz), matched the increasing complexity of visual feature representations in the DCNN. These findings show that the activity of the DCNN captures the essential characteristics of biological object recognition not only in space and time, but also in the frequency domain. These results also demonstrate the potential that modern artificial intelligence algorithms have in advancing our understanding of the brain.

Significance Statement

Recent advances in the field of artificial intelligence have revealed principles about neural processing, in particular about vision. Previous works have demonstrated a direct correspondence between the hierarchy of human visual areas and layers of deep convolutional neural networks (DCNNs), suggesting that DCNN is a good model of visual object recognition in primate brain. Studying intracranial depth recordings allowed us to extend previous works by assessing when and at which frequency bands the activity of the visual system corresponds to the DCNN. Our key finding is that signals in gamma frequencies along the ventral visual pathway are aligned with the layers of DCNN. Gamma frequencies play a major role in transforming visual input to coherent object representations.
SArKS:de novodiscovery of gene expression regulatory motifs and domains by suffix array kernel smoothing
Authors: Wylie Dennis , Hofmann Hans A. , Zemelman Boris V.
Published: May 2017

Motivation

We set out to develop an algorithm that can mine differential gene expression data to identify candidate cell type-specific DNA regulatory sequences. Differential expression is usually quantified as a continuous score—fold-change, test-statistic,p-value—comparing biological classes. Unlike existing approaches, ourde novostrategy, termed SArKS, applies nonparametric kernel smoothing to uncover promoter motifs that correlate with elevated differential expression scores. SArKS detects motifs by smoothing sequence scores over sequence similarity. A second round of smoothing over spatial proximity reveals multi-motif domains (MMDs). Discovered motifs can then be merged or extended based on adjacency within MMDs. False positive rates are estimated and controlled by permutation testing.

Results

We applied SArKS to published gene expression data representing distinct neocortical neuron classes inM. musculusand interneuron developmental states inH. sapiens. When benchmarked against several existing algorithms for correlative motif discovery using a cross-validation procedure, SArKS identified larger motif sets that formed the basis for regression models with higher correlative power.

Availability

https://github.com/denniscwylie/sarks.

Contact

denniswylie@austin.utexas.edu.

Supplementary information

appended to document.