bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced property of thin cuprous oxide film prepared through green synthetic route
Authors: Kasmi Achraf El , Vieker Henning , Wu Ling-nan , Beyer André , Chafik Tarik , Tian Zhen-yu
Published: May 2019

Thin cuprous oxide films have been prepared by chemical vapor deposition (pulsed spray evaporation-chemical vapor deposition) method without post-treatment. The synthesis of cuprous oxide was produced by applying a water strategy effect. Then, the effect of water on the morphology, topology, structure, optical properties and surface composition of the obtained films has been comprehensively investigated. The results reveal that a pure phase of Cu2O was obtained. The introduction of a small quantity of water in the liquid feedstock lowers the band gap energy from 2.16 eV to 2.04 eV. This finding was mainly related to the decrease of crystallite size due to the effect of water. The topology analyses, by using atomic force microscope, also revealed that surface roughness decreases with water addition, namely more uniform covered surface. Moreover, theoretical calculations based on density functional theory method were performed to understand the adsorption and reaction behaviors of water and ethanol on the Cu2O thin film surface. Formation mechanism of the Cu2O thin film was also suggested and discussed.
ADOPTing a new method of partner management for genital chlamydia in New South Wales: findings from a pilot implementation program of patient-delivered partner therapy
Authors: Lorch Rebecca , Bourne Christopher , Burton Leanne , Lewis Larissa , Brown Katherine , Bateson Deborah , Knight Vickie , Ooi Catriona , Hoffman Naomi , Mackson Judith , Bower Hilary , Stewart Mary , Moll Nicola , Micallef Joanne , Mooney-Somers Julie , Donovan Basil , Kaldor John , Guy Rebecca
Published: May 2019

Background Patient-delivered partner therapy (PDPT) for chlamydia is an effective and safe additional partner management strategy. Some Australian regulatory changes have been made to support PDPT, but implementation guidance is lacking. This paper describes a pilot implementation program of PDPT in New South Wales (NSW), the Australian Development and Operationalisation of Partner Therapy (ADOPT). Methods: ADOPT involved: (1) clarification of the NSW PDPT legal and policy framework; (2) development and implementation of PDPT service models, resources and data collection tools for select publicly funded sexual health services (PFSHS) and Family Planning (FP) NSW clinics; and (3) evaluation of PDPT uptake. Results: PDPT can be undertaken in NSW if accompanied by adequate provider, patient and partner information. Regulatory amendments enabled medication prescribing. The pilot implementation took place in four PFSHS and five FPNSW clinics from January to December 2016. In PFSHS, 30% of eligible patients were offered PDPT and 89% accepted the offer. In FPNSW clinics, 42% of eligible patients were offered PDPT and 63% accepted the offer. Most partners for whom PDPT was accepted were regular partners. Conclusions: A close collaboration of researchers, policy makers and clinicians allowed successful implementation of a PDPT model for chlamydia in heterosexual patients at select PFSHS and FPNSW clinics, providing guidance on its use as standard of care. However, for the full public health benefits of PDPT to be realised, it must be implemented in general practice, where most chlamydia is diagnosed. Further work is recommended to explore feasibility, develop guidelines and promote the integration of PDPT into general practice.
Predicting disease-causing variant combinations
Authors: Papadimitriou Sofia , Gazzo Andrea , Versbraegen Nassim , Nachtegael Charlotte , Aerts Jan , Moreau Yves , Van Dooren Sonia , Nowé Ann , Smits Guillaume , Lenaerts Tom
Published: May 2019

Notwithstanding important advances in the context of single-variant pathogenicity identification, novel breakthroughs in discerning the origins of many rare diseases require methods able to identify more complex genetic models. We present here the Variant Combinations Pathogenicity Predictor (VarCoPP), a machine-learning approach that identifies pathogenic variant combinations in gene pairs (called digenic or bilocus variant combinations). We show that the results produced by this method are highly accurate and precise, an efficacy that is endorsed when validating the method on recently published independent disease-causing data. Confidence labels of 95% and 99% are identified, representing the probability of a bilocus combination being a true pathogenic result, providing geneticists with rational markers to evaluate the most relevant pathogenic combinations and limit the search space and time. Finally, the VarCoPP has been designed to act as an interpretable method that can provide explanations on why a bilocus combination is predicted as pathogenic and which biological information is important for that prediction. This work provides an important step toward the genetic understanding of rare diseases, paving the way to clinical knowledge and improved patient care.
Structural determinants for peptide-bond formation by asparaginyl ligases
Authors: Hemu Xinya , El Sahili Abbas , Hu Side , Wong Kaho , Chen Yu , Wong Yee Hwa , Zhang Xiaohong , Serra Aida , Goh Boon Chong , Darwis Dina A. , Chen Ming Wei , Sze Siu Kwan , Liu Chuan-Fa , Lescar Julien , Tam James P.
Published: May 2019

Asparaginyl endopeptidases (AEPs) are cysteine proteases which break Asx (Asn/Asp)–Xaa bonds in acidic conditions. Despite sharing a conserved overall structure with AEPs, certain plant enzymes such as butelase 1 act as a peptide asparaginyl ligase (PAL) and catalyze Asx–Xaa bond formation in near-neutral conditions. PALs also serve as macrocyclases in the biosynthesis of cyclic peptides. Here, we address the question of how a PAL can function as a ligase rather than a protease. Based on sequence homology of butelase 1, we identified AEPs and PALs from the cyclic peptide-producing plants
Viola yedoensis
(
Vy
) and
Viola canadensis
(
Vc
) of the Violaceae family. Using a crystal structure of a PAL obtained at 2.4-Å resolution coupled to mutagenesis studies, we discovered ligase-activity determinants flanking the S1 site, namely LAD1 and LAD2 located around the S2 and S1′ sites, respectively, which modulate ligase activity by controlling the accessibility of water or amine nucleophile to the
S
-ester intermediate. Recombinantly expressed
Vy
PAL1–3, predicted to be PALs, were confirmed to be ligases by functional studies. In addition, mutagenesis studies on
Vy
PAL1–3,
Vy
AEP1, and
Vc
AEP supported our prediction that LAD1 and LAD2 are important for ligase activity. In particular, mutagenesis targeting LAD2 selectively enhanced the ligase activity of
Vy
PAL3 and converted the protease
Vc
AEP into a ligase. The definition of structural determinants required for ligation activity of the asparaginyl ligases presented here will facilitate genomic identification of PALs and engineering of AEPs into PALs.
Positron emission tomography reporter gene strategy for use in the central nervous system
Authors: Haywood Tom , Beinat Corinne , Gowrishankar Gayatri , Patel Chirag B. , Alam Israt S. , Murty Surya , Gambhir Sanjiv Sam
Published: May 2019

Significance

With any new treatment it is imperative the medical community has a way to monitor its effectiveness, tracking its location, monitoring its expression, and observing off-target effects. Gene/cell therapy is no exception. The growing number of studies creates a need to monitor them more accurately. A number of PET reporter gene systems have been reported; however, they have limitations, including regions of high endogenous gene expression in the central nervous system (CNS), low specificity, or endogenous expression of the reporter gene in microglia. One of these systems has been used in the clinical setting; however, its associated imaging agent lacks blood–brain barrier penetration. Our approach aims to overcome these limitations and facilitate monitoring of gene/cell therapy in the CNS.
SR9009 has REV-ERB–independent effects on cell proliferation and metabolism
Authors: Dierickx Pieterjan , Emmett Matthew J. , Jiang Chunjie , Uehara Kahealani , Liu Manlu , Adlanmerini Marine , Lazar Mitchell A.
Published: May 2019

The nuclear receptors REV-ERBα and -β link circadian rhythms and metabolism. Like other nuclear receptors, REV-ERB activity can be regulated by ligands, including naturally occurring heme. A putative ligand, SR9009, has been reported to elicit a range of beneficial effects in healthy as well as diseased animal models and cell systems. However, the direct involvement of REV-ERBs in these effects of SR9009 has not been thoroughly assessed, as experiments were not performed in the complete absence of both proteins. Here, we report the generation of a mouse model for conditional genetic deletion of REV-ERBα and -β. We show that SR9009 can decrease cell viability, rewire cellular metabolism, and alter gene transcription in hepatocytes and embryonic stem cells lacking both REV-ERBα and -β. Thus, the effects of SR9009 cannot be used solely as surrogate for REV-ERB activity.
Quantum phase-sensitive diffraction and imaging using entangled photons
Authors: Asban Shahaf , Dorfman Konstantin E. , Mukamel Shaul
Published: May 2019

Significance

A quantum diffraction imaging technique is proposed, whereby one photon of an entangled pair is diffracted off a sample and detected in coincidence with its twin. Scanning the photon that did not interact with matter, we show that the phase information imprinted in the state of the field is detectable. We discuss several experimental applications: (
i
) Obtaining real-space images in diffraction imaging avoids the “phase problem.” (
ii
) The image scales as

∝

I

p

1
/
2

with the interacting photons, where

I

p

is the source intensity, compared with

∝

I

p

of classical diffraction. This makes weak-field imaging possible, avoiding damage to delicate samples. (
iii
) A Schmidt decomposition of the field can be used for image enhancement by reweighting the Schmidt modes contributions.
Immune homeostasis and regulation of the interferon pathway require myeloid-derived Regnase-3
Authors: von Gamm Matthias , Schaub Annalisa , Jones Alisha N. , Wolf Christine , Behrens Gesine , Lichti Johannes , Essig Katharina , Macht Anna , Pircher Joachim , Ehrlich Andreas , Davari Kathrin , Chauhan Dhruv , Busch Benjamin , Wurst Wolfgang , Feederle Regina , Feuchtinger Annette , Tschöp Matthias H. , Friedel Caroline C. , Hauck Stefanie M. , Sattler Michael , Geerlof Arie , Hornung Veit , Heissmeyer Vigo , Schulz Christian , Heikenwalder Mathias , Glasmacher Elke
Published: May 2019

The RNase Regnase-1 is a master RNA regulator in macrophages and T cells that degrades cellular and viral RNA upon NF-κB signaling. The roles of its family members, however, remain largely unknown. Here, we analyzed Regnase-3–deficient mice, which develop hypertrophic lymph nodes. We used various mice with immune cell–specific deletions of Regnase-3 to demonstrate that Regnase-3 acts specifically within myeloid cells. Regnase-3 deficiency systemically increased IFN signaling, which increased the proportion of immature B and innate immune cells, and suppressed follicle and germinal center formation. Expression analysis revealed that Regnase-3 and Regnase-1 share protein degradation pathways. Unlike Regnase-1, Regnase-3 expression is high specifically in macrophages and is transcriptionally controlled by IFN signaling. Although direct targets in macrophages remain unknown, Regnase-3 can bind, degrade, and regulate mRNAs, such as Zc3h12a (Regnase-1), in vitro. These data indicate that Regnase-3, like Regnase-1, is an RNase essential for immune homeostasis but has diverged as key regulator in the IFN pathway in macrophages.
The Mirascope: an explanation on a conceptual level
Authors: Krumphals Ingrid
Published: May 2019

The main objective of this paper is to provide an explanation on a conceptual level of how the Mirascope and the occurring image formation work. The physics behind a Mirascope—a well-known device consisting of two concave mirrors—is very complex. In literature, only either high level or very simplified and deficient explanations can be found. These explanations often lack a basic but detailed description on a conceptual level of the phenomena observable with the human eye. Therefore, this paper aims to give a physical explanation on a conceptual level to support learning processes in optics. Phenomena such as the diverse direction of the projected real image and the formation of the virtual image are clarified. As the focus lies on providing a basis to foster a conceptual understanding, there is no claim for a full and detailed explanation on the level of an exact ray analysis. In addition to a clarification of the content on a conceptual and educational level, suggestions for further investigations of the Mirascope with everyday items are given. The Mirascope is seen as an appropriate device for creating a learning environment following an inquiry-based approach in physics (teacher) education. This paper focuses on describing and explaining aspects of the Mirascope on a conceptual level.
Prediction of image noise contributions in proton computed tomography and comparison to measurements
Authors: Dickmann J , Wesp P , Rädler M , Rit S , Pankuch M , Johnson R P , Bashkirov V , Schulte R W , Parodi K , Landry G , Dedes G
Published: May 2019

We present a method to accurately predict image noise in proton computed tomography (pCT) using data generated from a Monte Carlo simulation and a patient or object model that may be generated from a prior x-ray CT image. This enables noise prediction for arbitrary beam fluence settings and, therefore, the application of fluence-modulated pCT (FMpCT), which can achieve prescribed noise targets and may significantly reduce the integral patient dose.

We extended an existing Monte Carlo simulation of a prototype pCT scanner to include effects of quenching in the energy detector scintillators and constructed a beam model from experimental tracking data. Simulated noise predictions were compared to experimental data both in the projection domain and in the reconstructed image. Noise prediction agreement between simulated and experimental data in terms of the root-mean-square (RMS) error was better than 7% for a homogeneous water phantom and a sensitometry phantom with tubular inserts. For an anthropomorphic head phantom, modeling the anatomy of a five-year-old child, the RMS error was better than 9% in three evaluated slices. We were able to reproduce subtle noise features near heterogeneities. To demonstrate the feasibility of Monte Carlo simulated noise maps for fluence modulation, we calculated a fluence profile that yields a homogeneous noise level in the image. Unlike for bow-tie filters in x-ray CT this does not require constant fluence at the detector and the shape of the fluence profile is fundamentally different.

Using an improved Monte Carlo simulation, we demonstrated the feasibility of using simulated data for accurate image noise prediction for pCT. We believe that the agreement with experimental data is sufficient to enable the future optimization of FMpCT fluence plans to achieve prescribed noise targets in a fluence-modulated acquisition.
Elliptical generalized Maxwell fish-eye lens using conformal mapping
Authors: Eskandari Hossein , Majedi Mohammad Saeed , Attari Amir Reza , Quevedo-Teruel Oscar
Published: May 2019

A circular graded index lens is conformally transformed to an elliptical shape using a closed-form transformation. The proposed transformation is then employed to compress a Maxwell fish-eye and its generalized version. Since the transformation is conformal, the electromagnetic properties of the device are perfectly preserved after the transformation with fully isotropic and dielectric-only materials. Ray-tracing and full-wave simulations are carried out for several cases to verify the functionality of the optically transformed lenses in geometrical optics and wave optics regimes.
Unoccupied surface and interface states in Pd thin films deposited on Fe/Ir(111) surface
Authors: Bouhassoune Mohammed , Fernandes Imara Lima , Blügel Stefan , Lounis Samir
Published: May 2019

We present a systematic first-principles study of the electronic surface states and resonances occuring in thin films of Pd of various thicknesses deposited on a single ferromagnetic monolayer (ML) of Fe on top of Ir(111) substrate. This system is of interest since one Pd layer deposited on Fe/Ir(111) hosts small magnetic skyrmions. The latter are topological magnetic objects with swirling spin-textures with possible implications in the context of spintronic devices since they have the potential to be used as magnetic bits for information technology. The stabilization, detection and manipulation of such non-collinear magnetic entities require a quantitative investigation and a fundamental understanding of their electronic structure. Here we investigate the nature of the unoccupied electronic states in Pd/Fe/Ir(111), which are essential in the large spin-mixing magnetoresistance signature captured using non spin-polarized scanning tunneling microscopy (Crum et al 2015 Nat. Commun.
6 8541, Hanneken et al 2015 Nat. Nanotechnol.
10 1039). To provide a complete analysis, we investigate bare Fe/Ir(111) and Pd
n = 2,7/Fe/Ir(111) surfaces. Our results demonstrate the emergence of surface and interface states after deposition of Pd MLs, which are strongly impacted by the large spin–orbit coupling of Ir surface.
Nonlinear optical dynamics of a 2D semiconductor quantum dot super-crystal: Emerging multistability, self-oscillations and chaos
Authors: Malyshev V A , Zapatero P Á , Malyshev A V , Malikov R F , Ryzhov I V
Published: May 2019

We conduct a theoretical study of the nonlinear optical dynamics of a 2D super-crystal comprising regularly spaced identical semiconductor quantum dots (SQDs), subjected to a resonant continuous wave excitation. A single SQD is considered as three-level ladder-like systems involving the ground, one-exciton and bi-exction states. We show that the super - crystal reveals a rich nonlinear dynamics, exhibiting multistability, self-oscillations and chaos. The behaviour is driven by the retarded SQD-SQD interactions and bi-exciton binding energy.
Ultrafast photocontrol of proton-mediated organic ferroelectric cocrystal
Authors: Umanodan T , Ishikawa T , Koshihara S , Horiuchi S , Okimoto Y
Published: May 2019

Photoirradiation effect in a ferroelectric cocrystal Hdppz-Hca is investigated in terms of time-resolved second harmonic (SH) generation measurements. By the photoexcitation with a visible pulse (530 nm) causing the intramolecular transition of Hca molecule, the SH intensity was suddenly suppressed by ≈30% on the time scale of picosecond, while the reflectivity scarcely changed. This result is discussed based on reversal of the polarized domain by the photoexcitation.
Temperature dependence of photoluminescence properties of water-soluble ZnSe quantum dots
Authors: Lee Yong-Shin , Taniguchi Taichi , Kim DaeGwi
Published: May 2019

We have investigated the optical properties of ZnSe quantum dots (QDs) prepared by a hydrothermal method. The photoluminescence (PL)-decay profiles become slower with an increase in temperature up to 160 K, contrary to an ordinary behaviour due to thermal quenching. The temperature dependence of the PL-decay profile is explained by a three-state model consisting of a ground state and two excited states of the lower-lying bound-exciton and higher-lying dark-exciton states. The analysis of the temperature dependence of the decay time indicates that the dark-exciton state contributes to the PL-decay process in the ZnSe QDs.
Switching of radiation pressure acting on microparticles by using T-type photochromic reactions
Authors: Tanaka K , Setoura K , Ito S , Miyasaka H
Published: May 2019

Manipulation of small particles can be achieved by using the radiation pressure of a laser beam. The strength and direction of the radiation pressure depends on the dielectric constant of target materials. It can therefore be expected to induce mechanical motions of small materials in optical trap by changing their optical property by chemical reactions. Along this line, we recently demonstrated switching of radiation pressure acting on single optically trapped microparticles by using photochromic molecules (Refs. 3, 4). To explore more flexible mesoscopic motions synchronizing photochemical reactions, we have investigated in the present study the micromechanical motion of optically trapped particles containing a T-type photochromic molecule, naphthopyran (NP), with multiple thermal back-reaction rates. The single microparticle with NP was optically trapped with CW 532-nm laser and the photochromic reaction was induced by UV irradiation, resulting in the modification of the optomechanical responses of the particle under laser trapping.
Plasmonic optical trapping of pyrene-pendant polymer chains by controlling thermophoretic force
Authors: Ushiro Kenta , Shoji Tatsuya , Tsuboi Yasuyuki
Published: May 2019

Plasmonic optical tweezers (POT) has a high potential for manipulation of nanomaterials due to an enhanced optical force. However, unfavorable thermal effects induced by plasmon excitation have frequently hindered the manipulation. For this issue, we have recently developed a novel non-plasmonic optical tweezers using a nanostructured silicon substrate (B-Si). We called it “Nano-Structured Semi-Conductor-Assisted Optical Tweezers (NASSCA-OT)”. In the present study, we trapped pyrene-pendant polymer chains homogeneously dissolved in water for POT or NASSCA-OT. We used plasmonic gold nanopyramidal dimer arrays or B-Si in contact with the aqueous polymer solution. During plasmon excitation with a near-infrared laser light, any sign of optical trapping was never detected in fluorescence micro-spectroscopy. By contrast, trapping of the polymer chains was obviously observed for NASSCA-OT. Upon laser irradiation, pyrene excimer fluorescence was dramatically increased at the focal spot. These results indicate that NASSCA-OT is a powerful tool for manipulation of molecular materials.
Transient grating spectroscopy of β-carotene pumped with spectrally chirped pulses
Authors: Ooi Shintaro , Mitoma Sigehito , Nango Mamoru , Amao Yutaka , Sugisaki Mitsuru
Published: May 2019

Nonlinear optical responses of β-carotene were investigated upon excitation using chirped pulses. We especially focus on spectrally resolved transient grating (TG) signals to discuss the influence of the spectral chirp over a wide spectral range. A significant change in the TG signal was observed when negatively chirped pulses were used. The experimental results were qualitatively reproduced by employing the Brownian oscillator model. The relationship between the wave packet motion in the excited state and spectral chirp is discussed. It is concluded that the third order nonlinear optical response reflects the competition between the spectral chirp and the energy separation of the potential curves.
Raman scattering mediated by Majorana fermions in Kitaev nanoribbons
Authors: Suzuki Kosuke , Yamamoto Shoji
Published: May 2019

We study magnetic Raman, i.e. inelastic light, scattering of Kitaev’s quantum spin liquids realizable in honeycomb nanoribbons. Elementary excitations in the Kitaev spin liquids consist of itinerant Majorana (matter) fermions and localized gauge fluxes (visons). Matter fermions are characterized by the projective point (gauged rotation) group inherent in the lattice. Inelastic light scattering is mediated by a pair of matter fermions without any vison excitation. We can selectively “observe” matter fermions of the same symmetry and those of different symmetries depending on the polarization of incoming and/or outgoing lights. A pair of matter fermions with particular translational quantum numbers ±k cannot be Raman active.
Synthesis and characterization of quantum dot chains: Self-assembly of mercaptopropionic-acid-capped quantum dots conjugated with short single-stranded DNA
Authors: Oda M , Sasano K , Nishi A , Zako T , Tani T
Published: May 2019

In this paper, we describe the synthesis and characterization of quantum dot (QD) chains. We used small QD-DNA conjugates, i.e., short-ligand-capped QDs conjugated with short (15-mers) single-stranded DNA, as the building blocks. The small conjugates were separated based on the valence of the DNA, i.e., the amount of DNA per particle, using agarose gel electrophoresis. The conjugates formed self-assemblies composed of closely spaced (inter-particle spacing of 0.6–2 nm) QDs. We report the results of our investigation of the electrophoresis and hybridization of the conjugation.
Charge carrier migration and hole extraction from MAPbI3
Authors: Budzinauskas Kęstutis , Ewertowski Simon , Olthof Selina , Meerholz Klaus , Van Loosdrecht Paul H.M.
Published: May 2019

Linear as well as time resolved absorption measurements were performed on 40 nm and 170 nm thick MAPbL films with PEDOT:PSS hole extraction layer, spin-coated on quartz substrate. From linear absorption measurements exciton binding energy of 18 – 19 meV and band gap of 1.60 - 1.62 eV was deduced. Transient absorption spectra after the excitation at 1.77 eV showed a strong difference in carrier recombination dynamics for the two MAPbI3 films of different thicknesses. From the analysis on the decay dynamics, hole population lifetime of 0.3 ns and 3.5 ns for 40 nm and 170 nm films, respectively, are determined. A numerical 1D diffusion model was used to model the carrier relaxation dynamics yielding hole diffusion constants of 0.025 - 0.030 cm2s−1, which results in a hole mobility of 1 cm2(Vs)−1 in these MAPbI3 films.
Time-scale dependent Brownian motion of nanoparticles in clusters at a solid-liquid interface by laser trapping
Authors: Hanasaki Itsuo , Hosokawa Chie
Published: May 2019

Nanoparticles in a cluster trapped by laser-induced force field show Brownian motion at solid-liquid interfaces. The cluster formation means that the particles are highly concentrated. In general, the diffusion coefficients of particles in fluids decrease with substantially high concentration and also in the vicinity of solid walls due to the hydrodynamic effect. The particle trajectory data obtained from the experimental measurements show that the longer time span of observation leads to smaller diffusion coefficient due to the confinement effect. However, they also exhibit higher diffusion coefficient compared to the the bulk condition when evaluated at a sufficiently short time span of the frame interval under the condition of sufficiently high laser powers.
Electric-field induced magnetization in YIG observed by Faraday rotation
Authors: Fujimoto K , Hasunuma T , Kohmoto T
Published: May 2019

We studied the electric-field induced magnetization caused by the magnetoelectric effect in YIG. The magnetization was observed as the Faraday rotation of a transmitted continuous-wave probe light. From the observed dependence of the Faraday-rotation amplitude on the electric and magnetic fields, it was found that the two components linear and quadratic in the electric field coexist at low temperatures.
Collaborative intra-tumor heterogeneity detection
Authors: Khakabimamaghani Sahand , Malikic Salem , Tang Jeffrey , Ding Dujian , Morin Ryan , Chindelevitch Leonid , Ester Martin
Published: May 2019

Motivation

Despite the remarkable advances in sequencing and computational techniques, noise in the data and complexity of the underlying biological mechanisms render deconvolution of the phylogenetic relationships between cancer mutations difficult. Besides that, the majority of the existing datasets consist of bulk sequencing data of single tumor sample of an individual. Accurate inference of the phylogenetic order of mutations is particularly challenging in these cases and the existing methods are faced with several theoretical limitations. To overcome these limitations, new methods are required for integrating and harnessing the full potential of the existing data.

Results

We introduce a method called Hintra for intra-tumor heterogeneity detection. Hintra integrates sequencing data for a cohort of tumors and infers tumor phylogeny for each individual based on the evolutionary information shared between different tumors. Through an iterative process, Hintra learns the repeating evolutionary patterns and uses this information for resolving the phylogenetic ambiguities of individual tumors. The results of synthetic experiments show an improved performance compared to two state-of-the-art methods. The experimental results with a recent Breast Cancer dataset are consistent with the existing knowledge and provide potentially interesting findings.

Availability and implementation

The source code for Hintra is available at https://github.com/sahandk/HINTRA.
Toxic Chemical Governance Failure in the United States: Key Lessons and Paths Forward
Authors: Chiapella Ariana M , Grabowski Zbigniew J , Rozance Mary Ann , Denton Ashlie D , Alattar Manar A , Granek Elise F
Published: May 2019

Over 40 years of regulations in the United States have failed to protect human and environmental health. We contend that these failures result from the flawed governance over the continued production, use, and disposal of toxic chemicals. To address this failure, we need to identify the broader social, political, and technological processes producing, knowing, and regulating toxic chemicals, collectively referred to as toxic chemical governance. To do so, we create a conceptual framework covering five key domains of governance: knowledge production, policy design, monitoring and enforcement, evaluation, and adjudication. Within each domain, social actors of varying power negotiate what constitutes acceptable risk, creating longer-term path dependencies in how they are addressed (or not). Using existing literature and five case studies, we discuss four paths for improving governance: evolving paradigms of harm, addressing bias in the knowledge base, making governance more equitable, and overcoming path dependency.
Fecal Immunoglobulin A Against a Sporozoite Antigen at 12 Months Is Associated With Delayed Time to Subsequent Cryptosporidiosis in Urban Bangladesh: A Prospective Cohort Study
Authors: Steiner Kevin L , Kabir Mamun , Priest Jeffrey W , Hossain Biplob , Gilchrist Carol A , Cook Heather , Ma Jennie Z , Korpe Poonum S , Ahmed Tahmeed , Faruque A S G , Haque Rashidul , Petri William A
Published: May 2019

In this prospective cohort study of Bangladeshi children, greater fecal immunoglobulin A, but not plasma immunoglobulin G, directed against the Cryptosporidium sporozoite-expressed antigen Cp23 at 12 months of age was associated with delayed time to subsequent cryptosporidiosis. This finding suggests a protective role for mucosal antibody-mediated immunity in naturally exposed children.
Natural Course of Nonalcoholic Fatty Liver Disease and Type 2 Diabetes in Patients With Human Immunodeficiency Virus With and Without Combination Antiretroviral Therapy–associated Lipodystrophy: A 16-Year Follow-up Study
Authors: Lallukka-Brück Susanna , Isokuortti Elina , Luukkonen Panu K , Hakkarainen Antti , Lundbom Nina , Sutinen Jussi , Yki-Järvinen Hannele
Published: May 2019

Background

Abnormal glucose metabolism and nonalcoholic fatty liver disease (NAFLD) are common in patients with human immunodeficiency virus (HIV+ patients), but longitudinal data are lacking. We determined the natural course of NAFLD (liver fat [LFAT]) and type 2 diabetes mellitus (T2DM) in HIV+ patients with and without lipodystrophy (LD+ and LD–, respectively) during a 16-year longitudinal study.

Methods

LFAT (by proton magnetic resonance spectroscopy) and clinical characteristics were measured in 41 HIV+ patients at baseline and after 16 years. Liver fibrosis was estimated by measuring liver stiffness using transient elastography (TE) and magnetic resonance elastography (MRE) at 16 years. We also longitudinally studied 28 healthy subjects.

Results

During follow-up, the HIV+ patients gained more body fat (8.6% ± 0.7%) than the control patients (4.5% ± 0.6%, P < .001). Features of insulin resistance increased significantly in the HIV+ patients but not the control patients. A significant proportion (20%, P < .01 vs 0% at baseline) of the HIV+ but none of the control patients developed T2DM. LFAT was significantly higher at baseline in the LD+ (4.3 [1.9–11.8]) than the LD– (1.0 [0.5–1.5]; P < .001) HIV+ patients. LFAT remained stable during follow-up in all groups. At follow-up, liver stiffness measured with TE was similar among all HIV, LD+, LD–, and control patients and between the LD+ and LD– patients measured with MRE. Advanced fibrosis by MRE was observed in 3 of LD+ and none of LD– patients.

Conclusions

During 16 years of follow-up, progression of NAFLD is rare compared to development of T2DM in HIV+ patients.
Improving Tuberculosis Preventive Therapy Uptake: A Cluster-randomized Trial of Symptom-based Versus Tuberculin Skin Test–based Screening of Household Tuberculosis Contacts Less Than 5 Years of Age
Authors: Salazar-Austin Nicole , Cohn Silvia , Barnes Grace Link , Tladi Molefi , Motlhaoleng Katlego , Swanepoel Catharina , Motala Zarina , Variava Ebrahim , Martinson Neil , Chaisson Richard E
Published: May 2019

Background

Tuberculosis preventive therapy (TPT) is highly effective at preventing tuberculosis disease in household child contacts (<5 years), but is poorly implemented worldwide. In 2006, the World Health Organization recommended symptom-based screening as a replacement for tuberculin skin testing (TST) to simplify contact evaluation and improve implementation. We aimed to determine the effectiveness of this recommendation.

Methods

We conducted a pragmatic, cluster-randomized trial to determine whether contact evaluation using symptom screening improved the proportion of identified child contacts who initiated TPT, compared to TST-based screening, in Matlosana, South Africa. We randomized 16 clinics to either symptom-based or TST-based contact evaluations. Outcome data were abstracted from customized child contact management files.

Results

Contact tracing identified 550 and 467 child contacts in the symptom and TST arms, respectively (0.39 vs 0.32 per case, respectively; P = .27). There was no significant difference by arm in the adjusted proportion of identified child contacts who were screened (52% in symptom arm vs 60% in TST arm; P = .39). The adjusted proportion of identified child contacts who initiated TPT or tuberculosis treatment was 51.5% in the symptom clinics and 57.1% in the TST clinics (difference −5.6%, 95% confidence interval −23.7 to 12.6; P = .52). Based on the district’s historic average of 0.7 child contacts per index case, 14% and 15% of child contacts completed 6 months of TPT in the symptom and TST arms, respectively (P = .89).

Conclusions

Symptom-based screening did not improve the proportion of identified child contacts evaluated or initiated on TPT, compared to TST-based screening. Further research is needed to identify bottlenecks and evaluate interventions to ensure all child contacts receive TPT.

Clinical Trials Registration

NCT03074799.
Prevalence of Scabies and Impetigo 3 Years After Mass Drug Administration With Ivermectin and Azithromycin
Authors: Marks Michael , Romani Lucia , Sokana Oliver , Neko Lazarus , Harrington Relmah , Nasi Titus , Wand Handan , Whitfeld Margot J , Engelman Daniel , Solomon Anthony W , Kaldor John M , Steer Andrew C
Published: May 2019

Background

Ivermectin-based mass drug administration has emerged as a promising strategy for the control of scabies and impetigo in settings where the diseases are endemic. Current follow-up data are limited to 12 months for the majority of studies. Longer-term data are vital to inform the sustainability of interventions.

Methods

We conducted a prevalence survey for scabies and impetigo in 10 villages in Choiseul Province of the Solomon Islands 36 months after a single round of ivermectin and azithromycin mass drug coadministration. In the primary analysis, we compared the prevalence of scabies and impetigo at 36 months to the prevalence at baseline.

Results

At 36 months, the prevalence of scabies was 4.7% (95% confidence interval [CI], 3.6–6.1), which was significantly lower than at baseline (18.7%; relative reduction, 74.9%; 95% CI, 61.5%–87.7%; P < .001). The prevalence of impetigo was 9.6% (95% CI, 8.1%–11.4%), significantly lower than at baseline (24.7%; relative reduction, 61.3%; 95% CI, 38.7%–100%; P < .001). The highest prevalence of scabies was among children aged <5 years (12.5%; adjusted odds ratio, 33.2; 95% CI, 6.6–603.2), and the highest prevalence of impetigo was among children aged 5–9 years (16.4%; adjusted odds ratio, 8.1; 95% CI, 3.6–21.8).

Conclusions

There was a sustained impact of a single round of ivermectin and azithromycin mass drug coadministration on the prevalence of scabies and impetigo 3 years after the intervention. Our data provide further support to adopt this intervention as a central component of global scabies control efforts.

Clinical Trials Registration

Australian and New Zealand Trials Registry (ACTRN12615001199505).
Complexities in cardiovascular rhythmicity: perspectives on circadian normality, ageing and disease
Authors: Monfredi Oliver , Lakatta Edward G
Published: May 2019

Biological rhythms exist in organisms at all levels of complexity, in most organs and at myriad time scales. Our own biological rhythms are driven by energy emitted by the sun, interacting via our retinas with brain stem centres, which then send out complex messages designed to synchronize the behaviour of peripheral non-light sensing organs, to ensure optimal physiological responsiveness and performance of the organism based on the time of day. Peripheral organs themselves have autonomous rhythmic behaviours that can act independently from central nervous system control but is entrainable. Dysregulation of biological rhythms either through environment or disease has far-reaching consequences on health that we are only now beginning to appreciate. In this review, we focus on cardiovascular rhythms in health, with ageing and under disease conditions.
Myocardial infarction with non-obstructive coronary arteries as compared with myocardial infarction and obstructive coronary disease: outcomes in a Medicare population
Authors: Dreyer Rachel P , Tavella Rosanna , Curtis Jeptha P , Wang Yongfei , Pauspathy Sivabaskari , Messenger John , Rumsfeld John S , Maddox Thomas M , Krumholz Harlan M , Spertus John A , Beltrame John F
Published: May 2019

Aims

The prognosis of patients with MINOCA (myocardial infarction with non-obstructive coronary arteries) is poorly understood. We examined major adverse cardiac events (MACE) defined as all-cause mortality, re-hospitalization for acute myocardial infarction (AMI), heart failure (HF), or stroke 12-months post-AMI in patients with MINOCA versus AMI patients with obstructive coronary artery disease (MICAD).

Methods and results

Multicentre, observational cohort study of patients with AMI (≥65 years) from the National Cardiovascular Data Registry CathPCI Registry (July 2009–December 2013) who underwent coronary angiography with linkage to the Centers for Medicare and Medicaid (CMS) claims data. Patients were classified as MICAD or MINOCA by the presence or absence of an epicardial vessel with ≥50% stenosis. The primary endpoint was MACE at 12 months, and secondary endpoints included the components of MACE over 12 months. Among 286 780 AMI admissions (276 522 unique patients), 16 849 (5.9%) had MINOCA. The 12-month rates of MACE (18.7% vs. 27.6%), mortality (12.3% vs. 16.7%), and re-hospitalization for AMI (1.3% vs. 6.1%) and HF (5.9% vs. 9.3%) were significantly lower for MINOCA vs. MICAD patients (P < 0.001), but was similar between MINOCA and MICAD patients for re-hospitalization for stroke (1.6% vs. 1.4%, P = 0.128). Following risk-adjustment, MINOCA patients had a 43% lower risk of MACE over 12 months (hazard ratio = 0.57, 95% confidence interval 0.55–0.59), in comparison to MICAD patients. This pattern was similar for adjusted risks of the MACE components.

Conclusion

This study confirms an unfavourable prognosis in elderly patients with MINOCA undergoing coronary angiography, with one in five patients with MINOCA suffering a major adverse event over 12 months.
Combining LiDAR data and airborne imagery of very high resolution to improve aboveground biomass estimates in tropical dry forests
Authors: Reyes-Palomeque Gabriela , Dupuy Juan Manuel , Johnson Kristofer D , Castillo-Santiago Miguel Angel , Hernández-Stefanoni J Luis
Published: May 2019

Knowledge of the spatial distribution of aboveground biomass (AGB) is crucial to guide forest conservation and management to maintain carbon stocks. LiDAR has been highly successful for this purpose, but has limited availability. Very-high resolution (<1 m) orthophotos can also be used to estimate AGB because they allow a fine distinction of forest canopy grain. We evaluated the separate and joint performance of orthophotos and LiDAR data to estimate AGB in two types of tropical dry forests in the Yucatan Peninsula. Woody plants were surveyed in twenty 0.1 ha plots in a semideciduous forest at Kaxil Kiuic Biocultural Reserve (RBKK) and 28 plots in a semievergreen forest at Felipe Carrillo Puerto (FCP). We fitted three regression models: one based on LiDAR data, another based on orthophoto variables calculated for forest canopy and canopy opening fractions, and a third model that combined both sets of variables. Variation in AGB was decomposed into LiDAR, orthophotos and joint components using variation-partitioning analyses. In FCP, regression models using LiDAR data only showed higher fit (R2 = 0.82) than orthophoto variables only (R2 = 0.70). In contrast, orthophotos had a slightly higher fit (R2 = 0.91) than LiDAR (R2 = 0.88) in RBKK, because orthophoto variables characterize very well the horizontal structure of canopies on this site. The model that combined both data sets showed a better fit (R2 = 0.85) only in FCP, which has a more complex forest structure. The largest percentage of AGB variation (88 per cent in RBKK and 67 per cent in FCP) was explained by the joint contribution of LiDAR and orthophotos. We conclude that both LiDAR and orthophotos provide accurate estimation of AGB, but their relative performance varies with forest type and structural complexity. Combining the two sets of variables can further improve the accuracy of AGB estimation, particularly in forests with complex vegetation structure.
Genome-wide SNP Data Reveal an Overestimation of Species Diversity in a Group of Hawkmoths
Authors: Hundsdoerfer Anna K , Lee Kyung Min , Kitching Ian J , Mutanen Marko
Published: May 2019

The interface between populations and evolving young species continues to generate much contemporary debate in systematics depending on the species concept(s) applied but which ultimately reduces to the fundamental question of “when do nondiscrete entities become distinct, mutually exclusive evolutionary units”? Species are perceived as critical biological entities, and the discovery and naming of new species is perceived by many authors as a major research aim for assessing current biodiversity before much of it becomes extinct. However, less attention is given to determining whether these names represent valid biological entities because this is perceived as both a laborious chore and an undesirable research outcome. The charismatic spurge hawkmoths (Hyles euphorbiae complex, HEC) offer an opportunity to study this less fashionable aspect of systematics. To elucidate this intriguing systematic challenge, we analyzed over 10,000 ddRAD single nucleotide polymorphisms from 62 individuals using coalescent-based and population genomic methodology. These genome-wide data reveal a clear overestimation of (sub)species-level diversity and demonstrate that the HEC taxonomy has been seriously oversplit. We conclude that only one valid species name should be retained for the entire HEC, namely Hyles euphorbiae, and we do not recognize any formal subspecies or other taxonomic subdivisions within it. Although the adoption of genetic tools has frequently revealed morphologically cryptic diversity, the converse, taxonomic oversplitting of species, is generally (and wrongly in our opinion) accepted as rare. Furthermore, taxonomic oversplitting is most likely to have taken place in intensively studied popular and charismatic organisms such as the HEC.
An integrative approach to detect epigenetic mechanisms that putatively mediate the influence of lifestyle exposures on disease susceptibility
Authors: Richardson Tom G , Richmond Rebecca C , North Teri-Louise , Hemani Gibran , Davey Smith George , Sharp Gemma C , Relton Caroline L
Published: May 2019

Background

There is mounting evidence that our environment and lifestyle has an impact on epigenetic regulatory mechanisms, such as DNA methylation. It has been suggested that these molecular processes may mediate the effect of risk factors on disease susceptibility, although evidence in this regard has been challenging to uncover. Using genetic variants as surrogate variables, we have used two-sample Mendelian randomization (2SMR) to investigate the potential implications of putative changes to DNA methylation levels on disease susceptibility.

Methods

To illustrate our approach, we identified 412 CpG sites where DNA methylation was associated with prenatal smoking. We then applied 2SMR to investigate potential downstream effects of these putative changes on 643 complex traits using findings from large-scale genome-wide association studies. To strengthen evidence of mediatory mechanisms, we used multiple-trait colocalization to assess whether DNA methylation, nearby gene expression and complex trait variation were all influenced by the same causal genetic variant.

Results

We identified 22 associations that survived multiple testing (P < 1.89 × 10–7). In-depth follow-up analyses of particular note suggested that the associations between DNA methylation at the ASPSCR1 and REST/POL2RB gene regions, both linked with reduced lung function, may be mediated by changes in gene expression. We validated associations between DNA methylation and traits using independent samples from different stages across the life course.

Conclusion

Our approach should prove valuable in prioritizing CpG sites that may mediate the effect of causal risk factors on disease. In-depth evaluations of findings are necessary to robustly disentangle causality from alternative explanations such as horizontal pleiotropy.