bluuebunny/crossref_metadata_2025 huggingface dataset:
NEW RESEARCH AT TEOTIHUACAN’S TLAJINGA DISTRICT, 2012–2015
Authors: Carballo David M. , Hirth Kenneth G. , Hernández Sariñana Daniela , Buckley Gina M. , Mejía Ramón Andrés G. , Kennett Douglas J.
Published: April 2019

Teotihuacan's Tlajinga district is a cluster of neighborhoods on the southern periphery of the city best known for earlier investigations at Compound 33:S3W1. New research includes excavations at two other apartment compounds and along the southern extension of the Street of the Dead. Excavation contexts, major finds, chronology, and preliminary interpretations are the subject of this article. We highlight evidence attesting to a major obsidian-blade workshop at Compound 17:S3E1, offerings, and other features at that compound and Compound 18:S3E1, and the tempo and processes of urbanization viewed through well-recorded stratigraphic sequences of the compounds and the Street of the Dead. We conclude that significant occupation began in the Miccaotli phase, but it was not until some point in the Early Tlamimilolpa phase that the dominant housing type became apartment compounds; the continuation of the axis of Street of the Dead in the district was accomplished by excavating in the volcanic tuft substrate (tepetate) and could have been undertaken by the inhabitants of the district themselves; and the presence of items such as a sculpted stone face, marine shell, and polychrome pottery demonstrates that commoners at Teotihuacan enjoyed some access to finer items within the interregional economy.
The prognostic value of balloon occlusion in candidates for the various types of cavo-pulmonary anastomosis
Authors: Kusa Jacek , Bermúdez-Cañete Ramón , Herraiz Ignacio , Bialkowski Jacek , Szkutnik Malgorzata , Pilar Díaz Maria , Villagra Fernando , Antonio Sanchez Pedro
Published: April 2019

The purpose of our paper is to assess the prognostic value of balloon occlusion as a test for patients with various types of functionally single ventricle after different palliative surgical procedures who were candidates for further modifications of a cavo-pulmonary operation. In all patients, there were at least two sources of pulmonary arterial supply.

Our hypothesis was that, using balloon occlusion temporarily to produce changes in the haemodynamic situation, we could simulate the potential state subsequent to surgical palliation. We used balloon occlusion in 19 patients during diagnostic catheterisation, followed by interventional and or surgical procedures as considered necessary. This test was applied for temporary closure of the pulmonary valve in 8 patients, and a Blalock-Taussig anastomosis in 11 patients.
Abstracts for the British Congenital Cardiac Association Annual Meeting: The Barbican, London, 24–25 November 2005: Oral Presentations: Twenty year trends in recognition of life-threatening neonatal cardiac malformations
Authors: Reinhardt Zdenka , Wren Christopher
Published: April 2019

Background: Babies with cardiovascular malformations are usually asymptomatic at birth. Earlier diagnosis is likely to lead to a better outcome. This study examines trends in the timing of diagnosis of potentially life-threatening cardiovascular malformations. Methods: Ascertainment of all cardiovascular malformations diagnosed in infancy in the resident population of one English health region in 1985–2004. Babies considered to have a life-threatening cardiovascular malformation included all those with hypoplastic left heart, pulmonary atresia with intact ventricular septum, transposition of the great arteries, or interruption of the aorta; and babies dying or undergoing operation in the first 28 days with coarctation of the aorta, aortic stenosis, pulmonary stenosis, tetralogy of Fallot, pulmonary atresia with ventricular septal defect, or total anomalous pulmonary venous connection. Results: Of 688,167 live born babies in the 20 years of the study, 4444 had cardiovascular malformations diagnosed in infancy (6.5 per 1000). Cardiovascular malformations were potentially life-threatening in 685 (15%). Over the time of the study, 8% were recognised prenatally, 58% postnatally before discharge from hospital, 31% in life after discharge and 3% after death. Malformations most likely to remain undiagnosed at discharge were coarctation of the aorta (63%), interruption of the aortic arch (50%), and total anomalous pulmonary venous connection (47%). Over the 20 years of the study, the proportion of babies diagnosed antenatally increased from around 1% to 20% and no case was first diagnosed after death in the last 10 years. However, the recent proportion going home without a diagnosis remains around 25%. Conclusions: Overall one third of babies with potentially life-threatening cardiovascular malformations leave hospital undiagnosed. In recent years better antenatal diagnosis has reduced this proportion to one quarter. Better early recognition of such babies is unlikely to be achieved by clinical examination and is more likely to come from further improvements in antenatal diagnosis and more widespread adoption of routine pulse oximetry.
Abstracts for the British Congenital Cardiac Association Annual Meeting: The Barbican, London, 24–25 November 2005: Oral Presentations: Treatment with bosentan in children with an intracardiac communication and severe pulmonary arterial hypertension
Authors: Bonou P. , Hislop A. A. , Flynn Y. , Haworth S. G.
Published: April 2019

Aim: To present the experience of the UK Pulmonary Hypertensive Service for Children at Great Ormond Street Hospital in treating children with “Eisenmenger” type physiology with the dual endothelin receptor antagonist bosentan. Patients and methods: Fourteen inoperable patients were included in the study. These were selected based on a history of an unrestrictive intracardiac communication and established right to left shunt at rest. There was a female: male ratio 1: 0.75 and age range at initiation of treatment of 7–18.6 years (mean 12.5 yrs). Six patients had Trisomy 21. The cardiac diagnoses were: 6 large VSDs, 6 CAVSD (1 of which was not Trisomy 21) and 2 more complex congenital heart disease cases that underwent palliative surgery (DILV, DOLV, TGA, PA banding and DORV, TGA, VSD, PS, Waterston). Twelve patients received antiplatelet/anticoagulation therapy. WHO functional class, haemoglobin (Hb), oxygen saturation, 6 min walk tests, echocardiograms and ECGs were assessed before starting treatment with bosentan and after 6 and 12 months of follow up. Twelve patients had a cardiac catheterisation before treatment commenced. The parameters were compared for patients before treatment and at 6 and 12 months post treatment with paired t-test and ANOVA. Results: All patients were severely symptomatic the mean WHO functional class being 3.2 (range 3–4). The mean Hb was 18.3 g/dl (range 13.4–22.9). The mean PVR of all patients was 30.98 units m2 (7.6–57). The Trisomy 21 patients had a mean PVR of 34.4 units m2 and non Trisomy 21 patients had a mean of 28.6 units m2. Mean oxygen saturation at rest was 78.9% (range 67–93), mean 6 min walk test distance was 223.8 m (n = 10, range 108–360) and the lowest oxygen saturation during the walk test was 59.7% (42–79) at 6 min or below. Mean duration of therapy was 15.2 months (range 6–34 months). Bosentan was well tolerated in all patients but discontinued in one due to non compliance with monthly screening blood tests. All patients remained stable and their echocardiogram and ECG findings were unchanged throughout. After 6 months mean WHO functional class had decreased significantly to 2.96 (p = 0.029), whilst Hb and oxygen saturation at rest had not changed. Ten of the 14 patients were on treatment for more than a year and after 12 months the WHO functional class was maintained at the same improved level. The Hb and oxygen saturation at rest remained unchanged. After 12 months the 6 min walk mean distance had increased from 211 to 253 metres (non significant). Conclusion: Patients treated with bosentan for up to 1 year showed clinical improvement and remained stable. After 6 months treatment WHO functional class had significantly improved and improvement was sustained for up to 1 year.
Microstructural Characterization by Automated Crystal Orientation and Phase Mapping by Precession Electron Diffraction in TEM: Application to Hot Deformation of a γ-TiAl-based Alloy
Authors: Singh Vajinder , Mondal Chandan , Bhattacharjee P. P. , Ghosal P.
Published: April 2019

Microstructural evolution of a hot deformed γ-TiAl-based Ti–45Al–8Nb–2Cr–0.2B (at.%) alloy has been studied using an advanced characterization technique called automated crystal orientation and phase mapping by precession electron diffraction carried out in a transmission electron microscope (with a NanoMEGAS attachment). It has been observed that the technique, having a capability to recognize diffraction patterns with improved accuracy and reliability, is particularly suitable for characterization of complex microstructural features evolved during hot deformation of multiphase (α2 + γ + β)-based TiAl alloys. Examples of coupled orientations and phase maps of the present alloy demonstrate that the accurate reproduction of the very fine lamellar structure (α2 + γ + γ) is feasible due to its inherent high-spatial resolution and absence of a pseudo-symmetry effect. It enables identification of salient features of γ-TiAl deformation behavior in terms of misorientation analyses (GAM, GOS, and KAM) and transformation characteristics of very fine lamellar constituent phases. Apart from conventional strain analyses from the orientation database, an attempt has been made to image the dislocation sub-structure of γ-phases, which supplements the deformation structure evaluation using this new technique.
Does managed competition constrain hospitals' contract prices? Evidence from the Netherlands
Authors: Douven Rudy , Burger Monique , Schut Frederik
Published: April 2019

In the Dutch health care system, health insurers negotiate with hospitals about the pricing of hospital products in a managed competition framework. In this paper, we study these contract prices that became for the first time publicly available in 2016. The data show substantive price variation between hospitals for the same products, and within a hospital for the same product across insurers. About 27% of the contract prices for a hospital product are at least 20% higher or lower than the average contract price in the market. For about half of the products, the highest and the lowest contract prices across hospitals differ by a factor of three or more. Moreover, hospital product prices do not follow a consistent ranking across hospitals, suggesting substantial cross-subsidization between hospital products. Potential explanations for the large and seemingly random price variation are: (i) different cost pricing methods used by hospitals, (ii) uncertainty due to frequent changes in the hospital payment system, (iii) price adjustments related to negotiated lumpsum payments and (iv) differences in hospital and insurer market power. Several policy options are discussed to reduce variation and increase transparency of hospital prices.
Mean Heart Rate and Parameters of Heart Rate Variability in Depressive Children and the Effects of Antidepressant Medication
Authors: Vloet Timo D. , Jans Thomas , Frey Anna , Häußler Marie , Vloet Andrea , Geissler Julia , Susewind Moritz , von Dobschütz Bernadette , Frantz Stefan , Romanos Marcel
Published: April 2019

Abstract. Introduction: Researchers have repeatedly discovered an association between depression and autonomic cardiac dysregulation in adults. However, corresponding data concerning minors are still rare. Method: For this exploratory, cross-sectional study, we included N = 43 minors (age range 9–17 years). The subjects were depressive subjects with or without antidepressant medication (N = 23) or healthy control children (HC) (N = 20). We assessed several indices of cardiac functioning using long-term electrocardiogram data (mean heart rate, HR, and several parameters of heart rate variability, HRV). We hypothesized that increased HR and reduced HRV are associated with depressive disorders. Furthermore, we assessed the impact of age, sex, and antidepressant medication on HR and HRV. Results: When sex and age were controlled for, HR was significantly increased in depressive minors compared to HC. However, our preliminary data suggest that this might not be the case in medicated patients, and there were no differences between groups regarding HRV parameters. There was no significant correlation in the whole sample between severity of depression and both HR and HRV. In the subsample of patients with depression, antidepressant medication was associated with lower HR and higher indices of HRV. Conclusion: The data indicate an association between depression and altered autonomic cardiac regulation, which can already manifests in minors.
„Ist doch eh alles das Gleiche, oder?!“
Authors: Quernheim German
Published: April 2019

Zusammenfassung. Im deutschen Gesundheitswesen werden neben Auszubildenden der Gesundheits- und (Kinder-)Krankenpflege bzw. Altenpflege auch Studierende von (überwiegend noch dualen) Studiengängen für die Pflegearbeit qualifiziert. In der praktischen Ausbildung übernehmen Praxisanleitende (PAL) eine Schlüsselfunktion. Bei den beiden Lerngruppen Schüler – Studierende gibt es Gemeinsamkeiten aber auch Differenzen. Die veränderten Forderungen des neuen Pflegeberufegesetzes (PflBG) haben Auswirkungen auf die Qualifikationen der PAL.
Vorbilder in der Pflege: Eine monokulturelle Angelegenheit?
Authors: Schlegel Claudia , Siefers Martin , Engels Marion , Beatty Ingeborg , Delic Sinisa
Published: April 2019

Zusammenfassung. Auf dem Weg zur beruflichen Sozialisierung spielen Vorbilder eine wichtige Rolle. Sie vermitteln Halt und Orientierung. In einem Workshop haben sich Lehrpersonen aus verschiedenen europäischen Ländern mit der Vorbildfunktion auseinandergesetzt.
The Fundamental Aerosol Models Over China Region: A Cluster Analysis of the Ground‐Based Remote Sensing Measurements of Total Columnar Atmosphere
Authors: Li Zhengqiang , Zhang Ying , Xu Hua , Li Kaitao , Dubovik Oleg , Goloub Philippe
Published: April 2019

Ten fundamental aerosol models in China are derived from a cluster study based on the ground‐based remote sensing measurements of Sun‐sky radiometer Observation NETwork. The aerosol size distribution decomposition techniques are employed to yield individual fine and coarse mode size distribution functions with independent refractive indices. The total 10,773 records containing 18 kinds of aerosol microphysical parameters are used to yield 10 typical clusters with the verification of clustering robustness. Ten clusters suggest five typical fine particle aerosol models including urban polluted, secondary polluted, combined polluted, polluted fly ash, and continental background, as well as five coarse models including summer fly ash, winter fly ash, primary dust, transported dust, and background dust over China region. The representativeness and coappearance analyses again reveal five dominative aerosol patterns on the base of fundamental models. These models can be used in the chemical model simulation, satellite remote sensing, climate, and environment analyses.
Measuring endogenous changes in serotonergic neurotransmission with [11C]Cimbi-36 positron emission tomography in humans
Authors: da Cunha-Bang Sofi , Ettrup Anders , Mc Mahon Brenda , Skibsted Anine Persson , Schain Martin , Lehel Szabolcs , Dyssegaard Agnete , Jørgensen Louise Møller , Møller Kirsten , Gillings Nic , Svarer Claus , Knudsen Gitte M.
Published: April 2019

Developing positron emission tomography (PET) radioligands for the detection of endogenous serotonin release will enable the investigation of serotonergic deficits in many neuropsychiatric disorders. The present study investigates how acute challenges that aim to increase or decrease cerebral serotonin levels affect binding of the serotonin 2A receptor (5-HT2AR) agonist radioligand [11C]Cimbi-36. In a randomized, double-blind, placebo-controlled, three-arm design, 23 healthy volunteers were PET scanned twice with [11C]Cimbi-36: at baseline and following double-blind assignment to one of three interventions (1) infusion of the selective serotonin reuptake inhibitor (SSRI) citalopram preceded by oral dosing of the 5-HT1AR antagonist pindolol, (n = 8) (2) acute tryptophan depletion (ATD) (n = 7) and (3) placebo (n = 8). Two-sample t-tests revealed no significant group differences in percent change of neocortical [11C]Cimbi-36 binding from baseline to intervention between placebo and citalopram/pindolol (p = 0.4) or between placebo and ATD (p = 0.5). Notably, there was a significantly larger within-group variation in 5-HT2AR binding after intervention with citalopram/pindolol, as compared with placebo (p = 0.007). These findings suggest that neither ATD nor a combination of citalopram and pindolol elicit acute unidirectional changes in serotonin levels sufficient to be detected with [11C]Cimbi-36 PET in neocortex. We suggest that the large interindividual variation in 5-HT2AR binding after citalopram/pindolol reflects that after an acute SSRI intervention, individuals respond substantially different in terms of their brain serotonin levels. Our observation has a potential impact for the understanding of patient responses to SSRI.
Public Dental Service personnel facing a major health care reform in Finland
Authors: Widström Eeva , Tiira Hannele , Tillberg Anders
Published: April 2019

Objectives

A health care reform will replace the health care and social services centred on public provision with a market-oriented system and enhanced competition between public and private sectors. The aim was to ascertain Public Dental Services (PDS) changes personnel anticipated and how dental services in the new “public” undertakings could be made more cost-efficient.

Materials and methods

An electronic questionnaire was sent to the Chief Dentists of a random sample of 12 PDS units in southern and northern Finland for distribution to their personnel; 71.0% responded.

Results

Most respondents (64.3%) believed that their PDS unit would not change. However, 45.4% foresaw a merger with another unit. More dentists (51.2%) were aware of market- and competition-oriented organisational forms to be introduced in the public sector than dental hygienists (35.0%) and dental assistants (27.3%; p < 0.01). Only 12.4% thought of moving to the private sector. To increase cost-efficiency in the new system, a majority suggested improvement in preventive care (79.8%) and increased use of dental hygienists (75.7%). A smaller proportion suggested longer opening hours (23.1%), higher patient fees (17.9%) or more paying patients (12.4%).

Discussion

Public sector employees had little knowledge and understanding of the coming reform and were badly prepared for competition with the private sector.
Glutathione prevents chronic oscillating glucose intake-induced β-cell dedifferentiation and failure
Authors: Zhang Jitai , An Hui , Ni Kaidi , Chen Bin , Li Hui , Li Yanqin , Sheng Guilian , Zhou Chuanzan , Xie Mengzhen , Chen Saijing , Zhou Tong , Yang Gaoxiong , Chen Xiufang , Wu Gaojun , Jin Shengwei , Li Ming
Published: April 2019

Modern lifestyles have altered diet and metabolic homeostasis, with increased sugar intake, glycemic index, and prediabetes. A strong positive correlation between sugar consumption and diabetic incidence is revealed, but the underlying mechanisms remain obscure. Here we show that oral intake of long-term oscillating glucose (LOsG) (4 times/day) for 38 days, which produces physiological glycemic variability in rats, can lead to β-cells gaining metabolic memory in reactive oxygen species (ROS) stress. This stress leads to suppression of forkhead box O1 (FoxO1) signaling and subsequent upregulation of thioredoxin interacting protein, inhibition of insulin and SOD-2 expression, re-expression of Neurog3, and β-cell dedifferentiation and functional failure. LOsG-treated animals develop prediabetes exhibiting hypoinsulinemia and glucose intolerance. Dynamic and timely administration of antioxidant glutathione prevents LOsG/ROS-induced β-cell failure and prediabetes. We propose that ROS stress is the initial step in LOsG-inducing prediabetes. Manipulating glutathione-related pathways may offer novel options for preventing the occurrence and development of diabetes.
Diverse small molecules prevent macrophage lysis during pyroptosis
Authors: Loomis Wendy P. , den Hartigh Andreas B. , Cookson Brad T. , Fink Susan L.
Published: April 2019

Pyroptosis is a programmed process of proinflammatory cell death mediated by caspase-1-related proteases that cleave the pore-forming protein, gasdermin D, causing cell lysis and release of inflammatory intracellular contents. The amino acid glycine prevents pyroptotic lysis via unknown mechanisms, without affecting caspase-1 activation or pore formation. Pyroptosis plays a critical role in diverse inflammatory diseases, including sepsis. Septic lethality is prevented by glycine treatment, suggesting that glycine-mediated cytoprotection may provide therapeutic benefit. In this study, we systematically examined a panel of small molecules, structurally related to glycine, for their ability to prevent pyroptotic lysis. We found a requirement for the carboxyl group, and limited tolerance for larger amino groups and substitution of the hydrogen R group. Glycine is an agonist for the neuronal glycine receptor, which acts as a ligand-gated chloride channel. The array of cytoprotective small molecules we identified resembles that of known glycine receptor modulators. However, using genetically deficient Glrb mutant macrophages, we found that the glycine receptor is not required for pyroptotic cytoprotection. Furthermore, protection against pyroptotic lysis is independent of extracellular chloride conductance, arguing against an effect mediated by ligand-gated chloride channels. Finally, we conducted a small-scale, hypothesis-driven small-molecule screen and identified unexpected ion channel modulators that prevent pyroptotic lysis with increased potency compared to glycine. Together, these findings demonstrate that pyroptotic lysis can be pharmacologically modulated and pave the way toward identification of therapeutic strategies for pathologic conditions associated with pyroptosis.
A new type of DNA phosphorothioation-based antiviral system in archaea
Authors: Xiong Lei , Liu Siyi , Chen Si , Xiao Yao , Zhu Bochen , Gao Yali , Zhang Yujing , Chen Beibei , Luo Jie , Deng Zixin , Chen Xiangdong , Wang Lianrong , Chen Shi
Published: April 2019

Archaea and Bacteria have evolved different defence strategies that target virtually all steps of the viral life cycle. The diversified virion morphotypes and genome contents of archaeal viruses result in a highly complex array of archaea-virus interactions. However, our understanding of archaeal antiviral activities lags far behind our knowledges of those in bacteria. Here we report a new archaeal defence system that involves DndCDEA-specific DNA phosphorothioate (PT) modification and the PbeABCD-mediated halt of virus propagation via inhibition of DNA replication. In contrast to the breakage of invasive DNA by DndFGH in bacteria, DndCDEA-PbeABCD does not degrade or cleave viral DNA. The PbeABCD-mediated PT defence system is widespread and exhibits extensive interdomain and intradomain gene transfer events. Our results suggest that DndCDEA-PbeABCD is a new type of PT-based virus resistance system, expanding the known arsenal of defence systems as well as our understanding of host-virus interactions.
Excitation and coherent control of spin qudit modes in silicon carbide at room temperature
Authors: Soltamov V. A. , Kasper C. , Poshakinskiy A. V. , Anisimov A. N. , Mokhov E. N. , Sperlich A. , Tarasenko S. A. , Baranov P. G. , Astakhov G. V. , Dyakonov V.
Published: April 2019

One of the challenges in the field of quantum sensing and information processing is to selectively address and coherently manipulate highly homogeneous qubits subject to external perturbations. Here, we present room-temperature coherent control of high-dimensional quantum bits, the so-called qudits, associated with vacancy-related spins in silicon carbide enriched with nuclear spin-free isotopes. In addition to the excitation of a spectrally narrow qudit mode at the pump frequency, several other modes are excited in the electron spin resonance spectra whose relative positions depend on the external magnetic field. We develop a theory of multipole spin dynamics and demonstrate selective quantum control of homogeneous spin packets with sub-MHz spectral resolution. Furthermore, we perform two-frequency Ramsey interferometry to demonstrate absolute dc magnetometry, which is immune to thermal noise and strain inhomogeneity.
Dynamic anticipation by Cdk2/Cyclin A-bound p27 mediates signal integration in cell cycle regulation
Authors: Tsytlonok Maksym , Sanabria Hugo , Wang Yuefeng , Felekyan Suren , Hemmen Katherina , Phillips Aaron H. , Yun Mi-Kyung , Waddell M. Brett , Park Cheon-Gil , Vaithiyalingam Sivaraja , Iconaru Luigi , White Stephen W. , Tompa Peter , Seidel Claus A. M. , Kriwacki Richard
Published: April 2019

p27Kip1 is an intrinsically disordered protein (IDP) that inhibits cyclin-dependent kinase (Cdk)/cyclin complexes (e.g., Cdk2/cyclin A), causing cell cycle arrest. Cell division progresses when stably Cdk2/cyclin A-bound p27 is phosphorylated on one or two structurally occluded tyrosine residues and a distal threonine residue (T187), triggering degradation of p27. Here, using an integrated biophysical approach, we show that Cdk2/cyclin A-bound p27 samples lowly-populated conformations that provide access to the non-receptor tyrosine kinases, BCR-ABL and Src, which phosphorylate Y88 or Y88 and Y74, respectively, thereby promoting intra-assembly phosphorylation (of p27) on distal T187. Even when tightly bound to Cdk2/cyclin A, intrinsic flexibility enables p27 to integrate and process signaling inputs, and generate outputs including altered Cdk2 activity, p27 stability, and, ultimately, cell cycle progression. Intrinsic dynamics within multi-component assemblies may be a general mechanism of signaling by regulatory IDPs, which can be subverted in human disease.
Conformational dynamics of the human serotonin transporter during substrate and drug binding
Authors: Möller Ingvar R. , Slivacka Marika , Nielsen Anne Kathrine , Rasmussen Søren G. F. , Gether Ulrik , Loland Claus J. , Rand Kasper D.
Published: April 2019

The serotonin transporter (SERT), a member of the neurotransmitter:sodium symporter family, is responsible for termination of serotonergic signaling by re-uptake of serotonin (5-HT) into the presynaptic neuron. Its key role in synaptic transmission makes it a major drug target, e.g. for the treatment of depression, anxiety and post-traumatic stress. Here, we apply hydrogen-deuterium exchange mass spectrometry to probe the conformational dynamics of human SERT in the absence and presence of known substrates and targeted drugs. Our results reveal significant changes in dynamics in regions TM1, EL3, EL4, and TM12 upon binding co-transported ions (Na+/K+) and ligand-mediated changes in TM1, EL3 and EL4 upon binding 5-HT, the drugs S-citalopram, cocaine and ibogaine. Our results provide a comprehensive direct view of the conformational response of SERT upon binding both biologically relevant substrate/ions and ligands of pharmaceutical interest, thus advancing our understanding of the structure-function relationship in SERT.
Early warning signals of recovery in complex systems
Authors: Clements Christopher F. , McCarthy Michael A. , Blanchard Julia L.
Published: April 2019

Early warning signals (EWSs) offer the hope that patterns observed in data can predict the future states of ecological systems. While a large body of research identifies such signals prior to the collapse of populations, the prediction that such signals should also be present before a system’s recovery has thus far been overlooked. We assess whether EWSs are present prior to the recovery of overexploited marine systems using a trait-based ecological model and analysis of real-world fisheries data. We show that both abundance and trait-based signals are independently detectable prior to the recovery of stocks, but that combining these two signals provides the best predictions of recovery. This work suggests that the efficacy of conservation interventions aimed at restoring systems which have collapsed may be predicted prior to the recovery of the system, with direct relevance for conservation planning and policy.
Urbanity and the dynamics of language shift in Galicia
Authors: Mussa Juane Mariamo , Seoane Luis F. , Muñuzuri Alberto P. , Mira Jorge
Published: April 2019

Sociolinguistic phenomena often involve interactions across different scales and result in social and linguistic changes that can be tracked over time. Here, we focus on the dynamics of language shift in Galicia, a bilingual community in northwest Spain. Using historical data on Galician and Spanish speakers, we show that the rate at which shift dynamics unfold correlates inversely with the internal complexity of a region (approximated by the proportion of urban area). Less complex areas converge faster to steady states, while more complex ones sustain transitory dynamics longer. We further explore the contextual relevance of each region within the network of regions that constitute Galicia. The network is observed to sustain or reverse the dynamic rates. This model can introduce a competition between the internal complexity of a region and its contextual relevance in the network. Harnessing these sociodynamic features may prove useful in policy making to limit conflicts.
Flux flow spin Hall effect in type-II superconductors with spin-splitting field
Authors: Vargunin Artjom , Silaev Mikhail
Published: April 2019

We predict the very large spin Hall effect in type-II superconductors whose mechanism is drastically different from the previously known ones. We find that in the flux-flow regime the spin is transported by the spin-polarized Abrikosov vortices moving under the action of the Lorenz force in the direction perpendicular to the applied electric current. Due to the large vortex velocities the spin Hall angle can be of the order of unity in realistic systems based on the high-field superconductors, superconductor/ferromagnet hybrid structures or the recently developed superconductor/ferromagnetic insulator proximity structures. We propose the realization of high-frequency pure spin current generator based on the periodic structure of moving vortex lattices. We find the patterns of charge imbalance and spin accumulation generated by moving vortices, which can be used for the electrical detection of individual vortex motion. The new mechanism of inverse flux-flow spin Hall effect is found based on the driving force acting on the vortices in the presence of injected spin current which results in the generation of transverse voltage.
Author Correction: Reconstruction of cysteine biosynthesis using engineered cysteine-free enzymes
Authors: Fujishima Kosuke , Wang Kendrick M. , Palmer Jesse A. , Abe Nozomi , Nakahigashi Kenji , Endy Drew , Rothschild Lynn J.
Published: April 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Horizontal gene transfer in human-associated microorganisms inferred by phylogenetic reconstruction and reconciliation
Authors: Jeong Hyeonsoo , Arif Bushra , Caetano-Anollés Gustavo , Kim Kyung Mo , Nasir Arshan
Published: April 2019

Horizontal gene transfer (HGT) is widespread in the evolution of prokaryotes, especially those associated with the human body. Here, we implemented large-scale gene-species phylogenetic tree reconstructions and reconciliations to identify putative HGT-derived genes in the reference genomes of microbiota isolated from six major human body sites by the NIH Human Microbiome Project. Comparisons with a control group representing microbial genomes from diverse natural environments indicated that HGT activity increased significantly in the genomes of human microbiota, which is confirmatory of previous findings. Roughly, more than half of total genes in the genomes of human-associated microbiota were transferred (donated or received) by HGT. Up to 60% of the detected HGTs occurred either prior to the colonization of the human body or involved bacteria residing in different body sites. The latter could suggest ‘genetic crosstalk’ and movement of bacterial genes within the human body via hitherto poorly understood mechanisms. We also observed that HGT activity increased significantly among closely-related microorganisms and especially when they were united by physical proximity, suggesting that the ‘phylogenetic effect’ can significantly boost HGT activity. Finally, we identified several core and widespread genes least influenced by HGT that could become useful markers for building robust ‘trees of life’ and address several outstanding technical challenges to improve the phylogeny-based genome-wide HGT detection method for future applications.
Effects of abdominal visceral fat compared with those of subcutaneous fat on the association between PM10 and hypertension in Korean men: A cross-sectional study
Authors: Kim Hyun-Jin , Kwon Hyuktae , Jeong Su-Min , Hwang Seo Eun , Park Jin-Ho
Published: April 2019

We assessed whether visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT) has modifying effects on the cross-sectional association between ambient air pollution and hypertension in Korean men. This study included 1,417 adult men who visited a health checkup center. Abdominal fat depots were measured by computed tomography, and we used the annual average concentrations of ambient air pollutants such as particulate matter with an aerodynamic diameter of ≤10 μm (PM10), nitrogen dioxide, sulfur dioxide, and carbon monoxide (CO). The annual mean concentrations of PM10 (odds ratio [OR] = 1.30; 95% confidence interval [CI] = 1.12–1.52) and CO (OR = 1.20; 95% CI = 1.03–1.39) showed a positive association with hypertension. In particular, modifying effects on hypertension were found between PM10 and VAT-related traits such as VAT and visceral-to-subcutaneous fat ratio (VSR). The association between PM10 and hypertension was much stronger in the high-VAT (OR = 1.74; 95% CI = 1.12–2.71) and high-VSR groups (OR = 1.53; 95% CI = 1.23–1.91). However, the strength of association across levels of SAT was not observed (Pint = 0.4615). In conclusion, we found that association between PM10 exposure and hypertension is different by abdominal fat distribution.
Clinicopathological features and prognosis of young gastric cancer patients following radical gastrectomy: a propensity score matching analysis
Authors: Liu Wu , Quan Hu , Chen Xiaoyan , Ouyang Yongzhong , Xiao Hua
Published: April 2019

The aim of the this retrospective study was to investigate the clinicopathological features of gastric cancer (GC) in young patients and the potential impact of age on the prognosis of patients undergoing radical gastrectomy for GC. From November 2010 to November 2016, 317 young (≤45 years) and 1344 older patients (>45 years) who underwent radical gastrectomy for stage I-III GC were enrolled. The association between age and prognosis was estimated by univariate and multivariate analyses after propensity score matching (PSM). Compared with older patients, the proportion of females, poorly differentiated tumors, good nutritional status, and who received neo-adjuvant and/or adjuvant chemotherapy was significant higher in younger patients, but were less likely to suffer from comorbidities or post-operative complications (all P < 0.05). PSM analysis created 310 pairs of patients. After matching, the long-term survival in younger patients was significantly longer than in older patients at stage I, but similar at stages II and III. However, a young age was not identified as a significant prognostic factor. In conclusion, the prognosis of young GC patients is comparable with and even better than that in older patients after radical gastrectomy when matched for baseline characteristics. Early detection could improve the prognosis of young GC patients.
Highly parallel simulation and optimization of photonic circuits in time and frequency domain based on the deep-learning framework PyTorch
Authors: Laporte Floris , Dambre Joni , Bienstman Peter
Published: April 2019

We propose a new method for performing photonic circuit simulations based on the scatter matrix formalism. We leverage the popular deep-learning framework PyTorch to reimagine photonic circuits as sparsely connected complex-valued neural networks. This allows for highly parallel simulation of large photonic circuits on graphical processing units in time and frequency domain while all parameters of each individual component can easily be optimized with well-established machine learning algorithms such as backpropagation.
A sensitive scoring system for the longitudinal clinical evaluation and prediction of lethal disease outcomes in newborn mice
Authors: Fehlhaber Beate , Heinemann Anna S. , Rübensam Kathrin , Willers Maike , Völlger Lena , Pfeifer Sandra , von Köckritz-Blickwede Maren , Viemann Dorothee
Published: April 2019

Neonatal animal models are increasingly employed in order to unravel age-specific disease mechanisms. Appropriate tools objectifying the clinical condition of murine neonates are lacking. In this study, we tested a scoring system specifically designed for newborn mice that relies on clinical observation and examination. Both, in a neonatal sepsis model and an endotoxic shock model, the scoring results strongly correlated with disease-induced death rates. Full as well as observation-restricted scoring, reliably predicted fatality and the remaining time until death. Clinical scores even proved as more sensitive biomarker than 6 traditionally used plasma cytokine levels in detecting sepsis at an early disease stage. In conclusion, we propose a simple scoring system that detects health impairments of newborn mice in a non-invasive longitudinal and highly sensitive manner. Its usage will help to meet animal welfare requirements and might improve the understanding of neonatal disease mechanisms.
A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells
Authors: Yang Chunlin , Broncel Malgorzata , Dominicus Caia , Sampson Emily , Blakely William J. , Treeck Moritz , Arrizabalaga Gustavo
Published: April 2019

The propagation of Toxoplasma gondii is accomplished by repeated lytic cycles of parasite attachment to a host cell, invasion, replication within a parasitophorous vacuole, and egress from the cell. This lytic cycle is delicately regulated by calcium-dependent reversible phosphorylation of the molecular machinery that drives invasion and egress. While much progress has been made elucidating the protein kinases and substrates central to parasite propagation, little is known about the relevant protein phosphatases. In this study, we focused on the five protein phosphatases that are predicted to be membrane-associated either integrally or peripherally. We have determined that of these only PPM5C, a PP2C family member, localizes to the plasma membrane of Toxoplasma. Disruption of PPM5C results in a slow propagation phenotype in tissue culture. Interestingly, parasites lacking PPM5C divide and undergo egress at a normal rate, but have a deficiency in attaching to host cells. Both membrane localization and phosphatase activity are required for PPM5C’s role in attachment. Phosphoproteomic analysis show relatively few phosphorylation sites being affected by PPM5C deletion in extracellular parasites of which several are found on proteins involved in signaling cascades. This implies that PPM5C is part of a wider regulatory network important for attachment to host cells.
Fabrication of Stacked MoS2 Bilayer with Weak Interlayer Coupling by Reduced Graphene Oxide Spacer
Authors: Oh Hye Min , Kim Hyojung , Kim Hyun , Jeong Mun Seok
Published: April 2019

We fabricated the stacked bilayer molybdenum disulfide (MoS2) by using reduced graphene oxide (rGO) as a spacer for increasing the optoelectronic properties of MoS2. The rGO can decrease the interlayer coupling between the stacked bilayer MoS2and retain the direct band gap property of MoS2. We observed a twofold enhancement of the photoluminescence intensity of the stacked MoS2bilayer. In the Raman scattering, we observed that the E12gand A1gmodes of the stacked bilayer MoS2with rGO were further shifted compared to monolayer MoS2, which is due to the van der Waals (vdW) interaction and the strain effect between the MoS2and rGO layers. The findings of this study will expand the applicability of monolayer MoS2for high-performance optoelectronic devices by enhancing the optical properties using a vdW spacer.
Large Enriched Fragment Targeted Sequencing (LEFT-SEQ) Applied to Capture of Wolbachia Genomes
Authors: Lefoulon Emilie , Vaisman Natalie , Frydman Horacio M. , Sun Luo , Voland Lise , Foster Jeremy M. , Slatko Barton E.
Published: April 2019

Symbiosis is a major force of evolutionary change, influencing virtually all aspects of biology, from population ecology and evolution to genomics and molecular/biochemical mechanisms of development and reproduction. A remarkable example is Wolbachia endobacteria, present in some parasitic nematodes and many arthropod species. Acquisition of genomic data from diverse Wolbachia clades will aid in the elucidation of the different symbiotic mechanisms(s). However, challenges of de novo assembly of Wolbachia genomes include the presence in the sample of host DNA: nematode/vertebrate or insect. We designed biotinylated probes to capture large fragments of Wolbachia DNA for sequencing using PacBio technology (LEFT-SEQ: Large Enriched Fragment Targeted Sequencing). LEFT-SEQ was used to capture and sequence four Wolbachia genomes: the filarial nematode Brugia malayi, wBm, (21-fold enrichment), Drosophila mauritiana flies (2 isolates), wMau (11-fold enrichment), and Aedes albopictus mosquitoes, wAlbB (200-fold enrichment). LEFT-SEQ resulted in complete genomes for wBm and for wMau. For wBm, 18 single-nucleotide polymorphisms (SNPs), relative to the wBm reference, were identified and confirmed by PCR. A limit of LEFT-SEQ is illustrated by the wAlbB genome, characterized by a very high level of insertion sequences elements (ISs) and DNA repeats, for which only a 20-contig draft assembly was achieved.
Author Correction: Efficient Characterization and Classification of Contrast Sensitivity Functions in Aging
Authors: Yan Fang-Fang , Hou Fang , Lu Zhong-Lin , Hu Xiaopeng , Huang Chang-Bing
Published: April 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Detection of KRAS mutation via ligation-initiated LAMP reaction
Authors: Fu Yixin , Duan Xiaolei , Huang Jian , Huang Lizhen , Zhang Lutan , Cheng Wei , Ding Shijia , Min Xun
Published: April 2019

KRAS mutations are abnormalities widely found in genomic DNA and circulating tumor DNA (ctDNA) of various types of cancers. Thus, highly sensitive detection of KRAS mutations in genomic DNA is of great significance in disease diagnosis and personalized medicine. Here, we developed a ligation-initiated loop-mediated isothermal amplification (LAMP) assaying method for ultrasensitive detection of KRAS mutation. In the presence of mutant KRAS DNA (mutDNA), the dumbbell-shaped structure (DSS) is formed by the specific ligation of two substrates (SLS1 and SLS2), which act as a template to initiate the following LAMP amplification. Making use of the outstanding specificity of ligation reaction and superior amplification of LAMP, 10 aM mutDNA can be accurately determined. In addition, as low as 0.1% mutDNA can be detected in the presence of a large excess of wild-type KRAS DNA (wtDNA), indicating the high sensitivity and specificity of the method. Furthermore, this strategy has been successfully applied for detection of a KRAS mutation from tissue samples of colorectal cancer patients. Thus, the developed ligation-initiated LAMP fluorescence assaying strategy presents a promising prospect for ultrasensitive detection of mutations.
Detection of Early-Stage Degeneration in Human Articular Cartilage by Multiparametric MR Imaging Mapping of Tissue Functionality
Authors: Nebelung Sven , Post Manuel , Knobe Matthias , Tingart Markus , Emans Pieter , Thüring Johannes , Kuhl Christiane , Truhn Daniel
Published: April 2019

To assess human articular cartilage tissue functionality by serial multiparametric quantitative MRI (qMRI) mapping as a function of histological degeneration. Forty-nine cartilage samples obtained during total knee replacement surgeries were placed in a standardized artificial knee joint within an MRI-compatible compressive loading device and imaged in situ and at three loading positions, i.e. unloaded, at 2.5 mm displacement (20% body weight [BW]) and at 5 mm displacement (110% BW). Using a clinical 3.0 T MRI system (Achieva, Philips), serial T1, T1ρ, T2 and T2* maps were generated for each sample and loading position. Histology (Mankin scoring) and biomechanics (Young’s modulus) served as references. Samples were dichotomized as intact (int, n = 27) or early degenerative (deg, n = 22) based on histology and analyzed using repeated-measures ANOVA and unpaired Student’s t-tests after log-transformation. For T1ρ, T2 and T2*, significant loading-induced differences were found in deg (in contrast to int) samples, while for T1 significant decreases in all zones were observed, irrespective of degeneration. In conclusion, cartilage functionality may be visualized using serial qMRI parameter mapping and the response-to-loading patterns are associated with histological degeneration. Hence, loading-induced changes in qMRI parameter maps provide promising surrogate parameters of tissue functionality and status in health and disease.
MoTe2van der Waals homojunction p–n diode with low resistance metal contacts
Authors: Aftab Sikandar , Khan Muhammad Farooq , Gautam Praveen , Noh Hwayong , Eom Jonghwa
Published: April 2019

We present a van der Waals p-MoTe2/n-MoTe2homojunction p–n diode with low resistance metal contacts.
Ray-based optical visualisation of complex birefringent structures including energy transport
Authors: Poy Guilhem , Žumer Slobodan
Published: April 2019

We present a novel ray-tracing method in birefringent media able to accurately simulate bright-field and polarised optical micrographs.
Enhancing thermoelectric properties by using a surface polarization effect based on PEDOT:PSS thin films
Authors: Peng Liping , Liu Zhitian
Published: April 2019

Polarons of PEDOT:PSS contribute to the surface polarization effect in a metal/PEDOT:PSS/metal structure device. The polarons of PEDOT:PSS contribute to surface polarization due to the electron–phonon coupling. Surface polarization as a new driving force can develop the Seebeck effect based on a metal/semi-metal/metal design.
A highly specific and ultrasensitive probe for the imaging of inflammation-induced endogenous hypochlorous acid
Authors: Song Xinjian , Hu Wei , Wang Donghua , Mao Zhiqiang , Liu Zhihong
Published: April 2019

A two-photon fluorescent probe with high sensitivity and selectivity was constructed and applied to visualize endogenous HOCl in lipopolysaccharide-induced inflammation.
Glucosamine sulphate-loaded distearoyl phosphocholine liposomes for osteoarthritis treatment: combination of sustained drug release and improved lubrication
Authors: Ji Xiuling , Yan Yufei , Sun Tao , Zhang Qiang , Wang Yixin , Zhang Ming , Zhang Hongyu , Zhao Xin
Published: April 2019

A drug-loaded nanocarrier integrating the sustained drug release and improved lubrication ability is fabricated for the treatment of osteoarthritis.
Insights into NHC-catalyzed oxidative α-C(sp3)–H activation of aliphatic aldehydes and cascade [2 + 3] cycloaddition with azomethine imines
Authors: Li Xue , Li Shi-Jun , Wang Yanyan , Wang Yang , Qu Ling-Bo , Li Zhongjun , Wei Donghui
Published: April 2019

The NHC catalyst is identified to promote [2 + 3] cycloaddition by avoiding the poor FMO overlap mode in theory.