bluuebunny/crossref_metadata_2025 huggingface dataset:
A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma
Authors: van Groningen Tim , Akogul Nurdan , Westerhout Ellen M. , Chan Alvin , Hasselt Nancy E. , Zwijnenburg Danny A. , Broekmans Marloes , Stroeken Peter , Haneveld Franciska , Hooijer Gerrit K. J. , Savci-Heijink C. Dilara , Lakeman Arjan , Volckmann Richard , van Sluis Peter , Valentijn Linda J. , Koster Jan , Versteeg Rogier , van Nes Johan
Published: April 2019

Transition between differentiation states in development occurs swift but the mechanisms leading to epigenetic and transcriptional reprogramming are poorly understood. The pediatric cancer neuroblastoma includes adrenergic (ADRN) and mesenchymal (MES) tumor cell types, which differ in phenotype, super-enhancers (SEs) and core regulatory circuitries. These cell types can spontaneously interconvert, but the mechanism remains largely unknown. Here, we unravel how a NOTCH3 intracellular domain reprogrammed the ADRN transcriptional landscape towards a MES state. A transcriptional feed-forward circuitry of NOTCH-family transcription factors amplifies the NOTCH signaling levels, explaining the swift transition between two semi-stable cellular states. This transition induces genome-wide remodeling of the H3K27ac landscape and a switch from ADRN SEs to MES SEs. Once established, the NOTCH feed-forward loop maintains the induced MES state. In vivo reprogramming of ADRN cells shows that MES and ADRN cells are equally oncogenic. Our results elucidate a swift transdifferentiation between two semi-stable epigenetic cellular states.
Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms
Authors: De Suman , Wirthensohn David C. , Flagmeier Patrick , Hughes Craig , Aprile Francesco A. , Ruggeri Francesco S. , Whiten Daniel R. , Emin Derya , Xia Zengjie , Varela Juan A. , Sormanni Pietro , Kundel Franziska , Knowles Tuomas P. J. , Dobson Christopher M. , Bryant Clare , Vendruscolo Michele , Klenerman David
Published: April 2019

Protein aggregation is a complex process resulting in the formation of heterogeneous mixtures of aggregate populations that are closely linked to neurodegenerative conditions, such as Alzheimer’s disease. Here, we find that soluble aggregates formed at different stages of the aggregation process of amyloid beta (Aβ42) induce the disruption of lipid bilayers and an inflammatory response to different extents. Further, by using gradient ultracentrifugation assay, we show that the smaller aggregates are those most potent at inducing membrane permeability and most effectively inhibited by antibodies binding to the C-terminal region of Aβ42. By contrast, we find that the larger soluble aggregates are those most effective at causing an inflammatory response in microglia cells and more effectively inhibited by antibodies targeting the N-terminal region of Aβ42. These findings suggest that different toxic mechanisms driven by different soluble aggregated species of Aβ42 may contribute to the onset and progression of Alzheimer’s disease.
Anion-adaptive crystalline cationic material for 99TcO4− trapping
Authors: Mei Lei , Li Fei-ze , Lan Jian-hui , Wang Cong-zhi , Xu Chao , Deng Hao , Wu Qun-yan , Hu Kong-qiu , Wang Lin , Chai Zhi-fang , Chen Jing , Gibson John K. , Shi Wei-qun
Published: April 2019

Efficient anion recognition is of great significance for radioactive 99TcO4− decontamination, but it remains a challenge for traditional sorbents. Herein, we put forward a tactic using soft crystalline cationic material with anion-adaptive dynamics for 99TcO4− sequestration. A cucurbit[8]uril-based supramolecular metal-organic material is produced through a multi-component assembly strategy and used as a sorbent for effective trapping of TcO4−. Excellent separation of TcO4−/ReO4− is demonstrated by fast removal kinetics, good sorption capacity and high distribution coefficient. Remarkably, the most superior selectivity among metal-organic materials reported so far, together with good hydrolytic stability, indicates potential for efficient TcO4− removal. The structure incorporating ReO4− reveals that the supramolecular framework undergoes adaptive reconstruction facilitating the effective accommodation of TcO4−/ReO4−. The results highlight opportunities for development of soft anion-adaptive sorbents for highly selective anion decontamination.
A bacterial checkpoint protein for ribosome assembly moonlights as an essential metabolite-proofreading enzyme
Authors: Sachla Ankita J. , Helmann John D.
Published: April 2019

In eukaryotes, adventitious oxidation of erythrose-4-phosphate, an intermediate of the pentose phosphate pathway (PPP), generates 4-phosphoerythronate (4PE), which inhibits 6-phosphogluconate dehydrogenase. 4PE is detoxified by metabolite-proofreading phosphatases such as yeast Pho13. Here, we report that a similar function is carried out in Bacillus subtilis by CpgA, a checkpoint protein known to be important for ribosome assembly, cell morphology and resistance to cell wall-targeting antibiotics. We find that ΔcpgA cells are intoxicated by glucose or other carbon sources that feed into the PPP, and that CpgA has high phosphatase activity with 4PE. Inhibition of 6-phosphogluconate dehydrogenase (GndA) leads to intoxication by 6-phosphogluconate, a potent inhibitor of phosphoglucose isomerase (PGI). The coordinated shutdown of PPP and glycolysis leads to metabolic gridlock. Overexpression of GndA, PGI, or yeast Pho13 suppresses glucose intoxication of ΔcpgA cells, but not cold sensitivity, a phenotype associated with ribosome assembly defects. Our results suggest that CpgA is a multifunctional protein, with genetically separable roles in ribosome assembly and metabolite proofreading.
Precise segmentation of densely interweaving neuron clusters using G-Cut
Authors: Li Rui , Zhu Muye , Li Junning , Bienkowski Michael S. , Foster Nicholas N. , Xu Hanpeng , Ard Tyler , Bowman Ian , Zhou Changle , Veldman Matthew B. , Yang X. William , Hintiryan Houri , Zhang Junsong , Dong Hong-Wei
Published: April 2019

Characterizing the precise three-dimensional morphology and anatomical context of neurons is crucial for neuronal cell type classification and circuitry mapping. Recent advances in tissue clearing techniques and microscopy make it possible to obtain image stacks of intact, interweaving neuron clusters in brain tissues. As most current 3D neuronal morphology reconstruction methods are only applicable to single neurons, it remains challenging to reconstruct these clusters digitally. To advance the state of the art beyond these challenges, we propose a fast and robust method named G-Cut that is able to automatically segment individual neurons from an interweaving neuron cluster. Across various densely interconnected neuron clusters, G-Cut achieves significantly higher accuracies than other state-of-the-art algorithms. G-Cut is intended as a robust component in a high throughput informatics pipeline for large-scale brain mapping projects.
Miniaturised interaction proteomics on a microfluidic platform with ultra-low input requirements
Authors: Furlan Cristina , Dirks René A. M. , Thomas Peter C. , Jones Robert C. , Wang Jing , Lynch Mark , Marks Hendrik , Vermeulen Michiel
Published: April 2019

Essentially all cellular processes are orchestrated by protein-protein interactions (PPIs). In recent years, affinity purification coupled to mass spectrometry (AP-MS) has been the preferred method to identify cellular PPIs. Here we present a microfluidic-based AP-MS workflow, called on-chip AP-MS, to identify PPIs using minute amounts of input material. By using this automated platform we purify the human Cohesin, CCC and Mediator complexes from as little as 4 micrograms of input lysate, representing a 50─100-fold downscaling compared to regular microcentrifuge tube-based protocols. We show that our platform can be used to affinity purify tagged baits as well as native cellular proteins and their interaction partners. As such, our method holds great promise for future biological and clinical AP-MS applications in which sample amounts are limited.
Mutual coupling and synchronization of optically coupled quantum-dot micropillar lasers at ultra-low light levels
Authors: Kreinberg Sören , Porte Xavier , Schicke David , Lingnau Benjamin , Schneider Christian , Höfling Sven , Kanter Ido , Lüdge Kathy , Reitzenstein Stephan
Published: April 2019

Synchronization of coupled oscillators at the transition between classical physics and quantum physics has become an emerging research topic at the crossroads of nonlinear dynamics and nanophotonics. We study this unexplored field by using quantum dot microlasers as optical oscillators. Operating in the regime of cavity quantum electrodynamics (cQED) with an intracavity photon number on the order of 10 and output powers in the 100 nW range, these devices have high β-factors associated with enhanced spontaneous emission noise. We identify synchronization of mutually coupled microlasers via frequency locking associated with a sub-gigahertz locking range. A theoretical analysis of the coupling behavior reveals striking differences from optical synchronization in the classical domain with negligible spontaneous emission noise. Beyond that, additional self-feedback leads to zero-lag synchronization of coupled microlasers at ultra-low light levels. Our work has high potential to pave the way for future experiments in the quantum regime of synchronization.
The maternal to zygotic transition regulates genome-wide heterochromatin establishment in the zebrafish embryo
Authors: Laue Kathrin , Rajshekar Srivarsha , Courtney Abigail J. , Lewis Zachary A. , Goll Mary G.
Published: April 2019

The segregation of eukaryotic genomes into euchromatin and heterochromatin represents a fundamental and poorly understood process. Here, we demonstrate that genome-wide establishment of heterochromatin is triggered by the maternal to zygotic transition (MZT) during zebrafish embryogenesis. We find that prior to MZT, zebrafish lack hallmarks of heterochromatin including histone H3 lysine 9 trimethylation (H3K9me3) and condensed chromatin ultrastructure. Global establishment of heterochromatic features occurs following MZT and requires both activation of the zygotic genome and degradation of maternally deposited RNA. Mechanistically, we demonstrate that zygotic transcription of the micro RNA miR-430 promotes degradation of maternal RNA encoding the chromatin remodeling protein Smarca2, and that clearance of Smarca2 is required for global heterochromatin establishment in the early embryo. Our results identify MZT as a key developmental regulator of heterochromatin establishment during vertebrate embryogenesis and uncover functions for Smarca2 in protecting the embryonic genome against heterochromatinization.
Global synergies and trade-offs between multiple dimensions of biodiversity and ecosystem services
Authors: Girardello Marco , Santangeli Andrea , Mori Emiliano , Chapman Anna , Fattorini Simone , Naidoo Robin , Bertolino Sandro , Svenning Jens-Christian
Published: April 2019

Ensuring the persistence of biodiversity and ecosystem services represents a global challenge that need to be addressed with high urgency. Global priority areas can only be identified by means of an integrated prioritization approach that would not only preserve species numbers and ecosystem services, but also the evolutionary and functional components of diversity. In this study we combine global datasets on the distribution of mammals and birds with species traits and phylogenetic data and we identify conservation priorities for taxonomic, functional and phylogenetic diversity, as well as for three ecosystem services, including potential for carbon sequestration, pollination potential and groundwater recharge. We show that, when priority areas are identified based only on individual, e.g. functional diversity, or any combination of the three biodiversity components, these areas do not allow a sufficient protection of the three ecosystem services. However, an integrated approach whereby prioritization is based on all biodiversity components and ecosystem services would allow to identify areas that maximize protection of all ecosystem services with a minimal loss in biodiversity coverage. Our results highlight the need for an integrated conservation planning framework in order to optimally allocate resources and achieve the long-term preservation of the multiple dimensions of biodiversity and ecosystems services.
Three-dimensional imaging and quantitative analysis in CLARITY processed breast cancer tissues
Authors: Chen Yi , Shen Qi , White Sharla L. , Gokmen-Polar Yesim , Badve Sunil , Goodman Laurie J.
Published: April 2019

The tumor microenvironment can be spatially heterogenous, which makes it challenging to fully characterize with standard 2D histology-based methods. In this study, we determined the feasibility of a CLARITY tissue-processing approach to analyze biopsies from breast cancer patients. Formalin-fixed human breast cancer core-needle biopsy specimens, were embedded, lipid-cleared, and multiplexed immunostained to identify key biomarkers (pan-cytokeratin, Ki67, CD3). Confocal microscopy was then used to image the specimens after refractive index matching. These data sets were then quantitatively compared to conventional slide-based FFPE histology. Using CLARITY, the gross and cellular morphology of the tissues were well preserved, and high optical transparency was achieved, with the exception of fibrotic regions. Specific staining of various cellular and nuclear markers was achieved using optimized antibody conditions. Manually determined composite Ki67 scores from the CLARITY datasets agreed with histology results. However, the CLARITY datasets (3D) revealed variation in the intra-tumoral Ki67 expression that was not evident in individual FFPE sections (2D). We further demonstrated that archived FFPE clinical specimens can be CLARITY-processed, immunostained, and imaged. In short, CLARITY-processed specimens may enable a more accurate, unbiased analysis of tumor samples in comparison to conventional slide-based histology, thus allowing for improved visualization of intra-tumoral heterogeneity.
Simultaneous Electrochemical Deposition of Cobalt Complex and Poly(pyrrole) Thin Films for Supercapacitor Electrodes
Authors: Parnell Charlette M. , Chhetri Bijay P. , Mitchell Travis B. , Watanabe Fumiya , Kannarpady Ganesh , RanguMagar Ambar B. , Zhou Huajun , Alghazali Karrer M. , Biris Alexandru S. , Ghosh Anindya
Published: April 2019

Supercapacitors are beneficial as energy storage devices and can obtain high capacitance values greater than conventional capacitors and high power densities compared to batteries. However, in order to improve upon the overall cost, energy density, and charge-discharge rates, the electrode material of supercapacitors needs to be fine-tuned with an inexpensive, high conducting source. We prepared a Co(III) complex and polypyrrole (PPy) composite thin films (CoN4-PPy) that was electrochemically deposited on the surface of a glassy carbon working electrode. Cyclic voltammetry studies indicate the superior performance of CoN4-PPy in charge storage in acidic electrolyte compared to alkaline and organic solutions. The CoN4-PPy material generated the highest amount of specific capacitance (up to 721.9 F/g) followed by Co salt and PPy (Co-PPy) material and PPy alone. Cyclic performance studies showed the excellent electrochemical stability of the CoN4-PPy film in the acidic medium. Simply electrochemically depositing an inexpensive Co(III) complex with a high electrically conducting polymer of PPy delivered a superior electrode material for supercapacitor applications. Therefore, the results indicate that novel thin films derived from Co(III) metal complex and PPy can store a large amount of energy and maintain high stability over many cycles, revealing its excellent potential in supercapacitor devices.
The evolution and phylodynamics of serotype A and SAT2 foot-and-mouth disease viruses in endemic regions of Africa
Authors: Lycett S. , Tanya V. N. , Hall M. , King D. P. , Mazeri S. , Mioulet V. , Knowles N. J. , Wadsworth J. , Bachanek-Bankowska K. , Ngu Ngwa Victor , Morgan K. L. , Bronsvoort B. M. de C.
Published: April 2019

Foot-and-mouth disease (FMD) is a major livestock disease with direct clinical impacts as well as indirect trade implications. Control through vaccination and stamping-out has successfully reduced or eradicated the disease from Europe and large parts of South America. However, sub-Saharan Africa remains endemically affected with 5/7 serotypes currently known to be circulating across the continent. This has significant implications both locally for livestock production and poverty reduction but also globally as it represents a major reservoir of viruses, which could spark new epidemics in disease free countries or vaccination zones. This paper describes the phylodynamics of serotypes A and SAT2 in Africa including recent isolates from Cameroon in Central Africa. We estimated the most recent common ancestor for serotype A was an East African virus from the 1930s (median 1937; HPD 1922–1950) compared to SAT2 which has a much older common ancestor from the early 1700s (median 1709; HPD 1502–1814). Detailed analysis of the different clades shows clearly that different clades are evolving and diffusing across the landscape at different rates with both serotypes having a particularly recent clade that is evolving and spreading more rapidly than other clades within their serotype. However, the lack of detailed sequence data available for Africa seriously limits our understanding of FMD epidemiology across the continent. A comprehensive view of the evolutionary history and dynamics of FMD viruses is essential to understand many basic epidemiological aspects of FMD in Africa such as the scale of persistence and the role of wildlife and thus the opportunities and scale at which vaccination and other controls could be applied. Finally we ask endemic countries to join the OIE/FAO supported regional networks and take advantage of new cheap technologies being rolled out to collect isolates and submit them to the World Reference Laboratory.
The effect of locally delivered cisplatin is dependent on an intact immune function in an experimental glioma model
Authors: Enríquez Pérez Julio , Fritzell Sara , Kopecky Jan , Visse Edward , Darabi Anna , Siesjö Peter
Published: April 2019

Several chemotherapeutic drugs are now considered to exert anti-tumour effects, by inducing an immune-promoting inflammatory response. Cisplatin is a potent chemotherapeutic agent used in standard medulloblastoma but not glioblastoma protocols. There is no clear explanation for the differences in clinical efficacy of cisplatin between medulloblastomas and glioblastomas, despite the fact that cisplatin is effective in vitro against the latter. Systemic toxicity is often dose limiting but could tentatively be reduced by intratumoral administration. We found that intratumoral cisplatin can cure GL261 glioma-bearing C57BL/6 mice and this effect was abolished in GL261-bearing NOD-scid IL2rγnull (NSG) mice. Contrary to previous results with intratumoral temozolomide cisplatin had no additive or synergistic effect with whole cell either GL261 wild-type or GM-CSF-transfected GL261 cells whole cell vaccine-based immunotherapy. While whole tumour cell immunizations increased CD8+ T-cells and decreased F4/80+ macrophages intratumorally, cisplatin had no effect on these cell populations. Taken together, our results demonstrate that intratumoral cisplatin treatment was effective with a narrow therapeutic window and may be an efficient approach for glioma or other brain tumour treatment.
Emotional dysregulation subgroups in patients with adult Attention-Deficit/Hyperactivity Disorder (ADHD): a cluster analytic approach
Authors: Hirsch Oliver , Chavanon Mira Lynn , Christiansen Hanna
Published: April 2019

Emotion regulation deficits (ERD) are evident in about 34–70% of the adults with ADHD. In contrast to this, they are not considered in the diagnostic criteria of the disorder. In a recent study of our research group using confirmatory factor analysis, we modeled positive and negative emotion as well as emotion regulation skills along with the classical ADHD-core symptoms. We showed that negative affect and the failure to apply adaptive emotion regulation skills were distinct and indicative dimensions in adult ADHD. In this study, we used a person-centered approach based on cluster analysis to subtype patients on the presence or relative absence of ERD. This results in important information to individualize treatment decisions. We found two clusters, with cluster 2 showing high ERD that were associated with higher impairments indicated by depressive mood, negative affect and elevated psychological distress. There were also higher rates of comorbidity in cluster 2 such as somatoform disorders which were associated with ERD. Women were overrepresented in this cluster 2. Neuropsychological variables did not contribute significantly to cluster formation. In conclusion, ADHD in adults is a heterogeneous disorder with specific subgroups that need differential treatment approaches.
High intensity training improves cardiac function in healthy rats
Authors: Verboven Maxim , Cuypers Anne , Deluyker Dorien , Lambrichts Ivo , Eijnde Bert O. , Hansen Dominique , Bito Virginie
Published: April 2019

Exercise training is a low cost and safe approach for reducing the risk of cardiovascular disease development. Currently, moderate-intensity training (MIT) is the most preferred exercise type. However, high-intensity interval training (HIIT) is gaining interest especially among athletes and healthy individuals. In this study, we examined cardiac remodeling resulting from MIT and HIIT in healthy rats. Healthy male Sprague-Dawley rats were randomly assigned to MIT or HIIT for 13 weeks. Animals kept sedentary (SED) were used as control. Cardiac function was evaluated with echocardiography and hemodynamic measurements. Heart tissue was stained for capillary density and fibrosis. After 13 weeks of training, only HIIT induced beneficial cardiac hypertrophy. Overall global cardiac parameters (such as ejection fraction, cardiac output and volumes) were improved similarly between both training modalities. At tissue level, collagen content was significantly and similarly reduced in both exercise groups. Finally, only HIIT increased significantly capillary density. Our data indicate that even if very different in design, HIIT and MIT appear to be equally effective in improving cardiac function in healthy rats. Furthermore, HIIT provides additional benefits through improved capillary density and should therefore be considered as a preferred training modality for athletes and for patients.
Serum of patients with acute myocardial infarction prevents inflammation in iPSC-cardiomyocytes
Authors: Sattler Katherine , El-Battrawy Ibrahim , Zhao Zhihan , Schrottenberg Christoph , Yücel Gökhan , Lan Huan , Li Xin , Lang Siegfried , Zimmermann Wolfram-Hubertus , Cyganek Lukas , Utikal Jochen , Wieland Thomas , Ravens Ursula , Bieback Karen , Borggrefe Martin , Zhou Xiaobo , Akin Ibrahim
Published: April 2019

Acute myocardial infarction (MI) evokes a systemic inflammatory response and locally the degradation of the necrotic tissue, followed by scar formation. The mechanisms for containment of the infarct zone are not studied well. The study aimed to examine the response of healthy cardiomyocytes to serum of patients with myocardial infarction. Human iPSC-cardiomyocytes (iPSC-CM) generated from two healthy donors were incubated with serum of patients with MI with and without ventricular fibrillation (VF) or of healthy controls. Different cell adhesion molecules were studied by flow cytometry and immunostaining. Cellular electrophysiology was studied by patch clamp. The cell adhesion molecules CD54/ICAM-1, CD58/LFA-3 and CD321/JAM-A were expressed on iPSC-CM within the plasma membrane. Incubation with serum of MI patients reduced the levels of expression of CD54/ICAM-1 and CD321/JAM-A by 15–20%. VF serum was less effective than serum of MI patients without VF. MI serum or VF serum did not affect resting potential, action potential duration or maximum depolarization velocity. Myocardial infarction serum exerts anti-inflammatory effects on healthy cardiomyocytes without affecting their electrical activity, thus helping to contain the infarct zone and to protect healthy tissue. Ventricular fibrillation during MI drives healthy cardiomyocytes towards a pro-inflammatory phenotype.
Controlling the transverse proton relaxivity of magnetic graphene oxide
Authors: Thapa Bibek , Diaz-Diestra Daysi , Badillo-Diaz Dayra , Sharma Rohit Kumar , Dasari Kiran , Kumari Shalini , Holcomb Mikel B. , Beltran-Huarac Juan , Weiner Brad R. , Morell Gerardo
Published: April 2019

The engineering of materials with controlled magnetic properties by means other than a magnetic field is of great interest in nanotechnology. In this study, we report engineered magnetic graphene oxide (MGO) in the nanocomposite form of iron oxide nanoparticles (IO)-graphene oxide (GO) with tunable core magnetism and magnetic resonance transverse relaxivity (r2). These tunable properties are obtained by varying the IO content on GO. The MGO series exhibits r2 values analogous to those observed in conventional single core and cluster forms of IO in different size regimes—motional averaging regime (MAR), static dephasing regime (SDR), and echo-limiting regime (ELR) or slow motion regime (SMR). The maximum r2 of 162 ± 5.703 mM−1s−1 is attained for MGO with 28 weight percent (wt%) content of IO on GO and hydrodynamic diameter of 414 nm, which is associated with the SDR. These findings demonstrate the clear potential of magnetic graphene oxide for magnetic resonance imaging (MRI) applications.
Effect of regional wind circulation and meteorological factors on long-range migration of mustard aphids over indo-gangetic plain
Authors: Ghosh Sayantan , Roy Arindam , Chatterjee Abhijit , Sikdar Samir Ranjan
Published: April 2019

Mustard aphids are a serious problem for Brassica oilseed in India causing up to 90% of the crop damage. It was hypothesized that Aphids migrate into the Indo Gangetic plain (IGP) from hilly regions of every year. Exact source and migration pattern of this pest is unknown till date. During their long range migration they infested various places over IGP, which fall on their way of migration. The wind, blown from the hilly regions helps aphids to migrate. Meteorological parameters play a crucial role in this migration of aphids. In this study, we have done the 24 hours air-mass backward trajectory at 100 m above ground level (agl) to detect the source regions of mustard aphids. We have found that mainly Western Himalayan hilly regions act as the source of mustard aphids for IGPs. The dependence upon the micro-meteorological parameters and population dynamics are analyzed and discussed elaborately in this work. In this study, we have proposed the ‘Hop and Fly’ behavior of mustard aphid and further discussed how this migrating behavior could help us to reduce the yield loss of Brassica.
Gut resistome plasticity in pediatric patients undergoing hematopoietic stem cell transplantation
Authors: D’Amico Federica , Soverini Matteo , Zama Daniele , Consolandi Clarissa , Severgnini Marco , Prete Arcangelo , Pession Andrea , Barone Monica , Turroni Silvia , Biagi Elena , Brigidi Patrizia , Masetti Riccardo , Rampelli Simone , Candela Marco
Published: April 2019

The gut microbiome of pediatric patients undergoing allo-hematopoietic stem cell transplantation (HSCT) has recently been considered as a potential reservoir of antimicrobial resistance, with important implications in terms of patient mortality rate. By means of shotgun metagenomics, here we explored the dynamics of the gut resistome – i.e. the pattern of antibiotic resistance genes provided by the gut microbiome – in eight pediatric patients undergoing HSCT, half of whom developed acute Graft-versus-Host Disease (aGvHD). According to our findings, the patients developing aGvHD are characterized by post-HSCT expansion of their gut resistome, involving the acquisition of new resistances, as well as the consolidation of those already present before HSCT. Interestingly, the aGvHD-associated bloom in resistome diversity is not limited to genes coding for resistance to the antibiotics administered along the therapeutic course, but rather involves a broad pattern of different resistance classes, including multidrug resistance, as well as resistance to macrolides, aminoglycosides, tetracyclines and beta-lactams. Our data stress the relevance of mapping the gut resistome in HSCT pediatric patients to define the most appropriate anti-infective treatment post HSCT.
A unified and straightforward total synthesis of (+)-porantheridine and (−)-6-epi-porantheridine
Authors: Wang Jiwu , Li Wang , Liu Lixia , Wang Bo , Zhou Yi , Huang Shuangping , Wang Xiaoji
Published: April 2019

A unified asymmetric total synthesis of (+)-porantheridine and (−)-6-epi-porantheridine has been accomplished from a common intermediate.
Down-regulation of MRPS23 inhibits LPS-induced proliferation and invasionviaregulation of the NF-κB signaling pathway in osteosarcoma cells
Authors: Liu Ai-Guo , Xu Ke-Lin , Wang Wei-Lin , Zhou Bing-Kang , Guo Qing-Gong
Published: April 2019

Mitochondrial ribosomal protein S23 (MRPS23), encoded by a nuclear gene, is a participant in the translation of mitochondrial proteins.
A liposomal curcumol nanocomposite for magnetic resonance imaging and endoplasmic reticulum stress-mediated chemotherapy of human primary ovarian cancer
Authors: Wang Jing , Song Yonghong , Zhang Mingxun , Wu Zhensheng , Xu Yun-Jun , Lin Jun , Ling Daishun , Sheng Youjing , Lu Yang , Wu Qiang
Published: April 2019

A liposomal curcumol nanocomposite has been successfully synthesized for the theranostics of human primary ovarian cancer cells from solid tumor tissue in patients.
Surface-controlled dissolution rates: a case study of nanoceria in carboxylic acid solutions
Authors: Grulke Eric A. , Beck Matthew J. , Yokel Robert A. , Unrine Jason M. , Graham Uschi M. , Hancock Matthew L.
Published: April 2019

Nanoparticle dissolution in local milieu can affect its ecotoxicity and therapeutic applications.
Gasdermin D (GSDMD) as a new target for the treatment of infection
Authors: Pandeya Ankit , Li Lan , Li Zhenyu , Wei Yinan
Published: April 2019

Inhibition of pyroptosis through targeting the activation or pore-formation of GSDMD.
Bifunctional oxindole-chromone 4C building block directed asymmetric synthesis of bispirocyclic hexahydroxanthones featuring five contiguous stereocenters and two side-by-side oxindoles
Authors: Liu Xiong-Li , Gong Yi , Chen Shuang , Zuo Xiong , Yao Zhen , Zhou Ying
Published: April 2019

Optically active small molecules based on privileged natural product frameworks and rich in three-dimensional complexity are in high demand.
Why electrostatically enhanced thiourea is better than Schreiner's thiourea in both catalytic activity and regioselectivity?
Authors: Yan Chao-Xian , Wu Rui-Zhi , Lu Ka , Yang Fang-Ling , Yang Xiao-Shan , Wang Rui , Yang Xing , Zhou Pan-Pan , Shao Xiangfeng
Published: April 2019

Electrostatically enhanced thiourea is more active and efficient than Schreiner's thiourea in the ring-opening aminolysis of styrene oxide with aniline, and the underlying reasons were explored by DFT calculations.
Pitch-based carbon/nano-silicon composite, an efficient anode for Li-ion batteries
Authors: Escamilla-Pérez Angel Manuel , Roland Aude , Giraud Sophie , Guiraud Céline , Virieux Héloïse , Demoulin Kévin , Oudart Yohan , Louvain Nicolas , Monconduit Laure
Published: April 2019

Composites are prepared by simple mixture of laser pyrolysed silicon nanoparticles and petroleum pitch, a low cost carbon source. Helped by a homogeneous dispersion of Si nanoparticles into the pitch matrix high stability over cycling is observed.
A two-dimensional GeSe/SnSe heterostructure for high performance thin-film solar cells
Authors: Mao Yuliang , Xu Congsheng , Yuan Jianmei , Zhao Hongquan
Published: April 2019

Based on first-principles calculations, we demonstrated that a GeSe/SnSe heterostructure has a type-II band alignment and a direct band gap. The predicted photoelectric conversion efficiency (PCE) for the GeSe/SnSe heterostructure reaches 21.47%.
Strong, tough, and repeatable adhesion of an alternating peptide comprising phenyl glycine as a repeating unit
Authors: Ihsan Abu Bin , Kawaguchi Yuta , Endo Hiroshi , Koyama Yasuhito
Published: April 2019

An alternating peptide comprising phenyl glycine as a repeating unit skeleton shows strong, tough, and repeatable adhesion originating from its viscoelastic properties and microfibril formation.
Dip-coated colloidal quantum-dot films for high-performance broadband photodetectors
Authors: Shen Ting , Yuan Jifeng , Zhong Xinhua , Tian Jianjun
Published: April 2019

Homogeneous large-area QD films were obtained by a dip-coating method. Photodetectors assembled with these films possess excellent detectivity.
Control of hexagonal boron nitride dielectric thickness by single layer etching
Authors: Ma Zichao , Prawoto Clarissa , Ahmed Zubair , Xiao Ying , Zhang Lining , Zhou Changjian , Chan Mansun
Published: April 2019

Single layer etching of h-BN is achieved using a two-step remote plasma process.
Three-dimensional acoustic sub-diffraction focusing by coiled metamaterials with strong absorption
Authors: Ma Fuyin , Chen Jianyu , Wu Jiu Hui
Published: April 2019

The diffraction limit restricts the smallest diameter of a wave's focal spot in a homogeneous medium to no less than half of the operating wavelength.
Efficacy of traditional Chinese medication Tangminling pill in Chinese patients with type 2 diabetes
Authors: Cheng Jing , Zheng Jia , Liu Yanping , Hao Panpan
Published: April 2019

The morbidity of type 2 diabetes mellitus (T2DM) has been increasing rapidly worldwide. Tangminling pill, consisting of ten Chinese herbal medications, is usually prescribed for T2DM in mainland China. Whether treatment with Tangminling can improve clinical outcomes of T2DM patients was still debated. Four studies comparing Tangminling vs. placebo treatment in T2DM patients were included and 767 T2DM patients were enrolled in our analyses. Tangminling treatment exhibited better efficacy than placebo in reducing hemoglobin A1c (HbA1c) (1.11 vs. 0.32%; pooled weighted mean difference [WMD]: 0.80; 95% confidence interval [CI]: 0.65–0.96; P<0.001), fasting plasma glucose (0.82 vs. −0.40 mM; WMD: 1.10; 95% CI: 0.56–1.64; P<0.001), 2-h postprandial glucose (2-hr PG) (2.81 vs. 1.11 mM; WMD: 1.80; 95% CI: 1.72–1.88; P<0.001), homeostatic model assessment-β level (4.28 vs. 0.41; WMD: 0.44; 95% CI: 0.27–0.61; P<0.001), waist circumference (WC) (1.04 vs. 0.36 cm; WMD: 0.78; 95% CI: 0.37–1.19; P<0.001) and body weight index (0.37 vs. 0.11 kg/m2; WMD: 0.30; 95% CI: −0.00 to 0.61; P=0.05). Tangminling pill might reduce glucose level and body weight and improve β-cell function in T2DM patients. Our study highlights the important role of Tangminling pill in the management of T2DM.
Retrieval-Based Word Learning in Young Typically Developing Children and Children With Development Language Disorder II: A Comparison of Retrieval Schedules
Authors: Haebig Eileen , Leonard Laurence B. , Deevy Patricia , Karpicke Jeffrey , Christ Sharon L. , Usler Evan , Kueser Justin B. , Souto Sofía , Krok Windi , Weber Christine
Published: April 2019

Purpose

Retrieval practice has been found to be a powerful strategy to enhance long-term retention of new information; however, the utility of retrieval practice when teaching young children new words is largely unknown, and even less is known for young children with language impairments. The current study examined the effect of 2 different retrieval schedules on word learning at both the behavioral and neural levels.

Method

Participants included 16 typically developing children (
M
TD
= 61.58 months) and 16 children with developmental language disorder (
M
DLD
= 59.60 months). Children participated in novel word learning sessions in which the spacing of retrieval practice was manipulated: Some words were retrieved only after other words had been presented (i.e., repeated retrieval that required contextual reinstatement [RRCR]); others were taught using an immediate retrieval schedule. In Experiment 1, children's recall of the novel word labels and their meanings was tested after a 5-min delay and a 1-week delay. In Experiment 2, event-related brain potentials were obtained from a match–mismatch task utilizing the novel word stimuli.

Results

Experiment 1 findings revealed that children were able to label referents and to retain the novel words more successfully if the words were taught in the RRCR learning condition. Experiment 2 findings revealed that mismatching picture–word pairings elicited a robust N400 event-related brain potential only for words that were taught in the RRCR condition. In addition, children were more accurate in identifying picture–word matches and mismatches for words taught in the RRCR condition, relative to the immediate retrieval condition.

Conclusions

Retrieval practice that requires contextual reinstatement through spacing results in enhanced word learning and long-term retention of words. Both typically developing children and children with developmental language disorder benefit from this type of retrieval procedure.

Supplemental Material

https://doi.org/10.23641/asha.7927112
Expressive Language in Preschoolers Born Preterm: Results of Language Sample Analysis and Standardized Assessment
Authors: Imgrund Caitlin M. , Loeb Diane F. , Barlow Steven M.
Published: April 2019

Purpose

Preschoolers born preterm are at an increased risk for the development of language impairments. The primary objective of this study was to document the expressive language skills of preschoolers born preterm through 2 assessment procedures, language sample analysis, and standardized assessment. A secondary objective was to investigate the role of nonlinguistic factors in standardized assessment scores.

Method

The language skills of 29 children born preterm (mean gestational age of 31 weeks) were compared to a group of 29 preschoolers born full term. Language samples were collected during free play and objective measures of semantic and grammatical skills were calculated. Likewise, grammatical and semantic measures of language were obtained from a standardized assessment. Information on nonlinguistic factors, including attention, hyperactivity, and nonverbal intelligence quotient, was also collected.

Results

The results of analyses of variance indicated that the children in the PT group had significantly poorer performance than the children born full term on all of the measures of language skill obtained from the language sample analysis. Group differences were found for only 1 measure of language skill obtained from the standardized assessments. Nonverbal factors were not found to account for group differences in assessment scores.

Conclusions

Generally, the children born preterm performed more poorly when language skill was measured via language sample analysis than standardized assessment. These findings underscore the importance of using language sample analysis in conjunction with standardized assessment in the evaluation of children's developing language skills.
Second‐order sequence filter based control algorithm for single‐phase grid interfaced solar PV system
Authors: Rajput Aakanksha , Beniwal Neha , Singh Bhim , Mishra Sukumar
Published: April 2019

This work deals with an implementation of a unique control approach for the power quality enhancement in solar photovoltaic (PV) based grid interfaced system. In this work, a robust control technique with strong filtering capabilities is implemented. A single‐phase two‐stage grid interacted solar PV topology is considered with a second‐order sequence filter as a test system for the validation of the power quality enhancement features. The system constitutes a PV array, a boost converter, a DC link capacitance, a voltage source converter (VSC), an interfacing inductor and a ripple filter. A boost converter is used at a primary stage of proposed topology, which supports the extraction of maximum power from the solar PV array. In addition, the VSC feeds the solar PV power into the grid. It also provides harmonics elimination and power factor correction. A new maximum power point tracking technique avoiding a drift feature is adopted for the fast dynamic performance. The implementation of the solar PV system is performed and the harmonic profile of grid current is observed in compliance to the IEEE‐519 standard.
Carrier‐based PWM control strategy for three‐level indirect matrix converter
Authors: Wang Rutian , Zhong Zhefu , Zhang Jiawei , Wang Weiquan
Published: April 2019

This article proposes a new carrier‐based pulse width modulation (CBPWM) strategy for the control of TLIMC. The duty ratios of the rectifier stage and inverter stage are calculated by the SVPWM method. A carrier is constructed and combined with duty ratios to obtain modulation waves, which are regular and determined by the input voltage and output reference voltage. Then, the modulation waves are compared with the same carrier to obtain pulse signals. The pulse signals are used to produce driving signals of power switches through logic operation. The rectifier stage and inverter stage are controlled by the driving signals to obtain three‐phase symmetrical sinusoidal input and output waveforms. The proposed method is identical in output to the original SVPWM method. Finally, simulation and experimental results are provided to verify the feasibility and validity of the proposed method.
Transit least-squares survey
Authors: Heller René , Rodenbeck Kai , Hippke Michael
Published: April 2019

We apply for the first time the transit least-squares (TLS) algorithm to search for new transiting exoplanets. TLS has been developed as a successor to the box least-squares (BLS) algorithm, which has served as a standard tool for the detection of periodic transits. In this proof-of-concept paper, we demonstrate that TLS finds small planets that have previously been missed. We show the capabilities of TLS using the K2 EVEREST-detrended light curve of the star K2-32 (EPIC 205071984), which has been known to have three transiting planets. TLS detects these known Neptune-sized planets K2-32 b, d, and c in an iterative search and finds an additional transit signal with a high signal detection efficiency (SDETLS) of 26.1 at a period of 4.34882−0.00075+0.00069 d. We show that this additional signal remains detectable (SDETLS = 13.2) with TLS in the K2SFF light curve of K2-32, which includes a less optimal detrending of the systematic trends. The signal is below common detection thresholds if searched with BLS in the K2SFF light curve (SDEBLS = 8.9), however, as in previous searches. Markov chain Monte Carlo sampling with the emcee software shows that the radius of this candidate is 1.01−0.09+0.10 R⊕. We analyzed its phase-folded transit light curve using the vespa software and calculated a false-positive probability FPP = 3.1  × 10−3. Taking into account the multiplicity boost of the system, we estimate an FPP < 3.1  × 10−4, which formally validates K2-32 e as a planet. K2-32 now hosts at least four planets that are very close to a 1:2:5:7 mean motion resonance chain. The offset of the orbital periods of K2-32 e and b from a 1:2 mean motion resonance agrees very well with the sample of transiting multiplanet systems from Kepler, lending further credence to the planetary nature of K2-32 e. We expect that TLS can find many more transits of Earth-sized and even smaller planets in the Kepler and K2 data that have so far remained undetected with algorithms that search for box-like signals.
Comparison on various machinability aspects between mixed and reinforced ceramics when machining hardened steels
Authors: Aouici Hamdi , Elbah Mohamed , Benkhelladi Asma , Fnides Brahim , Boulanouar Lakhdar , Yallese Mohamed Athmane
Published: April 2019

The hard turning process has an attracting interest in different industrial sectors for finishing operations of hard materials. However, it still presents disadvantages with respect to process capability and reliability. This paper describes a comparison of surface roughness, specific cutting force and flank wear between mixed ceramic CC650 (Al2O3 (70%) + TiC (30%)) and reinforced ceramic CC670 (Al2O3 (75%) + SiC (25%)) cutting tools when machining in dry hard turning of AISI 4140, treated at 52 HRC using the response surface methodology (RSM). A mathematical prediction model of the machining responses has been developed in terms of cutting speed, feed rate and cutting time parameters. Experimental observations show that the surface roughness obtained with the mixed ceramic insert significantly improved when compared with reinforced ceramic insert with a ratio of 1.44. In the same way, insert CC650 has better performance compared to reinforced ceramic inserts CC670, in terms of the specific cutting force and flank wear.
On spectral and boundary properties of the volume potential for the Helmholtz equation
Authors: Kalmenov Tynysbek Sharipovich , Ruzhansky Michael , Suragan Durvudkhan
Published: April 2019

In this paper, we study boundary properties and some questions of spectral geometry for certain volume potential type operators (Bessel potential operators) in an open bounded Euclidean domains. In particular, the results can be valid for differential operators, which are related to a nonlocal boundary value problem for the Helmholtz equation, so we obtain isoperimetric inequalities for its eigenvalues as well, namely, analogues of the Rayleigh-Faber-Krahn inequality.
Resilienz aus multifaktorieller Perspektive
Authors: Friederichs Edgar , Kärner Tobias , Ratsch Michaela W. , Friederichs Katja M.
Published: April 2019

In Anlehnung an Gruhl gehen wir im Beitrag von 3 Resilienzfacetten aus, welche die Fähigkeiten beschreiben, dynamisch Veränderungen gestalten zu können, flexibel auf Erfordernisse reagieren zu können sowie sich angemessen von den Erwartungen anderer abgrenzen zu können, d. h., resistent zu sein. Da kein Instrument zur Erfassung dieser Resilienzfacetten vorliegt, setzt sich der Beitrag das Ziel, ein solches fragebogenbasiertes Instrument vorzustellen und interindividuelle Unterschiede herauszuarbeiten. Zur Bearbeitung der Fragestellung wird auf Daten von 200 Personen zurückgegriffen. In den Ergebnissen ließen sich auf Grundlage des multifaktoriellen Resilienzmodells mittels explorativer und konfirmatorischer Faktorenanalyse die 3 Resilienzfacetten Resistenz, Dynamik und Flexibilität identifizieren, welche mit jeweils 4 Items gemessen werden. Zur Identifikation verschiedener Personengruppen, die sich hinsichtlich ihrer Resilienzfacetten unterscheiden, kam eine latente Klassenanalyse zum Einsatz. Implikationen aus unseren Befunden ergeben sich u. a. für die Resilienzförderung in Lern- und Arbeitskontexten, da hieraus erste Ansatzpunkte einer personen- bzw. organisationsspezifischen Förderung gewonnen werden können.