bluuebunny/crossref_metadata_2025 huggingface dataset:
A qualitative study on harmonization of postgraduate medical education in Europe: negotiating flexibility is key
Authors: Van der Aa Jessica E. , Scheele Fedde , Goverde Angelique J. , Teunissen Pim W.
Published: July 2019

Introduction International harmonization of postgraduate medical education is gaining importance in the globalization of medical education. Harmonization is regarded as the establishment of common standards in education, while maintaining regional or local freedom to adapt training to contexts. During the development of a harmonized curriculum, tensions between standardization and contextualization may surface. To allow future harmonization projects to recognize these tensions and deal with them in a timely manner, this study aims to gain insight into tensions that may arise when developing a harmonized curriculum for postgraduate medical education in Obstetrics and Gynaecology in Europe.
Methods Focus groups were held with international curriculum developers to discuss challenges that resulted from tensions between standardization and contextualization when developing a harmonized European curriculum for postgraduate medical education in Obstetrics and Gynaecology. Data were analyzed through conventional content analysis, using the principles of template analysis.
Results and Discussion Tensions between standardization and contextualization in the development of a harmonized curriculum were apparent in two domains: 1) Varying ideas about what the harmonized curriculum means for the current curriculum and 2) Inconsistencies between educational principles and the reality of training. Additionally, we identified ways of dealing with these tensions, which were characterized as ‘negotiating flexibility’. Tensions between standardization and contextualization surfaced in the development phase of harmonizing a curriculum, partly because it was anticipated that there would be problems when implementing the curriculum.
Public perceptions of the rights of persons with disability
Authors: McConkey Roy
Published: July 2019

Since 2006, three nationally representative surveys in Ireland have assessed public agreement to three rights inherent in the UNCRPD (United Nations Convention on the Rights of Persons with Disabilities): attendance at ordinary schools, to have sexual fulfilment and to have children. Three questions are posed in this paper: do the Irish public perceive people with different impairments as having the same rights? Are they more supportive of certain rights than others? How has public perceptions changed in 2017? The Irish public are more sympathetic to the rights of persons with physical and sensorial disabilities than to those with cognitive or emotional impairments. They are more supportive of people having sexual fulfilment than they are of school attendance. By 2017 they were more supportive of these rights and especially those of people with mental health difficulties. Monitoring public perceptions nationally would help to inform the advocacy and awareness raising efforts needed to make the public allies in achieving the Convention’s aims.
Cortec Mining Kenya Limited, Cortec (Pty) Limited, and Stirling Capital Limited v. Republic of Kenya
Authors: Cotula Lorenzo , Gathii James T.
Published: July 2019

In Cortec v. Kenya, an investor-state arbitral tribunal established under a bilateral investment treaty (BIT) held it lacked jurisdiction to hear a dispute concerning a mining project that the tribunal found did not comply with domestic environmental law. The award raises significant issues of public international law, including how questions of investor compliance are considered in investor-state dispute settlement and the legal implications of investor noncompliance. The issues resonate with wider debates about balancing investor rights and obligations in the international investment regime.
Case of Barrios Altos and La Cantuta v. Peru
Authors: Contesse Jorge
Published: July 2019

On May 30, 2018, the Inter-American Court of Human Rights (Court) ordered Peru to review the presidential pardon granted to former president and dictator Alberto Fujimori, who had been convicted and imprisoned for his role in serious human rights violations. The Peruvian Supreme Court obliged and, after examining the merits of the presidential pardon through a special procedure set up to assess the pardon's conformity with international human rights law, invalidated the pardon, effectively reinstating Fujimori's imprisonment for crimes against humanity.
Fast and slow points of Birkhoff sums
Authors: BAYART FRÉDÉRIC , BUCZOLICH ZOLTÁN , HEURTEAUX YANICK
Published: July 2019

We investigate the growth rate of the Birkhoff sums $S_{n,\unicode[STIX]{x1D6FC}}f(x)=\sum _{k=0}^{n-1}f(x+k\unicode[STIX]{x1D6FC})$, where $f$ is a continuous function with zero mean defined on the unit circle $\mathbb{T}$ and $(\unicode[STIX]{x1D6FC},x)$ is a ‘typical’ element of $\mathbb{T}^{2}$. The answer depends on the meaning given to the word ‘typical’. Part of the work will be done in a more general context.
Cognitive bias in professional hand hygiene and feedback: A national online-survey on overconfidence in Germany
Authors: Bushuven Stefan , Weidenbusch Marc , Mohr Stefan , Delis Achilles , Fischer Martin R. , Juenger Jana , Dettenkofer Markus
Published: July 2019

To evaluate learning motivation barriers in infection control and feedback competences, we conducted a national online survey in Germany. Among 767 healthcare workers, overconfidence effects could be detected independent from age, gender, profession, education, and hospital-size. The identified effects may impair learning motivation relevant for supervisors and educators in infection control.
Things as They Seem
Authors: Scruton Roger
Published: July 2019

I respond to the five papers of criticism in this issue of Philosophy. I argue that my cognitive dualism, which may be open to the theological objections levelled by Fiona Ellis, is vindicated by its ability to explain both freedom and inter-personal relations. I defend the inter-subjectivity of aesthetic judgment against Simon Blackburn's argument from ‘the acquaintance principle’, and my vision of cultural decline against the sceptical arguments of Samuel Hughes. The crucial role played by subjectivity in my fiction, discussed by Alicja Gescinska, enables me to add to David McPherson's account of existential conservatism, with which I largely concur. I end on a note of puzzlement, as to why such innocent arguments should be the target of such implacable hatred.
Compact filtering power dividers with wide upper stopband
Authors: Dong Gaoya , Wang Weimin , Liu Yuanan
Published: July 2019

A series of compact filtering power dividers (FPDs) with simple layouts are proposed based on coupling topology. The structure of the presented FPD1 is composed of three resonators and one isolating resistor. These FPDs can be designed based on coupling matrix filter theory. A half-wave transmission line is employed in FPD2 to introduce a transmission zero (TZ) locating at 1.27f0. The FPD3 is designed by replacing quarter-wave transmission lines in FPD2 with quarter-wave coupled lines, which will produce a TZ locating at 1.96 f0 and extend upper stopband bandwidth. For verification, three FPDs centered at 2.45 GHz are fabricated and measured. All measured results are in good agreement with the full-wave simulation results.
Stress and Coping in Pediatric Asthma: The Experiences of Low-SES Latinx Families
Authors: Rodríguez Erin M. , Gulbas Lauren E. , Horner Sharon D. , Alba-Suarez Juliana , George-Jones Julia , Davidson Savannah , Lehning Emily , Esperanza Catherine , Alvarado Cinthia
Published: July 2019

Objective: Low-socioeconomic status (SES) Latinx youth experience disproportionate rates of poor asthma control, which can disrupt school, work, and quality of life. The current study examined low-SES Latinx families’ experiences of asthma-related stress and coping to inform intervention approaches with this population. Method: We used a sequential mixed-method design, with qualitative findings used to enrich interpretation of quantitative results. Cross-sectional quantitative data was collected from low-SES Latinx youth with asthma ages 9–17 and their parents ( N = 39), who reported on their levels of asthma-related stressors and their coping with asthma. Focus groups were conducted with additional low-SES Latinx youth with asthma and their parents ( N = 11). Qualitative data were coded using a grounded theory approach. Results: Parents reported higher levels of asthma-related stressors than children. Higher levels of stress were correlated with less secondary control coping for children, and less primary and secondary control coping for parents. SES-relevant processes (e.g., health literacy) and Latinx-relevant processes (e.g., spirituality, transnational health care) shaped families’ experiences of asthma-related stressors and coping. Conclusions: Findings highlight the challenges of controlling asthma and the consequences of poorly controlled asthma, as well as potential intervention strategies to support asthma management and psychosocial adjustment for low-SES Latinx families.

Implications for Impact Statement

This study examined the stress and coping experiences of low-SES Latinx families of children with asthma. Coping that involved trying to change stressors (for parents) or trying to adapt to stressors (for children and parents) was related to lower levels of asthma-related stress. It may be helpful for clinicians to leverage cultural factors such as spirituality to promote more effective coping and asthma management in low-SES Latinx families.
Caspase-2 and p75 neurotrophin receptor (p75NTR) are involved in the regulation of SREBP and lipid genes in hepatocyte cells
Authors: Pham Dan Duc , Bruelle Céline , Thi Do Hai , Pajanoja Ceren , Jin Congyu , Srinivasan Vignesh , Olkkonen Vesa M. , Eriksson Ove , Jauhiainen Matti , Lalowski Maciej , Lindholm Dan
Published: July 2019

Lipid-induced toxicity is part of several human diseases, but the mechanisms involved are not fully understood. Fatty liver is characterized by the expression of different growth and tissue factors. The neurotrophin, nerve growth factor (NGF) and its pro-form, pro-NGF, are present in fatty liver together with p75 neurotrophin receptor (p75NTR). Stimulation of human Huh7 hepatocyte cells with NGF and pro-NGF induced Sterol-regulator-element-binding protein-2 (SREBP2) activation and increased Low-Density Lipoprotein Receptor (LDLR) expression. We observed that phosphorylation of caspase-2 by p38 MAPK was essential for this regulation involving a caspase-3-mediated cleavage of SREBP2. RNA sequencing showed that several genes involved in lipid metabolism were altered in p75NTR-deficient mouse liver. The same lipogenic genes were downregulated in p75NTR gene-engineered human Huh7 cells and reciprocally upregulated by stimulation of p75NTRs. In the knock-out mice the serum cholesterol and triglyceride levels were reduced, suggesting a physiological role of p75NTRs in whole-body lipid metabolism. Taken together, this study shows that p75NTR signaling influences a network of genes involved in lipid metabolism in liver and hepatocyte cells. Modulation of p75NTR signaling may be a target to consider in various metabolic disorders accompanied by increased lipid accumulation.
Cell-free DNA analysis in healthy individuals by next-generation sequencing: a proof of concept and technical validation study
Authors: Alborelli Ilaria , Generali Daniele , Jermann Philip , Cappelletti Maria Rosa , Ferrero Giuseppina , Scaggiante Bruna , Bortul Marina , Zanconati Fabrizio , Nicolet Stefan , Haegele Jasmin , Bubendorf Lukas , Aceto Nicola , Scaltriti Maurizio , Mucci Giuseppe , Quagliata Luca , Novelli Giuseppe
Published: July 2019

Pre-symptomatic screening of genetic alterations might help identify subpopulations of individuals that could enter into early access prevention programs. Since liquid biopsy is minimally invasive it can be used for longitudinal studies in healthy volunteers to monitor events of progression from normal tissue to pre-cancerous and cancerous condition. Yet, cell-free DNA (cfDNA) analysis in healthy individuals comes with substantial challenges such as the lack of large cohort studies addressing the impact of mutations in healthy individuals or the low abundance of cfDNA in plasma. In this study, we aimed to investigate the technical feasibility of cfDNA analysis in a collection of 114 clinically healthy individuals. We first addressed the impact of pre-analytical factors such as cfDNA yield and quality on sequencing performance and compared healthy to cancer donor samples. We then confirmed the validity of our testing strategy by evaluating the mutational status concordance in matched tissue and plasma specimens collected from cancer patients. Finally, we screened our group of healthy donors for genetic alterations, comparing individuals who did not develop any tumor to patients who developed either a benign neoplasm or cancer during 1–10 years of follow-up time. To conclude, we have established a rapid and reliable liquid biopsy workflow that allowed us to study genomic alterations with a limit of detection as low as 0.08% of variant allelic frequency in healthy individuals. We detected pathogenic cancer mutations in four healthy donors that later developed a benign neoplasm or invasive breast cancer up to 10 years after blood collection. Even though larger prospective studies are needed to address the specificity and sensitivity of liquid biopsy as a clinical tool for early cancer detection, systematic screening of healthy individuals will help understanding early events of tumor formation.
Discovery of N-phenyl-(2,4-dihydroxypyrimidine-5-sulfonamido) phenylurea-based thymidylate synthase (TS) inhibitor as a novel multi-effects antitumor drugs with minimal toxicity
Authors: Li Xin-yang , Zhang Ting-jian , Kamara Mohamed Olounfeh , Lu Guo-qing , Xu Hai-li , Wang De-pu , Meng Fan-hao
Published: July 2019

Thymidylate synthase (TS) is a hot target for tumor chemotherapy, and its inhibitors are an essential direction for anti-tumor drug research. To our knowledge, currently, there are no reported thymidylate synthase inhibitors that could inhibit cancer cell migration. Therefore, for optimal therapeutic purposes, combines our previous reports and findings, we hope to obtain a multi-effects inhibitor. This study according to the principle of flattening we designed and synthesized 18 of N-phenyl-(2,4-dihydroxypyrimidine-5-sulfonamido)phenyl urea derivatives as multi-effects inhibitors. The biological evaluation results showed that target compounds could significantly inhibit the hTS enzyme, BRaf kinase and EGFR kinase activity in vitro, and most of the compounds had excellent anti-cell viability for six cancer cell lines. Notably, the candidate compound L14e (IC50 = 0.67 μM) had the superior anti-cell viability and safety to A549 and H460 cells compared with pemetrexed. Further studies had shown that L14e could cause G1/S phase arrest then induce intrinsic apoptosis. Transwell, western blot, and tube formation results proved that L14e could inhibit the activation of the EGFR signaling pathway, then ultimately achieve the purpose of inhibiting cancer cell migration and angiogenesis in cancer tissues. Furthermore, in vivo pharmacology evaluations of L14e showed significant antitumor activity in A549 cells xenografts with minimal toxicity. All of these results demonstrated that the L14e has the potential for drug discovery as a multi-effects inhibitor and provides a new reference for clinical treatment of non-small cell lung cancer.
A next-generation sequencing method for gene doping detection that distinguishes low levels of plasmid DNA against a background of genomic DNA
Authors: de Boer Eddy N. , van der Wouden Petra E. , Johansson Lennart F. , van Diemen Cleo C. , Haisma Hidde J.
Published: July 2019

Gene doping confers health risks for athletes and is a threat to fair competition in sports. Therefore the anti-doping community has given attention on its detection. Previously published polymerase chain reaction-based methodologies for gene doping detection are targeting exon–exon junctions in the intron-less transgene. However, because these junctions are known, it would be relatively easy to evade detection by tampering with the copyDNA sequences. We have developed a targeted next-generation sequencing based assay for the detection of all exon–exon junctions of the potential doping genes,EPO,IGF1,IGF2,GH1,andGH2, which is resistant to tampering. Using this assay, all exon–exon junctions of copyDNA of doping genes could be detected with a sensitivity of 1296 copyDNA copies in 1000 ng of genomic DNA. In addition, promotor regions and plasmid-derived sequences are readily detectable in our sequence data. While we show the reliability of our method for a selection of genes, expanding the panel to detect other genes would be straightforward. As we were able to detect plasmid-derived sequences, we expect that genes with manipulated junctions, promotor regions, and plasmid or virus-derived sequences will also be readily detected.
Author Correction: Building a global alliance of biofoundries
Authors: Hillson Nathan , Caddick Mark , Cai Yizhi , Carrasco Jose A. , Chang Matthew Wook , Curach Natalie C. , Bell David J. , Feuvre Rosalind Le , Friedman Douglas C. , Fu Xiongfei , Gold Nicholas D. , Herrgård Markus J. , Holowko Maciej B. , Johnson James R. , Johnson Richard A. , Keasling Jay D. , Kitney Richard I. , Kondo Akihiko , Liu Chenli , Martin Vincent J. J. , Menolascina Filippo , Ogino Chiaki , Patron Nicola J. , Pavan Marilene , Poh Chueh Loo , Pretorius Isak S. , Rosser Susan J. , Scrutton Nigel S. , Storch Marko , Tekotte Hille , Travnik Evelyn , Vickers Claudia E. , Yew Wen Shan , Yuan Yingjin , Zhao Huimin , Freemont Paul S.
Published: July 2019

The original version of this Comment contained errors in the legend of Figure 2, in which the locations of the fifteenth and sixteenth GBA members were incorrectly given as ‘(15) Australian Genome Foundry, Macquarie University; (16) Australian Foundry for Advanced Biomanufacturing, University of Queensland.’. The correct version replaces this with ‘(15) Australian Foundry for Advanced Biomanufacturing (AusFAB), University of Queensland and (16) Australian Genome Foundry, Macquarie University’. This has been corrected in both the PDF and HTML versions of the Comment.
NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region
Authors: Oldfield Andrew J. , Henriques Telmo , Kumar Dhirendra , Burkholder Adam B. , Cinghu Senthilkumar , Paulet Damien , Bennett Brian D. , Yang Pengyi , Scruggs Benjamin S. , Lavender Christopher A. , Rivals Eric , Adelman Karen , Jothi Raja
Published: July 2019

Faithful transcription initiation is critical for accurate gene expression, yet the mechanisms underlying specific transcription start site (TSS) selection in mammals remain unclear. Here, we show that the histone-fold domain protein NF-Y, a ubiquitously expressed transcription factor, controls the fidelity of transcription initiation at gene promoters in mouse embryonic stem cells. We report that NF-Y maintains the region upstream of TSSs in a nucleosome-depleted state while simultaneously protecting this accessible region against aberrant and/or ectopic transcription initiation. We find that loss of NF-Y binding in mammalian cells disrupts the promoter chromatin landscape, leading to nucleosomal encroachment over the canonical TSS. Importantly, this chromatin rearrangement is accompanied by upstream relocation of the transcription pre-initiation complex and ectopic transcription initiation. Further, this phenomenon generates aberrant extended transcripts that undergo translation, disrupting gene expression profiles. These results suggest NF-Y is a central player in TSS selection in metazoans and highlight the deleterious consequences of inaccurate transcription initiation.
Crystal structures of Rea1-MIDAS bound to its ribosome assembly factor ligands resembling integrin–ligand-type complexes
Authors: Ahmed Yasar Luqman , Thoms Matthias , Mitterer Valentin , Sinning Irmgard , Hurt Ed
Published: July 2019

The Rea1 AAA+-ATPase dislodges assembly factors from pre-60S ribosomes upon ATP hydrolysis, thereby driving ribosome biogenesis. Here, we present crystal structures of Rea1-MIDAS, the conserved domain at the tip of the flexible Rea1 tail, alone and in complex with its substrate ligands, the UBL domains of Rsa4 or Ytm1. These complexes have structural similarity to integrin α-subunit domains when bound to extracellular matrix ligands, which for integrin biology is a key determinant for force-bearing cell–cell adhesion. However, the presence of additional motifs equips Rea1-MIDAS for its tasks in ribosome maturation. One loop insert cofunctions as an NLS and to activate the mechanochemical Rea1 cycle, whereas an additional β-hairpin provides an anchor to hold the ligand UBL domains in place. Our data show the versatility of the MIDAS fold for mechanical force transmission in processes as varied as integrin-mediated cell adhesion and mechanochemical removal of assembly factors from pre-ribosomes.
Strain-level metagenomic assignment and compositional estimation for long reads with MetaMaps
Authors: Dilthey Alexander T. , Jain Chirag , Koren Sergey , Phillippy Adam M.
Published: July 2019

Metagenomic sequence classification should be fast, accurate and information-rich. Emerging long-read sequencing technologies promise to improve the balance between these factors but most existing methods were designed for short reads. MetaMaps is a new method, specifically developed for long reads, capable of mapping a long-read metagenome to a comprehensive RefSeq database with >12,000 genomes in <16 GB or RAM on a laptop computer. Integrating approximate mapping with probabilistic scoring and EM-based estimation of sample composition, MetaMaps achieves >94% accuracy for species-level read assignment and r2 > 0.97 for the estimation of sample composition on both simulated and real data when the sample genomes or close relatives are present in the classification database. To address novel species and genera, which are comparatively harder to predict, MetaMaps outputs mapping locations and qualities for all classified reads, enabling functional studies (e.g. gene presence/absence) and detection of incongruities between sample and reference genomes.
Practical access to axially chiral sulfonamides and biaryl amino phenols via organocatalytic atroposelective N-alkylation
Authors: Lu Shenci , Ng Shawn Voon Hwee , Lovato Kaitlyn , Ong Jun-Yang , Poh Si Bei , Ng Xiao Qian , Kürti László , Zhao Yu
Published: July 2019

The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic N-alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral N-aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis.
Regulation of tumor angiogenesis and mesenchymal–endothelial transition by p38α through TGF-β and JNK signaling
Authors: Batlle Raquel , Andrés Eva , Gonzalez Lorena , Llonch Elisabet , Igea Ana , Gutierrez-Prat Núria , Berenguer-Llergo Antoni , Nebreda Angel R.
Published: July 2019

The formation of new blood vessels is essential for normal development, tissue repair and tumor growth. Here we show that inhibition of the kinase p38α enhances angiogenesis in human and mouse colon tumors. Mesenchymal cells can contribute to tumor angiogenesis by regulating proliferation and migration of endothelial cells. We show that p38α negatively regulates an angiogenic program in mesenchymal stem/stromal cells (MSCs), multipotent progenitors found in perivascular locations. This program includes the acquisition of an endothelial phenotype by MSCs mediated by both TGF-β and JNK, and negatively regulated by p38α. Abrogation of p38α in mesenchymal cells increases tumorigenesis, which correlates with enhanced angiogenesis. Using genetic models, we show that p38α regulates the acquisition of an endothelial-like phenotype by mesenchymal cells in colon tumors and damage tissue. Taken together, our results indicate that p38α in mesenchymal cells restrains a TGF-β-induced angiogenesis program including their ability to transdifferentiate into endothelial cells.
Structures of autoinhibited and polymerized forms of CARD9 reveal mechanisms of CARD9 and CARD11 activation
Authors: Holliday Michael J. , Witt Axel , Rodríguez Gama Alejandro , Walters Benjamin T. , Arthur Christopher P. , Halfmann Randal , Rohou Alexis , Dueber Erin C. , Fairbrother Wayne J.
Published: July 2019

CARD9 and CARD11 drive immune cell activation by nucleating Bcl10 polymerization, but are held in an autoinhibited state prior to stimulation. Here, we elucidate the structural basis for this autoinhibition by determining the structure of a region of CARD9 that includes an extensive interface between its caspase recruitment domain (CARD) and coiled-coil domain. We demonstrate, for both CARD9 and CARD11, that disruption of this interface leads to hyperactivation in cells and to the formation of Bcl10-templating filaments in vitro, illuminating the mechanism of action of numerous oncogenic mutations of CARD11. These structural insights enable us to characterize two similar, yet distinct, mechanisms by which autoinhibition is relieved in the course of canonical CARD9 or CARD11 activation. We also dissect the molecular determinants of helical template assembly by solving the structure of the CARD9 filament. Taken together, these findings delineate the structural mechanisms of inhibition and activation within this protein family.
Interface-based tuning of Rashba spin-orbit interaction in asymmetric oxide heterostructures with 3d electrons
Authors: Lin Weinan , Li Lei , Doğan Fatih , Li Changjian , Rotella Hélène , Yu Xiaojiang , Zhang Bangmin , Li Yangyang , Lew Wen Siang , Wang Shijie , Prellier Wilfrid , Pennycook Stephen J. , Chen Jingsheng , Zhong Zhicheng , Manchon Aurelien , Wu Tom
Published: July 2019

The Rashba effect plays important roles in emerging quantum materials physics and potential spintronic applications, entailing both the spin orbit interaction (SOI) and broken inversion symmetry. In this work, we devise asymmetric oxide heterostructures of LaAlO3//SrTiO3/LaAlO3 (LAO//STO/LAO) to study the Rashba effect in STO with an initial centrosymmetric structure, and broken inversion symmetry is created by the inequivalent bottom and top interfaces due to their opposite polar discontinuities. Furthermore, we report the observation of a transition from the cubic Rashba effect to the coexistence of linear and cubic Rashba effects in the oxide heterostructures, which is controlled by the filling of Ti orbitals. Such asymmetric oxide heterostructures with initially centrosymmetric materials provide a general strategy for tuning the Rashba SOI in artificial quantum materials.
Bio-inspired creation of heterogeneous reaction vessels via polymerization of supramolecular ion pair
Authors: Dong Ke , Sun Qi , Tang Yongquan , Shan Chuan , Aguila Briana , Wang Sai , Meng Xiangju , Ma Shengqian , Xiao Feng-Shou
Published: July 2019

Precise control of the outer-sphere environment around the active sites of heterogeneous catalysts to modulate the catalytic outcomes has long been a challenge. Here, we demonstrate how this can be fulfilled by encapsulating catalytic components into supramolecular capsules, used as building blocks for materials synthesis, whereby the microenvironment of each active site is tuned by the assembled wall. Specifically, using a cationic template equipped with a polymerizable functionality, anionic ligands can be encapsulated by ion pair-directed supramolecular assembly, followed by construction into porous frameworks. The hydrophilic ionic wall enables reactions to be achieved in water that usually requires organic solvents and also facilitates the enrichment of the substrate into the hydrophobic pocket, leading to superior catalytic performances as demonstrated by the industrially relevant hydroformylation. Remarkably, the formation of the supramolecular assembly and catalyst encapsulation further engenders reaction selectivity, which reaches an even greater extent after construction of the porous framework.
High-throughput computational discovery of In2Mn2O7 as a high Curie temperature ferromagnetic semiconductor for spintronics
Authors: Chen Wei , George Janine , Varley Joel B. , Rignanese Gian-Marco , Hautier Geoffroy
Published: July 2019

Materials combining strong ferromagnetism and good semiconducting properties are highly desirable for spintronic applications (e.g., in spin-filtering devices). In this work, we conduct a search for concentrated ferromagnetic semiconductors through high-throughput computational screening. Our screening reveals the limited availability of semiconductors combining ferromagnetism and a low effective mass. We identify the manganese pyrochlore oxide In2Mn2O7 as especially promising for spin transport as it combines low electron effective mass (0.29 m0), a large exchange splitting of the conduction band (1.1 eV), stability in air, and a Curie temperature (about 130 K) among the highest of concentrated ferromagnetic semiconductors. We rationalise the high performance of In2Mn2O7 by the unique combination of a pyrochlore lattice favouring ferromagnetism with an adequate alignment of O–2p, Mn–3d, and In–5s forming a dispersive conduction band while enhancing the Curie temperature.
Adherence to guideline recommendations for asthma care in community pharmacies: actual and needed performance
Authors: Kuipers Esther , Wensing Michel , Wong-Go Elaine , Daemen Bernard J. G. , De Smet Peter A. G. M. , Teichert Martina
Published: July 2019

Pharmaceutical care guidelines aim to provide recommendations for pharmaceutical care, reduce unwanted pharmacy practice variation and ultimately improve the quality of healthcare. This study evaluated community pharmacists’ adherence to recommendations for the provision of care to asthma patients with first dispensing and follow-up refill encounters in The Netherlands. Data were pharmacists’ self-assessment of adherence to guideline recommendations, independent observations of dispensing encounters and a nationwide questionnaire on pharmacists’ views on the desirable (clinical) necessity of applying guideline recommendations to their patient population. The 21 pharmacists who performed self-assessment judged their adherence concerning inhalation instructions as high. The lowest scores were reported for recommendations to collect additional information on the type of lung disease and for asking patients’ expectations, wishes and concerns. Sixty-eight dispensing encounters were observed. In 83% of the 35 first dispensing observations, inhalation instruction was provided. This percentage was lower (62%) at refill dispensings. During all encounters, pharmacy staff seldom explored patients’ perceptions or responded to patients’ expectations, wishes and concerns. One hundred and four pharmacists completed the feasibility questionnaire. Pharmacists judged that all patients should receive inhalation instruction at first dispensing. They regarded it necessary to check on patients’ expectations, wishes and concerns regarding the treatment for only up to 70% of the patients. More efforts on guideline implementation are needed, especially on follow-up dispensings and on gaining relevant information from patients and other healthcare professionals. Pharmacists still have opportunities to grow in applying a patient-tailored approach and exploring patients’ individual needs, rather than providing practical information.
Predicting the loss of organic archaeological deposits at a regional scale in Greenland
Authors: Hollesen Jørgen , Matthiesen Henning , Fenger-Nielsen Rasmus , Abermann Jakob , Westergaard-Nielsen Andreas , Elberling Bo
Published: July 2019

Across the Arctic, microbial degradation is actively destroying irreplaceable cultural and environmental records that have been preserved within archaeological deposits for millennia. Because it is not possible to survey the many sites in this remote part of the world, new methods are urgently needed to detect and assess the potential degradation. Here, we investigate organic deposits at seven archaeological sites located along the dominating west-east climatic gradient in West Greenland. We show that, regardless of age, depositional history and environmental conditions, all organic deposits are highly vulnerable to degradation. A state-of-the-art model that simulates the effect of future climate change on degradation indicates that 30–70% of the archaeological fraction of organic carbon (OC) could disappear within the next 80 years. This range reflects the variation within the climatic gradient and the future climate scenario applied (RCP 4.5 and RCP 8.5). All archaeological deposits are expected to experience a substantial loss, but the most rapid degradation seems to occur in the continental inland areas of the region, dominated by dry and warm summers. This suggests that organic remains from the Norse Viking Age settlers are especially under threat in the coming years.
Quantification of the flux of tyrosine pathway metabolites during nitisinone treatment of Alkaptonuria
Authors: Milan A. M. , Hughes A. T. , Davison A. S. , Khedr M. , Rovensky J. , Psarelli E. E. , Cox T. F. , Rhodes N. P. , Gallagher J. A. , Ranganath L. R.
Published: July 2019

Nitisinone decreases homogentisic acid (HGA) in Alkaptonuria (AKU) by inhibiting the tyrosine metabolic pathway in humans. The effect of different daily doses of nitisinone on circulating and 24 h urinary excretion of phenylalanine (PA), tyrosine (TYR), hydroxyphenylpyruvate (HPPA), hydroxyphenyllactate (HPLA) and HGA in patients with AKU was studied over a four week period. Forty AKU patients, randomised into five groups of eight patients, received doses of 1, 2, 4 or 8 mg of nitisinone daily, or no drug (control). Metabolites were analysed by tandem mass spectrometry in 24 h urine and serum samples collected before and after nitisinone. Serum metabolites were corrected for total body water and the sum of 24 hr urine plus total body water metabolites of PA, TYR, HPPA, HPLA and HGA were determined. Body weight and urine urea were used to check on stability of diet and metabolism over the 4 weeks of study. The sum of quantities of urine metabolites (PA, TYR, HPPA, HPLA and HGA) were similar pre- and post-nitisinone. The sum of total body water metabolites were significantly higher post-nitisinone (p < 0.0001) at all doses. Similarly, combined 24 hr urine:total body water ratios for all analytes were significantly higher post-nitisinone, compared with pre-nitisinone baseline for all doses (p = 0.0002 – p < 0.0001). Significantly higher concentrations of metabolites from the tyrosine metabolic pathway were observed in a dose dependant manner following treatment with nitisinone and we speculate that, for the first time, experimental evidence of the metabolite pool that would otherwise be directed towards pigment formation, has been unmasked.
Comparative Brain Morphology of the Greenland and Pacific Sleeper Sharks and its Functional Implications
Authors: Yopak Kara E. , McMeans Bailey C. , Mull Christopher G. , Feindel Kirk W. , Kovacs Kit M. , Lydersen Christian , Fisk Aaron T. , Collin Shaun P.
Published: July 2019

In cartilaginous fishes, variability in the size of the brain and its major regions is often associated with primary habitat and/or specific behavior patterns, which may allow for predictions on the relative importance of different sensory modalities. The Greenland (Somniosus microcephalus) and Pacific sleeper (S.pacificus) sharks are the only non-lamnid shark species found in the Arctic and are among the longest living vertebrates ever described. Despite a presumed visual impairment caused by the regular presence of parasitic ocular lesions, coupled with the fact that locomotory muscle power is often depressed at cold temperatures, these sharks remain capable of capturing active prey, including pinnipeds. Using magnetic resonance imaging (MRI), brain organization ofS.microcephalusandS.pacificuswas assessed in the context of up to 117 other cartilaginous fish species, using phylogenetic comparative techniques. Notably, the region of the brain responsible for motor control (cerebellum) is small and lacking foliation, a characteristic not yet described for any other large-bodied (>3 m) shark. Further, the development of the optic tectum is relatively reduced, while olfactory brain regions are among the largest of any shark species described to date, suggestive of an olfactory-mediated rather than a visually-mediated lifestyle.
Integration of machine learning and mechanistic models accurately predicts variation in cell density of glioblastoma using multiparametric MRI
Authors: Gaw Nathan , Hawkins-Daarud Andrea , Hu Leland S. , Yoon Hyunsoo , Wang Lujia , Xu Yanzhe , Jackson Pamela R. , Singleton Kyle W. , Baxter Leslie C. , Eschbacher Jennifer , Gonzales Ashlyn , Nespodzany Ashley , Smith Kris , Nakaji Peter , Mitchell J. Ross , Wu Teresa , Swanson Kristin R. , Li Jing
Published: July 2019

Glioblastoma (GBM) is a heterogeneous and lethal brain cancer. These tumors are followed using magnetic resonance imaging (MRI), which is unable to precisely identify tumor cell invasion, impairing effective surgery and radiation planning. We present a novel hybrid model, based on multiparametric intensities, which combines machine learning (ML) with a mechanistic model of tumor growth to provide spatially resolved tumor cell density predictions. The ML component is an imaging data-driven graph-based semi-supervised learning model and we use the Proliferation-Invasion (PI) mechanistic tumor growth model. We thus refer to the hybrid model as the ML-PI model. The hybrid model was trained using 82 image-localized biopsies from 18 primary GBM patients with pre-operative MRI using a leave-one-patient-out cross validation framework. A Relief algorithm was developed to quantify relative contributions from the data sources. The ML-PI model statistically significantly outperformed (p < 0.001) both individual models, ML and PI, achieving a mean absolute predicted error (MAPE) of 0.106 ± 0.125 versus 0.199 ± 0.186 (ML) and 0.227 ± 0.215 (PI), respectively. Associated Pearson correlation coefficients for ML-PI, ML, and PI were 0.838, 0.518, and 0.437, respectively. The Relief algorithm showed the PI model had the greatest contribution to the result, emphasizing the importance of the hybrid model in achieving the high accuracy.
Decomposition of sediment-oil-agglomerates in a Gulf of Mexico sandy beach
Authors: Bociu Ioana , Shin Boryoung , Wells Wm. Brian , Kostka Joel E. , Konstantinidis Konstantinos T. , Huettel Markus
Published: July 2019

Sediment-oil-agglomerates (SOA) are one of the most common forms of contamination impacting shores after a major oil spill; and following the Deepwater Horizon (DWH) accident, large numbers of SOAs were buried in the sandy beaches of the northeastern Gulf of Mexico. SOAs provide a source of toxic oil compounds, and although SOAs can persist for many years, their long-term fate was unknown. Here we report the results of a 3-year in-situ experiment that quantified the degradation of standardized SOAs buried in the upper 50 cm of a North Florida sandy beach. Time series of hydrocarbon mass, carbon content, n-alkanes, PAHs, and fluorescence indicate that the decomposition of golf-ball-size DWH-SOAs embedded in beach sand takes at least 32 years, while SOA degradation without sediment contact would require more than 100 years. SOA alkane and PAH decay rates within the sediment were similar to those at the beach surface. The porous structure of the SOAs kept their cores oxygen-replete. The results reveal that SOAs buried deep in beach sands can be decomposed through relatively rapid aerobic microbial oil degradation in the tidally ventilated permeable beach sand, emphasizing the role of the sandy beach as an aerobic biocatalytical reactor at the land-ocean interface.
Incense Burning is Associated with Human Oral Microbiota Composition
Authors: Vallès Yvonne , Inman Claire K. , Peters Brandilyn A. , Wareth Laila Abdel , Abdulle Abdishakur , Alsafar Habiba , Anouti Fatme Al , Dhaheri Ayesha Al , Galani Divya , Haji Muna , Hamiz Aisha Al , Hosani Ayesha Al , Houqani Mohammed Al , Aljunaibi Abdulla , Kazim Marina , Kirchhoff Tomas , Mahmeed Wael Al , Maskari Fatma Al , Alnaeemi Abdullah , Oumeziane Naima , Ramasamy Ravichandran , Schmidt Ann Marie , Vallès Henri , Zaabi Eiman Al , Sherman Scott , Ali Raghib , Ahn Jiyoung , Hayes Richard B.
Published: July 2019

Incense burning is common worldwide and produces environmental toxicants that may influence health; however, biologic effects have been little studied. In 303 Emirati adults, we tested the hypothesis that incense use is linked to compositional changes in the oral microbiota that can be potentially significant for health. The oral microbiota was assessed by amplification of the bacterial 16S rRNA gene from mouthwash samples. Frequency of incense use was ascertained through a questionnaire and examined in relation to overall oral microbiota composition (PERMANOVA analysis), and to specific taxon abundances, by negative binomial generalized linear models. We found that exposure to incense burning was associated with higher microbial diversity (p < 0.013) and overall microbial compositional changes (PERMANOVA, p = 0.003). Our study also revealed that incense use was associated with significant changes in bacterial abundances (i.e. depletion of the dominant taxonStreptococcus), even in occasional users (once/week or less) implying that incense use impacts the oral microbiota even at low exposure levels. In summary, this first study suggests that incense burning alters the oral microbiota, potentially serving as an early biomarker of incense-related toxicities and related health consequences. Although a common indoor air pollutant, guidelines for control of incense use have yet to be developed.
Transcriptome and digital gene expression analysis unravels the novel mechanism of early flowering in Angelica sinensis
Authors: Yu Guang , Zhou Yuan , Yu Juanjuan , Hu Xueqin , Tang Ye , Yan Hui , Duan Jinao
Published: July 2019

Angelica sinensis (Oliv.) Diels is a widely used medicinal plant mainly originated in Gansu, China. Angelica sinensis is greatly demanded in the clinical practice of Chinese medicine due to its broad pharmacological activities of hematopoietic and anti-inflammatory properties. But, the percentage of early flowering in Angelica sinensis arrives to 20%~30%, which severely affects its quality and quantity. Here, transcriptome profiling and digital gene expression analysis were applied to study the mechanism of early flowering in Angelica sinensis. A total of 49,183,534 clean reads were obtained and assembled into 68,262 unigenes, and 49,477 unigenes (72.5%) could be annotated to a minimum of one database in the Nr, Nt, Swiss-Pro, GO, COG and KEGG. Taking the above transcriptome data as a reference, digital gene expression result showed that 5,094 genes expression level were significant changed during early flowering. These annotated genes offered much information promoting that the biosynthesis of secondary metabolites pathway, the hormone signal transduction pathway, and the transcription regulation system may be closely related to the early flowering phenomenon of Angelica sinensis. Further expression patterns of key genes contribute to early flowering were analyzed using quantitative real-time PCR. The transcriptome result offered important gene expression information about early flowering in Angelica sinensis.
Effects of Temperature and Photoperiod on the Immature Development in Cassida rubiginosa Müll. and C. stigmatica Sffr. (Coleoptera: Chrysomelidae)
Authors: Kutcherov Dmitry , Lopatina Elena B. , Yermakov Stepan
Published: July 2019

Tortoise beetles (Cassida and related genera) are a large cosmopolitan group that includes several pests of agricultural crops and natural enemies of weeds but their biology and ecology remain poorly known. Using a set of environmental chambers, we address simultaneous effects of temperature and photoperiod on immature development and adult body mass in two European species, C. rubiginosa and C. stigmatica. Consistent with its broader distribution range, the former species is less susceptible to low rearing temperatures, develops faster and has a larger body mass than the latter. However, C. rubiginosa seems to be less adapted to late-season conditions as a short-day photoperiod accelerates its immature development to a lesser extent than it does in C. stigmatica, which nevertheless results in greater larval mortality and slightly but significantly smaller adults. By contrast, in C. stigmatica, which is more likely to encounter late-season conditions due to its slower life cycle, short-day acceleration of development is achieved at no cost to survivorship and final body mass. The experiment with C. stigmatica was repeated during two consecutive years with different methods and the main results proved to be well reproducible. In addition, laboratory results for C. rubiginosa agree with field data from literature.
Modeling vitamin B1 transfer to consumers in the aquatic food web
Authors: Ejsmond M. J. , Blackburn N. , Fridolfsson E. , Haecky P. , Andersson A. , Casini M. , Belgrano A. , Hylander S.
Published: July 2019

Vitamin B1 is an essential exogenous micronutrient for animals. Mass death and reproductive failure in top aquatic consumers caused by vitamin B1 deficiency is an emerging conservation issue in Northern hemisphere aquatic ecosystems. We present for the first time a model that identifies conditions responsible for the constrained flow of vitamin B1 from unicellular organisms to planktivorous fishes. The flow of vitamin B1 through the food web is constrained under anthropogenic pressures of increased nutrient input and, driven by climatic change, increased light attenuation by dissolved substances transported to marine coastal systems. Fishing pressure on piscivorous fish, through increased abundance of planktivorous fish that overexploit mesozooplankton, may further constrain vitamin B1 flow from producers to consumers. We also found that key ecological contributors to the constrained flow of vitamin B1 are a low mesozooplankton biomass, picoalgae prevailing among primary producers and low fluctuations of population numbers of planktonic organisms.