bluuebunny/crossref_metadata_2025 huggingface dataset:
Ctf4 organizes sister replisomes and Pol α into a replication factory
Authors: Yuan Zuanning , Georgescu Roxana , Santos Ruda de Luna Almeida , Zhang Daniel , Bai Lin , Yao Nina Y , Zhao Gongpu , O'Donnell Michael E , Li Huilin
Published: October 2019

The current view is that eukaryotic replisomes are independent. Here we show that Ctf4 tightly dimerizes CMG helicase, with an extensive interface involving Psf2, Cdc45, and Sld5. Interestingly, Ctf4 binds only one Pol α-primase. Thus, Ctf4 may have evolved as a trimer to organize two helicases and one Pol α-primase into a replication factory. In the 2CMG–Ctf43–1Pol α-primase factory model, the two CMGs nearly face each other, placing the two lagging strands toward the center and two leading strands out the sides. The single Pol α-primase is centrally located and may prime both sister replisomes. The Ctf4-coupled-sister replisome model is consistent with cellular microscopy studies revealing two sister forks of an origin remain attached and are pushed forward from a protein platform. The replication factory model may facilitate parental nucleosome transfer during replication.
Visualizing endogenous opioid receptors in living neurons using ligand-directed chemistry
Authors: Arttamangkul Seksiri , Plazek Andrew , Platt Emily J , Jin Haihong , Murray Thomas F , Birdsong William T , Rice Kenner C , Farrens David L , Williams John T
Published: October 2019

Identifying neurons that have functional opioid receptors is fundamental for the understanding of the cellular, synaptic and systems actions of opioids. Current techniques are limited to post hoc analyses of fixed tissues. Here we developed a fluorescent probe, naltrexamine-acylimidazole (NAI), to label opioid receptors based on a chemical approach termed ‘traceless affinity labeling’. In this approach, a high affinity antagonist naltrexamine is used as the guide molecule for a transferring reaction of acylimidazole at the receptor. This reaction generates a fluorescent dye covalently linked to the receptor while naltrexamine is liberated and leaves the binding site. The labeling induced by this reagent allowed visualization of opioid-sensitive neurons in rat and mouse brains without loss of function of the fluorescently labeled receptors. The ability to locate endogenous receptors in living tissues will aid considerably in establishing the distribution and physiological role of opioid receptors in the CNS of wild type animals.
Stimulation of Piezo1 by mechanical signals promotes bone anabolism
Authors: Li Xuehua , Han Li , Nookaew Intawat , Mannen Erin , Silva Matthew J , Almeida Maria , Xiong Jinhu
Published: October 2019

Mechanical loading, such as caused by exercise, stimulates bone formation by osteoblasts and increases bone strength, but the mechanisms are poorly understood. Osteocytes reside in bone matrix, sense changes in mechanical load, and produce signals that alter bone formation by osteoblasts. We report that the ion channel Piezo1 is required for changes in gene expression induced by fluid shear stress in cultured osteocytes and stimulation of Piezo1 by a small molecule agonist is sufficient to replicate the effects of fluid flow on osteocytes. Conditional deletion of Piezo1 in osteoblasts and osteocytes notably reduced bone mass and strength in mice. Conversely, administration of a Piezo1 agonist to adult mice increased bone mass, mimicking the effects of mechanical loading. These results demonstrate that Piezo1 is a mechanosensitive ion channel by which osteoblast lineage cells sense and respond to changes in mechanical load and identify a novel target for anabolic bone therapy.
Leveraging aspect phrase embeddings for cross-domain review rating prediction
Authors: Jiang Aiqi , Zubiaga Arkaitz
Published: October 2019

Online review platforms are a popular way for users to post reviews by expressing their opinions towards a product or service, and they are valuable for other users and companies to find out the overall opinions of customers. These reviews tend to be accompanied by a rating, where the star rating has become the most common approach for users to give their feedback in a quantitative way, generally as a Likert scale of 1–5 stars. In other social media platforms like Facebook or Twitter, an automated review rating prediction system can be useful to determine the rating that a user would have given to the product or service. Existing work on review rating prediction focuses on specific domains, such as restaurants or hotels. This, however, ignores the fact that some review domains which are less frequently rated, such as dentists, lack sufficient data to build a reliable prediction model. In this paper, we experiment on 12 datasets pertaining to 12 different review domains of varying level of popularity to assess the performance of predictions across different domains. We introduce a model that leverages aspect phrase embeddings extracted from the reviews, which enables the development of both in-domain and cross-domain review rating prediction systems. Our experiments show that both of our review rating prediction systems outperform all other baselines. The cross-domain review rating prediction system is particularly significant for the least popular review domains, where leveraging training data from other domains leads to remarkable improvements in performance. The in-domain review rating prediction system is instead more suitable for popular review domains, provided that a model built from training data pertaining to the target domain is more suitable when this data is abundant.
CELSR3 mRNA expression is increased in hepatocellular carcinoma and indicates poor prognosis
Authors: Gu Xuefeng , Li Hongbo , Sha Ling , Mao Yuan , Shi Chuanbing , Zhao Wei
Published: October 2019

Objective

Hepatocellular carcinoma (HCC) is a disease that is associated with high mortality; currently, there is no curative and reliable treatment. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) is the key signaling molecule in the wingless and INT-1/planar cell polarity (WNT/PCP) pathway. This study aimed to elucidate the prognostic significance of CELSR3 in HCC patients.

Methods

The Cancer Genome Atlas (TCGA) database, the Cancer Cell Line Encyclopedia (CCLE) database and the Gene Expression Omnibus (GEO) database were used to analyze the expression of CELSR3 mRNA in HCC samples and cells. The relationship between CELSR3 mRNA and clinical features was assessed by the chi-square test. the diagnostic and predictive value of CELSR3 mRNA expression were analyzed using the receiver operating characteristic (ROC) curve. Kaplan–Meier curve and Cox regression analyses were performed to assess the prognostic value of CELSR3 mRNA in HCC patients. Finally, all three cohorts database was used for gene set enrichment analysis(GSEA) and the identification of CELSR3-related signal transduction pathways.

Results

The expression of CELSR3 mRNA was upregulated in HCC, and its expression was correlated with age (P = 0.025), tumor status (P = 0.022), clinical stage (P = 0.003), T classification (P = 0.010), vital status (P = 0.001), and relapse (P = 0.005). The ROC curve assessment indicated that CELSR3 mRNA expression has high diagnostic value in HCC and in the subgroup analysis of stage. In addition, the Kaplan-Meier curve and Cox analyses suggested that patients with high CELSR3 mRNA expression have a poor prognosis, indicating that CELSR3 mRNA is an independent prognostic factor for the overall survival of HCC patients. GSEA showed that GO somatic diversification of immune receptors, GO endonuclease activity, GO DNA repair complex and GO somatic cell DNA recombination, were differentially enriched in the meta-GEO cohort, the HCC cell line cohort and the TCGA cohort of the high CELSR3 mRNA expression phenotype.

Conclusion

Our results indicate that CELSR3 mRNA is involved in the progression of cancer and can be used as a biomarker for the prognosis of HCC patients.
Analyzing the interpretative ability of landscape pattern to explain thermal environmental effects in the Beijing-Tianjin-Hebei urban agglomeration
Authors: Wang Dongchuan , Sun Zhichao , Chen Junhe , Wang Xiao , Zhang Xian , Zhang Wei
Published: October 2019

The development of the urban agglomeration has caused drastic changes in landscape pattern and increased anthropogenic heat emission and lead to the urban heat island (UHI) effect more serious. Therefore, understanding the interpretation ability of landscape pattern on the thermal environment has gradually become an important focus. In the study, the spatial heterogeneity of the surface temperature was analyzed using the hot-spot analysis method which was improved by changing the calculation of space weight. Then the interpretation ability of a single landscape and a combination of landscapes to explain surface temperature was explored using the Pearson correlation coefficient and ordinary least squares regression from different spatial levels, and the spatial heterogeneity of the interpretation ability was explored using geographical weighted regression under the optimal granularity (5 × 5 km). The results showed that: (1) The hot spots of surface temperature were distributed mainly in the plains and on the southeast hills, where the landscapes primarily include artificial landscape (ArtLS) and farmland landscape (FarmLS). The cold spots were distributed mainly in the northern hills, which are dominated by forest landscape (ForLS). (2) On the whole, the interpretative ability of ForLS, FarmLS, ArtLS, green space landscape pattern, and ecological landscape pattern to explain surface temperature was stronger, whereas the interpretative ability of grassland landscape and wetland landscape to explain surface temperature was weaker. The interpretation ability of landscape pattern to explain surface temperature was obviously different in different areas. Specifically, the ability was stronger in the hills than in the plain and plateau. The results are intended to provide a scientific basis for adjusting landscape structural, optimizing landscape patterns, alleviating the UHI effect, and coordinating the balance among cities within the urban agglomeration.
Magnetic and Electric Control of Circularly Polarized Emission through Tuning Chirality‐Generated Orbital Angular Momentum in Organic Helical Polymeric Nanofibers
Authors: Wang Zhongxuan , Gao Mingsheng , Ren Shenqiang , Hao Xiaotao , Qin Wei
Published: October 2019

Circularly polarized light emission promotes the development of smart photonic materials for advanced applications in chiral sensing and information storage. The orbital angular momentum is a unique property for organic chiral helical materials. In this work, a type of organic chiral polymeric nanowires is designed with strong chirality induced orbital angular momentum. Under the stimulus of an external magnetic field of 600 mT, circularly polarized emission from the chiral polymeric nanowire becomes more pronounced, where the g factor increases from 0.21 to 0.3. The observed phenomena mainly originate from the chirality‐dependent orbital angular momentum. Moreover, the orbital angular momentum in helical chiral nanowire structures can be suppressed by inhibiting electron transport in a helical way to diminish circularly polarized light emission at room temperature.
Cofunction of Protons as Dopant and Reactant Activate the Electrocatalytic Hydrogen Evolution in Emeraldine‐Polyguanine
Authors: Coskun Halime , Aljabour Abdalaziz , Schöfberger Wolfgang , Hinterreiter Andreas , Stifter David , Sariciftci Niyazi Serdar , Stadler Philipp
Published: October 2019

Functional conductive polymers represent an emerging class of nonmetallic electrocatalysts attractive to substitute scarce and expensive elements used today. Here the synthesis of emeraldine‐polyguanine as structural‐molecular analog to polyaniline is shown and the conducting biopolymer as molecular hydrogen electrocatalyst is applied. The polymerized and protonated nucleobase aids the catalytic electroreduction of protons over a peculiar mechanism, where, over amino‐association, protons coserve as dopant and reactant. In acidic media the electrocatalytic evolution of hydrogen at a Tafel slope of 79 mV dec−1 at 290 mV overpotential (10 mA cm−2) is reported. The 140h initial stability test demonstrates that the functionality of polymerized nucleobases can be harnessed for heterogeneous catalysis, i.e., as here demonstrated for the electroconversion of hydrogen.
Bioactive Hydrogel Platforms for Spatiotemporal Delivery of Baculoviruses in Biomedical Applications
Authors: Whitlow Jonathan , Pacelli Settimio , Walston Towne , Paul Arghya
Published: October 2019

Baculoviruses offer a multitude of advantages over other gene carriers due to their non‐pathogenicity and inability to replicate in mammalian cells, ease of production, and high transduction efficiencies. To expand their functionality in vivo, baculoviruses containing mammalian transcription promoters (BacMam) can be physically entrapped within biocompatible hydrogels to modulate their release and transduction efficiency. The present work demonstrates several techniques in which BacMam viruses can be encapsulated and delivered in fibrin gel, an FDA‐approved sealant and adhesive with numerous clinical applications, to provide spatiotemporal control over the delivery of BacMam viruses to mammalian cells. Fibrin is shown to be an effective biomaterial carrier for the delivery of BacMam viruses to mammalian cells growing in 2D culture, 3D culture, and in the co‐delivery of stem cells and baculoviruses in the aerosolized delivery of fibrin films. Overall, the results of this work provide a valuable insight on the therapeutic potential of fibrin gels for in vivo BacMam‐mediated gene delivery in regenerative medicine.
Molecular Architecture and Charging Effects Enhance the In Vitro and In Vivo Performance of Multi‐Arm Antimicrobial Agents Based on Star‐Shaped Poly(l‐lysine)
Authors: Lu Chao , Quan Guilan , Su Ma , Nimmagadda Alekhya , Chen Weidong , Pan Miao , Teng Peng , Yu Feiyuan , Liu Xi , Jiang Ling , Du Wenyi , Hu Wei , Yao Fen , Pan Xin , Wu Chuanbin , Liu Daojun , Cai Jianfeng
Published: October 2019

Molecular architecture is a largely neglected and unexplored factor that could impart a significant difference to the antimicrobial activity of antimicrobial peptides. In this article, the advantages (i.e., improved charging effect and enhanced proteolytic stability) of star‐shaped poly(l‐lysine)s (PLLs) over their linear analogs are extensively explored by the methods of computational simulation and experiments. A series of PEI‐g‐PLL with a hyperbranched polyethylenimine (PEI) core and PLL peripheral chains are designed as a class of versatile molecular scaffold for the development of star‐shaped antimicrobial peptides. Computational simulations and zeta‐potential measurements reveal that the change in PLL conformation from linear to star‐shaped significantly increases the cationic charge density, allowing enhanced binding affinity toward the bacterial membrane. The minimum inhibitory concentration and killing kinetics measurements demonstrate that PEI‐g‐PLLs exhibit higher antimicrobial activity and bactericidal efficiency in vitro than the linear PLL counterparts. The absence of hydrophobic segments in PEI‐g‐PLLs weakens the nonspecific interactions with eukaryotic cells and offers remarkable selectivity, as evidenced by their negligible hemolytic activity. Furthermore, PEI‐g‐PLLs demonstrate enhanced proteolytic stability and unprecedented antimicrobial activity in vivo. PEI‐g‐PLLs, with their high antimicrobial activity, enormous selectivity, and remarkable proteolytic stability, represent a new series of potent antimicrobial peptides to treat drug‐resistant infections.
Gene‐Hydrogel Microenvironment Regulates Extracellular Matrix Metabolism Balance in Nucleus Pulposus
Authors: Chen Wei , Chen Hao , Zheng Dandan , Zhang Hongbo , Deng Lianfu , Cui Wenguo , Zhang Yuhui , Santos Hélder A. , Shen Hongxing
Published: October 2019

Gene therapy provides an ideal potential treatment for intervertebral disk degeneration by delivering synthetic microRNAs (miRNAs) to regulate the gene expression levels. However, it is very challenging to deliver miRNAs directly, which leads to inactivation, low transfection efficiency, and short half‐life. Here, Agomir is loaded in hydrogel to construct a gene‐hydrogel microenvironment for regulating the synthesis/catabolism balance of the tissue extracellular matrix (ECM) to treat degenerative diseases. Agomir is a cholesterol‐, methylation‐, and phosphorothioate‐modified miRNA, which can mimic the function of miRNA to regulate the expression of the target gene. Agomir874 that mimics miRNA874 is synthesized to down regulate the expression of matrix metalloproteinases (MMPs) in nucleus pulposus (NP). At the same time, a polyethylene glycol (PEG) hydrogel is synthesized through Ag‐S coordination of 4‐arm PEG‐SH and silver ion solution, which has injectable, self‐healing, antimicrobial, degradable, and superabsorbent properties and matches perfectly with the mechanism of intervertebral disk. By delivering Agomir‐loaded PEG‐hydrogel to a degenerative intervertebral disk, a gene‐hydrogel microenvironment is constructed in situ, which reduces the expression of MMPs, regulates the synthesis/catabolism balance of ECM in the NP of the intervertebral disk, and improves the tissue microenvironment regeneration.
Managing Matters: Three Top Neutrals on Mega‐Cases' Common Grounds And Fundamental Divides
Authors: Bleemer Russ
Published: October 2019

During the CPR Institute's 2019 Annual Meeting earlier this year, three of the nation's top neutrals—all best known for tackling mass torts and cases involving the government—spoke in a roundtable discussion, in person and by telephone with Alternatives.
Back to Scotus's Schein: A Separability Analysis that Resolves the Problem with the Fifth Circuit's Remand
Authors: Loree Philip J.
Published: October 2019

Contracting parties are presumed not to agree to arbitrate arbitrability questions. But if they clearly and unmistakably agree to arbitrate arbitrability, then courts are supposed to enforce that agreement.
How Mediation Can REALLY Allow The Clients to Talk and Decide
Authors: Creo Robert A.
Published: October 2019

Master mediator Paul Monicatti, of Impartial Dispute Resolution in Troy, Mich.,say that he has “conducted an entire mediation with only the clients present while their lawyers sat in an adjoining conference room just gabbing.”
A New Global ADR Star is Born: The Singapore Convention on Mediation
Authors: Wójtowicz Piotr , Gevaerd Franco
Published: October 2019

Finally, the United Nations Convention on International Settlement Agreements Resulting from Mediation has been officially launched. The Singapore signing ceremony took place on Aug. 7.
Quantum Probing Topological Phase Transitions by Non‐Markovianity
Authors: Giorgi Gian Luca , Longhi Stefano , Cabot Albert , Zambrini Roberta
Published: October 2019

Understanding the physical significance and probing the global invariants characterizing quantum topological phases in extended systems is a main challenge in modern physics with major impact in different areas of science. Here, a quantum‐information‐inspired probing method is proposed where topological phase transitions are revealed by a non‐Markovianity quantifier. The idea is illustrated by considering the decoherence dynamics of an external read‐out qubit that probes a Su–Schrieffer–Heeger (SSH) chain with either pure dephasing or dissipative coupling. Qubit decoherence features and non‐Markovianity measure clearly signal the topological phase transition of the SSH chain.
Preparation of novel hydrophobic magnetic Fe3O4/waterborne polyurethane nanocomposites
Authors: Yang Lei , Fu Qi , Fu Heqing
Published: October 2019

Magnetic Fe3O4/waterborne polyurethane nanocomposites were synthesized based on waterborne polyurethane (WPU) and amino‐functionalized Fe3O4 by in situ polymerization. The Fe3O4 nanoparticle was found to be uniformly distributed in Fe3O4/WPU nanocomposites with linear or crosslinked structure. In addition, the formation mechanism and magnetic conduction mechanism of stable inorganic–organic nanocomposites were discussed. The experimental results showed that the thermal stability, magnetic, and mechanical properties of magnetic Fe3O4/waterborne polyurethane nanocomposites were improved by amino functionalized Fe3O4. Furthermore, the defoaming property of the emulsion and the hydrophobic property of magnetic Fe3O4/waterborne polyurethane nanocomposites were improved by the 1‐hexadecanol‐terminated prepolymer. What more, polycaprolactone (PCL)‐based Fe3O4/WPU nanocomposites have excellent mechanical properties (The tensile strength is over 30 MPa, the elongation rate is above 300%.) and magnetic properties. Magnetic Fe3O4/waterborne polyurethane nanocomposites will be used in the field of hydrophobic and microwave absorbent materials. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48546.
Evaluating the ion exchange chromatography for matrix‐assisted PEGylation and purification of consensus interferon
Authors: Bajwa Fakiha , Ahmed Nadeem , Khan Mohsin Ahmad , Azam Farhana , Akram Muhammad , Tahir Saad , Zafar Ahmad Usman
Published: October 2019

Scientists have implemented protein‐PEGylation technology for boosting‐up the pharmacokinetics and stability of recombinant therapeutic proteins. In the present study, (a) matrix‐assisted PEGylation was compared with solution‐phase PEGylation and (b) matrix‐assisted PEGylation was performed with different ion exchange resins for impact of chromatography medium on yield and purity of PEGylated product. DEAE Sepharose CL 6B, DEAE Fracto gel, and Macro cap Q ion exchange chromatography medium were compared for on column PEGylation and purification of cIFN. A MSC‐PEG of 12.0 KDa was selected. cIFN was bound to ion exchange medium, and PEG solution was passed through resin for 180 Min, and protein was eluted by sodium chloride linear gradient. Yield and purity for mono‐PEGylated cIFN with Macro cap Q matrix was 75% and 99%, respectively, whereas for DEAE Sepharose was 45% and 60%. DEAE Fracto gelTM purity was 85% with 50% yield of mono‐PEGylated cIFN. Further investigation of in vitro biological activities demonstrated that about 30% antiviral activity was reduced as compared to unmodified cIFN. However, thermal stability was significantly improved. The present study proved that matrix‐assisted PEGylation can improve the yield and purity of mono‐PEGylated product, and Macro Cap resin provided the highest yield of a homogeneous product.

In present study, (a) matrix‐assisted PEGylation was compared with solution‐phase PEGylation and (b) matrix‐assisted PEGylation was performed with different ion exchange resins for impact of chromatography medium on yield and purity of PEGylated product. Matrix‐assisted PEGylation increases the yield of mono‐PEGylated product and further Macro CapTM produced highest yield and purity of PEGylated cIFN.
Einbeziehung der Öffentlichkeit und Kommunikation bei Großprojekten
Authors: Knorr Susanne , Möller Christian , Schulz Christian
Published: October 2019

Die Erwartungshaltung der Öffentlichkeit hat sich in den letzten Jahren geändert: Die formelle Beteiligung von Bürgerinnen und Bürgern, die durch Infrastrukturmaßnahmen betroffen sind, greift zu kurz. Betroffene und Nutzer möchten nicht nur frühzeitig und umfangreich informiert werden, sondern bisweilen sogar selbst an der Planung mitwirken. Dieser Anspruch, der positive Auswirkungen auf das jeweilige Vorhaben beinhaltet, muss in den Projektablauf integriert werden. Technische Planer, Projektmanager und Verantwortliche für die Kommunikation müssen gut zusammenarbeiten. Ein Projektdesign, das eine enge Verzahnung von Dialog und Projektmanagement über den gesamten Projektzeitraum vorsieht, lohnt sich. Die Vorteile der geänderten Herangehensweise sind weit mehr als die Steigerung der öffentlichen Akzeptanz von Infrastrukturprojekten. Mögliche Konflikte, die im weiteren Verfahren zu Protesten führen können, werden frühzeitig sichtbar, wenn ein Eingriff in die Planungen noch nicht ausgeschlossen ist. Verzögerungen im Projektablauf können verringert werden, was auch zur Wirtschaftlichkeit beiträgt.

Doch wie können Stakeholder gewinnbringend in die Planung integriert werden? Welcher Ansatz ist für das jeweilige Projekt der vielversprechendste? Reicht umfangreiche Information der Stakeholder, ist ein kontinuierlicher Dialog sinnvoll oder sind Formate der Beteiligung am aussichtsreichsten? Eine gute Orientierung bieten die VDI Richtlinien 7000/7001.
Der Stahlüberbau des Hochmoselübergangs – konsequent ganzheitliche Lösung
Authors: Käsmaier Manfred , Heiland Uwe
Published: October 2019

Die Errichtung der Hochmoselbrücke führte zu einer der größten Brückenneubauten Deutschlands der letzten Jahrzehnte. Mit Parametern wie Bauhöhe über Grund von 158 m, der Gesamtlänge von 1 704 m und der max. Einzelstützweite von rd. 210 m, die auch während des Montagevorgangs nicht durch Hilfsabstützungen zu reduzieren war, verlässt die Hochmoselbrücke übliche Dimensionen des Ganzstahlbrückenbaus. Durch den im Taktschiebeverfahren hergestellten Überbau wurde mit Überwindung der max. Einzelstützweite von 210 m ein in Europa bislang nicht erreichter freier Kragarm ausgeführt. Die hohen Pfeiler, die sehr große Schlankheiten aufweisen, stellten eine weitere Schwierigkeit beim Taktschieben dar. Es zeigte sich, dass technische Lösungen für Konstruktionen, bei denen maßgebliche Parameter den Bereich üblicher Dimensionen verlassen, als oft nicht kompatibel für die Anwendung der gewöhnlichen Konstruktions‐ und Dimensionierungsprinzipien sind. Bei scheinbarer phänomenologischer Analogie zweier zu vergleichender Konstruktionen bei gleichzeitiger offensichtlicher Maßstabsveränderung ist keine ungeprüfte Übertragung von Erfahrungswerten in Bezug auf die Auslegung einer Konstruktion oder Montageverfahren möglich, sondern sind sinnvolle Sonderlösungen anzuwenden. Durch die vorhandenen Dimensionen stellten Herstellung und Bau dieser Großbrücke in vieler Hinsicht eine Herausforderung für alle am Projekt Beteiligten dar und führten zu zahlreichen innovativen Entwicklungen und Lösungen in der Montagetechnologie.
Gründung und Unterbauten der Hochmoselbrücke – Planung und Ausführung
Authors: Schmidt‐Hurtienne Björn , Krumbein Olaf
Published: October 2019

Mit einer Höhe von 160 m über Grund und Einzelstützweiten bis 209,5 m befindet sich die Hochmoselbrücke im Grenzbereich der Brückenbaunormen. Geologisch anspruchsvoll wird die Brücke am Westufer der Mosel in einem rutschgefährdeten Steilhang tief gegründet. Die schlanken Pfeiler erfahren neben hohen Windbeanspruchungen auch eine Anregung durch wirbelerregte Querschwingungen. Um unter Beachtung dieser Faktoren konstruktive Lösungen zu entwickeln, waren bei der Planung und Ausführung der Gründungsbauteile und der Pfeiler im Bau‐ und Endzustand ergänzende Untersuchungen einschließlich Windkanalversuchen erforderlich. Die aeroelastische Stabilisierung der Pfeiler gegen wirbelerregte Querschwingungen im Bauzustand wurde mit Spoilern in Form von Gerüstkuben erreicht. Die Windbeanspruchung der frei stehenden hohen Pfeiler war maßgebend für die Bemessung und führte zu hohen Bewehrungsgraden in den Pfählen und Pfeilern. Die Bauausführung hat darauf mit einer optimierten Baulogistik und einer daran angepassten Kletterschalung reagiert, um den Vorlauf gegenüber dem Einschub des Stahlüberbaus zu gewährleisten.
Adjustment for exploratory cut‐off selection in randomized clinical trials with survival endpoint
Authors: Götte Heiko , Kirchner Marietta , Kieser Meinhard
Published: October 2019

Defining the target population based on predictive biomarkers plays an important role during clinical development. After establishing a relationship between a biomarker candidate and response to treatment in exploratory phases, a subsequent confirmatory trial ideally involves only subjects with high potential of benefiting from the new compound. In order to identify those subjects in case of a continuous biomarker, a cut‐off is needed. Usually, a cut‐off is chosen that resulted in a subgroup with a large observed treatment effect in an exploratory trial. However, such a data‐driven selection may lead to overoptimistic expectations for the subsequent confirmatory trial. Treatment effect estimates, probability of success, and posterior probabilities are useful measures for deciding whether or not to conduct a confirmatory trial enrolling the biomarker‐defined population. These measures need to be adjusted for selection bias. We extend previously introduced Approximate Bayesian Computation techniques for adjustment of subgroup selection bias to a time‐to‐event setting with cut‐off selection. Challenges in this setting are that treatment effects become time‐dependent and that subsets are defined by the biomarker distribution. Simulation studies show that the proposed method provides adjusted statistical measures which are superior to naïve Maximum Likelihood estimators as well as simple shrinkage estimators.
Development and evaluation of the General Surgery Objective Structured Assessment of Technical Skill (GOSATS)
Authors: Halwani Y , Sachdeva A K , Satterthwaite L , de Montbrun S
Published: October 2019

Background

Technical skill acquisition is important in surgery specialty training. Despite an emphasis on competency-based training, few tools are currently available for direct technical skills assessment at the completion of training. The aim of this study was to develop and validate a simulated technical skill examination for graduating (postgraduate year (PGY)5) general surgery trainees.

Methods

A simulated eight-station, procedure-based general surgery technical skills examination was developed. Board-certified general surgeons blinded to the level of training rated performance of PGY3 and PGY5 trainees by means of validated scoring. Cronbach's α was used to calculate reliability indices, and a conjunctive model to set a pass score with borderline regression methodology. Subkoviak methodology was employed to assess the reliability of the pass–fail decision. The relationship between passing the examination and PGY level was evaluated using χ2 analysis.

Results

Ten PGY3 and nine PGY5 trainees were included. Interstation reliability was 0·66, and inter-rater reliability for three stations was 0·92, 0·97 and 0·76. A pass score of 176·8 of 280 (63·1 per cent) was set. The pass rate for PGY5 trainees was 78 per cent (7 of 9), compared with 30 per cent (3 of 10) for PGY3 trainees. Reliability of the pass–fail decision had an agreement coefficient of 0·88. Graduating trainees were significantly more likely to pass the examination than PGY3 trainees (χ2 = 4·34, P = 0·037).

Conclusion

A summative general surgery technical skills examination was developed with reliability indices within the range needed for high-stakes assessments. Further evaluation is required before the examination can be used in decisions regarding certification.
Benzoate Surfactants for Enhancing the Activity of Lipoprotein Lipase from Burkholderia Species in Organic Solvent
Authors: Oh Yeonock
Published: October 2019

Two benzoate surfactants were synthesized and examined as the additives for enhancing the activity of a lipoprotein lipase from Burkholderia species (BSLPL) in organic solvent. It was found that the benzoate surfactants enhanced the turnover number (kcat) by four orders of magnitude and the catalytic efficiency (kcat/K
m) by three orders of magnitude. These results strongly suggest that the favorable interaction between the aromatic rings of surfactant tails and the hydrophobic residues around the active site of enzyme may help BSLPL maintain highly active open conformation in organic solvent.
Detection of unrecognized pregnancy prior to a fluoroscopy‐guided interventional procedure: A case report
Authors: Gungor Semih , Celebi Ersu
Published: October 2019

The aim of this case report is to increase the awareness about patient and fetus safety through preprocedure assessment and screening of unrecognized pregnancy for fluoroscopy‐guided procedures.
Advanced transverse colon cancer highly indicative of invasion to the duodenum and pancreas
Authors: Yamada Takayuki , Sakamoto Ichiro , Ohwada Susumu
Published: October 2019

Our images showed an advanced transverse colon cancer highly indicative of an invasion to the duodenum and pancreas. For en bloc tumor resection, surgeons should make a deliberate operative plan.
Cervical ribs—An anatomical obstacle for upper limb regional blocks
Authors: Moreno Enrique , Dirzu Dan Sebastian , Bastías Moraga María Fernanda , Fajardo Pérez Mario
Published: October 2019

Anatomic variations of the cervical and supraclavicular regions are possible with an impact on regional anesthesia strategy. The presence of cervical ribs may obstruct needle visualization for brachial plexus block in those regions. Preprocedural scan may help in choosing the appropriate technique.
Newborn with a solitary hairless skin defect on the scalp vertex
Authors: Koumaki Dimitra , Koumaki Vasiliki , Boumpoucheropoulos Sotirios , Baltaga Ludmila , Bitados Panagiotis , Katoulis Alexander , Krasagakis Konstantinos
Published: October 2019

Aplasia cutis congenita is a rare congenital disorder usually presenting as an isolated lesion on the scalp that may be associated with genetic syndromes and congenital anomalies. Therefore, it is important to be aware of this syndrome.
Determining Conditions of Intermittently Fed Digesters from Biogas Production Rate Data
Authors: Eccleston Robin , Bongards Michael
Published: October 2019

As the contribution from renewable energy to the power grid increases, biogas plants could profit from on‐demand production. Flexible feeding can supplement gas storage for further benefits. Changing to flexible feeding introduces transient events to the feeding, and by monitoring the system response to the feeding transients it is possible to gain information about the system stability. Testing was performed at the laboratory and pilot scale to investigate the response characteristics. A statistical analysis was carried out to assess the response to feeding events and make an estimate of the system stability. This analysis was then used as the input to a proportional integral derivative controller for controlling the feeding rate for an anaerobic digestion model No. 1 simulation.
Access to Photoreactive Core‐Shell Nanomaterials by Photoinitiated Polymerization‐Induced Self‐Assembly
Authors: Molle Edgar , Le Dao , Norizadeh Abbariki Tannaz , Akdemir Meryem S. , Takamiya Masanari , Miceli Enrico , Kassel Olivier , Delaittre Guillaume
Published: October 2019

We report the straightforward synthesis of photoreactive nanoobjects exhibiting various colloidal morphologies by photoinitiated polymerization‐induced self‐assembly (PISA). Poly(oligoethylene glycol methyl ether methacrylate) copolymers with pendent UV‐activatable diaryl tetrazole moieties were employed as macromolecular chain‐transfer agents in water for the dispersion photopolymerization of 2‐hydroxypropyl methacrylate under visible light. This led to the in situ formation of amphiphilic block copolymers, driving the self‐assembly into core‐shell nanoparticles, nanofibers, and nano/microvesicles. The tetrazole group present in the shell of the nanoobjects permitted functionalization with various functional molecules and polymers via UV‐triggered nitrile imine‐mediated tetrazole–ene cycloaddition (NITEC), enabling the alteration of surface properties of the nanomaterials (fluorescence, charge, hydrophilicity).
African American Muslims: Intersectionality and Cultural Competence
Authors: Al'Uqdah Shareefah N. , Hamit Sahran , Scott Sabrina
Published: October 2019

Although African American Muslims constitute 40% of all American‐born Muslims (Pew Research Center, 2011), they are virtually absent from the literature. Increasing the presence of African American Muslims in the literature may improve counselors' cultural competence when working with them. Using intersectional theory, the authors outline the rich history of African American Muslims and highlight ways counselors can improve their cultural and spiritual competence when working with African American Muslims.
A Study of Student Counselors' Experiences With Meditation
Authors: Gutierrez Daniel , Merrill Erica , Conley Abigail H. , Young Mark E.
Published: October 2019

The positive effects of meditation have been shown to be helpful to a variety of client populations and counselors in practice. Researchers analyzed the journals of 60 counselor education students who volunteered to learn Jyoti meditation (JM) over a 6‐week period. Analysis revealed 5 major themes: (a) the scheduling of time for meditation, (b) issues with concentrating, (c) environment for meditation, (d) effects on wellness, and (e) adherence to daily practice. These themes suggest avenues for how counselor educators and supervisors can help student counselors integrate JM as a self‐care strategy.
A Simple Strategy for Easily Assembling 3D Printed Miniaturized Cells Suitable for Simultaneous Electrochemical and Spectrophotometric Analyses
Authors: Dossi Nicolò , Toniolo Rosanna , Terzi Fabio , Grazioli Cristian , Svigelj Rossella , Gobbi Filippo , Bontempelli Gino
Published: October 2019

A rapid and user‐friendly approach is here presented for assembling smart and versatile platforms for simultaneous electrochemical and spectrophotometric measurements. They consist of an optically transparent pencil‐drawn electrochemical cell, including reference, counter and working carbon electrodes, assembled on flexible PVC supports, exploiting a commercial desktop digitally controlled plotter/cutter. This cell is installed on a U shaped 3D printed polylactic frame where a second transparent window consisting of an unmodified PVC layer was also applied. After optimization of the fabrication procedure, the electrochemical and optical characterization of the assembled miniaturized platforms was performed by using aqueous electrolytes and potassium hexacyanoferrate(II) as redox probe. These devices were then tested by a proof‐of‐concept direct and simultaneous electrochemical and spectrophotometric quantification of a commonly used food dye (Brilliant Blue, E‐133) in soft‐drinks and candies. Spectrophotometric and electrochemical determinations can be performed at the same time, providing simultaneous information and enabling a concomitant comparison and validation of the results obtained.
Isthmusectomy in selected patients with well‐differentiated thyroid carcinoma
Authors: Park Hakyoung , Harries Victoria , McGill Marlena R. , Ganly Ian , Shah Jatin P.
Published: October 2019

Background

Isthmusectomy in the treatment of well‐differentiated thyroid carcinoma (WDTC) is controversial. In this study, we analyze the outcomes of WDTC managed by isthmusectomy alone.

Methods

Forty‐three patients treated with isthmusectomy alone were identified from an institutional database of 6259 surgically treated patients with WDTC. Patient and tumor characteristics were analyzed. Disease‐specific survival (DSS) and recurrence‐free survival (RFS) were calculated using the Kaplan‐Meier method.

Results

The pT classification was T1 for 41 and T2 for two patients. All were clinical N0, but 10 pts were pN1a. Using the American Thyroid Association risk stratification system, 9 patients were low‐risk and 22 were intermediate‐risk. One patient developed local recurrence, and two developed regional lymph node metastases; the 5‐ and 10‐year DSS was 100.0%. The 5‐ and 10‐year RFS was 93.1%.

Conclusions

Isthmusectomy alone is an acceptable procedure in selected patients with low‐ and intermediate‐risk WDTC limited to the isthmus.
Malignant development in patients with oral potentially malignant disorders detected through nationwide screening: Outcomes of 5‐year follow‐up at a single hospital
Authors: Chiang Wei‐Fan , Liu Shyun‐Yeu , Lin Jen‐Fen , Chiu Sheng‐Fu , Gou Shin‐Bin , Chiou Chang‐Ta , Chang Chi‐Hua
Published: October 2019

Background

Although survival rate and quality of life are improved if patients with oral carcinoma can be detected early, however, such lesions are usually asymptomatic; therefore, it is hard to raise awareness. Screening has proved to be cost‐effective for early detection.

Methods

Sixty‐two patients with oral carcinomas and 555 patients with oral potentially malignant disorders (OPMDs) who were detected through screening were examined the relationship between clinicopathological features and follow‐up outcomes.

Results

The 5‐year cumulative cancer‐free interval rate was 94.1%, and the annual malignant transformation rate was 1.16%. The rate of interval carcinoma development from Candida hyperplasia, oral submucous fibrosis, homogeneous leukoplakia, non‐homogenous leukoplakia, and verrucous hyperplasia, was 13.6%, 5.7%, 4.6%, 12.1%, and 21.3%, respectively. Significant independent risk factors for interval carcinoma development were heavy betel quid chewing, verrucous hyperplasia, and surgery refusal.

Conclusions

Well‐designed risk assessment, treatment, and surveillance program could lead to earlier cancer detection and thereby reduce mortality and morbidity.
Denosumab Prevents Early Periprosthetic Bone Loss After Uncemented Total Hip Arthroplasty: Results from a Randomized Placebo-Controlled Clinical Trial
Authors: Nyström Andreas , Kiritopoulos Demostenis , Ullmark Gösta , Sörensen Jens , Petrén-Mallmin Marianne , Milbrink Jan , Hailer Nils P , Mallmin Hans
Published: October 2019

Implant loosening is the most common indication for revision surgery after total hip arthroplasty (THA). Although bone resorption around the implants plays a pivotal role in the pathophysiology of loosening, it is unknown whether potent early inhibition of osteoclasts could mitigate this process and thus reduce the need for revision surgery. We performed a randomized, double-blind, placebo-controlled phase 2 trial in 64 patients aged 35 to 65 years with unilateral osteoarthritis of the hip. They underwent surgery with an uncemented THA and were randomized to either two subcutaneous doses of denosumab (n = 32) or placebo (n = 32) given 1 to 3 days and 6 months after surgery. Patients were followed for 24 months. Primary outcome was periprosthetic bone mineral density (BMD) of the hip at 12 months as measured by dual-energy X-ray absorptiometry (DXA). In addition, [18F] sodium fluoride positron emission tomography/CT (F-PET) was performed in half of the patients for analysis of periprosthetic standardized uptake value (SUV). Analyses were made according to intention-to-treat principles. The trial was registered at ClinicalTrials.gov 2011-001481-18, NCT01630941. Denosumab potently inhibited early periprosthetic bone loss. After 12 months, BMD in the denosumab group was 32% (95% confidence interval [CI] 22–44) higher in Gruen zone 7 and 11% (95% CI 8–15) higher in zones 1 to 7. After 24 months, the difference in BMD between groups had decreased to 15% (95% CI 4–27) in zone 7 and 4% (95% CI 0–8) in zones 1 to 7. In both groups, SUV increased after surgery, but the increase was less pronounced in the denosumab group. Biochemical markers of bone metabolism decreased in the denosumab group in the first 12 months, but a rebound effect with marker concentrations above baseline was observed after 24 months. Denosumab potently prevents early periprosthetic bone loss after uncemented THA; however, the effect diminishes after discontinuation of treatment. Further research is needed to determine whether this bone loss will prove to be of clinical importance and, if so, whether the positive effect observed in this study could be preserved by either prolonged treatment with denosumab or additional antiresorptive treatment. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.
Retention in care and factors critical for effectively implementing antiretroviral adherence clubs in a rural district in South Africa
Authors: Bock Peter , Gunst Colette , Maschilla Leonard , Holtman Rory , Grobbelaar Nelis , Wademan Dillon , Dunbar Rory , Fatti Geoffrey , Kruger James , Ford Nathan , Hoddinott Graeme , Meehan Sue‐Ann
Published: October 2019

Introduction

Differentiated models of care that include referral of antiretroviral treatment (ART) clients to adherence clubs are an important strategy to help clinics manage increased number of clients living with HIV in resource‐constrained settings. This study reported on (i) clinical outcomes among ART clients attending community‐based adherence clubs and (ii) experiences of adherence clubs and perceptions of factors key to successful adherence club implementation among clients and healthcare workers.

Methods

A retrospective cohort analysis of routine data and a descriptive analysis of data collected through self‐administered surveys completed by clients and healthcare workers were completed. Clients starting ART at the study clinic, between January 2014 and December 2015, were included in the cohort analysis and followed up until December 2016. The survey data were collected from August to September 2017. The primary outcome for the cohort analysis was a comparison of loss to follow‐up (LTFU) between clients staying in clinic care and those referred to adherence clubs. Survey data reported on client experiences of and healthcare worker perceptions of adherence club care.

Results

Cohort analysis reported on 465 participants, median baseline CD4 count 374 (IQR: 234 to 532) cells/μl and median follow‐up time 20.7 (IQR 14.1 to 27.7) months. Overall, 202 (43.4%) participants were referred to an adherence club. LTFU was lower in those attending an adherence club (aHR =0.25, 95% CI: 0.11 to 0.56). This finding was confirmed on analysis restricted to those eligible for adherence club referral (aHR =0.28, 95% CI: 0.12 to 0.65). Factors highlighted as associated with successful adherence club implementation included: (i) referral of stable clients to the club, (ii) an ideal club size of ≥20 members, (iii) club services led by a counsellor (iv) using churches or community halls as venues (v) effective communication between all parties, and (vi) timely delivery of prepacked medication.

Conclusions

This study showed good clinical outcomes, positive patient experiences and healthcare worker perceptions of the adherence club model. Factors associated with successful adherence club implementation, highlighted in this study, can be used to guide implementers in the scale‐up of adherence club services across varied high‐burden settings.
Dispersive solid‐phase extraction combined with dispersive liquid‐liquid microextraction for simultaneous determination of seven succinate dehydrogenase inhibitor fungicides in watermelon by ultra high performance liquid chromatography with tandem mass spectrometry
Authors: Wu Junxue , Zhi Shenwei , Jia Chunhong , Li Xinghai , Zhu Xiaodan , Zhao Ercheng
Published: October 2019

In this study, a simple and accurate sample preparation method based on dispersive solid‐phase extraction and dispersive liquid‐liquid microextraction has been developed for the determination of seven novel succinate dehydrogenase inhibitor fungicides (isopyrazam, fluopyram, pydiflumetofen, boscalid, penthiopyrad, fluxapyroxad, and thifluzamide) in watermelon. The watermelon samples were extracted with acetonitrile, cleaned up by dispersive solid‐phase extraction procedure using primary secondary amine, extracted and concentrated by the dispersive liquid‐liquid microextraction procedure with 1,1,2,2‐tetrachloroethane, and then analyzed by ultra high performance liquid chromatography with tandem mass spectrometry. The main experimental factors affecting the performance of dispersive solid‐phase extraction and dispersive liquid‐liquid microextraction procedure on extraction efficiency were investigated. The proposed method had a good linearity in the range of 0.1–100 µg/kg with correlation coefficients (r) of 0.9979–0.9999. The limit of quantification of seven fungicides was 0.1 µg/kg in the method. The fortified recoveries of seven succinate dehydrogenase inhibitor fungicides at three levels ranged from 72.0 to 111.6% with relative standard deviations of 3.4–14.1% (n = 5). The proposed method was successfully used for the rapid determination of seven succinate dehydrogenase inhibitor fungicides in watermelon.