bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein phosphatase 2 regulatory subunit B''Alpha silencing inhibits tumor cell proliferation in liver cancer
Authors: Chen Huijuan , Xu Jing , Wang Peixiao , Shu Qingming , Huang Lihong , Guo Jing , Zhang Xuyi , Zhang Hongying , Wang Ying , Shen Zhongyang , Chen Xinguo , Zhang Qing
Published: October 2019

Aim

To explore the effects of protein phosphatase 2 regulatory subunit B''Alpha (PPP2R3A) on the proliferation and migration of liver cancer cells.

Methods

Expression of PPP2R3A in tumor tissues of hepatocellular carcinoma (HCC) patients was detected by immunohistochemistry and western blotting. In two liver cancer cell lines (HepG2 and HuH7), PPP2R3A expression was silenced and then overexpression with PPP2R3A lentiviral vectors, and the effects of PPP2R3A knockdown or overexpression on the proliferation, cell cycle, migration, and invasion of HCC cells were determined in vitro. In a xenograft cancer model in nude mice, the in vivo effects of PPP2R3A knockdown on tumor growth and cancer cell proliferation were evaluated.

Results

PPP2R3A expression was found in tumor foci in six of eight HCC samples, at a level higher than that in the adjacent para‐tumor tissues. PPP2R3A expression was observed primarily in the cytoplasm of the cancer cells. Knockdown of PPP2R3A resulted in significant inhibition of hepatoma cell proliferation (P < .05), migration (P < .01), and invasion (P < .01) as well as a significant delay in the G1/S transition in both liver cancer lines (P < .05) and increased p53 expression. Conversely, overexpression of PPP2R3A promoted the proliferation (P < .05) and altered cell cycle progression (P < .05) of both liver cancer cell lines. In vivo, PPP2R3A knockdown in liver cancer cells led to significant reductions in the tumor volume (P < .001) and the expression of Ki‐67 in tumor tissues (P < .05).

Conclusion

PPP2R3A may play a role in liver cancer via the regulation of tumor cell proliferation and invasion.
Relational processes and the emergence of harmful supervision events: A narrative analysis of a single case
Authors: Cartwright Duncan
Published: October 2019

Background

Harmful supervision practices have been found to be fairly common in clinic supervision. Although a number of possible factors linked to harmful supervision have been identified, the relational processes and dynamics associated with the emergence of harmful supervision events still remain largely unexplored.

Aim

This study explores a case of harmful supervision with the aim of understanding relational factors that contributed to the difficulties encountered. Both the supervisor's and supervisee's perspectives are considered.

Method

Narrative inquiry was used to analyse supervisor and supervisee interviews. Interviews focused on reconstructing supervision stories associated with critical incidents.

Findings

Poor orientation to the goals and tasks of supervision and the early undermining of the supervisee's experiences appeared to set up a negative relational process. This led to a cycle of escalating anxiety, amplification, avoidance and non‐disclosure on both sides of the supervisory dyad. In turn, this seemed to contribute towards the emergence of a pseudo‐supervisory alliance. Given the erosion of trust, unresolved issues constantly re‐emerged. The relational processes associated with the case are explored using Jessica Benjamin's Recognition Theory.
Chemical‐Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors
Authors: Creutznacher Robert , Schulze Eric , Wallmann Georg , Peters Thomas , Stein Matthias , Mallagaray Alvaro
Published: October 2019

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low‐affinity bile acid binding site of a human GII.4 NoV strain. Long‐timescale MD simulations reveal the formation of a ligand‐accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo‐blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus‐like particles of seven different strains suggest that low‐affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.
Multicentric Castleman disease with TAFRO syndrome and Sjögren's
Authors: Li Zi Ying , Kim Shirley , Huang SiYi , Mian Raza
Published: October 2019

We describe a patient with Castleman's disease with TAFRO syndrome and concurrent Sjögren's syndrome and investigate whether the autoimmune process may have accelerated the onset of her Castleman's disease. Patient was treated with R‐CVP therapy with remission of symptoms although there is no current standard treatment.
Cobalt‐Catalyzed Cross‐Couplings and Electrophilic Aminations using Organozinc Pivalates
Authors: Lutter Ferdinand H. , Graßl Simon , Grokenberger Lucie , Hofmayer Maximilian S. , Chen Yi‐Hung , Knochel Paul
Published: October 2019

The front cover artwork for Issue 21/2019 is provided by researchers from Ludwig‐Maximilians‐Universität (Germany) and Wuhan University (China). The image shows an artist with benzene‐shaped hair painting polyfunctional (hetero)arenes on a canvas in dark blue with a big zinc brush. The color symbolizes the active cobalt catalyst, which is used for several transformations described in the Minireview. This marvelous combination of a zinc brush together with the cobalt dye enables the creation of pure art. See the Minireview itself at https://doi.org/10.1002/cctc.201900070.
The Route from the Folded to the Amyloid State: Exploring the Potential Energy Surface of a Drug‐Like Miniprotein
Authors: Taricska Nóra , Horváth Dániel , Menyhárd Dóra K. , Ákontz‐Kiss Hanna , Noji Masahiro , So Masatomo , Goto Yuji , Fujiwara Toshimichi , Perczel András
Published: October 2019

The amyloid formation of the folded segment of a variant of Exenatide (a marketed drug for type‐2 diabetes mellitus) was studied by electronic circular dichroism (ECD) and NMR spectroscopy. We found that the optimum temperature for E5 protein amyloidosis coincides with body temperature and requires well below physiological salt concentration. Decomposition of the ECD spectra and its barycentric representation on the folded‐unfolded‐amyloid potential energy surface allowed us to monitor the full range of molecular transformation of amyloidogenesis. We identified points of no return (e.g.; T=37 °C, pH 4.1, cE5=250 μm, cNaCl=50 mm, t>4–6 h) that will inevitably gravitate into the amyloid state. The strong B‐type far ultraviolet (FUV)‐ECD spectra and an unexpectedly strong near ultraviolet (NUV)‐ECD signal (Θ≈275–285 nm) indicate that the amyloid phase of E5 is built from monomers of quasi‐elongated backbone structure (φ≈−145°, ψ≈+145°) with strong interstrand Tyr↔Trp interaction. Misfolded intermediates and the buildup of “toxic” early‐stage oligomers leading to self‐association were identified and monitored as a function of time. Results indicate that the amyloid transition is triggered by subtle misfolding of the α‐helix, exposing aromatic and hydrophobic side chains that may provide the first centers for an intermolecular reorganization. These initial clusters provide the spatial closeness and sufficient time for a transition to the β‐structured amyloid nucleus, thus the process follows a nucleated growth mechanism.
Pathways to Triplet or Singlet Oxygen during the Dissociation of Alkali Metal Superoxides: Insights by Multireference Calculations of Molecular Model Systems
Authors: Zaichenko Aleksandr , Schröder Daniel , Janek Jürgen , Mollenhauer Doreen
Published: October 2019

Recent experimental investigations demonstrated the generation of singlet oxygen during charging at high potentials in lithium/oxygen batteries. To contribute to the understanding of the underlying chemical reactions a key step in the mechanism of the charging process, namely, the dissociation of the intermediate lithium superoxide to oxygen and lithium, was investigated. Therefore, the corresponding dissociation paths of the molecular model system lithium superoxide (LiO2) were studied by CASSCF/CASPT2 calculations. The obtained results indicate the presence of different dissociation paths over crossing points of different electronic states, which lead either to the energetically preferred generation of triplet oxygen or the energetically higher lying formation of singlet oxygen. The dissociation to the corresponding superoxide anion is energetically less preferred. The understanding of the detailed reaction mechanism allows the design of strategies to avoid the formation of singlet oxygen and thus to potentially minimize the degradation of materials in alkali metal/oxygen batteries. The calculations demonstrate a qualitatively similar but energetically shifted behavior for the homologous alkali metals sodium and potassium and their superoxide species. Fundamental differences were found for the covalently bound hydroperoxyl radical.
A Screening Platform to Identify and Tailor Biocompatible Small‐Molecule Catalysts
Authors: Rubini Rudy , Ivanov Ilya , Mayer Clemens
Published: October 2019

Interfacing biocompatible, small‐molecule catalysis with cellular metabolism promises a straightforward introduction of new function into organisms without the need for genetic manipulation. However, identifying and optimizing synthetic catalysts that perform new‐to‐nature transformations under conditions that support life is a cumbersome task. To enable the rapid discovery and fine‐tuning of biocompatible catalysts, we describe a 96‐well screening platform that couples the activity of synthetic catalysts to yield non‐canonical amino acids from appropriate precursors with the subsequent incorporation of these nonstandard building blocks into GFP (quantifiable readout). Critically, this strategy does not only provide a common readout (fluorescence) for different reaction/catalyst combinations, but also informs on the organism's fitness, as stop codon suppression relies on all steps of the central dogma of molecular biology. To showcase our approach, we have applied it to the evaluation and optimization of transition‐metal‐catalyzed deprotection reactions.
Population Genetic Inference With MIGRATE
Authors: Beerli Peter , Mashayekhi Somayeh , Sadeghi Marjan , Khodaei Marzieh , Shaw Kyle
Published: October 2019

Many evolutionary biologists collect genetic data from natural populations and then need to investigate the relationship among these populations to compare different biogeographic hypotheses. MIGRATE, a useful tool for exploring relationships between populations and comparing hypotheses, has existed since 1998. Throughout the years, it has steadily improved in both the quality of algorithms used and in the efficiency of carrying out those calculations, thus allowing for a larger number of loci to be evaluated. This efficiency has been enhanced, as MIGRATE has been developed to perform many of its calculations concurrently when running on a computer cluster. The program is based on the coalescence theory and uses Bayesian inference to estimate posterior probability densities of all the parameters of a user‐specified population model. Complex models, which include migration and colonization parameters, can be specified. These models can be evaluated using marginal likelihoods, thus allowing a user to compare the merits of different hypotheses. The three presented protocols will help novice users to develop sophisticated analysis techniques useful for their research projects. © 2019 The Authors.

Basic Protocol 1: First steps with MIGRATE

Basic Protocol 2: Population model specification

Basic Protocol 3: Prior distribution specification

Basic Protocol 4: Model selection

Support Protocol 1: Installing the program MIGRATE

Support Protocol 2: Installation of parallel MIGRATE
Tandem Hydrogenolysis–Hydrogenation of Lignin‐Derived Oxygenates over Integrated Dual Catalysts with Optimized Interoperations
Authors: Fang Huihuang , Chen Weikun , Li Shuang , Li Xuehui , Duan Xinping , Ye Linmin , Yuan Youzhu
Published: October 2019

The efficient hydrodeoxygenation (HDO) of lignin‐derived oxygenates is essential but challenging owing to the inherent complexity of feedstock and the lack of effective catalytic approaches. A catalytic strategy has been developed that separates C−O hydrogenolysis and aromatic hydrogenation on different active catalysts with interoperation that can achieve high oxygen removal in lignin‐derived oxygenates. The flexible use of tungsten carbide for C−O bond cleavage and a nickel catalyst with controlled particle size for arene hydrogenation enables the tunable production of cyclohexane and cyclohexanol with almost full conversion of guaiacol. Such integration of dual catalysts in close proximity enables superior HDO of bio‐oils into liquid alkanes with high mass and carbon yields of 27.9 and 45.0 wt %, respectively. This finding provides a new effective strategy for practical applications.
High‐Sulfur‐Content Graphene‐Based Composite through Ethanol Evaporation for High‐Energy Lithium‐Sulfur Battery
Authors: Carbone Lorenzo , Del Rio Castillo Antonio Esau , Kumar Panda Jaya , Pugliese Giammarino , Scarpellini Alice , Bonaccorso Francesco , Pellegrini Vittorio
Published: October 2019

Lithium‐sulfur batteries are the most promising candidates for next‐generation energy storage devices owing to their high theoretical specific capacity of 1675 mAh g−1 and high theoretical energy density of approximately 3500 Wh kg−1. However, the lack of cathode active materials with appropriate electrical conductivities and stability coupled with an inexpensive and industrially compatible production process has so far hindered the development of practical devices. Here, a facile preparation pathway is reported for the production of a sulfur–carbon composite active material by drying a mixture of highly conductive few‐layer graphene (FLG) flakes (produced by exploiting an innovative wet jet milling process with a yield of ≈100 % and production capability of ≈23.5 g h−1) with elemental sulfur, using ethanol as an environmentally friendly solvent. The designed sulfur–FLG composite shows excellent electrochemical results. The assembled lithium–sulfur battery exhibits a stable rate capability up to a current rate of 2C, a coulombic efficiency approaching 100 % for 300 cycles at the current rate of C/4 (420 mA g−1), and a long cycle life up to 500 cycles delivering around 600 mAh g−1 at 2C (3350 mA g−1).
Ultrasmall Co@Co(OH)2 Nanoclusters Embedded in N‐Enriched Mesoporous Carbon Networks as Efficient Electrocatalysts for Water Oxidation
Authors: Munir Akhtar , ul Haq Tanveer , Hussain Iqtidar , Qurashi Ahsanulhaq , Ullah Ubaid , Iqbal Javed , Hussain Irshad
Published: October 2019

Metal nanoclusters (NCs, size ≤2 nm) are emerging materials in catalysis owing to their unique catalytic and electronic properties such as high surface/volume ratio, high redox potential, plethora of surface active sites, and dynamic behavior on a suitable support during catalysis. Herein, in situ growth of ultrasmall and robust Co@β‐Co(OH)2 NCs (≈2 nm) hosted in a honeycomb‐like 3D N‐enriched carbon network was developed for water‐oxidation catalysis with extremely small onset potential (1.44 V). Overpotentials of 220 and 270 mV were required to achieve a current density of 10 mA cm−2 and 100 mA cm−2, respectively, in alkaline medium (1 m KOH). More promisingly, at η10=240 mV, the prolonged oxygen evolution process (>130 h) with faradaic efficiency >95 % at a reaction rate of 22 s−1 at 1.46 V further substantiated the key role of the ultrasmall supported NCs, which outperformed the benchmark electrocatalysts (RuO2/IrO2) and NCs reported so far. It is anticipated that the high redox potential of NCs with regeneratable active sites and their concerted synergistic effects with the N‐enriched porous/flexible carbon network are inherently worth considering to enhance the mass/charge transport owing to the nanoscale interfacial collaboration across the electrode/electrolyte boundary, thereby efficiently energizing the sluggish/challenging oxygen evolution process.
First Principle Material Genome Approach for All Solid‐State Batteries
Authors: Xu Hongjie , Yu Yuran , Wang Zhuo , Shao Guosheng
Published: October 2019

Due to ever‐increasing concern about safety issues in using alkali metal ionic batteries, all solid‐state batteries (ASSBs) have attracted tremendous attention. The foundation to enable high‐performance ASSBs lies in delivering ultra‐fast ionic conductors that are compatible with both alkali anodes and high‐voltage cathodes. Such a challenging task cannot be fulfilled, without solid understanding covering materials stability and properties, interfacial reactions, structural integrity, and electrochemical windows. Here in this work, we will review recent advances on fundamental modeling in the framework of material genome initiative based on the density functional theory (DFT), focusing on solid alkali batteries. Efforts are made in offering a dependable road chart to formulate competitive materials and construct “better” batteries.
Selective Cα Alcohol Oxidation of Lignin Substrates Featuring a β‐O‐4 Linkage by a Dinuclear Oxovanadium Catalyst via Two‐Electron Redox Processes
Authors: Tsai Yan‐Ting , Chen Chih‐Yao , Hsieh Yi‐Ju , Tsai Ming‐Li
Published: October 2019

Developing highly efficient catalyst systems to transform lignin biomass into value‐added chemical feedstocks is imperative for utilizing lignin as renewable alternatives to fossil fuels. Recently, the pre‐activated strategy involving the selective oxidation of Cα alcohol of lignin substrates containing (β‐O‐4 linkage mode has been demonstrated to significantly increase the depolymerization efficiency of native aspen lignin from 10–20 to 60 wt.‐%. In this study, we reported the synthesis of a dinuclear oxovanadium complex 2 that is capable of selectively oxidizing the Cα alcohol (80 – 100% selectivity) of various dimeric lignin substrates under a mild condition. Further investigation of catalytic mechanism has revealed that two V=O motifs of complex 2 could serve as proton abstraction sites for both Cα and Cγ alcohol of dimeric lignin substrates, respectively. Interestingly, the dinuclear vanadium intermediate 4 demonstrates the ability to uptake two electrons resulting from the oxidation of Cα alcohol and yields two corresponding mononuclear VIV intermediate 5. The mononuclear VIV intermediate 5 exhibits a characteristic 8‐line EPR spectrum and possesses one unpaired electron determined by the Evans method. The established structure‐reactivity relationships will be able to shed light on the future directions for rational design of highly efficient catalysts for selective oxidation of lignin biomass.
N‐Heterocyclic Carbene Platinum Complexes: A Big Step Forward for Effective Antitumor Compounds
Authors: Bellemin‐Laponnaz Stéphane
Published: October 2019

The discovery of cisplatin is an important milestone in the history of successful anticancer drugs. This is also a notable example of the translational scientific achievement that remains a driving force in multidisciplinary research. The clinical success of cisplatin has led chemists to vary the ligands around the platinum metal to improve cisplatin's effectiveness while reducing its side effects. While there have been more failures than successes, key developments in the elucidation of mechanisms of the tumor‐resistance properties have been accomplished. N‐Heterocyclic carbene as ligand for organometallic chemistry is a relatively young area that offers new opportunities in many fields including bio‐inorganic chemistry. These ligands fit the prerequisites for metal drug development and recent achievements have demonstrated the great potential of these compounds. The properties of these metal NHC complexes also allow for easy post‐functionalization, thus enabling molecular diversity for efficient drug design. Overall, N‐heterocyclic carbene ligands reveal new opportunities for Pt drug development.
Crystal Structure and Properties of a UV‐Transparent High‐Pressure Polymorph of Mg3TeO6 with Second Harmonic Generation Response
Authors: Selb Elisabeth , Declara Lisa , Bayarjargal Lkhamsuren , Podewitz Maren , Tribus Martina , Heymann Gunter
Published: October 2019

Mg3TeO6 can be synthesized at ambient pressure conditions and temperatures of 920–1070 K in a centrosymmetric, rhombohedral structure‐type (R3). By means of high‐pressure/high‐temperature synthesis at 12.5 GPa and 1570 K a new, colorless, non‐centrosymmetric high‐pressure (HP) phase of Mg3TeO6 is formed, crystallizing in the Ni3TeO6‐type structure with the following unit cell parameters and refinement results: R3, a = 513.82(7) pm, c = 1380.7(2) pm, V = 31.57(1) nm3, R1 = 0.0283, wR2 = 0.0732, and GooF = 1.096. High‐temperature PXRD measurements on HP‐Mg3TeO6 revealed exceptionally high temperature stability for a metastable high‐pressure compound of up to 1220 K. Additionally, vibrational spectra (IR/Raman) were recorded and compared to theoretical calculations obtained by Density Functional Theory. Due to the acentric crystal structure, SHG measurements on a powdery sample exhibited an SHG efficiency of 0.83 times KH2PO4 (KDP) and a wide transparency range up to an absorption edge of 260 nm was determined by UV/Vis measurements. Overall, HP‐Mg3TeO6 is therefore interesting for UV‐laser applications.
Recent Progress in the Synthesis of Naturally Occurring Siderophores
Authors: Garzón‐Posse Fabián , Quevedo‐Acosta Yovanny , Mahecha‐Mahecha Camilo , Acosta‐Guzmán Paola
Published: October 2019

Iron is an indispensable element for the development of almost all living things, and its acquisition is a key process for organisms. However, the low solubility of Fe3+ in aqueous systems causes its reduced bioavailability. Thus, organisms confronted with low iron availability have developed several iron scavenging strategies, and one of these ways is to use low molecular‐weight organic molecules, which are specific ferric ion chelators called siderophores. These compounds exhibit an extremely high affinity and specificity for Fe3+ and are produced and secreted by bacteria, fungi, and plants. Recently, siderophores have attracted much attention due to their applications in areas such as microbial ecology, specific crop production, detoxification of heavy metal‐contaminated samples, biodetection of metals, and the selective delivery of antibiotics to resistant bacterial strains. Nevertheless, the limited supply of these natural products has been an obstacle that needs to be overcome. This review provides an overview of the contemporary developments in the total synthesis of naturally occurring siderophores during the last two decades.
Kinetic and thermodynamic properties of purified alkaline protease from Bacillus pumilus Y7 and non‐covalent immobilization to poly(vinylimidazole)/clay hydrogel
Authors: Duman Yonca Avcı , Tekin Nalan
Published: October 2019

The characterization of the hydrogel was performed using Fourier‐transform infrared spectroscopy, X‐ray diffraction, and scanning electron microscopy. Purified Bacillus pumilus Y7‐derived alkaline protease was immobilized in Poly (vinylimidazole)/clay (PVI/SEP) hydrogel with 95% yield of immobilization. Immobilization decreased the pH optimum from 9 to 6 for free and immobilized enzyme, respectively. Temperature optimum 3°C decreased for immobilized enzyme. The Km, Vm, and kcat of immobilized enzyme were 4.4, 1.7, and 7.5‐fold increased over its free counterpart. Immobilized protease retained about 65% residual activity for 16th reuse. The immobilized protease endured its 35% residual activity in the material after six cycle's batch applications. The results of thermodynamic analysis for casein hydrolysis showed that the ΔG≠ (activation free energy) and ΔG≠E‐T (activation free energy of transition state formation) obtained for the immobilized enzyme decreased in comparison to those obtained for the free enzyme. On the other hand, the value of ΔG≠ES (free energy of substrate binding) was observed to have increased. These results indicate an increase in the spontaneity of the biochemical reaction post immobilization. Enthalpy value of immobilized enzyme that was 2.2‐fold increased over the free enzyme indicated lower energy for the formation of the transition state, and increased ΔS≠ value implied that the immobilized form of the enzyme was more ordered than its free form.
5‐exo versus 6‐endo Thiyl‐Radical Cyclizations in Organic Synthesis
Authors: McCourt Ruairí , Scanlan Eoin M.
Published: October 2019

Since the discovery of the radical mediated thiol‐ene and thiol‐yne reactions, these reactions have been employed in an intramolecular manner for the synthesis of sulfur‐containing heterocycles. Although closely related on a mechanistic basis, the thiol‐ene and thiol‐yne cyclization can differ greatly in regioselectivity and product distribution, with the thiol‐ene process being more predictable and thus attracting greater utilization. Herein, we review intramolecular thiyl‐radical addition reactions and the factors leading to the observed regioselectivity in examples in which both the 5‐exo and 6‐endo mode of cyclization are feasible. We highlight the applications of these important reactions for organic synthesis in the recent literature.
Experimental study of the synergistic effect and network regulation mechanisms of an applied combination of BMP‐2, VEGF, and TGF‐β1 on osteogenic differentiation
Authors: Wang Zhihao , Sun Jian , Li Yali , Chen Chen , Xu Yaoxiang , Zang Xiaolong , Li Li , Meng Kun
Published: October 2019

The study aimed to explore the osteogenic effect induced by the combined use of bone morphogenetic protein‐2 (BMP‐2), vascular endothelial growth factor (VEGF), and transforming growth factor‐β1 (TGF‐β1), attain the best combination for osteogenic quality and efficiency, and explore the network regulation mechanisms of induced osteogenesis. MC3T3‐E1 cells were cultured in vitro, and BMP‐2, VEGF, and TGF β1 were added to osteogenic induction mediums in different combinations to conduct experiments. At 7 and 14 days, the alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining of the applied BMP‐2 and VEGF combination were deeper and the quantitative analysis were higher than those of the other groups. After optimizing the time–effect relationship of the combined application, with BMP‐2, VEGF, and TGF‐β1 adding in the early stage and BMP‐2 and VEGF adding in the late, the ALP and ARS staining of these groups were deeper and the quantitative analyses were meaningfully higher than the BMP‐2 and VEGF combination group at 7 and 14 days. The expression of the RUNX2 gene and the Smad1 signaling pathway in the optimized combination group was also significantly higher. The results demonstrate that the combination of BMP‐2, VEGF, and TGF‐β1 applied according to the time–effect relationship can significantly promote osteogenic differentiation mainly through the classical BMP‐receptor‐Smad signal pathway.
Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment
Authors: Jahanafrooz Zohreh , Mosafer Jaffar , Akbari Morteza , Hashemzaei Mahmoud , Mokhtarzadeh Ahad , Baradaran Behzad
Published: October 2019

Despite many advances and optimization in colon cancer treatment, tumor recurrence and metastases make the development of new therapies necessary. Colon cancer stem cells (CCSCs) are considered as the main triggering factor of cancer progression, recurrence, and metastasis. CCSCs as a result of accumulated genetic and epigenetic alterations and also complex interconnection with the tumor microenvironment (TME) can evolve and convert to full malignant cells. Mounting evidence suggests that in cancer therapy both CCSCs and non‐CCSCs in TME have to be regarded to break through the limitation of current therapies. In this regard, stem cell capabilities of some non‐CCSCs may arise inside the TME condition. Therefore, a deep knowledge of regulatory mechanisms, heterogeneity, specific markers, and signaling pathways of CCSCs and their interconnection with TME components is needed to improve the treatment of colorectal cancer and the patient's life quality. In this review, we address current different targeted therapeutic options that target cell surface markers and signaling pathways of CCSCs and other components of TME. Current challenges and future perspectives of colon cancer personalized therapy are also provided here. Taken together, based on the deep understanding of biology of CCSCs and using three‐dimensional culture technologies, it can be possible to reach successful colon cancer eradication and improvise combination targeted therapies against CCSCs and TME.
Phenolic composition of Tempranillo Blanco (Vitis vinifera L.) grapes and wines after biostimulation via a foliar seaweed application
Authors: Gutiérrez‐Gamboa Gastón , Garde‐Cerdán Teresa , Martínez‐Lapuente Leticia , Costa Bianca Souza‐da , Rubio‐Bretón Pilar , Pérez‐Álvarez Eva P
Published: October 2019

BACKGROUND

Seaweeds are defined as novel elicitors in many crops, allowing the synthesis of secondary metabolites to be triggered in different plant tissues. Currently, the phenolic composition of Tempranillo Blanco grapes and wines is unreported. The present study aimed to investigate the effects of an Ascophyllum nodosum seaweed extract applied to Tempranillo Blanco grapevines, at low (Ld) and high (Hd) dosages, on grape and wine phenolic compounds during two consecutive seasons (2017–2018).

RESULTS

The results obtained showed that catechin was the most abundant phenolic compound in Tempranillo Blanco grapes and wines. Season affected the weight of 100 berries and some enological parameters. Catechin and flavonols concentrations in grapes were increased after Hd application to grapevines, independently of season. The concentration of hydroxycinnamic and hydroxybenzoic acids in wines was affected by vintage, probably as a result of oxidation reactions, as well as pinking phenomena, whereas the stilbenes content in wines was conditioned by the affect of cryptogamic diseases in grapes.

CONCLUSION

Seaweeds might act as an elicitor of several phenolic compounds in grapes, enhancing the content of some phenolic compounds in wines. © 2019 Society of Chemical Industry
The concentration of the cleaved suPAR forms in pre‐ and postoperative plasma samples improves the prediction of survival in colorectal cancer: A nationwide multicenter validation and discovery study
Authors: Rolff Hans C. , Christensen Ib J. , Svendsen Lars B. , Wilhelmsen Michael , Lund Ida K. , Thurison Tine , Høyer‐Hansen Gunilla , Illemann Martin , Nielsen Hans J. ,   on behalf of the Danish Collaborative Research Group on Colorectal Cancer
Published: October 2019

Background and Objectives

The aim was to evaluate the prognostic biomarker potential of the soluble urokinase‐type plasminogen activator receptor (suPAR) in plasma samples collected pre‐ and postoperatively from patients resected for colorectal cancer (CRC).

Methods

Patients with CRC were recruited prospectively at six centers from 2006 to 2008. Preoperative plasma samples were available from 494 patients and from 328 of these patients at 6 months postoperatively. Determinations of intact soluble uPAR (suPAR) suPAR(I‐III) and the cleaved forms suPAR(I‐III) + (II‐III) and uPAR(I) were performed. Clinical data were retrieved retrospectively.

Results

In a multivariable model based on preoperative plasma samples suPAR(I‐III) + (II‐III) and uPAR(I) showed an independent statistically significant association to long term survival. When including the change in biomarker level between the pre‐ and postoperatively samples the hazard ratios were 3.06 (95% confidence interval [CI], 1.78‐5.28; P < .0001) and 2.24 (95% CI, 1.59‐3.16; P < .0001) for suPAR(I‐III) + (II‐III) and uPAR(I), respectively. A one‐unit decrease in biomarker levels between the pre‐ and postoperative levels resulted in a 55% and 34% reduction in the risk estimate of death for suPAR(I‐III) + (II‐III) and uPAR(I), respectively.

Conclusion

This study validates previously findings regarding the prognostic significance of suPAR in preoperative samples. The inclusion of postoperative samples added further prognostic information.
Carotid Artery Corrected Flow Time and Respiratory Variations of Peak Blood Flow Velocity for Prediction of Hypotension After Induction of General Anesthesia in Adult Patients Undergoing Elective Surgery: A Prospective Observational Study
Authors: Maitra Souvik , Baidya Dalim K. , Anand Rahul K. , Subramanium Rajeshwari , Bhattacharjee Sulagna
Published: October 2019

Objectives

Hypotension is common after induction of general anesthesia, and intraoperative hypotension is associated with postoperative end‐organ injury such as acute kidney injury and myocardial ischemia. This study was designed to determine the utility of the carotid corrected flow time (cFT) and carotid artery peak blood flow velocity variation (ðVpeak) for prediction of hypotension after induction of general anesthesia.

Methods

Adult patients (n = 112) undergoing any elective surgery under general anesthesia who fasted for at least 6 to 8 hours were recruited in this prospective observational study. The common carotid artery cFT and ðVpeak were measured with ultrasound 10 minutes before induction of general anesthesia. After that, general anesthesia with propofol was used, and hemodynamic data were collected until 3 minutes after induction of anesthesia.

Results

The carotid cFT was significantly correlated with percentages of the fall in the systolic blood pressure at 2 minutes (P < .0001) and 3 minutes (P < .0001) and percentages of the fall in the mean arterial pressure at 1 minute (P = .0006), 2 minutes (P < .0001), and 3 minutes (P < .0001). The cFT was a predictor of hypotension after induction of general anesthesia, with an area under the receiver operating characteristic curve of 0.91. The best cutoff value obtained from this study was 330.2 milliseconds or less, which predicted postinduction hypotension with sensitivity and specificity of 85.7% and 96.8%, respectively. The ðVpeak was an inferior predictor of postinduction hypotension, with an area under the receiver operating characteristic curve of 0.68. The optimum cutoff value was 18.8%, with sensitivity and specificity of 61.9% and 67.4%.

Conclusions

The cFT measured in the common carotid artery is a reasonable predictor of hypotension after induction of general anesthesia in American Society of Anesthesiologists physical status I and II patients. Further studies are required to identify its role in high‐risk patients such as older groups and patients with cardiovascular diseases and also to identify interobserver and intraobserver variability of cFT and ðVpeak measurements.
Antenna alignment by using computer vision technology
Authors: Chen Biao , Liu Yuzhe
Published: October 2019

An automatic alignment approach is proposed for tracking unmanned aerial vehicle (UAV) antennas by using computer vision technology. In this approach, UAV carries a low‐gain omnidirectional antenna and a ground station uses high gain directional antenna which can be driven by a pan‐tilt to point to UAV's antenna. A camera is bound together with the antenna and a computer is employed to recognize the video and control motion of the pan‐tilt, so as to move the image of UAV's antenna toward the center of the whole picture. If the distance between center of UAV image and center of the picture is kept within a few pixels, then the antennas are aligned. Performance analysis and experiment results are given, showing that the proposed antenna autoalignment approach can achieve accurate alignment of the antennas with an angle error of less than 1°.
DiGeorge syndrome chromosome region deletion and duplication: Prenatal genotype‐phenotype variability in fetal ultrasound and MRI
Authors: Tramontana Allessandra , Hartmann Beda , Hafner Erich
Published: October 2019

Objective

The aim of the study was to assess genotype‐phenotype correlation of prenatally diagnosed fetal DGS and dup22q11 syndrome by fetal molecular genetic analysis, fetal ultrasound, and/or MRI.

Methods

In this retrospective consecutive case series, pregnant women were screened for fetal anomalies during a period of 10 years. Fetal genotype was assessed in 72 cases upon the occurrence of five prenatal fetal phenotypic features: cardiac anomalies, hypo/aplastic thymus, craniofacial malformations, urinary abnormalities, or IUGR; genotype‐phenotype correlation was tested to potentially improve prenatal diagnosis of fetal DGS and dup22q11 syndrome.

Results

Fetal genotypes of deletions or duplications in proximal clusters of LCR22s (A‐B) were associated with fetal cardiac anomalies in combination with hypo/aplastic thymus and craniofacial malformations, suggesting a correlation with deleted HIRA. TOF associated with aplastic thymus in combination with renal defects indicated a relevant correlation with TBX1 deletion. Deletions in central LCR22s (B‐D) with the loss of CRKL supposed a trend of genotype‐phenotype correlation with fetal urinary abnormalities.

Conclusion

Genotype‐phenotype correlation might improve prenatal diagnosis of fetal DGS and dup22q11 syndrome. Hence, prenatal screening and counseling is highly enhanced by a combination of fetal molecular genetic analysis, fetal ultrasound, and/or MRI. The implications of these findings remain to be explored.
Semi‐Polar InGaN‐Based Green Light‐Emitting Diodes Grown on Silicon
Authors: Shen Shuoheng , Zhao Xuanming , Yu Xiang , Zhu Chenqi , Bai Jie , Wang Tao
Published: October 2019

High‐quality semi‐polar (11‐22) GaN is obtained by means of growth on patterned (113) silicon substrates featured with stripy grooves and extra periodic gaps which are perpendicular to the grooves. Ga melting‐back during the GaN growth at a high temperature is eliminated as a result of special patterning design. On‐axis X‐ray rocking curve measurements show that the linewidth is significantly reduced down to 339 arcsec. Photoluminescence (PL) measurements at 10 K show strong GaN band‐edge emission only, meaning that any basal stacking fault‐related emission is not observed. Furthermore, green InGaN/GaN light‐emitting diodes (LEDs) with an emission wavelength of around 530 nm are achieved on the semi‐polar GaN grown on the patterned Si substrates. Excitation power‐dependent PL measurements do not show a shift in wavelength, meaning a significant reduction in polarization‐induced piezoelectric fields. Electroluminescence (EL) measurements exhibit that the output power of the semi‐polar LED increases linearly with increasing injection current. It is worth highlighting that the overgrowth technology on designed patterned (113) silicon is a potential approach to manufacturing high‐performance semi‐polar GaN emitters on Si substrates in a long wavelength region.
Buoyancy‐driven entrainment in dry thermals
Authors: McKim Brett , Jeevanjee Nadir , Lecoanet Daniel
Published: October 2019

Over 50 years ago it was proposed that dry thermals entrain because of buoyancy (via a constraint which requires an increase in the radius a). However, this runs counter to the scaling arguments commonly used to derive the entrainment rate, which rely on either the self‐similarity or a turbulent entrainment hypothesis. The assumption of turbulence‐driven entrainment has been investigated and it has been found that the entrainment efficiency e varies by less than 20% between laminar (Re=630) and turbulent (Re=6300) thermals. This motivated us to utilize the argument of buoyancy‐controlled entrainment in addition to the thermal's vertical momentum equation to build a model for thermal dynamics which does not invoke turbulence or self‐similarity. We derive simple expressions for the thermals' kinematic properties and their fractional entrainment rate ϵ and find close quantitative agreement with the values in direct numerical simulations. In particular, our expression for entrainment rate is consistent with the parametrization ϵ∼B/w2, for Archimedean buoyancy B and vertical velocity w. We also directly validate the role of buoyancy‐driven entrainment by running simulations where gravity is turned off midway through a thermal's rise. The entrainment efficiency e is observed to drop to less than one third of its original value in both the laminar and turbulent cases when g=0, affirming the central role of buoyancy in entrainment for dry thermals.
Generalized relativistic effective core potentials for superheavy elements
Authors: Mosyagin Nikolai S. , Zaitsevskii Andrei V. , Titov Anatoly V.
Published: October 2019

The generalized relativistic effective core potentials (GRECPs) for calculations of electronic structure and physical‐chemical properties of compounds containing superheavy elements (Z ≥ 104) are presented. Features of accounting for the finite nuclear size effects which are unusually large for superheavy elements are discussed in details. Accuracy of the GRECPs is analyzed in atomic calculations compared to all‐electron studies with the Dirac‐Coulomb‐Breit Hamiltonian. Applications of the GRECP method in molecular and cluster calculations are surveyed.
A graphon approach to limiting spectral distributions of Wigner‐type matrices
Authors: Zhu Yizhe
Published: October 2019

We present a new approach, based on graphon theory, to finding the limiting spectral distributions of general Wigner‐type matrices. This approach determines the moments of the limiting measures and the equations of their Stieltjes transforms explicitly with weaker assumptions on the convergence of variance profiles than previous results. As applications, we give a new proof of the semicircle law for generalized Wigner matrices and determine the limiting spectral distributions for three sparse inhomogeneous random graph models with sparsity ω(1/n): inhomogeneous random graphs with roughly equal expected degrees, W‐random graphs and stochastic block models with a growing number of blocks. Furthermore, we show our theorems can be applied to random Gram matrices with a variance profile for which we can find the limiting spectral distributions under weaker assumptions than previous results.
Identifying inconsistency in network meta‐analysis: Is the net heat plot a reliable method?
Authors: Freeman Suzanne C. , Fisher David , White Ian R. , Auperin Anne , Carpenter James R.
Published: October 2019

One of the biggest challenges for network meta‐analysis is inconsistency, which occurs when the direct and indirect evidence conflict. Inconsistency causes problems for the estimation and interpretation of treatment effects and treatment contrasts. Krahn and colleagues proposed the net heat approach as a graphical tool for identifying and locating inconsistency within a network of randomized controlled trials. For networks with a treatment loop, the net heat plot displays statistics calculated by temporarily removing each design one at a time, in turn, and assessing the contribution of each remaining design to the inconsistency. The net heat plot takes the form of a matrix which is displayed graphically with coloring indicating the degree of inconsistency in the network. Applied to a network of individual participant data assessing overall survival in 7531 patients with lung cancer, we were surprised to find no evidence of important inconsistency from the net heat approach; this contradicted other approaches for assessing inconsistency such as the Bucher approach, Cochran's Q statistic, node‐splitting, and the inconsistency parameter approach, which all suggested evidence of inconsistency within the network at the 5% level. Further theoretical work shows that the calculations underlying the net heat plot constitute an arbitrary weighting of the direct and indirect evidence which may be misleading. We illustrate this further using a simulation study and a network meta‐analysis of 10 treatments for diabetes. We conclude that the net heat plot does not reliably signal inconsistency or identify designs that cause inconsistency.
Assessment of reliability of EN 1992‐1‐1 variable strut inclination method of shear design provisions for stirrup failure
Authors: Olalusi Oladimeji B. , Viljoen Celeste
Published: October 2019

The best estimate shear strength predictions of the operational EN 1992‐1‐1 (EC2) variable strut inclination method (VSIM) have been shown to underestimate shear capacity at low stirrup quantities. Conversely, the model overestimates shear capacity at high stirrup quantities (Cladera and Mari, 2007; Olalusi and Viljoen, 2019). Sufficient safety performance of the design formulation should be confirmed at high levels of stirrup reinforcement, and over conservatism at low stirrup reinforcement is not ideal. This contribution assesses the consistency and uniformity of the reliability index of EC2 shear design formulation over the range of practical design situations. Prediction model uncertainty is an important parameter in the assessment (Olalusi and Viljoen, 2019). The principal reliability assessment was performed using as general probabilistic model (GPM), the probabilistic representation of the modified compression field theory (MCFT) as implemented in analysis program Response 2000 (R2k), which was shown to provide the most accurate estimates of shear capacity (Bentz, 2000). This was validated by means of a similar reliability analysis using the compression chord capacity model (CCC) as GPM. The outcome of EC2 reliability analysis indicated uneconomically high reliability at low levels of shear reinforcement, high concrete strength and large beam depth, and actively reducing reliability with increased levels of shear reinforcement, reduced concrete strength and reduced beam depth for both rectangular and I‐shaped beam cross‐sections. Reliability indices of all the test sections investigated meet the target reliability requirements for Reliability Class 2 structures prescribed by basis of design standards SANS 10160 and EN 1990, for the design range considered.
Architecting systems‐of‐systems and their constituents: A case study applying Industry 4.0 in the construction domain
Authors: Axelsson Jakob , Fröberg Joakim , Eriksson Peter
Published: October 2019

The development of system‐of‐systems (SoS) requires a continuous interplay between design decisions on the SoS level and those on the level of its constituent systems (CS), which often preexist and need to be adapted as the SoS evolves. This involves not only preparing the CS to participate in a particular SoS, but also designing the CS architecture to make it easily adaptable to a future SoS context. The problem is in part addressed in an emerging SoS framework in the manufacturing domain called Industry 4.0. It focuses on connected and digitalized production with the ambition of increasing flexibility and efficiency. This paper investigates how Industry 4.0 standards can be used in an SoS context to make CS more flexible and adaptive, and evaluates their usefulness outside manufacturing. The study is based on a case from the construction domain, for which a generic SoS architecture is developed. Several extensions and adaptations of Industry 4.0 are suggested, including specifications of ontologies for missions and workflows.