bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoassembly of Oligopeptides and DNA Mimics the Sequential Disassembly of a Spherical Virus
Authors: Ni Rong , Chau Ying
Published: November 2019

Protein subunits of a low aspect ratio (width over length) with stimuli‐responsiveness are hallmark building blocks of spherical viruses. The interaction of these repeating subunits enables hierarchical assembly for genome packaging and sequential disassembly for optimal genome release. Here, we mimicked these features and constructed a functional spherical artificial virus. The rationally designed 22‐amino acid peptide containing pH‐sensitive histidines and aromatic residues self‐assembled into homogenous nanodiscs of a low aspect ratio (≈7×7×4 nm). In the presence of DNA, the inter‐nanodisc interactions drove the formation of a viral capsid‐like structure enclosing DNA in the interior. This artificial virus roughly 50 nm in diameter underwent partial disassembly in response to acidic pH. The resulting intermediate with lowered DNA‐binding affinity continued to protect DNA from nuclease digestion. Such nanostructures, which mimic the intricate morphology and the intracellular transformation of spherical viruses, can be useful for constructing synthetic gene delivery vehicles, as evidenced by their efficient transgene expression.
It's in the Fine Print: Erasable Three‐Dimensional Laser‐Printed Micro‐ and Nanostructures
Authors: Gräfe David , Walden Sarah L. , Blinco James , Wegener Martin , Blasco Eva , Barner‐Kowollik Christopher
Published: November 2019

3D printing, on all scales, is currently a vibrant topic in scientific and industrial research as it has enormous potential to radically change manufacturing. Owing to the inherent nature of the manufacturing process, 3D printed structures may require additional material to structurally support complex features. Such support material must be removed after printing—sometimes termed subtractive manufacturing—without adversely affecting the remaining structure. An elegant solution is the use of photoresists containing labile bonds that allow for controlled cleavage with specific triggers. Herein, we explore state‐of‐the‐art cleavable photoresists for 3D direct laser writing, as well as their potential to combine additive and subtractive manufacturing in a hybrid technology. We discuss photoresist design, feature resolution, cleavage properties, and current limitations of selected examples. Furthermore, we share our perspective on possible labile bonds, and their corresponding cleavage trigger, which we believe will have a critical impact on future applications and expand the toolbox of available cleavable photoresists.
Adaptive predictive path following control based on least squares support vector machines for underactuated autonomous vessels
Authors: Liu Chenguang , Zheng Huarong , Negenborn Rudy , Chu Xiumin , Xie Shuo
Published: November 2019

Since vessel dynamics could vary during maneuvering because of load changes, speed changing, environmental disturbances, aging of mechanism, etc., the performance of model‐based path following control may be degraded if the controller uses the same motion model all the time. This article proposes an adaptive path following control method based on least squares support vector machines (LS‐SVM) to deal with parameter changes of the motion model. The path following controller consists of two components: the online identification of varying parameters and model predictive control (MPC) using the adaptively identified models. For the online parameter identification, an improved online LS‐SVM identification method is proposed based on weighted LS‐SVM. Specifically, the objective function of LS‐SVM is modified to decrease the errors of parameter estimation, an index is proposed to detect the possible model changes, which speeds up the rate of parameter convergence, and the sliding data window strategy is used to realize the online identification. MPC is combined with the line‐of‐sight guidance to track straight line reference paths. Finally, case studies are conducted to verify the effectiveness of the proposed path following adaptive controller. Typical parameter varying scenarios, such as rudder aging, current variations and changes of the maneuverability are considered. Simulation results show that the proposed method can handle the above situations effectively.
Synthesis and characterization of luminescent SiO2@Eu(phen–Si) core–shell nanospheres
Authors: Li Wen‐Xian , Zheng Yu‐Shan , Zhang Hong‐Bo , Bao Jin‐Rong , Li Yi‐Lian , Ma Yang‐Yang , Feng Li‐Na , Feng Shu‐Yan
Published: November 2019

Four core–shell structured nanometre luminescent composites with different kernel sizes and different shell layer thicknesses (SiO2(500)@Eu (phen–Si)(50), SiO2(500)@Eu (phen–Si)(15), SiO2(250)@Eu (phen–Si)(5) and SiO2(250)@Eu (phen–Si)(10)) were made by changing synthesis conditions. Here, initial subscript numbers in parentheses refer to the particle size of the SiO2 core, whereas the final subscript numbers in parentheses refer to shell layer thickness. In these composites, silica spheres of 500 nm or 250 nm were identified as the core. The shell layer was composited of silicon, 1,10‐phenanthroline and europium perchlorate, abbreviated as Eu(phen–Si); the chemical formula of phen–Si was phen‐N‐(CONH (CH2)Si(OCH2CH3)3)2. The composites were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and infrared spectroscopy. The monodispersed spherical SiO2 showed characteristics of a regular microstructure and a smooth surface, as well as the advantage of dispersity, shown by SEM. The Eu(phen–Si) complex was able to self‐assemble into monodispersed SiO2 spheres, as seen using TEM.

Fluorescence spectra indicated that the four composites had excellent luminescence properties. Furthermore, composites composed of a SiO2 core and a 250 nm kernel size exhibited stronger fluorescence than 500 nm kernel‐sized composites. Fluorescence properties were affected by shell thickness: the thicker the shell, the greater the fluorescence intensity. For the four composites, quantum yield values and fluorescence lifetime corresponded to fluorescence emission intensity data as quantum yield values and fluorescence lifetime were higher, and luminescence properties increased.
A review of bioanalytical methods for chronic lymphocytic leukemia drugs and metabolites in biological matrices
Authors: P S Suresh , Trivedi Ravi Kumar , Srinivas Nuggehally R. , Mullangi Ramesh
Published: November 2019

Quantitation of drugs used for the treatment of chronic lymphocytic leukemia in various biological matrices during both pre‐clinical and clinical developments is very important, often in routine therapeutic drug monitoring. The first developed methods for quantitation were traditionally done on LC in combination with either UV or fluorescence detection. However, the emergence of LC with mass spectrometry in tandem in early 1990s has revolutionized the quantitation as it has provided better sensitivity and selectivity within a shorter run time; therefore it has become the choice of method for the analysis of various drugs. In this article, an overview of various bioanalytical methods (HPLC or LC–MS/MS) for the quantification of drugs for the treatment of chronic lymphocytic leukemia, along with applicability of these methods, is given.
Adult‐onset neuronal intranuclear inclusion disease presenting with typical MRI changes
Authors: Han Xinsheng , Han Miao , Liu Ning , Xu Jianke , Zhang Yan , Zhang Yun , Hong Daojun , Zhang Wei
Published: November 2019

Background

This study aims to analyze the clinical, imaging, electrophysiological, and dermatopathological features of a patient with adult‐onset neuronal intranuclear inclusion disease (NIID) and to explore the diagnostic methods of adult‐onset NIID.

Case presentation

We here report a 63‐year‐old male with recurrent acute encephalopathy syndrome and autonomic nervous system damage syndrome characterized by sexual dysfunction and urinary and fecal dysfunction. Cranial diffusion‐weighted magnetic resonance imaging (DWI) demonstrated symmetrically distributed strip‐shaped high‐intensity signal in bilateral fronto‐occipital‐parietal cortical‐medullary junction. Electrophysiological test revealed that the main site of injury was myelin sheath in both motor and sensory nerves. Skin biopsy revealed eosinophilic spherical inclusion bodies in the nucleus of sweat gland epithelial cells.

Conclusion

This case suggests that adult NIID is a chronic neurodegenerative disease with high clinical heterogeneity. Subcortical strip‐shaped high‐intensity signal on DWI has high diagnostic significance. Eosinophilic intranuclear inclusion bodies detected by skin biopsy contribute to diagnosis.
Selective microstructural integrity impairments of the anterior corpus callosum are associated with cognitive deficits in obstructive sleep apnea
Authors: Zhang Biao , Zhu Dao‐min , Zhao Wenming , Zhang Yu , Yang Ying , Zhang Cun , Zhu Jiajia , Yu Yongqiang
Published: November 2019

Background

There is some evidence that obstructive sleep apnea (OSA) patients have white matter integrity abnormality in the corpus callosum (CC). However, whether the CC subregions are differentially affected in OSA is largely unknown.

Methods

Twenty patients with OSA and 24 well‐matched healthy controls were enrolled and underwent diffusion tensor imaging (DTI) and clinical and cognitive assessments. DTI tractography was used to reconstruct the CC which was divided into five subregions. Intergroup differences in multiple diffusion metrics of each CC subregion and their correlations with clinical and cognitive parameters were tested.

Results

In comparison with healthy controls, OSA patients exhibited white matter integrity alterations in the anterior CC, characterized by increased radial diffusivity (RD) in the subregion 1 and decreased fractional anisotropy (FA) along with increased mean diffusivity (MD) and RD in the subregion 2. Moreover, we found that the lower microstructural integrity in the anterior CC was correlated with worse prospective memory and sustained attention in OSA patients.

Conclusions

These findings indicate that the selective impairments of the anterior CC may help clarify the neural correlates of cognitive impairments in OSA.
Whole‐brain radiotherapy plus sequential or simultaneous integrated boost for the treatment of a limited number of brain metastases in non‐small cell lung cancer: A single‐institution study
Authors: Qing Dong , Zhao Bin , Zhou Yi‐Chen , Zhu Hong‐Lei , Ma Dai‐Yuan
Published: November 2019

Background

To compare the survival outcomes and neurocognitive dysfunction in non‐small cell lung cancer (NSCLC) patients with brain metastases (BM ≤10) treated by whole‐brain radiotherapy (WBRT) with sequential integrated boost (SEB) or simultaneous integrated boost (SIB).

Materials

Fifty‐two NSCLC patients with a limited number of BMs were retrospectively analyzed. Twenty cases received WBRT+SEB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*3 fractions; SEB group), and 32 cases received WBRT+SIB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*10 fractions; SIB group). The survival and mini‐mental state examination (MMSE) scores were compared between the groups.

Results

The cumulative 1‐, 2‐, and 3‐year survival rates in the SEB vs SIB groups were 60.0% vs 47.8%, 41.1% vs 19.1%, and 27.4% vs 0%, respectively. The median survival times in the SEB and SIB groups were 15 and 10 months, respectively. The difference in survival rate was significant (P = .046). Subgroup analysis revealed that 1‐, 2‐, and 3‐year survival rates and median survival time in the SEB group were significantly superior to those of the SIB group, especially for male patients (age <60 years) with 1‐2 BMs (P < .05). The MMSE score of the SEB group at 3 months after radiation was higher than that of the SIB group (P < .05). Nevertheless, WBRT+SEB required a longer treatment time and greater cost (P < .005).

Conclusions

WBRT + SEB results in better survival outcomes than WBRT+SIB, especially for male patients (age <60 years) with 1‐2 BMs. WBRT+SEB also appeared to induce less neurocognitive impairment than WBRT+SIB.
In Yarrowia lipolytica erythritol catabolism ends with erythrose phosphate
Authors: Niang Papa Makhona , Arguelles‐Arias Anthony , Steels Sebastien , Denies Olivia , Nicaud Jean‐Marc , Fickers Patrick
Published: November 2019

In response to osmotic stress, the yeast Yarrowia lipolytica produces erythritol, a four‐carbon sugar alcohol, from erythrose‐P, an intermediate of the pentose phosphate pathway. Under non‐stressing conditions (isotonic environment), the produced erythritol is subsequently recycled into erythrose‐P that can feed the pentose phosphate pathway. Herein, gene YALI0F01584g was characterized as involved in the erythritol catabolic pathway. Several experimental evidences suggested that it encodes an erythrulose‐1P isomerase that converts erythrulose‐1P into erythrulose‐4P. On the basis of our previous reports and results gathered in this study with genetically modified strains, including ΔYALI0F01584g and ΔYALI0F01628g disrupted mutants, the entire erythritol catabolic pathway has been characterized.
Solvent‐Free Synthesis of Zeolitic Imidazolate Frameworks and the Catalytic Properties of Their Carbon Materials
Authors: Xiao Yuchen , Hong Anh N. , Hu Dandan , Wang Yanxiang , Bu Xianhui , Feng Pingyun
Published: November 2019

Zeolitic imidazolate frameworks (ZIFs) are traditionally synthesized solvothermally by using cost‐ and waste‐incurring organic solvents. Here, a direct synthesis method is reported for ZIF‐8, ZIF‐67, and their heterometallic versions from solid precursors only. This solvent‐free crystallization method not only completely avoids organic solvents, but also provides an effective path for the synthesis of homogeneous mixed‐metal ZIFs. Furthermore, under templating by NaCl/ZnCl2 eutectic salt, carbonization of the ZIF materials gives rise to a series of N‐containing high‐surface‐area carbon materials with impressive catalytic properties for the oxygen reduction reaction.
Synthesis of Highly Fluorinated Arene Complexes of [Rh(Chelating Phosphine)]+ Cations, and their use in Synthesis and Catalysis
Authors: McKay Alasdair I. , Barwick‐Silk James , Savage Max , Willis Michael C. , Weller Andrew S.
Published: November 2019

The synthesis of rhodium complexes with weakly binding highly fluorinated benzene ligands is described: 1,2,3‐F3C6H3, 1,2,3,4‐F4C6H2 and 1,2,3,4,5‐F5C6H are shown to bind with cationic [Rh(Cy2P(CH2)xPCy2)]+ fragments (x=1, 2). Their structures and reactivity with alkenes, and use in catalysis for promoting the Tishchenko reaction of a simple aldehyde, are demonstrated. Key to the synthesis of these complexes is the highly concentrated reaction conditions and use of the [Al{OC(CF3)3}4]− anion.
3D Carbon Foam Supported Edge‐Rich N‐Doped MoS2 Nanoflakes for Enhanced Electrocatalytic Hydrogen Evolution
Authors: Jia Xueying , Ren Hongyuan , Hu Hanbin , Song Yu‐Fei
Published: November 2019

Molybdenum disulfide (MoS2) is one of the most promising alternatives to the Pt‐based electrocatalysts for the hydrogen evolution reaction (HER). However, its performance is currently limited by insufficient active edge sites and poor electron transport. Hence, enormous efforts have been devoted to constructing more active edge sites and improving conductivity to obtain enhanced electrocatalytic performance. Herein, the 3D carbon foam (denoted as CF) supported edge‐rich N‐doped MoS2 nanoflakes were successfully fabricated by using the commercially available polyurethane foam (PU) as the 3D substrate and PMo12O403− clusters (denoted as PMo12) as the Mo source through redox polymerization, followed by sulfurization. Owing to the uniform distribution of nanoscale Mo sources and 3D carbon foam substrate, the as‐prepared MoS2‐CF composite possessed well‐exposed active edge sites and enhanced electrical conductivity. Systematic investigation demonstrated that the MoS2‐CF composite showed high HER performance with a low overpotential of 92 mV in 1.0 m KOH and 155 mV in 0.5 m H2SO4 at a current density of 10 mA cm−2. This work offers a new pathway for the rational design of MoS2‐based HER electrocatalysts.
Chemical Reactions of Cationic Metallofullerenes: An Alternative Route for Exohedral Functionalization
Authors: Hu Yajing , Solé‐Daura Albert , Yao Yang‐Rong , Liu Xuechen , Liu Sijie , Yu Ao , Peng Ping , Poblet Josep M. , Rodríguez‐Fortea Antonio , Echegoyen Luis , Li Fang‐Fang
Published: November 2019

The chemistry of cationic forms of clusterfullerenes remain less explored than that of the corresponding neutral or anionic species. In the present work, M3N@Ih‐C80(M=Sc or Lu) cations were generated by both electrochemical and chemical oxidation methods. The as‐obtained cations successfully underwent the typical Bingel–Hirsch reaction that fails with neutral Sc3N@Ih‐C80. Two isomeric Sc3N@Ih‐C80cation derivatives, [5,6]‐open and [6,6]‐open adducts, were synthesized, and the former has never been prepared by means of a Bingel–Hirsch reaction with neutral clusterfullerenes. In the case of the Lu3N@Ih‐C80cation, however, only a [6,6]‐open adduct was obtained. Density functional theory (DFT) calculations indicated that the oxidized M3N@Ih‐C80was much more reactive than the neutral compound upon addition of the diethyl bromomalonate anion. The Bingel–Hirsch reaction of M3N@Ih‐C80cations occurred by means of an unusual outer‐sphere single‐electron transfer (SET) process from the diethyl bromomalonate anion to the stable intermediate [M3N@C80(C2H5COO)2CBr].. Remarkably, the diethyl bromomalonate anion was found to act as both a nucleophile and an electron donor.
Intercalation of a Heterocyclic Ligand between Quartets in a G‐Rich Tetrahelical Structure
Authors: Kotar Anita , Kocman Vojč , Plavec Janez
Published: November 2019

YES G‐rich oligonucleotide VK2 folds into an AGCGA‐quadruplex tetrahelical structure distinct and significantly different from G‐quadruplexes, even though it contains four G3tracts. Herein, a bis‐quinolinium ligand 360A with high affinity for G‐quadruplex structures and selective telomerase inhibition is shown to strongly bind to VK2. Upon binding, 360A does not induce a conformational switch from VK2 to an expected G‐quadruplex. In contrast, NMR structural study revealed formation of a well‐defined VK2–360A complex with a 1:1 binding stoichiometry, in which 360A intercalates between GAGA‐ and GCGC‐quartets in the central cavity of VK2. This is the first high‐resolution structure of a G‐quadruplex ligand intercalating into a G‐rich tetrahelical fold. This unique mode of ligand binding into tetrahelical DNA architecture offers insights into the stabilization of an AGCGA‐quadruplex by a heterocyclic ligand and provides guidelines for rational design of novel VK2 binding molecules with selectivity for different DNA secondary structures.
Galactose‐Grafted 2D Nanosheets from the Self‐Assembly of Amphiphilic Janus Dendrimers for the Capture and Agglutination of Escherichia coli
Authors: Krishnan Nithiyanandan , Perumal Devanathan , Atchimnaidu Siriki , Harikrishnan Kaloor S. , Golla Murali , Kumar Nilima Manoj , Kalathil Jemshiya , Krishna Jithu , Vijayan Dileep K. , Varghese Reji
Published: November 2019

High aspect ratio, sugar‐decorated 2D nanosheets are ideal candidates for the capture and agglutination of bacteria. Herein, the design and synthesis of two carbohydrate‐based Janus amphiphiles that spontaneously self‐assemble into high aspect ratio 2D sheets are reported. The unique structural features of the sheets include the extremely high aspect ratio and dense display of galactose on the surface. These structural characteristics allow the sheet to act as a supramolecular 2D platform for the capture and agglutination of E. coli through specific multivalent noncovalent interactions, which significantly reduces the mobility of the bacteria and leads to the inhibition of their proliferation. Our results suggest that the design strategy demonstrated here can be applied as a general approach for the crafting of biomolecule‐decorated 2D nanosheets, which can perform as 2D platforms for their interaction with specific targets.
Economic complexity, product space network and Quebec's global competitiveness
Authors: Wang Yihan , Turkina Ekaterina
Published: November 2019

This exploratory study uncovers how the economic complexity of local production and global connectivity contribute to a subnational region's competitiveness and sustainable development. Addressing the knowledge generation and exchange processes orchestrated by global value chains, we demonstrate that the composition of a subnational region's product space network does not necessarily replicate the same configuration of the country‐level network. By applying social network analysis (SNA) techniques, we analyze the structural features of Quebec's product space network and compare the complexity indices of the province's advantageous sectors with those of Canada. Finally, we conclude with policy insights for sustainable development and suggest future research directions.
Tumor‐derived cell‐free DNA in body cavity effusion supernatants: A promising alternative for genomic profiling
Authors: Roy‐Chowdhuri Sinchita
Published: November 2019

Genomic profiling of tumor from malignant effusions have conventionally been performed on tumor cells derived from cytologic preparations such as cell block preparations, direct smears, cytospin preparations and liquid based cytologic preparations. The study by Yang et al. exemplifies the rapid progress of molecular cytopathology as cytopathologists increasingly delve into novel sources for genomic testing in an attempt to provide the theranostic information necessary for patient care.
Proteomic Detection and Validation of Translated Small Open Reading Frames
Authors: Khitun Alexandra , Slavoff Sarah A.
Published: November 2019

Small open reading frames (smORFs) encode previously unannotated polypeptides or short proteins that regulate translation in cis (eukaryotes) and/or are independently functional (prokaryotes and eukaryotes). Ongoing efforts for complete annotation and functional characterization of smORF‐encoded proteins have yielded novel regulators and therapeutic targets. However, because they are excluded from protein databases, initiate at non‐AUG start codons, and produce few unique tryptic peptides, unannotated small proteins cannot be detected with standard proteomic methods. Here,, we outline a procedure for mass spectrometry‐based detection of translated smORFs in cultured human cells from protein extraction, digestion, and LC‐MS/MS, to database preparation and data analysis. Following proteomic detection, translation from a unique smORF may be validated via siRNA‐based silencing or overexpression and epitope tagging. This is necessary to unambiguously assign a peptide to a smORF within a specific transcript isoform or genomic locus. Provided that sufficient starting material is available, this workflow can be applied to any cell type/organism and adjusted to study specific (patho)physiological contexts including, but not limited to, development, stress, and disease. © 2019 by John Wiley & Sons, Inc.

Basic Protocol 1: Protein extraction, size selection, and trypsin digestion

Alternate Protocol 1: In‐solution C8 column size selection

Support Protocol 1: Chloroform/methanol precipitation

Support Protocol 2: Reduction, alkylation, and in‐solution protease digestion

Support Protocol 3: Peptide de‐salting

Basic Protocol 2: Two‐dimensional LC‐MS/MS with ERLIC fractionation

Basic Protocol 3: Transcriptomic database construction

Alternate Protocol 2: Transcriptomics database generation with gffread

Basic Protocol 4: Non‐annotated peptide identification from LC‐MS/MS data

Basic Protocol 5: Validation using isotopically labeled synthetic peptide standards and siRNA

Basic Protocol 6: Transcript validation using transient overexpression
Density peaks clustering based on circular partition and grid similarity
Authors: Zhao Jia , Tang Jingjing , Fan Tanghuai , Li Chenming , Xu Lizhong
Published: November 2019

In density peaks clustering, its complexity for computing local density and relative distance of samples raises a scalability issue for processing large datasets. To address the issue, density peaks clustering based on circular partition and grid similarity has been proposed. The algorithm partitions the data space into circular grids, with each grid treated as a sample, for determining the number of clusters and searching for the density peaks; then, a new grid similarity is calculated to effectively assign unallocated grids. The proposed circular partition method effectively reduces the number of samples and the computational complexity. Extensive experiments have been conducted on several datasets with arbitrary shapes and scales, and the proposed method outperforms other density peaks clustering variants in terms of clustering accuracy and efficiency.
PROMIS: Global Analysis of PROtein‐Metabolite Interactions
Authors: Sokolowska Ewelina M. , Schlossarek Dennis , Luzarowski Marcin , Skirycz Aleksandra
Published: November 2019

Small molecules are not only intermediates of metabolism, but also play important roles in signaling and in controlling cellular metabolism, growth, and development. Although a few systematic studies have been conducted, the true extent of protein–small molecule interactions in biological systems remains unknown. PROtein–metabolite interactions using size separation (PROMIS) is a method for studying protein–small molecule interactions in a non‐targeted, proteome‐ and metabolome‐wide manner. This approach uses size‐exclusion chromatography followed by proteomics and metabolomics liquid chromatography–mass spectrometry analysis of the collected fractions. Assuming that small molecules bound to proteins would co‐fractionate together, we found numerous small molecules co‐eluting with proteins, strongly suggesting the formation of stable complexes. Using PROMIS, we identified known small molecule–protein complexes, such as between enzymes and cofactors, and also found novel interactions. © 2019 The Authors.

Basic Protocol 1: Preparation of native cell lysate from plant material

Support Protocol: Bradford assay to determine protein concentration

Basic Protocol 2: Separation of molecular complexes using size‐exclusion chromatography

Basic Protocol 3: Simultaneous extraction of proteins and metabolites using single‐step extraction protocol

Basic Protocol 4: Metabolomics analysis

Basic Protocol 5: Proteomics analysis
Tissue‐specific tumor microenvironments influence responses to immunotherapies
Authors: Oliver Amanda J , Davey Ashleigh S , Keam Simon P , Mardiana Sherly , Chan Jack D , von Scheidt Bianca , Beavis Paul A , House Imran G , Van Audernaerde Jonas RM , Darcy Phillip K , Kershaw Michael H , Slaney Clare Y
Published: November 2019

Objectives

Investigation of variable response rates to cancer immunotherapies has exposed the immunosuppressive tumor microenvironment (TME) as a limiting factor of therapeutic efficacy. A determinant of TME composition is the tumor location, and clinical data have revealed associations between certain metastatic sites and reduced responses. Preclinical models to study tissue‐specific TMEs have eliminated genetic heterogeneity, but have investigated models with limited clinical relevance.

Methods

We investigated the TMEs of tumors at clinically relevant sites of metastasis (liver and lungs) and their impact on αPD‐1/αCTLA4 and trimAb (αDR5, α4‐1BB, αCD40) therapy responses in the 67NR mouse breast cancer and Renca mouse kidney cancer models.

Results

Tumors grown in the lungs were resistant to both therapies whereas the same tumor lines growing in the mammary fat pad (MFP), liver or subcutaneously could be completely eradicated, despite greater tumor burden. Assessment of tumor cells and drug delivery in 67NR lung or MFP tumors revealed no differences and prompted investigation into the immune TME. Lung tumors had a more immunosuppressive TME with increased myeloid‐derived suppressor cell infiltration, decreased T cell infiltration and activation, and decreased NK cell activation. Depletion of various immune cell subsets indicated an equivalent role for NK cells and CD8+ T cells in lung tumour control. Thus, targeting T cells with αPD‐1/αCTLA4 or trimAb was not sufficient to elicit a robust antitumor response in lung tumors.

Conclusion

Taken together, these data demonstrate that tissue‐specific TMEs influence immunotherapy responses and highlight the importance in defining tissue‐specific response patterns in patients.
The association between mothers’ and daughters’ positive affect is moderated by child cardiac vagal regulation
Authors: Rousseau Sofie , Kritzman Lior , Frenkel Tahl I. , Levit‐Binnun Nava , Golland Yulia
Published: November 2019

Introduction

Extensive research has supported the importance of children's positive affect in fostering prosperous psychosocial adjustment. Children's positive affect is believed to be significantly shaped by their environment in general and their caregivers’ positive affect in particular. The current study investigates the role of child cardiac vagal regulation, a psychophysiological marker for social engagement, in shaping the association between maternal positive affect and child positive affect.

Methods

Mothers and daughters (ndyads = 28) participated in two experimental conditions. In the non‐interactive condition, they separately drew a picture without interacting. In the cooperative condition, they drew a picture together. We measured child respiratory sinus arrhythmia (RSA), a widely used indicator of cardiac vagal regulation, during both conditions. We also coded maternal and child positive affect during the cooperative condition.

Results

Maternal positive affect was related to child positive affect, but only for children with medium‐to‐high tonic levels of RSA and RSA increases from non‐interaction to interaction.

Discussion

Results suggest that child RSA plays a significant role in positive emotion socialization, by making children more susceptible to the emotional cues of their caregivers. Hence, child RSA should be taken into account in preventive and therapeutic efforts regarding child positive affect socialization.
In‐hospital ventricular arrhythmia in heart failure patients: 7 year follow‐up of the multi‐centric HEARTS registry
Authors: Alenazy Basel , Tharkar Shabana , Kashour Tarek , Alhabib Khalid Faiz , Alfaleh Hussam , Hersi Ahmad
Published: November 2019

Aims

The aim of this study was to determine the incidence, predictors, and short‐term and long‐term outcomes associated with in‐hospital sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) collectively termed ventricular arrhythmia (VA) in the heart failure (HF) patients.

Methods and results

The HEart function Assessment Registry Trial in Saudi Arabia (HEARTS registry) is a prospective national registry of patients with chronic HF from18 tertiary care hospitals across Saudi Arabia. Diagnosis of HF was in accordance with American Heart Association/European Society of Cardiology definition criteria. The registry had enrolled 2610 HF patients during the 14 month recruitment period between October 2009 and December 2010. Occurrence of in‐hospital cardiac events, prognosis, and outcome were monitored during the 7 year follow‐up period. The incidence of in‐hospital VA in HF was 4.2%. VA was more common among men, and mean age was lesser than non‐VA patients (58.5 ± 16: 61.5 ± 15 years; P = 0.042). Smoking and family history of cardiomyopathy were significant risk factors of VA. Previous history of arrhythmia, ST elevated myocardial infarction, infections, and hypotension remained significant predictors of in‐hospital VA associated with three to seven times more risk. Patients with VA had higher rates of in‐hospital events like recurrent HF, haemodialysis, shock, sepsis, major bleeding, intra‐aortic balloon pump, and stroke compared with those without VA, all being highly significant (P < 0.001). After adjustment for age, gender, and co‐morbidities, in‐hospital VA increased the risk of cardiogenic shock by 24 times, dialysis and major bleeding by 10 times, and recurrent congestive HF and pacing by five times. Survival analysis showed that all‐cause mortality was significantly higher in the VA patients (P < 0.001). Presence of VA increased in‐hospital and 1 month mortality to 23 and 17 times, respectively.

Conclusions

Lower mean age of VA complicated HF patients is a matter of concern in the Saudi population. HF associated with VA increased in‐hospital events and all‐cause mortality indicating poor prognosis and survival. These findings enable risk stratification and reflect on the importance of early recognition of the clinical markers and predictors of VA prompting immediate management.
New Synthetic Route for Cobalt(III) Dissymmetric Bisalkynyl Complexes Based on Cobalt(III)(cyclam)(C2NAPMes)
Authors: Banziger Susannah D. , Zeller Matthias , Ren Tong
Published: November 2019

The synthesis and characterization of dissymmetric CoIII‐bis‐alkynyl complexes supported by cyclam (1,4,8,11‐tetraazacyclotetradecane) are reported. A series of trans‐[Co(cyclam)(C2NAPR)Cl]Cl were prepared from the reaction between [Co(cyclam)Cl2]Cl and HC2NAPR in the presence of Et3N, where NAPR is N‐R‐1,8‐naphthalimide with R as mesityl (Mes, 1a), methyl (Me, 1b), 1‐ethylpropyl (Pen, 1c), 2‐ethylhexyl (2‐ethhex, 1d), or n‐octyl (Oct, 1e). Treating compounds 1a and 1b with AgOTf in NCCH3 resulted in trans‐[Co(cyclam)(C2NAPR)(NCCH3)](OTf)2 (2a and 2b, respectively), while reactions with 1c, 1d and 1e under the same conditions yielded only intractable mixtures. More soluble 2a reacted further with HC2Ar in the presence of Et3N to afford trans‐[Co(cyclam)(C2NAPR)(C2Ar)](OTf) with Ar as C6H4‐4‐NMe2 (3a), NAPMes (3b) and Ph (3c). All new complexes were characterized using X‐ray diffraction (1a, 1c and 3b), IR, 1H NMR, UV/Vis and fluorescent spectroscopy, and cyclic voltammetry.
Helicene Bis(pyrazol‐1‐yl)pyridine Ligands for Luminescent Transition‐Metal Complexes
Authors: Abhervé Alexandre , Martin Kévin , Hauser Andreas , Avarvari Narcis
Published: November 2019

Invited for the cover of this issue is Narcis Avarvari from the University of Angers, France. The cover image shows one of the helicene‐based ligands that has been designed and coordinated to transition metal ions for the preparation of luminescent complexes.
Synthesis of Functionalized Naphthalene Diimides and their Redox Properties
Authors: Shukla Jyoti , Mukhopadhyay Pritam
Published: November 2019

In this article, we have discussed the recently developed synthetic routes to amplify the electron‐poor nature of the naphthalenediimides (NDIs) as well as the integration of electron‐rich donor groups towards ambipolar and strongly electron donating NDIs. Non‐conventional electron withdrawing groups (EWGs) have been applied, leading to highly electron deficient NDIs. Highly π‐acidic molecules with LUMO levels up to –5.0 eV have now been realized. Cationic EWGs have been integrated at the NDI‐core resulting in six‐electron acceptors called “electron‐sponge”. Electron donating groups like tetrathiafulvalene, dicyanomethides, amino‐groups, etc. have been substituted to realize ambipolar NDIs with high HOMO levels and “electron‐reservoir” properties. Diverse coupling reactions such as, Suzuki, Sonogashira, Stille, Buchwald–Hartwig, etc. have been performed to achieve attractive redox properties. Double cross‐coupling reactions have been successful with metallacyclopentadienes to establish highly extended NDIs. The new synthetic routes to NDIs have significantly extended the electrochemical window, improved their optical properties and have resulted in attractive panchromatic systems and driven new applications.
Metal‐Free Arylation‐Lactonization Sequence of γ‐Alkenoic Acids Using Anilines as Aryl Radical Precursors
Authors: Felipe‐Blanco Diego , Gonzalez‐Gomez Jose C.
Published: November 2019

The presence of salicylic acid (10 mol‐%) and H2O (10 equiv.) significantly improves the arylation‐lactonization sequence of γ‐alkenoic acids with in situ formed diazonium salts (from bench stable anilines). The reaction is finished in less than 5 h without thermal or photochemical activation, giving access to a variety of γ,γ‐disubstituted butyrolactones. The protocol is user‐friendly and can be used at gram‐scale or adapted to transform alkenols into phthalanes. Control experiments revealed that aryl radicals participate in the reaction and a plausible mechanism is proposed to include this and other mechanistic investigations, for the catalyzed and the background reaction.
Food safety governance in China: From supervision to coregulation
Authors: Liu Zhe , Mutukumira Anthony N. , Chen Hongjun
Published: November 2019

The food control and regulatory system in China is beset by several challenges. While firms have to reduce their costs in pursuit of benefits, customers are increasingly focusing on safety and quality of food products. Although the Chinese government has developed more stringent regulatory measures, food safety incidents still occur, including abuse of food additives, adulterated products as well as contamination by pathogenic microorganisms, pesticides, veterinary drug residues, and heavy metals, and use of substandard materials. A national food safety strategy has been proposed to assure food safety from “farm to table.” This paper begins with the analysis of current food regulatory systems and then discusses cogovernance of food safety management in China. We explore the practice in the city of Shenzhen where government intervention has strengthened food control, thereby creating an opportunity to form a coregulatory system. The review highlights that the current food safety regulatory system of multi‐agency structure can inevitably lead to insufficient incentives for business entities. Due to asymmetric information, lack of regulatory resources, and consumer advocacy, coregulation has been developed and is increasingly being promoted as an important instrument of food regulation.
Double dissociation of learned approach–avoidance conflict processing and spatial pattern separation along the dorsoventral axis of the dentate gyrus
Authors: Yeates Dylan C. M. , Ussling Alicia , Lee Andy C. H. , Ito Rutsuko
Published: November 2019

The ventral portion of the rodent hippocampus (HPC; anterior in primates) has been implicated in the detection and resolution of approach–avoidance conflict, which arises when an organism encounters a stimulus that predicts both positive and negative outcomes. Previous work has found differential regulation of approach–avoidance conflict behavior by the CA3 and CA1 subfields, with inhibition of ventral CA3 increasing approach toward conflicting stimuli and inhibition of the ventral CA1 potentiating avoidance. Here, we sought to extend these findings by investigating the role of the dentate gyrus (DG), the input region of the HPC, in learned approach–avoidance conflict processing in rats. Animals were first trained to acquire three different visuotactile cue‐outcome associations in separate arms of a Y‐maze (appetitive, aversive, and neutral). Postacquisition, they were administered a “conflict test,” in which they were presented with a choice between exploring an arm in which the appetitive and aversive cues were concurrently presented (conflict stimulus), and another arm containing the neutral stimulus. GABAR‐mediated inactivation of the ventral DG, but not dorsal DG, potentiated approach behavior toward the conflict stimulus, similar to the effects of ventral CA3 inactivation. In contrast, dorsal DG, but not ventral DG, inactivation was found to impair performance on a metric spatial discrimination task, which is commonly used as a test of pattern separation. The findings of this study demonstrate a robust double dissociation between the ventral and dorsal aspects of the DG, in line with previous reports of functional differences along the longitudinal axis of the HPC.
Should accountants care about blockchain?
Authors: Fuller Stephen H. , Markelevich Ariel
Published: November 2019

The use of blockchain technology has increased tremendously over the last decade. Blockchain continues to evolve and new features and capabilities are developed continuously. Although the use of the technology started in cryptocurrency (specifically, Bitcoin), it has expanded to other areas that can benefit from a shared, secure, ledger. This article investigates the potential impact of blockchain technology on the accounting profession. This article analyzes data security and privacy considerations, technology, adoption, and implementation considerations, and some considerations that relate specifically to accounting and auditing. We find that the unique needs of an accounting information system may not be a good match for blockchain as it currently exists. While we explain that blockchain may deliver many benefits, particularly in the areas of data reliability and the financial statement audit, we identify several factors, which raise significant questions about whether blockchain will ever be significantly integrated in the accounting function. Chief among those concerns is the scalability of the technology at an acceptable cost. While significant investment has and will be made for further development of blockchain business applications, it is our assessment that proponents of blockchain integration in accounting have not yet made the economic case for it. We also have significant concerns about whether blockchain technology can adequately address risks associated with data security and privacy. Addressing all these issues will be a minimum requirement for gaining widespread acceptance by firms and their accountants.
Kinetics and Thermodynamics of Reactions Involving Criegee Intermediates: An Assessment of Density Functional Theory and Ab Initio Methods Through Comparison with CCSDT(Q)/CBS Data
Authors: Smith Cameron D. , Karton Amir
Published: November 2019

Reactions involving Criegee intermediates (CIs, R1R2COO) are important in atmospheric ozonolysis models. In recent years, density functional theory (DFT) and CCSD(T)‐based ab initio methods are increasingly being used for modeling reaction profiles involving CIs. We obtain highly accurate CCSDT(Q)/CBS reaction energies and barrier heights for ring‐closing reactions involving atmospherically important CIs (R1/R2 = H, Me, OH, OMe, F, CN, cyclopropene, ethylene, acetaldehyde, and acrolein). We use this benchmark data to evaluate the performance of DFT, double‐hybrid DFT (DHDFT), and ab initio methods for the kinetics and thermodynamics of these reactions. We find that reaction energies are more challenging for approximate theoretical procedures than barrier heights. Overall, taking both reaction energies and barrier heights into account, only one of the 58 considered DFT methods (the meta‐GGA MN12‐L) attains near chemical accuracy, with root‐mean‐square deviations (RMSDs) of 3.5 (barrier heights) and 4.7 (reaction energies) kJ mol−1. Therefore, MN12‐L is recommended for investigations where CCSD(T)‐based methods are not computationally feasible. For reaction barrier heights performance does not strictly follow Jacob's Ladder, for example, DHDFT methods do not perform better than conventional DFT methods. Of the ab initio methods, the cost‐effective CCSD(T)/CBS(MP2) approach gives the best performance for both reaction energies and barrier heights, with RMSDs of 1.7 and 1.4 kJ mol−1, respectively. All the considered Gaussian‐n methods show good performance with RMSDs below the threshold of chemical accuracy for both reaction energies and barrier heights, where G4(MP2) shows the best overall performance with RMSDs of 2.9 and 1.5 kJ mol−1, respectively. © 2019 Wiley Periodicals, Inc.
Novel missense alteration in LRP4 gene underlies Cenani–Lenz syndactyly syndrome in a consanguineous family
Authors: Alrayes Nuha , Aziz Abdul , Ullah Farman , Ishfaq Muhammad , Jelani Musharraf , Wali Abdul
Published: November 2019

Background

Syndactyly is a clinical feature of split‐hand foot malformation (SHFM), ectodermal‐dysplasia‐syndactyly (EDSS1) and Cenani–Lenz syndactyly syndromes (CLSS). In EDSS1, only cutaneous syndactyly is observed, with sparse hair, abnormal nails and dentition. In SHFM, bony syndactyly may vary from hypoplasia of one phalanx to aplasia of central digits, extending to complete fusion of all fingers and toes in CLSS. Several genes have been assigned to these syndromes. Performing a single step molecular diagnostics becomes a challenge when a phenotype has overlaps with several syndromes or when some of the clinical features are not fully expressed in patients.

Methods

Whole exome sequencing (WES) analysis on one sample derived from a consanguineous family was performed. A causative variant in WES data was prioritized via standard bioinformatics tools. The selected variant was Sanger sequenced in all the available family members for autosomal recessive segregation.

Results

A novel missense variant (c.1151A>G; p.Tyr384Cys) was identified in the LRP4 gene. Sanger validation confirmed that all affected individuals were homozygous and the obligate carriers were heterozygous for this variant. The variant is neither reported in 1000 human genomes, nor in 60 706 exomes databases, and is predicted as “pathogenic” by SIFT, Polyphen‐2 and MutationTaster software.

Conclusions

The present study broadens the pathogenic spectrum of the LRP4 gene in syndactyly syndromes. WES is a powerful tool for genetic analysis in research and can be readily used as a first‐line diagnostic test in syndactyly and related phenotypes.
Epidemiologic features of children with Epstein‐Barr virus associated diseases in Hangzhou, China
Authors: Shi Jianrong , Ma Wangqian , Li Wei
Published: November 2019

Epstein‐Barr virus (EBV) infection is the causative agent of multiple diseases. EBV DNA in blood is a useful diagnostic marker of primary EBV infection and reactivation. This study aimed to provide epidemiological information on children with EBV‐associated diseases identified by positive EBV DNA in Hangzhou, a city in East China. All children admitted to the Children's Hospital of Zhejiang University School of Medicine from 2010 to 2015 with suspected EBV‐related diseases and serum EBV DNA tested by quantitative real‐time polymerase chain reaction were included. Of the 10 470 children, 1205 were determined to have positive EBV DNA, and the positive rate was 11.5%. 15.8% (973 of 6162) of the illnesses of patients aged 1 to 7 years were caused by EBV as compared to that of 6.6% (179 of 2708) of children older than 7 years (P < .01) and 3.3% (53 of 1600) of of that of infants <1 year of age (P < .01). Among positive EBV DNA patients, 80.7% of EBV infections occurred in children at the age stage of 1 to 7 years. IM was the most common EBV‐related disease, accounting for 75.7% of 581 hospitalized patients. Children aged 1 to 3 years were the age group most commonly hospitalized with EBV‐IM (32.7% of the cohort) and EBV‐hemophagocytic lymphohistiocytosis (HLH) (52.6%), while EBV‐lymphoma was more common in children over 9‐year old (58.3% of the cohort). The serum EBV‐DNA load was much higher in patients with EBV‐HLH than in patients with IM (P < .05). This is a large sample study, which revealed the epidemiological characteristics of children with EBV‐associated diseases, including age, monthly and disease distribution.