bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrochemical Water Oxidation Catalyzed by N4‐Coordinate Copper Complexes with Different Backbones: Insight into the Structure‐Activity Relationship of Copper Catalysts
Authors: Shen Junyu , Zhang Xiongfei , Cheng Minglun , Jiang Jian , Wang Mei 
Published: December 2019

AbstractCopper complexes with a general formula of [(L)Cu(OH2)](BF4)2 (1, L1=N,N′‐dimethyl‐N,N′‐bis(pyridin‐2‐ylmethyl)‐1,2‐diaminoethane; 2, L2=N,N′‐bis(pyridin‐2‐ylmethyl)piperazine); 3, L3=N,N′‐bis(pyridin‐2‐ylmethyl)diazepane) were prepared as molecular catalysts for oxygen evolution reaction. These catalysts have the same first coordination environment but different backbones of diamine‐dipyridine N4‐ligands. Single crystal X‐ray diffraction studies on the molecular structures of 1–3 revealed that the backbone rigidity of the N4‐ligand has apparent influence on the Npy−Cu−N′py open angle of copper complexes. Comparative studies manifested that the subtle structural change caused by the backbone rigidity of N4‐ligands has an important influence on the catalytic performance and reaction pathway of copper catalysts for electrochemical water splitting.
Non‐Conventional Media as Strategy to Overcome the Solvent Dilemma in Chemoenzymatic Tandem Catalysis
Authors: Kourist Robert , González‐Sabín Javier 
Published: December 2019

AbstractThe amazing potential of multi‐catalytic cascade reactions to reduce the number of reaction steps and to solve synthetic problems brings the challenge of an increasing complexity that must be controlled. Particularly chemo‐enzymatic reactions are prone to conflicts regarding different optimal reaction conditions for chemical and biological catalysts. The preference of many chemical catalysts for hydrophobic (and often water‐free) solvent and of many enzymes for water poses a solvent dilemma. Recently, non‐conventional solvents have been very successful to provide suitable reaction media for catalysts that otherwise require very different solvents, and to alleviate fundamental problems such as the low solubility of many substrates in aqueous solvents. In the last few years, several examples underlined the considerable potential of ionic liquids and deep eutectic solvents for the engineering of cascade reactions. This mini‐review showcases the recent developments on the implementation of the so‐called non‐conventional media in such processes.
Intramolecular Metal‐Free N−N Bond Formation with Heteroaromatic Amines: Mild Access to Fused‐Triazapentalene Derivatives
Authors: Daniel Matthieu , Hiebel Marie‐Aude , Guillaumet Gérald , Pasquinet Eric , Suzenet Franck 
Published: December 2019

AbstractFormation of N−N bonds may offer an original approach to various nitrogen‐containing heterocycles with numerous applications. For this purpose, we found that readily available heteroaromatic amines are appropriate substrates for providing an efficient and innovative approach for the formation of N−N bonds in the presence of iodine (III) reagent in very mild conditions. This method makes it possible to synthesize nitrogen rich triazapentalene derivatives exhibiting fluorescent properties, inaccessible with existing approaches.
Efficacy and safety of dronedarone in patients with a prior ablation for atrial fibrillation/flutter: Insights from the ATHENA study
Authors: Vamos Mate , Calkins Hugh , Kowey Peter R. , Torp‐Pedersen Christian T. , Corp dit Genti Valérie , Wieloch Mattias , Koren Andrew , Hohnloser Stefan H. 
Published: December 2019

AbstractBackgroundThe role of antiarrhythmic drugs for atrial fibrillation/atrial flutter (AF/AFL) after catheter ablation is not well established.HypothesisWe hypothesized that changing the myocardial substrate by ablation may alter the responsiveness to dronedarone.MethodsWe assessed the efficacy and safety of dronedarone in the treatment of paroxysmal/persistent atrial fibrillation/atrial flutter (AF/AFL) post‐ablation, based on a post hoc analysis of the ATHENA study. A total of 196 patients (dronedarone 90, placebo 106) had an ablation for AF/AFL before study entry. In these patients, the effect of treatment on the first hospitalization because of cardiovascular (CV) events/all‐cause death was assessed, as was AF/AFL recurrence in individuals with sinus rhythm at baseline. The safety of dronedarone vs placebo was also determined.ResultsIn patients with prior ablation, dronedarone reduced the risk of AF/AFL recurrence (hazard ratio [HR]: 0.65 [95% confidence interval [CI]: 0.42, 1.00]; P < .05) as well as the median time to first AF/AFL recurrence (561 vs 180 days) compared with placebo. The HR for first CV hospitalization/all‐cause death with dronedarone vs placebo was 0.98 (95% CI: 0.62, 1.53; P = .91). Rates of treatment‐emergent adverse events were 83.1% vs 75.5% and rates of serious TEAEs were 27.0% vs 18.9% in the dronedarone and placebo groups, respectively. One death occurred with dronedarone (not treatment‐emergent) and five occurred with placebo.ConclusionIn patients with prior ablation for AF/AFL, dronedarone reduced the risk of AF/AFL recurrence compared with placebo, but not the risk of first CV hospitalization/all‐cause death. Safety outcomes were consistent with those of the overall ATHENA study.
Antibodies to the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 contribute to neuronal cell loss in an animal model of multiple sclerosis
Authors: Libner Cole D. , Salapa Hannah E. , Hutchinson Catherine , Lee Sangmin , Levin Michael C. 
Published: December 2019

AbstractNeurodegeneration, including loss of neurons and axons, is a feature of progressive forms of multiple sclerosis (MS). The mechanisms underlying neurodegeneration are mostly unknown. Research implicates autoimmunity to nonmyelin self‐antigens as important contributors to disease pathogenesis. Data from our lab implicate autoimmunity to the RNA binding protein (RBP) heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a possible mechanism of neurodegeneration in MS. MS patients make antibodies to hnRNP A1, which have been shown to lead to neuronal dysfunction in vitro. Using an animal model of MS, experimental autoimmune encephalomyelitis (EAE), we show here that injection of anti‐hnRNP A1 antibodies, in contrast to control antibodies, resulted in worsened disease and increased neurodegeneration. We found a reduction of NeuN+ neuronal cell bodies in areas of the ventral gray matter of the spinal cord where anti‐hnRNP A1 antibodies localized. Neurons displayed increased levels of hnRNP A1 nucleocytoplasmic mislocalization and stress granule formation, both markers of neuronal injury. Anti‐hnRNP A1 antibodies were found to surround neuronal cell bodies and interact with CD68+ immune cells via Fc receptors. Additionally, anti‐hnRNP A1 antibodies were found within neuronal cell bodies including those of the ventral spinocerebellar tract (VSCT), a tract previously shown to undergo neurodegeneration in anti‐hnRNP A1 antibody injected EAE mice. Finally, both immune cells and neurons showed increased levels of inducible nitric oxide synthase, another indicator of cell damage. These findings suggest that autoimmunity to RBPs, such as hnRNP A1, play a role in neurodegeneration in EAE with important implications for the pathogenesis of MS.
Ablation of spinal cord estrogen receptor α‐expressing interneurons reduces chemically induced modalities of pain and itch
Authors: Tran May , Braz Joao Manuel , Hamel Katherine , Kuhn Julia , Todd Andrew J. , Basbaum Allan I. 
Published: December 2019

AbstractEstrogens are presumed to underlie, at least in part, the greater pain sensitivity and chronic pain prevalence that women experience compared to men. Although previous studies revealed populations of estrogen receptor‐expressing neurons in primary afferents and in superficial dorsal horn neurons, there is little to no information as to the contribution of these neurons to the generation of acute and chronic pain. Here we molecularly characterized neurons in the mouse superficial spinal cord dorsal horn that express estrogen receptor α (ERα) and explored the behavioral consequences of their ablation. We found that spinal ERα‐positive neurons are largely excitatory interneurons and many coexpress substance P, a marker for a discrete subset of nociceptive, excitatory interneurons. After viral, caspase‐mediated ablation of spinal ERα‐expressing cells, we observed a significant decrease in the first phase of the formalin test, but in male mice only. ERα‐expressing neuron‐ablation also reduced pruritogen‐induced scratching in both male and female mice. There were no ablation‐related changes in mechanical or heat withdrawal thresholds or in capsaicin‐induced nocifensive behavior. In chronic pain models, we found no change in Complete Freund's adjuvant‐induced thermal or mechanical hypersensitivity, or in partial sciatic nerve injury‐induced mechanical allodynia. We conclude that ERα labels a subpopulation of excitatory interneurons that are specifically involved in chemically evoked persistent pain and pruritogen‐induced itch.
Spatial models of cell distribution in human lumbar dorsal root ganglia
Authors: Sperry Zachariah J. , Graham Robert D. , Peck‐Dimit Nicholas , Lempka Scott F. , Bruns Tim M. 
Published: December 2019

AbstractDorsal root ganglia (DRG), which contain the somata of primary sensory neurons, have increasingly been considered as novel targets for clinical neural interfaces, both for neuroprosthetic and pain applications. Effective use of either neural recording or stimulation technologies requires an appropriate spatial position relative to the target neural element, whether axon or cell body. However, the internal three‐dimensional spatial organization of human DRG neural fibers and somata has not been quantitatively described. In this study, we analyzed 202 cross‐sectional images across the length of 31 human L4 and L5 DRG from 10 donors. We used a custom semi‐automated graphical user interface to identify the locations of neural elements in the images and normalize the output to a consistent spatial reference for direct comparison by spinal level. By applying a recursive partitioning algorithm, we found that the highest density of cell bodies at both spinal levels could be found in the inner 85% of DRG length, the outer‐most 25–30% radially, and the dorsal‐most 69–76%. While axonal density was fairly homogeneous across the DRG length, there was a distinct low density region in the outer 7–11% radially. These findings are consistent with previous qualitative reports of neural distribution in DRG. The quantitative measurements we provide will enable improved targeting of future neural interface technologies and DRG‐focused pharmaceutical therapies, and provide a rigorous anatomical description of the bridge between the central and peripheral nervous systems.
RALB‐HC: A resource‐aware load balancer for heterogeneous cluster
Authors: Ahmed Usman , Aleem Muhammad , Noman Khalid Yasir , Arshad Islam Muhammad , Azhar Iqbal Muhammad 
Published: December 2019

SummaryIn the heterogeneous computing environment, programmers map the applications either on CPUs or GPUs. However, this default mapping process does not produce improved results, particularly on the heterogeneous clusters. If one resource of the cluster is more compute capable, then most of the scheduling schemes favor that powerful device. In this scenario, the scheduling schemes overload the powerful resources while making all other compute resources remain under utilized. This load imbalance problem results in higher energy consumption and increased execution time. In this research, a novel Resource‐Aware Load Balancer for the Heterogeneous Cluster (RALB‐HC) is proposed that distributes workload based on resources computing capabilities and applications computing needs. The RALB‐HC uses supervised machine learning approach to classify applications using the static code‐features. The RALB‐HC framework comprises of two phases: (1) job mapping based on the availability of the resources and (2) the resource‐aware load balancing to achieve the higher resource utilization ratio. The experimental results on a large set of real‐world and synthetic workloads show that the RALB‐HC reduces execution time by 31.61%, increased resource utilization ratio by 67.8% and improved throughout 147.35% as compared to baseline scheduling schemes.
Use of the CRISPR‐Cas9 System in Drosophila Cultured Cells to Introduce Fluorescent Tags into Endogenous Genes
Authors: Bosch Justin A. , Knight Shannon , Kanca Oguz , Zirin Jonathan , Yang‐Zhou Donghui , Hu Yanhui , Rodiger Jonathan , Amador Gabriel , Bellen Hugo J. , Perrimon Norbert , Mohr Stephanie E. 
Published: December 2019

AbstractThe CRISPR‐Cas9 system makes it possible to cause double‐strand breaks in specific regions, inducing repair. In the presence of a donor construct, repair can involve insertion or ‘knock‐in’ of an exogenous cassette. One common application of knock‐in technology is to generate cell lines expressing fluorescently tagged endogenous proteins. The standard approach relies on production of a donor plasmid with ∼500 to 1000 bp of homology on either side of an insertion cassette that contains the fluorescent protein open reading frame (ORF). We present two alternative methods for knock‐in of fluorescent protein ORFs into Cas9‐expressing Drosophila S2R+ cultured cells, the single‐stranded DNA (ssDNA) Drop‐In method and the CRISPaint universal donor method. Both methods eliminate the need to clone a large plasmid donor for each target. We discuss the advantages and limitations of the standard, ssDNA Drop‐In, and CRISPaint methods for fluorescent protein tagging in Drosophila cultured cells. © 2019 by John Wiley & Sons, Inc.Basic Protocol 1: Knock‐in into Cas9‐positive S2R+ cells using the ssDNA Drop‐In approachBasic Protocol 2: Knock‐in into Cas9‐positive S2R+ cells by homology‐independent insertion of universal donor plasmids that provide mNeonGreen (CRISPaint method)Support Protocol 1: sgRNA design and cloningSupport Protocol 2: ssDNA donor synthesisSupport Protocol 3: Transfection using EffecteneSupport Protocol 4: Electroporation of S2R+‐MT::Cas9 Drosophila cellsSupport Protocol 5: Single‐cell isolation of fluorescent cells using FACS
Automated Dynamic Clamp for Simulation of IK1 in Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes in Real Time Using Patchliner Dynamite8
Authors: Becker Nadine , Horváth András , De Boer Teun , Fabbri Alan , Grad Christian , Fertig Niels , George Michael , Obergrussberger Alison 
Published: December 2019

AbstractCurrent in vitro assays typically poorly predict cardiac liability as they focus on single ion channels overexpressed in cell lines. Human induced pluripotent stem cell–derived cardiomyocytes (hiPSC‐CMs), on the other hand, provide a unique opportunity for drug testing on human cardiomyocytes using high‐throughput systems. However, these cells can differ from adult cardiomyocytes in their ion channel expression and, therefore, electrophysiologic properties. One of the main challenges of hiPSC‐CMs is the physiologic expression of ion channels such as the inward rectifiers (e.g., Kir2.1–2.3), which conduct the cardiac inward rectifier potassium current (IK1). IK1 is one of the primary contributors in maintaining a stable resting membrane potential in cardiac cells, which is essential for excitability. This is only expressed in low levels, or sometimes not at all, in hiPSC‐CMs as shown by patch clamp studies. Dynamic clamp is a method of electronically introducing ion currents (e.g., IK1) into cells to compensate for the lack of endogenous expression, thus offering the potential to record more stable action potentials in hiPSC‐CMs. In this article, we describe the method of using hiPSC‐CMs on an automated patch clamp device (Patchliner) coupled with the automated dynamic clamp add‐on (Dynamite8). We describe protocols for optimized cell handling and harvesting for use on the Patchliner and the steps required for automated execution of experiments and data analysis in dynamic clamp mode. © 2019 by John Wiley & Sons, Inc.Basic Protocol: Recording action potential pharmacology from human induced pluripotent stem cell–derived cardiomyocytes in automated patch clamp combined with dynamic clamp to introduce simulated IK1 and compensate seal resistanceSupport Protocol 1: Cardiomyocyte plating and cultureSupport Protocol 2: Cell harvesting and dissociationAlternate Protocol: Recording action potential pharmacology at physiologic temperatures
Magnetic Resonance Relaxometry for Determination of Protein Concentration and Aggregation
Authors: Taraban Marc B. , Briggs Katharine T. , Yu Yihua Bruce 
Published: December 2019

AbstractThe water‐proton signal, overwhelmingly considered a nuisance in nuclear magnetic resonance spectroscopy, is advantageously used as a tool to assess protein concentration and to detect protein aggregates in aqueous solutions. The protocols in this article describe use of the water‐proton transverse relaxation rate to determine concentration and aggregate content in protein solutions. Detailed recommendations and description of the parameter settings and data processing ensure successful implementation of this technique, even by a user with limited experience in magnetic resonance relaxometry. All measurements are done noninvasively, in a sealed container, without sampling or otherwise aliquoting the solution. The magnetic resonance relaxometry approach offered in this article could be advantageous for analysis of biologics formulations or when use of conventional analytical techniques is not possible. © 2019 by John Wiley & Sons, Inc.Basic Protocol 1: Nuclear magnetic resonance (NMR) relaxometry to measure protein concentrationBasic Protocol 2: NMR relaxometry to measure protein aggregation
A potential association between IL‐3 and type I and III interferons in systemic lupus erythematosus
Authors: Oon Shereen , Monaghan Katherine , Ng Milica , Hoi Alberta , Morand Eric , Vairo Gino , Maraskovsky Eugene , Nash Andrew D , Wicks Ian P , Wilson Nicholas J 
Published: December 2019

AbstractObjectivesPlasmacytoid dendritic cells (pDCs), through the production of type 1 interferons (IFNs) and other cytokines, are major contributors to systemic lupus erythematosus (SLE) pathogenesis. IL‐3 promotes pDC survival, but its role in SLE is not well characterised. This study investigated serum IL‐3 and IFN levels, and a whole blood ‘IL‐3 gene signature’, in human SLE.MethodsSerum cytokine levels were measured by ELISA in n = 42 SLE patients, and n = 44 healthy donors. IL‐3‐regulated genes were determined by RNASeq of healthy donor whole blood cells (WBCs) stimulated in vitro with IL‐3 for 6 or 24 h. Whole blood cell RNASeq analysis was undertaken in a separate cohort of n = 31 SLE patients, and n = 28 healthy donors.ResultsSerum IL‐3 levels correlated with IFNα (r = 0.612, 95% CI 0.455–0.733, P < 0.001) and type III IFN (r = 0.585, 95% CI 0.406–0.720, P < 0.0001). IL‐3 stimulation of WBC in vitro altered 794 genes (−1 ≥ logFC ≥ 1, FDR < 0.05), of which 35 overlapped with genes differentially expressed between SLE and healthy donors. These 35 genes were expressed in 27/31 SLE donors, revealing the presence of an ‘IL‐3 gene signature’. There was strong correlation between the IL‐3 signature and an IFN signature, as determined by hierarchical clustering of the 500 most variable genes in SLE donors (r = 0.939, 95% CI 0.898–0.964, P < 0.0001).ConclusionA dual IL‐3/IFN gene signature is a feature of SLE. An association between IL‐3 and IFN raises the possibility that dual blockade of IL‐3 and IFN may be especially useful for SLE patients with this dual cytokine gene signature.
Bone marrow infiltration by flow cytometry at diffuse large B‐cell lymphoma NOS diagnosis implies worse prognosis without considering bone marrow histology
Authors: Martín‐Moro Fernando , Piris‐Villaespesa Miguel , Marquet‐Palomanes Juan , García‐Cosío Mónica , Villarrubia Jesús , Lario Ana , García Irene , Michael Berta , Roldán Ernesto , García‐Vela José Antonio , Lopez‐Jiménez Javier 
Published: December 2019

AbstractBackgroundThe significance of discrepant findings between histology (BMB) and flow cytometry (FC) in bone marrow (BM) examination at diffuse large B‐cell lymphoma (DLBCL) diagnosis is uncertain.MethodsWe performed a 5‐year retrospective single‐center study of patients diagnosed by DLBCL not otherwise specified (n = 82), divided into three groups according to BM infiltration at diagnosis: BMB−/FC− (75.6%), BMB+/FC+ (13.4%), and BMB−/FC+ (11%).ResultsMedian infiltration by FC analysis of the BMB−/FC+ group was 0.8% and if we considered BM infiltration as positive in all cases, 4/9 would be upstaged. Median follow was 33 months. Event‐free survival (EFS) after 18 months was 82, 23, and 27% for BMB−/FC−, BMB−/FC+, and BMB+/FC+, respectively (p < .001). After 18 months of observation, OS was 87, 46, and 55% for BMB−/FC−, BMB−/FC+, and BMB+/FC+, respectively (p = .001). In multivariate analysis (BM infiltration vs. cell‐of‐origin according to Hans algorithm and standard IPI), BM infiltration was independently associated with EFS (HR: 1.94, 95% CI: 1.3–2.9) and overall survival (HR: 1.69, 95% CI: 1.1–2.7).ConclusionIn summary, minimal BM infiltration, detected by FC but not by BMB, has same prognostic implications than overt BM infiltration and should be considered as extranodal involvement regardless the infiltration quantity.
Fine needle aspiration of malignant melanoma with myxoid features: A case report with molecular analysis
Authors: Felty Cameron C. , Jackson Christopher R. , Marotti Jonathan D. , Liu Xiaoying 
Published: December 2019

AbstractMalignant melanoma with myxoid features (MMM) is a rare melanoma variant in which tumor cells are embedded within a basophilic myxoid stroma. The stromal matrix is composed of acidic mucopolysaccharides, which are thought to be produced by mesenchymal stromal cells in response to melanoma invasion. Interestingly, this myxoid matrix is more often seen in metastasis from a primary tumor that does not have a myxoid stroma. The diagnosis of MMM on fine needle aspiration (FNA) can be confused with other myxoid tumors. Herein, we present a case of MMM diagnosed by FNA of a peri‐auricular lymph node in an 89‐year‐old man with a history of resected malignant melanoma. We describe the clinical, cytohistological, and immunohistochemical findings, and present the unique molecular alterations that were identified. We also discuss the differential diagnosis and potential diagnostic pitfalls associated with MMM.