bluuebunny/crossref_metadata_2025_split huggingface dataset:
The T‐Reflection and the Deep Crustal Structure of the Vøring Margin, Offshore mid‐Norway
Authors: Abdelmalak M. M. , Faleide J. I. , Planke S. , Gernigon L. , Zastrozhnov D. , Shephard G. E. , Myklebust R. 
Published: October 2017

AbstractSeismic reflection data along volcanic passive margins frequently provide imaging of strong and laterally continuous reflections in the middle and lower crust. We have completed a detailed 2‐D seismic interpretation of the deep crustal structure of the Vøring Margin, offshore mid‐Norway, where high‐quality seismic data allow the identification of high‐amplitude reflections, locally referred to as the T‐Reflection. Using a dense seismic grid, we have mapped the geometry of the T‐Reflection in order to compare it with filtered Bouguer gravity anomalies and seismic refraction data. The T‐Reflection is identified between 7 and 10 s. Sometimes it consists of one single smooth reflection. However, it is frequently associated with a set of rough multiple reflections displaying discontinuous segments with varying geometries, amplitudes, and contact relationships. The T‐Reflection seems to be connected to deep sill networks and is locally identified at the continuation of basement high structures or terminates over fractures and faults. The T‐Reflection presents a low magnetic signal. The spatial correlation between the filtered positive Bouguer gravity anomalies and the deep dome‐shaped reflections indicates that the latter represent a high‐impedance boundary contrast associated with a high‐density and high‐velocity body. In ~50% of the outer Vøring Margin, the depth of the mapped T‐Reflection is found to correspond to the depth of the top of the Lower Crustal Body (LCB), which is characterized by high P wave velocities (>7 km/s). We present a tectonic scenario, where a large part of the deep crustal structure is composed of preserved upper continental crustal blocks and middle to lower crustal lenses of inherited high‐grade metamorphic rocks. Deep intrusions into the faulted crustal blocks are responsible for the rough character of the T‐Reflection, whereas intrusions into the ductile lower crust and detachment faults are likely responsible for its smoother character. Deep magma intrusions can be responsible for regional metamorphic processes leading to an increasing velocity of the lower crust to more than 7 km/s. The result is a heterogeneous LCB that likely represents a complex mixture of pre‐ to syn‐breakup mafic and ultramafic rocks (cumulates and sills) and old metamorphic rocks such as granulites and eclogites. An increasing degree of melting toward the breakup axis is responsible for an increasing proportion of cumulates and sill intrusions in the lower crust.
4‐Hydroxybenzoic acid restores CoQ10 biosynthesis in human COQ2 deficiency
Authors: Herebian Diran , Seibt Annette , Smits Sander H. J. , Rodenburg Richard J. , Mayatepek Ertan , Distelmaier Felix 
Published: October 2017

AbstractThe clinical phenotypes of human CoQ10‐deficiency caused by COQ2 mutations range from fatal neonatal disease to adult‐onset multisystem atrophy. So far, treatment options for these diseases are unsatisfactory. Here, we demonstrate that supplementation of 4‐hydroxybenzoic acid (4‐HBA) fully restores endogenous CoQ10‐biosynthesis in COQ2‐deficient cell lines. This was accompanied by increased protein expression of CoQ10‐biosynthesis‐enzymes as well as a rescue of cell viability during stress conditions. In silico analysis suggested a ligand transportation path for 4‐HBA through the COQ2 protein towards the mitochondrial matrix side. This process is apparently hindered by disease‐causing mutations, which can be overcome by increasing 4‐HBA concentrations.
Minimum Performance on Clinical Tests of Physical Function to Predict Walking 6,000 Steps/Day in Knee Osteoarthritis: An Observational Study
Authors: Master Hiral , Thoma Louise M. , Christiansen Meredith B. , Polakowski Emily , Schmitt Laura A. , White Daniel K. 
Published: October 2017

ObjectiveEvidence of physical function difficulties, such as difficulty rising from a chair, may limit daily walking for people with knee osteoarthritis (OA). The purpose of this study was to identify minimum performance thresholds on clinical tests of physical function predictive to walking ≥6,000 steps/day. This benchmark is known to discriminate people with knee OA who develop functional limitation over time from those who do not.MethodsUsing data from the Osteoarthritis Initiative, we quantified daily walking as average steps/day from an accelerometer (Actigraph GT1M) worn for ≥10 hours/day over 1 week. Physical function was quantified using 3 performance‐based clinical tests: 5 times sit‐to‐stand test, walking speed (tested over 20 meters), and 400‐meter walk test. To identify minimum performance thresholds for daily walking, we calculated physical function values corresponding to high specificity (80–95%) to predict walking ≥6,000 steps/day.ResultsAmong 1,925 participants (mean ± SD age 65.1 ± 9.1 years, mean ± SD body mass index 28.4 ± 4.8 kg/m2, and 55% female) with valid accelerometer data, 54.9% walked ≥6,000 steps/day. High specificity thresholds of physical function for walking ≥6,000 steps/day ranged 11.4–14.0 seconds on the 5 times sit‐to‐stand test, 1.13–1.26 meters/second for walking speed, or 315–349 seconds on the 400‐meter walk test.ConclusionNot meeting these minimum performance thresholds on clinical tests of physical function may indicate inadequate physical ability to walk ≥6,000 steps/day for people with knee OA. Rehabilitation may be indicated to address underlying impairments limiting physical function.
Autoantibodies Targeting Ficolin‐2 in Systemic Lupus Erythematosus Patients With Active Nephritis
Authors: Colliard Sophie , Jourde‐Chiche Noémie , Clavarino Giovanna , Sarrot‐Reynauld Françoise , Gout Evelyne , Deroux Alban , Fougere Mélanie , Bardin Nathalie , Bouillet Laurence , Cesbron Jean‐Yves , Thielens Nicole M. , Dumestre‐Pérard Chantal 
Published: October 2017

ObjectiveSystemic lupus erythematosus (SLE) is a multisystem inflammatory disease characterized by the production of various autoantibodies. The aim of this study was to investigate the presence of anti–ficolin‐2 antibodies in SLE patients and to evaluate the association between the levels of these autoantibodies, clinical manifestations, and disease activity.MethodsThis is a comparative study using a cohort of 165 SLE patients and 48 healthy subjects. SLE patients were further divided into 2 groups (low disease activity [SLE Disease Activity Index (SLEDAI) score ≤4, n = 88] and high disease activity [SLEDAI score >4, n = 77]). Clinical manifestations were defined according to the physician in charge. Active lupus nephritis (LN) was documented by kidney biopsy. Detection of anti–ficolin‐2 antibodies was performed by enzyme‐linked immunosorbent assay.ResultsLevels of anti–ficolin‐2 autoantibodies were significantly higher in SLE patients as compared to healthy subjects and associated with SLEDAI score. They were found to be positive in 61 of 165 SLE patients (37%). The presence of anti–ficolin‐2 antibodies was significantly related only to renal involvement, with a very high prevalence (86%) of anti–ficolin‐2 antibodies in SLE patients with active LN. Patients with active proliferative LN had significantly more positive anti–ficolin‐2 antibodies than those with nonproliferative LN. The combination of anti–ficolin‐2, anti–ficolin‐3, and anti‐C1q demonstrated a very high specificity (98%) for the diagnosis of active LN.ConclusionOur results support the usefulness of anti–ficolin‐2 as a complementary serologic biomarker for the diagnosis of active lupus with renal manifestations.
Lateral Graphene‐Contacted Vertically Stacked WS2/MoS2 Hybrid Photodetectors with Large Gain
Authors: Tan Haijie , Xu Wenshuo , Sheng Yuewen , Lau Chit Siong , Fan Ye , Chen Qu , Tweedie Martin , Wang Xiaochen , Zhou Yingqiu , Warner Jamie H. 
Published: October 2017

AbstractA demonstration is presented of how significant improvements in all‐2D photodetectors can be achieved by exploiting the type‐II band alignment of vertically stacked WS2/MoS2 semiconducting heterobilayers and finite density of states of graphene electrodes. The photoresponsivity of WS2/MoS2 heterobilayer devices is increased by more than an order of magnitude compared to homobilayer devices and two orders of magnitude compared to monolayer devices of WS2 and MoS2, reaching 103 A W−1 under an illumination power density of 1.7 × 102 mW cm−2. The massive improvement in performance is due to the strong Coulomb interaction between WS2 and MoS2 layers. The efficient charge transfer at the WS2/MoS2 heterointerface and long trapping time of photogenerated charges contribute to the observed large photoconductive gain of ≈3 × 104. Laterally spaced graphene electrodes with vertically stacked 2D van der Waals heterostructures are employed for making high‐performing ultrathin photodetectors.
Effective Synthesis of Guanosine 5′‐Diphospho‐β‐l‐galactose Using Bacterial l‐Fucokinase/Guanosine 5′‐Diphosphate‐l‐fucose Pyrophosphorylase
Authors: Ohashi Hiroyuki , Wahl Claudia , Ohashi Takao , Elling Lothar , Fujiyama Kazuhito 
Published: October 2017

AbstractThe nucleotide sugar guanosine 5′‐diphospho‐β‐l‐galactose (GDP‐l‐Gal) is known as a key intermediate of the l‐ascorbic acid biosynthesis pathway of plants and algae. In addition, GDP‐l‐Gal serves as a donor substrate of l‐galactosyltransferase, which transfers l‐Gal on the non‐reducing ends of glycoconjugates. To synthesize varieties of l‐Gal‐containing glycoconjugates and explore the novel l‐galactosyltransferases, GDP‐l‐Gal needs to be prepared since it is not commercially available. In plants, GDP‐d‐mannose‐3′,5′‐epimerase (GME) converts GDP‐α‐d‐mannose (GDP‐d‐Man) to GDP‐l‐Gal and GDP‐l‐gulose. GDP‐l‐Gal has been previously prepared using GME and GDP‐d‐Man, for which the equilibrium ratio was biased to GDP‐d‐Man. In this study, the efficient GDP‐l‐Gal production from l‐Gal was established using bacterial l‐fucokinase/GDP‐l‐fucose pyrophosphorylase (FKP), l‐fucose (l‐Fuc), adenosine 5′‐triphosphate (ATP) and guanosine 5′‐triphosphate (GTP). A high synthesis yield was obtained after screening of the optimum FKP reaction conditions in a 96‐well format and analysis by multiplexed capillary electrophoresis (MP‐CE). Conversion of l‐Gal substrate yielded 97% GDP‐l‐Gal using purified recombinant FKP expressed in E. coli. Moreover, GDP‐l‐Gal was successfully purified with 92% (34.5 mg) overall yield from the FKP reaction mixture. GDP‐l‐Gal is now readily available for studies on l‐galactosyltransferases and l‐fucosyltransferases.magnified image
Toughening of polyamide 12/nanoclay nanocomposites by incompatible styrene‐butadiene‐styrene rubber through tailoring interfacial adhesion and fracture mechanism
Authors: Naeim Abadi Ali , Garmabi Hamid , Hemmati Farkhondeh 
Published: October 2017

AbstractThe main drawback of polyamide 12 (PA 12)/nanoclay nanocomposites in their wide range of potential engineering applications known as diminished toughness was overcome using incompatible styrene‐butadiene‐styrene block copolymer (SBS) rubber. Applying optimal processing parameters for co‐rotating twin‐screw extrusion resulted in strong interfacial adhesion of matrix and rubber and intercalated and delaminated nanoclay stacks confined in the matrix. The formulation of compatibilized PA 12/SBS/nanoclay nanocomposites was optimized by employing response surface Box–Behnken methodology. A combination of microscopic methods, that is, atomic force microscopy, transmission and scanning electron microscopy, and transmission optical microscopy, along with single‐edge‐double‐notch four‐point‐bending technique, was exploited to exhaustively explore the toughening mechanisms and microstructure. The findings verify that by tailoring the rubber/matrix interfacial strength and nanocomposite morphology, the Izod impact strength of PA 12/nanoclay nanocomposites is noticeably improved even by incorporating an incompatible rubber and tough fracture mechanisms including rubber particle cavitation and large‐scale shear yielding are attained.
World Health Organization‐defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management
Authors: Gotlib Jason 
Published: October 2017

AbstractDisease overviewThe eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end‐organ damage.DiagnosisHypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1500/mm3 and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ‐hybridization, flow immunocytometry, and T‐cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder.Risk stratificationDisease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi‐molecular classification scheme of disease subtypes which includes the major category “myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1‐JAK2,” and the “MPN subtype, chronic eosinophilic leukemia, not otherwise specified” (CEL, NOS). Lymphocyte‐variant hypereosinophilia is an aberrant T‐cell clone‐driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.Risk‐adapted therapyThe goal of therapy is to mitigate eosinophil‐mediated organ damage. For patients with milder forms of eosinophilia (e.g., < 1500/mm3) without symptoms or signs of organ involvement, a watch and wait approach with close‐follow‐up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first‐line therapy for patients with lymphocyte‐variant hypereosinophilia and HES. Hydroxyurea and interferon‐alpha have demonstrated efficacy as initial treatment and steroid‐refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents and hematopoietic cell transplant have been used for aggressive forms of HES and CEL with outcomes reported for limited numbers of patients. The use of antibodies against interleukin‐5 (IL‐5) (mepolizumab), the IL‐5 receptor (benralizumab), and CD52 (alemtuzumab), as well as other targets on eosinophils remains an active area of investigation.
Patient, disease, and treatment factors associated with overall survival in esthesioneuroblastoma
Authors: Carey Ryan M. , Godovchik Joseph , Workman Alan D. , Kuan Edward C. , Parasher Arjun K. , Chen Jinbo , Palmer James N. , Adappa Nithin D. , Newman Jason G. , Brant Jason A. 
Published: October 2017

BackgroundEsthesioneuroblastomas (ENB) are uncommon and data regarding outcomes are often limited to single‐institution series. The National Cancer Database (NCDB), which contains outcomes information from treatment centers across the United States, represents an opportunity to evaluate outcomes for rare diseases such as ENB across multiple institutions.MethodsThe NCDB was queried for location codes corresponding to the nasal cavity and paranasal sinuses and the histology code for ENB. Multivariate analyses were performed to evaluate for contributing factors to overall survival.ResultsA total of 1225 patients with ENB met the inclusion criteria. The 5‐year overall survival was 76.2% (95% confidence interval [CI], 73.4‐79.0%). Overall survival was associated with Kadish stage, grade, treatment sequence, margin status, Charlson/Deyo score, age, and gender (p < 0.05). Multivariate analysis demonstrated that, compared with surgery alone, surgery followed by radiation without chemotherapy had improved all‐cause mortality (odds ratio [OR], 0.61; 95% CI, 0.40‐0.95). Surgery with chemotherapy alone was associated with increased odds of all‐cause mortality (OR, 4.86; 95% CI, 2.31‐10.25). Multivariate subanalysis for Kadish stages A and B demonstrated no difference in survival between surgery and surgery followed by radiation, but surgery followed by chemoradiation had worse overall survival (OR, 3.03; 95% CI, 1.07‐8.56). For Kadish stage C, surgery followed by radiation had improved overall survival compared with surgery alone (OR, 0.44; 95% CI, 0.24‐0.81).ConclusionThe most common treatment for ENB is surgery followed by radiation, which is associated with the highest overall survival. The role of adjunctive chemotherapy needs to be re‐evaluated in further studies.
Single‐Molecule Observation of the Photoregulated Conformational Dynamics of DNA Origami Nanoscissors
Authors: Willner Elena M. , Kamada Yuu , Suzuki Yuki , Emura Tomoko , Hidaka Kumi , Dietz Hendrik , Sugiyama Hiroshi , Endo Masayuki 
Published: October 2017

AbstractWe demonstrate direct observation of the dynamic opening and closing behavior of photocontrollable DNA origami nanoscissors using high‐speed atomic force microscopy (HS‐AFM). First the conformational change between the open and closed state controlled by adjustment of surrounding salt concentration could be directly observed during AFM scanning. Then light‐responsive moieties were incorporated into the nanoscissors to control these structural changes by photoirradiation. Using photoswitchable DNA strands, we created a photoresponsive nanoscissors variant and were able to distinguish between the open and closed conformations after respective irradiation with ultraviolet (UV) and visible (Vis) light by gel electrophoresis and AFM imaging. Additionally, these reversible changes in shape during photoirradiation were directly visualized using HS‐AFM. Moreover, four photoswitchable nanoscissors were assembled into a scissor–actuator‐like higher‐order object, the configuration of which could be controlled by the open and closed switching induced by irradiation with UV and Vis light.
Mechanism‐Based Inhibitors of the Human Sirtuin 5 Deacylase: Structure–Activity Relationship, Biostructural, and Kinetic Insight
Authors: Rajabi Nima , Auth Marina , Troelsen Kathrin R. , Pannek Martin , Bhatt Dhaval P. , Fontenas Martin , Hirschey Matthew D. , Steegborn Clemens , Madsen Andreas S. , Olsen Christian A. 
Published: October 2017

AbstractThe sirtuin enzymes are important regulatory deacylases in a variety of biochemical contexts and may therefore be potential therapeutic targets through either activation or inhibition by small molecules. Here, we describe the discovery of the most potent inhibitor of sirtuin 5 (SIRT5) reported to date. We provide rationalization of the mode of binding by solving co‐crystal structures of selected inhibitors in complex with both human and zebrafish SIRT5, which provide insight for future optimization of inhibitors with more “drug‐like” properties. Importantly, enzyme kinetic evaluation revealed a slow, tight‐binding mechanism of inhibition, which is unprecedented for SIRT5. This is important information when applying inhibitors to probe mechanisms in biology.
Ein einfach herzustellender elektrochemischer Flussmikroreaktor: effiziente Isoindolinon‐Synthese und Funktionalisierung im Fluss
Authors: Folgueiras‐Amador Ana A. , Philipps Kai , Guilbaud Sébastien , Poelakker Jarno , Wirth Thomas 
Published: October 2017

AbstractElektrochemie im Fluss ist eine effiziente Methode zur Erzeugung radikalischer Zwischenstufen. Ein elektrochemischer Flussmikroreaktor wurde entwickelt, um die Effizienz von elektrochemischen Flussreaktionen zu verbessern. Mit diesem Gerät werden nur wenig oder keine Leitelektrolyte benötigt, wodurch die Prozesse kostengünstiger werden und saubereres Produkt entsteht. Dies wird anhand einer einfachen Synthese von Amidylradikalen gezeigt, die in intramolekularen Hydroaminierungen zu Isoindolinonen umgesetzt werden. Die Kombination mit Inline‐Massenspektrometrie ermöglicht eine einfachere Kombination verschiedener chemischer Schritte in einem einzigen Flussprozess.
An Easy‐to‐Machine Electrochemical Flow Microreactor: Efficient Synthesis of Isoindolinone and Flow Functionalization
Authors: Folgueiras‐Amador Ana A. , Philipps Kai , Guilbaud Sébastien , Poelakker Jarno , Wirth Thomas 
Published: October 2017

AbstractFlow electrochemistry is an efficient methodology to generate radical intermediates. An electrochemical flow microreactor has been designed and manufactured to improve the efficiency of electrochemical flow reactions. With this device only little or no supporting electrolytes are needed, making processes less costly and enabling easier purification. This is demonstrated by the facile synthesis of amidyl radicals used in intramolecular hydroaminations to produce isoindolinones. The combination with inline mass spectrometry facilitates a much easier combination of chemical steps in a single flow process.
Brief Report: Association of Natural Killer Cell Ligand Polymorphism HLA–C Asn80Lys With the Development of Anti‐SSA/Ro–Associated Congenital Heart Block
Authors: Ainsworth Hannah C. , Marion Miranda C. , Bertero Tiziana , Brucato Antonio , Cimaz Rolando , Costedoat‐Chalumeau Nathalie , Fredi Micaela , Gaffney Patrick , Kelly Jennifer , Levesque Kateri , Maltret Alice , Morel Nathalie , Ramoni Veronique , Ruffatti Amelia , Langefeld Carl D. , Buyon Jill P. , Clancy Robert M. 
Published: October 2017

ObjectiveFetal exposure to maternal anti‐SSA/Ro antibodies is necessary but not sufficient for the development of autoimmune congenital heart block (CHB), suggesting that other factors, such as fetal genetic predisposition, are important. Given the previously described association between major histocompatibility complex alleles and CHB risk, we undertook the present study to test the hypothesis that a variant form of HLA–C Asn80Lys, which binds with high affinity to an inhibitory killer cell immunoglobulin‐like receptor (KIR) and thus renders natural killer (NK) cells incapable of restricting inflammation, contributes to the development of CHB.MethodsMembers of 192 pedigrees in the US and Europe (194 cases of CHB, 91 unaffected siblings, 152 fathers, 167 mothers) and 1,073 out‐of‐study controls were genotyped on the Immunochip single‐nucleotide polymorphism microarray. Imputation was used to identify associations at HLA–C Asn80Lys (Asn, C1; Lys, C2) and KIR. Tests for association were performed using logistic regression. McNemar's test and the pedigree disequilibrium test (PDT) were used for matched analyses between affected and unaffected children.ResultsCompared with out‐of‐study controls of the same sex, the C2 allele was less frequent in the mothers (odds ratio [OR] 0.63, P = 0.0014) and more frequent in the fathers (OR 1.40, P = 0.0123), yielding a significant sex‐by‐C2 interaction (P = 0.0002). The C2 allele was more frequent in affected siblings than in unaffected siblings (OR 3.67, P = 0.0025), which was consistent with the PDT results (P = 0.016); these results were observed in both sexes and across the US and European cohorts. There was no difference in the frequency of the inhibitory KIR genotype (KIR AA) between affected and unaffected children (P = 0.55).ConclusionThese data establish C2 as a novel genetic risk factor associated with CHB. This observation supports a model in which fetuses with C2 ligand expression and maternal anti‐SSA/Ro positivity may have impaired NK cell surveillance, resulting in unchecked cardiac inflammation and scarring.