bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress and mass changes at a “wet” volcano: Example during the 2011–2012 volcanic unrest at Kawah Ijen volcano (Indonesia)
Authors: Caudron Corentin , Lecocq Thomas , Syahbana Devy K. , McCausland Wendy , Watlet Arnaud , Camelbeeck Thierry , Bernard Alain , Surono
Published: April 2015

Since 2010, Kawah Ijen volcano has been equipped with seismometers, and its extremely acid volcanic lake has been monitored using temperature and leveling sensors, providing unprecedented time resolution of multiparametric data for an acidic volcanic lake. The nature of stress and mass changes of the volcano is studied by combining seismic analyses and volcanic lake measurements that were made during the strongest unrest ever recorded by the seismic network at Kawah Ijen. The distal VT earthquake swarm that occurred in May 2011 was the precursor of volcanic unrest in October 2011 that caused an increase in shallow earthquakes. The proximal VT earthquakes opened pathways for fluids to ascend by increasing the permeability of the rock matrix. The following months were characterized by two periods of strong heat and mass discharge into the lake and by the initiation of monochromatic tremor (MT) activity when steam/gases interacted with shallow portions of the aquifer. Significant seismic velocity variations, concurrent with water level rises in which water contained a large amount of steam/gas, were associated with the crises, that caused an although the unrest did not affect the shallow hydrothermal system at a large scale. Whereas shallow VT earthquakes likely reflect a magmatic intrusion, MT and relative seismic velocity changes are clearly associated with shallow hydrothermal processes. These results will facilitate the forecast of future crises.
Can we define an asymptotic value for the ice active surface site density for heterogeneous ice nucleation?
Authors: Niedermeier Dennis , Augustin‐Bauditz Stefanie , Hartmann Susan , Wex Heike , Ignatius Karoliina , Stratmann Frank
Published: April 2015

The immersion freezing behavior of droplets containing size‐segregated, monodisperse feldspar particles was investigated. For all particle sizes investigated, a leveling off of the frozen droplet fraction was observed reaching a plateau within the heterogeneous freezing temperature regime (T >− 38°C). The frozen fraction in the plateau region was proportional to the particle surface area. Based on these findings, an asymptotic value for ice active surface site density ns, which we named , could be determined for the investigated feldspar sample. The comparison of these results with those of other studies not only elucidates the general feasibility of determining such an asymptotic value but also shows that the value of strongly depends on the method of the particle surface area determination. However, such an asymptotic value might be an important input parameter for atmospheric modeling applications. At least it shows that care should be taken when ns is extrapolated to lower or higher temperature.
Fate of the Amazon River dissolved organic matter in the tropical Atlantic Ocean
Authors: Medeiros Patricia M. , Seidel Michael , Ward Nicholas D. , Carpenter Edward J. , Gomes Helga R. , Niggemann Jutta , Krusche Alex V. , Richey Jeffrey E. , Yager Patricia L. , Dittmar Thorsten
Published: April 2015

Constraining the fate of dissolved organic matter (DOM) delivered by rivers is a key to understand the global carbon cycle, since DOM mineralization directly influences air‐sea CO2 exchange and multiple biogeochemical processes. The Amazon River exports large amounts of DOM, and yet the fate of this material in the ocean remains unclear. Here we investigate the molecular composition and transformations of DOM in the Amazon River‐ocean continuum using ultrahigh resolution mass spectrometry and geochemical and biological tracers. We show that there is a strong gradient in source and composition of DOM along the continuum, and that dilution of riverine DOM in the ocean is the dominant pattern of variability in the system. Alterations in DOM composition are observed in the plume associated with the addition of new organic compounds by phytoplankton and with bacterial and photochemical transformations. The relative importance of each of these drivers varies spatially and is modulated by seasonal variations in river discharge and ocean circulation. We further show that a large fraction (50–76%) of the Amazon River DOM is surprisingly stable in the coastal ocean. This results in a globally significant river plume with a strong terrigenous signature and in substantial export of terrestrially derived organic carbon from the continental margin, where it can be entrained in the large‐scale circulation and potentially contribute to the long‐term storage of terrigenous production and to the recalcitrant carbon pool found in the deep ocean.
Fractal particle size distribution of pulverized fault rocks as a function of distance from the fault core
Authors: Muto Jun , Nakatani Tsurugi , Nishikawa Osamu , Nagahama Hiroyuki
Published: April 2015

The size distributions of particle in pulverized rocks from the San Andreas fault and the Arima‐Takatsuki Tectonic Line were measured. The rocks are characterized by the development of opening mode fractures with an apparent lack of shear. Fragments in the rocks in both fault zones show a fractal size distribution down to the micron scale. Fractal dimensions, dependent on mineral type, decrease from 2.92 to 1.97 with increasing distance normal to the fault core. The fractal dimensions of the rocks are higher than those of both natural and experimentally created fault gouges measured in previous studies. Moreover, the dimensions are higher than the theoretically estimated upper fractal limit under confined comminution. Dimensions close to 3.0 have been reported in impact loading experiments. The observed characteristics indicate that pulverization is likely to have occurred by a dynamic stress pulse with instantaneous volumetric expansion, possibly during seismic rupture propagation similar to impact loading.
Role of dust direct radiative effect on the tropical rain belt over Middle East and North Africa: A high‐resolution AGCM study
Authors: Bangalath Hamza Kunhu , Stenchikov Georgiy
Published: April 2015

To investigate the influence of direct radiative effect of dust on the tropical summer rain belt across the Middle East and North Africa (MENA), the present study utilizes the high‐resolution capability of an Atmospheric General Circulation Model, the High‐Resolution Atmospheric Model. Ensembles of Atmospheric Model Intercomparison Project style simulations have been conducted with and without dust radiative impacts, to differentiate the influence of dust on the tropical rain belt. The analysis focuses on summer season. The results highlight the role of dust‐induced responses in global‐ and regional‐scale circulations in determining the strength and the latitudinal extent of the tropical rain belt. A significant response in the strength and position of the local Hadley circulation is predicted in response to meridionally asymmetric distribution of dust and the corresponding radiative effects. Significant responses are also found in regional circulation features such as African Easterly Jet and West African Monsoon circulation. Consistent with these dynamic responses at various scales, the tropical rain belt across MENA strengthens and shifts northward. Importantly, the summer precipitation over the semiarid strip south of Sahara, including Sahel, increases up to 20%. As this region is characterized by the “Sahel drought,” the predicted precipitation sensitivity to the dust loading over this region has a wide range of socioeconomic implications. Overall, the study demonstrates the extreme importance of incorporating dust radiative effects and the corresponding circulation responses at various scales, in the simulations and future projections of this region's climate.
Groundwater in the Earth's critical zone: Relevance to large‐scale patterns and processes
Authors: Fan Ying
Published: April 2015

Although we have an intuitive understanding of the behavior and functions of groundwater in the Earth's critical zone at the scales of a column (atmosphere‐plant‐soil‐bedrock), along a toposequence (ridge to valley), and across a small catchment (up to third‐order streams), this paper attempts to assess the relevance of groundwater to understanding large‐scale patterns and processes such as represented in global climate and Earth system models. Through observation syntheses and conceptual models, evidence are presented that groundwater influence is globally prevalent, it forms an environmental gradient not fully captured by the climate, and it can profoundly shape critical zone evolution at continental to global scales. Four examples are used to illustrate these ideas: (1) groundwater as a water source for plants in rainless periods, (2) water table depth as a driver of plant rooting depth, (3) the accessibility of groundwater as an ecological niche separator, and (4) groundwater as the lower boundary of land drainage and a global driver of wetlands. The implications to understanding past and future global environmental change are briefly discussed, as well as critical discipline, scale, and data gaps that must be bridged in order for us to translate what we learn in the field at column, hillslope and catchment scales, to what we must predict at regional, continental, and global scales.
Effects of combustor size and filling condition on stability limits of premixed H2‐air flames in planar microcombustors
Authors: Li Jun , Wang Yuantao , Chen Jinxing , Liu Xueling , Guo Zhaoli
Published: April 2015

An experimental study on stability limits of premixed hydrogen‐air flames in planar microcombustors (H = 1 mm and 1.5 mm) partially filled with porous medium is carried out, focusing on the effects of combustor sizes and filling conditions. Critical conditions for blow‐off, flashback, and breaking through the porous medium are experimentally measured. The blow‐off limits are nearly independent of combustor sizes and filling conditions, while the flashback limits are strongly influenced by the combustor size and the filling conditions. Critical values for breaking through are identified with two different methods, and it is shown that standing combustion waves are settled over a range of velocities, instead of a fixed value of filtration velocity, which is considered an important characteristic of microcombustion. Most results can be explained by the classic boundary velocity gradient theory by von Elbe and Lewis, and thus the validity of the theory to the present channel spacings is confirmed. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2571–2580, 2015
An attenuated phenotype of Costello syndrome in three unrelated individuals with a HRAS c.179G>A (p.Gly60Asp) mutation correlates with uncommon functional consequences
Authors: Gripp Karen W. , Sol‐Church Katia , Smpokou Patroula , Graham Gail E. , Stevenson David A. , Hanson Heather , Viskochil David H. , Baker Laura C. , Russo Bridget , Gardner Nick , Stabley Deborah L. , Kolbe Verena , Rosenberger Georg
Published: April 2015

Heterozygous germline mutations in the proto‐oncogene HRAS cause Costello syndrome (CS), an intellectual disability condition with severe failure to thrive, cardiac abnormalities, predisposition to tumors, and neurologic abnormalities. More than 80% of patients share the HRAS mutation c.34G>A (p.Gly12Ser) associated with the typical, relatively homogeneous phenotype. Rarer mutations occurred in individuals with an attenuated phenotype and less characteristic facial features. Most pathogenic HRAS alterations affect hydrolytic HRAS activity resulting in constitutive activation. “Gain‐of‐function” and “hyperactivation” concerning downstream pathways are widely used to explain the molecular basis and dysregulation of the RAS‐MAPK pathway is the biologic mechanism shared amongst rasopathies. Panel testing for rasopathies identified a novel HRAS mutation (c.179G>A; p.Gly60Asp) in three individuals with attenuated features of Costello syndrome. De novo paternal origin occurred in two, transmission from a heterozygous mother in the third. Individuals showed subtle facial features; curly hair and relative macrocephaly were seen in three; atrial tachycardia and learning difficulties in two, and pulmonic valve dysplasia and mildly thickened left ventricle in one. None had severe failure to thrive, intellectual disability or cancer, underscoring the need to consider HRAS mutations in individuals with an unspecific rasopathy phenotype. Functional studies revealed strongly increased HRASGly60Asp binding to RAF1, but not to other signaling effectors. Hyperactivation of the MAPK downstream signaling pathways was absent. Our results indicate that an increase in the proportion of activated RAS downstream signaling components does not entirely explain the molecular basis of CS. We conclude that the phenotypic variability in CS recapitulates variable qualities of molecular dysfunction. © 2015 Wiley Periodicals, Inc.
Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome
Authors: Olson Heather E. , Tambunan Dimira , LaCoursiere Christopher , Goldenberg Marti , Pinsky Rebecca , Martin Emilie , Ho Eugenia , Khwaja Omar , Kaufmann Walter E. , Poduri Annapurna
Published: April 2015

Rett syndrome and neurodevelopmental disorders with features overlapping this syndrome frequently remain unexplained in patients without clinically identified MECP2 mutations. We recruited a cohort of 11 patients with features of Rett syndrome and negative initial clinical testing for mutations in MECP2. We analyzed their phenotypes to determine whether patients met formal criteria for Rett syndrome, reviewed repeat clinical genetic testing, and performed exome sequencing of the probands. Using 2010 diagnostic criteria, three patients had classical Rett syndrome, including two for whom repeat MECP2 gene testing had identified mutations. In a patient with neonatal onset epilepsy with atypical Rett syndrome, we identified a frameshift deletion in STXBP1. Among seven patients with features of Rett syndrome not fulfilling formal diagnostic criteria, four had suspected pathogenic mutations, one each in MECP2, FOXG1, SCN8A, and IQSEC2. MECP2 mutations are highly correlated with classical Rett syndrome. Genes associated with atypical Rett syndrome, epilepsy, or intellectual disability should be considered in patients with features overlapping with Rett syndrome and negative MECP2 testing. While most of the identified mutations were apparently de novo, the SCN8A variant was inherited from an unaffected parent mosaic for the mutation, which is important to note for counseling regarding recurrence risks. © 2015 Wiley Periodicals, Inc.
Respiratory motile cilia dysfunction in a patient with cranioectodermal dysplasia
Authors: Li You , Garrod Andrea S. , Madan‐Khetarpal Suneeta , Sreedher Gayathri , McGuire Marianne , Yagi Hisato , Klena Nikolai T. , Gabriel George C. , Khalifa Omar , Zahid Maliha , Panigrahy Ashok , Weiner Daniel J. , Lo Cecilia W.
Published: April 2015

Ciliopathies such as cranioectodermal dysplasia, Sensenbrenner syndrome, short‐rib polydactyly, and Jeune syndrome are associated with respiratory complications arising from rib cage dysplasia. While such ciliopathies have been demonstrated to involve primary cilia defects, we show motile cilia dysfunction in the airway of a patient diagnosed with cranioectodermal dysplasia. While this patient had mild thoracic dystrophy not requiring surgical treatment, there was nevertheless newborn respiratory distress, restrictive airway disease with possible obstructive airway involvement, repeated respiratory infections, and atelectasis. High‐resolution videomicroscopy of nasal epithelial biopsy showed immotile/dyskinetic cilia and nasal nitric oxide was reduced, both of which are characteristics of primary ciliary dyskinesia, a sinopulmonary disease associated with mucociliary clearance defects due to motile cilia dysfunction in the airway. Exome sequencing analysis of this patient identified compound heterozygous mutations in WDR35, but no mutations in any of the 30 known primary ciliary dyskinesia genes or other cilia‐related genes. Given that WDR35 is only known to be required for primary cilia function, we carried out WDR35 siRNA knockdown in human respiratory epithelia to assess the role of WDR35 in motile cilia function. This showed WDR35 deficiency disrupted ciliogenesis in the airway, indicating WDR35 is also required for formation of motile cilia. Together, these findings suggest patients with WDR35 mutations have an airway mucociliary clearance defect masked by their restrictive airway disease. © 2015 Wiley Periodicals, Inc.
What does Medicare pay rhinologists? An analysis of Medicare payment data
Authors: Clair Brandon , Goyal Parul
Published: April 2015

Background

Information about charges and payments for physician services continues to be scrutinized. Recently, the Centers for Medicare and Medicaid Services (CMS) released data regarding Medicare charges and payments to all physicians for calendar year 2012. The purpose of this study was to investigate the variability and patterns in Medicare charges and payments among a large sample of rhinologists.

Methods

Charge and payment data were obtained from publicly available CMS datasets (http://www.cms.gov). Data for all otolaryngologists and rhinology subsets were extracted. Charges, payments, fee multipliers, and total submitted claims were compared. Unequal variance 2‐tailed t tests were used for analysis.

Results

Mean submitted charges for rhinologists were $291,464 compared to $211,209 for all otolaryngologists (p = 0.0014). Mean payments to rhinologists were $70,172 compared to $77,275 for all otolaryngologists (p = 0.24). Fees for services ranged from 1.33 to 14.29 times Medicare reimbursement rates (mean = 4.47). The fee multiplier was significantly higher for operating room–based codes compared to office‐based codes (9.43 vs 3.44, p < 0.001). Academic rhinologists submitted fewer claims and had a higher fee multiplier than private rhinologists (p < 0.001). Academic and private rhinologists had no difference in submitted charges (p = 0.28).

Conclusion

The wide availability of Medicare payment information makes it important for physicians to understand how their individual data compares to that of their colleagues. Medicare payments to rhinologists were comparable to otolaryngologists as a whole. Charges for services commonly performed by rhinologists vary widely. Academic rhinologists submitted fewer claims than their private colleagues, but overall charges and payments were comparable between the 2 groups.
A pharmacogenetic study implicates SLC9a9 in multiple sclerosis disease activity
Authors: Esposito Federica , Sorosina Melissa , Ottoboni Linda , Lim Elaine T. , Replogle Joseph M. , Raj Towfique , Brambilla Paola , Liberatore Giuseppe , Guaschino Clara , Romeo Marzia , Pertel Thomas , Stankiewicz James M. , Martinelli Vittorio , Rodegher Mariaemma , Weiner Howard L. , Brassat David , Benoist Christophe , Patsopoulos Nikolaos A. , Comi Giancarlo , Elyaman Wassim , Martinelli Boneschi Filippo , De Jager Philip L.
Published: April 2015

Objective

A proportion of multiple sclerosis (MS) patients experience disease activity despite treatment. The early identification of the most effective drug is critical to impact long‐term outcome and to move toward a personalized approach. The aim of the present study is to identify biomarkers for further clinical development and to yield insights into the pathophysiology of disease activity.

Methods

We performed a genome‐wide association study in interferon‐β (IFNβ)‐treated MS patients followed by validation in 3 independent cohorts. The role of the validated variant was examined in several RNA data sets, and the function of the presumed target gene was explored using an RNA interference approach in primary T cells in vitro.

Results

We found an association between rs9828519G and nonresponse to IFNβ (pdiscovery = 4.43 × 10−8) and confirmed it in a meta‐analysis across 3 replication data sets (preplication = 7.78 × 10−4). Only 1 gene is found in the linkage disequilibrium block containing rs9828519: SLC9A9. Exploring the function of this gene, we see that SLC9A9 mRNA expression is diminished in MS subjects who are more likely to have relapses. Moreover, SLC9A9 knockdown in T cells in vitro leads an increase in expression of IFNγ, which is a proinflammatory molecule.

Interpretation

This study identifies and validates the role of rs9828519, an intronic variant in SLC9A9, in IFNβ‐treated subjects, demonstrating a successful pharmacogenetic screen in MS. Functional characterization suggests that SLC9A9, an Na+‐H+ exchanger found in endosomes, appears to influence the differentiation of T cells to a proinflammatory fate and may have a broader role in MS disease activity, outside of IFNβ treatment. Ann Neurol 2015;78:115–127
Micromotor‐Based Energy Generation
Authors: Singh Virendra V. , Soto Fernando , Kaufmann Kevin , Wang Joseph
Published: April 2015

A micromotor‐based strategy for energy generation, utilizing the conversion of liquid‐phase hydrogen to usable hydrogen gas (H2), is described. The new motion‐based H2‐generation concept relies on the movement of Pt‐black/Ti Janus microparticle motors in a solution of sodium borohydride (NaBH4) fuel. This is the first report of using NaBH4 for powering micromotors. The autonomous motion of these catalytic micromotors, as well as their bubble generation, leads to enhanced mixing and transport of NaBH4 towards the Pt‐black catalytic surface (compared to static microparticles or films), and hence to a substantially faster rate of H2 production. The practical utility of these micromotors is illustrated by powering a hydrogen–oxygen fuel cell car by an on‐board motion‐based hydrogen and oxygen generation. The new micromotor approach paves the way for the development of efficient on‐site energy generation for powering external devices or meeting growing demands on the energy grid.
Rate and Equilibrium Constants for the Addition of N‐Heterocyclic Carbenes into Benzaldehydes: A Remarkable 2‐Substituent Effect
Authors: Collett Christopher J. , Massey Richard S. , Taylor James E. , Maguire Oliver R. , O'Donoghue AnnMarie C. , Smith Andrew D.
Published: April 2015

Rate and equilibrium constants for the reaction between N‐aryl triazolium N‐heterocyclic carbene (NHC) precatalysts and substituted benzaldehyde derivatives to form 3‐(hydroxybenzyl)azolium adducts under both catalytic and stoichiometric conditions have been measured. Kinetic analysis and reaction profile fitting of both the forward and reverse reactions, plus onwards reaction to the Breslow intermediate, demonstrate the remarkable effect of the benzaldehyde 2‐substituent in these reactions and provide insight into the chemoselectivity of cross‐benzoin reactions.
A Planarized Triphenylborane Mesogen: Discotic Liquid Crystals with Ambipolar Charge‐Carrier Transport Properties
Authors: Kushida Tomokatsu , Shuto Ayumi , Yoshio Masafumi , Kato Takashi , Yamaguchi Shigehiro
Published: April 2015

A discotic liquid‐crystalline (LC) material, consisting of a planarized triphenylborane mesogen, was synthesized. X‐ray diffraction analysis confirmed that this compound forms a hexagonal columnar LC phase with an interfacial distance of 3.57 Å between the discs. At ambient temperature, this boron‐centered discotic liquid crystal exhibited ambipolar carrier transport properties with electron and hole mobility values of approximately 10−3 and 3×10−5 cm2 V−1 s−1, respectively.
Mechanical properties of biodegradable polylactide/poly(ether‐block‐amide)/thermoplastic starch blends: Effect of the crosslinking of starch
Authors: Zhou Linyao , Zhao Guiyan , Jiang Wei
Published: April 2015

Corn starch was crosslinked with epichlorohydrin (ECH) and then plasticized with glycerol. Subsequently, this thermoplasticized crosslinked starch (TPCLS) was melt‐compounded with polylactide (PLA) and poly(ether‐block‐amide) (PEBA) to prepare biodegradable PLA/PEBA/TPCLS blend with high impact resistance. It was found that the crosslinking agent ECH had critical effect on the impact strength, tensile properties, and internal morphology of the ternary blend. The impact strength, tensile strength, and elongation at break increased with ECH content; thereafter, they decreased on further increasing the ECH content. At 0.5 wt % ECH content, impact strength, tensile strength, and elongation at break reached the maximum values and smaller salami structure particles were observed accordingly. These results were attributed to the competition of shear resistance of TPCLS and the chemical linkage between the crosslinked starch and PLA‐g‐MA. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42297.
One‐Step Synthesis of Amorphous Silver Silicates with Tunable Light Absorption Spectra and Photocatalytic Activities in the Visible Region
Authors: Lou Zaizhu , Wang Zeyan , Huang Baibiao , Dai Ying , Wang Gang , Jiang Zaiyong , Zhang Xiaoyang , Qin Xiaoyan , Li Yanqing
Published: April 2015

A series of amorphous silver silicates with different compositions were synthesized for the first time by one‐step co‐precipitation. Silicate ions were found to have important role on determining visible light absorption and photocatalytic activities of amorphous silver silicates, and the sample with Ag/Si ratio of 3.20 exhibits optimal photocatalytic activity.
Dienamine and Friedel–Crafts One‐Pot Synthesis, and Antitumor Evaluation of Diheteroarylalkanals
Authors: Frías María , Padrón José M. , Alemán José
Published: April 2015

An asymmetric synthesis of diheteroarylalkanals through one‐pot dienamine and Friedel–Crafts reaction is presented. The reaction tolerates a large variety of substituents at different positions of the starting aldehyde and also in the indole nucleophile, and a range of diheterocyclic alkanals can be achieved. Furthermore, we have studied the antiproliferative activity of these new compounds in representative cancer tumor cell lines.
Staugrenze bei der Begasung mit Lochböden
Authors: Ruff Klaus
Published: April 2015

Bei der Flüssigkeitsbegasung mit Lochböden existiert eine bestimmte Gasgeschwindigkeit, ab der die nach unten austretende Regenrate merklich abnimmt. Durch erneute Experimente konnte diese Staugrenze mit einer früher abgeleiteten Grenze zwischen Blasengasen und Strahlgasen identifiziert werden. Erstmals konnte auch für Lochböden bei Gas‐Feststoff‐Wirbelschichten dasselbe Kriterium festgestellt werden.
Spectroscopic Observation of Calcium‐Induced Reorientation of Cellobiose Dehydrogenase Immobilized on Electrodes and its Effect on Electrocatalytic Activity
Authors: Kielb Patrycja , Sezer Murat , Katz Sagie , Lopez Francesca , Schulz Christopher , Gorton Lo , Ludwig Roland , Wollenberger Ulla , Zebger Ingo , Weidinger Inez M.
Published: April 2015

Cellobiose dehydrogenase catalyzes the oxidation of various carbohydrates and is considered as a possible anode catalyst in biofuel cells. It has been shown that the catalytic performance of this enzyme immobilized on electrodes can be increased by presence of calcium ions. To get insight into the Ca2+‐induced changes in the immobilized enzyme we employ surface‐enhanced vibrational (SERR and SEIRA) spectroscopy together with electrochemistry. Upon addition of Ca2+ions electrochemical measurements show a shift of the catalytic turnover signal to more negative potentials while SERR measurements reveal an offset between the potential of heme reduction and catalytic current. Comparing SERR and SEIRA data we propose that binding of Ca2+to the heme induces protein reorientation in a way that the electron transfer pathway of the catalytic FAD center to the electrode can bypass the heme cofactor, resulting in catalytic activity at more negative potentials.
Case study interpretation: Report from the ICCS Annual Meeting, Seattle, 2014
Authors: Fromm Jonathan R. , Tagliente Damian J. , Shaver Aaron C. , Neppalli Vishala , Craig Fiona E.
Published: April 2015

The Case Study Interpretation (CSI) cases presented at the 2014 International Clinical Cytometry Society (ICCS) meeting in Seattle illustrate the utility of state‐of‐the art multiparameter flow cytometry in the diagnosis of hematolymphoid neoplasms. Download the listmode files (Supporting Information) and test your analysis skills before reading the case reports, keeping in mind the following questions. How many separate abnormal mature B‐cell populations can you identify, and how many of these represent different subtypes of B‐cell neoplasm? How many separate abnormal mature T‐cell populations can you identify, and do these represent different subtypes of T‐cell neoplasm or phenotypic heterogeneity in one neoplasm? How many separate immature/blastic cell populations can you identify, and do they meet criteria for mixed phenotype leukemia? Is there a population of blasts that lacks T‐cell, B‐cell, and myeloid lineage defining antigens and if so, what entities should you consider and what additional antigens should you assess for? © 2015 International Clinical Cytometry Society
Benign chondroblastoma on fine‐needle aspiration smears: A seven‐case experience and review of the literature
Authors: Cozzolino Immacolata , Zeppa Pio , Zabatta Assunta , Merolla Francesco , Vetrani Antonio , Sadile Francesco
Published: April 2015

We report seven cases of chondroblastoma (CB) of bone, diagnosed by Fine‐Needle Aspiration Cytology (FNAC), and confirmed by histomorphological examination. The concurrence of some cytomorphologic findings — mononucleated cells, multinucleated cells, and intercellular chondroid substance — unequivocally suggested the cytological diagnosis of CB. We also reviewed the literature on this topic in order to discuss morphological criteria and the importance of needle size. The differential diagnosis between CB, Giant Cell Tumor of Bone, and Eosinophilic Granuloma is further discussed. Diagn. Cytopathol. 2015;43:734–738. © 2015 Wiley Periodicals, Inc.
Orai1 controls C5a‐induced neutrophil recruitment in inflammation
Authors: Sogkas Georgios , Vögtle Timo , Rau Eduard , Gewecke Britta , Stegner David , Schmidt Reinhold E. , Nieswandt Bernhard , Gessner J. Engelbert
Published: April 2015

Stromal interaction molecule 1 (STIM1)‐dependent store operated calcium‐entry (SOCE) through Orai1‐mediated calcium (Ca2+) influx is considered a major pathway of Ca2+ signaling, serving T‐cell, mast cell, and platelet responses. Here, we show that Orai1 is critical for neutrophil function. Orai1‐deficient neutrophils present defects in fMLP and complement C5a‐induced Ca2+ influx and migration, although they respond normally to another chemoattractant, CXCL2. Up until now, no specific contribution of Orai1 independent from STIM1 or SOCE has been recognized in immune cells. Here, we observe that Orai1‐deficient neutrophils exhibit normal STIM1‐dependent SOCE and STIM1‐deficient neutrophils respond to fMLP and C5a efficiently. Despite substantial cytokine production, Orai1−/− chimeric mice show impaired neutrophil recruitment in LPS‐induced peritonitis. Moreover, Orai1 deficiency results in profoundly defective C5a‐triggered neutrophil lung recruitment in hypersensitivity pneumonitis. Comparative evaluation of inflammation in Stim1−/− chimeras reveals a distinct pathogenic contribution of STIM1, including its involvement in IgG‐induced C5a production. Our data establish Orai1 as key signal mediator of C5aR activation, contributing to inflammation by a STIM1‐independent pathway of Ca2+‐influx in neutrophils.
HSP90 inhibitors decrease AID levels and activity in mice and in human cells
Authors: Montamat‐Sicotte Damien , Litzler Ludivine C , Abreu Cecilia , Safavi Shiva , Zahn Astrid , Orthwein Alexandre , Müschen Markus , Oppezzo Pablo , Muñoz Denise P , Di Noia Javier M
Published: April 2015

Activation induced deaminase (AID) initiates somatic hypermutation and class switch recombination of the Ig genes in antigen‐activated B cells, underpinning antibody affinity maturation and isotype switching. AID can also be pathogenic by contributing to autoimmune diseases and oncogenic mutations. Moreover, AID can exert noncanonical functions when aberrantly expressed in epithelial cells. The lack of specific inhibitors prevents therapeutic applications to modulate AID functions. Here, we have exploited our previous finding that the HSP90 molecular chaperoning pathway stabilizes AID in B cells, to test whether HSP90 inhibitors could target AID in vivo. We demonstrate that chronic administration of HSP90 inhibitors decreases AID protein levels and isotype switching in immunized mice. HSP90 inhibitors also reduce disease severity in a mouse model of acute B‐cell lymphoblastic leukemia in which AID accelerates disease progression. We further show that human AID protein levels are sensitive to HSP90 inhibition in normal and leukemic B cells, and that HSP90 inhibition prevents AID‐dependent epithelial to mesenchymal transition in a human breast cancer cell line in vitro. Thus, we provide proof‐of‐concept that HSP90 inhibitors indirectly target AID in vivo and that endogenous human AID is widely sensitive to them, which could have therapeutic applications.
Mutagenicity monitoring following battlefield exposures: Longitudinal study of HPRT mutations in gulf war i veterans exposed to depleted uranium
Authors: Albertini Richard J. , Vacek Pamela M. , Carter Elizabeth W. , Nicklas Janice A. , Squibb Katherine S. , Gucer Patricia W. , Engelhardt Susan M. , McDiarmid Melissa A.
Published: April 2015

A total of 70 military Veterans have been monitored for HPRT T‐cell mutations in five separate studies at 2‐year intervals over an 8‐year period. Systemic depleted uranium (DU) levels were measured at the time of each study by determining urinary uranium (uU) excretion. Each HPRT study included 30–40 Veterans, several with retained DU‐containing shrapnel. Forty‐nine Veterans were evaluated in multiple studies, including 14 who were in all five studies. This permitted a characterization of the HPRT mutation assay over time to assess the effects of age, smoking and non‐selected cloning efficiencies, as well as the inter‐ and intra‐individual variability across time points. Molecular analyses identified the HPRT mutation and T‐cell receptor (TCR) gene rearrangement in 1,377 mutant isolates. An unexpected finding was that in vivo clones of HPRT mutant T‐cells were present in some Veterans, and could persist over several years of the study. The calculated HPRT mutant frequencies (MFs) were repeatedly elevated in replicate studies in three outlier Veterans with elevated urinary uranium excretion levels. However, these three outlier Veterans also harbored large and persistent in vivo HPRT mutant T‐cell clones, each of which was represented by a single founder mutation. Correction for in vivo clonality allowed calculation of HPRT T‐cell mutation frequencies (MutFs). Despite earlier reports of DU associated increases in HPRT MFs in some Veterans, the results presented here demonstrate that HPRT mutations are not increased by systemic DU exposure. Additional battlefield exposures were also evaluated for associations with HPRT mutations and none were found. Environ. Mol. Mutagen. 56:581–593, 2015. © 2015 Wiley Periodicals, Inc.
Mutagenicity monitoring following battlefield exposures: Molecular analysis of HPRT mutations in gulf war i veterans exposed to depleted uranium
Authors: Nicklas Janice A. , Albertini Richard J. , Vacek Pamela M. , Ardell Stephanie K. , Carter Elizabeth W. , McDiarmid Melissa A. , Engelhardt Susan M. , Gucer Patricia W. , Squibb Katherine S.
Published: April 2015

Molecular studies that involved cDNA and genomic DNA sequencing as well as multiplex PCR of the HPRT gene were performed to determine the molecular mutational spectrum for 1,377 HPRT mutant isolates obtained from 61 Veterans of the 1991 Gulf War, most of whom were exposed to depleted uranium (DU). Mutant colonies were isolated from one to four times from each Veteran (in 2003, 2005, 2007, and/or 2009). The relative frequencies of the various types of mutations (point mutations, deletions, insertions, etc.) were compared between high versus low DU exposed groups, (based on their urine U concentration levels), with HPRT mutant frequency (as determined in the companion paper) and with a database of historic controls. The mutational spectrum includes all classes of gene mutations with no significant differences observed in Veterans related to their DU exposures. Environ. Mol. Mutagen. 56:594–608, 2015. © 2015 Wiley Periodicals, Inc.
Modified in vivo comet assay detects the genotoxic potential of 14‐hydroxycodeinone, an α,β‐unsaturated ketone in oxycodone
Authors: Pant Kamala , Roden Nicholas , Zhang Charles , Bruce Shannon , Wood Craig , Pendino Kimberly
Published: April 2015

14‐Hydroxycodeinone (14‐HC) is an α,β‐unsaturated ketone impurity found in oxycodone drug substance and has a structural alert for genotoxicity. 14‐HC was tested in a combined Modified and Standard Comet Assay to determine if the slight decrease in % Tail DNA noted in a previously conducted Standard Comet Assay with 14‐HC could be magnified to clarify if the response was due to cross‐linking activity. One limitation of the Standard Comet Assay is that DNA cross‐links cannot be reliably detected. However, under certain modified testing conditions, DNA cross‐links and chemical moieties that elicit such cross‐links can be elucidated. One such modification involves the induction of additional breakages of DNA strands by gamma or X‐ray irradiation. To determine if 14‐HC is a DNA crosslinker in vivo, a Modified Comet Assay was conducted using X‐ray irradiation as the modification to visualize crosslinking activity. In this assay, 14‐HC was administered orally to mice up to 320 mg/kg/day. Results showed a statistically significant reduction in percent tail DNA in duodenal cells at 320 mg/kg/day, with a nonstatistically significant but dose‐related reduction in percent tail DNA also observed at the mid dose of 160 mg/kg/day. Similar decreases were not observed in cells from the liver or stomach, and no increases in percent tail DNA were noted for any tissue in the concomitantly conducted Standard Comet Assay. Taken together, 14‐HC was identified as a cross‐linking agent in the duodenum in the Modified Comet Assay. Environ. Mol. Mutagen. 56:777–787, 2015. © 2015 Wiley Periodicals, Inc.
Ovarian structure protein 1: A sensitive molecular biomarker of gonadal intersex in female Japanese medaka after androgen exposure
Authors: Abdel-Moneim Ahmed , Mahapatra Cecon T. , Hatef Azadeh , Sepúlveda Maria S.
Published: April 2015

Intersex in gonochoristic fish can be induced after exposure to androgens and estrogens. The main objective of the present study was to identify biomarkers that would be predictive of intersex in Japanese medaka (Oryzias latipes) after exposure to synthetic hormones. First a gene was identified, ovarian structure protein 1 (osp1), with strong female-specific expression during gonadal differentiation. The authors hypothesized that osp1 expression would decrease to male levels in females after the exposure of larvae (15–25 d postfertilization [dpf]) to 17β-trenbolone (TRB; 5 ng/L) and would increase to female levels in males exposed to 17α-ethinylestradiol (EE2; 5 ng/L) and that gonadal intersex would be induced later in life (60 dpf). Tissue distribution and cellular localization of OSP1 was investigated using Western blot and immunohistochemistry. The results indicate that this exposure regime delays testicular maturation in males and development of ovarian intersex in females. Although decreased osp1 expression in females exposed to TRB correlated to changes in ovarian phenotype, up-regulation of osp1 was not observed in males exposed to EE2. In addition, OSP1 was only observed in ovaries and localized in the cytoplasm and follicular layer of immature and mature oocytes. The authors conclude that osp1 is a promising biomarker of androgen exposure and gonadal intersex in female medaka. Environ Toxicol Chem 2015;34:2087–2094. © 2015 SETAC
DNA damage and genetic methylation changes caused by Cd in Arabidopsis thaliana seedlings
Authors: Li Zhaoling , Liu Zhihong , Chen Ruijuan , Li Xiaojun , Tai Peidong , Gong Zongqiang , Jia Chunyun , Liu Wan
Published: April 2015

Amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MASP) techniques are sensitive to deoxyribonucleic acid (DNA) damage and genetic methylation, respectively. Using these 2 techniques, Arabidopsis thaliana cultured with 0 mg/L (control), 0.5 mg/L, 1.5 mg/L, and 5.0 mg/L Cd2+ for 16 d was used to analyze the DNA damage and methylation changes as a result of cadmium (Cd). The DNA was amplified by 14 AFLP primer pairs and 13 MSAP primer combinations. In the AFLP experiment, 62 polymorphic sites were found in the patterns of 11 primer combinations and a total of 1116 fragments were obtained in these patterns. There were no polymorphic bands in the remaining 3 pairs. The proportions of polymorphic sites in the 0.5-mg/L Cd2+ and 5.0-mg/L Cd2+ treatments were significantly different. Seven polymorphic fragments were then separated and successfully sequenced, yielding 6 nucleobase substitutions and 1 nucleobase deletion. Similarly, in the MSAP experiment, the MSAP% and number of demethylated-type bands were unchanged after Cd treatment, but the number of methylated-type bands was increased significantly in the 5.0-mg/L Cd2+ treatment group, a finding that may be associated with the AFLP results. The polymorphic bands were also sequenced and the functions of their homologous genes were determined. The DNA damage and methylation changes may be the primary cause of certain pathology changes as a result of Cd uptake in plants. Environ Toxicol Chem 2015;34:2095–2103. © 2015 SETAC
Accumulative and Assimilative Learning, Institutional Infrastructure, and Innovation Orientation of Developing Economy Firms
Authors: Chittoor Raveendra , Aulakh Preet S. , Ray Sougata
Published: April 2015

We examine the role of internationally acquired knowledge and supra‐firm institutional infrastructure on developing firms' innovation orientation. Empirical results, based on a panel of 11,048 Indian manufacturing firms during the period 1990 to 2009, show that the macro‐ and micro‐institutional context in which firms are embedded condition the effect of global resource and product market participation on indigenous innovation efforts. In particular, technology imports (accumulative learning) have a stronger effect on inducing investments in innovation when the macro‐institutional development is weak and for firms that are affiliated to business groups. However, product market internationalization (assimilative learning) plays a more important role in facilitating innovation efforts as the institutional environment becomes stronger and for independent firms that do not possess the network advantages inherent in business groups.
Does Ergonomics Improve Product Quality and Reduce Costs? A Review Article
Authors: Zare Mohsen , Croq Michel , Hossein‐Arabi Farhad , Brunet Rene , Roquelaure Yves
Published: April 2015

Competition is an ongoing challenge confronting industrial corporations, particularly automobile manufacturing. Striving to improve product quality and productivity, automotive industries have used different quality management approaches, such as reduced variability, total quality management, and lean management, over recent years. Furthermore, incorporating proactive ergonomics such as physical and organizational ergonomics and psychosocial factors into the structure of a company is considered to be a support for productivity and quality. Several studies have shown the effects of ergonomics on better quality. Application of both quality management approaches and ergonomics in an integrated manner in the manufacturing production system is emphasized because they are similar concepts with the same objectives, that is, to improve efficiency. In this study, a comprehensive review was undertaken and 25 studies were reviewed in order to define how integration of an ergonomic approach in the manufacturing production system can reduce defects and improve quality in the production process.
Ischemic LTP: NMDA‐dependency and dorso/ventral distribution within the hippocampus
Authors: Maggio Nicola , Shavit Stein Efrat , Segal Menahem
Published: April 2015

A transient ischemic episode causes a reduction in evoked EPSPs in hippocampal slices, followed by an NMDA dependent LTP. We explored the relations between ischemic LTP (iLTP) and the more conventional tetanic LTP (tLTP) in CA1 region of slices along the dorsal/ventral axis of the hippocampus. Dorsal hippocampal (DH) slices produced a much larger iLTP than their ventral hippocampal (VH) counterparts. In both regions, iLTP and tLTP shared the same NMDA mediated potentiation, such that one LTP saturated the ability of the other treatment to generate LTP. The smaller LTP in VH was correlated with a lower NMDA‐mediated EPSP, and a parallel lower density of NMDA receptors. Calcium permeable AMPA receptors did not contribute to the DH/VH disparity. We conclude that a differential distribution of NMDA receptor subunits along the septotemporal axis of the hippocampus controls the diverse ability to evoke iLTP and tLTP in the two regions and may underlie their characteristic behavioral outputs as well as their differential sensitivity to ischemia. © 2015 Wiley Periodicals, Inc.