bluuebunny/crossref_metadata_2025 huggingface dataset:
Lasing transition at 1.06 μm emission in Nd3+‐doped borate‐based tellurium calcium zinc niobium oxide glasses for high‐power solid‐state lasers
Authors: Ravi O. , Prasad K. , Jain Rajiv , Venkataswamy M. , Chaurasia Shivanand , Deva Prasad Raju B.
Published: November 2016

The spectroscopic properties of Tellurium Calcium Zinc Niobium oxide Borate (TCZNB) glasses of composition (in mol%) 10TeO2 + 15CaO + 5ZnO + 10 Nb2O5 + (60 – x)B2O3 + Nd2O3 (x = 0.1, 0.5, 1.0 or 1.5 mol%) have been investigated experimentally. The three phenomenological intensity parameters Ω2, Ω4, Ω6 have been calculated using the Judd–Ofelt theory and in turn radiative properties such as radiative transition probabilities, emission cross‐sections, branching ratios and radiative lifetimes have been estimated. The trend found in the JO intensity parameter is Ω2 > Ω6 > Ω4 If Ω6 > Ω4, the glass system is favourable for the laser emission 4F3/2 → 4I11/2 in the infrared (IR) wavelength. The experimental values of branching ratio of 4F3/2 → 4I11/2 transition indicate favourable lasing action with low threshold power. The evaluated total radiative transition probabilities (AT), stimulated emission cross‐section (σe) and gain bandwidth parameters (σe × Δλp) were compared with earlier reports. An energy level analysis has been carried out considering the experimental energy positions of the absorption and emission bands.
Simultaneous detection of sulfoxaflor and its metabolites, X11719474 and X11721061, in lettuce using a modified QuEChERS extraction method and liquid chromatography–tandem mass spectrometry
Authors: Kim Sung‐Woo , Rahman Md. Musfiqur , Abd El‐Aty A. M. , Kabir Md. Humayun , Na Tae Woong , Choi Jeong‐Heui , Shin Ho‐Chul , Shim Jae‐Han
Published: November 2016

An analytical method has been developed to quantify the residual levels of sulfoxaflor and its metabolites (X11719474 and X11721061) in/on cultivated lettuce grown under greenhouse conditions. Samples were extracted and purified using a quick, easy, cheap, effective, rugged, and safe ‘QuEChERS’ method (original version) following systematic method optimization and were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Good linearity with coefficient of determination ≥0.9930 was obtained and the limits of detection (LOD) and quantification (LOQ) were in the ranges of 0.003–0.006 and 0.01–0.02 mg/kg, respectively. The recovery rates of both the parent compound and its metabolites (fortified at 10 and 50× the LOQ) estimated from six replicates ranged between 81.9 and 115.5% with a relative standard deviation <12%. The validated method was applied to field‐incurred samples (collected over 7 days) sprayed once or twice with a water‐dispersible granule formulation. Notably, a substantial reduction in rate was observed after 3 days and the half‐life was short, only 1.5 days. The developed method is simple and versatile and can be used for various leafy vegetables.
Verifying the frequency ratios in the musical scale of just intonation with “hear‐and‐see” learning tools
Authors: Pejuan Arcadi
Published: November 2016

In engineering colleges, Acoustics often includes the musical scale topic, which is not very popular with most engineering students. In order to face this situation, this paper presents two alternative or complementary “hear‐and‐see” learning tools for the musical scale of just intonation. The first one combines the hearing of musical notes from an electric organ with the display on an oscilloscope from which the frequency ratios are inferred. Alternatively, the frequencies are computed in advance on the basis of the theoretical frequency ratios, and an audio editor allows to hear the resulting notes, while the PC screen can display similar graphs to those on the oscilloscope. © 2016 Wiley Periodicals, Inc. Comput Appl Eng Educ 25:5–14, 2017; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21771
National trends in incidence and survival of chronic lymphocytic leukemia in Norway for 1953–2012: a systematic analysis of population‐based data
Authors: Lenartova Andrea , Johannesen Tom Børge , Tjønnfjord Geir Erland
Published: November 2016

Chronic lymphocytic leukemia is a disease of the elderly, and despite major advances in treatment, remains incurable. The Cancer Registry of Norway has registered data on patients with chronic lymphocytic leukemia since 1953. We aimed to analyze trends in incidence and survival of chronic lymphocytic leukemia in Norway. We identified 7664 patients reported with chronic lymphocytic leukemia to the registry between 1953 and 2012. We gathered information on sex, age at diagnosis, date of death and basis for diagnosis. The age‐standardized incidence increased from 0.6/100.000 person‐years in 1953 to 3.1/100,000 person‐years in 2012. We found a significant decrease in median age between 1993–2002 and 2003–2012 (75 vs. 72 years, 95%CI: 2.52–3.98, P < 0.001). Men were diagnosed at a significantly younger age than women. Immunophenotyping has become the most important diagnostic method after 2002. Median observed survival increased from 3 years in 1952–1963 to 8.5 years in 2003–2012. Five‐ and 10‐year age‐standardized net survival increased throughout the whole period across age groups and reached 79% and 57%, respectively. Median observed survival was significantly shorter in men than in women in 1993–2002 (4.9 vs. 6.1 years, P < 0.001). The gap between survival rates for men and women was diminishing in 2003–2012 in patients younger than 60 years while it remained considerable in older patients. Despite an aging Norwegian population, chronic lymphocytic leukemia (CLL) patients become younger at diagnosis. A fourfold increase in incidence, a prolonged survival, and major changes in diagnostic methods in Norway were observed.
Peptoid Efficacy against Polymicrobial Biofilms Determined by Using Propidium Monoazide‐Modified Quantitative PCR
Authors: Luo Yu , Bolt Hannah L. , Eggimann Gabriela A. , McAuley Danny F. , McMullan Ronan , Curran Tanya , Zhou Mei , Jahoda Professor Colin A. B. , Cobb Steven L. , Lundy Fionnuala T.
Published: November 2016

Biofilms containing Candida albicans are responsible for a wide variety of clinical infections. The protective effects of the biofilm matrix, the low metabolic activity of microorganisms within a biofilm and their high mutation rate, significantly enhance the resistance of biofilms to conventional antimicrobial treatments. Peptoids are peptide‐mimics that share many features of host defence antimicrobial peptides but have increased resistance to proteases and therefore have better stability in vivo. The activity of a library of peptoids was tested against monospecies and polymicrobial bacterial/fungal biofilms. Selected peptoids showed significant bactericidal and fungicidal activity against the polymicrobial biofilms. This coupled with low cytotoxicity suggests that peptoids could offer a new option for the treatment of clinically relevant polymicrobial infections.
Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter‐Alkyl‐Chain Distance and Alkyl Chain Length
Authors: Cho Kyung Ho , Hariharan Parameswaran , Mortensen Jonas S. , Du Yang , Nielsen Anne K. , Byrne Bernadette , Kobilka Brian K. , Loland Claus J. , Guan Lan , Chae Pil Seok
Published: November 2016

Membrane proteins encapsulated by detergent micelles are widely used for structural study. Because of their amphipathic property, detergents have the ability to maintain protein solubility and stability in an aqueous medium. However, conventional detergents have serious limitations in their scope and utility, particularly for eukaryotic membrane proteins and membrane protein complexes. Thus, a number of new agents have been devised; some have made significant contributions to membrane protein structural studies. However, few detergent design principles are available. In this study, we prepared meta and ortho isomers of the previously reported para‐substituted xylene‐linked maltoside amphiphiles (XMAs), along with alkyl chain‐length variation. The isomeric XMAs were assessed with three membrane proteins, and the meta isomer with a C12 alkyl chain was most effective at maintaining solubility/stability of the membrane proteins. We propose that interplay between the hydrophile–lipophile balance (HLB) and alkyl chain length is of central importance for high detergent efficacy. In addition, differences in inter‐alkyl‐chain distance between the isomers influence the ability of the detergents to stabilise membrane proteins.
Response Profiling Using Shotgun Proteomics Enables Global Metallodrug Mechanisms of Action To Be Established
Authors: Kreutz Dominique , Bileck Andrea , Plessl Kerstin , Wolrab Denise , Groessl Michael , Keppler Bernhard K. , Meier Samuel M. , Gerner Christopher
Published: November 2016

Response profiling using shotgun proteomics for establishing global metallodrug mechanisms of action in two colon carcinoma cell lines, HCT116 and SW480, has been applied and evaluated with the clinically approved arsenic trioxide. Surprisingly, the complete established mechanism of action of arsenic trioxide was observed by protein regulations in SW480, but not HCT116 cells. Comparing the basal protein expression in the two cell lines revealed an 80 % convergence of protein identification, but with significant expression differences, which in turn seem to affect the extent of protein regulation. A clear‐cut redox response was observed in SW480 cells upon treatment with arsenic, but hardly in HCT116 cells. Response profiling was then used to investigate four anti‐cancer metallodrugs (KP46, KP772, KP1339 and KP1537). Proteome alterations were mapped to selected functional groups, including DNA repair, endocytosis, protection from oxidative stress, protection from endoplasmatic reticulum (ER) stress, cell adhesion and mitochondrial function. The present data suggest that knowledge of the mechanism of action of anti‐cancer metallodrugs and improved patient stratification strategies are imperative for the design of clinical studies.
RhII‐Catalyzed β‐C(sp2)−H Alkylation of Enol Ethers, Enamides and Enecarbamates with α‐Diazo Dicarbonyl Compounds
Authors: McLarney Brett D. , Cavitt Marchello A. , Donnell Theodore M. , Musaev Djamaladdin G. , France Stefan
Published: November 2016

A RhII‐catalyzed method for intermolecular alkylation of the β‐C(sp2)−H bond of enol ethers, enamides, and enecarbamates with α‐diazo‐1,3‐dicarbonyl compounds is reported. The products are formed in up to 99 % yield and can be readily derivatized under a variety of conditions. By utilizing a combination of experimental and computational studies, the presumptive addition–elimination reaction mechanism was investigated and found to proceed under thermodynamic control at higher temperature. The acquired fundamental knowledge was translated into a strategic reaction design and yielded the first example of the β‐C−H functionalizations of acyclic enol ethers using α‐diazo‐1,3‐dicarbonyl compounds.
A Zirconium Macrocyclic Metal–Organic Framework with Predesigned Shape‐Persistent Apertures
Authors: Chen Teng‐Hao , Popov Ilya , Miljanić Ognjen Š.
Published: November 2016

A microporous metal–organic framework (MOF) was synthesized from [Zr6O4(OH)4(C6H5COO)12] clusters and a triacid ligand based on a shape‐persistent arylene ethynylene macrocycle. This framework, dubbed Zr‐MCMOF, is held together by metal–ligand coordination and multiple weak interactions: hydrogen bonding, [π⋅⋅⋅π] stacking, and [C−H⋅⋅⋅π] interactions. The rigid ligand has a 9 Å‐wide central void, which serves as a predesigned aperture for the 1D channels; all of the porosity of Zr‐MCMOF comes from the ligand. The resulting framework possesses high hydrolytic and thermal stability and a flexible structure unique among Zr‐based MOFs.
Photochemical Reduction of CO2 with Visible Light Using a Polyoxometalate as Photoreductant
Authors: Haviv Eynat , Shimon Linda J. W. , Neumann Ronny
Published: November 2016

The photochemical reduction of CO2 to CO requires two electrons and two protons that, in the past, have been derived from sacrificial amine donors that are also non‐innocent in the catalytic cycle. Towards the realization of a water‐splitting reaction as the source of electrons and protons for CO2 reduction, we have found that a reduced acidic polyoxometalate, H5PWV2W10O40, is a photoactive electron and proton donor with visible light through excitation of the intervalence charge‐transfer band. Upon linking the polyoxometalate to a dirhenium molecular catalyst, a cascade of transformations occurs where the polyoxometalate is electrochemically reduced at a relatively low negative potential of 1.3 V versus Ag/AgNO3 and visible light, a 60 W tungsten lamp, or a red LED is used to transfer electrons from the polyoxometalate to the dirhenium catalyst active for the selective reduction of CO2 to CO.
Magneto‐Thermal Release from Nanoscale Unilamellar Hybrid Vesicles
Authors: Bixner Oliver , Bello Gianluca , Virk Mudassar , Kurzhals Steffen , Scheberl Andrea , Gal Noga , Matysik Artur , Kraut Rachel , Reimhult Erik
Published: November 2016

Hybrid vesicles of lipid and amphiphilic block copolymer combine the biological and functional versatility of lipid delivery systems with the mechanical stability and robustness of polymersomes. While studies of hybrid systems for ease of characterization have focused on giant vesicles, most encapsulation and release applications require nanoscale (large) unilamellar vesicles. We investigate the structure and physical characteristics important for thermal actuation of vesicle‐forming blends of saturated phospholipid, polybutadiene‐b‐poly(ethylene oxide) and thermoresponsive polyisoprene‐b‐poly(N‐isopropylacryl amide) that are additionally loaded with hydrophobic superparamagnetic nanoparticles in the vesicle membrane and resized to large unilamellar vesicles. Lipid/diblock copolymer hybrid vesicles are shown to be the most efficient option to trigger release of encapsulated compounds by application of an external magnetic field causing local hyperthermia. This superiority is shown to depend on the controlled formation of nanoscale lipid domains in the hybrid vesicle membrane and the efficient loading of hydrophobic nanoparticles into the diblock copolymer membrane that retains its stability.
Study of the Chemical Space of Selected Bacteriostatic Sulfonamides from an Information Theory Point of View
Authors: López‐Rosa Sheila , Molina‐Espíritu Moyocoyani , Esquivel Rodolfo O. , Soriano‐Correa Catalina , Dehesa Jésus S.
Published: November 2016

The relative structural location of a selected group of 27 sulfonamide‐like molecules in a chemical space defined by three information theory quantities (Shannon entropy, Fisher information, and disequilibrium) is discussed. This group is composed of 15 active bacteriostatic molecules, 11 theoretically designed ones, and para‐aminobenzoic acid. This endeavor allows molecules that share common chemical properties through the molecular backbone, but with significant differences in the identity of the chemical substituents, which might result in bacteriostatic activity, to be structurally classified and characterized. This is performed by quantifying the structural changes on the electron density distribution due to different functional groups and number of electrons. The macroscopic molecular features are described by means of the entropy‐like notions of spatial electronic delocalization, order, and uniformity. Hence, an information theory three‐dimensional space (IT‐3D) emerges that allows molecules with common properties to be gathered. This space witnesses the biological activity of the sulfonamides. Some structural aspects and information theory properties can be associated, as a result of the IT‐3D chemical space, with the bacteriostatic activity of these molecules. Most interesting is that the active bacteriostatic molecules are more similar to para‐aminobenzoic acid than to the theoretically designed analogues.
Precursor States of Organic Adsorbates on Semiconductor Surfaces are Chemisorbed and Immobile
Authors: Pecher Lisa , Tonner Ralf
Published: November 2016

Intermediate states to covalent attachment of molecules on surfaces, so called precursors, are usually considered to be physisorbed and mobile. We show that this view should be reconsidered and provide evidence for a chemisorbed precursor for ethylene on Si(001). The character of the molecule‐surface bond as a π complex is determined and quantified using our recently developed method for energy and charge analysis in extended systems. In contrast to previous assumptions, the precursor should thus be immobile, which is underlined by computation of high diffusion energy barriers. This has important implications for understanding and modelling of adsorption kinetics. Our analysis highlights that taking the viewpoint of molecular chemistry helps uncover important aspects in the adsorption process on surfaces. Previous experimental results that appear to be in contrast to our model are examined and reinterpreted.
Effect of everolimus on the pharmacokinetics of octreotide long‐acting repeatable in patients with advanced neuroendocrine tumors: An analysis of the randomized phase III RADIANT‐2 trial
Authors: Pavel ME , Becerra C , Grosch K , Cheung W , Hasskarl J , Yao JC
Published: November 2016

In the RADIANT‐2 trial, addition of everolimus to octreotide long‐acting repeatable (LAR) exhibited a clinically meaningful 5.1‐month improvement in progression‐free survival (PFS) in patients with advanced functional neuroendocrine tumors. In this study, we characterized the effects of everolimus co‐administration on octreotide LAR pharmacokinetics and its relationship with efficacy and safety. At least one evaluable blood everolimus and plasma octreotide predose minimum concentration (Cmin) was available for 182 patients and 294 patients, respectively. Concomitant everolimus administration increased octreotide Cmin with a geometric mean ratio (everolimus/placebo) of 1.47 (90% confidence interval [CI] = 1.32–1.64). Risk for progression was consistently reduced when everolimus Cmin was increased twofold, regardless of octreotide exposure (hazard ratio [HR] = 0.74; 95% CI = 0.46–1.18; HR = 0.54; 95% CI = 0.32–0.92 for 6 ng/mL and 4 ng/mL octreotide, respectively). Risk for pulmonary or metabolic events was associated with increased everolimus Cmin. Co‐administration of everolimus plus octreotide LAR increased octreotide Cmin, which did not impact efficacy.
Properties of Sm‐doped CaNb2O6 thin films deposited by radio‐frequency magnetron sputtering
Authors: Cho Shinho
Published: November 2016

Sm‐doped CaNb2O6 (CaNb2O6:Sm) phosphor thin films were prepared by radio‐frequency magnetron sputtering on sapphire substrates. The thin films were grown at several growth temperatures and subsequently annealed at 800 °C in air. The crystallinity, surface morphology, optical transmittance, and photoluminescence of the thin films were investigated by X‐ray diffraction, scanning electron microscopy, ultraviolet‐visible spectrophotometry, and fluorescence spectrophotometry, respectively. All of the thin films showed a main red emission radiated by the transition from the 4G5/2 excited state to the 6H9/2 ground state of the Sm3+ ions and several weak bands under ultraviolet excitation with a 279 nm wavelength. The optimum growth temperature for depositing the high‐quality CaNb2O6:Sm thin films, which was determined from the luminescence intensity, was found to be 400 °C, where the thin film exhibited an orthorhombic structure with a thickness of 370 nm, an average grain size of 220 nm, a band gap energy of 3.99 eV, and an average optical transmittance of 85.9%. These results indicate that the growth temperature plays an important role in controlling the emission intensity and optical band gap energy of CaNb2O6:Sm thin films.
Role of JNK during buccopharyngeal membrane perforation, the last step of embryonic mouth formation
Authors: Houssin Nathalie S. , Bharathan Navaneetha Krishnan , Turner Stephen D. , Dickinson Amanda J.G.
Published: November 2016

Background: The buccopharyngeal membrane is a thin layer of cells covering the embryonic mouth. The perforation of this structure creates an opening connecting the external and the digestive tube which is essential for oral cavity formation. In humans, persistence of the buccopharyngeal membrane can lead to orofacial defects such as choanal atresia, oral synechiaes, and cleft palate. Little is known about the causes of a persistent buccopharyngeal membrane and, importantly, how this structure ruptures. Results: We have determined, using antisense and pharmacological approaches, that Xenopus embryos deficient c‐Jun N‐terminal kinase (JNK) signaling have a persistent buccopharyngeal membrane. JNK deficient embryos have decreased cell division and increased cellular stress and apoptosis. However, altering these processes independently of JNK did not affect buccopharyngeal membrane perforation. JNK deficient embryos also have increased intercellular adhesion and defects in e‐cadherin localization. Conversely, embryos with overactive JNK have epidermal fragility, increased E‐cadherin internalization, and increased membrane localized clathrin. In the buccopharyngeal membrane, clathrin is colocalized with active JNK. Furthermore, inhibition of endocytosis results in a persistent buccopharyngeal membrane, mimicking the JNK deficient phenotype. Conclusions: The results of this study suggest that JNK has a role in the disassembly adherens junctions by means of endocytosis that is required during buccopharyngeal membrane perforation. Developmental Dynamics 246:100–115, 2017. © 2016 Wiley Periodicals, Inc.
Adapting the eating disorder examination for use during pregnancy: Preliminary results from a community sample of women with overweight and obesity
Authors: Emery Rebecca L. , Grace Jennifer L. , Kolko Rachel P. , Levine Michele D.
Published: November 2016

Objective

The Eating Disorder Examination (EDE) is a structured clinical interview that is widely used for assessing disordered eating. Although the EDE has been used in pregnant women, no standard pregnancy version has been developed. Accordingly, the present study aimed to document adaptations made to a pregnancy version of the EDE (EDE‐PV) and to describe the internal reliability of this adapted version.

Method

Three major modifications were made in the development of the EDE‐PV. First, disordered eating was assessed during and prior to pregnancy to account for changes across the perinatal period. Second, items were adapted and rules governing ratings were altered to distinguish eating attitudes and behaviors that are considered normative during pregnancy from disordered eating. Third, several items were omitted.

Results

The EDE‐PV was administered to 129 women with overweight and obesity who were between 12 and 20 weeks gestation. Women were 27.25 (SD = 5.48) years of age and 56% were African American. Women endorsed low levels of disordered eating on the EDE‐PV, and the internal reliability was similar to previous reports.

Conclusion

These findings provide support for use of the EDE‐PV to assess disordered eating among pregnant women with overweight and obesity. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:597–601)
Dual‐polarization radar products for biological applications
Authors: Stepanian Phillip M. , Horton Kyle G. , Melnikov Valery M. , Zrnić Dušan S. , Gauthreaux Sidney A.
Published: November 2016

The upgrade of the national network of next‐generation weather surveillance radars (NEXRAD) in the United States to dual polarizations has been completed, providing three additional routine data products: total differential phase (ψDP), differential reflectivity (ZDR), and copolar correlation coefficient (ρHV). The application and interpretation of these products in the context of aerial bird, bat, and insect movements is an actively developing research front, with potential implications for ecological and conservation studies. The following conceptually derives the definition of these products specifically for NEXRAD weather surveillance radars in the case of biological scatterers. Several cases are presented that illustrate characteristic values and variability of polarimetric quantities for birds and insects, and highlight site‐specific differences within the NEXRAD network. Finally, a short prospectus of future directions and applications within the field of polarimetric radar aeroecology is outlined.
An integrated data model to estimate spatiotemporal occupancy, abundance, and colonization dynamics
Authors: Williams Perry J. , Hooten Mevin B. , Womble Jamie N. , Esslinger George G. , Bower Michael R. , Hefley Trevor J.
Published: November 2016

Ecological invasions and colonizations occur dynamically through space and time. Estimating the distribution and abundance of colonizing species is critical for efficient management or conservation. We describe a statistical framework for simultaneously estimating spatiotemporal occupancy and abundance dynamics of a colonizing species. Our method accounts for several issues that are common when modeling spatiotemporal ecological data including multiple levels of detection probability, multiple data sources, and computational limitations that occur when making fine‐scale inference over a large spatiotemporal domain. We apply the model to estimate the colonization dynamics of sea otters (Enhydra lutris) in Glacier Bay, in southeastern Alaska.
Factors associated with reported challenging behavior in young people with epilepsy and neurodevelopmental problems: Data from a specialist epilepsy center
Authors: Reilly Colin , Scott Rod C.
Published: November 2016

Reported incidents of challenging behavior over a 6‐month period (December 2011–May 2012) were systematically recorded in young people (8–23 years) with epilepsy (n = 125), and a comparison group of young people without epilepsy (n = 64) at a specialist epilepsy center in the United Kingdom. Factors associated with such incidents were analyzed via regression analysis. The presence of epilepsy was not a significant predictor of recorded challenging behavior. Factors associated with increases in recorded challenging behavior on multivariable analysis in the epilepsy sample were the use of medication for behavioral/psychiatric conditions (p < 0.05) and attending the center on a residential basis (p < 0.001). In the total sample, use of medication for behavioral/psychiatric conditions (p < 0.05), younger age (p < 0.01), IQ < 50 (p < 0.01), and residential status (p < 0.001) were associated with increases in recorded challenging behavior. The presence of depression was associated with reduced challenging behavior in the total sample (p < 0.05).The association between the use of psychopharmacology and increased challenging behavior in those with epilepsy and nonepilepsy could indicate a difficult to treat behavioral/psychiatric burden, lack of treatment efficacy, and/or an increased side effect profile and needs further examination.
Finite element methods for a class of continuum models for immiscible flows with moving contact lines
Authors: Reusken Arnold , Xu Xianmin , Zhang Liang
Published: November 2016

In this paper, we present a finite element method for two‐phase incompressible flows with moving contact lines. We use a sharp interface Navier–Stokes model for the bulk phase fluid dynamics. Surface tension forces, including Marangoni forces and viscous interfacial effects, are modeled. For describing the moving contact lines, we consider a class of continuum models that contains several special cases known from the literature. For the whole model, describing bulk fluid dynamics, surface tension forces, and contact line forces, we derive a variational formulation and a corresponding energy estimate. For handling the evolving interface numerically, the level‐set technique is applied. The discontinuous pressure is accurately approximated by using a stabilized extended finite element space. We apply a Nitsche technique to weakly impose the Navier slip conditions on the solid wall. A unified approach for discretization of the (different types of) surface tension forces and contact line forces is introduced. Results of numerical experiments are presented, which illustrate the performance of the solver. Copyright © 2016 John Wiley & Sons, Ltd.
Ph‐like acute lymphoblastic leukemia with a novel PAX5‐KIDINS220 fusion transcript
Authors: Sakamoto Kenichi , Imamura Toshihiko , Kanayama Takuyo , Yano Mio , Asai Daisuke , Deguchi Takao , Hashii Yoshiko , Tanizawa Akihiko , Ohshima Yusei , Kiyokawa Nobutaka , Horibe Keizo , Sato Atsushi
Published: November 2016

Although “paired box 5” (PAX5)‐related fusion genes are well documented in childhood B‐cell precursor acute lymphoblastic leukemia (ALL), these types of fusion with the exception of PAX5‐JAK2 are rarely seen in patients with gene expression profiles similar to those of BCR‐ABL1 (Philadelphia)‐positive ALL (Ph‐like ALL). We report a novel fusion of the genes PAX5 and “kinase D‐interacting substrate of 220 kDa” (KIDINS220, also known as ARMS) in a Ph‐like ALL. As PAX5 is a master regulator of B‐lymphocyte differentiation, PAX5 rearrangements induce a differentiation block in B lymphocytes. KIDINS220 is a mediator of multiple receptor signaling pathways, interacts with both T‐ and B‐cell receptors, and is necessary for sustained extracellular signal‐regulated kinase (ERK) signaling. Although functional studies are needed, the PAX5‐KIDINS220 fusion protein might not only inhibit wild‐type PAX5 function, but also promote sustained activation of the ERK signaling pathway through upregulation of KIDINS220. © 2016 Wiley Periodicals, Inc.
Hospital Policy and Productivity – Evidence from German States
Authors: Karmann Alexander , Roesel Felix
Published: November 2016

Total factor productivity (TFP) growth allows for additional healthcare services under restricted resources. We examine whether hospital policy can stimulate hospital TFP growth. We exploit variation across German federal states in the period 1993–2013. State governments decide on hospital capacity planning (number of hospitals, departments, and beds), ownership, medical students, and hospital investment funding. We show that TFP growth in German hospital care reflects quality improvements rather than increases in output volumes. Second‐stage regression results indicate that reducing the length of stay is generally a proper way to foster TFP growth. The effects of other hospital policies depend on the reimbursement scheme: Under activity‐based (German Diagnosis‐related Group) hospital funding, scope‐related policies (privatization and specialization) come with TFP growth. Under fixed daily rate funding, scale matters to TFP (hospital size and occupancy rates). Differences in capitalization in East and West Germany allow to show that deepening capital may enhance TFP growth if capital is scarce. We also show that there is less scope for hospital policies after large‐scale restructurings of the hospital sector. Copyright © 2016 John Wiley & Sons, Ltd.
Hepatitis B virus infection and decreased risk of nonalcoholic fatty liver disease: A cohort study
Authors: Joo Eun‐Jeong , Chang Yoosoo , Yeom Joon‐Sup , Ryu Seungho
Published: November 2016

The presence of an association between chronic hepatitis B virus (HBV) infection and fatty liver is controversial. We examined the association between HBV infection and the development of nonalcoholic fatty liver disease (NAFLD). We conducted a cohort study of 83,339 participants without NAFLD at baseline who underwent serologic testing for hepatitis B surface antigen (HBsAg) between 2002 and 2006 and were followed annually or biennially until December 2014. NAFLD was defined as the presence of ultrasonographic fatty liver in the absence of excessive alcohol use or other identifiable causes. We used a parametric Cox model to estimate adjusted hazard ratios with 95% confidence intervals of incident NAFLD. During 484,736.1 person‐years of follow‐up, 20,200 incident NAFLD cases were identified. In models adjusted for age, sex, year of visit, smoking status, alcohol intake, regular exercise, education level, and body mass index, the adjusted hazard ratio (95% confidence interval) for incident NAFLD comparing HBsAg‐positive to HBsAg‐negative participants was 0.83 (0.73‐0.94). After introducing HBV infection and confounders (including homeostasis model assessment of insulin resistance and metabolic factors) as time‐dependent exposures, the association between HBV infection and decreased risk of incident NAFLD was attenuated but persisted. These associations were consistently observed across clinically relevant, prespecified subgroups. Conclusion: In this large cohort of apparently healthy Korean adults, HBsAg seropositivity was associated with lower risk of developing NAFLD, indicating a possible effect of HBV infection on the pathogenesis of NAFLD development. (Hepatology 2017;65:828‐835).
Shp2 promotes liver cancer stem cell expansion by augmenting β‐catenin signaling and predicts chemotherapeutic response of patients
Authors: Xiang Daimin , Cheng Zhuo , Liu Hui , Wang Xue , Han Tao , Sun Wen , Li Xiaofeng , Yang Wen , Chen Cheng , Xia Mingyang , Liu Na , Yin Shengyong , Jin Guangzhi , Lee Terence , Dong Liwei , Hu Heping , Wang Hongyang , Ding Jin
Published: November 2016

Src‐homology 2 domain–containing phosphatase 2 (Shp2) has been reported to play an important role in the maintenance and self‐renewal of embryonic and adult stem cells, but its role in cancer stem cells (CSCs) remains obscure. Herein, we observed high expression of Shp2 in both chemoresistant hepatocellular carcinomas (HCCs) and recurrent HCCs from patients. A remarkable increase of Shp2 was detected in sorted epithelial cell adhesion molecule–positive or cluster of differentiation 133–positive liver CSCs and in CSC‐enriched hepatoma spheroids from patients. Up‐regulated Shp2 facilitated liver CSC expansion by promoting the dedifferentiation of hepatoma cells and enhancing the self‐renewal of liver CSCs. Mechanistically, Shp2 dephosphorylated cell division cycle 73 in the cytosol of hepatoma cells, and the dephosphorylated cell division cycle 73 bound β‐catenin and facilitated the nuclear translocation of β‐catenin, which promoted the dedifferentiation of hepatoma cells. Shp2 increased β‐catenin accumulation by inhibiting glycogen synthase kinase 3β–mediated β‐catenin degradation in liver CSCs, thereby enhancing the self‐renewal of liver CSCs. Blockage of β‐catenin abolished the discrepancy in liver CSC proportion and the self‐renewal capacity between Shp2‐depleted hepatoma cells and control cells, which further confirmed that β‐catenin is required in Shp2‐promoted liver CSC expansion. More importantly, HCC patients with low Shp2 levels benefited from transcatheter arterial chemoembolization or sorafenib treatment, but patients with high Shp2 expression did not, indicating the significance of Shp2 in personalized HCC therapy. Conclusion: Shp2 could promote HCC cell dedifferentiation and liver CSC expansion by amplifying β‐catenin signaling and may be useful in predicting patient response to chemotherapeutics. (Hepatology 2017;65:1566‐1580).
Farnesoid X receptor ablation sensitizes mice to hepatitis b virus X protein–induced hepatocarcinogenesis
Authors: Niu Yongdong , Xu Meishu , Slagle Betty L. , Huang Haihua , Li Song , Guo Grace L. , Shi Ganggang , Qin Wenxin , Xie Wen
Published: November 2016

Chronic hepatitis B virus infection is a major risk factor for hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) is a hepatitis B virus protein that has multiple cellular functions, but its role in HCC pathogenesis has been controversial. Farnesoid X receptor (FXR) is a nuclear receptor with activities in anti‐inflammation and inhibition of hepatocarcinogenesis. However, whether or how FXR can impact hepatitis B virus/HBx‐induced hepatocarcinogenesis remains unclear. In this study, we showed that HBx can interact with FXR and function as a coactivator of FXR. Expression of HBx in vivo enhanced FXR‐responsive gene regulation. HBx also increased the transcriptional activity of FXR in a luciferase reporter gene assay. The HBx–FXR interaction was confirmed by coimmunoprecipitation and glutathione S‐transferase pull‐down assays, and the FXR activation function 1 domain was mapped to bind to the third α helix in the C terminus of HBx. We also found that the C‐terminally truncated variants of HBx, which were found in clinical HCC, were not effective at transactivating FXR. Interestingly, recruitment of the full‐length HBx, but not the C‐terminally truncated HBx, enhanced the binding of FXR to its response element. In vivo, FXR ablation markedly sensitized mice to HBx‐induced hepatocarcinogenesis. Conclusions: We propose that transactivation of FXR by full‐length HBx may represent a protective mechanism to inhibit HCC and that this inhibition may be compromised upon the appearance of C‐terminally truncated HBx or when the expression and/or activity of FXR is decreased. (Hepatology 2017;65:893‐906)
Optimal timing of hepatitis C treatment for patients on the liver transplant waiting list
Authors: Chhatwal Jagpreet , Samur Sumeyye , Kues Brian , Ayer Turgay , Roberts Mark S. , Kanwal Fasiha , Hur Chin , Donnell Drew Michael S. , Chung Raymond T.
Published: November 2016

The availability of oral direct‐acting antivirals has altered the hepatitis C virus (HCV) treatment paradigm for both pre–liver transplant (LT) and post‐LT patients. There is a perceived trade‐off between pre‐LT versus post‐LT treatment of HCV—treatment may improve liver function but potentially decrease the likelihood of a necessary LT. Our objective was to identify LT‐eligible patients with decompensated cirrhosis who would benefit (and not benefit) from pre‐LT treatment based on their Model for End‐Stage Liver Disease (MELD) scores. We simulated a virtual trial comparing long‐term outcomes of pre‐LT versus post‐LT HCV treatment with oral direct‐acting antivirals for patients with MELD scores between 10 and 40. We developed a Markov‐based microsimulation model, which simulated the life course of patients on the transplant waiting list and after LT. Simulation of LT integrated data from recent trials of oral direct‐acting antivirals (SOLAR 1 and 2), the United Network for Organ Sharing (UNOS), and other studies. The outcomes of the model included life expectancy, 1‐year and 5‐year patient survival, and mortality. Model‐predicted patient survival was validated with UNOS data. We found that, at the national level, treating HCV before LT increased life expectancy if MELD was ≤27 but could decrease life expectancy at higher MELD scores. Depending on the UNOS region, the threshold MELD score to treat HCV pre‐LT varied between 23 and 27 and was lower for UNOS regions 3, 10, and 11 and higher for regions 1, 2, 4, 5, 8, and 9. Sensitivity analysis showed that the thresholds were stable. Conclusion: Our findings suggest that the optimal MELD threshold below which decompensated cirrhosis patients should receive HCV treatment while awaiting LT is between 23 and 27, depending on the UNOS region. (Hepatology 2017;65:777‐788)
Functional defect of variants in the adenosine triphosphate–binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX‐770)
Authors: Delaunay Jean‐Louis , Bruneau Alix , Hoffmann Brice , Durand‐Schneider Anne‐Marie , Barbu Véronique , Jacquemin Emmanuel , Maurice Michèle , Housset Chantal , Callebaut Isabelle , Aït‐Slimane Tounsia
Published: November 2016

ABCB4 (MDR3) is an adenosine triphosphate (ATP)‐binding cassette (ABC) transporter expressed at the canalicular membrane of hepatocytes, where it mediates phosphatidylcholine (PC) secretion. Variations in the ABCB4 gene are responsible for several biliary diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3), a rare disease that can be lethal in the absence of liver transplantation. In this study, we investigated the effect and potential rescue of ABCB4 missense variations that reside in the highly conserved motifs of ABC transporters, involved in ATP binding. Five disease‐causing variations in these motifs have been identified in ABCB4 (G535D, G536R, S1076C, S1176L, and G1178S), three of which are homologous to the gating mutations of cystic fibrosis transmembrane conductance regulator (CFTR or ABCC7; i.e., G551D, S1251N, and G1349D), that were previously shown to be function defective and corrected by ivacaftor (VX‐770; Kalydeco), a clinically approved CFTR potentiator. Three‐dimensional structural modeling predicted that all five ABCB4 variants would disrupt critical interactions in the binding of ATP and thereby impair ATP‐induced nucleotide‐binding domain dimerization and ABCB4 function. This prediction was confirmed by expression in cell models, which showed that the ABCB4 mutants were normally processed and targeted to the plasma membrane, whereas their PC secretion activity was dramatically decreased. As also hypothesized on the basis of molecular modeling, PC secretion activity of the mutants was rescued by the CFTR potentiator, ivacaftor (VX‐770). Conclusion: Disease‐causing variations in the ATP‐binding sites of ABCB4 cause defects in PC secretion, which can be rescued by ivacaftor. These results provide the first experimental evidence that ivacaftor is a potential therapy for selected patients who harbor mutations in the ATP‐binding sites of ABCB4. (Hepatology 2017;65:560‐570)
Associations between early maternal sensitivity and children's sleep throughout early childhood
Authors: Tétreault Émilie , Bouvette‐Turcot Andrée‐Anne , Bernier Annie , Bailey Heidi
Published: November 2016

Despite strong theoretical reasons to believe that the quality of parent–infant interactions should influence child sleep, the empirical evidence for links between maternal behavior and children's sleep is equivocal. Notably, it is unclear at which ages such influences might be particularly salient. The current study aimed to examine prospective longitudinal associations between early maternal sensitivity and children's sleep during early childhood. Maternal sensitivity was assessed at 12 months during a home visit. Children's sleep was measured at 12 and 18 months as well as at 2, 3, and 4 years, using a sleep diary completed by mothers. Results revealed significant or marginal positive associations between maternal sensitivity and children's sleep consolidation (percentage of nighttime sleep) at 2, 3, and 4 years, but not at the most proximal assessments of 12 and 18 months. These findings suggest that child age could potentially be a key factor in the associations between maternal behavior and children's sleep.

Highlights

Associations between three dimensions of early maternal sensitivity and children's sleep from 1 to 4 years of age were investigated.

Maternal sensitivity was positively associated with children's sleep between 2 and 4 years, but not at 12 and 18 months.

The results suggest that child age could be a key factor in the associations between maternal behavior and children's sleep.
The absence of HLA class I expression in non‐small cell lung cancer correlates with the tumor tissue structure and the pattern of T cell infiltration
Authors: Perea Francisco , Bernal Mónica , Sánchez‐Palencia Abel , Carretero Javier , Torres Cristina , Bayarri Clara , Gómez‐Morales Mercedes , Garrido Federico , Ruiz‐Cabello Francisco
Published: November 2016

We wanted to analyze whether tumor HLA class I (HLA‐I) expression influences the pattern of the immune cell infiltration and stromal cell reaction in the tumor microenvironment. Tumor tissues obtained from 57 patients diagnosed with lung carcinomas were analyzed for HLA expression and leukocyte infiltration. 28 patients out of the 57 were completely negative for HLA‐I expression (49.1%) or showed a selective HLA‐A locus downregulation (three patients, 5.2%). In 26 out of 57 tumors (47.8%) we detected a positive HLA‐I expression but with a percentage of HLA‐I negative cells between 10 and 25%. The HLA‐I negative phenotype was produced by a combination of HLA haplotype loss and a transcriptional downregulation of β2‐microglobulin (β2‐m) and LMP2 and LMP7 antigen presentation machinery genes. The analysis and localization of different immune cell populations revealed the presence of two major and reproducible patterns. One pattern, which we designated “immune‐permissive tumor microenvironment (TME),” was characterized by positive tumor HLA‐I expression, intratumoral infiltration with cytotoxic T‐CD8+ cells, M1‐inflammatory type macrophages, and a diffuse pattern of FAP+ cancer‐associated fibroblasts. In contrast, another pattern defined as “non‐immune‐permissive TME” was found in HLA‐I negative tumors with strong stromal‐matrix interaction, T‐CD8+ cells surrounding tumor nests, a dense layer of FAP+ fibroblasts and M2/repair‐type macrophages. In conclusion, this study revealed marked differences between HLA class I‐positive and negative tumors related to tissue structure, the composition of leukocyte infiltration and stromal response in the tumor microenvironment.
Synthesis and stability studies of Ga‐67 labeled phosphonium salts
Authors: Kardashinsky Mingyue , Lengkeek Nigel , Rendina Louis M.
Published: November 2016

Delocalized lipophilic cations such as tri‐ and tetra‐arylphosphonium are able to diffuse across the mitochondrial membrane, which allows them to selectively accumulate in cells with a high transmembrane potential (ΔΨm). The mitochondrial membrane potential of cancer cells and cardiomyocytes has been reported to be significantly higher than that of normal epithelial cells. This feature can be exploited for the selective accumulation of phosphonium derivatives for the purposes of molecular imaging using radionuclides. Four structurally related Ga(III)‐phosphonium salts were synthesized and fully characterized and found to be modest in toxicity toward T98G human glioblastoma cells (IC50 > 4 mM). High‐activity (100 MBq) analogs containing Ga‐67 were also synthesized and their stabilities in phosphate‐buffered saline and human serum were determined.