bluuebunny/crossref_metadata_2025 huggingface dataset:
The local dayside reconnection rate for oblique interplanetary magnetic fields
Authors: Komar C. M. , Cassak P. A.
Published: May 2016

We present an analysis of local properties of magnetic reconnection at the dayside magnetopause for various interplanetary magnetic field (IMF) orientations in global magnetospheric simulations. This has heretofore not been practical because it is difficult to locate where reconnection occurs for oblique IMF, but new techniques make this possible. The approach is to identify magnetic separators, the curves separating four regions of differing magnetic topology, which map the reconnection X line. The electric field parallel to the X line is the local reconnection rate. We compare results to a simple model of local two‐dimensional asymmetric reconnection. To do so, we find the plasma parameters that locally drive reconnection in the magnetosheath and magnetosphere in planes perpendicular to the X line at a large number of points along the X line. The global magnetohydrodynamic simulations are from the three‐dimensional Block‐Adaptive, Tree Solarwind Roe‐type Upwind Scheme (BATS‐R‐US) code with a uniform resistivity, although the techniques described here are extensible to any global magnetospheric simulation model. We find that the predicted local reconnection rates scale well with the measured values for all simulations, being nearly exact for due southward IMF. However, the absolute predictions differ by an undetermined constant of proportionality, whose magnitude increases as the IMF clock angle changes from southward to northward. We also show similar scaling agreement in a simulation with oblique southward IMF and a dipole tilt. The present results will be an important component of a full understanding of the local and global properties of dayside reconnection.
Survey of Galileo plasma observations in Jupiter's plasma sheet
Authors: Bagenal Fran , Wilson Robert J. , Siler Scott , Paterson William R. , Kurth William S.
Published: May 2016

The plasma science (PLS) instrument on the Galileo spacecraft (orbiting Jupiter from December 1995 to September 2003) measured properties of the ions that were trapped in the magnetic field. The PLS data provide a survey of the plasma properties between ~5 and 30 Jupiter radii (RJ) in the equatorial region. We present plasma properties derived via two analysis methods: numerical moments and forward modeling. We find that the density decreases with radial distance by nearly 5 orders of magnitude from ~2 to 3000 cm−3 at 6 RJ to ~0.05 cm−3 at 30 RJ. The density profile did not show major changes from orbit to orbit, suggesting that the plasma production and transport remained constant within about a factor of 2. The radial profile of ion temperature increased with distance which implied that contrary to the concept of adiabatic cooling on expansion, the plasma heats up as it expands out from Io's orbit (where Ti ~ 60–80 eV) at ~6 RJ to a few keV at 30 RJ. There does not seem to be a long‐term, systematic variation in ion temperature with either local time or longitude. This latter finding differs from earlier analysis of Galileo PLS data from a selection of orbits. Further examination of all data from all Galileo orbits suggests that System III variations are transitory on timescales of weeks, consistent with the modeling of Cassini Ultraviolet Imaging Spectrograph observations. The plasma flow is dominated by azimuthal flow that is between 80% and 100% of corotation out to 25 RJ.
Age‐dependent transcriptional and epigenomic responses to light exposure in the honey bee brain
Authors: Becker Nils , Kucharski Robert , Rössler Wolfgang , Maleszka Ryszard
Published: May 2016

Light is a powerful environmental stimulus of special importance in social honey bees that undergo a behavioral transition from in‐hive to outdoor foraging duties. Our previous work has shown that light exposure induces structural neuronal plasticity in the mushroom bodies (MBs), a brain center implicated in processing inputs from sensory modalities. Here, we extended these analyses to the molecular level to unravel light‐induced transcriptomic and epigenomic changes in the honey bee brain. We have compared gene expression in brain compartments of 1‐ and 7‐day‐old light‐exposed honey bees with age‐matched dark‐kept individuals. We have found a number of differentially expressed genes (DEGs), both novel and conserved, including several genes with reported roles in neuronal plasticity. Most of the DEGs show age‐related changes in the amplitude of light‐induced expression and are likely to be both developmentally and environmentally regulated. Some of the DEGs are either known to be methylated or are implicated in epigenetic processes suggesting that responses to light exposure are at least partly regulated at the epigenome level. Consistent with this idea light alters the DNA methylation pattern of bgm, one of the DEGs affected by light exposure, and the expression of microRNA miR‐932. This confirms the usefulness of our approach to identify candidate genes for neuronal plasticity and provides evidence for the role of epigenetic processes in driving the molecular responses to visual stimulation.
Launch of
UAVs
Authors: Gleason Thomas J. , Fahlstrom Paul G.
Published: May 2016

Launching an unmanned aerial vehicle (UAV) can be accomplished by anything from tossing it into the air by hand to a conventional wheeled takeoff from a runway at a fully developed airfield. So‐called “zero‐length launch” for fixed‐wing UAVs may vary from a large slingshot through various types of portable rail launchers to an aircraft carrier catapult. Mixed in with these approaches are rocket‐assisted takeoffs (from a runway or a rail) and launches in mid‐air from a larger manned or unmanned aircraft. Some UAVs have been launched from the back of pickup trucks speeding across open fields. In the case of UAVs that can takeoff vertically, the launch pad may vary from a patch of grass to a helipad on a ship. Each of these approaches has different requirements, advantages, and disadvantages that must be considered during the tradeoff process that determines the overall design of a UAV system.
A framework for interpreting the coarsening and structural evolution of two co‐continuous immiscible viscous fluids
Authors: McMaster Lee P.
Published: May 2016

Experimental data from multiple studies show the coarsening of co‐continuous, high interfacial tension fluid systems is driven by capillary instabilities. Coarsening of low interfacial tension systems follows viscosity ratio dependence consistent with the pinch‐off of suspended short filaments although there is uncertainty of this interpretation. The attenuation of coarsening rates for both types follows a common dependence on phase volume fraction and viscosity ratio. Dimensional analysis provides an interpretation of the transition from linear coarsening to slower nonlinear coarsening as a balance of interfacial tension driven flow and a critical level of interconnectivity. The slowdown of coarsening is consistent with the formation of discrete domains which subsequently coexist with the remaining co‐continuous structure. © 2016 American Institute of Chemical Engineers AIChE J, 62: 4140–4156, 2016
Phase behavior of system methane + hydrogen sulfide
Authors: Langè Stefano , Campestrini Marco , Stringari Paolo
Published: May 2016

An accurate description of the phase behavior of the CH4 + H2S system is given for temperatures from 70 K to the critical temperature of H2S and pressures up to 250 MPa. The study includes the solid phases of CH4 and H2S. A global pressure‐temperature diagram is presented. The types of temperature‐composition and pressure‐composition phase diagrams that can be encountered in the studied temperature and pressure ranges have been described. The temperature and pressure ranges where the phase behavior of the system changes have been identified and a representative phase diagram is presented for each range. Phase diagrams have been obtained through the solid–liquid–vapor equation of state proposed by Yokozeki. The parameters of the equation of state have been regressed on all the available phase equilibrium data for the considered system. © 2016 American Institute of Chemical Engineers AIChE J, 62: 4090–4108, 2016
Final results of a single institution experience with a pediatric‐based regimen, the augmented Berlin–Frankfurt–Münster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper‐CVAD regimen
Authors: Rytting Michael E. , Jabbour Elias J. , Jorgensen Jeffrey L. , Ravandi Farhad , Franklin Anna R. , Kadia Tapan M. , Pemmaraju Naveen , Daver Naval G. , Ferrajoli Alessandra , Garcia‐Manero Guillermo , Konopleva Marina Y. , Borthakur Gautam , Garris Rebecca , Wang Sa , Pierce Sherry , Schroeder Kurt , Kornblau Steven M. , Thomas Deborah A. , Cortes Jorge E. , O'Brien Susan M. , Kantarjian Hagop M.
Published: May 2016

Several studies reported improved outcomes of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric‐based ALL regimens. This prompted the prospective investigation of a pediatric Augmented Berlin–Frankfurt–Münster (ABFM) regimen, and its comparison with hyper‐fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone (hyper‐CVAD) in AYA patients. One hundred and six AYA patients (median age 22 years) with Philadelphia chromosome‐ (Ph) negative ALL received ABFM from October 2006 through March 2014. Their outcome was compared to 102 AYA patients (median age 27 years), treated with hyper‐CVAD at our institution. The complete remission (CR) rate was 93% with ABFM and 98% with hyper‐CVAD. The 5‐year complete remission duration (CRD) were 53 and 55%, respectively (P = 0.98). The 5‐year overall survival (OS) rates were 60 and 60%, respectively. The MRD status on Day 29 and Day 84 of therapy was predictive of long‐term outcomes on both ABFM and hyper‐CVAD. Severe regimen toxicities with ABFM included hepatotoxicity in 41%, pancreatitis in 11%, osteonecrosis in 9%, and thrombosis in 19%. Myelosuppression‐associated complications were most significant with hyper‐CVAD. In summary, ABFM and hyper‐CVAD resulted in similar efficacy outcomes, but were associated with different toxicity profiles, asparaginase‐related with ABFM and myelosuppression‐related with hyper‐CVAD. Am. J. Hematol. 91:819–823, 2016. © 2016 Wiley Periodicals, Inc.
Synergistic effect of silica nanoparticles in the matrix of a poly(ethylene glycol) diacrylate coating layer for the surface modification of polyamide nanofiltration membranes
Authors: Vatanpour Vahid , Kavian Mostafa
Published: May 2016

In this study, a commercial polyamide nanofiltration membrane was modified by a combination of poly(ethylene glycol) diacrylate (PEGDA) in situ polymerization and silica (SiO2) nanoparticles. The PEGDA layer was polymerized on the surface of the membranes alone or mixed with SiO2 nanoparticle. The surface modification influence on the water flux, salt rejection, and antifouling behavior was investigated. The effects of the nanoparticles and PEGDAylation on the membrane properties were characterized by Fourier transform infrared spectroscopy, contact angle measurement, and scanning electron microscopy analyses. The membranes that were in contact with 30 wt % PEGDA and then treated with ultraviolet light for 5 min had a better water flux than the unmodified membrane. The fouling resistance of the membranes to a foulant solution containing bovine serum albumin, humic acid, and sodium sulfate were studied, and the results show that the membrane with 30 wt % PEGDA had better antifouling properties. After the weight percentage of PEGDA for the prepolymerization solution was optimized (30 wt % was the best), the SiO2 nanoparticle concentration in the prepolymerization matrix was optimized. The presence of SiO2 nanoparticles in the PEGDA layer increased the membrane flux. The maximum water flux and good antifouling properties were obtained for 0.5 wt % SiO2 nanoparticles in a 30 wt % PEGDA layer. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43793.
The morphology and gas‐separation performance of membranes comprising multiwalled carbon nanotubes/polysulfone–Kapton
Authors: Soleymanipour Seyed Farzad , Dehaghani Amir Hossein Saeedi , Pirouzfar Vahid , Alihosseini Afahar
Published: May 2016

The development of desirable chemical structures and properties in nanocomposite membranes involve steps that need to be carefully designed and controlled. This study investigates the effect of adding multiwalled nanotubes (MWNT) on a Kapton–polysulfone composite membrane on the separation of various gas pairs. Data from Fourier transform infrared spectroscopy and scanning electron microscopy confirm that some studies on the Kapton–polysulfone blends are miscible on the molecular level. In fact, the results indicate that the chemical structure of the blend components, the Kapton–polysulfone blend compositions, and the carbon nanotubes play important roles in the transport properties of the resulting membranes. The results of gas permeability tests for the synthesized membranes specify that using a higher percentage of polysulfone (PSF) in blends resulted in membranes with higher ideal selectivity and permeability. Although the addition of nanotubes can increase the permeability of gases, it decreases gas pair selectivity. Furthermore, these outcomes suggest that Kapton–PSF membranes with higher PSF are special candidates for CO2/CH4 separation compared to CO2/N2 and O2/N2 separation. High CH4, CO2, N2, and O2 permeabilities of 0.35, 6.2, 0.34, and 1.15 bar, respectively, are obtained for the developed Kapton–PSF membranes (25/75%) with the highest percentage of carbon nanotubes (8%), whose values are the highest among all the resultant membranes. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43839.
Neoliberalism and the (internal) marketisation of primary school assessment in England
Authors: Pratt Nick
Published: May 2016

This paper considers the effect of recent education policy on assessment practices in English primary schools and how these affect relationships between teachers and pupils in an increasingly market‐driven school system. Previous research has focused largely on the effect of markets at a systemic level, but less attention has been paid to how marketisation plays out in teachers' work at classroom level. Similarly, research on assessment has tended to examine teachers' practices in relation to pupils' learning rather than examining it in terms of the role it plays in teachers' professional working lives. This paper brings these ideas together, using the latter as the context for understanding the former. In particular, it focuses on recent policy changes to the way schools in England are evaluated, moving from final attainment to pupils' progress ‘in‐year’, and considers their potential for altering the dynamics within schools rather than just between them. It draws on a small‐scale, interpretive, empirical study involving interviews with primary teachers in England. Data from this study are used to illustrate how tensions can arise for teachers and how internal market competition can be set up between them in which pupils' achievements become a commodity to be made use of, encouraging teachers to consider pupils' achievements as private, rather than public, goods. The paper thus provides a starting point for exploring the effect of market‐orientated education policy on teachers' assessment practices at the in‐school level and briefly examines some of the implications of this effect.
Effect of acidic pH on the stability of α‐synuclein dimers
Authors: Lv Zhengjian , Krasnoslobodtsev Alexey V. , Zhang Yuliang , Ysselstein Daniel , Rochet Jean Christophe , Blanchard Scott C. , Lyubchenko Yuri L.
Published: May 2016

Environmental factors, such as acidic pH, facilitate the assembly of α‐synuclein (α‐Syn) in aggregates, but the impact of pH on the very first step of α‐Syn aggregation remains elusive. Recently, we developed a single‐molecule approach that enabled us to measure directly the stability of α‐Syn dimers. Unlabeled α‐Syn monomers were immobilized on a substrate, and fluorophore‐labeled monomers were added to the solution to allow them to form dimers with immobilized α‐Syn monomers. The dimer lifetimes were measured directly from the fluorescence bursts on the time trajectories. Herein, we applied the single‐molecule tethered approach for probing of intermolecular interaction to characterize the effect of acidic pH on the lifetimes of α‐Syn dimers. The experiments were performed at pH 5 and 7 for wild‐type α−Syn and for two mutants containing familial type mutations E46K and A53T. We demonstrate that a decrease of pH resulted in more than threefold increase in the α‐Syn dimers lifetimes with some variability between the α‐Syn species. We hypothesize that the stabilization effect is explained by neutralization of residues 96–140 of α‐Syn and this electrostatic effect facilitates the association of the two monomers. Given that dimerization is the first step of α‐Syn aggregation, we posit that the electrostatic effect thereby contributes to accelerating α‐Syn aggregation at acidic pH. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 715–724, 2016.
FGFR1, 2 and 3 protein overexpression and molecular aberrations of FGFR3 in early stage non‐small cell lung cancer
Authors: Theelen Willemijn SME , Mittempergher Lorenza , Willems Stefan M , Bosma Astrid J , Peters Dennis DGC , van der Noort Vincent , Japenga Eva J , Peeters Ton , Koole Koos , Šuštić Tonći , Blaauwgeers JL , van Noesel Carel J , Bernards René , van den Heuvel Michel M
Published: May 2016

This study aimed to determine protein expression levels of fibroblast growth factor receptors (FGFR) 1, 2 and 3 in early stage non‐small cell lung cancer (NSCLC). Additionally, a screen to define the frequency of FGFR3‐TACC3 translocation and FGFR3 amplification was performed. Archived tissues from 653 NSCLC samples (adenocarcinoma (AC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC)) were analysed with immunohistochemistry (IHC) for expression of FGFR1, 2 and 3. Expression levels of FGFR1, 2 and 3 were correlated with clinicopathological features. The presence of FGFR3‐TACC3 translocation was detected by RT‐PCR and FGFR3 amplification was detected by fluorescence in situ hybridization. FGFR1, 2 and 3 proteins were highly expressed in 64 (10.6%), 76 (12.9%) and 20 (3.3%) NSCLC tumour samples, respectively. Protein expression of FGFR1 was significantly related to worse overall survival in NSCLC. Furthermore, FGFR1 protein expression was associated with light smoking and histological subtype (AC), FGFR2 protein expression with female gender, younger age, histological subtype (AC) and lower tumour stage, and FGFR3 protein was significantly overexpressed in tumours of older patients and SCC histology. The FGFR3‐TACC3 fusion was detected in 3.0% (6/200) of NSCLC samples and the FGFR3 gene was amplified in 4.7% of IHC positive NSCLC samples (2/43). FGFR1, 2 and 3 proteins are expressed in a high number of early stage NSCLC and FGFR1 protein expression may serve as a prognostic biomarker. Recurrent translocations and amplifications in FGFR3 can be found in NSCLC. This study shows that FGFR family members are frequently aberrant in NSCLC and could be interesting therapeutic targets for the treatment of NSCLC.
Genetic testing to guide warfarin dosing: Impact of direct oral anticoagulants
Authors: Lentz SR
Published: May 2016

Despite rapid growth in the use of direct oral anticoagulants (DOACs), warfarin remains a widely prescribed anticoagulant drug. It is likely that the overall use of warfarin will continue to decline, but not completely disappear, as indications for DOACs expand. This changing anticoagulation landscape, along with the likelihood that personalized genomic information will become increasingly available, has several implications for the future of warfarin dosing strategies.
Development of a flow cytometric method for quantification of BCL‐2 family members in chronic lymphocytic leukemia and correlation with sensitivity to BCL‐2 family inhibitors
Authors: Smith Morey L. , Chyla Brenda , McKeegan Evelyn , Tahir Stephen K.
Published: May 2016

Background

We have developed a quantitative fluorescence cytometry (QFCM) method that can be used to measure BCL‐2 family member proteins in cell lines and clinical samples. We described the validation of antibodies, methods development and application of the assay.

Method

We characterized and validated antibodies to BCL‐2, BCL‐XL, and MCL‐1 in cell lines to confirm specificity for flow cytometry. Each protein was measured in a panel of leukemia/lymphoma cell lines and B‐cells from chronic lymphocytic leukemia (CLL) patients treated with the BCL‐2/BCL‐XL inhibitor navitoclax. The cellular activity of various BCL‐2 family member inhibitors alone and in combination was determined to demonstrate utility of our assay to correlate protein levels with efficacy.

Results

We identified antibodies that were highly specific for each protein. The expression profile in cell lines as determined by molecules of equivalent soluble fluorochrome was comparable to western blot. Using our assay, BCL‐2, BCL‐XL, and MCL‐1 protein levels were shown to correlate with response to BCL‐2 family inhibitors in vitro and could be measured in clinical samples.

Conclusions

This method can quantify BCL‐2 family members in a specific, highly reproducible and sensitive fashion, and requires fewer cells compared to western blot. It is particularly useful for identifying BCL‐2, BCL‐XL, and MCL‐1 protein levels in a specific cell population within a heterogeneous population like those collected from CLL patients. These data show that our QFCM method can be used to facilitate the quantification and evaluation of biomarkers predictive of response in patients treated with BCL‐2 family member inhibitors. © 2016 International Clinical Cytometry Society
Pulmonary hydatid cyst with co‐existent aspergillosis: A rare cytology finding
Authors: Nayak Suprita , Kowe Balwant , Kumbhalkar Dinkar , Badkhal Ashish
Published: May 2016

Pulmonary hydatid cyst with co‐existing aspergillosis is rare. Till date, there are only two documented reports of this double pathology being diagnosed on cytology. The present case is of a young immunocompetent female who presented with respiratory complaints including intermittent hemoptysis. Chest X‐ray and CT thorax revealed two well‐defined lesions in the lower lobe of left lung that was suggestive of either infective or benign neoplastic etiology. But as hydatid cyst was not suspected either clinically or radiologically, FNA was performed. Based on the typical cytomorphological features a definitive diagnosis of hydatid cyst with aspergillosis was offered on cytology that was later confirmed on histopathology. To the best of our knowledge this is only the third report of pulmonary echinococcosis with aspergillus co‐infection being diagnosed on cytology. The purpose of reporting this case is to draw attention to the rare possibility of co‐existing aspergillus infection in pulmonary echinococcosis even in immunocompetent individuals, which can complicate the clinico‐radiological picture. However, both pathologies can be effectively and accurately diagnosed on cytology, based on which proper treatment can be initiated. Diagn. Cytopathol. 2016;44:696–699. © 2016 Wiley Periodicals, Inc.
Cytopathologic characteristics of SMARCB1 (INI‐1) deficient sinonasal carcinoma: A potential diagnostic pitfall
Authors: Allison Derek B. , Bishop Justin A. , Ali Syed Z.
Published: May 2016

Tumors of the head and neck are extremely diverse and a subset are poorly differentiated and difficult to classify. Recently, a new entity has been described with rhabdoid and/or plasmacytoid cytologic features and a characteristic genetic signature—inactivation of the SMARCB1 (INI‐1) tumor suppressor gene. To date, only 16 cases of SMARCB1 (INI‐1) deficient sinonasal carcinoma have been described, and there are currently no reports of the cytopathologic features by fine needle aspiration (FNA) cytology. A case of a 77‐year‐old man who presented with a posterior ethmoid sinus lesion with invasion into the skull base and bone was reported. FNA cytology of a right retropharyngeal lymph node revealed relatively monomorphic, loosely cohesive clusters of plasmacytoid cells with occasional nucleoli, rare intranuclear cytoplasmic inclusions, and mitotic figures in a background of necrosis and absence of overt squamous or glandular differentiation. A diagnosis of metastatic myoepithelial carcinoma was made; however, retrospectively, the surgical excision showed loss of the SMARCB1 (INI‐1) tumor suppressor gene by immunohistochemistry. In summary, the cytomorphologic features of SMARCB1 (INI‐1) deficient sinonasal carcinoma are relatively nonspecific and overlap with other regional tumors, including myoepithelial neoplasms. As a result, this entity should be considered in the differential diagnosis for a plasmacytoid tumor arising in the sinonasal tract by FNA cytology. Diagn. Cytopathol. 2016;44:700–703. © 2016 Wiley Periodicals, Inc.
Beyond DNA puffs: What can we learn from studying sciarids?
Authors: Simon Claudio Roberto , Siviero Fábio , Monesi Nadia
Published: May 2016

Summary: Members of the Sciaridae family attracted the interest of researchers because of the demonstration that the DNA puff regions, which are formed in the salivary gland polytene chromosomes at the end of the fourth larval instar, constitute sites of developmentally regulated gene amplification. Besides contributing to a deeper understanding of the process of gene amplification, the study of sciarids has also provided important insights on other biological processes such as sex determination, programmed cell death, insect immunity, telomere maintenance, and nucleolar organizing regions (NOR) formation. Open questions in sciarids include among others, early development, the role of noncoding RNAs in gene amplification and the relationship between gene amplification and transcription in DNA puff forming regions. These and other questions can now be pursued with next generation sequencing techniques and experiments using RNAi experiments, since this latter technique has been shown to be feasible in sciarids. These new perspectives in the field of sciarid biology open the opportunity to consolidate sciarid species as important emerging models. genesis 54:361–378, 2016. © 2016 Wiley Periodicals, Inc.
Deterministic and stochastic processes lead to divergence in plant communities 25 years after the 1988 Yellowstone fires
Authors: Romme William H. , Whitby Timothy G. , Tinker Daniel B. , Turner Monica G.
Published: May 2016

Young, recently burned forests are increasingly widespread throughout western North America, but forest development after large wildfires is not fully understood, especially regarding effects of variable burn severity, environmental heterogeneity, and changes in drivers over time. We followed development of subalpine forests after the 1988 Yellowstone fires by periodically resampling permanent plots established soon after the fires. We asked two questions about patterns and processes over the past 25 years: (1) Are plant species richness and community composition converging or diverging across variation in elevation, soils, burn severity, and post‐fire lodgepole pine (Pinus contorta var. latifolia) density? (2) What are the major controls on post‐fire species composition, and has the relative importance of controls changed over time? For question 1, we sampled 10‐m2 plots (n = 552) distributed among three geographic areas that differ in elevation and substrate; plots spanned the spectrum of fire severities and were resampled periodically from 1991 to 2013. For question 2, we sampled 0.25‐ha plots (n = 72), broadly distributed across areas that burned as stand‐replacing fire, in 1999 and 2012. Richness and species composition diverged early on between infertile low‐elevation areas (lower richness) and more fertile high‐elevation areas (greater richness). Richness increased rapidly for the first 5 yr post‐fire, then leveled off or increased only slowly thereafter. Only 6% of 227 recorded species were nonnative. Some annuals and species with heat‐stimulated soil seed banks were associated with severely burned sites. However, most post‐fire species had been present before the fire; many survived as roots or rhizomes and regenerated rapidly by sprouting. Among the 72 plots, substrate, temperature, and precipitation (the abiotic template) were consistently important drivers of community composition in 1999 and 2012. Post‐fire lodgepole pine abundance was not significant in 1999 but was the most important driving variable by 2012, with a negative effect on presence of most understory species, especially annuals and shade‐intolerant herbs. Burn severity was significant in 1999 but not in 2012, and distance to unburned forest had no influence in either year. The 1988 fires did not fundamentally alter subalpine forest community assemblages in Yellowstone, and ecological memory conferred resilience to high‐severity fire.
Hepatocellular carcinoma repression by TNFα‐mediated synergistic lethal effect of mitosis defect‐induced senescence and cell death sensitization
Authors: Li Dan , Fu Jing , Du Min , Zhang Haibin , Li Lu , Cen Jin , Li Weiyun , Chen Xiaotao , Lin Yunfei , Conway Edward M. , Pikarsky Eli , Wang Hongyan , Pan Guoyu , Ji Yuan , Wang Hong‐Yang , Hui Lijian
Published: May 2016

Hepatocellular carcinoma (HCC) is a cancer lacking effective therapies. Several measures have been proposed to treat HCCs, such as senescence induction, mitotic inhibition, and cell death promotion. However, data from other cancers suggest that single use of these approaches may not be effective. Here, by genetic targeting of Survivin, an inhibitor of apoptosis protein (IAP) that plays dual roles in mitosis and cell survival, we identified a tumor necrosis factor alpha (TNFα)‐mediated synergistic lethal effect between senescence and apoptosis sensitization in malignant HCCs. Survivin deficiency results in mitosis defect‐associated senescence in HCC cells, which triggers local inflammation and increased TNFα. Survivin inactivation also sensitizes HCC cells to TNFα‐triggered cell death, which leads to marked HCC regression. Based on these findings, we designed a combination treatment using mitosis inhibitor and proapoptosis compounds. This treatment recapitulates the therapeutic effect of Survivin deletion and effectively eliminates HCCs, thus representing a potential strategy for HCC therapy. Conclusion: Survivin ablation dramatically suppresses human and mouse HCCs by triggering senescence‐associated TNFα and sensitizing HCC cells to TNFα‐induced cell death. Combined use of mitotic inhibitor and second mitochondrial‐derived activator of caspases mimetic can induce senescence‐associated TNFα and enhance TNFα‐induced cell death and synergistically eliminate HCC. (Hepatology 2016;64:1105‐1120)
Genotype‐phenotype correlation of CTNNB1 mutations reveals different ß‐catenin activity associated with liver tumor progression
Authors: Rebouissou Sandra , Franconi Andrea , Calderaro Julien , Letouzé Eric , Imbeaud Sandrine , Pilati Camilla , Nault Jean‐Charles , Couchy Gabrielle , Laurent Alexis , Balabaud Charles , Bioulac‐Sage Paulette , Zucman‐Rossi Jessica
Published: May 2016

CTNNB1 mutations activating ß‐catenin are frequent somatic events in hepatocellular carcinoma (HCC) and adenoma (HCA), particularly associated with a risk of malignant transformation. We aimed to understand the relationship between CTNNB1 mutation types, tumor phenotype, and level of ß‐catenin activation in malignant transformation. To this purpose, CTNNB1 mutation spectrum was analyzed in 220 HCAs, 373 HCCs, and 17 borderline HCA/HCC lesions. ß‐catenin activation level was assessed in tumors by quantitative reverse‐transcriptase polymerase chain reaction and immunohistochemistry (IHC), in cellulo by TOP‐Flash assay. Overall, ß‐catenin activity was higher in malignant mutated tumors, compared to adenomas, and this was related to a different spectrum of CTNNB1 mutations in HCCs and HCAs. In benign tumors, we defined three levels of ß‐catenin activation related to specific mutations: (1) S45, K335, and N387 mutations led to weak activation; (2) T41 mutations were related to moderate activity; and (3) highly active mutations included exon 3 deletions and amino acid substitutions within the ß‐TRCP binding site (D32‐S37). Accordingly, in vitro, K335I and N387K mutants showed a lower activity than S33C. Tumors with highly active mutations demonstrated strong/homogeneous glutamine synthase (GS) staining and were associated with malignancy. In contrast, weak mutants demonstrated heterogeneous pattern of GS staining and were more frequent in HCAs except for the S45 mutants identified similarly in 20% of mutated HCAs and HCCs; however, in most of the HCCs, the weak S45 mutant alleles were duplicated, resulting in a final high ß‐catenin activity. Conclusion: High ß‐catenin activity driven by specific CTNNB1 mutations and S45 allele duplication is associated with malignant transformation. Consequently, HCAs with S45 and all high/moderate mutants should be identified with precise IHC criteria or mutation screening. (Hepatology 2016;64:2047‐2061)
Mechanistic target of rapamycin complex 1 is an essential mediator of metabolic and mitogenic effects of fibroblast growth factor 19 in hepatoma cells
Authors: Wan Zhi Yi , Tian Johann Shane , Tan Hayden Weng Siong , Chow Ai Lee , Sim Arthur Yi Loong , Ban Kenneth Hon Kim , Long Yun Chau
Published: May 2016

Fibroblast growth factor 19 (FGF19) is an important postprandial enterokine which regulates liver metabolism and hepatocyte proliferation. However, the precise mechanism by which FGF19 regulates these cellular effects is poorly understood. Given that mechanistic target of rapamycin complex 1 (mTORC1) regulates numerous postprandial adaptations, we investigated the potential role of mTORC1 in FGF19 action. We found that FGF19 activated mTORC1 in HepG2 and HuH7 human hepatoma cells, differentiated 3T3‐L1 adipocytes and mouse liver. FGF19 activates the mTORC1‐p70S6K and extracellular signal‐regulated kinase (Erk)‐p90RSK pathways independently to regulate S6 in an additive manner in hepatoma cells, but it uses mTORC1 as the primary pathway to regulate S6 in 3T3‐L1 adipocytes. Thus, mTORC1 is a novel mediator of FGF19 signaling, which can act in parallel with Erk or function as the primary pathway to regulate S6. The FGF19‐induced mTORC1 pathway requires amino acids for efficient signaling; thus, involvement of mTORC1 confers amino acid sensitivity to FGF19 signaling. Although Akt and Erk are known to activate mTORC1, we found that FGF19 signals to mTORC1 through a third recently identified mTORC1 regulator, Ras‐like (Ral) protein. Pharmacological or genetic inhibition of RalA or RalB abolished FGF19‐induced mTORC1 activation, demonstrating that Ral proteins are required for FGF19 to activate mTORC1. FGF19 induced metabolic gene expression, fatty acid oxidation, cell growth, and proliferation in HepG2 cells; and these effects were abolished by mTORC1 inhibition, demonstrating an essential role of mTORC1 in FGF19 action. Conclusion: mTORC1 is a novel and essential mediator of FGF19 action on metabolic and mitogenic programs; thus, the involvement of mTORC1 in FGF19 signaling is an important factor to consider when targeting the pathway for cancer or diabetes therapy. (Hepatology 2016;64:1289‐1301)
Chronic expression of interferon‐gamma leads to murine autoimmune cholangitis with a female predominance
Authors: Bae Heekyong R. , Leung Patrick S.C. , Tsuneyama Koichi , Valencia Julio C. , Hodge Deborah L. , Kim Seohyun , Back Tim , Karwan Megan , Merchant Anand S. , Baba Nobuyuki , Feng Dechun , Park Ogyi , Gao Bin , Yang Guo‐Xiang , Gershwin M. Eric , Young Howard A.
Published: May 2016

In most autoimmune diseases the serologic hallmarks of disease precede clinical pathology by years. Therefore, the use of animal models in defining early disease events becomes critical. We took advantage of a “designer” mouse with dysregulation of interferon gamma (IFNγ) characterized by prolonged and chronic expression of IFNγ through deletion of the IFNγ 3′‐untranslated region adenylate uridylate‐rich element (ARE). The ARE‐Del‐/‐ mice develop primary biliary cholangitis (PBC) with a female predominance that mimics human PBC that is characterized by up‐regulation of total bile acids, spontaneous production of anti‐mitochondrial antibodies, and portal duct inflammation. Transfer of CD4 T cells from ARE‐Del‐/‐ to B6/Rag1‐/‐ mice induced moderate portal inflammation and parenchymal inflammation, and RNA sequencing of liver gene expression revealed that up‐regulated genes potentially define early stages of cholangitis. Interestingly, up‐regulated genes specifically overlap with the gene expression signature of biliary epithelial cells in PBC, implying that IFNγ may play a pathogenic role in biliary epithelial cells in the initiation stage of PBC. Moreover, differentially expressed genes in female mice have stronger type 1 and type 2 IFN signaling and lymphocyte‐mediated immune responses and thus may drive the female bias of the disease. Conclusion: Changes in IFNγ expression are critical for the pathogenesis of PBC. (Hepatology 2016;64:1189‐1201)
Exosome‐mediated activation of toll‐like receptor 3 in stellate cells stimulates interleukin‐17 production by γδ T cells in liver fibrosis
Authors: Seo Wonhyo , Eun Hyuk Soo , Kim So Yeon , Yi Hyon‐Seung , Lee Young‐Sun , Park Seol‐Hee , Jang Mi‐Jin , Jo Eunjung , Kim Sun Chang , Han Yong‐Mahn , Park Keun‐Gyu , Jeong Won‐Il
Published: May 2016

During liver injury, hepatocytes secrete exosomes that include diverse types of self‐RNAs. Recently, self‐noncoding RNA has been recognized as an activator of Toll‐like receptor 3 (TLR3). However, the roles of hepatic exosomes and TLR3 in liver fibrosis are not yet fully understood. Following acute liver injury and early‐stage liver fibrosis induced by a single or 2‐week injection of carbon tetrachloride (CCl4), increased interleukin (IL)‐17A production was detected primarily in hepatic γδ T cells in wild‐type (WT) mice. However, liver fibrosis and IL‐17A production by γδ T cells were both significantly attenuated in TLR3 knockout (KO) mice compared with WT mice. More interestingly, IL‐17A‐producing γδ T cells were in close contact with activated hepatic stellate cells (HSCs), suggesting a role for HSCs in IL‐17A production by γδ T cells. In vitro treatments with exosomes derived from CCl4‐treated hepatocytes significantly increased the expression of IL‐17A, IL‐1β, and IL‐23 in WT HSCs but not in TLR3 KO HSCs. Furthermore, IL‐17A production by γδ T cells was substantially increased upon coculturing with exosome‐treated WT HSCs or conditioned medium from TLR3‐activated WT HSCs. However, similar increases were not detected when γδ T cells were cocultured with exosome‐treated HSCs from IL‐17A KO or TLR3 KO mice. Using reciprocal bone marrow transplantation between WT and TLR3 KO mice, we found that TLR3 deficiency in HSCs contributed to decreased IL‐17A production by γδ T cells, as well as liver fibrosis. Conclusion: In liver injury, the exosome‐mediated activation of TLR3 in HSCs exacerbates liver fibrosis by enhancing IL‐17A production by γδ T cells, which might be associated with HSC stimulation by unknown self‐TLR3 ligands from damaged hepatocytes. Therefore, TLR3 might be a novel therapeutic target for liver fibrosis. (Hepatology 2016;64:616‐631)
Reading Fluency and College Readiness
Authors: Rasinski Timothy V. , Chang Shu‐Ching , Edmondson Elizabeth , Nageldinger James , Nigh Jennifer , Remark Linda , Kenney Kristen Srsen , Walsh‐Moorman Elizabeth , Yildirim Kasim , Nichols William Dee , Paige David D. , Rupley William H.
Published: May 2016

The Common Core State Standards suggest that an appropriate goal for secondary education is college and career readiness. Previous research has identified reading fluency as a critical component for proficient reading. One component of fluency is word recognition accuracy and automaticity. The present study attempted to determine the word recognition accuracy and automaticity indicators for incoming college students and to examine the relationship between oral reading rate and ACT scores. Knowledge of such performance may provide secondary literacy educators with another tool for assessing reading proficiency and college readiness. Eighty‐one students were asked to read a college‐level narrative passage. Mean student accuracy and automacity scores were determined, as well as correlations between accuracy, automacity, and students’ ACT scores. Results suggest a moderate and significant relationship between measures of automaticity and both the ACT reading subtest and ACT composite scores.
Regulation of cellular behaviors of fibroblasts related to wound healing by sol–gel derived bioactive glass particles
Authors: Xie Weihan , Chen Xiaofeng , Miao Guohou , Tang Jieying , Fu Xiaoling
Published: May 2016

Sol–gel derived bioactive glass (BG) holds great potential in the application of skin repair. However, the specific regulation of BG on skin cells is still unclear and demands more investigation. Herein, we synthesized sol–gel derived BGs with different compositions (60S, 70S, 80S, and 90S) and found 90S BGs (90 mol % SiO2, 6 mol % CaO, 4 mol % P2O5) exhibited the best supportiveness for the proliferation of normal human foreskin fibroblasts. Thus, 90S BG particles were used as a model to systematically study the wound healing related cellular response of fibroblasts to BGs. Time‐lapse imaging revealed a promoted fibroblast motility stimulated by 90S BG particles. Results on the expression of extracellular matrix (ECM) related genes illustrated that 90S BG particles modulated the synthesis capacity for critical ECM molecules including type I collagen, type III collagen, fibronectin, and tenascin‐C. Moreover, the myofibroblastic differentiation of fibroblasts was greatly inhibited by 90S BG particles. Further analysis on the intracellular signaling pathways demonstrated that 90S BG particles down‐regulated the collagen synthesis and fibroblast‐to‐myofibroblast differentiation via TGF‐β1‐Smad2 signaling, evidenced by the decreased expression levels of TGF‐β receptor I and its downstream effector Smad2. Our study provided a further understanding of the specific regulation of 90S BG particles on fibroblasts, which may guide the future design of BG based wound dressing and benefit the clinical application of BG particles in skin repair. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2420–2429, 2016.
A new photocrosslinkable polycaprolactone‐based ink for three‐dimensional inkjet printing
Authors: He Yinfeng , Tuck Christopher J. , Prina Elisabetta , Kilsby Sam , Christie Steven D. R. , Edmondson Stephen , Hague Richard J. M. , Rose Felicity R. A. J. , Wildman Ricky D.
Published: May 2016

A new type of photocrosslinkable polycaprolactone (PCL) based ink that is suitable for three‐dimensional (3D) inkjet printing has been developed. Photocrosslinkable Polycaprolactone dimethylacrylate (PCLDMA) was synthesized and mixed with poly(ethylene glycol) diacrylate (PEGDA) to prepare an ink with a suitable viscosity for inkjet printing. The ink performance under different printing environments, initiator concentrations, and post processes was studied. This showed that a nitrogen atmosphere during printing was beneficial for curing and material property optimization, as well as improving the quality of structures produced. A simple structure, built in the z‐direction, demonstrated the potential for this material for the production of 3D printed objects. Cell tests were carried out to investigate the biocompatibility of the developed ink. © 2016 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1645–1657, 2017.
A two‐step method using air plasma and carbodiimide crosslinking to enhance the biocompatibility of polycaprolactone
Authors: Sahapaibounkit Paramaporn , Prasertsung Isarawut , Mongkolnavin Rattachat , Wong Chiow San , Damrongsakkul Siriporn
Published: May 2016

In this study, polycaprolactone (PCL) film, a high potential material used in biomedical applications, was treated by air plasma prior to a conjugation by carbodiimide cross‐linking with various types of proteins, including type A gelatin, type B gelatin, and collagen hydrolysate. The properties of modified PCL films were characterized by X‐ray photoelectron spectroscopy (XPS), contact angle measurement, and atomic force microscopy. The XPS results showed that oxygen and nitrogen atoms were successfully introduced on the air plasma‐treated PCL surface. Primary amine was found on the air plasma‐treated PCL films. All proteins were shown to be successfully cross‐linked on air plasma‐treated PCL films. The wettability and roughness of protein‐conjugated PCL films were significantly increased compared to those of neat PCL film. In vitro biocompatibility test using L929 mouse fibroblast showed that the attachment percentage and spreading area of attached cells on all protein‐conjugated PCL films were markedly increased. Comparing among modified PCL films, no significant difference on the attachment of L929 on modified PCL films was noticed. However, the spreading areas of cells after 24 hours of culture on type A gelatin‐ and type B gelatin‐modified PCL surfaces were higher than that on collagen hydrolysate‐modified surface, possibly related to the lower percentage of amide bond on collagen hydrolysate‐conjugated surface compared to those on both gelatin‐conjugated PCL ones. This indicated that the two‐step modification of PCL film via air plasma and carbodiimide cross‐linking with collagen‐derived proteins could enhance the biocompatibility of PCL films. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1658–1666, 2017.
A new mercury‐accumulating Mucor hiemalis strain EH8 from cold sulfidic spring water biofilms
Authors: Hoque Enamul , Fritscher Johannes
Published: May 2016

Here, we report about a unique aquatic fungus Mucor hiemalisEH8 that can remove toxic ionic mercury from water by intracellular accumulation and reduction into elemental mercury (Hg0). EH8 was isolated from a microbial biofilm grown in sulfidic‐reducing spring water sourced at a Marching's site located downhill from hop cultivation areas with a history of mercury use. A thorough biodiversity survey and mercury‐removal function analyses were undertaken in an area of about 200 km2 in Bavaria (Germany) to find the key biofilm and microbe for mercury removal. After a systematic search using metal removal assays we identified Marching spring's biofilm out of 18 different sulfidic springs' biofilms as the only one that was capable of removing ionic Hg from water. EH8 was selected, due to its molecular biological identification as the key microorganism of this biofilm with the capability of mercury removal, and cultivated as a pure culture on solid and in liquid media to produce germinating sporangiospores. They removed 99% of mercury from water within 10–48 h after initial exposure to Hg(II). Scanning electron microscopy demonstrated occurrence of intracellular mercury in germinating sporangiospores exposed to mercury. Not only associated with intracellular components, but mercury was also found to be released and deposited as metallic‐shiny nanospheres. Electron‐dispersive x‐ray analysis of such a nanosphere confirmed presence of mercury by the HgMα peak at 2.195 keV. Thus, a first aquatic eukaryotic microbe has been found that is able to grow even at low temperature under sulfur‐reducing conditions with promising performance in mercury removal to safeguard our environment from mercury pollution.