bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing river temperatures in northern Germany: trends and drivers of change
Authors: Arora Roshni , Tockner Klement , Venohr Markus 
Published: March 2016

AbstractClimate change is one of the main drivers of river warming worldwide. However, the response of river temperature to climate change differs with the hydrology and landscape properties, making it difficult to generalize the strength and the direction, of river temperature trends across large spatial scales and various river types. Additionally, there is a lack of long‐term and large‐scale trend studies in Europe as well as globally. In this study, we investigated the long‐term (25 years; 132 sites) and the short‐term (10 years; 475 sites) river temperature trends, patterns and underlying drivers within the period 1985–2010 in seven river basins of Germany. The majority of the sites underwent significant river warming during 1985–2010 (mean warming trend: 0.03 °C year−1, SE = 0.003), with a faster warming observed during individual decades (1985–1995 and 2000–2010) within this period. Seasonal analyses showed that, while rivers warmed in all seasons, the fastest warming had occurred during summer. Among all the considered hydro‐climatological variables, air temperature change, which is a response to climate forcing, was the main driver of river temperature change because it had the strongest correlation with river temperature, irrespective of the period. Hydrological variables, such as average flow and baseflow, had a considerable influence on river temperature variability rather than on the overall trend direction. However, decreasing flow probably assisted in a faster river temperature increase in summer and in rivers in NE basins (such as the Elbe basin). The North Atlantic Oscillation Index had a greater significant influence on the winter river temperature variability than on the overall variability. Landscape and basin variables, such as altitude, ecoregion and catchment area, induced spatially variable river temperature trends via affecting the thermal sensitivity of rivers, with the rivers in large catchments and in lowland areas being most sensitive. Copyright © 2016 John Wiley & Sons, Ltd.
Forecasting Tail Risks
Authors: De Nicolò Gianni , Lucchetta Marcella 
Published: March 2016

SummaryThis paper presents an early warning system as a set of multi‐period forecasts of indicators of tail real and financial risks obtained using a large database of monthly US data for the period 1972:1–2014:12. Pseudo‐real‐time forecasts are generated from: (a) sets of autoregressive and factor‐augmented vector autoregressions (VARs), and (b) sets of autoregressive and factor‐augmented quantile projections. Our key finding is that forecasts obtained with AR and factor‐augmented VAR forecasts significantly underestimate tail risks, while quantile projections deliver fairly accurate forecasts and reliable early warning signals for tail real and financial risks up to a 1‐year horizon. Copyright © 2016 John Wiley & Sons, Ltd.
Let‐7a modulates particulate matter (≤ 2.5 μm)‐induced oxidative stress and injury in human airway epithelial cells by targeting arginase 2
Authors: Song Lei , Li Dan , Gu Yue , Li Xiaoping , Peng Liping 
Published: March 2016

AbstractEpidemiological studies show that particulate matter (PM) with an aerodynamic diameter ≤ 2.5 μm (PM2.5) is associated with cardiorespiratory diseases via the induction of excessive oxidative stress. However, the precise mechanism underlying PM2.5‐mediated oxidative stress injury has not been fully elucidated. Accumulating evidence has indicated the microRNA let‐7 family might play a role in PM‐mediated pathological processes. In this study, we investigated the role of let‐7a in oxidative stress and cell injury in human bronchial epithelial BEAS2B (B2B) cells after PM2.5 exposure. The let‐7a level was the most significantly decreased in B2B cells after PM2.5 exposure. The overexpression of let‐7a suppressed intracellular reactive oxygen species levels and the percentage of apoptotic cells after PM2.5 exposure, while the let‐7a level decreased arginase 2 (ARG2) mRNA and protein levels in B2B cells by directly targeting the ARG2 3′‐untranslated region. ARG2 expression was upregulated in B2B cells during PM2.5 treatment, and ARG2 knockdown could remarkably reduce oxidative stress and cellular injury. Moreover, its restoration could abrogate the protective effects of let‐7a against PM2.5‐induced injury. In conclusion, let‐7a decreases and ARG2 increases resulting from PM2.5 exposure may exacerbate oxidative stress, cell injury and apoptosis of B2B cells. The let‐7a/ARG2 axis is a likely therapeutic target for PM2.5‐induced airway epithelial injury. Copyright © 2016 John Wiley & Sons, Ltd.
Nanoporous metals for biodegradable implants: Initial bone mesenchymal stem cell adhesion and degradation behavior
Authors: Heiden Michael , Huang Sabrina , Nauman Eric , Johnson David , Stanciu Lia 
Published: March 2016

AbstractNanostructured Fe‐Mn and Fe‐Mn‐Zn metal scaffolds were generated through a well‐controlled selective leaching process in order to fulfill the growing demand for adjustable degradation rates and improved cellular response of resorbable materials. Mouse bone marrow mesenchymal stem cells (D1 ORL UVA) were seeded onto eleven, carefully chosen nanoporous surfaces for 24 hin vitro. Using a combination of fluorescence microscopy, scanning electron microscopy (SEM), and an MTS assay, it was discovered that scaffolds with nanoscale roughened surfaces had increased cell attachment by up to 123% compared to polished smooth Fe‐Mn surfaces. Significant cell spreading and construction of cell multilayers were also apparent after 24 h, suggesting better adhesion. Additionally, static electrochemical polarization experiments revealed an improvement of up to 26% in the actual rate of biodegradation for Fe‐Mn surface‐modified materials. However, any residual concentration of zinc after leaching was shown to slightly increase corrosion resistance. The results demonstrate that selectively leached, nanostructured Fe‐Mn surfaces have the potential of being tailored to a diverse set of transient implant scenarios, while also effectively boosting overall biocompatibility, initial cell attachment, and degradation rate. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1747–1758, 2016.
Comparison of clinical explants and accelerated hydrolytic aging to improve biostability assessment of silicone‐based polyurethanes
Authors: Cosgriff‐Hernandez Elizabeth , Tkatchouk Ekaterina , Touchet Tyler , Sears Nick , Kishan Alysha , Jenney Christopher , Padsalgikar Ajay D. , Chen Emily 
Published: March 2016

AbstractAlthough silicone‐based polyurethanes have demonstrated increased oxidative stability, there have been conflicting reports of the long‐term hydrolytic stability of Optim™ and PurSil® 35 based on recent temperature‐accelerated hydrolysis studies. The goal of the current study was to identify in vitro–in vivo correlations to determine the relevance of this accelerated in vitro model for predicting clinical outcomes. Temperature‐accelerated hydrolytic aging of three commonly used cardiac lead insulation materials, Optim™, Elasthane™ 55D, Elasthane™ 80A, and a related silicone‐polyurethane, PurSil® 35, was performed. After 1 year at 85°C, similar losses in Mn and Mz were observed for the poly(ether urethanes), but an increase in Mz loss as compared to Mn loss was observed for the silicone‐based polyurethanes. A similar trend of increased Mz loss as compared to Mn loss was observed in explanted Optim™ leads after 2–3 years; however, no statistically significant Mn loss was detected between 2–3 and 7–8 years of implantation. Given this preferential loss of high molecular weight chains, it was hypothesized that the observed differences between the polyurethanes were due to allophanate dissociation rather than backbone chain scission. Following full dissociation of the small percentage of allophanates in vivo, the observed molecular weight stability and proven clinical performance of Optim™ was attributed to the well‐documented stability of the urethane bond under physiological conditions. This allophanate dissociation reaction is incompatible with the first order mechanism proposed in previous temperature‐accelerated hydrolysis studies and may be the reason for the model's inaccurate prediction of significant and progressive molecular weight loss in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1805–1816, 2016.
Effects of electromagnetic field frequencies on chondrocytes in 3D cell‐printed composite constructs
Authors: Yi Hee‐Gyeong , Kang Kyung Shin , Hong Jung Min , Jang Jinah , Park Moon Nyeo , Jeong Young Hun , Cho Dong‐Woo 
Published: March 2016

AbstractIn cartilage tissue engineering, electromagnetic field (EMF) therapy has been reported to have a modest effect on promoting cartilage regeneration. However, these studies were conducted using different frequencies of EMF to stimulate chondrocytes. Thus, it is necessary to investigate the effect of EMF frequency on cartilage formation. In addition to the stimulation, a scaffold is required to satisfy the characteristics of cartilage such as its hydrated and dense extracellular matrix, and a mechanical resilience to applied loads. Therefore, we 3D‐printed a composite construct composed of a polymeric framework and a chondrocyte‐laden hydrogel. Here, we observed frequency‐dependent positive and negative effects on chondrogenesis using a 3D cell‐printed cartilage tissue. We found that a frequency of 45 Hz promoted gene expression and secretion of extracellular matrix molecules of chondrocytes. In contrast, a frequency of 7.5 Hz suppressed chondrogenic differentiation in vitro. Additionally, the EMF‐treated composite constructs prior to implantation showed consistent results with those of in vitro, suggesting that in vitro pre‐treatment with different EMF frequencies provides different capabilities for the enhancement of cartilage formation in vivo. This correlation between EMF frequency and 3D‐printed chondrocytes suggests the necessity for optimization of EMF parameters when this physical stimulus is applied to engineered cartilage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1797–1804, 2016.
Nitrate Medications, Fractures, and Change in Bone Mineral Density in Postmenopausal Women: Results from the Women's Health Initiative
Authors: Golchin Negar , Hohensee Chancellor , LaCroix Andrea , Gray Shelly L 
Published: March 2016

ABSTRACT

Nitrate medications may increase bone mineral density (BMD), although information on fracture outcomes is sparse. We examined the association of nitrate medications with fractures (hip, wrist/arm, and total fractures) and changes in BMD (hip, spine, and whole body) in the Women's Health Initiative (WHI) Clinical Trials and Observational Study. A total of 139,211 postmenopausal women 50 to 79 years old without history of hip fracture were included in this prospective study. Medication use was ascertained directly from drug containers at baseline during in-person interviews in 1993 to 1998. Exposure measures included any use (use/non-use), type of nitrate (as-needed, maintenance) and duration of use (≤5 years, &gt;5 years). We used separate multivariable Cox proportional hazard models to analyze associations between each exposure and fracture outcome, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Multivariable linear regression models were used to examine 3-year and 6-year changes in BMD. At baseline, 1.2% (n = 1647) women were using a nitrate. During the mean ± SD follow-up of 7.7 ± 1.5 years through 2005, women experienced 1582 hip fractures, 5156 wrist or arm fractures, and 22, 589 total fractures. After adjustment for confounders, nitrate use was not statistically associated with risk for hip (HR, 0.81; 95% CI, 0.56 to 1.18), wrist/arm (HR, 0.95; 95% CI, 0.74 to 1.23), or total fractures (HR, 0.96; 95% CI, 0.85 to 1.08). As-needed nitrate use, but not maintenance therapy, was associated with a lower risk of total fractures (HR, 0.77; 95% CI, 0.62 to 0.95) and wrist/arm fractures (HR, 0.57; 95% CI, 0.34 to 0.98). Nitrate use was not associated with 3-year or 6-year changes in BMD at any site. We conclude that any nitrate use was not significantly associated with lower risk of fractures or higher BMD; however, as-needed nitrate use was associated with lower risks of total and wrist/arm fractures. © 2016 American Society for Bone and Mineral Research.
γ‐Secretase Dependent Nuclear Targeting of Dystroglycan
Authors: Leocadio Daniel , Mitchell Andrew , Winder Steve J. 
Published: March 2016

ABSTRACTDystroglycan is frequently lost in adenocarcinoma. α‐dystroglycan is known to become hypoglycosylated due to transcriptional silencing of LARGE, whereas β‐dystroglycan is proteolytically cleaved and degraded. The mechanism and proteases involved in the cleavage events affecting β‐dystroglycan are poorly understood. Using LNCaP prostate cancer cells as a model system, we have investigated proteases and tyrosine phosphorylation affecting β‐dystroglycan proteolysis and nuclear targeting. Cell density or phorbol ester treatment increases dystroglycan proteolysis, whereas furin or γ‐secretase inhibitors decreased dystroglycan proteolysis. Using resveratrol treatment of LNCaP cells cultured at low cell density in order to up‐regulate notch and activate proteolysis, we identified significant increases in the levels of a 26 kDa β‐dystroglycan fragment. These data, therefore, support a cell density‐dependent γ‐secretase and furin mediated proteolysis of β‐dystroglycan, which could be notch stimulated, leading to nuclear targeting and subsequent degradation. 117: 2149–2157, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.
Anacardic Acid, Salicylic Acid, and Oleic Acid Differentially Alter Cellular Bioenergetic Function in Breast Cancer Cells
Authors: Radde Brandie N. , Alizadeh‐Rad Negin , Price Stephanie M. , Schultz David J. , Klinge Carolyn M. 
Published: March 2016

ABSTRACTAnacardic acid is a dietary and medicinal phytochemical that inhibits breast cancer cell proliferation and uncouples oxidative phosphorylation (OXPHOS) in isolated rat liver mitochondria. Since mitochondrial‐targeted anticancer therapy (mitocans) may be useful in breast cancer, we examined the effect of anacardic acid on cellular bioenergetics and OXPHOS pathway proteins in breast cancer cells modeling progression to endocrine‐independence: MCF‐7 estrogen receptor α (ERα)+ endocrine‐sensitive; LCC9 and LY2 ERα+, endocrine‐resistant, and MDA‐MB‐231 triple negative breast cancer (TNBC) cells. At concentrations similar to cell proliferation IC50s, anacardic acid reduced ATP‐linked oxygen consumption rate (OCR), mitochondrial reserve capacity, and coupling efficiency while increasing proton leak, reflecting mitochondrial toxicity which was greater in MCF‐7 compared to endocrine‐resistant and TNBC cells. These results suggest tolerance in endocrine‐resistant and TNBC cells to mitochondrial stress induced by anacardic acid. Since anacardic acid is an alkylated 2‐hydroxybenzoic acid, the effects of salicylic acid (SA, 2‐hydroxybenzoic acid moiety) and oleic acid (OA, monounsaturated alkyl moiety) were tested. SA inhibited whereas OA stimulated cell viability. In contrast to stimulation of basal OCR by anacardic acid (uncoupling effect), neither SA nor OA altered basal OCR‐ except OA inhibited basal and ATP‐linked OCR, and increased ECAR, in MDA‐MB‐231 cells. Changes in OXPHOS proteins correlated with changes in OCR. Overall, neither the 2‐hydroxybenzoic acid moiety nor the monounsaturated alky moiety of anacardic acid is solely responsible for the observed mitochondria‐targeted anticancer activity in breast cancer cells and hence both moieties are required in the same molecule for the observed effects. J. Cell. Biochem. 117: 2521–2532, 2016. © 2016 Wiley Periodicals, Inc.
Potential Underprediction of Warfarin Drug Interaction From Conventional Interaction Studies and Risk Mitigation: A Case Study With Epacadostat, an IDO1 Inhibitor
Authors: Shi Jack G. , Chen Xuejun , Punwani Naresh G. , Williams William V. , Yeleswaram Swamy 
Published: March 2016

AbstractDrug–drug interaction (DDI) studies involving warfarin are typically conducted with subtherapeutic doses of warfarin to ensure the safety of volunteers. However, this approach may potentially have a systemic bias of underestimating pharmacodynamic (PD) DDI effect on warfarin at therapeutic levels of anticoagulation. We demonstrate here the utility of model‐based DDI prediction for a clinically relevant warfarin regimen, using the example of epacadostat (INCB024360), the first‐in‐class indoleamine 2,3‐dioxygenase 1 inhibitor in clinical development as a novel orally active immuno‐oncological therapy. Observed data from a dedicated clinical DDI study using subtherapeutic warfarin suggested warfarin pharmacokinetics (PK), but not PD (anticoagulation), was significantly affected by concomitant epacadostat. However, subsequent PK/PD modeling and simulations indicated a clinically important DDI effect on warfarin PD at a higher baseline of the international normalization ratio (INR) and enabled recommendation of warfarin dose adjustment that is dependent on epacadostat dosing regimen and target INR.
Effects of motion segment level, Pfirrmann intervertebral disc degeneration grade and gender on lumbar spine kinematics
Authors: Muriuki Muturi G. , Havey Robert M. , Voronov Leonard I. , Carandang Gerard , Zindrick Michael R. , Lorenz Mark A. , Lomasney Laurie , Patwardhan Avinash G. 
Published: March 2016

ABSTRACTMRI allows non‐invasive assessment of intervertebral disc degeneration with the added clinical benefit of using non‐ionizing radiation. What has remained unclear is the relationship between assessed disc degeneration and lumbar spine kinematics. Kinematic outcomes of 54 multi‐segment (L1‐Sacrum) lumbar spine specimens were calculated to discover if such an underlying relationship exists with degeneration assessed using the Pfirrmann grading system. Further analyses were also conducted to determine if kinematic outcomes were affected by motion segment level, gender or applied compressive preload. Range of motion, hysteresis, high flexibility zone size and rotational stiffness in flexion‐extension, lateral bending and axial rotation were the kinematic outcomes. Caudal intervertebral discs in our study sample were more degenerative than cranial discs. L5‐S1 discs had the largest flexion‐extension range of motion (p < 0.005) and L1‐L2 discs the lowest flexion high flexibility zone size (p < 0.013). No other strict cranial‐caudal differences in kinematic outcomes were found. Low flexibility zone rotational stiffness increased with disc degeneration grade in extension, lateral bending and axial rotation (p < 0.001). Trends towards higher hysteresis and lower range of motion with increased degeneration were observed in flexion‐extension and lateral bending. Applied compressive preload increased flexion‐extension hysteresis and augmented the effect of degeneration on hysteresis (p < 0.0005). Female specimens had about one degree larger range of motion in all rotational modes, and higher flexion extension hysteresis (p = 0.016). These results suggest that gender differences exist in lumbar spine kinematics. Additionally high disc loads, applied compressive preload or applied moment, are needed to kinematically distinguish discs with different levels of degeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1389–1398, 2016.
BMPR1A antagonist differentially affects cartilage and bone formation during fracture healing
Authors: Morgan Elise F. , Pittman Jason , DeGiacomo Anthony , Cusher Daniel , de Bakker Chantal M. J. , Mroszczyk Keri A. , Grinstaff Mark W. , Gerstenfeld Louis C. 
Published: March 2016

ABSTRACTA soluble form of BMP receptor type 1A (mBMPR1A‐mFC) acts as an antagonist to endogenous BMPR1A and has been shown to increase bone mass in mice. The goal of this study was to examine the effects of mBMPR1A‐mFC on secondary fracture healing. Treatment consisted of 10 mg/kg intraperitoneal injections of mBMPR1A‐mFC twice weekly in male C57BL/6 mice. Treatment beginning at 1, 14, and 21 days post‐fracture assessed receptor function during endochondral bone formation, at the onset of secondary bone formation, and during coupled remodeling, respectively. Control animals received saline injections. mBMPR1A‐mFC treatment initiated on day 1 delayed cartilage maturation in the callus and resulted in large regions of fibrous tissue. Treatment initiated on day 1 also increased the amount of mineralized tissue and up‐regulated many bone‐associated genes (p = 0.002) but retarded periosteal bony bridging and impaired strength and toughness at day 35 (p < 0.035). Delaying the onset of treatment to day 14 or 21 partially mitigated these effects and produced evidence of accelerated coupled remodeling. These results indicate that inhibition of the BMPR1A‐mediated signaling has negative effects on secondary fracture healing that are differentially manifested at different stages of healing and within different cell populations. These effects are most pronounced during the endochondral period and appear to be mediated by selective inhibition of BMPRIA signaling within the periosteum. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2096–2105, 2016.
The Middle Pleistocene glacial evolution of northern East Anglia, UK: a dynamic tectonostratigraphic–parasequence approach
Authors: Lee Jonathan R. , Phillips Emrys , Rose James , Vaughan‐Hirsch David 
Published: March 2016

ABSTRACTThe Middle Pleistocene glacial history of northern East Anglia is a controversial topic with differing opinions surrounding chronology, provenance and the relative stratigraphic framework. Reconciling the stratigraphic framework of the region is an essential first step to developing onshore–offshore geological models and a robust event‐driven chronological framework. Within this study a dynamic tectonostratigraphic–parasequence methodology is applied to deposits traditionally attributed to the Anglian Glaciation (Marine Isotope Stage 12). This approach offers an insight into ice‐bed coupling during glaciation and how evolving boundary conditions influenced glacier dynamics. Six major tectonostratigraphic–parasequence assemblages (A1–A6) are recognized in northern East Anglia and correlate with successive advances into the region of North Sea or Pennine lobes of the British Ice Sheet. Individual tectonostratigraphic–parasequence assemblages are bound at their base by a sedimentary contact or, more commonly, a glacitectonic zone. The geometry and structural characteristics of these glacitectonic zones reflect temporal and spatial variations in ice‐bed coupling (traction), a function of substrate rheology and, in turn, variations in lithology, porewater availability and thermo‐mechanical properties. The role of permafrost may also be significant, promoting proglacial/ice‐marginal thrust stacking in front of advancing ice and enhanced ice‐bed decoupling during subsequent overriding and subglacial till accretion. © 2016 British Geological Survey, NERC Journal of Quaternary Science © 2016 John Wiley & Sons Ltd