bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of intracellular redox imbalance in nanomaterial induced cellular damage and genotoxicity: A review
Authors: Kermanizadeh Ali , Chauché Caroline , Brown David M. , Loft Steffen , Møller Peter
Published: November 2014

The terms oxidative stress, free radical generation, and intracellular antioxidant protection have become part of everyday nanotoxicology terminology. In recent years, an ever increasing number of in vitro and in vivo studies have implicated disruptions to the redox balance and oxidative stress as one of the main contributors to nanomaterial (NM) induced adverse effects. One of the most important and widely investigated of these effects is genotoxicity. In general, systems that defend an organism against oxidative damage to DNA are very complex and include prevention of reactive oxygen species (ROS) production, neutralizing ROS (scavengers), enzymatic nucleotide pool sanitation, and DNA repair. This review discusses the importance of the maintenance of the redox balance in this context before examining studies that have investigated engineered NM induced redox imbalance and genotoxicity. Furthermore, we identify data gaps, and highlight a number of issues that exist with the methodologies that are routinely utilized to investigate intracellular ROS production or anti‐oxidant depletion. We conclude that for a large number of engineered NM types changes in the redox balance toward oxidative stress are normally associated with DNA damage. Environ. Mol. Mutagen. 56:111–124, 2015. © 2014 Wiley Periodicals, Inc.
Trace metals distribution pattern in floodplain sediments of a lowland river in relation to contemporary valley bottom morphodynamics
Authors: Falkowska Ewa , Falkowski Tomasz
Published: November 2014

The distribution of trace metals in alluvial sediments depends on their natural background concentrations, and on the dynamics of contemporary depositional and erosional (mainly flood‐induced) processes. Geological and geochemical investigations were carried out in the valley of Vistula River near Magnuszew (central Poland). Sediment samples were collected from a depth of 35 cm and comprise sediments of all defined geomorphological features. Identification and geological interpretation of the morphodynamic sediment features was supported by aerial photographs and high‐resolution satellite images. These studies revealed that the distribution of trace metals is closely linked to the morphogenesis of the alluvial floodplain. The highest concentrations of Cu, Co, Zn, V, Cr and Ni were observed in crevasse‐splays deposits. By contrast, Sr, Pb and As were concentrated in deposits which fill oxbow lakes (partly infilled with organic deposits). The lowest concentrations of trace metals were detected in flood sediments deposited within erosional troughs. The geomorphological and sedimentological history of the fluvial features explains the pattern of heavy metal distribution on the current floodplain surface. Copyright © 2014 John Wiley & Sons, Ltd.
Towards an improved understanding of erosion rates and tidal notch development on limestone coasts in the Tropics: 10 years of micro‐erosion meter measurements, Phang Nga Bay, Thailand
Authors: Moses Cherith , Robinson David , Kazmer Miklos , Williams Rendel
Published: November 2014

Knowledge and understanding of shore platform erosion and tidal notch development in the tropics and subtropics relies mainly on short‐term studies conducted on recently deposited carbonate rocks, predominantly Holocene and Quaternary reef limestones and aeolianites. This paper presents erosion rates, measured over a 10 year period on notches and platforms developed on the Permian, Ratburi limestone at Phang Nga Bay, Thailand. In so doing it contributes to informing a particular knowledge gap in our understanding of the erosion dynamics of shore platform and tidal notch development in the tropics and subtropics – notch erosion rates on relatively hard, ancient limestones measured directly on the rock surface using a micro‐erosion meter (MEM) over time periods of a decade or more.

The average intertidal erosion rate of 0.231 mm/yr is lower than erosion rates measured over 2–3 years on recent, weaker carbonate rocks. Average erosion rates at Phang Nga vary according to location and site and are, in rank order from highest to lowest: Mid‐platform (0.324 mm/yr) > Notch floor (0.289 mm/yr) > Rear notch wall (0.228 mm/yr) > Lower platform (0.140 mm/yr) > Notch roof (0.107 mm/yr) and Supratidal (0.095 mm/yr). The micro‐relief of the eroding rock surfaces in each of these positions exhibits marked differences that are seemingly associated with differences in dominant physical and bio‐erosion processes. The results begin to help inform knowledge of longer term shore platform erosion dynamics, models of marine notch development and have implications for the use of marine notches as indicators of changes in sea level and the duration of past sea levels. Copyright © 2014 John Wiley & Sons, Ltd.
Capacity region of the Gaussian doubly dirty two‐way channel in the presence of partial side information
Authors: Monemizadeh Narges , Hodtani Ghosheh Abed
Published: November 2014

In this paper, we characterize capacity region of the Gaussian doubly dirty two‐way channel (TWC) with partial side information at users, where there are two additive interference signals that, although similar to the channel noise sequences, corrupt the transmitted signals but are non‐causally and partially known to the users. First, by employing adaptation (considering the previously received signals in encoding process), we derive an adaptive outer bound on the capacity region of the channel. Then, we utilize lattice strategies and obtain a non‐adaptive inner bound that coincides with the adaptive outer bound and hence gives the capacity region. This also shows that for the doubly dirty TWC with partial side information, adaptation is useless and cannot increase the capacity region. Finally, we prove that Costa's dirty paper coding is optimal like lattice strategies and therefore, the Gaussian doubly dirty TWC is an instance of multi‐user channels in which lattice strategy and Costa's strategy have the same performance from the capacity region perspective. It is worth noting that our results subsume the previous related works as special cases. Copyright © 2014 John Wiley & Sons, Ltd.
Validation of the multiscale mixed finite‐element method
Authors: Pal Mayur , Lamine Sadok , Lie Knut‐Andreas , Krogstad Stein
Published: November 2014

Subsurface reservoirs generally have a complex description in terms of both geometry and geology. This poses a continuing challenge in modeling and simulation of petroleum reservoirs owing to variations of static and dynamic properties at different length scales. Multiscale methods constitute a promising approach that enables efficient simulation of geological models while retaining a level of detail in heterogeneity that would not be possible via conventional upscaling methods. Multiscale methods developed to solve coupled flow equations for reservoir simulation are based on a hierarchical strategy in which the pressure equation is solved on a coarsened grid and the transport equation is solved on the fine grid, and the two equations are treated as a decoupled system. In particular, the multiscale mixed finite‐element (MsMFE) method attempts to capture subgrid geological heterogeneity directly into the coarse‐scale equations via a set of numerically computed basis functions. These basis functions are able to capture the predominant multiscale information and are coupled through a global formulation to provide good approximation of the subsurface flow solution. In the literature, the general formulation of the MsMFE method for incompressible two‐phase and compressible three‐phase flow has mainly addressed problems with idealized flow physics. In this paper, we first outline a recent formulation that accounts for compressibility, gravity, and spatially dependent rock‐fluid parameters. Then, we validate the method by evaluating its computational efficiency and accuracy on a series of representative benchmark tests that have a high degree of realism with respect to flow physics, heterogeneity in the petrophysical models, and geometry/topology of the corner‐point grids. In particular, the MsMFE method is validated and compared against an industry‐standard fine‐scale solver. The fine‐scale flux, pressure, and saturation fields computed by the multiscale simulation show a noteworthy improvement in resolution and accuracy compared with coarse‐scale models. Copyright © 2014 John Wiley & Sons, Ltd.
Performance analysis of a 3D unstructured mesh hydrodynamics code on multi‐core and many‐core architectures
Authors: Waltz J. , Wohlbier J. G. , Risinger L. D. , Canfield T. R. , Charest M. R. J. , Long A. R. , Morgan N. R.
Published: November 2014

Several next generation high performance computing platforms are or will be based on the so‐called many‐core architectures, which represent a significant departure from commodity multi‐core architectures. A key issue in transitioning large‐scale simulation codes from multi‐core to many‐core systems is closing the serial performance gap, that is, overcoming the large difference in single‐core performance between multi‐core and many‐core systems. In this paper, we discuss how this problem was addressed for a 3D unstructured mesh hydrodynamics code, describe how Amdahl's law can be used to estimate performance targets and guide optimization efforts, and present timing studies performed on multi‐core and many‐core platforms. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Novel oncogene and tumor suppressor mutations in KIT and PDGFRA wild type gastrointestinal stromal tumors revealed by next generation sequencing
Authors: Hechtman Jaclyn Frances , Zehir Ahmet , Mitchell Talia , Borsu Laetitia , Singer Samuel , Tap William , Oultache Alifya , Ladanyi Marc , Nafa Khedoudja
Published: November 2014

Among gastrointestinal stromal tumors (GISTs) of 10–15% are negative for KIT and PDGFRA, and most of these cases are SDH deficient. Recent studies have provided data on additional molecular alterations such as KRAS in KIT mutant GISTs. We aimed to assess the frequency and spectrum of somatic mutations in common oncogenes as well as copy number variations in GISTs negative for KIT and PDGFRA mutations. GISTs with wild type KIT/PDGFRA were tested via next generation sequencing for somatic mutations in 341 genes. SDHB immunohistochemistry to evaluate for SDH deficiency was also performed. Of 267 GISTs tested for KIT and PDGFRA mutations, 15 were wild type, of which eight cases had material available for further testing. All eight cases had loss of SDHB expression and had various molecular alterations involving ARID1A, TP53, and other genes. One case had a KRAS G12V (c.35G>T) mutation in both the primary gastric tumor and a post‐imatinib recurrence. This tumor had anaplastic features and was resistant to multiple tyrosine kinase inhibitors, ultimately resulting in cancer‐related mortality within 2 years of diagnosis. In conclusion, KRAS mutations occur in rare GISTs with wild type KIT and PDGFRA. These tumors may display immunohistochemical positivity for KIT and primary resistance to tyrosine kinase inhibitors. © 2014 Wiley Periodicals, Inc.
Does job insecurity deteriorate health?
Authors: Caroli Eve , Godard Mathilde
Published: November 2014

This paper estimates the causal effect of perceived job insecurity – that is, the fear of involuntary job loss – on health in a sample of men from 22 European countries. We rely on an original instrumental variable approach on the basis of the idea that workers perceive greater job security in countries where employment is strongly protected by the law and more so if employed in industries where employment protection legislation is more binding; that is, in induastries with a higher natural rate of dismissals. Using cross‐country data from the 2010 European Working Conditions Survey, we show that, when the potential endogeneity of job insecurity is not accounted for, the latter appears to deteriorate almost all health outcomes. When tackling the endogeneity issue by estimating an instrumental variable model and dealing with potential weak‐instrument issues, the health‐damaging effect of job insecurity is confirmed for a limited subgroup of health outcomes; namely, suffering from headaches or eyestrain and skin problems. As for other health variables, the impact of job insecurity appears to be insignificant at conventional levels. Copyright © 2014 John Wiley & Sons, Ltd.
Long‐term effect of HCV eradication in patients with mixed cryoglobulinemia: A prospective, controlled, open‐label, cohort study
Authors: Gragnani Laura , Fognani Elisa , Piluso Alessia , Boldrini Barbara , Urraro Teresa , Fabbrizzi Alessio , Stasi Cristina , Ranieri Jessica , Monti Monica , Arena Umberto , Iannacone Claudio , Laffi Giacomo , Zignego Anna Linda ,   for the MaSVE Study Group
Published: November 2014

Limited data are available about the efficacy of antiviral treatment in hepatitis C virus (HCV)–associated mixed cryoglobulinemia (MC), especially concerning the long‐term effects of HCV eradication. The aim of this study was to evaluate the influence of MC on the virological response and the long‐term effects of viral eradication on MC. We prospectively enrolled 424 HCV+ patients belonging to the following groups: MC syndrome (MCS)‐HCV (121 patients with symptomatic MC), MC‐HCV (132 patients with asymptomatic MC), and HCV (158 patients without MC). Pegylated interferon plus ribavirin treatment was administered according to standard protocols. Posttreatment follow‐up ranged from 35 to 124 months (mean 92.5 months). A significant difference was observed in the rate of sustained virological response between the HCV group and both the MC‐HCV (P = 0.009) and MC‐HCV+MCS‐HCV (P = 0.014) groups. Multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of nonresponse. The clinical–immunological response in MCS‐HCV correlated with the virological one. All patients with sustained virological response also experienced a sustained clinical response, either complete or partial. In the majority of sustained virological response patients all MCS symptoms persistently disappeared (36 patients, 57%); in only two (3%) did definite MCS persist. All virological nonresponders were also clinical nonresponders, in spite of a transient improvement in some cases. No evolution to lymphoma was observed. For the first time we have evaluated both the effects of interferon‐based therapy on HCV patients with and without MC and with and without symptoms, as well as the long‐term effects of viral eradication on MC. Conclusion: MC is a negative prognostic factor of virological response. Clearance of HCV led to persistent resolution or improvement of MCS, strongly suggesting the need for a next generation of highly effective antiviral drugs. (Hepatology 2015;61:1145‐1153)
A distributed TOPMODEL for modelling impacts of land‐cover change on river flow in upland peatland catchments
Authors: Gao Jihui , Holden Joseph , Kirkby Mike
Published: November 2014

There is global concern about headwater management and associated impacts on river flow. In many wet temperate zones peatlands can be found covering headwater catchments. In the UK there is major concern about how environmental change, driven by human interventions, has altered the surface cover of headwater blanket peatlands. However, the impact of such land‐cover changes on river flow is poorly understood. In particular, there is poor understanding of the impacts of different spatial configurations of bare peat or well‐vegetated, restored peat on river flow peaks in upland catchments. In this paper, a physically based, distributed and continuous catchment hydrological model was developed to explore such impacts. The original TOPMODEL, with its process representation being suitable for blanket peat catchments, was utilized as a prototype acting as the basis for the new model. The equations were downscaled from the catchment level to the cell level. The runoff produced by each cell is divided into subsurface flow and saturation‐excess overland flow before an overland flow calculation takes place. A new overland flow module with a set of detailed stochastic algorithms representing overland flow routing and re‐infiltration mechanisms was created to simulate saturation‐excess overland flow movement. The new model was tested in the Trout Beck catchment of the North Pennines of England and found to work well in this catchment. The influence of land cover on surface roughness could be explicitly represented in the model and the model was found to be sensitive to land cover. Copyright © 2014 John Wiley & Sons, Ltd.
Tracer‐based assessment of flow paths, storage and runoff generation in northern catchments: a review
Authors: Tetzlaff Doerthe , Buttle Jim , Carey Sean K. , McGuire Kevin , Laudon Hjalmar , Soulsby Chris
Published: November 2014

We examine how tracer studies have enhanced our understanding of flow paths, residence times and sources of stream flow in northern catchments. We define northern catchments as non‐glacial sites in the temperate conifer/boreal/permafrost zone, focussing our review mainly on sites in North America and Europe. Improved empirical and theoretical understanding of hydrological functioning has advanced the analytical tools available for tracer‐based hydrograph separations, derivation of transit time distributions and tracer‐aided rainfall‐runoff models that are better able to link hydrological response to storage changes. However, the lack of comprehensive tracer data sets still hinders development of a generalized understanding of how northern catchments will respond to change. This paucity of empirical data leads to many outstanding research needs, particularly in rapidly changing areas that are already responding to climatic warming and economic development. To continually improve our understanding of hydrological processes in these regions our knowledge needs to be advanced using a range of techniques and approaches. Recent technological developments for improved monitoring, distributed hydrological sensor systems, more economic analysis of large sample numbers in conjunction with novel, tracer‐aided modelling approaches and the use of remote sensing have the potential to help the understanding of the northern hydrological systems as well as inform policy at a time of rapid environmental change. Copyright © 2014 John Wiley & Sons, Ltd.
Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon
Authors: Gansmo Liv B. , Knappskog Stian , Romundstad Pål , Hveem Kristian , Vatten Lars , Lønning Per E.
Published: November 2014

MDM2 is a key regulator of the p53 tumor suppressor protein and is overexpressed in many human cancers. Two single nucleotide polymorphisms (SNPs) located in the MDM2 intronic promoter (P2) have been found to exert biological function. The G‐allele of SNP309T>G; rs2279744 increases MDM2 transcription and has been linked to increased cancer risk. In contrast, the less frequent SNP285G>C; rs117039649, which is in complete linkage disequilibrium with SNP309 (generating a SNP285C/309G variant haplotype), has been related to reduced MDM2 transcription and to reduced risk of breast, endometrial and ovarian cancer. In this large population‐based case–control study, we genotyped SNP309 and SNP285 in 10,830 individuals, including cases with cancer of the breast (n=1,717), colon (n=1,532), lung (n=1,331) and prostate (n=2,501), as well as 3,749 non‐cancer controls. We found a slightly reduced risk for lung cancer among individuals harboring the SNP309TG/GG genotypes compared to the SNP309TT genotype (OR= 0.86; CI = 0.67–0.98), but this association was restricted to women (OR = 0.77; CI = 0.63–0.95) and was not present among men (OR = 0.91; CI = 0.77–1.08). Consistent with previous findings, we found a reduced risk for breast cancer among individuals carrying the SNP285GC/309GG genotype versus the SNP285GG/309GG genotype (OR = 0.55; CI = 0.33–0.93). In conclusion, our data support the hypothesis that the effects of both SNP285 and SNP309 status are tissue dependent.
A prospective study of alcohol consumption and renal cell carcinoma risk
Authors: Karami Sara , Daugherty Sarah E. , Purdue Mark P.
Published: November 2014

Recent epidemiological studies suggest that alcohol consumption may reduce renal cell carcinoma (RCC) risk, although inconsistent findings have been reported by sex and alcoholic beverage type. To better understand the relationship between alcohol consumption and RCC risk, we conducted an analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We followed up participants in the analytic cohort (N = 107,998) through 2010 for incident RCC (N = 408), and computed hazard ratios (HRs) and 95% confidence intervals (CIs) for alcohol intake using Cox regression with adjustment for age, sex, race, study center, hypertension, body mass index, and smoking status. In this study population increasing alcohol consumption was associated with reduced RCC risk compared to non‐drinkers (>9.75 g day−1: HR, 0.67; 95%CI, 0.50 to 0.89; p trend = 0.002). We observed similar patterns of association for men and women as well as by alcohol beverage type. In analyses stratified by smoking status, the inverse association with consumption was apparent for ever smokers (HR, 0.51; 95%CI, 0.36 to 0.73; p trend<0.0001) but not among never smokers (HR, 1.08; 95%CI, 0.66 to 1.76; P trend = 0.78; p interaction = 0.01). Our study findings offer further support that alcohol consumption is associated with reduced RCC risk, regardless of sex or alcoholic beverage type. The finding of interaction with smoking is novel and requires confirmation.
Ribose‐5‐phosphate isomerase A regulates hepatocarcinogenesis viaPP2A and ERK signaling
Authors: Ciou Shih‐Ci , Chou Yu‐Ting , Liu Yu‐Ling , Nieh Yu‐Chin , Lu Jeng‐Wei , Huang Shiu‐Feng , Chou Yu‐Ting , Cheng Li‐Hao , Lo Jeng‐Fan , Chen Ming‐Jen , Yang Ming‐Chi , Yuh Chiou‐Hwa , Wang Horng‐Dar
Published: November 2014

The deregulated nonoxidative pentose phosphate pathway (PPP) is known to promote oncogenesis, but the molecular mechanism remains unknown. Here, we report that human ribose‐5‐phosphate isomerase A (RPIA) plays a role in human hepatocellular carcinoma (HCC). A significant increase in RPIA expression was detected both in tumor biopsies of HCC patients and in a liver cancer tissue array. Importantly, the clinicopathological analysis indicated that RPIA mRNA levels were highly correlated with clinical stage, grade, tumor size, types, invasion and alpha‐fetoprotein levels in the HCC patients. In addition, we demonstrated that the ability of RPIA to regulate cell proliferation and colony formation in different liver cancer cell lines required ERK signaling as well as the negative modulation of PP2A activity and that the effects of RPIA could be modulated by the addition of either a PP2A inhibitor or activator. Furthermore, the xenograft studies in nude mice revealed that the modulation of RPIA in liver cancer cells regulated tumor growth and that NIH3T3 cells overexpressing RPIA exhibited increased proliferation, enhanced colony formation, elevated levels of p‐ERK1/2 and accelerated tumor growth. This study provides new insight into the molecular mechanisms by which RPIA overexpression can induce oncogenesis in HCC. Furthermore, it suggests that RPIA can be a good prognosis biomarker and a potential target for HCC therapy.
Sphingosine kinase 1 as a potential therapeutic target in epithelial ovarian cancer
Authors: Lee Jeong‐Won , Ryu Ji‐Yoon , Yoon Gun , Jeon Hye‐Kyung , Cho Young‐Jae , Choi Jung‐Joo , Song Sang Yong , Do In‐Gu , Lee Yoo‐Young , Kim Tae‐Joong , Choi Chel Hun , Kim Byoung‐Gie , Bae Duk‐Soo
Published: November 2014

Sphingosine kinase 1 (SK1) is over‐expressed in multiple types of human cancer. SK1 has growth‐promoting effects and has been proposed as a potential therapeutic target. We investigated the therapeutic effects of SK1 inhibition in epithelial ovarian carcinoma (EOC). SK1 siRNA or inhibitors were tested in EOC cell lines, including A2780, SKOV3ip1, A2780‐CP20, SKOV3‐TR, ES2 and RMG2. Cells were treated with SK inhibitor or FTY720, and cell proliferation, apoptosis, angiogenesis and invasion were examined by MTT, FACS, ELISA and wound‐healing assays, respectively. In vivo experiments were performed to test the effects of FTY720 on tumor growth in orthotopic mouse xenografts of EOC cell lines A2780 or SKOV3ip1 and a patient‐derived xenograft (PDX) model of clear cell ovarian carcinoma (CCC). Blocking SK1 with siRNA or inhibitors significantly reduced proliferation, angiogenesis and invasion, and increased apoptosis in chemosensitive (A2780 and SKOV3ip1) and chemoresistant (A2780‐CP20, SKOV3‐TR, ES2 and RMG2) EOC cells. SK1 inhibitors also decreased the intracellular enzymatic activity of SK1. Furthermore, FTY720 treatment significantly decreased the in vivo tumor weight in xenograft models of established cell lines (A2780 and SKOV3ip1) and a PDX model for CCC compared to control (p < 0.05). These results support therapeutic targeting of SK1 as a potential new strategy for EOC.
Fabrication of three‐dimensional porous scaffold based on collagen fiber and bioglass for bone tissue engineering
Authors: Long Teng , Yang Jun , Shi Shan‐Shan , Guo Ya‐Ping , Ke Qin‐Fei , Zhu Zhen‐An
Published: November 2014

An ideal scaffold for bone tissue engineering should have interconnected porous structure, good biocompatibility, and mechanical properties well‐matched with natural bones. Collagen is the key component in the extracellular matrix (ECM) of natural bones, and plays an important role in bone regeneration. The biological activity of collagen has promoted it to be an advantageous biomaterial for bone tissue engineering; however, the mechanical properties of these scaffolds are insufficient and the porous structures are not stable in the wet state. An effective strategy to solve this problem is to fabricate a hybrid scaffold of biologically derived and synthetic material, which have the necessary bioactivity and mechanical stability needed for bone synthesis. In this work, a three‐dimensional macroporous bone scaffold based on collagen (CO) fiber and bioglass (BG) is fabricated by a slurry‐dipping technique, and its relevant mechanical and biological properties are evaluated. The CO/BG scaffold is interconnected with a porosity of 81 ± 4.6% and pore size of 40–200 μm. Compared with CO scaffold, water absorption value of CO/BG scaffold decreases greatly from 889% to 52%, which significantly alleviates the swelling behavior of collagen and improves the stability of scaffold structure. The CO/BG scaffold has a compression strength of 5.8 ± 1.6 MPa and an elastic modulus of 0.35 ± 0.01 Gpa, which are well‐matched with the mechanical properties of trabecular bones. In vitro cell assays demonstrate that the CO/BG scaffold has good biocompatibility to facilitate the spreading and proliferation of human bone marrow stromal cells. Hence, the CO/BG scaffold is promising for bone tissue engineering application. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1455–1464, 2015.
The Excess Risk of Major Osteoporotic Fractures in Hypothyroidism Is Driven by Cumulative Hyperthyroid as Opposed to Hypothyroid Time: An Observational Register-Based Time-Resolved Cohort Analysis
Authors: Abrahamsen Bo , Jørgensen Henrik L. , Laulund Anne Sofie , Nybo Mads , Bauer Doug C. , Brix Thomas H. , Hegedüs Laszlo
Published: November 2014

The long-term relationship between hypothyroidism and fracture risk is challenging to dissect because of the modifying influence of subsequent thyroxine replacement with the potential for excessive replacement doses. We studied changes in serum thyrotropin concentration (TSH) over time and association with fracture risk in real-world patients presenting with elevated TSH. All TSH determinations were done in the same laboratory, which served all hospitals and general practices. The study population consisted of all adults with a first measurement of TSH >4.0 mIU/L (n = 8414) or normal TSH (n = 222,138; comparator). We used a Cox proportional hazards analysis incorporating additional time-dependent covariates to represent initiation of thyroxine replacement and cumulative number of periods with high versus low TSH after index date with a mean follow-up of 7.2 years. Elevated baseline TSH was not associated with an increased risk of hip fracture (HR 0.90; 95% CI, 0.80 to 1.02) or major osteoporotic fractures (HR 0.97; 95% CI, 0.90 to 1.05), nor was subsequent thyroxine prescription predictive of increased risk of fractures. The number of subsequent 6-month periods with low TSH—suggesting excessive thyroxine dosing—was significantly associated with increased risk of both hip fracture (HR 1.09; 95% CI, 1.04 to 1.15) and major osteoporotic fracture (HR 1.10; 95% CI, 1.06 to 1.14). When gender- and age-stratified analyses for major osteoporotic fractures were undertaken, hyperthyroid time was identified as a predictor of fracture risk in postmenopausal women whereas hypothyroid time predicted increased fracture risk in men below age 75 years. In conclusion, among patients who present with an elevated TSH, the long-term risk of hip and other osteoporotic fractures is strongly related to the cumulative duration of periods with low TSH—likely from excessive replacement. An independent effect of elevated TSH could only be observed in young and middle-aged men, suggesting gender-discrepant consequences on risk. © 2015 American Society for Bone and Mineral Research.
A DNA Segment Spanning the Mouse Tnfsf11 Transcription Unit and Its Upstream Regulatory Domain Rescues the Pleiotropic Biologic Phenotype of the RANKL Null Mouse
Authors: Onal Melda , Bishop Kathleen A , St. John Hillary C , Danielson Allison L , Riley Erin M , Piemontese Marilina , Xiong Jinhu , Goellner Joseph J , O'Brien Charles A , Pike J Wesley
Published: November 2014

Receptor activator of NF-κB ligand (RANKL) is a TNFα-like cytokine that is produced by a diverse set of lineage-specific cells and is involved in a wide variety of physiological processes that include skeletal remodeling, lymph node organogenesis, mammary gland development, and thermal regulation. Consistent with these diverse functions, control of RANKL expression is accomplished in a cell-specific fashion via a set of at least 10 regulatory enhancers that are located up to 170 kb upstream of the gene's transcriptional start site. Here we examined the in vivo consequence of introducing a contiguous DNA segment containing these components into a genetically deleted RANKL null mouse strain. In contrast to RANKL null littermates, null mice containing the transgene exhibited normalized body size, skeletal development, and bone mass as well as normal bone marrow cavities, normalized spleen weights, and the presence of developed lymph nodes. These mice also manifested normalized reproductive capacity, including the ability to lactate and to produce normal healthy litters. Consistent with this, the transgene restored endogenous-like RANKL transcript levels in several RANKL-expressing tissues. Most importantly, restoration of RANKL expression from this segment of DNA was fully capable of rescuing the complex aberrant skeletal and immune phenotype of the RANKL null mouse. RANKL also restored appropriate levels of B220+IgM+ and B220+IgD+ B cells in spleen. Finally, we found that RANKL expression from this transgene was regulated by exogenously administered 1,25(OH)2D3, parathyroid hormone (PTH), and lipopolysaccharide (LPS), thus recapitulating the ability of these same factors to regulate the endogenous gene. These findings fully highlight the properties of the Tnfsf11 gene locus predicted through previous in vitro dissection. We conclude that the mouse Tnfsf11 gene locus identified originally through unbiased chromatin immunoprecipitation with DNA microarray (ChIP-chip) analysis contains the necessary genetic information to direct appropriate tissue-specific and factor-regulated RANKL expression in vivo. © 2014 American Society for Bone and Mineral Research.
Features of CPB: A Poisson–Boltzmann solver that uses an adaptive cartesian grid
Authors: Fenley Marcia O. , Harris Robert C. , Mackoy Travis , Boschitsch Alexander H.
Published: November 2014

The capabilities of an adaptive Cartesian grid (ACG)‐based Poisson–Boltzmann (PB) solver (CPB) are demonstrated. CPB solves various PB equations with an ACG, built from a hierarchical octree decomposition of the computational domain. This procedure decreases the number of points required, thereby reducing computational demands. Inside the molecule, CPB solves for the reaction‐field component (ϕrf) of the electrostatic potential (ϕ), eliminating the charge‐induced singularities in ϕ. CPB can also use a least‐squares reconstruction method to improve estimates of ϕ at the molecular surface. All surfaces, which include solvent excluded, Gaussians, and others, are created analytically, eliminating errors associated with triangulated surfaces. These features allow CPB to produce detailed surface maps of ϕ and compute polar solvation and binding free energies for large biomolecular assemblies, such as ribosomes and viruses, with reduced computational demands compared to other Poisson–Boltzmann equation solvers. The reader is referred to http://www.continuum‐dynamics.com/solution‐mm.html for how to obtain the CPB software. © 2014 Wiley Periodicals, Inc.
Improving the Q2MM method for transition state force field modeling
Authors: Limé Elaine , Norrby Per‐Ola
Published: November 2014

The Quantum‐to‐molecular mechanics method (Q2MM) for converting quantum mechanical transition states (TSs) to molecular mechanical minima has been modified to allow a fit to the “natural” reaction mode eigenvalue. The resulting force field gives an improved representation of the energy curvature at the TS, but can potentially give false responses to steric interactions. Ways to address this problem while staying close to the “natural” TS force field are discussed. © 2014 Wiley Periodicals, Inc.
Reactive extraction of amino acids mixture in hydrolysate from cottonseed meal with di(2‐ethylhexyl) phosphoric acid
Authors: Zhang Jian , Zhang Shunxi , Yang Xinni , Qiu Ling , Gao Bing , Li Rui , Chen Jiwang
Published: November 2014

BACKGROUND

In recent years there has been a noticeable growth of amino acid utilization throughout the world. How to separate and purify amino acids from fermentation broths or protein hydrolysates in an effective and low cost way is increasingly becoming an urgent problem. The utilization of solvent extraction technology for amino acids separation offers one solution.

RESULTS

Extractions of individual amino acids in aqueous solution with di(2‐ethyl‐hexyl)phosphoric acid (D2EPHA) are dominated by aqueous pH and their hydrophobicity. The degree of extraction of amino acids increases with increasing pH (1.0<pH<3.0), but changes only slightly in the range 3.0<pH<7.0. Amino acids with a longer carbon chain or cyclic structure have higher degrees of extraction, while those with additional polar groups have lower degrees of extraction. Protein hydrolysate from cottonseed meal was obtained by combination of microbial fermentation and HCl hydrolysis. The greatest extraction of amino acids from the hydrolysate was found at initial feed pH 6.5, and byproducts (e.g. reducing sugars and sodium chloride) were completely retained in raffinate. Amino acids loading the organic phase can be completely stripped by using an aqueous solution having an equal volume of 0.5 mol L−1 HCl.

CONCLUSION

Use of D2EPHA reactive extraction enabled avoidance of a sequence of purification stages and provided purer back‐extracts. © 2014 Society of Chemical Industry
Bioactive compounds and advanced processing technology: Phaleria macrocarpa (sheff.) Boerl, a review
Authors: Easmin Mst. Sabina , Sarker Md. Zaidul Islam , Ferdosh Sahena , Shamsudin Siti Hadijah , Yunus Kamaruzzaman Bin , Uddin Md. Salim , Sarker Md. Moklesur Rahman , Akanda Md. Jahurul Haque , Hossain Md. Sohrab , Khalil HPS Abdul
Published: November 2014

Recent technological advances and the development of new methods has provided an opportunity to obtain highly purified natural bioactive compound extracts with potential for the treatment and prevention of human diseases. The use of hazardous and toxic solvents for the extraction and processing of bioactive compounds from plant materials is considered a problem for health, safety and environmental pollution. Advanced technology aims to increase production of the desired compounds and find an alternative to using toxic solvents in the extraction of bioactive compounds from plant materials. The ever growing interest in plant bioactive compounds and today's concerns about environment issues have led to an increased need for an efficient and green extraction method. This review is focused on the extraction of bioactive compounds from plants using advanced and environment‐friendly methods such as supercritical fluid extraction, microwave‐assisted extraction, ultrasound‐assisted extraction and similar techniques that can extract rapidly and free from organic residues. An updated overview of the bioactive compounds present in the plant Phaleria macrocarpa and its extraction, fractionation, purification and isolation is provided. The advantages and disadvantages of both conventional and non‐conventional extraction methods are also discussed in this review. © 2014 Society of Chemical Industry
MRT Letter: Two‐photon excitation‐based 2pi Light‐sheet system for nano‐lithography
Authors: Mohan Kavya , Mondal Partha Pratim
Published: November 2014

We propose two‐photon excitation‐based light‐sheet technique for nano‐lithography. The system consists of 2
‐configured cylindrical lens system with a common geometrical focus. Upon superposition, the phase‐matched counter‐propagating light‐sheets result in the generation of identical and equi spaced nano‐bump pattern. Study shows a feature size of as small as few tens of nanometers with a inter‐bump distance of few hundred nanometers. This technique overcomes some of the limitations of existing nano‐lithography techniques, thereby, may pave the way for mass‐production of nano‐structures. Potential applications can also be found in optical microscopy, plasmonics, and nano‐electronics. Microsc. Res. Tech. 78:1–7, 2015. © 2014 Wiley Periodicals, Inc.
Morphology‐function relationships and repeatability in the sperm of Passer sparrows
Authors: Cramer Emily R.A. , Laskemoen Terje , Stensrud Even , Rowe Melissah , Haas Fredrik , Lifjeld Jan T. , Sætre Glenn‐Peter , Johnsen Arild
Published: November 2014

Sperm performance is likely to be an important determinant of male reproductive success, especially when females copulate with multiple males. Understanding sperm performance is therefore crucial to fully understand the evolution of male reproductive strategies. In this study, we examined the repeatability of sperm morphology and motility measures over three breeding seasons, and we studied relationships between sperm morphology and function. We conducted this study in wild‐derived captive house sparrows (Passer domesticus) and Spanish sparrows (P. hispaniolensis). Results for the two species were similar. As predicted from results in other passerine species, total sperm length was highly repeatable across ejaculates, and repeatability for the length of other components was moderate. The repeatability of sperm swimming speed across ejaculates was lower, but statistically significant, suggesting that sperm velocity may be a relatively dynamic trait. Surprisingly, swimming speed did not correlate with the relative length of the midpiece, and it correlated negatively with the relative length of the flagellum and with total sperm length. This pattern is the opposite of what theory predicts and differs from what has been found in house sparrows before. Also contrary to previous work, we found no evidence that total sperm length correlates with sperm longevity. These results therefore highlight the need for a better understanding of relationships between sperm morphology and function in passerine birds. J. Morphol. 276:370–377, 2015. © 2014 Wiley Periodicals, Inc.
Ontogeny of an iridescent nanostructure composed of hollow melanosomes
Authors: Shawkey Matthew D. , D'Alba Liliana , Xiao Ming , Schutte Matthew , Buchholz Richard
Published: November 2014

Iridescent colors in feathers are some of the brightest in nature, and are produced by coherent light scattering from periodic arrangements of melanosomes (melanin‐containing organelles). Hollow melanosomes, an evolutionary innovation largely restricted to birds, contain an optically powerful combination of high and low refractive indices (from the melanin and air, respectively) that enables production of brighter and more saturated colors than solid melanosomes. However, despite their significance to avian color and potential utility as optical biomaterials, little is known about the ontogeny of either the melanosomes themselves or the nanostructures they comprise. We used light and electron microscopy to characterize nanostructural development in regenerating feathers of wild turkeys, a species with iridescent color produced by a hexagonally close‐packed array of hollow melanosomes. We found that melanosomes form as solid bodies in melanocytes. Later in development, largely after placement in developing barbules, their interiors dissolve and leave hollow cores. These now hollow melanosomes are initially disorganized in the barbule, but become close‐packed as they are pulled to the edge of the barbule, likely through a combination of forces including depletion–attraction. These data suggest that these structurally colored tissues are self‐assembled and represent novel pathways of development. J. Morphol. 276:378–384, 2015. © 2014 Wiley Periodicals, Inc.
Emulsion stability, thermo‐rheology and quality characteristics of ground pork patties prepared with soy protein isolate and carrageenan
Authors: Gao Xue‐qin , Zhang Wan‐gang , Zhou Guang‐hong
Published: November 2014

BACKGROUND

Plant proteins and polysaccharides are often utilised in ground meat products as meat binders, gelling agents, texture stabilisers or fat substitutes. The aim of this study was to investigate the effects of the incorporation of 57 g kg−1 soy protein isolate (SPI), 7 g kg−1 carrageenan (CAR) and SPI/CAR mixture on the quality of ground pork patties.

RESULTS

Ground pork patties with individual SPI and CAR or SPI/CAR mixture showed either retained or improved emulsion stability, physicochemical properties and dynamic rheology compared with control samples. Although there were no significant colour differences among treatments, samples with SPI/CAR mixture presented higher texture profile values for hardness and chewiness compared with other treatments (P < 0.05). Patties with additives showed significantly lower cooking loss and better thermal emulsion stability than control samples owing to a lower release rate of water and fat (P < 0.05). Compared with control samples or those with individual SPI and CAR, patties with SPI/CAR mixture formed a smoother and more continuous structure with a more compact protein matrix.

CONCLUSION

The results indicate that a mixture of SPI and CAR can be effectively used as a functional ingredient to improve the quality of ground pork patties. © 2014 Society of Chemical Industry
CERES‐Maize model‐based simulation of climate change impacts on maize yields and potential adaptive measures in Heilongjiang Province, China
Authors: Lin Yumei , Wu Wenxiang , Ge Quansheng
Published: November 2014

BACKGROUND

Climate change would cause negative impacts on future agricultural production and food security. Adaptive measures should be taken to mitigate the adverse effects. The objectives of this study were to simulate the potential effects of climate change on maize yields in Heilongjiang Province and to evaluate two selected typical household‐level autonomous adaptive measures (cultivar changes and planting time adjustments) for mitigating the risks of climate change based on the CERES‐Maize model.

RESULTS

The results showed that flowering duration and maturity duration of maize would be shortened in the future climate and thus maize yield would reduce by 11–46% during 2011–2099 relative to 1981–2010. Increased CO2 concentration would not benefit maize production significantly. However, substituting local cultivars with later‐maturing ones and delaying the planting date could increase yields as the climate changes.

CONCLUSION

The results provide insight regarding the likely impacts of climate change on maize yields and the efficacy of selected adaptive measures by presenting evidence‐based implications and mitigation strategies for the potential negative impacts of future climate change. © 2014 Society of Chemical Industry
Quality attributes of pistachio nuts as affected by rootstock and deficit irrigation
Authors: Carbonell‐Barrachina Ángel A , Memmi Houssem , Noguera‐Artiaga Luis , Gijón‐López María del Carmen , Ciapa Rafał , Pérez‐López David
Published: November 2014

BACKGROUND

In this work, the influence of two regulated deficit irrigation (RDI) treatments and three different rootstocks on the quality of pistachios was evaluated by analyzing different parameters: morphological analysis, physicochemical analysis and sensory analysis.

RESULTS

The results obtained in terms of the choice of rootstock revealed that Pistacia atlantica had increased production yields, nut weight, mineral content, higher intensities of characteristic sensory attributes and a higher degree of consumer satisfaction, than the other rootstocks studied. Moreover, the results established that the application of RDI on pistachio cultivation had no significant influence on production yield, weight, size, colour, water activity or mineral composition. Furthermore, T1 treatment (stem water potential < −1.3 MPa) resulted in higher intensities of characteristic sensory attributes and a greater level of satisfaction among international consumers.

CONCLUSION

These results confirm that the application of deficit irrigation (T1) contributes to an increase in overall product quality. Furthermore, Pistacia atlantica rootstock provided better yield and quality than the other rootstocks studied. © 2014 Society of Chemical Industry