bluuebunny/crossref_metadata_2025 huggingface dataset:
Microarray‐based genomic profiling as a diagnostic tool in acute lymphoblastic leukemia
Authors: Simons Annet , Stevens‐Kroef Marian , Idrissi‐Zaynoun Najat El , van Gessel Sabine , Weghuis Daniel Olde , van den Berg Eva , Waanders Esmé , Hoogerbrugge Peter , Kuiper Roland , van Kessel Ad Geurts
Published: September 2011

In acute lymphoblastic leukemia (ALL) specific genomic abnormalities provide important clinical information. In most routine clinical diagnostic laboratories conventional karyotyping, in conjunction with targeted screens using e.g., fluorescence in situ hybridization (FISH), is currently considered as the gold standard to detect such aberrations. Conventional karyotyping, however, is limited in its resolution and yield, thus hampering the genetic diagnosis of ALL. We explored whether microarray‐based genomic profiling would be feasible as an alternative strategy in a routine clinical diagnostic setting. To this end, we compared conventional karyotypes with microarray‐deduced copy number aberration (CNA) karyotypes in 60 ALL cases. Microarray‐based genomic profiling resulted in a CNA detection rate of 90%, whereas for conventional karyotyping this was 61%. In addition, many small (<5 Mb) genetic lesions were encountered, frequently harboring clinically relevant ALL‐related genes such as CDKN2A/B, ETV6, PAX5, and IKZF1. From our data we conclude that microarray‐based genomic profiling serves as a robust tool in the genetic diagnosis of ALL, outreaching conventional karyotyping in CNA detection both in terms of sensitivity and specificity. We also propose a practical workflow for a comprehensive and objective interpretation of CNAs obtained through microarray‐based genomic profiling, thereby facilitating its application in a routine clinical diagnostic setting. © 2011 Wiley Periodicals, Inc.
Brain activation and functional connectivity in premanifest Huntington's disease during states of intrinsic and phasic alertness
Authors: Wolf Robert Christian , Grön Georg , Sambataro Fabio , Vasic Nenad , Wolf Nadine Donata , Thomann Philipp Arthur , Saft Carsten , Landwehrmeyer G. Bernhard , Orth Michael
Published: September 2011

Previous functional neuroimaging studies have shown brain activation abnormalities in clinically presymptomatic carriers of the Huntington's disease (preHD) gene mutation when performing complex cognitive tasks. However, little is known about the neural correlates of attentional processes in preHD. In this study, we used functional magnetic resonance imaging to investigate basic aspects of attentional processing in preHD individuals (n = 18) compared to healthy participants (n = 18) during an alertness task. Uni‐ and multivariate statistical techniques were used to assess task‐related regional brain activation and functional network connectivity. Compared to healthy controls, preHD individuals near to the estimated onset of clinical signs showed lower activation of right frontostriatal regions during phasic alertness (P < 0.001, uncorrected). Decreased striatal activation in this preHD subgroup was also evident when compared with those preHD individuals far from the estimated onset of HD signs. Lower putaminal activity was associated with longer reaction times and with proximity to onset. In addition, preHD participants near to onset had lower functional connectivity of motor regions when compared with controls and preHD individuals far from onset. Our data suggest that while alertness‐related performance remains normal, the underlying frontostriatal activity and motor cortex connectivity decline only when approaching the onset of unequivocal signs of HD. However, these attentional network changes might not be the sole explanation for the differences in cognitive task performance previously observed in preHD. Hum Brain Mapp 33:2161–2173, 2012. © 2011 Wiley Periodicals, Inc.
ACCOUNTING FOR BETWEEN‐STUDY VARIATION IN INCREMENTAL NET BENEFIT IN VALUE OF INFORMATION METHODOLOGY
Authors: Willan Andrew R. , Eckermann Simon
Published: September 2011

Previous applications of value of information methods for determining optimal sample size in randomized clinical trials have assumed no between‐study variation in mean incremental net benefit. By adopting a hierarchical model, we provide a solution for determining optimal sample size with this assumption relaxed. The solution is illustrated with two examples from the literature. Expected net gain increases with increasing between‐study variation, reflecting the increased uncertainty in incremental net benefit and reduced extent to which data are borrowed from previous evidence. Hence, a trial can become optimal where current evidence is sufficient assuming no between‐study variation. However, despite the expected net gain increasing, the optimal sample size in the illustrated examples is relatively insensitive to the amount of between‐study variation. Further percentage losses in expected net gain were small even when choosing sample sizes that reflected widely different between‐study variation. Copyright © 2011 John Wiley & Sons, Ltd.
Transoral robotic surgery: Role in the management of upper aerodigestive tract tumors
Authors: Genden Eric M. , O'Malley Bert W. , Weinstein Gregory S. , Stucken Chaz L. , Selber Jesse C. , Rinaldo Alessandra , Hockstein Neil G. , Ozer Enver , Mallet Yann , Satava Richard M. , Moore Eric J. , Silver Carl E. , Ferlito Alfio
Published: September 2011

The toxicity associated with concomitant chemoradiation for the management of laryngeal and pharyngeal carcinoma has been well documented. Minimally invasive surgical techniques offer the potential to extirpate the malignancy as a single‐modality therapy and provide essential information that may direct subsequent treatment. In selected patients, radiation doses may be reduced and systemic chemotherapy may be withheld after tumor extirpation. Transoral laser microsurgery has proven effective, although inability to manipulate and suture tissue by this modality limits ablation and reconstruction of extensive defects. Transoral robotic surgery is a relatively new technique that provides several unique advantages, which include a 3‐dimensional magnified view, ability to see and work around curves or angles, and the availability of 2 or 3 robotic arms that can be used to reconstruct extensive defects using either local, regional, or free flaps. Preliminary data suggest that transoral robotic surgery may provide a technique for ablation and reconstruction of pharyngeal defects that may be superior to other transoral techniques. It may also provide a means for personalizing therapy for oropharyngeal and supraglottic carcinoma. Head Neck, 2011
Association between severity of dysphagia and survival in patients with head and neck cancer
Authors: Shune Samantha E. , Karnell Lucy Hynds , Karnell Michael P. , Van Daele Douglas J. , Funk Gerry F.
Published: September 2011

Background

This study examined risk factors for dysphagia, a common and serious condition in patients with head and neck cancer, and the association between severity of dysphagia and survival.

Methods

Chart reviews were performed on patients diagnosed with head and neck cancer between January 2001 and April 2003, who had dysphagia diagnoses or swallowing evaluations. Regression analyses determined factors associated with dysphagia and the association between observed survival and severity of dysphagia.

Results

Almost 50% of the 407 patients had dysphagia. Risk factors included advanced stage, older age, female sex, and hypopharyngeal tumors. The most severe dysphagia ([L.] nil per os or “nothing by mouth” status), which was associated with lower survival rates, was the strongest independent predictor of survival.

Conclusions

Swallowing problems should be considered when determining appropriate cancer‐directed treatment and posttreatment care. Because of dysphagia's high incidence rate and association with survival, a speech‐language pathologist should be involved to ensure routine diagnostic and therapeutic swallowing interventions. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Genetic profile of second primary tumors and recurrences in head and neck squamous cell carcinomas
Authors: Gutiérrez Virginia Franco , Marcos César Álvarez , Llorente José Luis , Guervós Marta Alonso , Iglesias Francisco Domínguez , Tamargo Luis Argüelles , Hermsen Mario
Published: September 2011

Background

Second primary tumors and recurrences are an important problem in patients with head and neck squamous cell carcinoma. The purpose of this study was to determine the genetic changes in tumor samples to improve knowledge of tumor progression.

Methods

Copy number changes of 37 genes were analyzed by multiplex ligation‐dependent probe amplification (MLPA) in 36 primary tumors and their corresponding 21 second primary tumors and 15 recurrences.

Results

CCND1 and EMS1 amplifications and gain of BCL2L1 were the most common genetic alterations in the primary tumor, second primary tumor, and recurrence samples. Gains of ERBB2 and PTPN1 were associated with recurrences.

Conclusion

Specific genetic profiles for each group have been found. Similarities between primary tumor and second primary tumor and dissimilarity between primary tumor and recurrence suggest that clinicopathological criteria do not always accurately differentiate these entities. Genetic profiling may aid in the diagnosis and prognosis of these difficult cases. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Significance of molecular markers in survival prediction of oral squamous cell carcinoma
Authors: Kim Ki–Yeol , Li ShengJin , Cha Jeong–Dan , Zhang Xianglan , Cha In–Ho
Published: September 2011

Background

An accurate system for predicting the survival of patients with oral squamous cell carcinoma (OSCC) will be useful for deciding appropriate therapies. The prediction accuracy of prediction models can be improved by using molecular biomarkers. We constructed a nomogram for predicting the survival of patients with OSCC using clinical variables and molecular markers.

Methods

Protein 53 (p53), insulin‐like growth factor II mRNA‐binding protein 3 (IMP3), cyclooxygenase 2 (COX2), and HuR were localized immunohistochemistry in 96 patients with primary OSCC who underwent surgical resection between January 1994 and June 2003 at the Yonsei Dental Hospital in Seoul, Korea.

Results

On univariate and multivariate analysis, the expression of IMP3 was significantly associated with the risk of death. P53 was also significantly associated with survival of OSCC in the case of negative IMP3 and the prediction accuracy was improved by including these 2 factors in the prediction model.

Conclusion

Survival in OSCC can be predicted more accurately by using biomarkers. The constructed nomogram predicted survival after treatment for an individual patient with OSCC, and it can be practically used as a tool to help decide which adjuvant treatment is most appropriate. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Association of Gene Expression Involving Innate Immunity and Genetic Variation in Interleukin 28B With Antiviral Response
Authors: Asahina Yasuhiro , Tsuchiya Kaoru , Muraoka Masaru , Tanaka Keisuke , Suzuki Yuichiro , Tamaki Nobuharu , Hoshioka Yoshihide , Yasui Yutaka , Katoh Tomoji , Hosokawa Takanori , Ueda Ken , Nakanishi Hiroyuki , Itakura Jun , Takahashi Yuka , Kurosaki Masayuki , Enomoto Nobuyuki , Nitta Sayuri , Sakamoto Naoya , Izumi Namiki
Published: September 2011

Innate immunity plays an important role in host antiviral response to hepatitis C viral (HCV) infection. Recently, single nucleotide polymorphisms (SNPs) of

IL28B

and host response to peginterferon α (PEG–IFNα) and ribavirin (RBV) were shown to be strongly associated. We aimed to determine the gene expression involving innate immunity in

IL28B

genotypes and elucidate its relation to response to antiviral treatment. We genotyped

IL28B

SNPs (rs8099917 and rs12979860) in 88 chronic hepatitis C patients treated with PEG–IFNα–2b/RBV and quantified expressions of viral sensors (

RIG–I, MDA5

, and

LGP2

), adaptor molecule (

IPS–1

), related ubiquitin E3–ligase (

RNF125

), modulators (

ISG15

and

USP18

), and

IL28

(

IFN

λ). Both

IL28B

SNPs were 100% identical; 54 patients possessed rs8099917 TT/rs12979860 CC (

IL28B

major patients) and 34 possessed rs8099917 TG/rs12979860 CT (

IL28B

minor patients). Hepatic expressions of viral sensors and modulators in

IL28B

minor patients were significantly up–regulated compared with that in

IL28B

major patients (≈3.3–fold,

P

< 0.001). However, expression of

IPS–1

was significantly lower in

IL28B

minor patients (1.2–fold,

P

= 0.028). Expressions of viral sensors and modulators were significantly higher in nonvirological responders (NVR) than that in others despite stratification by

IL28B

genotype (≈2.6–fold,

P

< 0.001). Multivariate and ROC analyses indicated that higher

RIG–I

and

ISG15

expressions and

RIG–I/IPS–1

expression ratio were independent factors for NVR. IPS–1 down–regulation in

IL28B

minor patients was confirmed by western blotting, and the extent of IPS–1 protein cleavage was associated with the variable treatment response.

Conclusion:

Gene expression involving innate immunity is strongly associated with

IL28B

genotype and response to PEG–IFNα/RBV. Both

IL28B

minor allele and higher

RIG–I

and

ISG15

expressions and

RIG–I/IPS–1

ratio are independent factors for NVR. (Hepatology 2012)
Early Changes in Interferon Signaling Define Natural Killer Cell Response and Refractoriness to Interferon–Based Therapy of Hepatitis C Patients
Authors: Edlich Birgit , Ahlenstiel Golo , Azpiroz Aintzane Zabaleta , Stoltzfus Jonathan , Noureddin Mazen , Serti Elisavet , Feld Jordan J. , Liang Jake T. , Rotman Yaron , Rehermann Barbara
Published: September 2011

Natural killer (NK) cells exhibit a polarized phenotype with increased cytotoxicity and decreased interferon gamma (IFN–γ) production in chronic hepatitis C virus (HCV) infection. Here, we asked whether this is caused by type I interferon (IFN)–induced expression and phosphorylation levels of signal transducer and activator of transcription (STAT) molecules in NK cells and whether it affects the response and refractoriness of NK cells to IFN–α–based therapy of HCV. STAT1 levels in NK cells were significantly higher in patients with chronic HCV infection than in uninfected controls. STAT1 levels and induction of phosphorylated STAT1 (pSTAT1) increased further during IFN–α–based therapy with preferential STAT1 over STAT4 phosphorylation. Induction of pSTAT1 correlated with increased NK cytotoxicity (tumor necrosis factor–apoptosis–inducing ligand [TRAIL] expression and degranulation) and decreased IFN–γ production. NK cells from patients with a greater than 2 log10 first–phase HCV RNA decline to IFN–α–based therapy (>99% IFN effectiveness) displayed strong pSTAT1 induction

in vivo

and were refractory to further stimulation

in vitro

. In contrast, NK cells from patients with a less than 2 log10 first–phase HCV RNA decline exhibited lower pSTAT1 induction

in vivo

(

P

= 0.024), but retained greater IFN–α responsiveness

in vitro

(

P

= 0.024). NK cells of all patients became refractory to

in vivo

and

in vitro

stimulation by IFN–α during the second–phase virological response.

Conclusion:

These data show that IFN–α–induced modulation of STAT1/4 phosphorylation underlies the polarization of NK cells toward increased cytotoxicity and decreased IFN–γ production in HCV infection, and that NK cell responsiveness and refractoriness correlate to the antiviral effectiveness of IFN–α–based therapy. (Hepatology 2012)
Genetic Interactions Between Hepatocyte Nuclear Factor–6 and Notch Signaling Regulate Mouse Intrahepatic Bile Duct Development in Vivo
Authors: Vanderpool Charles , Sparks Erin E. , Huppert Kari A. , Gannon Maureen , Means Anna L. , Huppert Stacey S.
Published: September 2011

Notch signaling and hepatocyte nuclear factor–6 (HNF–6) are two genetic factors known to affect lineage commitment in the bipotential hepatoblast progenitor cell (BHPC) population. A genetic interaction involving Notch signaling and HNF–6 in mice has been inferred through separate experiments showing that both affect BHPC specification and bile duct morphogenesis. To define the genetic interaction between HNF–6 and Notch signaling in an

in vivo

mouse model, we examined the effects of BHPC–specific loss of HNF–6 alone and within the background of BHPC–specific loss of recombination signal binding protein immunoglobulin kappa J (RBP–J), the common DNA–binding partner of all Notch receptors. Isolated loss of HNF–6 in this mouse model fails to demonstrate a phenotypic variance in bile duct development compared to control. However, when HNF–6 loss is combined with RBP–J loss, a phenotype consisting of cholestasis, hepatic necrosis, and fibrosis is observed that is more severe than the phenotype seen with Notch signaling loss alone. This phenotype is associated with significant intrahepatic biliary system abnormalities, including an early decrease in biliary epithelial cells, evolving to ductular proliferation and a decrease in the density of communicating peripheral bile duct branches. In this

in vivo

model, simultaneous loss of both HNF–6 and RBP–J results in down–regulation of both HNF–1β and Sox9 (sex determining region Y–related HMG box transcription factor 9).

Conclusion

: HNF–6 and Notch signaling interact

in vivo

to control expression of downstream mediators essential to the normal development of the intrahepatic biliary system. This study provides a model to investigate genetic interactions of factors important to intrahepatic bile duct development and their effect on cholestatic liver disease phenotypes. (Hepatology 2012;55:232–242)
Numerical investigation on the use of nanofluids in natural convection heat exchangers using a mixture‐phase approach
Authors: Tahery Amir Asgary , Zehforoosh Aydin , Pesteei S. M.
Published: September 2011

In the present research, the behavior of a Newtonian nanofluid (water–Al2O3) in a mixture phase model approach is numerically examined. The process of heating is done in two different ways. Deterioration was found in the mean Nusselt number of a nanofluid in the mixture‐phase model approach when compared to the mean Nusselt number of pure water. However, in the single‐phase model there was an increase in the Nusselt number when compared to the Nusselt number of pure water. © 2011 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.20383
An analysis of change in alpine annual maximum discharges: implications for the selection of design discharges
Authors: Castellarin Attilio , Pistocchi Alberto
Published: September 2011

The paper presents an analysis of 17 long annual maximum series (AMS) of flood flows for Swiss Alpine basins, aimed at checking the presence of changes in the frequency regime of annual maxima. We apply Pettitt's change point test, the nonparametric sign test and Sen's test on trends. We also apply a parametric goodness‐of‐fit test for assessing the suitability of distributions estimated on the basis of annual maxima collected up to a certain year for describing the frequency regime of later observations. For a number of series the tests yield consistent indications for significant changes in the frequency regime of annual maxima and increasing trends in the intensity of annual maximum discharges. In most cases, these changes cannot be explained by anthropogenic causes only (e.g. streamflow regulation, construction of dams). Instead, we observe a statistically significant relationship between the year of change and the elevation of the catchment outlet. This evidence is consistent with the findings of recent studies that explain increasing discharges in alpine catchments with an increase in the temperature controlling the portion of mountain catchments above the freezing point. Finally, we analyse the differences in return periods (RPs) estimated for a given flood flow on the basis of recent and past observations. For a large number of the study AMS, we observe that, on average, the 100‐year flood for past observations corresponds to a RP of approximately 10 to 30 years on the basis of more recent observation. From a complementary perspective, we also notice that estimated RP‐year flood (i.e. flood quantile (FQ) associated with RP) increases on average by approximately 20% for the study area, irrespectively of the RP. Practical implications of the observed changes are illustrated and discussed in the paper. Copyright © 2011 John Wiley & Sons, Ltd.
Organic carbon fluxes from the upper Yangtze basin: an example of the Longchuanjiang River, China
Authors: Lu X. X. , Li Siyue , He Min , Zhou Yue , Li Li , Ziegler Alan D.
Published: September 2011

To investigate the effects of anthropogenic activity, namely, land use change and reservoir construction, on particulate organic carbon (POC) transport, we collected monthly water samples during September 2007 to August 2009 from the Longchuanjiang River to understand seasonal variations in the concentrations of organic carbon species and their sources and the yield of organic and inorganic carbon from the catchment in the Upper Yangtze basin. The contents of riverine POC, total organic carbon and total suspended sediment (TSS) changed synchronously with water discharge, whereas the contents of dissolved organic carbon had a small variation. The POC concentration in the suspended sediment decreased non‐linearly with increasing TSS concentration. Higher molar C/N ratio of particulate organic matter (average 77) revealed that POC was dominated by terrestrially derived organic matter in the high flows and urban wastewaters in the low flows. The TSS transported by this river was 2.7 × 105 t/yr in 2008. The specific fluxes of total organic carbon and dissolved inorganic carbon (DIC) were 5.6 and 6 t/km2/yr, respectively, with more than 90% in the high flow period. A high carbon yield in the catchment of the upper Yangtze was due to human‐induced land use alterations and urban wastes. Consistent with most rivers in the monsoon climate regions, the dissolved organic carbon–POC ratio of the export flux was low (0.41). Twenty‐two percent (0.9 t/km2/yr) of POC out of 4 t/km2/yr was from autochthonous production and 78% (3.1 t/km2/yr) from allochthonous production. The annual sediment load and hence the organic carbon flux have been affected by environmental alterations of physical, chemical and hydrological conditions in the past 50 years, demonstrating the impacts of human disturbances on the global and local carbon cycling. Finally, we addressed that organic carbon flux should be reassessed using adequate samples (i.e. at least two times in low‐flow month, four times in high‐flow month and one time per day during the flood period), daily water discharge and sediment loads and appropriate estimate method. Copyright © 2011 John Wiley & Sons, Ltd.
Development of a thresholds approach for real‐time flash flood prediction in complex geomorphological river basins
Authors: Kourgialas Nektarios N. , Karatzas George P. , Nikolaidis Nikolaos P.
Published: September 2011

Flash floods represent one of the deadliest and costliest natural disasters worldwide. The hydrological analysis of a flash flood event contributes in the understanding of the runoff creation process. This study presents the analysis of some flash flood events that took place in a complex geomorphological Mediterranean River basin. The objective of the present work is to develop the thresholds for a real‐time flash flood forecasting model in a complex geomorphological watershed, based on high‐frequency data from strategically located hydrological and meteorological telemetric stations. These stations provide hourly real‐time data which were used to determine hydrological and meteorological parameters. The main characteristics of various hydrographs specified in this study were the runoff coefficients, lag time, time to peak, and the maximum potential retention. The estimation of these hydrometeorological parameters provides the necessary information in order to successfully manage flash floods events. Especially, the time to peak is the most significant hydrological parameter that affects the response time of an oncoming flash flood event. A study of the above parameters is essential for the specification of thresholds which are related to the geomorphological characteristics of the river basin, the rainfall accumulation of an event, the rainfall intensity, the threshold runoff through karstic area, the season during which the rainfall takes place and the time intervals between the rainstorms that affect the soil moisture conditions. All these factors are combined into a real‐time‐threshold flash flood prediction model. Historical flash flood events at the downstream are also used for the validation of the model. An application of the proposed model is presented for the Koiliaris River basin in Crete, Greece. Copyright © 2011 John Wiley & Sons, Ltd.
Hydrological processes in the different landscape zones of alpine cold regions in the wet season, combining isotopic and hydrochemical tracers
Authors: Yang Yonggang , Xiao Honglang , Wei Yongping , Zhao Liangju , Zou Songbing , Yang Qiu , Yin Zhenliang
Published: September 2011

Studies on hydrological processes are often emphasized in resource and environmental studies. This paper identifies the hydrological processes in different landscape zones during the wet season based on the isotopic and hydrochemical analysis of glacier, snow, frozen soil, groundwater and other water sources in the headwater catchment of alpine cold regions. Hydrochemical tracers indicated that the chemical compositions of the water are typically characterized by: (1) CaHCO3 type in glacier snow zone, (2) MgCaSO4 type for surface runoff and CaMgHCO3 type for groundwater in alpine desert zone, (3) CaMgSO4 type for surface water and CaMgHCO3 type for groundwater in alpine shrub zone, and (4) CaNaSO4 type in surface runoff in the alpine grassland zone. The End‐Members Mixing Analysis (EMMA) was employed for hydrograph separation. The results showed that the Mafengou River in the wet season was mainly recharged by groundwater in alpine cold desert zones and shrub zones (52%), which came from the infiltration and transformation of precipitation, thawed frozen soil water and glacier‐snow meltwater. Surface runoff in the glacier‐snow zone accounted for 11%, surface runoff in alpine cold desert zones and alpine shrub meadow zones accounted for 20%, thawed frozen soil water in alpine grassland zones accounted for 9% of recharge and precipitation directly into the river channel (8%). This study suggested that the whole catchment precipitation did not produce significant surface runoff directly, but mostly transformed into groundwater or interflow, and finally arrived in the river channel. Copyright © 2011 John Wiley & Sons, Ltd.
Runoff evolution in the Swiss Alps: projections for selected high‐alpine catchments based on ENSEMBLES scenarios
Authors: Farinotti Daniel , Usselmann Stephanie , Huss Matthias , Bauder Andreas , Funk Martin
Published: September 2011

The Alps are often referred to as the ‘water tower of Europe’. In Switzerland, many branches of the economy, especially the hydropower industry, are closely linked to and dependent on the availability of water. Assessing the impact of climate change on streamflow runoff is, thus, of great interest. Major efforts have already been made in this respect, but the analyses often focus on individual catchments and are difficult to intercompare. In this article, we analysed nine high‐alpine catchments spread over the Swiss Alps, selected for their relevance to a wide range of morphological characteristics. Runoff projections were carried out until the end of the current century by applying the Glacier Evolution Runoff Model (GERM) and climate scenarios generated in the framework of the ENSEMBLES project. We focused on assessing the uncertainty induced by the unknown climate evolution and provided general, statistically based statements, which should be useful as a ‘rule of thumb’ for analyses addressing questions related to water management. Catchments with a high degree of glacierization will undergo the largest changes. General statements about absolute variations in discharge are unreliable, but an overall pattern, with an initial phase of increased annual discharge, followed by a phase with decreasing discharge, is recognizable for all catchments with a significant degree of glacierization. In these catchments, a transition from glacial and glacio‐nival regime types to nival will occur. The timing of maximal annual runoff is projected to occur before 2050 in all basins. The time of year with maximal daily discharges is expected to occur earlier at a rate of 4·4 ± 1·7 days per decade. Compared to its present level, the contribution of snow‐ and icemelt to annual discharge is projected to drop by 15 to 25% until the year 2100. Copyright © 2011 John Wiley & Sons, Ltd.
Ways to improve water governance
Authors: Dukhovny Viktor A. , Ziganshina Dinara
Published: September 2011

Given the growing destabilizing factors (climate change demographic growth financial instability desertification) the water supply for future development of our planet will become even more an issue. In order to guarantee access to water for different countries regions and individuals it is necessary to elaborate and adopt for governance in general a body of legal financial institutional and economic tools and mechanisms that would become an indisputable set of rules as a kind of Bible for modern humankind and as a way to survive. Water governance should prevent any attempt to use water as a means of political or economic pressure or as a good like oil transformed into the subject of profiteering. Water is a holy thing and we all must take care of and save it so that everyone might have access to water in adequate quantity and quality. Copyright © 2011 John Wiley & Sons Ltd.
MODEL‐BASED ASSESSMENT OF LAND USE IMPACTS ON RUNOFF AND INUNDATION CAUSED BY FLOOD EVENTS
Authors: Quast Joachim , Messal Hilmar , Ehlert Volker , Sbjeschni André , Schmidt Walter
Published: September 2011

After extreme river flood events, the role of agricultural land use and its contribution to flood risks are often the subject of controversial discussion. The possibilities and potential of mitigating flood risks using non‐structural measures within the agricultural sector were investigated for both runoff formation zones and inundation zones. Based on infiltration and erosion models, the development of runoff formation and erosion‐caused matter loads was assessed for schematised surfaces under different rainfall conditions and different farming practices. These schematised model approaches enabled a more distinct understanding of impact reactions and processes than can be achieved by using complex river basin models. The results show the range, potential, and limits of agricultural practices and land use in terms of runoff generation and flood water levels. Copyright © 2011 John Wiley & Sons, Ltd.
Radio frequency glow discharge‐induced acidification of fluoropolymers
Authors: Krawczyk Benjamin M. , Baltrusaitis Jonas , Yoder Colin M. , Vargo Terrence G. , Bowden Ned B. , Kader Khalid N.
Published: September 2011

Fluoropolymer surfaces are unique in view of the fact that they are quite inert, have low surface energies, and possess high thermal stabilities. Attempts to modify fluoropolymer surfaces have met with difficulties in that it is difficult to control the modification to maintain bulk characteristics of the polymer. In a previously described method, the replacement of a small fraction of surface fluorine by acid groups through radio frequency glow discharge created a surface with unexpected reactivity allowing for attachment of proteins in their active states. The present study demonstrates that 1‐ethyl‐3‐[3‐dimethylaminopropyl] carbodiimide hydrochloride (EDC) reacts with the acid groups on fluoropolymer surfaces in a novel reaction not previously described. This reaction yields an excellent leaving group in which a primary amine on proteins can substitute to form a covalent bond between a protein and these surfaces. In an earlier study, we demonstrated that collagen IV could be deposited on a modified PTFE surface using EDC as a linker. Once collagen IV is attached to the surface, it assembles to form a functional stratum resembling collagen IV in native basement membrane. In this study, we show data suggesting that the fluorine to carbon ratio determines the acidity of the fluoropolymer surfaces and how well collagen IV attaches to and assembles on four different fluoropolymer surfaces. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
In vitro evaluation of 45S5 Bioglass®‐derived glass‐ceramic scaffolds coated with carbon nanotubes
Authors: Meng Decheng , Rath Subha Narayan , Mordan Nichola , Salih Vehid , Kneser Ulrich , Boccaccini Aldo R.
Published: September 2011

Highly porous (>90% porosity) 45S5 Bioglass®‐derived glass‐ceramic scaffolds were fabricated by foam replication method, and coated with carbon nanotubes (CNT) (coating thickness: 1 μm) using electrophoretic deposition (EPD). In vitro cell culture using mesenchymal stem cells (MSCs) was carried out on both scaffold systems (with and without CNT coating) over a 4‐week period. By using AlamarBlue™, BSA and alkaline phosphatase assays; the cell viability and differentiation were measured quantitatively measured and compared between the two scaffold types. The results showed that both scaffold systems are biocompatible with MSCs and they can support the cellular activity. No cytotoxic effects of CNT were observed under the conditions of the present experiments. Although a lower initial cell viability on the CNT‐coated scaffolds was observed, no significant differences were found after 4 weeks of culture compared with the uncoated scaffolds. This work therefore shows that there is in principle no significant improvement of cellular responses by creating a CNT‐coating on this type of highly bioactive scaffolds. However, the electrical conductivity introduced by the coating might have the potential to increase cell viability and differentiation when cell culture is carried out under the effect of electrical stimulation. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Novel injectable biodegradable glycol chitosan‐based hydrogels crosslinked by Michael‐type addition reaction with oligo(acryloyl carbonate)‐b‐poly(ethylene glycol)‐b‐oligo(acryloyl carbonate) copolymers
Authors: Yu Yuexin , Deng Chao , Meng Fenghua , Shi Qin , Feijen Jan , Zhong Zhiyuan
Published: September 2011

Novel injectable biodegradable glycol chitosan hydrogels were developed based on thiolated glycol chitosan (GC‐SH) and water soluble oligo(acryloyl carbonate)‐b‐ poly(ethylene glycol)‐b‐oligo(acryloyl carbonate) (OAC‐PEG‐OAC) triblock copolymers via Michael‐type addition reaction. The rheology measurements showed that robust hydrogels were formed rapidly upon mixing aqueous solutions of GC‐SH and OAC‐PEG‐OAC at remarkably low total polymer concentrations of 1.5–4.5 wt % under physiological conditions. The gelation times (varying from 10 s to 17 min) and storage moduli (100 to 4300 Pa) of hydrogels could be controlled by degrees of substitution (DS) of GC‐SH, solution pH, and polymer concentration. These glycol chitosan hydrogels had microporous structures, low swelling and slow hydrolytic degradation (stable for over 6 months) under physiological conditions. Notably, these hydrogels were prone to enzymatic degradation with lysozyme. The multiple acryloyl functional groups of OAC‐PEG‐OAC allowed facile conjugation with thiol‐containing biomolecules prior to gelation endowing hydrogels with specific bioactivity. The preliminary cell culture studies revealed that these glycol chitosan hydrogels were cell non‐adhesive while Gly‐Arg‐Gly‐Asp‐Cys (GRGDC) peptide modified hydrogels could well support adhesion and growth of both MG63 osteoblast and L929 fibroblast cells. These rapidly in situ forming enzymatically biodegradable hybrid hydrogels have great potentials in the development of injectable cell‐specific bioactive extracellular matrices for tissue engineering. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Dual‐functional electrospun poly(2‐hydroxyethyl methacrylate)
Authors: Zhang Bo , Lalani Reza , Cheng Fang , Liu Qingsheng , Liu Lingyun
Published: September 2011

Poly(2‐hydroxyethyl methacrylate) (pHEMA) has been widely used in many biomedical applications due to its well‐known biocompatibility. For tissue engineering applications, porous scaffolds that mimic fibrous structures of natural extracellular matrix and possess high surface‐area‐to‐volume ratios are highly desirable. So far, a systematic approach to control diameter and morphology of pHEMA fibers has not been reported and potential applications of pHEMA fibers have barely been explored. In this work, pHEMA was synthesized and processed into fibrous scaffolds using an electrospinning approach. Fiber diameters from 270 nm to 3.6 μm were achieved by controlling polymer solution concentration and electrospinning flow rate. Post‐electrospinning thermal treatment significantly improves integrity of the electrospun membranes in water. The pHEMA microfibrous membranes exhibited water absorption up to 280% (w/w), whereas the pHEMA hydrogel only absorbed 70% water. Fibrinogen adsorption experiments demonstrate that the electrospun pHEMA fibers highly resist nonspecific protein adsorption. Hydroxyl groups on electrospun pHEMA fibers were further activated for protein immobilization. A bovine serum albumin (BSA) binding capacity as high as 120 mg BSA/g membrane was realized at an intermediate fiber diameter. The pHEMA fibrous scaffolds functionalized with collagen I significantly promoted fibroblast adhesion, spreading, and proliferation. We conclude that the electrospun pHEMA fibers are dual functional, that is, they resist nonspecific protein adsorption meanwhile abundant hydroxyl groups on fibers allow effective conjugation of biomolecules in a nonfouling background. High water absorption and dual functionality of the electrospun pHEMA fibers may lead to a number of potential applications such as wound dressings, tissue scaffolds, and affinity membranes. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Electrospun nanofiber‐based regeneration of cartilage enhanced by mesenchymal stem cells
Authors: Shafiee Abbas , Soleimani Masoud , Chamheidari Gholamreza Abedi , Seyedjafari Ehsan , Dodel Masumeh , Atashi Amir , Gheisari Yousof
Published: September 2011

Application of biomaterials in combination with stem cells is a novel tissue engineering approach to regenerate cartilage. The objective of this study was to investigate the potential of poly(vinyl alcohol)/polycaprolactone (PVA/PCL) nanofiber scaffolds seeded with rabbit bone marrow‐mesenchymal stem cell (BM‐MSC) for cartilage tissue engineering in vitro and in vivo. We tested the biocompatibility and mechanical properties of nanofibrous scaffolds using scanning electron microscope, MTT assay, and tensile measurements. The capacity of MSC for chondrogenic differentiation on scaffolds was examined using reverse transcription‐polymer chain reaction and immunostaining. For in vivo assessments, PVA/PCL nanofiber scaffolds with or without MSC were implanted into rabbit full‐thickness cartilage defects. To evaluate cartilage regeneration, semi‐quantitative grading and histological analysis were performed. Our results showed that PVA/PCL scaffolds supported the proliferation and chondrogenic differentiation of MSC in vitro. Moreover, the animals treated with cell‐seeded PVA/PCL scaffolds showed improved healing of defects compared with untreated control and those which received cell‐free scaffolds. Our findings suggest that PVA/PCL scaffolds incorporated with MSC can serve as a suitable graft for articular cartilage reconstruction. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A:467–467, 2011.
Biological constraints that limit compensation of a common skeletal trait variant lead to inequivalence of tibial function among healthy young adults
Authors: Jepsen Karl J , Centi Amanda , Duarte G Felipe , Galloway Kathleen , Goldman Haviva , Hampson Naomi , Lappe Joan M , Cullen Diane M , Greeves Julie , Izard Rachel , Nindl Bradley C , Kraemer William J , Negus Charles H , Evans Rachel K
Published: September 2011

Having a better understanding of how complex systems like bone compensate for the natural variation in bone width to establish mechanical function will benefit efforts to identify traits contributing to fracture risk. Using a collection of pQCT images of the tibial diaphysis from 696 young adult women and men, we tested the hypothesis that bone cells cannot surmount the nonlinear relationship between bone width and whole bone stiffness to establish functional equivalence across a healthy population. Intrinsic cellular constraints limited the degree of compensation, leading to functional inequivalence relative to robustness, with slender tibias being as much as two to three times less stiff relative to body size compared with robust tibias. Using Path Analysis, we identified a network of compensatory trait interactions that explained 79% of the variation in whole-bone bending stiffness. Although slender tibias had significantly less cortical area relative to body size compared with robust tibias, it was the limited range in tissue modulus that was largely responsible for the functional inequivalence. Bone cells coordinately modulated mineralization as well as the cortical porosity associated with internal bone multicellular units (BMU)-based remodeling to adjust tissue modulus to compensate for robustness. Although anecdotal evidence suggests that functional inequivalence is tolerated under normal loading conditions, our concern is that the functional deficit of slender tibias may contribute to fracture susceptibility under extreme loading conditions, such as intense exercise during military training or falls in the elderly. Thus, we show the natural variation in bone robustness was associated with predictable functional deficits that were attributable to cellular constraints limiting the amount of compensation permissible in human long bone. Whether these cellular constraints can be circumvented prophylactically to better equilibrate function among individuals remains to be determined. © 2011 American Society for Bone and Mineral Research
Physiological function of the angiotensin AT1a receptor in bone remodeling
Authors: Kaneko Keiko , Ito Masako , Fumoto Toshio , Fukuhara Ryoji , Ishida Junji , Fukamizu Akiyoshi , Ikeda Kyoji
Published: September 2011

In order to determine whether the renin-angiotensin system (RAS) has any physiologic function in bone metabolism, mice lacking the gene encoding the major angiotensin II receptor isoform, AT1a, were studied using micro CT scanning, histomorphometric, and biochemical techniques. Three-dimensional (3D) micro CT analysis of the tibial metaphysis revealed that both male and female AT1a knockout mice exhibited an increased trabecular bone volume along with increased trabecular number and connectivity. Histomorphometric analysis of the tibial metaphysis indicated that the parameters of bone formation as well as resorption were increased, which was also supported by elevated serum osteocalcin and carboxy-terminal collagen crosslink (CTX) concentrations in the AT1a-deficient mice. Osteoclastogenesis and osteoblastogenesis assays in ex vivo cultures, however, did not reveal any intrinsic alterations in the differentiation potential of AT1a-deficient cells. Quantitative RT-PCR using RNA isolated from the tibia and femur revealed that the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio and the expression of stromal cell-derived factor (SDF)1α were increased, whereas that of SOST was decreased in AT1a-deficient bone, which may account for the increased bone resorption and formation, respectively. AT1a-deficient mice also displayed a lean phenotype with reduced serum leptin levels. They maintained high bone mass with advancing age, and were protected from bone loss induced by ovariectomy. Collectively, the data suggest that RAS has a physiologic function in bone remodeling, and that signaling through AT1a negatively regulates bone turnover and bone mass. © 2011 American Society for Bone and Mineral Research
Apoptosis‐ and endoplasmic reticulum stress‐related genes were regulated by estrogen and progesterone in the uteri of calbindin‐D9kand ‐D28kknockout mice
Authors: Jung Eui‐Man , An Beum‐Soo , Choi Kyung‐Chul , Jeung Eui‐Bae
Published: September 2011

Calcium (Ca2+) is an important regulator of apoptotic signaling. Calbindin‐D9k(CaBP‐9k) and ‐D28k(CaBP‐28k) have a high affinity for Ca2+ions. Uterine calbindins appear to be involved in the regulation of myometrial activity by intracellular Ca2+. In addition, uterine calbindins are expressed in the mouse endometrium and are regulated by steroid hormones during implantation and development. The aim of the present study was to evaluate the regulation of apoptosis in the uteri of CaBP‐9k, CaBP‐28k, and CaBP‐9k/28k knockout (KO) mice. Our findings indicated that Bax protein was enhanced in the uteri of CaBP‐28k and CaBP‐9k/28k KO mice compared to wild‐type (WT) and CaBP‐9k KO mice, but no difference was observed in Bcl‐2 protein expression. The expressions of caspase 3, 6, and 7 proteins were higher in both CaBP‐28k and CaBP‐9k/28k KO mice than in WT and CaBP‐9k KO mice. These results suggest that the absence of CaBP‐28k increases apoptotic signaling. We also investigated the expression of endoplasmic reticulum (ER) stress genes by Western blot analysis in calbindin KO mice. C/EBP homologous protein and immunoglobulin heavy chain‐binding protein protein levels were elevated in CaBP‐28k KO mice compared to WT mice. When immature mice were treated with 17β‐estradiol (E2) or progesterone (P4) for 3 days, we found that the expressions of Bax and caspase 3 protein were increased by E2 treatment in WT and CaBP‐9k KO mice, and by P4 treatment in CaBP‐28k KO mice. These results indicate that CaBP‐28k blocks the up‐regulation of apoptosis‐related genes and ER stress genes, implying that CaBP‐28k may decrease the expression of genes involved in apoptosis and ER stress in murine uterine tissue. J. Cell. Biochem. 113: 194–203, 2012. © 2011 Wiley Periodicals, Inc.
The coupling constant polarizability and hyperpolarizabilty of 1J(NH) in N‐methylacetamide, and its application for the multipole spin–spin coupling constant polarizability/reaction field approach to solvation
Authors: Kjær Hanna , Sauer Stephan P. A. , Kongsted Jacob
Published: September 2011

We present a benchmark study of a combined multipole spin–spin coupling constant (SSCC) polarizability/reaction field (MJP/RF) approach to the calculation of both specific and bulk solvation effects on SSCCs of solvated molecules. The MJP/RF scheme is defined by an expansion of the SSCCs of the solvated molecule in terms of coupling constant dipole and quadrupole polarizabilities and hyperpolarizabilities derived from single molecule ab initio calculations. The solvent electric field and electric field gradient are calculated based on data derived from molecular dynamics (MD) simulations thereby accounting for solute–solvent dynamical effects. The MJP/RF method is benchmarked against polarizable QM/MM calculations for the one‐bond N–H coupling constant in N‐methylacetamide. The best agreement between the MJP/RF and QM/MM approaches is found by truncating the electric field expansion in the MJP/RF approach at the linear electric field level. In addition, we investigate the sensitivity of the results due to the choice of one‐electron basis set in the ab initio calculations of the coupling constant (hyper‐)polarizabilities and find that they are affected by the basis set in a way similar to the coupling constants themselves. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011