bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Catalytic Base for Sugar Oxidation in the Pyranose 2‐Oxidase Reaction
Authors: Wongnate Thanyaporn , Sucharitakul Jeerus , Chaiyen Pimchai
Published: October 2011

Pyranose 2‐oxidase (P2O) catalyzes the oxidation of aldopyranoses to form 2‐keto sugars and H2O2. In this study, the mechanistic role of the conserved residues His548 and Asn593 in P2O was investigated by using site‐directed mutagenesis, transient kinetics, and pH‐dependence studies. As single mutants of H548 resulted in mixed populations of noncovalently bound and covalently linked FAD, double mutants containing H167A were constructed, in which the covalent histidyl‐FAD linkage was removed in addition to having the H548 mutation. Single mutants H548A, H548N, H548S, H548D and double mutants (with H167A) could not be reduced by D‐glucose. For the H167A/H548R mutant, the flavin could be reduced by D‐glucose with the reduction rate constant about 220 times lower than that of the H167A mutant. The pH‐dependence studies of H167A/H548R indicated that the rate constant of flavin reduction increased about 360‐fold upon a pH rise corresponding to pKa>10.1, whereas the reactions of the wild‐type and H167A mutant enzymes were pH independent. Therefore, the data suggest that a pKa value of >10.1 in the mutant enzyme is associated with the Arg548 residue, and that this residue must be unprotonated to efficiently catalyze flavin reduction. The data imply that for the wild‐type P2O, the conserved His548 should be unprotonated in the pH range studied. The unprotonated His548 can act as a general base to abstract the 2‐hydroxyl proton of D‐glucose and initiate hydride transfer from the substrate to the flavin. Studies of the single mutant N593H showed that the flavin reduction rate constant was 114 times lower than that of the wild‐type enzyme and was pH independent, while the Kd for D‐glucose binding was 19 times greater.
Nanoscale Inhomogeneities in Thermoresponsive Triblock Copolymers
Authors: Kurzbach Dennis , Reh Miriam N. , Hinderberger Dariush
Published: October 2011

We present continuous‐wave (CW) electron paramagnetic resonance (EPR) spectroscopy data of the spin probe 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) in aqueous solutions of poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) (PEO–PPO–PEO) triblock copolymers (Pluronic or Poloxamer). TEMPO is notably smaller than the spin probes conventionally used in the context of polymer science and reveals the early emergence of small hydrophobic cavities when PPO strands of several molecules aggregate and collapse upon temperature increase. The occurrence of hydrophobic cavities appears independent of the overall molecular weight of the Pluronics, but clearly depends on the relative PPO/PEO contents. In all the cases studied, the volume fraction of hydrophobic cavities increases in a broad temperature range of ≥40 °C. The appearance of the hydrophobic regions does not seem to be directly correlated to micellization of the polymers. A decrease of the relative PPO amount in the polymers not only hinders collapse of the PPO strands, it can also be described as a site exchange of the spin probes between hydrophobic cavities and the surrounding medium. On the other hand, in cases of high PPO contents, spin probe exchange could not be observed. This suggests that one may potentially control the diffusion of small molecules between the micellar cores and the surrounding medium by adjusting the PEO/PPO ratio of the used Pluronics.
Daily stress increases risky decision‐making in adolescents: A preliminary study
Authors: Galván Adriana , McGlennen Kristine M.
Published: October 2011

Adolescence is characterized as a developmental period of risky decision‐making. During this developmental window there is also a marked increase in actual and perceived stress. Acute stress increases risky decision‐making in adults, but no research has examined this phenomenon in adolescents. In this study, an ecologically relevant approach was used to document daily self‐reports of stress in adolescents and an emerging adult comparison group. Participants visited the laboratory twice: once each when they endorsed a high and low level of stress, where they performed a risky decision‐making task and a response inhibition task. In both groups, participants showed greater risky decision‐making under high (vs. low) stress conditions but no stress‐related effects on response inhibition. The dissociation between decision‐making and response inhibition under stress suggests that, across development, individuals show greater vulnerability to contextual influence in decision‐making domains. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 54:433–440, 2012.
Application of artificial neural network to predict the retention time of drug metabolites in two‐dimensional liquid chromatography
Authors: Noorizadeh H. , Sobhan‐Ardakani S. , Raoofi F. , Noorizadeh M. , Mortazavi S. S. , Ahmadi T. , Pournajafi K.
Published: October 2011

Genetic algorithm and partial least square (GA‐PLS) and Levenberg‐ Marquardt artificial neural network (L‐M ANN) techniques were used to investigate the correlation between retention time and descriptors for drug metabolites which obtained by two‐dimensional liquid chromatography. The applied internal (leave‐group‐out cross validation (LGO‐CV)) and external (test set) validation methods were used for the predictive power of four models. Both methods resulted in accurate prediction whereas more accurate results were obtained by L‐M ANN model. The best model obtained from L‐M ANN showed a good R2 value (determination coefficient between observed and predicted values) for all compounds, which was superior to GA‐PLS models. Copyright © 2011 John Wiley & Sons, Ltd.
Isolation of rat embryonic stem‐like cells: A tool for stem cell research and drug discovery
Authors: Fernández M. , Pirondi S. , Chen B. L. , Del Vecchio G. , Alessandri M. , Farnedi A. , Pession A. , Feki A. , Jaconi M.E.E. , Calzà L.
Published: October 2011

The establishment of rat embryonic stem cells constitutes a precious tool since rat has been extensively used in biomedical research, in particular for the generation of human neurodisease animal models. Up to now only a few studies have described the isolation of rat embryonic stem‐like cells. One out of 9 isolated rat embryonic stem‐like cell lines (B1‐RESC) obtained from a 4.5‐day post‐coitum blastocyst were extensively characterized and kept in culture for up to 80 passages on feeders with LIF. The stable growth of these cells and the expression of pluripotent markers were confirmed up to a high number of passages in culture, also in the absence of feeders and LIF. B1‐RESC expresses the three germ layers markers both in vitro, within differentiating embryoid bodies, and in vivo through teratoma formation. Collectively, the B1‐RESC line with a stable near‐diploid karyotype can be used as a highly sensitive tool for testing anti‐proliferative molecules. Developmental Dynamics 240:2482–2494, 2011. © 2011 Wiley Periodicals, Inc.
Unique effects of sulfur and water on the syntheses of thiaheterocycles
Authors: Sun Dong‐Qing , Yang Jing‐Kui
Published: October 2011

A series of thiaheterocycles were produced by the reaction of diethyl 2,3‐dibromomaleate or diethyl 2,3‐dibromofumarate with different sulfides without any catalyst. The major products shifted in different conditions. Water was found playing a key role in the generation of carbon–carbon single bonds. Meanwhile, the addition of sulfur could accelerate the reaction and greatly improve the yield of certain products. In addition, unusual, broad single peaks were found in 13C NMR spectra of some compounds. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:84–90, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20755
Predicting the dependencies of rainfall‐runoff responses on human forest disturbances with soil loss based on the runoff mechanisms in granite and sedimentary rock mountains
Authors: Tani Makoto , Fujimoto Masamitsu , Katsuyama Masanori , Kojima Nagahiro , Hosoda Ikuhiro , Kosugi Ken'ichirou , Kosugi Yoshiko , Nakamura Sho
Published: October 2011

Understanding the effects of severe human induced forest disturbances with soil loss on rainfall‐runoff responses is important for future forest management. However, few studies have addressed this issue, which is methodologically difficult compared with the hydrological assessments of the effects of logging. In this study, several small catchments in Japan with different soil and geological conditions were compared using the runoff model HYCYMODEL to reveal their runoff characteristics. The results were then examined on the basis of runoff mechanisms to demonstrate the possible ranges of the effects derived from human disturbances for each geological type. For granite mountains, bare land can be considered the severest case of disturbances leading to high stormflow peaks, although a large baseflow remains because of the water storage fluctuation in weathered bedrock. For sedimentary rock mountains, the severest case may be a forest on the clayey soil without brown forest soil producing flashy runoff characteristics including a large stormflow volume with a sensitive response to the antecedent dryness and a low baseflow rate. Copyright © 2011 John Wiley & Sons, Ltd.
Numerical investigations on the relationships between watershed characteristics and water balance model parameters: searching for universal relationships among regional relationships
Authors: Yokoo Yoshiyuki , Kazama So
Published: October 2011

The present study attempts to identify universal relationships between the geographical characteristics of a basin and the streamflow within a basin by using the parameter regionalization method of a water balance model, with the aim of gaining hydrological knowledge that might enable predictions of streamflow in ungauged basins. To this end, we first revisited existing regional relationships between the parameters of a Tank model and the geographical characteristics in Japanese mountainous basins, and translated the regional relationships between the geographical characteristics of a basin and streamflow. Second, we used a physically distributed rainfall–runoff model to perform a sensitivity analysis on the effect of the geographical characteristics of a hypothetical basin on its streamflow, with the aim of obtaining physically explainable relationships between these factors. Finally, we selected regional relationships that were also explained in the sensitivity analysis as potentially representing universal hydrological knowledge that might help to predict streamflow in ungauged basins. As a result, we obtained the following potentially universal hydrological knowledge: (1) the fraction of surface flow is less in large basins than in small basins; (2) the infiltration at the ground surface is higher if a basin is covered by soil with a high vertical permeability; (3) the fraction of prompt interflow is higher if a basin is covered by soil with a high horizontal permeability; (4) the fraction of delayed interflow is lower in large basins than in small basins and (5) the storage capacity at the ground surface is high if the ground surface is very rough. Copyright © 2011 John Wiley & Sons, Ltd.
Numerical investigation of apparent multifractality of samples from processes subordinated to truncated fBm
Authors: Guadagnini Alberto , Neuman Shlomo P. , Riva Monica
Published: October 2011

We investigate numerically apparent multi‐fractal behavior of samples from synthetically generated processes subordinated to truncated fractional Brownian motion (tfBm) on finite domains. We are motivated by the recognition that many earth and environmental (including hydrological) variables appear to be self‐affine (monofractal) or multifractal with Gaussian or heavy‐tailed distributions. The literature considers self‐affine and multifractal types of scaling to be fundamentally different, the first arising from additive and the second from multiplicative random fields or processes. It has been demonstrated theoretically by one of us that square or absolute increments of samples from Gaussian/Lévy processes subordinated to tfBm exhibit apparent/spurious multifractality at intermediate ranges of separation lags, with breakdown in power‐law scaling at small and large lags as is commonly exhibited by real data. A preliminary numerical demonstration of apparent multifractality by the same author was limited to Gaussian fields having nearest neighbor autocorrelations and led to rather noisy results. Here, we adopt a new generation scheme that allows us to investigate apparent multifractal behaviors of samples taken from a broad range of processes including Gaussian with and without symmetric Lévy and log‐normal (as well as potentially other) subordinators. Our results shed new light on the nature of apparent multifractality, which has wide implications vis‐a‐vis the scaling of many hydrological as well as other earth and environmental variables. Copyright © 2011 John Wiley & Sons, Ltd.
Modelling wetland connectivity during overbank flooding in a tropical floodplain in north Queensland, Australia
Authors: Karim Fazlul , Kinsey‐Henderson Anne , Wallace Jim , Arthington Angela H. , Pearson Richard G.
Published: October 2011

Hydrological connectivity between floodplain wetlands and rivers is one of the principal driving mechanisms for the diversity, productivity and interactions of the major biota in river–floodplain systems. This article describes a method of quantifying flood‐induced overbank connectivity using a hydrodynamic model (MIKE 21) to calculate the timing, the duration and the spatial extent of the connections between several floodplain wetlands and rivers in the Tully–Murray catchment, north Queensland, Australia. Areal photogrammetry and field surveyed stream cross data were used to reproduce floodplain topography and rivers in the model. Laser altimetry (LiDAR)–derived fine resolution elevation data, for the central floodplain, were added to the topography model to improve the resolution of key features including wetlands, flow pathways and natural and artificial flow barriers. The hydrodynamic model was calibrated using a combination of in‐stream and floodplain gauge records. A range of off‐stream wetlands including natural and artificial, small and large were investigated for their connectivity with two main rivers (Tully and Murray) flowing over the floodplain for flood events of 1‐, 20‐ and 50‐year recurrence intervals. The duration of the connection of individual wetlands varied from 1 to 12 days, depending on flood magnitude and location in the floodplain, with some wetlands only connected during large floods. All of the wetlands studied were connected to the Tully River for shorter periods than they were to the Murray River because of the higher bank heights and levees on the Tully River and wetland proximity to the Murray River. Other than hydrology, land relief, riverbank elevation and levee banks along the river were found key factors controlling the degree of connectivity. These variations in wetland connectivity could have important implications for aquatic biota that move between rivers and off‐stream habitats during floods. Copyright © 2011 John Wiley & Sons, Ltd.
Molecular detection of viral causes of encephalitis and meningitis in New York State
Authors: Dupuis Michelle , Hull Rene , Wang Heng , Nattanmai Seela , Glasheen Bernadette , Fusco Heather , Dzigua Lela , Markey Katie , Tavakoli Norma P.
Published: October 2011

The etiology of encephalitis and meningitis, serious diseases of the central nervous system (CNS), in most cases remains unknown. The importance of establishing a diagnosis however, becomes even more important as advances are made in effective therapy. Molecular methods of detection, in particular, PCR, are being used routinely and have established a place in the arsenal of tools for diagnosis of CNS infections. In this study a viral etiological agent was detected by PCR in 340 of the total 2,357 specimens from patients who exhibited symptoms of encephalitis or meningitis. The detection rate increased from 8.9% during the first year of the study to 14.8% during the second year of the study with improved methodology and an expanded panel of viral agents. Methods were enhanced by developing real‐time PCR assays (some multiplexed), using increased automation, superior nucleic acid extraction, and reverse transcription (RT) methods, and incorporation of an internal extraction control. Additionally, adenovirus and human herpes virus 6 (HHV‐6) were added to the original panel of 10 viruses that included enteroviruses, herpesviruses, and arboviruses. The most common viruses detected were enteroviruses (129; 5.5%), Epstein‐Barr virus (EBV) (85; 3.6%), herpes simplex viruses (HSVs) 1 and 2 (67; 2.8%), and varicella zoster virus (VZV) (44; 1.9%). J. Med. Virol. 83:2172–2181, 2011. © 2011 Wiley Periodicals, Inc.
Genotyping of human rotaviruses circulating among children with diarrhea in Valencia, Venezuela
Authors: Vizzi Esmeralda , Piñeros Oscar , González Germán Gabriel , Zambrano José L. , Ludert Juan E. , Liprandi Ferdinando
Published: October 2011

Rotavirus infection is the most common cause of severe gastroenteritis during childhood worldwide, especially in developing countries. Two rotavirus vaccines are available for childhood immunization programs. Evaluation of the vaccine performance will benefit from knowledge of the epidemiological features of rotavirus infection in regional settings. Limited information on the molecular characteristics of the rotavirus types circulating in Venezuela is available. Eighty seven (89.7%) of the 97 ELISA rotavirus positive stool samples collected from children with diarrhea aged <5 years during 2003 in Valencia (Carabobo State), were G‐, P‐ and NSP4‐genotyped by RT‐PCR and/or automated sequencing. Four common combinations, G3P[8]/NSP4‐E1, G2P[4]/NSP4‐E2, G9P[8]/NSP4‐E1, and G1P[8]/NSP4‐E1 were responsible for 50.6%, 35.6%, 5.7%, and 1.1%, respectively of cases of rotavirus diarrhea, most of them (66%) in children ≤12 months. One uncommon G8P[14]/NSP4‐E2 strain was also detected. Temporal fluctuation of genotype distribution occurred, but no differences by age, diarrhea severity score, sex, treatment type or patient medical attention were observed, except for the G3P[8]/NSP4‐E1, associated with a more severe dehydration than any other type (P < 0.01). The results confirm the broad diversity among rotavirus strains circulating in Venezuela prior to vaccine implementation, showing the predominance of G3, significant proportion of G2 and moderate circulation of G9 strains. Epidemiological surveillance is needed to detect the emergence of new genotypes that could escape protection induced by vaccination. J. Med. Virol. 83:2225–2232, 2011. © 2011 Wiley Periodicals, Inc.
Merkel cell polyomavirus DNA in immunocompetent and immunocompromised patients with respiratory disease
Authors: Abedi Kiasari Bahman , Vallely Pamela J. , Klapper Paul E.
Published: October 2011

Merkel cell polyomavirus (MCPyV) was identified originally in association with a rare but aggressive skin cancer, Merkel cell carcinoma. The virus has since been found in the respiratory tract of some patients with respiratory disease. However, the role of MCPyV in the causation of respiratory disease has not been established. To determine the prevalence of MCPyV in 305 respiratory samples from immunocompetent and immunocompromised patients and evaluate their contribution to respiratory diseases, specimens were screened for MCPyV using single, multiplex, or real‐time PCR; co‐infection with other viruses was examined. Of the 305 samples tested, 10 (3.27%) were positive for MCPyV. The virus was found in two groups of patients: in 6 (2%) nasopharyngeal aspirate samples from children aged 26 days to 7 months who were immunocompetent; and in 4 (1.3%) of nasopharyngeal aspirate samples taken from patients aged 41 to 69 years who were severely immunosuppressed from leukemia or transplant therapy. Both groups had upper or lower respiratory tract infection. Co‐infections with other viruses were found in 30% of the MCPyV positive samples. The data present a pattern of infection similar to that seen with the polyomaviruses JC and BK in which the virus is acquired during childhood, probably by the respiratory route. The viruses then establish latency and become reactivated in the event of immunosuppression. J. Med. Virol. 83:2220–2224, 2011. © 2011 Wiley Periodicals, Inc.
Hepatitis A Virus genotype and its correlation with the clinical outcome of acute hepatitis A in Korea: 2006–2008
Authors: Yun Haesun , Lee Hyeok Jin , Jang Je‐Hyuck , Kim Jeong Sim , Lee Sang Hyub , Kim Jin‐Wook , Park Sang Jong , Park Young Min , Hwang Seong Gyu , Rim Kyu Sung , Kang Sook‐Kyoung , Lee Hyun Seok , Jeong Sook‐Hyang
Published: October 2011

Korea has recently experienced a nationwide outbreak of hepatitis A. This study aimed to investigate hepatitis A virus (HAV) genotypes and to compare clinical features between patients infected with HAV genotype IA and those with genotype IIIA. From September 2006 to August 2008, 595 patients with symptomatic hepatitis A were enrolled prospectively in four hospitals in Korea. Among them, 556 patients participated in this study by providing serum or stool samples for genotypic analysis. HAV RNA was detected in 499 patients (89.7%). Major genotypes included IA (n = 244, 48.9%) and IIIA (n = 244, 48.9%), and the remaining genotype was IB (n = 11, 2.2%). From September 2006 to August 2007, the distribution of genotypes IA and IIIA were 64.6% and 35.6%, respectively, which changed to 42.3% and 54.6%, respectively, from September 2007 to August 2008, indicating change of circulating HAV genotypes in the study period from IA to IIIA. Major patterns of amino acid substitution in the VP3/VP1 junction region were observed at position 512 (P → L) in genotype IA and at 520 (R → K) in genotype IIIA. Patients with genotype IIIA infection showed significantly higher aminotransferase levels, prothrombin time, and leukocyte count, with more severe symptoms than those with genotype IA at the time of admission. These results suggest the occurrence of a change of circulating HAV genotypes in recent community‐wide outbreaks of hepatitis A in Korea, and genotype IIIA infection, compared with genotype IA infection, might show more severe clinical manifestations. J. Med. Virol. 83:2073–2081, 2011. © 2011 Wiley Periodicals, Inc.
Comparison of a UL111a real‐time PCR and pp65 antigenemia for the detection of cytomegalovirus
Authors: Beckmann Christiane , Dumoulin Alexis , Rinaldo Christine Hanssen , Hirsch Hans H.
Published: October 2011

Surveillance of cytomegalovirus (CMV) replication in transplant patients is crucial for the success of transplantation. To compare a CMV pp65 antigenemia (pp65Ag) and a quantitative real‐time PCR targeting the CMV‐UL111a (UL111aPCR), all whole blood samples taken between July 2008 and October 2009 were identified which had been analyzed prospectively by both assays in parallel. Discordant results were re‐analyzed using a published CMV duplex PCR targeting regions UL55 and UL123exon4. Of 720 samples from 81 transplant patients, CMV replication was detected in 244 specimens (34%) by the UL111aPCR (median, 1,019 geq/ml), compared to 113 (16%) detected by the pp65Ag (median, 2/250,000 leukocytes). Concordant UL111aPCR/pp65Ag results were obtained in 561 (78%) samples, being positive in 99 (14%), and negative in 462 (64%). As a rule of thumb, 1 pp65Ag‐positive cell per 250,000 leukocytes corresponded to 1,000 geq/ml CMV DNA of whole blood. Discordant results were found in 159 samples (22%), being UL111aPCR‐positive/pp65Ag‐negative in 145 (91%; median, 650 geq/ml), or UL111aPCR‐negative/pp65Ag‐positive in 14 (9%; median, 1/250,000 cells). Using the duplex PCR targeting the CMV UL55 and the UL123‐exon4 genes, 131 of 139 (94%) discordant UL111aPCR‐positives (median UL111aPCR, 639 geq/ml; median UL55PCR, 715 geq/ml; median UL123PCR, 1,103 geq/ml) were confirmed. Of 14 discordant pp65Ag‐positives, duplex PCR was also negative in 8, and of low copy number in 6. Thus, CMV UL111aPCR provides more sensitive quantitation of CMV replication than pp65Ag, however, discordant results can occur at very low viral loads. J. Med. Virol. 83:2143–2150, 2011. © 2011 Wiley Periodicals, Inc.
A rapid and efficient method BK polyomavirus genotyping by high‐resolution melting analysis
Authors: Matsuda Yasuhiro , Qazi Yasir , Iwaki Yuichi
Published: October 2011

A small percentage of renal patients become infected with the BK polyomavirus (BKV), a pathogenic virus that causes BKV‐associated nephropathy (BKVN), after kidney transplantation. This study presents a simple, rapid, high‐throughput method for BKV genotyping using high‐resolution melt analysis (HRMA). Using this novel method, BKV genotypes were analyzed in 49 samples taken from BKV‐positive renal transplantation patients for classification into 1 of 3 genotypes: GI‐1 (subgroups Ia, Ib1, and Ic), GI‐2 (subgroup Ib2), and GII‐IV (subtypes II, III, and IV). HRMA was performed to compare each sample sequence to a reference sequence that contained a combination of 2 of the 3 genotype groups, and the findings validated by conventional DNA sequencing. Of the 49 samples, 20 samples were classified as GI‐1, 18 as GI‐2, and 11 as GII‐IV, suggesting that the predominant BKV strain (77.6%) in these patients was subtype I (GI‐1 and GI‐2). The HRMA method presented here is a time‐saving, reliable, and low‐cost procedure that can be developed as a diagnostic tool in the detection of the specific BKV genotypes associated with BKVN. J. Med. Virol. 83:2128–2134, 2011. © 2011 Wiley Periodicals, Inc.
Enteric viruses in healthy children in cameroon: Viral load and genotyping of norovirus strains
Authors: Ayukekbong James , Lindh Magnus , Nenonen Nancy , Tah Ferdinand , Nkuo‐Akenji Theresa , Bergström Tomas
Published: October 2011

Data regarding prevalence of noroviruses (NoVs) among asymptomatic persons are scarce. The current study carried out on samples from Cameroon describes the asymptomatic shedding of NoVs and other enteric viruses in healthy children and in adults infected with HIV but lacking symptoms of gastroenteritis. Enteric viruses were common with a prevalence of 53.7% in the children, and 35.5% in the adult participants. Multiple enteric viruses (2–5 agents) were detected in fecal samples from 65% of the children, and co‐infection with NoV was demonstrated in almost all cases of multiple infections. NoV viral loads in the healthy children were within disease causing range and significantly higher than those observed in the adults (P < 0.01). Sequencing and genotyping of NoV strains by phylogeny showed a marked diversity within two distinct genogroups, GI and GII, and strains clustered with genotypes GI.3, GII.17, GII.8, and GII.4. Genetic similarities to recent outbreak strains from other continents suggest a rapid circulation of NoVs that includes healthy children, who may constitute a reservoir for pathogenic NoVs. J. Med. Virol. 83:2135–2142, 2011. © 2011 Wiley Periodicals, Inc.
Fine‐scale regional climate patterns in the Guianas, tropical South America, based on observations and reanalysis data
Authors: Bovolo C. Isabella , Pereira Ryan , Parkin Geoff , Kilsby Chris , Wagner Thomas
Published: October 2011

The dense, intact rainforests of the Guianas (northern Amazonia) are important for the regulation of the local and regional climate, but preclude easy access so a large data gap exists. The rainforest–savannah boundary may also be particularly susceptible to increasing pressures from ecosystem exploitation and climate change. It is important therefore to establish a baseline climate regime so that the impacts of any future change can be determined. Currently this area is not covered by the publicly available climate data sets, so interpolated data sets are not an accurate representation of the climate of this area, emphasizing the need for a more detailed analysis in this region. Here, we collate the available data sets and use these to derive maps of observed precipitation and temperature across the region. To overcome the limitations in the inadequate observational data sets, we also test and use the ECMWF ERA‐40 reanalysis data set for the period 1958–2001 at a ∼125 km2 (1.125°) resolution. Mean differences (biases) and annual average spatial correlations are examined between modelled and observed time series comparing the seasonal cycles and the yearly, monthly and monthly anomaly time series. The results show that with the exception of sub‐grid resolution mountain environments, reanalysis data for the Guianas provide a consistent and relatively accurate spatial distribution of temperature. Precipitation is modelled less accurately, with best results for the average timings, length and severity of the dry periods. This study provides consistent and quantitative details on the spatial variations in seasonality, particularly in areas lacking observations, thereby advancing beyond previous studies. Precipitation is highly variable in the region so care must be taken when averaging modelled data over large geographical areas for comparisons with gridded data sets based on few observations. This is the first comprehensive study of the recent historical climate and its variability in this area. Copyright © 2011 The Authors. Journal compilation © 2011 The Royal Meteorological Society
The bio‐tribological properties of anti‐adhesive agents commonly used during tendon repair
Authors: McGonagle Lorcan , Jones Michael D. , Dowson Duncan , Theobald Peter S.
Published: October 2011

Frictional resistance to tendon gliding is minimized by surrounding loose areolar tissue. During periods of prolonged immobilization, for example, post‐tendon‐repair, adhesions can form between these two adjacent tissues, thereby limiting tendon function. Anti‐adhesive agents can be applied during surgery to prevent adhesion formation, whilst reportedly providing some reduction in friction during in vitro tendon‐bony pulley investigations. This bio‐tribological study evaluates whether application of these agents can improve the lubrication between the tendon and surrounding tissue, thus potentially reducing the risk of re‐rupturing the tendon at the repair site. The use of bovine synovial fluid (BSF) enabled an approximation of the in vivo lubrication regime, and subsequent comparison of the performance of three synthetic agents (50 mg/ml 5‐fluorouracil; 5 mg/ml hyaluronic acid; ADCON–T/N). Coefficient of friction data was recorded and then compared with the Stribeck curve. BSF generated a fluid film that separated the two surfaces, giving rise to optimal lubrication conditions. This efficient regime was also generated following application of each anti‐adhesion agent. The use of phosphate‐buffered saline solution in generating only a boundary lubrication regime highlighted the effectiveness of the agents in reducing friction. Hyaluronic acid (5 mg/ml) was marginally deemed the most effective anti‐adhesive agent at lubricating the tendon. Subsequently, it is concluded that the application of anti‐adhesive agents post‐surgery has secondary, tribological benefits that serve to reduce friction, and thus potentially the risk of failure, at the tendon repair site. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:775–780, 2012
A phase I/II clinical trial of preoperative short‐course carbon‐ion radiotherapy for patients with squamous cell carcinoma of the esophagus
Authors: Akutsu Yasunori , Yasuda Shigeo , Nagata Matsuo , Izumi Yosuke , Okazumi Shinichi , Shimada Hideaki , Nakatani Yukio , Tsujii Hirohiko , Kamada Tadashi , Yamada Shigeru , Matsubara Hisahiro
Published: October 2011

Background

Carbon‐ion radiotherapy (CIR) has been under development. We report the results of a phase I/II clinical trial of preoperative CIR for esophageal squamous cell carcinoma (ESCC).

Methods

Thirty‐one thoracic ESCC patients were enrolled. They were first treated with CIR. The radiation dose was escalated from the initial dose of 28.8 GyE up to 36.8. Four to 8 weeks after CIR followed by clinical evaluation of the therapy, surgery was performed. Thereafter, a pathological evaluation was made.

Results

Acute toxicity was not seen except in one case (3.2%), and there were no late toxicities. Throughout the study period, there were no cases of withdrawal due to the effects of preoperative CIR. Twelve out of 31 (38.7%) patients achieved a clinical complete response (CR) and 13 patients (41.9%) achieved a partial response. Twelve out of 31 patients (38.7%) achieved a pathological CR. The overall 1‐, 3‐, and 5‐year survival rates in the stage I cases were 91%, 81%, and 61%, and was 100%, 85%, and 77% for the stage II, and 71%, 43%, and 29% for the stage III cases, respectively.

Conclusions

CIR showed strong local tumor control and is highly effective as a neoadjuvant therapy without severe adverse events. J. Surg. Oncol. 2012; 105:750–755. © 2011 Wiley Periodicals, Inc.
Thermoresponsive Polymer Colloids for Drug Delivery and Cancer Therapy
Authors: Abulateefeh Samer R. , Spain Sebastian G. , Aylott Jonathan W. , Chan Weng C. , Garnett Martin C. , Alexander Cameron
Published: October 2011

Many difficulties in treating cancer arise from the problems in directing highly cytotoxic agents to the deseased tissues, cells and intracellular compartments. Many drug delivery systems have been devised to address this problem, including those that show a change in properties in response to a temperature stimulus. In particular, colloidal materials based on thermoresponsive polymers offer a means to transport drugs selectively into tumour tissues that are hyperthermic, either intrinsically or through the application of clinical procedures such as localised heating. In this paper, the key attributes of thermoresponsive polymer colloids are considered, a number of important recent examples are discussed and the possible future developments of these materials are evaluated.

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Absolutely continuous spectrum for random Schrödinger operators on the Bethe strip
Authors: Klein Abel , Sadel Christian
Published: October 2011

The Bethe strip of width m is the cartesian product \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathbb {B}\times \lbrace 1,\ldots ,m\rbrace$\end{document}, where \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathbb {B}$\end{document} is the Bethe lattice (Cayley tree). We prove that Anderson models on the Bethe strip have “extended states” for small disorder. More precisely, we consider Anderson‐like Hamiltonians \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$H_\lambda =\frac{1}{2} \Delta \otimes 1 + 1 \otimes A\,+\,\lambda \mathcal {V}$\end{document} on a Bethe strip with connectivity K ≥ 2, where A is an m × m symmetric matrix, \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathcal {V}$\end{document} is a random matrix potential, and λ is the disorder parameter. Given any closed interval \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$I\subset \big (\!-\!\sqrt{K}+a_{{\rm max}},\sqrt{K}+a_{\rm {min}}\big )$\end{document}, where amin and amax are the smallest and largest eigenvalues of the matrix A, we prove that for λ small the random Schrödinger operator Hλ has purely absolutely continuous spectrum in I with probability one and its integrated density of states is continuously differentiable on the interval I.
Microarray meta‐analysis defines global angiogenesis‐related gene expression signatures in human carcinomas
Authors: Anders Mario , Fehlker Marion , Wang Qing , Wissmann Christoph , Pilarsky Christian , Kemmner Wolfgang , Höcker Michael
Published: October 2011

Angiogenesis is a prerequisite for progression of cancers. The number of genes linked to angiogenesis suggests the existence of complex gene‐networks, which remain to be elucidated. To identify angiogenesis genes deregulated in carcinomas, we performed a meta‐profiling analysis of published gene expression microarray studies. Own microarray and quantitative RT‐PCR data were obtained from a colorectal carcinoma cohort. Applying highly stringent inclusion criteria, 15 cancer array studies were suitable for our analysis. These studies provided 789 tumor specimens and 190 samples of healthy tissues yielding a total of approx. 1,000,000 gene expression measurements. Meta‐analysis on the expression of 480 angiogenesis‐related genes in 10 cancer types identified a characteristic, entity‐independent “global” cancer expression signature of 25 angiogenesis‐related genes showing high frequency down‐regulation when compared to corresponding healthy tissues. Furthermore, we characterized 25 genes displaying frequent up‐regulation, yet less often than the 25 down‐regulated genes. Comparative inter‐study cross‐validation revealed that both signatures discriminate cancers from healthy tissues with high accuracy in independent test sets. Moreover, own microarray data of colorectal carcinomas confirmed the specific and sensitive discriminating potential of both signatures. These results were validated by quantitative RT‐PCR for eight genes displaying the highest differences in the microarray analysis. Our study for the first time defines global gene expression signatures linked to angiogenesis in carcinomas. Our findings suggest that gene down‐regulation may represent a central aspect of tumor angiogenesis. © 2011 Wiley Periodicals, Inc.
Inhibition of NOTCH3 signalling significantly enhances sensitivity to cisplatin in EBV‐associated nasopharyngeal carcinoma
Authors: Man Cheuk‐Him , Wei‐Man Lun Samantha , Wai‐Ying Hui Jan , To Ka‐Fai , Choy Kwong‐Wai , Wing‐Hung Chan Anthony , Chow Chit , Tin‐Yun Chung Grace , Tsao Sai‐Wah , Tak‐Chun Yip Timothy , Busson Pierre , Lo Kwok‐Wai
Published: October 2011

Nasopharyngeal carcinoma (NPC) is an EBV‐associated epithelial malignancy which is prevalent in south‐east Asia and southern China. Despite the multiple genetic and epigenetic changes reported, the contribution of dysregulated signalling pathways to this distinct type of head and neck cancer is not well understood. Here we demonstrate the up‐regulation of NOTCH ligands (JAG1 or DLL4) and effector (HEY1) in the majority of EBV‐positive tumour lines and primary tumours. Among the NOTCH receptors, NOTCH3 was over‐expressed in all EBV‐positive tumour lines and 92.5% of primary tumours. Aberrant activation of NOTCH3 signalling was consistently detected in all these samples. These findings imply that NOTCH3 may play an crucial role in the development of NPC. By NOTCH3 specific siRNA, NOTCH3 signalling was suppressed and thereby significant growth inhibition and apoptosis induction occurred in NPC cells. Down‐regulation of a number of targets involved in cell proliferation, eg CCND1, C‐MYC,NFKB1, and survival, eg BCL2, BCL‐XL, SURVIVIN, was confirmed in the NOTCH3 knockdown NPC cells. Importantly, NOTCH3 knockdown highly enhanced the sensitivity of NPC cells to cisplatin treatment. Furthermore, we revealed that the ability of NPC cells to form spheroids in vitro and tumours in nude mice was also significantly decreased after knockdown of NICD3 expression. These findings indicate that activation of NOTCH3 pathway is a critical oncogenic event in NPC tumourigenesis. Targeting NOTCH3 signalling may serve as a potential therapeutic approach for treating patients suffering from EBV‐associated NPC. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Initial testing of the investigational NEDD8‐activating enzyme inhibitor MLN4924 by the pediatric preclinical testing program
Authors: Smith Malcolm A. , Maris John M. , Gorlick Richard , Kolb E. Anders , Lock Richard , Carol Hernan , Keir Stephen T. , Reynolds C. Patrick , Kang Min H. , Morton Christopher L. , Wu Jianrong , Smith Peter G. , Yu Jie , Houghton Peter J.
Published: October 2011

Background

MLN4924 is an investigational first‐in‐class small molecule inhibitor of NEDD8‐activating enzyme (NAE). NAE is an essential component of the NEDD8 conjugation pathway, controlling the activity of a subset of ubiquitin‐proteasome system (UPS) E3 ligases, multiprotein complexes that transfer ubiquitin molecules to substrate proteins.

Procedures

MLN4924 was tested against the PPTP in vitro panel using 96‐hour exposure time at concentrations ranging from 1.0 nM to 10 µM. It was tested in vivo at a dose of 100 mg/kg [66 mg/kg for the acute lymphoblastic leukemia (ALL) xenografts] administered orally twice daily × 5 days. Treatment duration was 3 weeks.

Results

The median relative IC50 for MLN4924 against the PPTP cell lines was 143 nM, (range: 15–678 nM) with that for the Ewing panel being significantly lower (31 nM). MLN4924 induced significant differences in EFS distribution compared to control in 20 of 34 (59%) evaluable solid tumor xenografts. MLN4924 induced intermediate activity (EFS T/C values >2) in 9 of the 33 evaluable xenografts (27%), including 4 of 4 glioblastoma xenografts, 2 of 3 Wilm's tumor xenografts, 2 of 5 rhabdomyosarcoma xenografts, and 1 of 4 neuroblastoma xenografts. For the ALL panel, 5 of 8 evaluable xenografts showed intermediate activity for the EFS T/C measure. MLN4924 did not induce objective responses in the PPTP solid tumor or ALL panels.

Conclusions

MLN4924 showed potent activity in vitro and in vivo showed tumor growth inhibitory activity against a subset of the PPTP solid tumor and ALL xenografts. Pediatr Blood Cancer 2012;59:246–253. © 2011 Wiley Periodicals, Inc.
Bleeding disorders in Noonan syndrome
Authors: Briggs Benjamin J. , Dickerman Joseph D.
Published: October 2011

Noonan Syndrome (NS) is a common genetic disease with multiple organ defects including bleeding disorders, which was last reviewed in 1997. Since then significant information has been acquired regarding bleeding problems in NS, specifically on the underlying genetics. Associations between mutated genes and bleeding disorders are reviewed along with prevalence and underlying etiologies. Between 50–89% of NS patients will have a bleeding disorder and since a significant number will require surgery it is important to identify which ones are at risk prior to their procedure. Recommendations regarding screening for bleeding disorders and their treatment are discussed. Pediatr Blood Cancer 2012; 58: 167–172. © 2011 Wiley Periodicals, Inc.
Physical and mental health status and health behaviors of childhood cancer survivors: Findings from the 2009 BRFSS survey
Authors: Phillips‐Salimi Celeste R. , Lommel Karen , Andrykowski Michael A.
Published: October 2011

Background

The growing number of childhood cancer survivors makes examination of their current physical and mental health status and health behaviors an important concern. Much of what is known about the long‐term outcomes of childhood cancer survivors comes from the Childhood Cancer Cohort Study (CCSS) which uses sibling controls.

Procedure

Using data from the 2009 Behavioral Risk Factor Surveillance System survey, 651 childhood cancer survivors and 142,932 non‐cancer peer controls were identified. The two groups were compared on a variety of physical and mental health status and health behavior variables using ANCOVA and binary logistic regression.

Results

While controlling for differences in age, sex, and minority status, survivors significantly (P ≤ 0.001) had poorer socioeconomic outcomes, more comorbid conditions, lower life satisfaction, less social and emotional support, poorer general health, and reported more days per month of poor physical and mental health than non‐cancer individuals. Survivors were more likely to report being a current smoker [odds ratio (OR) = 2.33; 95% confidence interval (CI), 1.98–2.73; P < 0.001]; tested for human immunodeficiency virus (HIV) (OR = 1.79; 95% CI, 1.52–2.11; P < 0.001); and that at least one HIV situation applied to them (OR = 2.06; 95% CI, 1.55–2.74; P < 0.001). No significant differences were found between groups in regards alcohol use and diet.

Conclusions

Results support and extend previous findings reported by the CCSS. New findings regarding survivors' increased likelihood to engage in risky behaviors proposes new directions for future research. Pediatr Blood Cancer 2012; 58: 964–970. © 2011 Wiley Periodicals, Inc.
The use of plerixafor in harvesting autologous stem cells in the pediatric setting
Authors: Vettenranta Kim , Möttönen Merja , Riikonen Pekka
Published: October 2011

The mobilization of stem cells using the standard approach, chemotherapy and G‐CSF, may not be successful in all cases heavily pretreated. Plerixafor (AMD3100) has emerged as a viable option in attempts to mobilize stem cells among these patients. The use of plerixafor in the adult setting has been established, but data on pediatric use is scarce. We report on the use of plerixafor in eight pediatric cases either as add‐on to chemotherapy plus G‐CSF or in remobilization. Pediatr Blood Cancer 2012; 59: 197–198. © 2011 Wiley Periodicals, Inc.
Genotoxicity associated with hydroxyurea exposure in infants with sickle cell anemia: Results from the BABY‐HUG phase III clinical trial
Authors: McGann Patrick T. , Flanagan Jonathan M. , Howard Thad A. , Dertinger Stephen D. , He Jin , Kulharya Anita S. , Thompson Bruce W. , Ware Russell E. ,   for the BABY HUG Investigators
Published: October 2011

Background

The laboratory and clinical benefits of hydroxyurea therapy for children with sickle cell anemia (SCA) are well recognized, but treatment in young patients is limited in part by concerns about long‐term genotoxicity, and specifically possible carcinogenicity.

Procedure

The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) was a multicenter double‐blinded placebo‐controlled randomized clinical trial (NCT00006400) testing whether hydroxyurea could prevent chronic organ damage in very young patients with SCA. An important secondary objective was the measurement of acquired genotoxicity using three laboratory assays: chromosomal karyotype, illegitimate VDJ recombination events, and micronucleated reticulocyte formation.

Results

Our data indicate that hydroxyurea treatment was not associated with any significant increases in genotoxicity compared to placebo treatment.

Conclusions

These data provide additional support to the safety profile of hydroxyurea for young patients with SCA, and suggest that genotoxicity in this patient population is low. Pediatr Blood Cancer 2012;59:254–257. © 2011 Wiley Periodicals, Inc.
Effect of carbon black structure on low‐strain conductivity of polypropylene and low‐density polyethylene composites
Authors: Fathi Atefeh , Hatami Kianoosh , Grady Brian P.
Published: October 2011

The influences of carbon black (CB) structure on the percolation threshold, mechanical properties, and strain‐resistivity response of polymer composites are studied. Low‐density polyethylene (LDPE) and polypropylene (PP) samples were blended with five different types of CB differing in structure. Relatively low strains were studied; the maximum strain was 10%. It was found that the CB concentration for maximum strain‐sensitivity of the electrical conductivity is higher for low structure carbon blacks but is essentially independent of the CB structure for medium‐ to high‐structure carbon blacks. However, the composite containing the largest particle size carbon black clearly showed the highest strain‐sensitivity to electrical conduction. The mechanical properties and sensitivity of electrical resistivity to tensile strain of the filled composites examined in the study are also presented and discussed. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers