bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Regioselective, Three‐Component Reactions of Diazoacetates with Anilines and β,γ‐Unsaturated α‐Keto Esters: 1,2‐Addition versus 1,4‐Addition
Authors: Zhu Yingguang , Zhai Changwei , Yang Liping , Hu Wenhao
Published: January 2011

The highly regioselective, three‐component reaction of diazoacetates with anilines and β,γ‐unsaturated α‐keto esters is presented. Ammonium ylides obtained in situ from diazoacetates and anilines can be trapped by β,γ‐unsaturated α‐keto esters through two distinctly different pathways: 1,2‐addition or tandem 1,4‐addition/cyclization followed by one‐pot dehydration. The course of the reaction is highly dependent on the electronic nature of the diazoacetates. When α‐unsubstituted or α‐alkyl‐substituted diazoacetates are used as the substrates, the three‐component reaction proceeds efficiently, in a regiospecific 1,2‐addition manner, to afford densely functionalized β‐hydroxy α‐amino acid derivatives in high yields (71–94 %) and good diastereoselectivities. When α‐aryl‐substituted diazoacetates are used as the substrates, the three‐component reaction occurs smoothly to yield polysubstituted 2,3‐dihydropyrrole derivatives through tandem 1,4‐addition/cyclization followed by one‐pot dehydration. The high regioselectivity observed in the three‐component reaction can be rationalized on the basis of the hard and soft acids and bases (HSAB) principle.
Lipid synthesized by micro‐algae grown in laboratory‐ and industrial‐scale bioreactors
Authors: Makri Anna , Bellou Stamatia , Birkou Maria , Papatrehas Konstantinos , Dolapsakis Nikolas P. , Bokas Dimitrios , Papanikolaou Seraphim , Aggelis George
Published: January 2011

Tetraselmis sp. and Nannochloropsis oculata, cultivated in industrial‐scale bioreactors, produced 2.33 and 2.44% w/w lipid (calculated as the sum of fatty acid methyl esters) in dry biomass, respectively. These lipids contained higher amounts of neutral lipids and glycolipids plus sphingolipids, than phospholipids. Lipids of Tetraselmis sp. were characterized by the presence of eicosapentaenoic acid (that was located mainly in phospholipids), and octadecatetraenoic acid (that was equally distributed among lipid fractions), while these fatty acids were completely absent in N. oculata lipids. Additionally, lipids produced by 16 newly isolated strains from Greek aquatic environments (cultivated in flask reactors) were studied. The highest percentage of lipids was found in Prorocentrum triestinum (3.69% w/w) while the lowest in Prymnesium parvum (0.47% w/w). Several strains produced lipids rich in eicosapentaenoic and docosahexaenoic acids. For instance, docosahexaenoic acid was found in high percentages in lipids of Amphidinium sp. S1, P. parvum, Prorocentrum minimum and P. triestinum, while lipids produced by Asterionella sp. (?) S2 contained eicosapentaenoic acid in high concentration. These lipids, containing ω‐3‐long‐chain polyunsaturated fatty acids, have important applications in the food and pharmaceutical industries and in aquaculture.
Serratia marcescens SYBC08 catalase isolated from sludge containing hydrogen peroxide shows increased catalase production by regulation of carbon metabolism
Authors: Zeng Hua‐Wei , Cai Yu‐Jie , Liao Xiang‐Ru , Zhang Feng , Li Yu‐Lin , Zeng Xiang‐Kang , Zhang Da‐Bing
Published: January 2011

A high‐catalase‐producing strain, which was isolated from sludge containing hydrogen peroxide, was identified as Serratia marcescens SYBC08 by 16S rDNA sequence analysis. Serratia spp. was reported as non‐spore‐forming bacterium (except S. marcescens spp. sakuensis), but in our study electron microscopic observation revealed that the strain did produce spores. The content of the main fatty acid C16:0 (14.8%) was significantly different from that of S. marcescens spp. sakuensis (33.2%) and S. marcescens spp. marcescens DSM 30121T (34.8%), and the biochemical characteristics were not identical to those of S. marcescens spp. sakuensis. We speculate that the relatively high catalase activity and the spore structures may enable the strain to survive in a hydrogen peroxide environment. The most suitable carbon and nitrogen sources for the catalase production by S. marcescens SYBC08 were citric acid and corn steep liquor powder. A strategy of carbon metabolism regulation to enhance the catalase production was exploited. In the 7‐L fermenter, catalase production (20 353 U/mL) obtained in the presence of glucose and citric acid was 1.68‐ and 1.31‐fold higher than that obtained in the presence of glucose or citric acid, at equimolar carbon concentration. This production yield was much higher than that of many catalase‐producing strains, but only slightly lower than the production by Micrococcus luteus (34 601 U/mL). The results suggest that the new spore‐forming S. marcescens SYBC08 is a potential candidate for the production of catalase.
Aquatic predicted no-effect-concentration derivation for perfluorooctane sulfonic acid
Authors: Qi Ping , Wang Ying , Mu Jingli , Wang Juying
Published: January 2011

Perfluorooctane sulfonic acid (PFOS), a representative perfluorinated surfactant, is an anthropogenic pollutant detected in various environmental and biological matrices. Some laboratory and field work has been conducted to assess the aquatic toxicity of PFOS, but little is known regarding its toxicity threshold to the aquatic ecosystem. In the present study, predicted no-effect concentrations (PNECs) were derived by four different approaches. The interspecies correlation estimation (ICE) program and final acute-to-chronic ratio (FACR) were applied to the development of PNEC based on the toxic mode of action (MOA) of PFOS. By comparison of the different PNECs, the recommended aquatic toxicity thresholds for PFOS are in the range of 0.61 to 6.66 µg/L. Based on comparison of PNEC values, microcosm results, and reported environmental concentrations, PFOS appears not to pose a serious threat to aquatic organisms. The present results demonstrate that MOA is an important consideration for the derivation of reliable PNECs; moreover, the ICE-based species sensitivity distribution (SSD) method can be used to derive PNECs when toxicological data are limited. The application of MOA and ICE for deriving PNEC values in the present study may facilitate studies on using a combination of quantitative structure–activity relationship (QSAR) models and ICE to estimate PNECs. Environ. Toxicol. Chem. 2011; 30:836–842. © 2010 SETAC
Lapatinib inhibits receptor phosphorylation and cell growth and enhances antibody‐dependent cellular cytotoxicity of EGFR‐ and HER2‐overexpressing esophageal cancer cell lines
Authors: Mimura Kousaku , Kono Koji , Maruyama Takanori , Watanabe Mitsuaki , Izawa Shinichiro , Shiba Shugo , Mizukami Yoshiki , Kawaguchi Yoshihiko , Inoue Masayuki , Kono Tetsuo , Choudhury Aniruddha , Kiessling Rolf , Fujii Hideki
Published: January 2011

Lapatinib is a dual tyrosine kinase inhibitor of the EGFR and HER2 tyrosine kinase domains. EGFR is expressed in 33.3% and HER2 in 30.3% of esophageal squamous cell carcinomas (ESCCs). To explore the potential utility of Lapatinib for therapy of ESCC patients, we evaluated the effect of Lapatinib on a panel of ESCC cell lines. EGFR and HER2 expression by the cell lines was established, and the effects of Lapatinib on inhibition of the phosphorylation of HER2, antiproliferative effect, apoptosis‐inducing activity and accumulation of HER2 and EGFR on cell surface were evaluated. Additionally, the combined effect of Lapatinib together with Herceptin or Cetuximab on cell‐mediated cytotoxicity was evaluated. Lapatinib inhibited HER2 phosphorylation in HER2‐overexpressing, HER2 gene amplification positive ESCC cell line. Lapatinib also inhibited cell proliferation, induced apoptosis and caused the surface accumulation of HER2 and EGFR in ESCC cell lines. Addition of Lapatinib increased Herceptin‐mediated antibody‐dependent cell‐mediated cytotoxicity by 15–25% with three ESCC target cell lines. Similarly, Cetuximab‐mediated antibody‐dependent cell‐mediated cytotoxicity also increased by 15–30% in two ESCC cell lines on addition of Lapatinib. Cumulatively, the data indicate that Lapatinib has activity in EGFR‐ and/or HER2‐expressing ESCC cells, and the combination therapy of Lapatinib and Cetuximab/Herceptin is a promising strategy in ESCC.
Glutamate increases pancreatic cancer cell invasion and migration via AMPA receptor activation and Kras‐MAPK signaling
Authors: Herner Alexander , Sauliunaite Danguole , Michalski Christoph W. , Erkan Mert , Oliveira Tiago De , Abiatari Ivane , Kong Bo , Esposito Irene , Friess Helmut , Kleeff Jörg
Published: January 2011

Glutamate has been implicated in tumorigenesis through activation of alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors (AMPAR). However, the function of a glutamate‐to‐AMPAR signal in pancreatic ductal adenocarcinoma (PDAC) has remained elusive. We now show that glutamate‐mediated AMPA receptor activation increases invasion and migration of pancreatic cancer cells via activation of the classical MAPK pathway. Glutamate levels were increased in pancreatic cancer accompanied by downregulation of GluR subunits 1, 2, and 4. In pancreatic cancer precursor lesions, pancreatic intraepithelial neoplasia (PanIN), GluR1 subunit levels were strikingly and step‐wise increased but its expression was rare in PDAC. Pharmacological inhibition or RNAi‐mediated suppression of GluR1 or GluR2 did not affect cancer cell growth but significantly decreased invasion. In a K‐ras wildtype cell line, AMPA receptor activation enhanced K‐ras activity and—further downstream—phosphorylation of p38 and of p44/42. Preemptive blockade of AMPA receptors in a mouse model of pancreatic cancer inhibited tumor cell settling. AMPA receptor activation thus not only activates MAPK signalling but also directly increases activity of K‐ras. Glutamate might serve as a molecular switch that decreases the threshold of K‐ras‐induced oncogenic signalling and increases the chance of malignant transformation of pancreatic cancer precursor lesions.
The spectrum of malignancies in HIV‐infected patients in 2006 in France: The ONCOVIH study
Authors: Lanoy Emilie , Spano Jean‐Philippe , Bonnet Fabrice , Guiguet Marguerite , Boué François , Cadranel Jacques , Carcelain Guislaine , Couderc Louis‐Jean , Frange Pierre , Girard Pierre‐Marie , Oksenhendler Eric , Poizot‐Martin Isabelle , Semaille Caroline , Agut Henri , Katlama Christine , Costagliola Dominique ,   the ONCOVIH study group
Published: January 2011

Since no large descriptive studies of incident cancers in HIV‐infected patients are available in France, the nationwide cross‐sectional ONCOVIH study aimed to prospectively report new malignancies diagnosed in HIV‐infected patients in cancer centers and HIV/AIDS centers. We estimated the number of cancers in France for the year 2006 using the capture–recapture methods with two sources: ONCOVIH and the FHDH ANRS‐CO4 cohort, as well as the completeness of the sources. Incidence and relative risks (RR) to the general population were estimated. In 2006, 672 new malignancies in 668 patients were reported in ONCOVIH; the most common were non Hodgkin's lymphoma (NHL, 21.5%), Kaposi's sarcoma (KS, 16.0%), lung cancer (9.4%), anal cancer (8.2%), Hodgkin's lymphoma (7.6%), skin cancers excluding melanoma (6.8%), and liver cancer (5.6%). Based on the capture‐recapture approach, the estimated number of malignancies was 1320 and non‐AIDS‐defining malignancies (NADM) represented 68% of cases. The overall ascertainment of malignancies were 53%, and 59%, in the ONCOVIH study, and the FHDH ANRS‐CO4 cohort, respectively. The estimated incidence of cancer among HIV‐infected patients was 14 per 1000 person‐years. Compared with the general population, the estimated RR in HIV–infected patients was 3.5 (95%CI 3.3–3.8) in men and 3.6 (95%CI 3.2–4.0) in women, and was particularly elevated in younger patients. Even in the era of combined antiretroviral therapy, the incidence of cancer is higher in HIV‐infected persons than in the general population. A large variety of malignancies were diagnosed, and the majority were NADM.
Regulatory BCL2 promoter polymorphism (−938C>A) is associated with adverse outcome in patients with prostate carcinoma
Authors: Bachmann Hagen S. , Heukamp Lukas C. , Schmitz Klaus J. , Hilburn Caroline F. , Kahl Philip , Buettner Reinhard , Nückel Holger , Eisenhardt Andreas , Rübben Herbert , Schmid Kurt Werner , Siffert Winfried , Eggert Angelika , Schramm Alexander , Schulte Johannes H.
Published: January 2011

Molecular markers predictive of prostate cancer prognosis are urgently needed. Overexpression of the antiapoptotic protein, Bcl‐2, has repeatedly been shown to be associated with adverse outcome in this malignancy. We hypothesized that a regulatory BCL2 −938C>A promoter polymorphism, which significantly affects promoter activity and Bcl‐2 expression in different malignancies, may influence survival. Reporter assays and electrophoretic mobility shift assays reveled that the −938C>A BCL2 promoter polymorphism significantly affects promoter activity and transcription factor binding in prostate cancer cells. Significantly higher BCL2 mRNA expression was observed in primary prostate carcinomas derived from patients with the AA, compared to CC, genotype. Survival analysis showed that the −938AA genotype was an independent, unfavorable prognostic factor for relapse‐free survival in a primary cohort of 142 patients and in an independent replication cohort of 148 patients, with hazard ratios (HR) of 4.4 (95% CI, 1.3–15.1; p = 0.018) and 4.6 (95% CI, 1.5–14.2; p = 0.009). Furthermore, the −938AA genotype was independently associated with worse overall survival in the replication series, with a HR of 10.9 (95% CI, 1.2–99.3; p = 0.034). We conclude that the BCL2 −938C>A polymorphism is an independent predictor of relapse‐free and overall survival in patients with prostate cancer. The BCL2 −938C>A polymorphism should be evaluated prospectively and may also have promise in assisting optimal patient choice for treatment with BCL2‐targeted drugs already in evaluation for prostate cancer treatment.
The association of body mass index with mortality in the California Teachers Study
Authors: Bessonova Leona , Marshall Sarah F. , Ziogas Argyrios , Largent Joan , Bernstein Leslie , Henderson Katherine D. , Ma Huiyan , West Dee W. , Anton‐Culver Hoda
Published: January 2011

Although underweight and obesity have been associated with increased risk of mortality, it remains unclear whether the associations differ by hormone therapy (HT) use and smoking. The authors examined the relationship between body mass index (BMI) and mortality within the California Teachers Study (CTS), specifically considering the impact of HT and smoking. The authors examined the associations of underweight and obesity with risks of all‐cause and cause‐specific mortality, among 115,433 women participating in the CTS, and specifically examined whether HT use or smoking modifies the effects of obesity. Multivariable Cox proportional hazards regression provided estimates of relative risks (RRs) and 95% confidence intervals (CIs). During follow up, 10,574 deaths occurred. All‐cause mortality was increased for underweight (BMI <18.5; adjusted RR = 1.33, 95% CI = 1.20–1.47) and obese participants (BMI ≥ 30: RR = 1.27, 95% CI = 1.19–1.37) relative to BMI of 18.5–24.9). Respiratory disease mortality was increased for underweight and obese participants. Death from any cancer, and breast cancer specifically, and cardiovascular disease was observed only for obese participants. The obesity and mortality association remained after stratification on HT and smoking. Obese participants remained at greater risk for mortality after stratification on menopausal HT and smoking. Obesity was associated with increased all‐cause mortality, as well as death from any cancer (including breast), and cardiovascular and respiratory diseases. These findings help to identify groups at risk for BMI‐related poor health outcomes.
High expression of stratifin is a universal abnormality during the course of malignant progression of early‐stage lung adenocarcinoma
Authors: Shiba‐Ishii Aya , Kano Junko , Morishita Yukio , Sato Yukio , Minami Yuko , Noguchi Masayuki
Published: January 2011

Adenocarcinoma in situ (AIS) of the lung has an extremely favorable prognosis, with a 5‐year survival rate of 100%. However, early invasive adenocarcinoma (EIA) often has a fatal outcome. In this study, we compared the expression profiles of AIS with those of EIA showing lymph node metastasis or a fatal outcome, and screened the differentially expressed genes by cDNA microarray. From the genes selected, we focused on Stratifin (SFN, 14‐3‐3 σ), which showed significantly higher expression in EIA than in AIS. Immunohistochemistry for SFN revealed that more than 95% of EIAs were immunopositive for SFN, in comparison to only 13% of AISs (p <0.05). Interestingly, positivity was detected not only in the invasive region but also in the in situ spreading component of EIA. Functionally, SFN facilitates the cell proliferation capacity of lung adenocarcinoma. These results indicate that SFN overexpression is a universal abnormality during the stepwise progression from in situ to invasive adenocarcinoma of the lung.
Association of tissue promoter methylation levels of APC, TGFβ2, HOXD3 and RASSF1A with prostate cancer progression
Authors: Liu Liyang , Kron Ken J. , Pethe Vaijayanti V. , Demetrashvili Nino , Nesbitt Michael E. , Trachtenberg John , Ozcelik Hilmi , Fleshner Neil E. , Briollais Laurent , van der Kwast Theodorus H. , Bapat Bharati
Published: January 2011

Aberrant promoter methylation is known to silence tumor‐suppressor genes in prostate cancer (PCa). We correlated quantitative promoter methylation levels of APC, TGFβ2 and RASSF1A in 219 radical prostatectomies diagnosed between 1998 and 2001 with clinicopathological follow‐up data available including Gleason Pattern (GP), Gleason Score (GS) and pathological stage and explored their potential in predicting biochemical recurrence using univariate and multivariate analyses. We observed that the average methylation levels of APC increased significantly from GS ≤ 6 to GS7, and pT2 to pT3a, and that of TGFβ2 increased from GS ≤ 6 to GS7, but not for RASSF1A. PCa samples were also stratified into high methylation (HM) and low methylation (LM) groups based on the PMR scores of all cases analyzed for each marker. The HM frequency of APC was greater in pT3a than pT2, and in GS ≥ 8 than GS ≤ 6. The HM frequency also increased significantly from GP3 to GP4 for APC, TGFβ2 and RASSF1A. APC methylation level was a significant predictor of biochemical recurrence in univariate analysis (p‐value = 0.028). Finally, we combined methylation data of these three genes with the previously reported novel methylation biomarker HOXD3. Quantitative methylation assessment of a multiplex panel of markers, consisting of APC, HOXD3 and TGFβ2, outperforms any single marker for the prediction of biochemical recurrence (p‐value = 0.017). Our study demonstrated that quantitative increase in promoter methylation levels of APC, HOXD3 and TGFβ2 are associated with PCa progression.
Eurogin 2010 roadmap on cervical cancer prevention
Authors: Franceschi Silvia , Denny Lynette , Irwin Kathleen L. , Jeronimo José , Lopalco Pier Luigi , Monsonego Joseph , Peto Julian , Ronco Guglielmo , Sasieni Peter , Wheeler Cosette M.
Published: January 2011

The EUROGIN 2010 roadmap represents a continuing effort to provide and interpret updated information on cervical cancer screening and vaccination against the cause of the disease, high‐risk human papillomavirus (HPV). Contrary to the two previous reports in 2008 and 2009, the present roadmap gives equal room to HPV‐based screening and HPV vaccination, as a result of the recent strengthening of the evidence on the efficacy and feasibility of both approaches. The superiority of HPV testing in primary screening compared to cytology (in more developed countries) and to cytology or visual inspection methods (in less developed countries) has been demonstrated in several randomised trials. High vaccine efficacy has been confirmed up to 7 years after vaccination; school‐based programmes in some countries have been able to reach over 70% coverage among adolescent girls. Demonstration projects have indicated that the delivery of HPV vaccines in less developed countries is feasible and favourably received by populations where cervical cancer is very common. HPV‐based screening can diminish cervical cancer incidence more quickly than HPV vaccination, but vaccination can eventually facilitate screening efforts, especially if new vaccines against a greater number of HPV types are introduced. The availability of two highly complementary prevention tools such as HPV testing and HPV vaccination makes it possible to conceive integrated strategies for the elimination of cervical cancer that have no precedent in the cancer field. HPV tests and HPV vaccines remain, however, too expensive, and large‐scale financing of screening and vaccination in less developed countries is sorely lacking.
Surface chemical patterning for long‐term single‐cell culture
Authors: Cheng Qian , Komvopoulos Kyriakos , Li Song
Published: January 2011

Surface chemical patterning of polystyrene (PS) dishes for long‐term single‐cell culture was accomplished by oxygen plasma treatment through the windows of a polydimethylsiloxane membrane mask that produced hydrophilic areas of different shapes and sizes, followed by overnight incubation with either Pluronic F108 solution or a mixture of Pluronic F108 solution and fibronectin. Selective cell attachment on pattern areas of PS dishes was investigated in light of cell seeding experiments and X‐ray photoelectron spectroscopy measurements. Activation of the hydrophilic areas of patterned PS surfaces by serum proteins in the culture medium was conducive to cell attachment on the pattern areas of dishes incubated with only Pluronic solution. Preferential adsorption of fibronectin on hydrophilic pattern areas enhanced selective cell attachment on patterned dishes incubated with a mixture of Pluronic solution and fibronectin. Cell‐culture experiments demonstrated an effect of surface patterning on both cell and nucleus shape and confirmed the long‐term (>2 weeks) stability of the produced single‐cell patterns in serum medium. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
PLGA‐chitosan/PLGA‐alginate nanoparticle blends as biodegradable colloidal gels for seeding human umbilical cord mesenchymal stem cells
Authors: Wang Qun , Jamal Syed , Detamore Michael S. , Berkland Cory
Published: January 2011

The natural polymers chitosan and alginate represent an attractive material choice for biodegradable inplants. These were used as coating materials to make positively and negatively charged PLGA nanoparticles, respectively. After blending at total solids concentration >10% wt/vol, these oppositely charged nanoparticles yielded a cohesive colloidal gel. Electrostatic forces between oppositely charged nanoparticles produced a stable 3D porous network that may be extruded or molded to the desired shape. This high concentration colloidal system demonstrated shear‐thinning behavior due to the disruption of interparticle interactions. Once the external force was removed, the cohesive property of the colloidal gel was recovered. Scanning electron micrographs of dried colloidal networks revealed an organized, 3D microporous structure. Rheological studies were employed to probe the differences in plasticity and shear sensitivity of colloidal gels. Viability tests of hUCMSCs seeded on the colloidal gels also demonstrated the negligible cytotoxicity of the materials. All the results indicated the potential application of the biodegradable colloidal gels as an injectable scaffold in tissue engineering and drug release. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Adhesion and growth of dental pulp stem cells on enamel‐like fluorapatite surfaces
Authors: Liu J. , Jin T. C. , Chang S. , Czajka‐Jakubowska A. , Clarkson B. H.
Published: January 2011

To study how apatite crystal alignment of an enamel‐like substrate affects DPSC cellular adhesion and growth as a precursor to produce an in vitro enamel/dentin superstructure for future studies. The cells were subcultured in 10% FBS DMEM up to seven weeks on the two surfaces. Specimens were observed under SEM, counted, and analyzed using the human pathway‐focused matrix and adhesion PCR array. After three days, the cell number on ordered FA surface was significantly higher than on the disordered surface. Of the 84 focused pathway genes, a total of 20 genes were either up or down regulated in the cells on ordered FA surface compared to the disordered surface. More interestingly, of the cell‐matrix adhesion molecules, integrin alpha 7 and 8 (ITGA 7 and 8), integrin beta 3 and 4 (ITGB3 and 4), and the vitronectin receptor‐integrin alpha V (ITGAV) and the key adhesion protein‐fibronectin1 (FN1) were up‐regulated. In SEM, both surfaces showed good biocompatibility and supported long term growth of DPSC cells but with functional cell‐matrix interaction on the ordered FA surfaces. Significance: The enhanced cellular response of DPSC cell to the ordered FA crystal surface involves a set of delicately regulated matrix and adhesion molecules which could be manipulated by treating the cells with a dentin extract, to produce a dentin/enamel superstructure. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Influence of polysaccharide composition on the biocompatibility of pullulan/dextran‐based hydrogels
Authors: Abed Aicha , Assoul Nabila , Ba Maguette , Derkaoui Sidi Mohamed , Portes Patrick , Louedec Liliane , Flaud Patrice , Bataille Isabelle , Letourneur Didier , Meddahi‐Pellé Anne
Published: January 2011

The implantation of a biomaterial for tissue engineering requires the presence of a suitable scaffold on which the tissue repair and regeneration will take place. Polymers have been frequently used for that purpose because they show similar properties to that of the natural extracellular matrix. Scaffold properties and biocompatibility are modulated by the composition of the polymers used. In this work four polysaccharide‐based hydrogels (PSH) made of dextran and pullulan were synthesized. Theirin vitroproperties were determined and then testedin vivoin a rat model. As pullulan concentration increased in dextran hydrogels, the glass transition temperature and the maximum modulus decreased.In vitrodegradation studies for 30 days demonstrated no significant degradation of PSH except for 100% pullulan hydrogel.In vivotissue response evaluated 30 days after PSH subcutaneous implantation in rats indicated that all PSH were surrounded by a fibrous capsule. Adding pullulan to dextran induced an increased inflammatory reaction compared to PSH‐D (100% dextran) or PSH‐D75P25(75% dextran).Thisin vitroandin vivodata can be used in the design of hydrogels appropriate for tissue engineering applications © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Osteoprotegerin deficiency attenuates strontium-mediated inhibition of osteoclastogenesis and bone resorption
Authors: Peng Songlin , Liu X Sherry , Zhou Guangqian , Li Zhaoyang , Luk Keith DK , Guo X Edward , Lu W William
Published: January 2011

Strontium (Sr) exerts an anabolic and antiresorptive effect on bone, but the mechanism remains unknown. Osteoprotegerin (OPG) expressed by osteoblasts plays an important role in regulating bone homeostasis by inhibiting osteoclastogenesis and bone resorption. This study aims at evaluating the role of OPG in Sr-mediated inhibition of osteoclastogenesis and bone resorption. Six-week-old Opg knockout (KO) male mice and their wild-type (WT) littermates were treated orally with vehicle (Veh) or Sr compound (4 mmol/kg) daily for 8 weeks. Bone mass and microstructure in the lumbar spine (L4) and proximal tibia were analyzed with micro–computed tomography (µCT). Bone remodeling was evaluated with serum biochemical analysis and static and dynamic bone histomorphometry. Osteoclast differentiation potential and gene expression were analyzed in bone marrow cells. The findings demonstrate that Sr compound treatment results in greater bone volume and trabecular number than Veh treatment in WT mice. The anabolic response of trabecular bone to Sr treatment is attenuated in KO mice. Although Sr treatment significantly decreases in vitro osteoclastogenesis and bone resorption in WT mice, these effects are attenuated in KO mice. Furthermore, Sr treatment profoundly increases Opg gene expression in the tibias and OPG protein levels in the sera of WT mice. This study concludes that the inhibition of osteoclastogenesis and bone resorption is possibly associated with OPG upregulation by Sr treatment. © 2011 American Society for Bone and Mineral Research.
Why the IOM recommendations for vitamin D are deficient
Authors: Heaney Robert P , Holick Michael F
Published: January 2011

The IOM recommendations for vitamin D fail in a major way on logic, on science, and on effective public health guidance. Moreover, by failing to use a physiological referent, the IOM approach constitutes precisely the wrong model for development of nutritional policy. © 2011 American Society for Bone and Mineral Research.
Identification of homogeneous genetic architecture of multiple genetically correlated traits by block clustering of genome-wide associations
Authors: Gupta Mayetri , Cheung Ching-Lung , Hsu Yi-Hsiang , Demissie Serkalem , Cupples L Adrienne , Kiel Douglas P , Karasik David
Published: January 2011

Genome-wide association studies (GWAS) using high-density genotyping platforms offer an unbiased strategy to identify new candidate genes for osteoporosis. It is imperative to be able to clearly distinguish signal from noise by focusing on the best phenotype in a genetic study. We performed GWAS of multiple phenotypes associated with fractures [bone mineral density (BMD), bone quantitative ultrasound (QUS), bone geometry, and muscle mass] with approximately 433,000 single-nucleotide polymorphisms (SNPs) and created a database of resulting associations. We performed analysis of GWAS data from 23 phenotypes by a novel modification of a block clustering algorithm followed by gene-set enrichment analysis. A data matrix of standardized regression coefficients was partitioned along both axes—SNPs and phenotypes. Each partition represents a distinct cluster of SNPs that have similar effects over a particular set of phenotypes. Application of this method to our data shows several SNP-phenotype connections. We found a strong cluster of association coefficients of high magnitude for 10 traits (BMD at several skeletal sites, ultrasound measures, cross-sectional bone area, and section modulus of femoral neck and shaft). These clustered traits were highly genetically correlated. Gene-set enrichment analyses indicated the augmentation of genes that cluster with the 10 osteoporosis-related traits in pathways such as aldosterone signaling in epithelial cells, role of osteoblasts, osteoclasts, and chondrocytes in rheumatoid arthritis, and Parkinson signaling. In addition to several known candidate genes, we also identified PRKCH and SCNN1B as potential candidate genes for multiple bone traits. In conclusion, our mining of GWAS results revealed the similarity of association results between bone strength phenotypes that may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in identifying novel genes and pathways that underlie several correlated phenotypes, as well as in deciphering genetic and phenotypic modularity underlying osteoporosis risk. © 2011 American Society for Bone and Mineral Research.
The great escape: World War II, neo‐Freudianism, and the origins of U.S. psychocultural analysis
Authors: Gitre Edward J. K.
Published: January 2011

Psychocultural analysis stands as a signal accomplishment of the 1930s U.S. assimilation of European refugee‐intellectuals. Scholars in the U.S. had been moving toward a kind of psychocultural analysis well in advance of the Great Migration—the U.S. was not an intellectual vacuum or wasteland—nevertheless, it was through their interdisciplinary collaboration, fueled by the specter of war, that these international peers stimulated one of the most wide‐ranging, dynamic, and productive exchanges of ideas of the century. Through the lens of Erich Fromm'sEscape from Freedom, this article explores psychoculturalism's emergence in the interstices between cultures, nations, ideas, and disciplines—between Europeans and Americans, psychoanalysts and social scientists. © 2011 Wiley Periodicals, Inc.
The end of drugging children: Toward the genealogy of the ADHD subject
Authors: Comstock Edward J.
Published: January 2011

This genealogy of the ADHD subject will demonstrate that over the course of the twentieth century a new relation between power, knowledge, the body, and ethical practices of self‐formation emerged around the ADHD‐type in ways that are not captured by the received critical perspective. By examining the history of knowledge and practices surrounding the ADHD‐type, this work will argue that the deviant subject that was located relative to external institutional moral/juridical values or standards is replaced over the course of the century by a new intelligibility of rational self‐management. A further analysis of this emergent intelligibility attempts to advance the critical understanding of the increasingly prevalent ADHD phenomenon by showing how novel drug and brain imaging technologies work to link behaviors to identity, establishing new relations of power to the subject not captured by the received medicalization perspective. This work will be of interest to anybody interested in the relations among knowledge, drugs, power, and the ADHD subject. © 2011 Wiley Periodicals, Inc.
The Euclidean model of measurement in Fechner's psychophysics
Authors: Zudini Verena
Published: January 2011

Historians acknowledge Euclid and Fechner, respectively, as the founders of classical geometry and classical psychophysics. At all times, their ideas have been reference points and have shared the same destiny of being criticized, corrected, and even radically rejected, in their theoretical and methodological aspects and in their epistemological value. According to a model of measurement of magnitudes which goes back to Euclid, Fechner (1860) developed a theory for psychical magnitudes that opened a lively debate among numerous scholars. Fechner's attempt to apply the model proposed by Euclid to subjective sensation magnitudes—and the debate that followed—generated ideas and concepts that were destined to have rich developments in the psychological and (more generally) scientific field of the twentieth century and that still animate current psychophysics. © 2011 Wiley Periodicals, Inc.
Characteristic 20th and 21st century precipitation and temperature patterns and changes over the Greater Horn of Africa
Authors: Anyah Richard O. , Qiu Weini
Published: January 2011

Characteristic patterns and changes in precipitation and temperature over the Greater Horn of Africa during the 20th and 21st century are analysed based on a sample of Coupled Model Intercomparison Project version 3 (CMIP3) models output. Analysis of the 11 CMIP3 models indicates that the equatorial eastern Africa region (including the entire Greater Horn of Africa (GHA)) have been experiencing a significant increase in temperature beginning in the early 1980s, in both A1B and A2 scenarios. All the Atmosphere Ocean Global Circulation Models (AOGCMs) analysed represent the correct mean annual cycle of precipitation, but there is a fairly large spread among the models in capturing the dominant bimodal peaks. In particular, all the models tend to overestimate the peak of the October–November–December (OND) season, while at the same time the peak of the March–April–May (MAM) season tends to be centered on May in the models instead of April as observed. The projected changes and probability distribution of minimum (Tmin) and maximum (Tmax) temperatures over the GHA sub‐region based on PDFs constructed from daily values showed very diverse distributions for the present (1981–2000) and future (2046–2065; 2081–2100) periods. Whereas in the reference (1981–2000) the probability distribution functions (PDFs) constructed for both Tmin and Tmax, and during all the seasons had a near normal (but narrow) distribution, those of the future periods were quite diverse but generally very elongated, with significant shifts toward the positive tail. This generally implies that there is consensus among models and the ensemble mean about high likelihood of increase in extreme warmer Tmin and Tmax (more so Tmin) in the future over the GHA region. Our results also show significant increase in the number of days with Tmin and Tmax greater the 2 °C (above 1981–2000 average) by the middle as well as the end of 21st century in both the A1B and A1 scenarios. This is especially so during the June, July, and August (JJA) season where all the 92 days of the season indicate projected minimum temperature to increase by more than 2 °C above the 1981–2000 average by the end of 21st century in both scenarios. Copyright © 2011 Royal Meteorological Society
A spatio‐temporal structure‐based approach to drought characterisation
Authors: Lloyd‐Hughes Benjamin
Published: January 2011

Drought characterisation is an intrinsically spatio‐temporal problem. A limitation of previous approaches to characterisation is that they discard much of the spatio‐temporal information by reducing events to a lower‐order subspace. To address this, an explicit 3‐dimensional (longitude, latitude, time) structure‐based method is described in which drought events are defined by a spatially and temporarily coherent set of points displaying standardised precipitation below a given threshold. Geometric methods can then be used to measure similarity between individual drought structures. Groupings of these similarities provide an alternative to traditional methods for extracting recurrent space‐time signals from geophysical data. The explicit consideration of structure encourages the construction of summary statistics which relate to the event geometry. Example measures considered are the event volume, centroid, and aspect ratio. The utility of a 3‐dimensional approach is demonstrated by application to the analysis of European droughts (15°W to 35°E, and 35°N to 70°N) for the period 1901–2006. Large‐scale structure is found to be abundant with 75 events identified lasting for more than 3 months and spanning at least 0.5 × 106 km2. Near‐complete dissimilarity is seen between the individual drought structures, and little or no regularity is found in the time evolution of even the most spatially similar drought events. The spatial distribution of the event centroids and the time evolution of the geographic cross‐sectional areas strongly suggest that large area, sustained droughts result from the combination of multiple small area (∼106 km2) short duration (∼3 months) events. The small events are not found to occur independently in space. This leads to the hypothesis that local water feedbacks play an important role in the aggregation process. Copyright © 2011 Royal Meteorological Society
Statistical downscaling with Bayesian inference: Estimating global solar radiation from reanalysis and limited observed data
Authors: Iizumi Toshichika , Nishimori Motoki , Yokozawa Masayuki , Kotera Akihiko , Duy Khang Nguyen
Published: January 2011

Daily global solar radiation (SR) is one of essential weather inputs for crop, hydrological, and other simulation models to calculate biomass production and potential evapotranspiration. The availability of long‐term observed SR data is, however, limited, especially in developing countries. This hinders climate applications in various sectors in these countries. To overcome this difficulty, we here propose a method to infer the reasonable daily SR condition for past decades from global reanalysis and limited observed SR data. The method consists of the regression‐based statistical downscaling method and two empirical models for estimating the SR condition (i.e. the S‐model and the DTR/RH‐model). These empirical models were independent in terms of the variables explaining the SR condition. The regression models were trained on the basis of the SR conditions estimated by the S‐model and the DTR/RH‐model instead of the observed SR data. The Markov Chain Monte Carlo (MCMC) technique was applied to determine the parameter values of these models that guide the models to provide SR conditions that are close in value to each other at both the site and domain‐mean scales. After that, we computed the SR condition over the 30 years from 1978 through 2007 at 17 sites in the Vietnam Mekong Delta area using the determined parameter values. The inferred SR condition was close in value to the corresponding observations available from the literature. This suggests that the proposed method yielded a reasonable inference of the SR condition at the sites despite the limited availability of observed SR data. The provided estimates of the daily SR condition over the past 30 years are useful for climate applications in agricultural, hydrological, and other sectors in this area. Copyright © 2011 Royal Meteorological Society
Statistical analysis of the relationship between summer monsoon precipitation extremes and foodgrain yield over India
Authors: Revadekar J. V. , Preethi B.
Published: January 2011

The Indian economy largely depends on agriculture which is highly influenced by the spatio‐temporal variability of precipitation. Kharif and rabi are the two main crop‐growing seasons which require major proportion of rainfall. Increase in heavy precipitation events, however, can have adverse effects on the crops. This study, therefore, is mainly focused on understanding the variation of extremes in precipitation during summer monsoon season and its impact on kharif foodgrain yield over India. For this, several objectively defined indices of observed precipitation extremes, in terms of frequencies and intensities, have been computed for the period 1951–2003 using daily gridded data of 1° latitude × 1° longitude resolution. Efforts have also been made to prepare the climatology of extremes in precipitation (1961–1990) to determine their basic characteristics over the Indian region.

Correlation analysis reveals that a large part of the country exhibits positive relationship between kharif foodgrain yield and the indices of extreme precipitation, significant at 5% level. Correlations with the indices of frequencies defined as seasonal count of days when rainfall exceeds 85th, 75th, and 65th percentiles (and 30, 20, and 10 mm) show that spatial extent and strength of the positive relationship decreases with increase in threshold values. This indicates that very heavy daily rainfall is less useful than the moderate daily rainfall. Strong negative relationship between the yield and indices of extreme precipitation observed over heavy precipitation areas of northeastern parts of the country indicate that very heavy daily rainfall have an adverse effect on crop. The study also points out that increase in heavy rainfall activities during July are favourable for the yield, but correlations become weak and statistically insignificant during the month of August. Individual crops show similar results as that obtained from aggregate kharif foodgrain, however, magnitude of the correlations varies from crop to crop. Copyright © 2011 Royal Meteorological Society
Changing patterns of heavy rainfall in upland areas: a case study from northern England
Authors: Burt T. P. , Ferranti E. J. S.
Published: January 2011

There has recently been a widespread shift in the pattern of UK rainfall towards more heavy falls of rain in winter and fewer in summer. Here, this change is examined in the context of orographic enhancement for a transect of rain gauges running across northern England from coast to coast and including both the Lake District and Pennine uplands. Gauges have been selected where very long records of daily rainfall exist; where data are missing, these have been infilled using data from nearby gauges. The very long records for Armagh and Durham are also included to provide additional context in time and space. For the upland gauges, the increase in total winter rainfall in recent decades and the simultaneous decrease in total summer rainfall are reflected in the number of heavy falls of rain, as defined using two threshold indices. The 1990s saw record numbers of heavy falls in winter and an almost complete absence of heavy summer rainfall in the uplands, in marked contrast to lowland gauges. Comparison of the rainfall record with the Lamb Weather Catalogue suggests that increased winter rainfall is related to an increase in the rainfall provided by westerly weather types. Decreased summer rainfall is related to a reduction in rainfall associated with cyclonic weather types. The results presented here underline the value of long‐term monitoring and the maintenance of records from key historic sites. Copyright © 2010 Royal Meteorological Society
Warm season streamflow variability in the Korean Han River Basin: Links with atmospheric teleconnections
Authors: Kim Jong‐Suk , Jain Shaleen , Yoon Sun‐Kwon
Published: January 2011

Warm season (June–September) hydroclimatology is a key determinant of freshwater supplies in the Korean Peninsula. In the Han River Basin, nearly three‐fourths of annual discharge occurs during the warm season. Given the increased reliance on water supplies for numerous human and ecosystem functions, an integrated view of water supplies within the context of the regional hydroclimate will aid efforts to achieve water resources sustainability. To that end, this diagnostic study investigates several key aspects of the Han River hydrologic regime: (i) the warm season hydroclimatology; (ii) understanding the relative contribution of typhoon and non‐typhoon precipitation events to warm season streamflow; and (iii) relationships with large‐scale atmospheric teleconnections patterns and the implied seasonal predictability. Statistical analysis of modelled unimpaired streamflow indicates that the East Atlantic‐Western Russia (EA–WR) teleconnection pattern modulates the Han River streamflow during the warm season. Furthermore, a linear modelling approach using the EA–WR and East Atlantic (EA) teleconnection indices offers a useful empirical framework for understanding the systematic shifts in streamflow probability distributions. Based on these results, potential use of this information for multi‐objective water resources management, environmental flow prescriptions, proactive use of seasonal forecasts, and some open questions are briefly discussed. Copyright © 2010 Royal Meteorological Society