bluuebunny/crossref_metadata_2025 huggingface dataset:
Looking for a Paradigm for the Reactivity of Phenonium Ions
Authors: Protti Stefano , Dondi Daniele , Mella Mariella , Fagnoni Maurizio , Albini Angelo
Published: April 2011

The addition of a photogenerated phenyl cation to an alkene offers an entry, under mild conditions, to the phenethyl cation/phenonium ion system in organic solvents. Taking advantage of this, a product study has been carried out in parallel with a computational characterization of the intermediates. Thus, 4‐methoxy‐ and 4‐dimethyaminophenyl cations have been photogenerated from the corresponding chlorobenzenes in the presence of mono‐ to tetrasubstituted olefins in polar or protic media. The chemistry that occurs has been correlated with the degree of anchimeric assistance offered by the phenyl group, as predicted by calculations. Two limiting situations arise, the first one when starting from mono‐ or 1,2‐disubstituted alkenes. In these cases, calculations evidence a large stabilization of the intermediate (phenonium character), particularly with electron‐donating substituents on the aromatic ring, and the main products in acetonitrile are phenethyl chlorides. Variation of the ion‐stabilizing solvent such as trifluoroethanol (TFE) leads to alkyl and hydride migration before chloride addition. In contrast, with less electron‐rich aromatics and highly substituted alkenes the stabilization of the intermediate is modest and the typical reaction is deprotonation to yield an allylbenzene or, in TFE, the formation of a phenethyl ether. In between these two extremes, there are intermediate cases, more easily directed by a change in the conditions. These generalizations and the mildness of the method help to assess the synthetic potential of this reaction.
A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C
Authors: Dienstag Jules L. , Ghany Marc G. , Morgan Timothy R. , Di Bisceglie Adrian M. , Bonkovsky Herbert L. , Kim Hae-Young , Seeff Leonard B. , Szabo Gyongyi , Wright Elizabeth C. , Sterling Richard K. , Everson Gregory T. , Lindsay Karen L. , Lee William M. , Lok Anna S. , Morishima Chihiro , Stoddard Anne M. , Everhart James E.
Published: April 2011

The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. Six hundred seventy-nine clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) (

P

< 0.0001). Child-Turcotte-Pugh (CTP) score ≥7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score ≥7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow-up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis.

Conclusion:

Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7. (Hepatology 2011)
Resistance mutations define specific antiviral effects for inhibitors of the hepatitis C virus p7 ion channel
Authors: Foster Toshana L. , Verow Mark , Wozniak Ann L. , Bentham Matthew J. , Thompson Joseph , Atkins Elizabeth , Weinman Steven A. , Fishwick Colin , Foster Richard , Harris Mark , Griffin Stephen
Published: April 2011

Abstract:

The hepatitis C virus (HCV) p7 ion channel plays a critical role during infectious virus production and represents an important new therapeutic target. Its activity is blocked by structurally distinct classes of small molecules, with sensitivity varying between isolate p7 sequences. Although this is indicative of specific protein–drug interactions, a lack of high-resolution structural information has precluded the identification of inhibitor binding sites, and their modes of action remain undefined. Furthermore, a lack of clinical efficacy for existing p7 inhibitors has cast doubt over their specific antiviral effects. We identified specific resistance mutations that define the mode of action for two classes of p7 inhibitor: adamantanes and alkylated imino sugars (IS). Adamantane resistance was mediated by an L20F mutation, which has been documented in clinical trials. Molecular modeling revealed that L20 resided within a membrane-exposed binding pocket, where drug binding prevented low pH-mediated channel opening. The peripheral binding pocket was further validated by a panel of adamantane derivatives as well as a bespoke molecule designed to bind the region with high affinity. By contrast, an F25A polymorphism found in genotype 3a HCV conferred IS resistance and confirmed that these compounds intercalate between p7 protomers, preventing channel oligomerization. Neither resistance mutation significantly reduced viral fitness in culture, consistent with a low genetic barrier to resistance occurring in vivo. Furthermore, no cross-resistance was observed for the mutant phenotypes, and the two inhibitor classes showed additive effects against wild-type HCV. Conclusion: These observations support the notion that p7 inhibitor combinations could be a useful addition to future HCV-specific therapies. (HEPATOLOGY 2011;)
Block of proliferation 1 (BOP1) plays an oncogenic role in hepatocellular carcinoma by promoting epithelial-to-mesenchymal transition
Authors: Chung Kit-Ying , Cheng Ibis K.-C. , Ching Arthur K.-K. , Chu Jian-Hong , Lai Paul B.-S. , Wong Nathalie
Published: April 2011

Abstract:

Genomic amplification of regional chromosome 8q24 is a common event in human cancers. In hepatocellular carcinoma (HCC), a highly aggressive malignancy that is rapidly fatal, recurrent 8q24 gains can be detected in >50% of cases. In this study, attempts to resolve the 8q24 region by way of array comparative genomic hybridization for affected genes in HCC revealed distinctive gains of block of proliferation 1 (BOP1). Gene expression evaluation in an independent cohort of primary HCC (n = 65) revealed frequent BOP1 up-regulation in tumors compared with adjacent nontumoral liver (84.6%; P < 0.0001). Significant associations could also be drawn between increased expressions of BOP1 and advance HCC staging (P = 0.004), microvascular invasion (P = 0.006), and shorter disease-free survival of patients (P = 0.02). Examination of expression of C-MYC, a well-known oncogene located in proximity to BOP1, in the same series of primary HCC cases did not suggest strong clinicopathologic associations. Functional investigations by small interfering RNA–mediated suppression of BOP1 in HCC cell lines indicated significant inhibition on cell invasion (P < 0.005) and migration (P < 0.05). Overexpression of BOP1 in the immortalized hepatocyte cell line L02 showed increase cellular invasiveness and cell migratory rate (P < 0.0001). In both gene knockdown and ectopic expression assays, BOP1 did not exert an effect on cell viability and proliferation. Evident regression of the epithelial-mesenchymal transition (EMT) phenotype was readily identified in BOP1 knockdown cells, whereas up-regulation of epithelial markers (E-cadherin, cytokeratin 18, and γ-catenin) and down-regulation of mesenchymal markers (fibronectin and vimentin) were seen. A corresponding augmentation of EMT was indicated from the ectopic expression of BOP1 in L02. In addition, BOP1 could stimulate actin stress fiber assembly and RhoA activation. Conclusion: Our findings underline an important role for BOP1 in HCC invasiveness and metastasis potentials through inducing EMT and promoting actin cytoskeleton remodeling. (HEPATOLOGY 2011;)
Mitochondria-targeted ubiquinone (MitoQ) decreases ethanol-dependent micro and macro hepatosteatosis
Authors: Chacko Balu K. , Srivastava Anup , Johnson Michelle S. , Benavides Gloria A. , Chang Mi Jung , Ye Yaozu , Jhala Nirag , Murphy Michael P. , Kalyanaraman Balaraman , Darley-Usmar Victor M.
Published: April 2011

Abstract:

Chronic alcohol-induced liver disease results in inflammation, steatosis, and increased oxidative and nitrosative damage to the mitochondrion. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate the steatosis associated with alcoholic liver disease. To test this we investigated the effects of mitochondria-targeted ubiquinone (MitoQ) (5 and 25 mg/kg/day for 4 weeks) in male Sprague-Dawley rats consuming ethanol using the Lieber-DeCarli diet with pair-fed controls. Hepatic steatosis, 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), hypoxia inducible factor α (HIF1α), and the activity of the mitochondrial respiratory chain complexes were assessed. As reported previously, ethanol consumption resulted in hepatocyte ballooning, increased lipid accumulation in the form of micro and macrovesicular steatosis, and induction of cytochrome P450 2E1 (CYP2E1). MitoQ had a minor effect on the ethanol-dependent decrease in mitochondrial respiratory chain proteins and their activities; however, it did decrease hepatic steatosis in ethanol-consuming animals and prevented the ethanol-induced formation of 3-NT and 4-HNE. Interestingly, MitoQ completely blocked the increase in HIF1α in all ethanol-fed groups, which has previously been demonstrated in cell culture models and shown to be essential in ethanol-dependent hepatosteatosis. Conclusion: These results demonstrate the antioxidant capacity of MitoQ in alleviating alcohol-associated mitochondrial reactive oxygen species (ROS) and several downstream effects of ROS/RNS (reactive nitrogen species) production such as inhibiting protein nitration and protein aldehyde formation and specifically ROS-dependent HIF1α stabilization. (HEPATOLOGY 2011;)
Ubiquitination is associated with lysosomal degradation of cell surface-resident ATP-binding cassette transporter A1 (ABCA1) through the endosomal sorting complex required for transport (ESCRT) pathway
Authors: Mizuno Tadahaya , Hayashi Hisamitsu , Naoi Sotaro , Sugiyama Yuichi
Published: April 2011

ATP-binding cassette transporter A1 (ABCA1) plays an essential role in the biogenesis of high-density lipoprotein in liver and in the prevention of foam cell formation in macrophages by mediating the efflux of cellular cholesterol and phospholipids to apolipoprotein A-I (apoA-I). Our current study investigated the mechanism of degradation of cell surface-resident ABCA1, focusing on ubiquitination. A coimmunoprecipitation study indicated the presence of ubiquitinated ABCA1 in the plasma membrane of the human hepatoma cell line, HuH-7, of cells from mouse liver, and of macrophages differentiated from the human acute monocytic leukemia cell line, THP-1 (THP-1 macrophages). In HuH-7 cells, degradation of cell surface-resident ABCA1 was inhibited by the overexpression of a dominant-negative form of ubiquitin. Moreover, the disruption of the endosomal sorting complex required for transport (ESCRT) pathway, a dominant mechanism for ubiquitination-mediated lysosomal degradation, by the knockdown of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), significantly delayed the degradation of cell surface-resident ABCA1. This was accompanied by an increase in ABCA1 expression as well as in apoA-I-mediated [3H]-cholesterol efflux function. The effect of HRS knockdown was also observed after calpain inhibitor treatment, which is reported to retard ABCA1 degradation. The induction of ABCA1 by HRS knockdown was confirmed in THP-1 macrophages.

Conclusion

: Together with the fact that lysosomal inhibitor treatments increased ABCA1 expression in HuH-7 and THP-1 macrophages, these results suggest that ubiquitination mediates the lysosomal degradation of cell surface-resident ABCA1 through the ESCRT pathway, and thereby controls the expression and cholesterol efflux function of ABCA1. This mechanism seems to mediate ABCA1 degradation independently of the calpain-involving pathway. The modulation of ABCA1 ubiquitination could thus be a potential new therapeutic target for antiatherogenic drugs. (Hepatology 2011;)
Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by allographic transplantation of adult subventricular zone‐derived neural stem cells
Authors: Turgeman Gadi , Pinkas Adi , Slotkin Theodore A. , Tfilin Matanel , Langford Rachel , Yanai Joseph
Published: April 2011

Neurobehavioral teratogenicity can be reversed with transplantation of neural stem cells. However, the usefulness of this therapy would be greatly enhanced by employing adult stem cells. In pursuit of this this goal, we developed a model that uses subventricular zone (SVZ) cells. HS/Ibg mice were exposed prenatally to chlorpyrifos on gestational days 9–18 (3 mg/kg/day, SC) in order to induce deficits in their performance in the Morris water maze test. Both the control and the exposed offspring were transplanted with SVZ cells (or vehicle) on postnatal day 35; this actually represents an allogenic transplantation, because the HS/Ibg strain is a heterogeneous stock. The transplanted cells were later observed in the host brain by DiI tracing, and their initial differentiation to cholinergic neurons and astrocytes was ascertained. On postnatal day 80, animals that had been exposed prenatally to chlorpyrifos displayed impaired Morris water maze performance, requiring more time to reach the platform. Transplantation of adult SVZ‐derived neural stem cells (NSC) reversed the deficits. Applying autologous transplantation provides an important demonstration that the methodological obstacles of immunological rejection and the ethical concerns related to using embryonic stem cells may be successfully bypassed in developing stem cell therapies for neurodevelopmental disorders. © 2011 Wiley‐Liss, Inc.
Acute and prolonged effect of static stretching on the passive stiffness of the human gastrocnemius muscle tendon unit in vivo
Authors: Nakamura Masatoshi , Ikezoe Tome , Takeno Yohei , Ichihashi Noriaki
Published: April 2011

Static stretching (SS) is commonly used to prevent or improve limited joint mobility. However, it is unclear whether the components of the muscle‐tendon unit (MTU) are affected by 5 min of SS. This study investigated the acute and prolonged effect of SS on the mechanical properties of the MTU. The subjects comprised 15 male participants (mean age: 21.5 ± 1.6 years). MTU stiffness, muscle stiffness, tendon stiffness, and fascicle length of the gastrocnemius muscle were measured by ultrasonography and a dynamometer while the ankle was passively dorsiflexed. The measurements were performed prior to the 5 min of SS, immediately after the SS, and 10 min after the SS. MTU stiffness and muscle stiffness significantly decreased at both immediately and 10 min after SS, whereas no significant differences in MTU stiffness and muscle stiffness were found between immediately and 10 min after SS. Tendon stiffness immediately after SS was significantly higher than prior to and 10 min after SS. No significant change in the fascicle length occurred after SS. These results suggest that 5 min of SS affects MTU and muscle stiffness both immediately and 10 min after SS, which may be associated with a change in the connective tissue properties. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1759–1763, 2011
Location and agricultural practices influence spring use of harvested cornfields by cranes and geese in Nebraska
Authors: Anteau Michael J. , Sherfy Mark H. , Bishop Andrew A.
Published: April 2011

Millions of ducks, geese, and sandhill cranes (Grus canadensis; hereafter cranes) stop in the Central Platte River Valley (CPRV) of Nebraska to store nutrients for migration and reproduction by consuming corn remaining in fields after harvest. We examined factors that influence use of cornfields by cranes and geese (all mid‐continent species combined; e.g., Anser, Chen, and Branta spp.) because it is a key step to efficient conservation planning aimed at ensuring that adequate food resources are available to migratory birds stopping in the CPRV. Distance to night‐time roost site, segment of the CPRV (west to east), and agricultural practices (post‐harvest treatment of cornfields: idle, grazed, mulched, mulched and grazed, and tilled) were the most important and influential variables in our models for geese and cranes. Probability of cornfield use by geese and cranes decreased with increasing distance from the closest potential roosting site. The use of cornfields by geese increased with the density of corn present there during the early migration period, but field use by cranes appeared not to be influenced by early migration corn density. However, probability of cornfield use by cranes did increase with the amount of wet grassland habitat within 4.8 km of the field. Geese were most likely to use fields that were tilled and least likely to use fields that were mulched and grazed. Cranes were most likely to use fields that were mulched and least likely to use fields that were tilled, but grazing appeared not to influence the likelihood of field use by cranes. Geese were more likely to use cornfields in western segments of the CPRV, but cranes were more likely to use cornfields in eastern segments. Our data suggest that managers could favor crane use of fields and reduce direct competition with geese by reducing fall and spring tilling and increasing mulching. Moreover, crane conservation efforts would be most beneficial if they were focused in the eastern portions of the CPRV and in fields as close as possible to both known roosting and large amounts of wet grassland habitats. © 2011 The Wildlife Society.
Capturing clapper rails using thermal imaging technology
Authors: Mills William E. , Harrigal Dean E. , Owen Sheldon F. , Dukes William F. , Barrineau Daniel A. , Wiggers Ernie P.
Published: April 2011

Capturing sufficient numbers of marsh birds for telemetry studies is difficult due to the secretive nature and inaccessible habitat of the birds. We experimented with thermal imaging technology to locate clapper rails and subsequently capture them from an airboat in South Carolina tidal marshes. This method produced a capture rate of up to 19.2 rails/hr, which exceeded other capture rates in the literature. We believe this technique will improve capture efficiency for clapper rails, and potentially other secretive marsh birds, enhancing opportunities for studying these important species. © 2011 The Wildlife Society.
Genetic mark–recapture population estimation in black bears and issues of scale
Authors: Coster Stephanie S. , Kovach Adrienne I. , Pekins Peter J. , Cooper Andrew B. , Timmins Andrew
Published: April 2011

Abundance estimates for black bears (Ursus americanus) are important for effective management. Recently, DNA technology has resulted in widespread use of noninvasive, genetic capture–mark–recapture (CMR) approaches to estimate populations. Few studies have compared the genetic CMR methods to other estimation methods. We used genetic CMR to estimate the bear population at 2 study sites in northern New Hampshire (Pittsburg and Milan) in 2 consecutive years. We compared these estimates to those derived from traditional methods used by the New Hampshire Fish and Game Department (NHFG) using hunter harvest and mortality data. Density estimates produced with genetic CMR methods were similar both years and were comparable to those derived from traditional methods. In 2006, the estimated number of bears in Pittsburg was 79 (95% CI = 60–98) corresponding to a density of 15–24 (95% CI) bears/100 km2; the 2007 estimate was 83 (95% CI = 67–99; density = 16–24 bears/100 km2). In 2006, the estimated number of bears in Milan was 95 (95% CI = 74–117; density = 16–25 bears/100 km2); the 2007 estimate was 96 (95% CI = 77–114; density = 17–25 bears/100 km2). We found that genetic CMR methods were able to identify demographic variation at a local scale, including a strongly skewed sex ratio (2 M:1 F) in the Milan population. Genetic CMR is a useful tool for wildlife managers to monitor populations of local concern, where abundance or demographic characteristics may deviate from regional estimates. Future monitoring of the Milan population with genetic CMR is recommended to determine if the sex ratio bias continues, possibly warranting a change in local harvest regimes. © 2011 The Wildlife Society.
Polysulfone/Metal Nanocomposites by Simultaneous Photoinduced Crosslinking and Redox Reaction
Authors: Sangermano Marco , Roppolo Ignazio , Camara V. H. Alves , Dizman Cemil , Ates Sahin , Torun Lokman , Yagci Yusuf
Published: April 2011

A diacrylate polysulfone oligomer is synthesized and used as the acrylic oligomer for the in situ synthesis of noble metal/PSU nanocomposites through UV‐induced simultaneous radical polymerization of acrylic functionalities and NP formation by reduction of their precursors. Thus, silver or gold NPs are formed in situ during polymer network formation. FESEM analysis of the morphology of the cured systems demonstrates that the nanoparticles of the noble metals are homogeneously distributed in the network without macroscopic agglomeration.

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Nerve growth factor in bladder dysfunction: Contributing factor, biomarker, and therapeutic target
Authors: Ochodnický Peter , Cruz Célia D. , Yoshimura Naoki , Michel Martin C.
Published: April 2011

In the last two decades, nerve growth factor (NGF), initially described as a prototypical trophic factor in the development of sensory and sympathetic innervation, has emerged as a complex regulator of neural plasticity along the micturition pathways. This review aims to summarize the current experimental and clinical evidence for a role of NGF in urinary bladder. Experimental administration of NGF elicits the states of increased sensation, urgency, and bladder hyperreflexia, resembling pathologies associated with bladder overactivity and inflammatory pain, such as overactive bladder syndrome (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS). There is strong experimental evidence, including the effective therapeutic targeting, on the direct causal role of NGF in rodent models of bladder outlet obstruction, spinal cord injury, diabetic bladder dysfunction, and interstitial inflammation. In humans, there are attempts to employ urinary NGF levels as a diagnostic marker in various forms of OAB and IC/PBS. In near future, use of novel experimental tools, such as urothelium‐specific NGF transgenic mice or more specific low‐molecular weight NGF receptor modulators, may provide better understanding of several unresolved issues in NGF‐related bladder dysfunction. Moreover, successful experimental therapeutic approaches, such as NGF sequestering proteins or modified NGF antibodies, await the translation to the clinical treatment of bladder disorders. Neurourol. Urodynam. 30:1227–1241, 2011. © 2011 Wiley‐Liss, Inc.
Clopidogrel protects from cell apoptosis and oxidative damage in a mouse model of renal ischaemia–reperfusion injury
Authors: Hu Honglin , Batteux Frédéric , Chéreau Christiane , Kavian Niloufar , Marut Wioleta , Gobeaux Camille , Borderie Didier , Dinh‐Xuan Anh Tuan , Weill Bernard , Nicco Carole
Published: April 2011

Renal ischaemia‐reperfusion injury (IRI) is consecutive to tissue oxidative damage and cell apoptosis that lead to acute renal failure (ARF) in renal allografts. The aim of this study was to investigate the beneficial effects of a pretreatment by clopidogrel on renal IRI in mice. IRI was induced by bilateral renal ischaemia for 45 min followed by reperfusion. Sixty‐two healthy male BALB/c mice were randomly assigned to one of the following groups: PBS + ischaemia‐reperfusion (IR); clopidogrel + IR; PBS + sham IR; clopidogrel + sham IR. Clopidogrel (25 mg/kg) or PBS was administered per os to the animals via a gastric cannula 24 h before operation. All mice were given a single dose of clopidogrel or PBS. Renal function histological damage, renal cell apoptosis, renal antioxidant activities, and CD41 expression were determined 24 h after reperfusion. The survival rates were evaluated over 7 days. Animals pretreated with clopidogrel had lower plasma levels of blood urea nitrogen (BUN) and creatinine, lower histopathological scores, and improved survival rates following IR. Renal cell apoptosis induced by IR was decreased in kidneys of mice pretreated by clopidogrel, with an increase in Bcl‐2 and Bcl‐xL expression and a decrease in caspase‐3, caspase‐8, and Bax expression. Renal reduced glutathione, superoxide dismutase, and catalase activities were unmodified by the pretreatment with clopidogrel. However, clopidogrel resulted in an increased total antioxidant capacity of the kidney. Furthermore, pretreatment by clopidogrel decreased the number of CD41‐positive cells. Thus, clopidogrel exerts protective effects on renal IRI in mice by abrogating renal cell apoptosis as a consequence of improved renal antioxidant capacity and could be tried as a novel therapeutic tool in renal IRI. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Expression of hypoxia‐associated proteins in sporadic medullary thyroid cancer is associated with desmoplastic stroma reaction and lymph node metastasis and may indicate somatic mutations in the VHL gene
Authors: Koperek Oskar , Bergner Oliver , Pichlhöfer Bettina , Oberndorfer Felicitas , Hainfellner Johannes A , Kaserer Klaus , Horvat Reinhard , Harris Adrian L , Niederle Bruno , Birner Peter
Published: April 2011

Medullary thyroid carcinomas (MTCs) are mostly aggressive but slowly growing malignant tumours that metastasize early to loco‐regional lymph nodes. Desmoplastic stroma reaction is a strong risk factor associated with lymph node metastases. We evaluated immunohistochemically the expression of two hypoxia‐associated proteins, carbonic anhydrase IX (CAIX) and hypoxia‐induced factor 1α (HIF1α), and ki‐67, intercellular matrix adhesion molecule E‐cadherin and the stroma remodelling marker tenascin C in a series of 100 sporadic MTCs and corresponding lymph node metastases, if present. Moderate to strong expression of CAIX was seen in 53 cases, and of HIF1α in 51 cases, showing a strong correlation (p < 0.001; Spearman's coefficient of correlation, 0.59). Expression correlated with the degree of desmoplasia ($p_{\rm{CAIX}} = 0.001$ and $p_{{\rm{HIF1}}\alpha} = 0.001$), with tenascin C expression ($p_{\rm{CAIX}} = 0.001$, $p_{{\rm{HIF1}}\alpha} = 0.038$), with the ki‐67 proliferation index ($p_{\rm{CAIX}} = 0.001$, p$_{{\rm{HIF1}}\alpha} = 0.001$) and with the presence of lymph node metastases ($p_{\rm{CAIX}} < 0.001$ and p$_{{\rm{HIF1}}\alpha} = 0.007$). The absence of membranous E‐cadherin staining was significantly associated with the grade of desmoplasia, tenascin expression and lymph node metastases (p≤0.05) but not with ki67 proliferation index or expression of hypoxia‐associated factors. Expression of hypoxia‐associated proteins was in most cases identical between primary tumours and lymph node metastases. Two cases showed strong uniform expression of CAIX and HIF1α in the primary tumour as well as in the lymph node metastases, and sequencing revealed mutations in the coding regions of the Von‐Hippel–Lindau gene (VHL). Our findings suggest that despite of the fact that MTCs have only slowly growth, tumour hypoxia plays an important role in the development of loco‐regional metastases. Since traditional cytotoxic chemotherapy has only little effect on MTCs, targeting hypoxia‐associated and ‐regulated proteins might be of benefit for patients. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Nitroxide‐mediated polymerization of 1,3‐butadiene in the presence of diphenylamine with hydrogen peroxide as initiator
Authors: Haghighat Hassan Rezaei , Barikani Mehdi , Morshedian Jalil
Published: April 2011

Living behavior of a nitroxide‐mediated polymerization of 1,3‐butadiene in the presence of diphenyl nitroxide (DPN) as counter radical and hydrogen peroxide (H2O2) as initiator has been studied to elucidate the bimodal molar mass distribution of the product by four approaches such as hydrolyzation of the oligomeric product, peak separation technique, which defines the oligobutadiene molar mass dependency in relation to α as a ratio of [nitroxide] to [H2O2], variation of hydroxyl value with respect to α, and para‐substituted DPN. It is demonstrated that the synthesized DPN shows efficient control of the polymerization of 1,3‐butadiene, but because of the formation of difunctional nitroxide during the oxidation process of aromatic diphenylamine, a bimodal distribution in the final product is observed. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Cu powder‐catalyzed single electron transfer‐living radical polymerization of acrylonitrile
Authors: Ma Jing , Chen Hou , Zhang Min , Chen Lingfang
Published: April 2011

Single electron transfer‐living radical polymerization (SET‐LRP) has been used as a new technique for the synthesis of polyacrylonitrile (PAN) catalyzed by Cu(0) powder with carbon tetrachloride (CCl4) as the initiator and hexamethylenetetramine (HMTA) as the ligand in N,N‐dimethylformamide (DMF) or mixed solvent. Well‐controlled polymerization has been achieved as evidenced by a linear increase of molecular weight with respect to monomer conversion as well as narrow molecular weight distribution. Kinetics data of the polymerizations at both ambient temperature and elevated temperature demonstrate living/controlled feature. An increase in the concentration of ligand yields a higher monomer conversion within the same time frame and almost no polymerization occurs in the absence of ligand due to the poor disproportionation reaction of Cu(I). The reaction rate exhibits an increase with the increase of the amount of catalyst Cu(0)/HMTA. Better control on the molecular weight distribution has been produced with the addition of CuCl2. In the presence of more polar solvent water, it is observed that there is a rapid increase in the polymerization rate. The effect of initiator on the polymerization is also preliminarily investigated. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Similarities between the discovery and regulation of pharmaceuticals and pesticides: in support of a better understanding of the risks and benefits of each
Authors: Swanton Clarence J , Mashhadi Hamid R , Solomon Keith R , Afifi Maha M , Duke Stephen O
Published: April 2011

An argument is presented by which the role of pharmaceuticals and pesticides can both be viewed in terms of contributing to human health. Comparisons are made in terms of discovery and development, regulatory policies and environmental and human impacts. Both technologies target particular biological functions, and in many cases they target similar molecular sites of action. Pharmaceuticals and pesticides undergo a similar registration process; however, both can enter the environment where they can have adverse effects on non‐target organisms and, if misused, will have detrimental effects on human health or the environment. It is suggested that the risks associated with the two technologies are similar. The rejection of pesticides by the general public is based primarily on personal value systems and the uncertainty of risk management. It is concluded that plant and animal health are vital to maintaining human health, and that pesticides used in food production are, as with pharmaceuticals, a vital tool used to maintain human health. Copyright © 2011 Society of Chemical Industry
Insecticidal compounds from the essential oil of Chinese medicinal herb Atractylodes chinensis
Authors: Chu Sha Sha , Jiang Guo Hua , Liu Zhi Long
Published: April 2011

BACKGROUND: In a screening programme for new agrochemicals from Chinese medicinal herbs, the essential oil of Atractylodes chinensis (DC.) Koidz was found to possess strong insecticidal activity against the common vinegar fly, Drosophila melanogaster L. The essential oil was extracted via hydrodistillation, and its constituents were determined by GC‐MS analysis.

RESULTS: The main components of A. chinensis essential oil were β‐eudesmol (21.05%), β‐selinene (11.75%), γ‐elemene (7.16%) and isopetasam (5.36%). Bioactivity‐directed chromatographic separation on repeated silica gel columns led to the isolation of five compounds, namely atractylon, α‐elemol, β‐eudesmol, hinesol and β‐selinene. β‐Selinene, α‐elemol and hinesol showed pronounced contact toxicity against D. melanogaster adults, with LD50 values of 0.55, 0.65 and 0.71 µg adult−1 respectively. Atractylon and β‐eudesmol were also toxic to the fruit flies (LD50 = 1.63 and 2.65 µg adult−1 respectively), while the crude oil had an LD50 value of 2.44 µg adult−1.

CONCLUSION: The findings suggested that the essential oil of Atractylodes chinensis and its active constituents may be explored as natural potential insecticides. Copyright © 2011 Society of Chemical Industry
Ab initio investigation of magnetism in Cr‐doped diamond‐like carbon
Authors: Komelj Matej
Published: April 2011

We constructed supercells for modeling diamond‐like carbon (DLC) structures and doped them with Cr atoms in order to investigate the presence of magnetism, which was recently observed experimentally. The total energies for the magnetic and non‐magnetic (NM) states were calculated ab initio within the framework of the density‐functional theory (DFT). We found that an external strain is required for the ferromagnetic state to be energetically the most favorable.
Recombination dynamics of localized excitons in AlxGa1‐xN (0.37<x<0.81) ternary alloys
Authors: Murotani Hideaki , Kittaka Ryo , Kurai Satoshi , Yamada Yoichi , Miyake Hideto , Hiramatsu Kazumasa
Published: April 2011

Recombination dynamics of localized excitons in AlxGa1‐xN ternary alloy epitaxial layers (0.37<x <0.81) has been studied by means of time‐resolved photoluminescence (PL) spectroscopy. An emission energy dependence of the PL lifetime was analyzed to estimate the degree of localization (E0) and the radiative recombination lifetime of localized excitons (τrad). The E0 increased with increasing Al composition from x =0.37 to 0.61, and decreased with further increasing Al composition. The value of τrad increased slightly from 903 to 958 ps for x =0.37 to 0.61, and then the rapid decrease occurred at the Al compositions above 0.61 (τrad=484 ps for x =0.81). The rapid decrease was well explained by considering the increase in the oscillator strength of excitons with increasing Al composition in addition to the decrease in the effect of exciton localization. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Measurement of the tuneable absorption in GaN‐based multi‐section laser diodes
Authors: Scheibenzuber W. , Schwarz U. , Sulmoni L. , Carlin J.‐F. , Castiglia A. , Grandjean N.
Published: April 2011

We present an experimental technique to measure the absorption spectra of the absorber section of GaNbased multi‐section laser diodes using optical gain spectroscopy. We find that the absorption of the examined laser diodes decreases with increasing negative bias, which results from a reduction of the internal field in the quantum wells by the external voltage. A maximum modal absorption as high as 250 cm–1 at the laser wavelength of 413 nm is measured at 1 V absorber voltage. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Towards nanorod LEDs: Numerical predictions and controlled growth
Authors: Kölper Christopher , Bergbauer Werner , Drechsel Philipp , Sabathil Matthias , Straßburg Martin , Lugauer Hans‐Jürgen , Witzigmann Bernd , Fündling Sönke , Li Shunfeng , Wehmann Hergo‐Heinrich , Waag Andreas
Published: April 2011

We present a numerical optimization of nanorod geometries with respect to the optical properties of an electrically driven LED emitting in the green spectral range. It is shown that an overall Purcell enhancement as well as directional emission can be achieved at an emission wavelength of 550 nm with nanorods of 110 nm radius. Position‐controlled growth on patterned substrates demonstrates that the required dimensions are accessible by varying growth parameters and growth time in a large volume MOVPE reactor. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
InGaN mini‐laser diode arrays with cw output power of 500 mW
Authors: Holc Katarzyna , Sarzyńska Agnieszka , Boćkowski Michał , Czernecki Robert , Leszczyński Michał , Suski Tadeusz , Kucharski Robert , Perlin Piotr
Published: April 2011

One of the required features of nitride‐based laser diodes is the possibility to obtain high output powers from devices, which is essential in e.g. RGB displays, lithography and high speed printing. This can be realized by means of multi emitter structures. We report on fabrication of a mini laser array, integrated on one laser chip and consisting of three emitters of the dimensions of 700 μm x 3 μm. The emitters structures was fabricated by MOVPE on top of the low defect density bulk GaN crystal obtained by ammonothermal method. We tested devices characterized by various pitches from 12 to 80 μm obtaining very similar results. Contrary to our previous study showing strong inter‐emitter coupling we obtained independent emission from each stripe. This fact is a result of better vertical mode confinement and the suppression of substrate mode leakage. These latter effects were the reason for emitters coupling, as we reported previously. The new devices produced up to 500 mW of optical power, this value was limited by the thermal resistance of the whole package. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Study on leakage current of pn diode on GaN substrate at reverse bias
Authors: Sugimoto Masahiro , Kanechika Masakazu , Uesugi Tsutomu , Kachi Tetsu
Published: April 2011

In this paper, we studied on a leakage current of a pn diode on a GaN substrate isolated by a mesa structure at a reverse bias. The leakage current flowed at a surface of the mesa sidewall across the pn junction. Results of scanning capacitance microscopy and scanning spread resistance microscopy indicated that the surface of the mesa sidewall in the p type region changed to a depleted or a n‐‐layer. Results of auger electron spectroscopy indicated that a concentration of nitrogen decreased near the surface of the mesa sidewall. From these results, we estimated the leakage current was caused by a change of the p type region at the surface of the mesa sidewall to the depleted or n‐‐layer by inductively coupled plasma dry etching, which was used to form the mesa structure. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electrical and optical properties of GaN studied by surface photovoltage and photoluminescence
Authors: Foussekis M. A. , Baski A. A. , Reshchikov M. A.
Published: April 2011

We have studied the electrical and optical properties of undoped and Si‐doped n ‐type GaN layers grown on c ‐plane sapphire by Kelvin probe and photoluminescence (PL) techniques. The maximum SPV value of ∼0.7 eV indicates that the band bending decreased by this amount. The PL intensity depended on ambient and surface treatments such as cleaning, storage in air ambient, and extended UV exposure. Interestingly, variations in PL intensity, at least for n ‐type GaN, were too large to be explained solely by changes in depletion region width under illumination. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ultrahigh‐speed growth of GaN by hydride vapor phase epitaxy
Authors: Yoshida Takehiro , Oshima Yuichi , Watanabe Kazutoshi , Tsuchiya Tadayoshi , Mishima Tomoyoshi
Published: April 2011

We demonstrate the ultrahigh‐speed growth of thick GaN layers by hydride vapor phase epitaxy (HVPE) and present an investigation of the properties of the resulting GaN crystals. A series of GaN layers with a thickness of around 700 μm were grown homoepitaxially on freestanding GaN substrates at various growth rates ranging from 107–1870 μm/h, using a conventional atmospheric HVPE reactor. The growth rate increased almost linearly with the feed rate of source materials, reaching 1870 μm/h when the HCl flow rate is 650 sccm. The surfaces of all the homoepitaxial layers were specular, and no cracks or pits were observed. The X‐ray rocking curve measurement showed that the full width at half maximum values did not depend on the growth rate, and had small values of 23–30 arcsec for (0002) reflections and 39–58 arcsec for (30‐32) reflections. Plan‐view cathodoluminescence imaging revealed that the dislocation density had virtually no dependence on the growth rate and had small values of around 3 × 106 cm‐2 even at the highest growth rate (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Control of in‐plane epitaxial relationship of c ‐plane AlN layers grown on a ‐plane sapphire substrates by hydride vapor phase epitaxy
Authors: Tajima Jumpei , Togashi Rie , Murakami Hisashi , Kumagai Yoshinao , Takada Kazuya , Koukitu Akinori
Published: April 2011

Control of the in‐plane epitaxial relationship of a c ‐plane AlN layer grown at 1450 °C by hydride vapor phase epitaxy on an a ‐plane sapphire substrate is achieved. In addition, two in‐plane epitaxial relationships are compared. It was possible to grow a c ‐plane AlN layer on an a ‐plane sapphire substrate with selectable in‐plane matching: AlN [10$ \bar 1 $0]//sapphire [0001] could be obtained by growing an intermediate AlN layer at 1065 °C, whereas AlN [11$ \bar 2 $0] // sapphire [0001] could be grown on the intermediate AlN layer at a low temperature of 700 °C. The full‐width at half‐maximums of X‐ray rocking curves for the (0002) and (10$ \bar 1 $0) planes were respectively 313.2 and 543.6 arcsec from the AlN layer with the AlN [10$ \bar 1 $0]//sapphire [0001] relationship and 428.4 and 788.0 arcsec from the AlN layer with the AlN [11$ \bar 2 $0] // sapphire [0001] relationship. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantification of scar margin in keloid different from atrophic scar by multiphoton microscopic imaging
Authors: Zhu Xiaoqin , Zhuo Shuangmu , Zheng Liqin , Jiang Xingshan , Chen Jianxin , Lin Bifang
Published: April 2011

Multiphoton microscopy (MPM) was applied to examine the marginal region at dermis of keloid compared with atrophic scar. High‐resolution large‐area image showed an obvious boundary at the scar margin and different morphological patterns of elastin and collagen on the two sides, further visualized by the focused three‐dimensional images. Content alteration of elastin or collagen between the two sides of boundary was quantified to show significant difference between keloid and atrophic scar. Owing to the raised property of keloid with overproduced collagen on the scar side, the content alteration was positive for elastin and negative for collagen. On the contrary, the content alteration was negative for elastin and positive for collagen in the atrophic scar case due to the atrophic collagen on the scar side. It indicated that examination of the scar margin by MPM may lead a new way to discriminate different types of scars and better understand the scarring mechanisms. SCANNING 33:
195–200, 2011. © 2011 Wiley Periodicals, Inc.
Smelting‐Reduction Export Gas as Syngas in the Chemical Industry
Authors: Wall Doris , Kepplinger Werner , Millner Robert
Published: April 2011

Export gases from iron‐making processes are typically used as an energy source for heat and power generation within the iron and steel industry, although their calorific value is comparatively low. The fact that COREX® and FINEX® smelting‐reduction export gases typically consist of the major syngas‐components CO and H2 (approx. 50% of gas composition), makes them attractive for utilization in the direct reduction of iron ores and in the chemical synthesis industry. This paper will discuss the required process steps for converting smelting‐reduction export gases into synthesis gas (syngas) using the example of methanol production. The calculated CO2‐balance shows promising results for chemical utilization of COREX® export gas compared to energy utilization in conventional or combined power plants.
Study on Mitigating Center Macro‐Segregation During Steel Continuous Casting Process
Authors: Long Mujun , Chen Dengfu
Published: April 2011

In the current paper, Methods of enlarging the area for the distribution of segregation solutes were introduced to mitigate center macro‐segregation in steel billets and steel slabs during continuous casting process, which cost less and have significant effect. The location of center macro‐segregation is relative to the shape of liquid‐core at the solidification end during steel continuous casting. A method of dissymmetrical cooling on different surfaces, by which the area for the precipitation of segregation solutes was enlarged, was introduced to mitigate the center macro‐segregation in billets during continuous casting process. Method of optimizing the uniformity of solidified shell in the transverse direction was introduced to mitigate the center macro‐segregation in steel slabs. The uniform cooling intensity along the transverse direction guaranteed a regular solidification end in the continuous casting slab, which aided in the effective application of dynamic soft reduction technology. A relevant 2‐D heat transfer model was developed for the optimization of uniform solidification. The current method was applied to the industrial slab continuous casting using the heat transfer model. The results indicated a better industrial slab quality with much less center macro‐segregation after the use of the method.
Fish Oil Supplementation During Lactation: Effects on Cognition and Behavior at 7 Years of Age
Authors: Cheatham Carol L. , Nerhammer Anne Sofie , Asserhøj Marie , Michaelsen Kim F. , Lauritzen Lotte
Published: April 2011

Early accumulation of n‐3 long‐chain PUFA (LCPUFA) in the brain may contribute to differences in later cognitive abilities. In this study, our objective was to examine whether fish oil (FO) supplementation during lactation affects processing speed, working memory, inhibitory control, and socioemotional development at 7 years. Danish mothers (n = 122) were randomized to FO [1.5 g/d n‐3 LCPUFA] or olive oil (OO) supplementation during the first 4 months of lactation. The trial also included a high‐fish intake (HFI) reference group (n = 53). Ninety‐eight children were followed‐up with an assessment of processing speed, an age‐appropriate Stroop task, and the Strength and Difficulties Questionnaire at 7 year. A group effect of the intervention (FO vs. OO) was found in prosocial behavior scores; this negative effect was carried by the boys. Exploratory analyses including all participants revealed the speed of processing scores were predicted by maternal n‐3 LCPUFA intake during the intervention period (negative relation) and maternal education (positive relation). Stroop scores indicative of working memory and inhibitory control were predicted by infant erythrocyte DHA status at 4 months of age (negative relation). Early fish oil supplementation may have a negative effect on later cognitive abilities. Speed of processing and inhibitory control/working memory are differentially affected, with speed of processing showing effects of fish oil intake as a whole, whereas inhibitory control/working memory was related more specifically to DHA status.