bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel regulatory role of gp49B on dendritic cells in T‐cell priming
Authors: Kasai Satoshi , Inui Masanori , Nakamura Kyohei , Kakizaki Yuta , Endo Shota , Nakamura Akira , Ito Sadayoshi , Takai Toshiyuki
Published: September 2008

Dendritic cells (DC) play pivotal roles in the induction and regulation of both innate and acquired immunity. DC express several cell‐surface immune inhibitory receptors. However, little is known about their potential immunoregulatory functions in the context of T‐cell activation. Here we report that murine gp49B, a member of the immunoglobulin superfamily, harboring immunoreceptor tyrosine‐based inhibitory motifs, is expressed on DC and downregulates cellular activity to prevent the excessive activation of T cells in vitro and in vivo. Bone marrow‐derived DC (BMDC) from newly generated gp49B‐deficient (gp49B−/−) mice induced enhanced proliferation and IL‐2 release of antigen‐specific CD4+ and CD8+ T cells compared with BMDC from wild‐type mice, in a cell–cell contact manner. The enhanced proliferation by gp49B−/− BMDC was also observed in allogeneic CD4+ and CD8+ T cells. Moreover, the transfer of allogeneic BALB/c splenocytes into C57BL/6 gp49B−/− mice induced severe acute graft‐versus‐host disease with an augmented upregulation of CD86 on CD11c+ splenic gp49B−/− DC, while transfer of C57BL/6 gp49B−/− splenocytes into BALB/c mice did not, suggesting the exacerbation of the disease was due, at least in part, to augmented activation of recipient gp49B−/− DC. These findings demonstrate a novel regulatory role of gp49B in the function of DC.
Enforced expression of GATA3 allows differentiation of IL‐17‐producing cells, but constrains Th17‐mediated pathology
Authors: van Hamburg Jan Piet , de Bruijn Marjolein J. W. , de Almeida Claudia Ribeiro , van Zwam Marloes , van Meurs Marjan , de Haas Edwin , Boon Louis , Samsom Janneke N. , Hendriks Rudi W.
Published: September 2008

The zinc‐finger transcription factor GATA3 serves as a master regulator of T‐helper‐2 (Th2) differentiation by inducing expression of the Th2 cytokines IL‐4, IL‐5 and IL‐13 and by suppressing Th1 development. Here, we investigated how GATA3 affects Th17 differentiation, using transgenic mice with enforced GATA3 expression. We activated naïve primary T cells in vitro in the presence of transforming growth factor‐β and IL‐6, and found that enforced GATA3 expression induced co‐expression of Th2 cytokines in IL‐17‐producing T cells. Although the presence of IL‐4 hampered Th17 differentiation, transforming growth factor‐β/IL‐6 cultures from GATA3 transgenic mice contained substantial numbers of IL‐17+ cells, partially because GATA3 supported Th17 differentiation by limiting IL‐2 and IFN‐γ production. GATA3 additionally constrained Th17 differentiation in vitro through IL‐4‐independent mechanisms, involving downregulating transcription of STAT3, STAT4, NFATc2 and the nuclear factor RORγt, which is crucial for Th17 differentiation. Remarkably, upon myelin oligodendrocyte glycoprotein immunization in vivo, GATA3 transgenic mice contained similar numbers of IL‐17‐producing T cells in their lymph nodes as wild‐type mice, but were not susceptible to autoimmune encephalomyelitis, possibly due to concomitant production of IL‐4 and IL‐10 induction. We therefore conclude that although GATA3 allows Th17 differentiation, it acts as an inhibitor of Th17‐mediated pathology, through IL‐4‐dependent and IL‐4‐independent pathways.
Protein/DNA vaccine‐induced antigen‐specific Treg confer protection against asthma
Authors: Jin Huali , Xiao Chong , Geng Shuang , Hu Yanxin , She Ruiping , Yu Yang , Kang Youmin , Wang Bin
Published: September 2008

Asthma is a chronic inflammatory disorder caused by T‐cell‐mediated inflammation within airways. No antigen‐specific treatment has been available. Using an OVA‐induced murine asthma model, we find that co‐immunization of an OVA epitope peptide with a DNA vaccine encoding the same epitope is able to prevent this experimental asthma as evidenced in the marked reduction of infiltrations of eosinophils and lymphocytes into the site of the allergen challenge. We demonstrate that the prevention of experimental asthma was directly related to the induction of a population of OVA‐specific T‐regulatory cells (Treg) exhibiting a CD4+CD25−FoxP3+ phenotype and expressing IL‐10, TGF‐β and IFN‐γ following the co‐immunization. Blockade of IL‐10 and TGF‐β of the Treg by anti‐IL‐10 and TGF‐β antibodies is partially able to reverse the suppression in vitro and in vivo, which caused the recurrence of the inflammation. Furthermore, adoptive transfer of the induced Treg is also able to suppress the OVA‐induced asthma. To our knowledge, the combination of peptide with its cognate DNA vaccine protect experimental asthma via the induced epitope‐specific Treg has not been previously reported and such strategy may lead to a novel immunotherapy against asthma in humans.
Protection against Plasmodium falciparum challenge induced in Aotus monkeys by liver‐stage antigen‐3‐derived long synthetic peptides
Authors: Perlaza Blanca‐Liliana , Valencia Anais Zully , Zapata Constanza , Castellanos Angélica , Sauzet Jean‐Pierre , Blanc Catherine , Cohen Joe , Arévalo‐Herrera Myriam , Corradin Giampietro , Herrera Sócrates , Druilhe Pierre
Published: September 2008

The vaccine potential of Plasmodium falciparum liver stage antigen‐3 (LSA3) was investigated in Aotus monkeys using two long synthetic peptides corresponding respectively to an N‐terminal non‐repeat peptide (NRP) and repeat 2 (R2) region of the LSA3, adjuvanted by ASO2. Both 100–222 (NRP) and 501–596 repeat peptides induced effector B‐ and T‐cell responses in terms of antigen‐driven antibodies and/or specific IFN‐γ secretion. Animals challenged with P. falciparum sporozoites were protected following immunization with either the NRP region alone or the NRP combined with the R2 repeat region, as compared with controls receiving the adjuvant alone. These results indicate that the NRP may be sufficient to induce full, sterile protection and confirm the vaccine potential of LSA3 previously demonstrated in chimpanzees and in Aotus.
Resting B cells expand a CD4+CD25+Foxp3+ Treg population via TGF‐β3
Authors: Shah Shivanee , Qiao Liang
Published: September 2008

Regulatory T cells (Treg) play critical roles in maintaining tolerance and preventing autoimmunity. It is not fully clear how these cells are generated and maintained. Here, we show that resting B cells are able to expand Treg. This expansion requires TGF‐β3 and signaling through the TCR and CD28. Upon activation, B cells express less TGF‐β3, which reduces their capacity to expand Treg and which also results in increased Treg death. This may ensure that B cells can function as potent professional antigen presenting cells during infections. However, in the absence of any infection, we find that B‐cell‐deficient µMT mice have decreased percentages of Treg in the periphery. Our data suggest that resting B cells, which may be presenting self‐antigens to T cells, can expand and maintain specific Treg and thus might be involved in the prevention of autoimmunity.
Optimising anti‐tumour CD8 T‐cell responses using combinations of immunomodulatory antibodies
Authors: Gray Juliet C. , French Ruth R. , James Sonya , Al‐Shamkhani Aymen , Johnson Peter W. , Glennie Martin J.
Published: September 2008

Immunostimulatory mAb as vaccine adjuvants for the treatment of cancer hold considerable potential for boosting weak responses when used against immunogenic tumours, or in combination with various other vaccines. We now show that when administered with OVA, the combination of anti‐4‐1BB mAb with anti‐CD40, anti‐OX40 or anti‐CD25 resulted in a fourfold enhancement in the antigen‐specific T‐cell response compared with anti‐4‐1BB mAb alone, with a similar enhancement in memory responses following rechallenge with OVA. Although the number of antigen‐specific T‐cells generated after treatment with each of the combinations was similar, marked functional differences were detected. In particular, anti‐4‐1BB/anti‐CD25 resulted in excellent expansion of specific CD8+ T cells but produced fewer IFN‐γ‐secreting effector cells than the other combinations. Anti‐4‐1BB/anti‐OX40 proved to be the most potent, inducing the most effective T‐cell responses in the RIPmOVA diabetes model with adoptively transferred OVA‐specific T cells, and, when given with a peptide vaccine, protecting mice against the poorly immunogenic B16‐F10 tumour. Overall the results suggest that although these combinations of mAb look promising in terms of their therapeutic potential, further functional assays are needed to compare their effects.
Proliferative signals mediated by CD28 superagonists require the exchange factor Vav1 but not phosphoinositide 3‐kinase in primary peripheral T cells
Authors: Gogishvili Tea , Elias Fernando , Emery Juliet L. , McPherson Kirsty , Okkenhaug Klaus , Hünig Thomas , Dennehy Kevin M.
Published: September 2008

Almost all responses of naive T cells require co‐stimulation, i.e. engagement of the clonotypic TCR with relevant antigen/MHC and the co‐stimulatory molecule CD28. How CD28 contributes to T‐cell proliferation remains poorly understood, with widely conflicting reports existing which may reflect different methods of co‐ligating receptors. Some CD28 mAb, however, can stimulate T‐cell proliferation without the need for TCR co‐ligation, and thus provide unique tools to dissect proliferative signals mediated through CD28 alone. Using primary peripheral T cells from CD28‐transgenic mice, we show that both the YMNM and Lck‐binding motifs, but not the Itk‐binding motif, in CD28 are required for proliferation. Given that the YMNM motif recruits both phosphoinositide 3‐kinase (PI3K) and the exchange factor Vav1, we investigated the role of these two molecules in CD28‐mediated proliferation. In p110δD910A/D910A transgenic T cells, which are defective in PI3K activation following CD28 ligation, proliferation was comparable to that in wild‐type cells. By contrast, T‐cell proliferation was abolished in Vav1−/− cells. Although we did not address the role of Grb2 in CD28 signalling, these results indicate that CD28 can mediate Lck‐ and Vav1‐dependent proliferative signals independently of PI3K.
Alterations of 3p21.31 tumor suppressor genes in head and neck squamous cell carcinoma: Correlation with progression and prognosis
Authors: Ghosh Susmita , Ghosh Amlan , Maiti Guru Prasad , Alam Neyaz , Roy Anup , Roy Bidyut , Roychoudhury Susanta , Panda Chinmay Kumar
Published: September 2008

The aim of our study was to analyze the alterations of some candidate tumor suppressor genes (TSGs) viz. LIMD1, LTF, CDC25A, SCOTIN, RASSF1A and CACNA2D2 located in the chromosomal region 3p21.31 associated with the development of early dysplastic lesions of head and neck. In analysis of 72 dysplastic lesions and 116 squamous cell carcinoma of head and neck, both deletion and promoter methylation have been seen in these genes except for CDC25A and SCOTIN where no methylation has been detected. The alteration of LIMD1 was highest (50%) in the mild dysplastic lesions and did not change significantly during progression of tumor indicating its association with this stage of the disease. It was evident that alterations of LTF, CDC25A and CACNA2D2 were associated with development of moderate dysplastic lesions, while alterations in RASSF1A and CACNA2D2 were needed for progression. Novel somatic mutations were seen in exon 1 of LIMD1 (7%), intron 3/exon4 splice junction of LTF (2%) and exon 7 of cdc25A (10%). Quantitative RT‐PCR analysis revealed mean reduced expression of the genes in the following order: LTF (67.6 ± 16.8) > LIMD1 (53.2 ± 20.1) > CACNA2D2 (23.7 ± 7.1) > RASSF1A (15.1 ± 5.6) > CDC25A (5.3 ± 2.3) > SCOTIN (0.58 ± 0.54). Immunohistochemical analysis of CDC25A showed its localization both in cytoplasm and nucleus in primary lesions and oral cancer cell lines. In absence of HPV infection, LTF and RASSF1A alterations jointly have adverse impact on survival of tobacco addicted patients. Thus, our data suggested that multiple candidate TSGs in the chromosomal 3p21.31 region were differentially associated with the early dysplastic lesions of head and neck. © 2008 Wiley‐Liss, Inc.
Intake of whole grain products and risk of breast cancer by hormone receptor status and histology among postmenopausal women
Authors: Egeberg Rikke , Olsen Anja , Loft Steffen , Christensen Jane , Johnsen Nina Føns , Overvad Kim , Tjønneland Anne
Published: September 2008

No clear relationship between whole grain products and risk of breast cancer has been established. In a large prospective cohort study, we investigated the association between intake of whole grain products and risk of breast cancer by tumour receptor status [oestrogen receptor (ER) and progesterone receptor (PR)] and tumour histology (ductal/lobular). It was further investigated whether the association differed by use of hormone replacement therapy (HRT). The study included 25,278 postmenopausal women participating in the Danish Diet, Cancer and Health cohort study (1993–1997). During a mean follow‐up time of 9.6 years, 978 breast cancer cases were diagnosed. Associations between intake of whole grain products and the breast cancer rate were analysed using Cox's regression model. A higher intake of whole grain products was not associated with a lower risk of breast cancer. Per an increment in intake of total whole grain products of 50 g per day the adjusted incidence rate ratio (95% confidence interval) was 1.01 (0.96–1.07). Intake of rye bread, oatmeal and whole grain bread was not associated with breast cancer risk. No association was observed between the intake of total or specific whole grain products and the risk of developing ER+, ER−, PR+, PR−, combined ER/PR status, ductal or lobular breast cancer. Furthermore, there was no interaction between intake of whole grain products and use of HRT on risk of breast cancer. In conclusion, intake of whole grain products was not associated with risk of breast cancer in a cohort of Danish postmenopausal women. © 2008 Wiley‐Liss, Inc.
Nonalcoholic steatohepatitis induced by a high‐fat diet promotes diethylnitrosamine‐initiated early hepatocarcinogenesis in rats
Authors: Wang Yan , Ausman Lynne M. , Greenberg Andrew S. , Russell Robert M. , Wang Xiang‐Dong
Published: September 2008

It has been suggested that patients with nonalcoholic steatohepatitis (NASH) may have high risk for liver cancer. However, it is unknown whether high‐fat diet (HFD) induced NASH promotes hepatocarcinogenesis. In this study, Sprague‐Dawley rats were injected with a low dose of hepatic carcinogen diethylnitrosamine (DEN) and then fed either Lieber‐DeCarli control diet (CD) or HFD for 6 weeks. Liver histology and the hepatic placental form of glutathione S‐transferase (P‐GST) positive foci were examined. Expression levels of proliferating cell nuclear antigen (PCNA), cyclinD1, phosphorylated mitogen‐activated protein kinase (MAPK) including extracellular signal‐regulated kinase (ERK) and p38, as well as tumor necrosis factor‐alpha (TNF‐α), and nuclear factor‐kappaB (NF‐κB) were measured in the liver. Induction of lipid peroxidation end products (malondialdehyde plus 4‐hydroxynonenal) in liver and apoptotic hepatocytes were also assessed. Results showed that HFD‐fed rats developed significantly higher incidence and multiplicity of P‐GST positive foci along with more fat accumulation, infiltration of inflammatory cells and higher lipid peroxidation in the liver, when compared with rats fed the CD. This high prevalence of hepatic lesions in the liver was accompanied by greater PCNA expression and cyclinD1 protein concentration but little change in hepatocyte apoptosis. HFD feeding elevated hepatic phosphorylated ERK but reduced phosphorylated p38 when compared with the CD feeding. In addition, a significantly higher expression of TNF‐α mRNA and nuclear NF‐κB p65 protein were observed in HFD group than in CD group. These data clearly demonstrate that NASH induced by HFD promoted DEN‐initiated early hepatocarcinogenesis, which was associated with elevated TNF‐α/NF‐κB signaling and MAPK related hepatocyte proliferation. © 2008 Wiley‐Liss, Inc.
HPV16/18 vaccination to prevent cervical cancer in The Netherlands: Model‐based cost‐effectiveness
Authors: Coupé Veerle M.H. , van Ginkel Joost , de Melker Hester E. , Snijders Peter J.F. , Meijer Chris J.L.M. , Berkhof Johannes
Published: September 2008

We evaluated the cost‐effectiveness of HPV16/18 vaccination for girls aged 12 years in The Netherlands in addition to cervical cancer screening. For this purpose, we developed a simulation model that describes the relation between each of the high‐risk human papillomavirus (hrHPV) types and cervical disease, allowing the occurrence of multiple type‐specific infections. Model parameters were derived from Dutch cohort studies, including a large population‐based screening trial, and from the national cervical cancer registry. The model satisfactorily reproduced Dutch data on HPV infection and the presence of cervical lesions. For our base‐case scenario in which 85% of the girls aged 12 years were vaccinated against types 16/18 (95% efficacy, lifelong protection), the model predicted a decrease of 60% in the number of cervical cancer cases and cervical cancer deaths indicating that substantial health benefits can be achieved. Health savings were robust against changes in the vaccine efficacy (varied from 85% to 98%) but savings showed a substantial reduction when the efficacy started waning 10 years after vaccination. The discounted costs per quality‐adjusted life year (QALY) were € 19,500/QALY (range € 11,000 to € 25,000/QALY) and lied near the cost‐effectiveness threshold of € 20,000/QALY used in The Netherlands. The simulations further showed that vaccination cannot replace screening because vaccination without screening was less effective than screening in preventing cancer in women over 40 years of age. In conclusion, our model results support the implementation of HPV16/18 vaccination in young women in addition to cervical cancer screening. © 2008 Wiley‐Liss, Inc.
Prognostic marker profile to assess risk in stage I–III hormone receptor‐positive breast cancer patients
Authors: Bremer Troy M. , Jacquemier Jocelyne , Charafe‐Jauffret Emmanuelle , Viens Patrice , Birnbaum Daniel , Linke Steven P.
Published: September 2008

Single markers are insufficient to accurately assess risk of relapse for adjuvant therapy guidance in operable breast cancer patients. In addition, the accuracy and interpretability of current multi‐marker tests is generally limited by their simply additive algorithms and their overlap with clinicopathologic risks. Here, we report the development and validation of a nonlinear algorithm that combines protein (ER, PGR, ERBB2, BCL2 and TP53) and genomic (MYC/8q24) markers with standard clinicopathologic features (tumor size, tumor grade and nodal status) into a global risk assessment profile. The algorithm was trained using statistical pattern recognition in 200 stage I–III hormone receptor‐positive patients treated with hormone therapy. Continuous risk scores (0–10+) were then generated for 232 independent patients. In hormone therapy‐treated patients, the profile achieved a hazard ratio of 6.2 (95% confidence interval [CI], 1.8–20) in high‐ vs. low‐risk groups for time to distant metastasis with the low‐risk group having a 10‐year metastasis rate of just 4% (95% CI, 0–8%). Similar results were achieved in untreated patients and for disease‐specific survival. In multivariate analyses with standard prognostic factors and clinical practice guidelines, the profile was the only significant variable. Furthermore, the profile reclassified as low risk over half of node‐negative patients at elevated risk according to the guidelines, which could have spared such patients from unnecessary cytotoxic chemotherapy. It also accurately identified a group of high‐risk patients within a guideline low‐risk group. In summary, the profile intelligently combines biologically relevant marker pathways and established clinicopathologic risks to help guide breast cancer patients to the most appropriate level of adjuvant therapy. © 2008 Wiley‐Liss, Inc.
Long‐term dietary acrylamide intake and risk of endometrial cancer in a prospective cohort of Swedish women
Authors: Larsson Susanna C. , Håkansson Niclas , Åkesson Agneta , Wolk Alicja
Published: September 2008

Acrylamide has been found in foods heated at high temperatures and there is evidence of carcinogenicity of acrylamide in experimental animals. However, the potential health risks of dietary acrylamide intake in humans remain uncertain. We examined the association between dietary acrylamide intake and the incidence of endometrial cancer among 61,226 participants of the Swedish Mammography Cohort who were cancer‐free at enrollment in 1987–1990 and completed a food frequency questionnaire at baseline and again in 1997. Cox proportional hazards models were used to estimate rate ratios with 95% confidence intervals, adjusted for endometrial cancer risk factors. During a mean follow‐up of 17.7 years, a total of 687 incident cases of endometrial adenocarcinoma were diagnosed in the cohort. We found no association between long‐term acrylamide intake and risk of endometrial cancer. The multivariate rate ratio of endometrial cancer for women in the highest quartile of acrylamide intake (mean, 33.8 μg/day) compared to those in the lowest quartile (mean, 15.9 μg/day) was 0.96 (95% CI, 0.76–1.21). The association did not vary materially by smoking status. In conclusion, these findings do not support the hypothesis that dietary acrylamide intake is positively associated with risk of endometrial cancer, at least not within the ranges of acrylamide consumed in this population. © 2008 Wiley‐Liss, Inc.
p38‐MAPK‐ and caspase‐3‐mediated superoxide‐induced apoptosis of rat hepatic stellate cells: Reversal by retinoic acid
Authors: Jameel Noor Mohamed , Thirunavukkarasu Chinnasamy , Wu Tong , Watkins Simon C. , Friedman Scott L. , Gandhi Chandrashekhar R.
Published: September 2008

Reactive oxygen species (ROS) activate retinoid‐containing quiescent hepatic stellate cells (qHSCs) to retinoid‐deficient fibrogenic myofibroblast‐like cells (aHSCs). However, ROS also cause apoptosis of aHSCs, and apoptotic aHSCs are observed in inflammatory fibrotic liver. Here, we investigated mechanisms of the effects of oxidative stress on the survival of qHSCs and aHSCs. HSCs from normal rat liver were used after overnight culture (qHSCs), or in 3–5 passages (aHSCs). For in vivo induction of oxidative stress, tert‐butylhydroperoxide was injected into control and CCl4‐induced cirrhotic rats. Spontaneous caspase‐3 activation and apoptosis, observed in cultured qHSCs, decreased with time and were unaffected by superoxide. In contrast, superoxide caused caspase‐3 and p38‐MAPK activation, reduction in Bcl‐xL expression, and apoptosis in aHSCs. Inhibition of caspase‐3 and p38‐MAPK did not affect the viability of qHSCs in the absence or presence of superoxide, but inhibited superoxide‐induced death of aHSCs. Glutathione (GSH) level and activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were lower in aHSCs than qHSCs. Superoxide increased GSH content, and activities of SOD, catalase and GPx in qHSCs but not in aHSCs. Incubation of 13‐cis‐retinoic acid (RA)‐treated aHSCs with superoxide increased their GSH content significantly, and prevented superoxide‐induced p38‐MAPK and caspase‐3 activation while dramatically reducing the extent of apoptosis. Finally, oxidative stress induced in vivo caused apoptosis of aHSCs in cirrhotic but not of qHSCs in control rats. These results suggest that the absence of retinoids render aHSCs susceptible to superoxide‐induced apoptosis via caspase‐3 and p38‐MAPK activation. J. Cell. Physiol. 218: 157–166, 2009. © 2008 Wiley‐Liss, Inc.
The therapeutic applications of multipotential mesenchymal/stromal stem cells in skeletal tissue repair
Authors: Arthur Agnieszka , Zannettino Andrew , Gronthos Stan
Published: September 2008

Four decades after the first isolation and characterization of clonogenic bone marrow stromal cells or mesenchymal stem cells (MSC) in the laboratory of Dr. Alexander Friedenstien, the therapeutic application of their progeny following ex vivo expansion are only now starting to be realized in the clinic. The multipotency, paracrine effects, and immune‐modulatory properties of MSC present them as an ideal stem cell candidate for tissue engineering and regenerative medicine. In recent years it has come to light that MSC encompass plasticity that extends beyond the conventional bone, adipose, cartilage, and other skeletal structures, and has expanded to the differentiation of liver, kidney, muscle, skin, neural, and cardiac cell lineages. This review will specifically focus on the skeletal regenerative capacity of bone marrow derived MSC alone or in combination with growth factors, biocompatible scaffolds, and following genetic modification. J. Cell. Physiol. 218: 237–245, 2009. © 2008 Wiley‐Liss, Inc.
Influence of isooctanol on the interfacial activity and mass transfer of ytterbium(III) using 2‐ethylhexylphosphonic acid mono‐2‐ethylhexyl ester as an acidic extractant
Authors: Wang Xianglan , Li Wei , Wang Weiwei , Meng Shulan , Li Deqian
Published: September 2008

BACKGROUND:Introducing an adduct into an extractant system is an effective method of improving extraction performance. The effect of additives upon extraction is very important, especially in the case of interfacial behaviour. In most work published in the literature, there is little data on the interfacial behaviour of extractants and modifiers. As the mass transfer must pass through an interface, the influence of isooctanol on the interfacial activity and mass transfer of ytterbium(III) using 2‐ethylhexylphosphonic acid mono‐2‐ethlhexyl ester has been investigated.

RESULTS:With increasing amounts of isooctanol, the interfacial tension and surface excess (Γmax) of the 2‐ethylhexylphosphonic acid mono‐2‐ethylhexyl ester(HEHEHP)–isooctanol system decreased, and the area of the absorbed HEHEHP molecule (Amin) increased. The interfacial activity of the HEHEHP–isooctanol system varied significantly depending on ionic strength and temperature and the mass transfer flux decreased with increasing isooctanol content.

CONCLUSION:Isooctanol has a strong influence on the interfacial activity of the HEHEHP system. The influence of isooctanol on the mass transfer rate of ytterbium extraction has been discussed qualitatively. Copyright © 2008 Society of Chemical Industry
Preparation of protein microarrays on non‐fouling and hydrated poly(ethylene glycol) hydrogel substrates using photochemical surface modification
Authors: Kim Dae‐Nyun , Lee Woojin , Koh Won‐Gun
Published: September 2008

BACKGROUND: Conventional protein microarrays prepared on hard, dry substrates, such as glass and silicone, have several limitations, as proteins may easily denature and lose their structure. To overcome such problems, the fabrication of wet protein microarrays on non‐fouling and hydrated PEG‐based hydrogels was investigated.

RESULT: Bovine serum albumin (BSA) and glucose oxidase (GOX), chosen as model proteins, were covalently immobilized on PEG hydrogel surfaces via 5‐azidonitrobenzoyloxy N‐hydroxysuccinimide, a photoreactive bifunctional linker. Successful fixation of the bifunctional linker and subsequent immobilization of the proteins on the PEG hydrogel surfaces were confirmed with X‐ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) studies. GOX immobilized on the hydrogel surface maintained approximately 50% of its initial activity after 24 h when left in dry conditions, but maintained only 20% when immobilized on a dry substrate. Photochemical fixation combined with photolithography produced well‐defined protein micropatterns with sizes ranging from 50–500 µm, and molecular recognition‐mediated specific binding between biotin and streptavidin was successfully assayed using microarrays on PEG hydrogels.

CONCLUSION: A protein‐repellent PEG hydrogel surface was photochemically modified to covalently immobilize proteins and create protein microarrays. The use of hydrated hydrogels as substrates for protein microarrays could minimize the deactivation of proteins in dry conditions, and the non‐fouling property of PEG hydrogels allows the passivation step of protein microarray preparation to be skipped. Copyright © 2008 Society of Chemical Industry
Development of a mathematical model for Bacillus circulans growth and alkaline protease production kinetics
Authors: Subba Rao Chaganti , Sathish Thadikamala , Pendyala Brahamaiah , Kumar Thella Prathap , Prakasham Reddy Shetty
Published: September 2008

BACKGROUND: An unstructured mathematical model was developed to understand information on the relationship between Bacillus circulans growth and metabolism‐related protease production (using logistic and Luedeking–Piret equations respectively) in a batch reactor with respect to glucose consumption and fermentation time. The objective was to develop an indispensable tool for the optimisation, control, design and analysis of alkaline protease production.

RESULTS: Biomass growth and enzyme production titres changed with a change in substrate concentration. Modelling analysis of biomass and enzyme production titres at different substrate concentrations revealed significant accuracy in terms of statistical consistency and robustness with respect to fermentation kinetic profiles.

CONCLUSION: With the B. circulans strain used, an economic protease yield (2837 × 103 U g−1) with respect to biomass and glucose ratio was achieved at low substrate concentration (10 g L−1). The developed model could be effectively utilised for designing, controlling and up‐scaling the protease production process in high‐density fermentation in selected bioreactors with statistical consistency. Copyright © 2008 Society of Chemical Industry
k‐shredders in k‐connected graphs
Authors: Egawa Yoshimi
Published: September 2008

For a graph G, a subset S of V(G) is called a shredder if G − S consists of three or more components. We show that if k ≥ 4 and G is a k‐connected graph, then the number of shredders of cardinality k of G is less than 2|V(G)|/3 (we show a better bound for k = 4). © 2008 Wiley Periodicals, Inc. J Graph Theory 59: 239–259, 2008
Disjoint cycles with chords in graphs
Authors: Babu Ch. Sobhan , Diwan Ajit A.
Published: September 2008

Let $n_1,n_2,\ldots,n_k$ be integers, $n=\sum n_i$, $n_i\ge 3$, and let for each $1\le i\le k$, $H_i$ be a cycle or a tree on $n_i$ vertices. We prove that every graph G of order at least n with $\sigma_2(G) \ge 2( n-k) -1$ contains k vertex disjoint subgraphs $H_1',H_2',\ldots,H_k'$, where $H_i'=H_i$, if $H_i$ is a tree, and $H_i'$ is a cycle with $n_i-3$ chords incident with a common vertex, if $H_i$ is a cycle. © 2008 Wiley Periodicals, Inc. J Graph Theory 60: 87–98, 2009
Macro and trace elements in edible tissues of Carcinus maenas and Necora puber
Authors: Teixeira Bárbara , Barrento Sara , Carvalho Maria Luísa , Nunes Maria Leonor , Marques António
Published: September 2008

BACKGROUND: Macro and trace elements have significant impacts on human health. Yet, information of elemental content in seafood is still scarce. Green crab Carcinus maenas and velvet crab Necora puber are mainly caught off English, Scottish and French coastal waters and live transported to Southern Europe, where they are consumed. During transportation, mortalities can reach 50% and dead animals are regularly commercialized for human consumption. The present study characterises the elemental composition of both species.

RESULTS: C. maenas exhibited higher K, Fe and Br contents than N. puber, and lower Mn, Cu, As, Hg and Pb levels. Hepatopancreas was the most distinct tissue, with higher Ca, Mn, Fe, Cu, Br, Sr, Cd and Pb levels compared to muscle and gonads. Differences between live and dead crabs were species and tissue dependent, though live C. maenas had higher Fe content and lower Mg and Se levels, whereas live N. puber exhibited higher As content and lower Na, Mg, Cl, Br, Sr and Cd values.

CONCLUSION: Both species were considered as safe food items since toxic elements were always below the maximum level or action level. In addition, they are good sources of Na, Cl, Ca, Cu, Zn and Se. Copyright © 2008 Society of Chemical Industry
PCR‐RFLP and DAMD‐PCR genotyping forSalviaspecies
Authors: Karaca Mehmet , Ince Ayse Gul , Ay Saadet Tugrul , Turgut Kenan , Onus Ahmet Naci
Published: September 2008

BACKGROUND:Identification of genotypes inSalviais complicated owing to the morphological similarity and common occurrence of natural hybridisation withinSalviaspecies. Species‐ and genotype‐specific DNA markers are very useful for plant identification, breeding and preservation programmes and can also provide a general overview on the prediction of plant essential oil yield.

RESULTS:Polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) was used for identification of species‐specific chloroplast and mitochondrial organelle DNA markers, and directed amplification of minisatellite DNA polymerase chain reaction (DAMD‐PCR) was used for genotyping of plant materials. Application of PCR‐RFLP resulted in species‐specific DNA markers, and use of DAMD‐PCR resulted in reproducible DNA patterns that are useful inSalviagenetic studies. Multivariate cluster analysis and principal coordinate analysis indicated that there were relationships between DNA marker patterns and essential oil yields at the species level.

CONCLUSION:Results showed that genetic variations inSalviaare wide, and DNA patterns of relatedness among plant species appeared to correlate with essential oil yields. Further studies are required to confirm the application of PCR‐RFLP and DAMD‐PCR markers for selection ofSalviaspecies with higher essential oil yield. Copyright © 2008 Society of Chemical Industry
Isolation and chemical characterisation of a polysaccharide from green tea (Camellia sinensisL.)
Authors: Chen Haixia , Wang Zhaoshuai , Lu Xueming , Xie Bijun
Published: September 2008

BACKGROUND:To contribute towards understanding the relationship of structure and bioactivity, a protein‐bound acidic polysaccharide named TPC3‐1 was isolated and purified from low‐grade green tea (Camellia sinensisL.). The homogeneity and weight average molecular weight of TPC3‐1 was determined by agarose gel electrophoresis and high‐performance gel permeation chromatography. The monosaccharide and amino acid composition of TPC3‐1 were analysed by gas chromatography and an amino acid analyser. The molecular structure of TPC3‐1 was characterised by Fourier transform infrared spectroscopy,13C nuclear magnetic resonance spectroscopy and atomic force microscopy.

RESULTS:Based on the data obtained, the average peak molecular weight of TPC3‐1 was about 120 kDa. TPC3‐1 was composed ofL‐arabinose,D‐ribose,D‐xylose,D‐glucose andD‐galactose with a molar ratio of 4.9:2.2:3.1:1.8:1.0. Fifteen amino acids were identified as components of the polymer. The TPC3‐1 molecule was found to have an anomeric carbon sign of both α and β configurations and high‐branched chains. The network structure of TPC3‐1 was observed.

CONCLUSION:The tea polysaccharide TPC3‐1 was an acid protein‐bound polysaccharide with an image of network structure. The results presented here will facilitate further study of the relationship between the chemical structure and biological role of tea polysaccharide. Copyright © 2008 Society of Chemical Industry
Hepatic epithelioid hemangioendothelioma: Long‐term results of surgical management
Authors: Mosoia Liviu , Mabrut Jean‐Yves , Adham Mustapha , Boillot Olivier , Ducerf Christian , Partensky Christian , Baulieux Jacques
Published: September 2008

Background and Objectives

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular neoplasm of the liver. Its therapeutic management remains difficult to define in curative intent. The aim of this study was to report long‐term results of surgically managed patients.

Methods

From 1990 to 2006, nine patients (25–64 years) were retrospectively enrolled in this study. Intrahepatic disease extent was monolobar and bilobar in two and seven patients, respectively. As primary treatment, liver resection (LR) and liver transplantation (LT) were performed in three (two monolobar and one bilobar extent) and six patients, respectively.

Results

Postoperative mortality was nil. During a median follow‐up of 117 months, four patients developed intrahepatic and/or extrahepatic recurrence. One resected patient (with bilobar extent) presented with intrahepatic recurrence was secondary treated by LT. At the time of the follow‐up, seven out of the nine patients treated (two after LR, and five after LT) were alive and disease‐free.

Conclusions

Surgical treatment offers good long‐term results in patients suffering from HEHE when LR is tailored to the intrahepatic disease extent: LT has to be considered in patients with bilobar intrahepatic disease whereas LR should be strictly limited to patients presenting with localized and monolobar intrahepatic disease. J. Surg. Oncol. © 2008 Wiley‐Liss, Inc.
Elevated levels of circulating endothelial progenitor cells in head and neck cancer patients
Authors: Brunner Markus , Thurnher Dietmar , Heiduschka Gregor , Grasl Matthaeus Ch , Brostjan Christine , Erovic Boban M.
Published: September 2008

Background and Objectives

Measurement of circulating endothelial cells (CECs) and progenitor cells (EPCs) has potential as a surrogate marker for monitoring anticancer treatment. This study evaluated the significance of CECs and EPCs in the blood of patients with head and neck squamous cell carcinoma.

Methods

In a prospective trial fresh blood samples from 22 tumor patients and 18 controls were tested using multiparametric flow‐cytometry. CECs were defined as CD31+/CD146+ and CD45−/7AAD−. EPCs were defined as CD133+/KDR+ and CD3−/CD19−/CD33−/7AAD−.

Results

Median levels (min/max) of CECs in the tumor group were 2 (0/5) at the time of diagnosis, 1 (0/5) 1 year after therapy and 2 (0/6) in the control cohort. Median levels of EPCs were 5 (1/41) before and 10 (0/21) after treatment in the tumor group compared to 2 (0/7) in the control cohort (P < 0.001 and P = 0.03). CEC and EPC levels showed no apparent correlation with tumor size and response to radiotherapy after 18 months of observation.

Conclusions

In this pilot study CD133+/KDR+ EPCs were significantly elevated in head and neck tumor patients before and after therapy. Our results warrant further studies on the use of EPCs as a surrogate marker for anticancer therapies in these patients. J. Surg. Oncol. 2008;98:545–550. © 2008 Wiley‐Liss, Inc.
Methoden zur mechanischen Charakterisierung von modifizierten Implantatoberflächen in der Orthopädischen Chirurgie
Authors: Fritsche A. , Haenle M. , Mittelmeier W. , Neumann H.‐G. , Heidenau F. , Fulda G. , Bader R.
Published: September 2008

Derzeit müssen in den ersten 10 Jahren nach Implantation durchschnittlich etwa 10 % aller Hüft‐ und Knieendoprothesen ausgetauscht werden. Eine Revision ist meist infolge aseptischer oder septischer Lockerung der Implantate erforderlich. Zur verbesserten Osteointegration werden Implantate für die Orthopädische Chirurgie heute zunehmend beschichtet. Beschichtungen müssen biokompatibel sein und hohen mechanischen Anforderungen gerecht werden. Hierbei spielen die Haftfestigkeit und die Abriebbeständigkeit der Schichten eine Schlüsselrolle. In der vorliegenden Arbeit werden Methoden zur experimentellen Bestimmung dieser Parameter mittels verschiedener Verfahren exemplarisch an zwei innovativen Implantatbeschichtungen (TiN und TiO2‐Cu) vorgestellt. Zur Ermittlung der Haftfestigkeit wurden unterschiedliche, standardisierte Verfahren verwendet. Dazu zählten der Dornbiegeversuch, die Ritzprüfung und der Stirnzugversuch. Die Abriebbeständigkeit wurde in einem speziellen Prüfstand nach 1,5 Mio Lastzyklen ermittelt. Die Untersuchungen zeigten, dass die beiden getesteten TiN‐ und TiO2‐Cu‐Schichten haftfest und abriebbeständig waren. Mit den genannten Verfahren lassen sich die Haftfestigkeit und die Abriebbeständigkeit von bioaktiven, verschleißmindernden oder anti‐allergenen Oberflächenbeschichtungen für Endoprothesen zuverlässig bestimmen.
Flussmittelfreies Hartlöten unter reaktiver Prozessgasatmosphäre – ein alternatives Verfahren zum Fügen von Aluminiumwerkstoffen
Authors: Bach Fr.‐W. , Möhwald K. , Holländer U. , Tiemann S.
Published: September 2008

Das Fügen von Aluminiumwerkstoffen ist aufgrund der hohen Sauerstoffaffinität des Aluminiums nach wie vor eine Herausforderung. Insbesondere die Wirtschaftlichkeit des Verfahrens sowie der Verzicht auf Flussmittel beim Schutzgasofenlöten stehen derzeit im Vordergrund aktueller Forschungsvorhaben. Die gezielte Zumischung reaktiver Gase zur inerten Prozessgasatmosphäre bietet eine geeignete Möglichkeit, Aluminiumwerkstoffe flussmittelfrei zu löten. Unter Einsatz von Chlorwasserstoff soll eine Aktivierung der Lot‐ und Werkstückoberfläche ermöglicht werden, die eine Zerstörung der Oxidschichten einleiten soll. Des Weiteren kommt das stark reduzierende Gas Silan zum Einsatz, dass die Schutzgasatmosphäre gezielt von Sauerstoff‐ und Wasserrückständen befreit. Anhand eines geeigneten Ofenlötprozesses sollen sowohl reduzierende als auch aktivierende Zusätze in Kombination eingesetzt und auf ihren Einfluss auf die verwendeten Gasmischungen und Werkstoffe getestet werden [1–5].
Verbundschmieden hybrider Stahl‐Aluminium Bauteile
Authors: Behrens B.‐A. , Holz F.
Published: September 2008

In Zeiten steigender Energiepreise kommt dem Leichtbau in der Automobilindustrie eine besondere Rolle zu. Die Herstellung hybrider Bauteile mittels Massivumformung stellt dabei eine Erfolg versprechende Methode dar, einbaufertige Funktionsteile in wenigen Prozessschritten ressourcenschonend herzustellen. Bei der Kombination von Stahl und Aluminium als hybrides Werkstoffsystem ist die Erwärmung der Bauteile eine besondere Herausforderung, da der Stahl bei einer Temperatur von mindestens 900 °C umgeformt wird, während das Aluminium eine Temperatur von 500 °C nicht überschreiten sollte. Für diese inhomogene Temperaturverteilung werden Erwärmungsmöglichkeiten aufgezeigt.
Kinematik und Spanungsformen beim Zirkularfräsen
Authors: Denkena B. , de Leon L. , Dege J.H.
Published: September 2008

Eine Alternative zur konventionellen Bohrbearbeitung mit Spiralbohrern ist das Zirkularfräsen, auch Orbitalbohren genannt. Hierbei bewegt sich ein Schaftfräswerkzeug auf einer helixförmigen Bahn in das Werkstück und erzeugt so die Bohrung. Im Rahmen dieser Arbeit wird zunächst die Kinematik beim Zirkularfräsen und anschließend die sich aus den Eingriffsbedingungen ergebenden Spanungsformen beschrieben. Für die Ermittlung der Spanungsform werden zwei Ansätze zur Berechnung der drehwinkelabhängigen axialen Schnitttiefe miteinander verglichen. Eine darauf basierende Berechnung des zerspanten Volumens an Axial‐ und Tangentialschneide zeigt, dass das Volumenverhältnis nur vom Verhältnis von Werkzeug‐ zu Bohrungsdurchmesser abhängt.
Identifying personality traits to enhance trust between organisations: an experimental approach
Authors: Fahr René , Irlenbusch Bernd
Published: September 2008

We investigate an experimental representatives' trust game which resembles trust relationships between representatives of organisations. Personality traits of subjects are elicited by a personality questionnaire (Cattell's 16 PF‐R) which is well established in personnel psychology. For the first time, personality traits are linked to actually observed behaviour in a trust game. Detailed personality profiles are derived and it is shown that they differ significantly between behavioural types. Individuals with low scores in anxiety turn out to be particularly qualified for enhancing trust between organisations. Copyright © 2008 John Wiley & Sons, Ltd.
Oxidation products of polyunsaturated fatty acids in infant formulas compared to human milk – A preliminary study
Authors: Michalski Marie‐Caroline , Calzada Catherine , Makino Asami , Michaud Sabine , Guichardant Michel
Published: September 2008

Information about lipid oxidation in fresh and stored human milk compared with infant formulas is scarce. We aimed to assess n‐6 and n‐3 PUFA oxidation in these milks by measuring the 4‐hydroxynonenal (4‐HNE) and 4‐hydroxyhexenal (4‐HHE) content. Human milk samples (n = 4), obtained from volunteer mothers, were analyzed fresh and after 1 wk at 4°C or 24 h at 18°C. Vitamin E and malondialdehyde (MDA) were measured by HPLC and fatty acid profile by GC. The 4‐HHE and 4‐HNE contents were measured by GC‐MS. Infant formulas (n = 10) were tested; their fat droplet size was measured by laser light scattering and observed by confocal laser scanning microscopy. Human milk samples contained 31.0 ± 6.3 g/L of lipids and 1.14 ± 0.26 mg/L of vitamin E. Fat droplets were smaller in infant formulas than reported in human milk. The (4‐HHE/n‐3 PUFA) ratio was 0.19 ± 0.01 μg/g in fresh human milk (unchanged after storage) versus 3.6 ± 3.1 μg/g in dissolved powder formulas and 4.3 ± 3.8 μg/g in liquid formula. (4‐HNE/n‐6 PUFA) was 0.004 ± 0.000 μg/g in fresh milk (0.03 ± 0.01 μg/g after storage) versus 1.1 ± 1.0 μg/g in dissolved powder formulas and 0.2 ± 0.3 μg/g in liquid formula. Infant formulas also contained more MDA than human milk. n‐3 PUFA were more prone to oxidation than n‐6 PUFA. Whether threshold levels of 4‐HHE and 4‐HNE would be of health concern should be elucidated.
Pyrrolizidine alkaloids in honey: Risk analysis by gas chromatography‐mass spectrometry
Authors: Kempf Michael , Beuerle Till , Bühringer Manuela , Denner Martina , Trost Daniela , von der Ohe Katharina , Bhavanam Vijaya B. R. , Schreier Peter
Published: September 2008

Recently, contamination of honey with pyrrolizidine alkaloids (PA) has been reported as potential health risk. Therefore, it was of interest to develop a reliable tool for selective and quantitative determination of PA in honey. Sample preparation of the novel method comprises strong cation exchange SPE (SCX‐SPE), followed by two reduction steps using zinc and LiAlH4, as well as subsequent silylation. During this procedure the separated PA are converted into the necin backbone, the common structural feature of PA toxicity, which is analyzed by GC‐MS in the SIM mode. The procedure was validated using PA from extracts of Senecio vernalis as well as authentic PA standards including their corresponding N‐oxides. The PA content of honey samples was quantified with heliotrine as internal standard. The method was applied to generate a dataset in order to evaluate the potential risk of PA contamination especially for retail honeys available on the German/European market. No selection criteria in terms of floral or geographical origin were applied on the samples before analysis. In total, 216 commercially available floral honey samples were analyzed. Among them 19 samples contained PA, in the range of 0.019–0.120 μg/g, calculated as retronecine equivalents. The reported method facilitates the selective determination of PA without the need to identify each individual PA independently. The PA contamination of honey is expressed in terms of a single sum parameter and no background information such as foraged plants and pollen analysis is necessary. The LOQ is 0.01 ppm with a S/N of 7:1.