bluuebunny/crossref_metadata_2025 huggingface dataset:
T‐bet, a Th1 transcription factor regulates the expression of Tim‐3
Authors: Anderson Ana C. , Lord Graham M. , Dardalhon Valerie , Lee David H. , Sabatos‐Peyton Catherine A. , Glimcher Laurie H. , Kuchroo Vijay K.
Published: January 2010

T‐cell immunoglobulin, mucin domain‐3 (Tim‐3) is a membrane protein expressed at late stages of IFN‐γ secreting CD4+ Th1 cell differentiation and constitutively on DC. Ligation of Tim‐3 on Th1 cells terminates Th1 immune responses. In addition, Tim‐3 plays a role in tolerance induction, although the mechanism by which this is accomplished has yet to be elucidated. While it is clear that Tim‐3 plays an important role in the immune system, little is known regarding the molecular pathways that regulate Tim‐3 expression. In the current study, we examine the role of Th1‐associated transcription factors in regulating Tim‐3 expression. Our experiments reveal that Tim‐3 expression is regulated by the Th1‐specific transcription factor T‐bet. This introduces a novel paradigm into the generation of a Th1 response, whereby a transcription factor responsible for effector Th1 cell differentiation also increases the expression of a specific counter‐regulatory molecule to ensure appropriate termination of pro‐inflammatory Th1 immune responses.
c‐Rel is crucial for the induction of Foxp3+ regulatory CD4+ T cells but not TH17 cells
Authors: Visekruna Alexander , Huber Magdalena , Hellhund Anne , Bothur Evita , Reinhard Katharina , Bollig Nadine , Schmidt Nicole , Joeris Thorsten , Lohoff Michael , Steinhoff Ulrich
Published: January 2010

The NF‐κB/Rel family member c‐Rel was described to be required for the development of TH1 responses. However, the role of c‐Rel in the differentiation of TH17 and regulatory CD4+Foxp3+ T cells (Treg) remains obscure. Here, we show that in the absence of c‐Rel, in vitro differentiation of pro‐inflammatory TH17 cells is normal. In contrast, generation of inducible Treg (iTreg) within c‐Rel‐deficient CD4+ T cells was severely hampered and correlated to reduced numbers of Foxp3+ T cells in vivo. Mechanistically, in vitro conversion of naive CD4+ T cells into iTreg was crucially dependent on c‐Rel‐mediated synthesis of endogenous IL‐2. The addition of exogenous IL‐2 was sufficient to rescue the development of c‐Rel‐deficient iTreg. Thus, c‐Rel is essential for the development of Foxp3+ Treg but not for TH17 cells via regulating the production of IL‐2.
Synthesis, Crystal Structure, and Catalytic Properties of Novel Dioxidomolybdenum(VI) Complexes with Tridentate Schiff Base Ligands in the Biomimetic and Highly Selective Oxygenation of Alkenes and Sulfides
Authors: Rezaeifard Abdolreza , Sheikhshoaie Iran , Monadi Niaz , Stoeckli‐Evans Helen
Published: January 2010

Four novel dioxidomolybdenum(VI) complexes [MoO2(Lx)(CH3OH)] have been synthesized, using 2[(E)‐(2‐hydroxy‐2‐phenylethylimino)methyl]phenol derivatives as tridentate ONO donor Schiff base ligands (H2Lx) and MoO2(acac)2. A monoclinic space group was determined by X‐ray crystallography from single‐crystal data of a sample of these new complexes. The epoxidation of alkenes by using tert‐butyl hydroperoxide and oxidation of sulfides to sulfoxides by urea hydrogen peroxide were efficiently enhanced with excellent selectivity under the catalytic influence these new MoVI complexes. The high efficiency and relative stability of the catalysts have been observed by turnover numbers and UV/Vis investigations. The electron‐poor and bulky ligands promoted the effectiveness of the catalysts.
On the Spin Behaviour of Iron(II)–Dipyridyltriazine Complexes and Their Performance as Thermal and Photonic Spin Switches (Eur. J. Inorg. Chem. 2/2010)
Authors: Hain Sophie K. , Heinemann Frank W. , Gieb Klaus , Müller Paul , Hörner Gerald , Grohmann Andreas
Published: January 2010

The cover picture shows the crystal structure of an iron(II) complex with a tridentate triazine‐based ligand, one of three complexes whose thermal and photonic spin‐dynamics are discussed in the article by G. Hörner, A. Grohmann et al. on p. 221 ff. While there is a competition between spin crossover and ligand exchange upon thermal excitation in solution, the complexes switch cleanly between their stable low‐spin and metastable high‐spin forms upon photoexcitation. Artwork: Holger Neumann, Gentura.
New Stable N‐H Oxaziridines – Synthesis and Reactivity
Authors: Blanc Sylvain , Bordogna Céline A. C. , Buckley Benjamin R. , Elsegood Mark R. J. , Page Philip C. Bulman
Published: January 2010

A number of stable new N‐H oxaziridines have been designed and prepared, and their reactivity as electrophilic sources of nitrogen investigated. 3‐tert‐Butyl‐3‐phenyloxaziridine is the most efficient and stable and has potential for use as a general reagent for this purpose.
One‐Pot Synthesis of 3‐Aryltetramic Acids
Authors: Mallinger Aurélie , Nadal Brice , Chopin Nicolas , Le Gall Thierry
Published: January 2010

Tetramic acids substituted in the 3‐position by various aryl groups were prepared in one‐pot from amino esters and methyl arylacetates, by treatment with potassium tert‐butoxide. A tandem process, involving the formation of an amide and a condensation reaction, is likely to occur. N‐Unsubstituted tetramic acids were obtained from adducts containing a N‐(2,4‐dimethoxybenzyl) group.
Oligoaryl Cruciform Structures as Model Compounds for Coordination‐Induced Single‐Molecule Switches
Authors: Grunder Sergio , Huber Roman , Wu Songmei , Schönenberger Christian , Calame Michel , Mayor Marcel
Published: January 2010

The synthesis of two new cruciform structures 3 and 4 comprising an oligo(phenylene‐vinylene) (OPV) and a perpendicular oligoaryl bar – namely an oligophenylene (OP) (3) and a naphthyl–phenyl–naphthyl system (4) – is reported. The OPV rod consists of two terminal pyridine units, whereas the oligoaryl rod bears two terminal acetylsulfanyl groups as protected anchor groups. The OPV bar was assembled via a Horner–Wadsworth–Emmons reaction, which directly led to the desired E,E isomers. The perpendicular oligoaryl bars were assembled with a Suzuki reaction using the corresponding boronic acids, which were already fitted with an ethyl‐trimethylsilane (ethyl‐TMS) sulfanyl group. In a last step, the ethyl‐TMS‐protected sulfur atoms were transprotected to the thioacetyl units. The cruciform structures 3 and 4 are model compounds to investigate a coordination‐induced single‐molecule switch exploiting the potential‐dependant different bonding strengths of the anchor groups to gold. Metal–molecule–metal junctions were formed using a mechanically controllable break junction (MCBJ) setup. Current traces of molecular junctions were statistically analyzed. Further investigations of model compounds consisting only of the single bar confirm that individual molecules carrying the required function for the switching experiments were trapped between two electrodes and were mainly immobilized via thiol–gold anchor bonds.
Furan Ring‐Opening/Indole Ring‐Closure: Pictet–Spengler‐Like Reaction of 2‐(o‐Aminophenyl)furans with Aldehydes
Authors: Butin Alexander V. , Uchuskin Maxim G. , Pilipenko Arkady S. , Tsiunchik Fatima A. , Cheshkov Dmitry A. , Trushkov Igor V.
Published: January 2010

A new simple approach to 3‐(2‐acylvinyl)‐2‐(hetero)arylindoles has been developed. The method is based on the acid‐catalysed interaction of 2‐(2‐aminophenyl)furans with(hetero)aromatic aldehydes. The reactions proceed under very mild conditions and lead to indoles containing a reactive α,β‐unsaturated ketone moiety, which is suitable for further transformations, in moderate to good yields.
Service restoration on distribution systems using Multi‐MicroGrids
Authors: Resende F. O. , Gil N. J. , Lopes J. A. Peças
Published: January 2010

Large scale integration of distributed generation of both medium and low voltage (LV) networks can be achieved by exploiting the Multi‐MicroGrid (MMG) concept, a new distribution system architecture comprising a hierarchical control system, which allows the coordination among distributed generation units and MicroGrids (MGs) and therefore the operation of such a system in islanded mode. After a general blackout the MMG capabilities can also be used to provide service restoration in distribution systems. A new procedure for MMGs black start is then addressed in this paper. A sequence of control actions is defined and evaluated through numerical simulations. Fully automation of the entire MMG black start procedure is discussed along the paper. The results obtained demonstrate the feasibility of the proposed sequence of control actions and highlight some accomplishments that should be considered in order to successfully restore the MMG service, ensuring system stability and power quality. Copyright © 2010 John Wiley & Sons, Ltd.
Family history of cancer and risk of pancreatic cancer: A pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan)
Authors: Jacobs Eric J. , Chanock Stephen J. , Fuchs Charles S. , LaCroix Andrea , McWilliams Robert R. , Steplowski Emily , Stolzenberg‐Solomon Rachael Z. , Arslan Alan A. , Bueno‐de‐Mesquita H. Bas , Gross Myron , Helzlsouer Kathy , Petersen Gloria , Zheng Wei , Agalliu Ilir , Allen Naomi E. , Amundadottir Laufey , Boutron‐Ruault Marie‐Christine , Buring Julie E. , Canzian Federico , Clipp Sandra , Dorronsoro Miren , Gaziano J. Michael , Giovannucci Edward L. , Hankinson Susan E. , Hartge Patricia , Hoover Robert N. , Hunter David J. , Jacobs Kevin B. , Jenab Mazda , Kraft Peter , Kooperberg Charles , Lynch Shannon M. , Sund Malin , Mendelsohn Julie B. , Mouw Tracy , Newton Christina C. , Overvad Kim , Palli Domenico , Peeters Petra H.M. , Rajkovic Aleksandar , Shu Xiao‐Ou , Thomas Gilles , Tobias Geoffrey S. , Trichopoulos Dimitrios , Virtamo Jarmo , Wactawski‐Wende Jean , Wolpin Brian M. , Yu Kai , Zeleniuch‐Jacquotte Anne
Published: January 2010

A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case‐control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case‐control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate‐adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19–2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI = 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52–1.31), breast cancer (OR = 1.21, 95% CI = 0.97–1.51) or colorectal cancer (OR = 1.17, 95% CI = 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study.
Cost‐effectiveness analysis of cervical cancer prevention based on a rapid human papillomavirus screening test in a high‐risk region of China
Authors: Levin Carol E. , Sellors John , Shi Ju‐Fang , Ma Li , Qiao You‐lin , Ortendahl Jesse , O'Shea Meredith K.H. , Goldie Sue J.
Published: January 2010

This study assessed the cost‐effectiveness of a new, rapid human papillomavirus (HPV)‐DNA screening test for cervical cancer prevention in the high‐risk region of Shanxi, China. Using micro‐costing methods, we estimated the resources needed to implement preventive strategies using cervical cytology or HPV‐DNA testing, including the Hybrid Capture 2 (hc2) test (QIAGEN Corp., Gaithersburg, MD) and the rapid HPV‐DNAcareHPV™ test (QIAGEN). Data were used in a previously published model and empirically calibrated to country‐specific epidemiological data. Strategies differed by initial test, targeted age, frequency of screening, number of clinic visits required (1, 2 or 3) and service delivery setting (national, county and township levels). Outcomes included lifetime risk of cancer, years of life saved (YLS), lifetime costs and incremental cost‐effectiveness ratios (cost per YLS). For all screening frequencies, the most efficient strategy used 2‐visit rapid HPV‐DNA testing at the county level, including screening and diagnostics in the first visit, and treatment in the second visit. Screening at ages 35, 40 and 45 reduced cancer risk by 50% among women compliant with all 3 screening rounds, and was US$ 150 per YLS, compared with this same strategy applied twice per lifetime. This would be considered very cost‐effective evaluated against China's per‐capita gross domestic product (US$ 1,702). By enhancing the linkage between screening and treatment through a reduced number of visits, rapid HPV‐DNA testing 3 times per lifetime is more effective than traditional cytology, and is likely to be cost‐effective in high‐risk regions of China.
Additional value of EGFR downstream signaling phosphoprotein expression to KRAS status for response to anti‐EGFR antibodies in colorectal cancer
Authors: Perkins Geraldine , Lièvre Astrid , Ramacci Carole , Méatchi Tchao , de Reynies Aurélien , Emile Jean‐François , Boige Valérie , Tomasic Gorana , Bachet Jean‐Baptiste , Bibeau Fréderic , Bouché Olivier , Penault‐Llorca Frédérique , Merlin Jean‐Louis , Laurent‐Puig Pierre
Published: January 2010

KRAS mutations are a strong predictive marker of resistance to anti‐epidermal growth factor receptor (EGFR) antibodies in advanced colorectal cancer (CRC) but only a subset of wild‐type (WT) KRAS patients are responders, suggesting the existence of additional markers of resistance to this treatment. The activation of EGFR downstream signaling pathways may be one of these ones. In a series of 42 patients with advanced CRC treated with cetuximab/panitumumab, for whom KRAS status was previously determined, we retrospectively analyzed the intratumor expression of EGFR downstream signaling phosphoproteins of the RAS/MAPK and PI3K/AKT pathways (pERK1/2, pMEK1, pAKT, pP70S6K and pGSK3β) using Bio‐Plex® phosphoprotein array. Association with tumor response, progression‐free survival (PFS) and overall survival (OS) was assessed. The expression of all the phosphoproteins was higher in KRAS mutated tumors than in WT tumors. The expression of pP70S6K was lower in responders than in nonresponder patients. In univariate analysis, patients with high pMEK1 or pP70S6K expression had a shorter PFS than those with low expression. Patients with high pP70S6K expression also had a shorter OS. In multivariate analysis, PFS was shorter for patients with high pMEK1 or pP70S6K expression, independently of KRAS status, as OS for patients with high pP70S6K expression. Therefore, WT KRAS patients with high pP70S6K expression had a shorter survival than those with low expression. Our results suggest the importance of EGFR downstream signaling phosphoproteins expression in addition to KRAS status to define the subgroup of patients who will not benefit from anti‐EGFR therapy.
Cancer incidence in people with AIDS in Italy
Authors: Polesel Jerry , Franceschi Silvia , Suligoi Barbara , Crocetti Emanuele , Falcini Fabio , Guzzinati Stefano , Vercelli Marina , Zanetti Roberto , Tagliabue Giovanna , Russo Antonio , Luminari Stefano , Stracci Fabrizio , De Lisi Vincenzo , Ferretti Stefano , Mangone Lucia , Budroni Mario , Limina Rosa Maria , Piffer Silvano , Serraino Diego , Bellù Francesco , Giacomin Adriano , Donato Andrea , Madeddu Anselmo , Vitarelli Susanna , Fusco Mario , Tessandori Roberto , Tumino Rosario , Piselli Pierluca , Dal Maso Luigino ,   for the Cancer and AIDS Registries Linkage (CARL) Study
Published: January 2010

People with HIV/AIDS (PWHA) have increased risk of some cancers. The introduction of highly active antiretroviral therapies (HAART) has improved their life expectancy, exposing them to the combined consequences of aging and of a prolonged exposure to cancer risk factors. The aim of this study was to estimate incidence rates (IR) in PWHA in Italy, before and after the introduction of HAART, after adjusting for sex and age through direct standardization. An anonymous record linkage between Italian AIDS Registry (21,951 cases) and Cancer Registries (17.3 million, 30% of Italian population) was performed. In PWHA, crude IR, sex‐ and age‐standardized IR and age‐specific IR were estimated. The standardized IR for Kaposi sarcoma and non‐Hodgkin lymphoma greatly declined in the HAART period. Although the crude IR for all non‐AIDS‐defining cancers increased in the HAART period, standardized IR did not significantly differ in the 2 periods (352 and 379/100,000, respectively). Increases were seen only for cancer of the liver (IR ratio = 4.6, 95% CI: 1.3–17.0) and lung (IR ratio = 1.8, 95% CI: 1.0–3.2). Age‐specific IRs for liver and lung cancers, however, largely overlapped in the 2 periods pointing to the strong influence of the shift in the age distribution of PWHA on the observed upward trends. In conclusion, standardized IRs for non‐AIDS‐defining cancers have not risen in the HAART period, even if crude IRs of these cancers increased. This scenario calls, however, for the intensification of cancer‐prevention strategies, notably smoking cessation and screening programs, in middle‐aged HIV‐patients.
Inter‐test agreement and quantitative cross‐validation of immunochromatographical fecal occult blood tests
Authors: Brenner Hermann , Haug Ulrike , Hundt Sabrina
Published: January 2010

Immunochromatographical fecal occult blood tests were shown to have higher sensitivity for detecting colorectal neoplasms than the commonly used guaiac‐based test. However, positivity rates, sensitivity and specificity vary widely. We aimed to assess the reasons for this heterogeneity. Six dichotomous (qualitative) immunochromatographical tests were used in the same stool samples, taken before cathartic bowel preparation, from 1,330 participants of the German colonoscopy screening program. Positivity rates were determined, and inter‐test agreement beyond chance was quantified by kappa coefficients (κ). In addition, kappa coefficients were expressed in relation to their maximum possible values given differences in test positivity rates (κ/κmax). Furthermore, the distribution of fecal hemoglobin concentration was assessed by an additional quantitative test in participants classified as clearly positive, borderline positive or clearly negative according to the qualitative tests. Positivity rates strongly varied from 6.4 to 46.8%. As a result, overall agreement between tests was only poor to moderate, with κ ranging from 0.14 to 0.61. However, apart from the different positivity rates, agreement was mostly very high, with κ/κmax ranging from 0.53 to 1.00, and exceeding 0.70 in 12 of 15 cases. Distribution of fecal hemoglobin concentrations in the various categories strongly varied across tests. The observed patterns suggest that the strongly different positivity rates essentially reflect different cutoff levels of tests with otherwise very high inter‐test agreement. Definition of cutoffs is a critical issue in the application of immunochromatographical tests and should be redefined for several of these tests.
Partners in treatment: relational psychoanalysis and harm reduction therapy
Authors: Rothschild Debra
Published: January 2010

A relational psychoanalytic harm reduction orientation to the treatment of substance misusers is presented and illustrated with a clinical example. Both harm reduction therapy and relational psychoanalysis rely on a two‐person model in which the therapist and client are collaborators in the treatment. In both, substance use is seen in the context of the user's internal psychodynamics and external environment, and there is an emphasis on treating the person as a whole individual whose substance use is one aspect of life, rather than focusing on the substance use itself as was often done in the past. Historically, psychoanalysis and substance abuse treatment were so different from each other that their paths rarely crossed. The introduction of harm reduction therapy to substance abuse and the relational orientation in psychoanalysis have brought the fields closer together such that the valuable contributions that each can make to the other can now be appreciated. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66: 1–14, 2010.
State of the art in harm reduction psychotherapy: an emerging treatment for substance misuse
Authors: Tatarsky Andrew , Marlatt G. Alan
Published: January 2010

Harm reduction psychotherapy is an exciting and emerging treatment for a broad spectrum of substance use problems. This article introduces an issue of the Journal of Clinical Psychology: In Session devoted to the state of the art of harm reduction psychotherapy. We describe the harm reduction paradigm, the context for and history of the development of harm reduction psychotherapy, and its clinical principles. We then outline and frame the contributions to the issue. Our goal is that this issue will encourage psychotherapists to employ more harm reduction principles in practice and will provide many evidence‐based methods to do so. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66: 1–6, 2010.
Src signaling in cancer invasion
Authors: Guarino Marcello
Published: January 2010

Src is a non‐receptor cytoplasmic tyrosine kinase which becomes activated following the stimulation of plasma membrane receptors including receptor tyrosine kinases and integrins, and is an indispensable player of multiple physiological homeostatic pathways. Once activated, Src is the starting point for several biochemical cascades that thereby propagate signals generated extracellularly along intracellular interconnected transduction pathways. Src transmits signals promoting cell survival and mitogenesis and, in addition, exerts a profound effect on the reorganization of the cytoskeleton and the adhesion systems that underpin cell migration and invasion. Because increased activity of Src is a frequent occurrence in many types of human cancer, and because there is evidence of a prominent role of Src in invasion and in other tumor progression‐related events such as epithelial–mesenchymal transition (EMT) and development of metastasis, inhibitors targeting Src are being viewed as promising drugs for cancer therapy. J. Cell. Physiol. 223: 14–26, 2010. © 2009 Wiley‐Liss, Inc.
Impact of growth factors and PTHrP on early and late chondrogenic differentiation of human mesenchymal stem cells
Authors: Weiss S. , Hennig T. , Bock R. , Steck E. , Richter W.
Published: January 2010

Common in vitro protocols for chondrogenesis of mesenchymal stem cells (MSCs) induce an inadequate, hypertrophic differentiation cascade reminiscent of endochondral bone formation. We aimed to modify chondrogenic protocols in order to identify potent inducers, promotors, and inhibitors to achieve better chondrogenesis. Nine factors suspected to stimulate or inhibit chondrogenesis were used for chondrogenic in vitro induction of MSC. Differentiation was assessed by immunohistochemistry, alcian‐blue staining, qRT‐PCR, and quantification of alkaline phosphatase (ALP) activity. Pre‐differentiated pellets were transplanted subcutaneously into SCID mice to investigate stable cartilage formation. Transforming growth factor (TGF)‐β was always required for chondrogenic differentiation and deposition of a collagen‐type‐II‐positive extracellular matrix, while bone morphogenetic protein (BMP)‐2, ‐4, ‐6, ‐7, aFGF, and IGF‐I (10 ng/ml) were alone not sufficiently inductive. Each of these factors allowed differentiation in combination with TGF‐β, however, without preventing collagen type X expression. bFGF or parathyroid hormone‐like peptide (PTHrP) inhibited the TGF‐β‐responsive COL2A1 and COL10A1 expression and ALP induction when added from day 0 or 21. In line with a reversible ALP inhibition, in vivo calcification of pellets was not prevented. Late up‐regulation of PTH1R mRNA suggests that early PTHrP effects may be mediated by a receptor‐independent pathway. While TGF‐β was a full inducer, bFGF and PTHrP were potent inhibitors for early and late chondrogenesis, seemed to induce a shift from matrix anabolism to catabolism, but did not selectively suppress COL10A1 expression. Within a developmental window of collagen type II+/collagen type X− cells, bFGF and PTHrP may allow inhibition of further differentiation toward hypertrophy to obtain stable chondrocytes for transplantation purposes. J. Cell. Physiol. 223: 84–93, 2010. © 2009 Wiley‐Liss, Inc.
The activation of liver X receptors inhibits toll‐like receptor‐9‐induced foam cell formation
Authors: Sorrentino Rosalinda , Morello Silvana , Chen Shuang , Bonavita Eduardo , Pinto Aldo
Published: January 2010

Toll‐like receptors (TLRs) are related to foam cell formation (FCF), key event in the establishment/progression of atherosclerosis. The activation of TLR2 and TLR4 can increase FCF. The aim of this study was to evaluate the role of TLR9 in FCF. Murine macrophages were treated with CpG‐ODN, TLR9 agonist, and oxidized particles of LDL (Paz‐PC) and FCF was analyzed by means of Oil Red O staining. The administration of CpG‐ODN plus Paz‐PC onto macrophages increased the amount of lipid droplets, correlated to increased levels of tumor necrosis factor (TNF)‐α, IFNβ, and IP‐10. The underlying mechanism by which TLR9 ligation influenced Paz‐PC in the FCF was NF‐κB‐ and IRF7‐dependent, as observed by higher levels of phosphorylated IκBα, increased nuclear translocation of the p65 subunit, lower levels of the total IKKα protein and higher release of interferon‐dependent cytokines, such as IP‐10. Liver X receptors (LXRs) regulate lipid cellular transport and negatively modulate TLR‐dependent signaling pathways. Indeed, the addition of GW3965, synthetic LXRs agonist, significantly reduced FCF after CpG‐ODN plus Paz‐PC stimulation. In this condition, we observed decreased levels of the nuclear translocation of the p65 subunit, related to the higher presence of LXRα into the nucleus. TNF‐α, IP‐10, and IFNβ levels were reduced by the administration of GW3965 following CpG‐ODN and Paz‐PC treatment. In conclusion, the activation of TLR9 facilitates the formation of foam cells in an NF‐κB‐ and IRF7‐dependent manner, countered by the activation of LXRs. This study further support LXRs as potential anti‐atherosclerotic target. J. Cell. Physiol. 223: 158–167, 2010. © 2009 Wiley‐Liss, Inc.
NF‐κB activation stimulates osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue by increasing TAZ expression
Authors: Cho Hyun Hwa , Shin Keun Koo , Kim Yeon Jeong , Song Ji Sun , Kim Jong Myung , Bae Yong Chan , Kim Chi Dae , Jung Jin Sup
Published: January 2010

Tumor necrosis factor‐alpha (TNF‐α) is a skeletal catabolic agent that stimulates osteoclastogenesis and inhibits osteoblast function. Although TNF‐α inhibits the mineralization of osteoblasts, the effect of TNF‐α on mesenchymal stem cells (MSC) is not clear. In this study, we determined the effect of TNF‐α on osteogenic differentiation of stromal cells derived from human adipose tissue (hADSC) and the role of NF‐κB activation on TNF‐α activity. TNF‐α treatment dose‐dependently increased osteogenic differentiation over the first 3 days of treatment. TNF‐α activated ERK and increased NF‐κB promoter activity. PDTC, an NF‐κB inhibitor, blocked the osteogenic differentiation induced by TNF‐α and TLR‐ligands, but U102, an ERK inhibitor, did not. Overexpression of miR‐146a induced the inhibition of IRAK1 expression and inhibited basal and TNF‐α‐ and TLR ligand‐induced osteogenic differentiation. TNF‐α and TLR ligands increased the expression of transcriptional coactivator with PDZ‐binding motif (TAZ), which was inhibited by the addition of PDTC. A ChIP assay showed that p65 was bound to the TAZ promoter. TNF‐α also increased osteogenic differentiation of human gastroepiploic artery smooth muscle cells. Our data indicate that TNF‐α enhances osteogenic differentiation of hADSC via the activation of NF‐κB and a subsequent increase of TAZ expression. J. Cell. Physiol. 223: 168–177, 2010. © 2009 Wiley‐Liss, Inc.
Discovery of a benzoxazine derivative promoting angiogenesis in vitro and in vivo
Authors: Dong ZhiWu , Cheng YiZhe , Zhao Jing , Su Le , Zhao BaoXiang , Zhang Yun , Zhang ShangLi , Miao JunYing
Published: January 2010

Angiogenesis is a multi‐step process that refers to the growth of new vessels from pre‐existing ones. Endothelial proliferation, migration, and tube formation constitute a critical step in angiogenesis. Recently, we demonstrated that a novel benzoxazine derivative, 6‐amino‐2,3‐dihydro‐3‐hydroxymethyl‐1,4‐benzoxazine (ABO) could improve the proliferation of human umbilical vein endothelial cells (HUVECs) without basic fibroblast growth factor (bFGF) and serum. In this study, we further tested its effect on endothelial angiogenesis with Matrigel assay, migration assay, and in vivo chick chorioallantoic membrane (CAM) assay. Our results showed that ABO effectively facilitated cell migration and promoted capillary‐like tube formation in vitro and in vivo. To elucidate the underlying mechanisms, we examined intracellular reactive oxygen species (ROS) level/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and superoxide dismutase (SOD) activities, nitric oxide (NO) level/endothelial nitric oxide synthase (eNOS) activity, and mitochondrial membrane potential (MMP). Our data indicated that ABO depressed ROS with inhibition of NADPH oxidase instead of SOD activity, stimulated NO production and eNOS activation, and restored MMP in HUVECs. Our findings suggest that ABO is a promising tool for exploring the mechanisms of angiogenesis and may have a therapeutic potential in ischemic pathologies. J. Cell. Physiol. 223: 202–208, 2010. © 2009 Wiley‐Liss, Inc.
Membrane lipid defects are responsible for the generation of reactive oxygen species in peripheral blood mononuclear cells from vitiligo patients
Authors: Dell'Anna Maria Lucia , Ottaviani Monica , Bellei Barbara , Albanesi Veronica , Cossarizza Andrea , Rossi Luisa , Picardo Mauro
Published: January 2010

The pathogenesis of vitiligo, an acquired depigmenting disease of the skin, involves oxidative stress. Based on that, the generation of reactive oxygen species (ROS) by the mitochondria may be relevant in the pathogenesis of vitiligo. Here, we evaluate the biochemical and functional alterations involved in the defective activity that has been previously described both in melanocytes and peripheral blood mononuclear cells (PBMC) from vitiligo patients. Moreover, we used a freeze–thaw test as a mild stress stimulus to disclose any latent defects in the assembly of membrane lipids that may compromise the functionality of the membrane itself. We show that the lipid constitution of the membrane is altered in vitiligo. Specifically, the cardiolipin (CL) level in the mitochondrial inner membrane is reduced and the level of cholesterol is increased. Furthermore, an increase in the expression level of 3‐hydroxy‐3methyl‐glutaryl‐CoenzymeA‐reductase (HMG‐CoA reductase), the rate‐limiting enzyme for cholesterol biosynthesis, was also seen. Associated with that, the expression of electron transport chain (ETC) lipid‐dependent subunits was also modified, and their expression was further affected by the freeze–thaw stress. The expression of CL‐independent mitochondrial proteins, such as porin and Bcl2, were unaffected in vitiligo PBMC. These data confirm that ETC protein expression mainly correlates with lipid arrangement and that loss of their expression is not due to generalized or random oxidative‐mediated damage. We suggest that the modification of membrane lipid components in vitiligo cells may be the biochemical basis for the mitochondrial impairment and the subsequent production of intracellular ROS following the exposure to a mild stress. J. Cell. Physiol. 223: 187–193, 2010. © 2009 Wiley‐Liss, Inc.
Voltage‐dependent calcium and chloride currents in S17 bone marrow stromal cell line
Authors: Silva Henrique B. , Medei Emiliano , Rodrigues Deivid C. , Rondinelli Edson , Almeida Norma A.S. , Goldenberg Regina C.S. , de Carvalho Antonio C. Campos , Nascimento José H.M.
Published: January 2010

The bone marrow stromal cell line S17 has been used to study hematopoiesis in vitro. In this study, we demonstrate the presence of calcium and chloride currents in cultured S17 cells. Calcium currents were of low amplitude or barely detectable (50–100 pA). Hence to amplify the currents, we have used barium as a charge carrier. Barium currents were identified based on their distinct voltage‐dependence, and sensitivity to dihydropyridines. S17 cells also exhibited a slowly activating outward current without inactivation, most commonly seen when the sodium of the extracellular solution was replaced either by TEA (TEA/Cs saline) or NMDG (NMDG saline), or by addition of amiloride to the extracellular solution. This current was abolished either by 500 µM SITS (4,4′‐diisothiocyanatostilbene‐2‐2′‐disulfonic acid) or 500 µM DPC (diphenylamine‐2‐carboxylic acid) a cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel blocker, identifying it as a Cl− current. RT‐PCR identified the presence of ENaC and CFTR transcripts. CFTR blockade reduced cell proliferation, suggesting that this channel plays a physiological role in regulation of S17 cell proliferation. J. Cell. Physiol. 223: 244–251, 2010. © 2009 Wiley‐Liss, Inc.
Novel synthesis of [13C4,15N]1H‐pyrrole‐2,3,5‐tricarboxylic acid: an important biomarker for melatonin metabolism
Authors: Skaddan Marc B.
Published: January 2010

1H‐pyrrole‐2,3,5‐tricarboxylic acid is a breakdown product of melatonin. A labeled version of this compound would serve as a key biomarker for drug candidates which track this substance to monitor their effectiveness (e.g. hyperpigmentation drugs). A Hantzsch synthesis using readily available starting materials was used to generate [13C4,15N]1H‐pyrrole‐2,3,5‐tricarboxylic acid in six steps (12% overall yield). Copyright © 2009 John Wiley & Sons, Ltd.
Mg2+modulates integrin–extracellular matrix interaction in vascular smooth muscle cells studied by atomic force microscopy
Authors: Trache Andreea , Trzeciakowski Jerome P. , Meininger Gerald A.
Published: January 2010

Atomic force microscopy (AFM) was used to investigate the interaction between α5β1 integrin and fibronectin (FN) in the presence of divalent cations. AFM probes were labeled with FN and used to measure binding strength between α5β1 integrin and FN by quantifying the force required to break single FN–integrin bonds on a physiological range of loading rates (100–10 000 pN/s). The force necessary to rupture single α5β1–FN bond increased twofold over the regime of loading rates investigated. Changes in Mg2+and Ca2+concentration affected the thermodynamical parameters of the interaction and modulated the binding energy. These data indicate that the external ionic environment in which vascular smooth muscle cells reside, influences the mechanical parameters that define the interaction between the extracellular matrix and integrins. Thus, in a dynamic mechanical environment such as the vascular wall, thermodynamic binding properties between FN and α5β1 integrin vary in relation to locally applied loads and divalent cations concentrations. These changes can be recorded as direct measurements on live smooth muscle cells by using AFM. Copyright © 2009 John Wiley & Sons, Ltd.
Localization and quantification of noise sources in four‐gate field‐effect‐transistors
Authors: Luque Rodríguez A. , Jiménez Tejada J. A. , Godoy A. , López Villanueva J. A. , Gómez‐Campos F. M. , Rodríguez‐Bolivar S.
Published: January 2010

In this paper the effects of different noise sources in a four‐gate field‐effect‐transistor have been studied and quantified in different operation regimes of the structure. To carry out this study, a model that captures the main features of generation–recombination noise, produced by the fluctuations of trapped charge in the depletion regions of the device, and 1/f noise, produced by the fluctuations of trapped charges at the silicon–oxide interfaces, has been incorporated into a two‐dimensional device simulator. The existence of different kinds of bulk traps in the semiconductor may complicate the interpretation of experimental noise measurements. Anomalies in the noise behavior, produced by certain traps at specific biased voltages, have been explained by means of the simulation of the device. Copyright © 2010 John Wiley & Sons, Ltd.
Accurate prediction of the volume inversion impact on undoped Double Gate MOSFET capacitances
Authors: Moldovan Oana , Chaves Ferney A. , Jiménez David , Raskin Jean‐Pierre , Iñiguez Benjamin
Published: January 2010

This paper demonstrates the capability of our previously published undoped Double‐Gate (DG) MOSFET explicit and analytical compact model to also forecast the effect of the volume inversion (VI) on the intrinsic capacitances. For that purpose, we present simulation results for these capacitances. We show now that the model presents an accurate dependence on the silicon layer thickness, consistent with two‐dimensional numerical simulations, for both thin and thick silicon films. As opposed to our previous work, here we test the capacitance model for three different film thicknesses and also show that the transition from VI regime to dual gate behaviour is well simulated. We demonstrate in this paper that even if the current drive and transconductance are enhanced in VI regime, our results show that intrinsic capacitances are higher as well, which may limit the high‐speed (delay time) behaviour of DG MOSFETs under VI regime. The good agreement between the numerical simulations and our model shows the high potential of our complete DG MOSFET model. Copyright © 2010 John Wiley & Sons, Ltd.
High‐Efficiency Silicon Solar Cells Demand New Process Tools
Authors: Colville Finlay
Published: January 2010

Laser‐based tools are becoming an essential part of new crystalline silicon cell lines which are configured for high‐efficiency performance. Different tooling types are required on a case‐by‐case basis, depending on the level of process development undertaken and how fast cell producers move to implement the laserbased tools within high‐throughput production lines.
Light as a Controlling Tool
Authors: Haase Jens
Published: January 2010

The photovoltaic industry is characterized by a permanent, substantial growing during the last years. Today improving efficiencies and reduction of manufacturing cost of solar cells is essential for the success in the competitive market. The reduction of manufacturing costs is associated with high volume manufacturing of the solar cells by perpetuation of high quality standards and requirements for small tolerances. Measurements of the topography of solar cells now start to play an important role in the quality assurance of the manufacturing process. It allows the three‐dimensional mapping of a complete area with subsequent parameter extraction: so the efficiency of a solar cell depends on the wafer structure: Perfect smooth surfaces absorb less photons than surfaces with a certain, optimized roughness, whereas protecting layers should be as smooth and flat as possible.

Similar to all Microsystems the structures can be investigated and compared to the target values: examples are layer thickness, widths and depths of structured lines, the volume‐determination of hollows, defects, pores or abrasion/deposition rates. It also encompasses the 3D profile of printed circuit board tracks or special structures for sophisticated high efficiency photovoltaic elements.
A general model for porous medium flow in squeezing film situations
Authors: Nabhani Mohamed , El Khlifi Mohamed , Bou‐Saïd Benyebka
Published: January 2010

The present paper deals with a numerical investigation of the hydrodynamic lubrication of a porous squeeze film between two circular discs. To this purpose, the thin film (reduced) Navier Stokes equations and a generalised porous medium model are solved. The numerical results show that the effect of the porous disc is to reduce the lubricating properties of the fluid film. This effect is increased during the squeezing action. In addition, it is shown that the film pressure, the load‐carrying capacity and the velocity field based only on the Darcy model are predicted higher than those obtained from the generalised porous medium model. Copyright © 2009 John Wiley & Sons, Ltd.
Free flap failure in an anticardiolipin antibody‐positive patient with neoplasm–A case report
Authors: Asai Emiko , Okouchi Masayuki , Momiyama Masanori , Kajikawa Akiyoshi , Ueda Kazuki
Published: January 2010

We present herein a case of massive arterial thrombosis of a free rectus abdominal musculocutaneous flap used for reconstructive surgery of gingival carcinoma that could not be rescued. A 54‐year‐old woman underwent the operation. She had experienced two miscarriages in her 20s, but medical history was otherwise uneventful. Intraoperatively, the anastomosed artery often showed massive arterial thrombosis, and the flaps had become necrotic after bilateral flaps were used. Laboratory findings, 7 days postoperatively, showed high levels of immunoglobulin G anticardiolipin antibody. This value normalized by 2 months postoperatively after using chemotherapy. This case does not match the criteria for antiphospholipid syndrome, but some English‐language reports have shown rising antiphospholipid antibody levels, particularly anticardiolipin antibodies, in patients with neoplasm. In those cases, levels have normalized after successful therapy. Antiphospholipid antibody levels should be examined before surgery to identify risks of hypercoagulability. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.
Diagnostic assessment and therapeutic approach for immunodeficiency due to chylous dysplasia: A case report
Authors: Boccardo Francesco , Bellini Carlo , Girino Margherita , Campisi Corrado , Vidali Francesca , Corazza Gino Roberto , Campisi Corradino
Published: January 2010

Among possible causes of a condition of immunodeficiency, we have to consider the presence of a serious chylous dysplasia, due to the great loss of proteins through the intestinal lumen. A 20‐year‐old male, suffered from diarrhoea (2–4 times a day), weight loss (8 kilos in 5 years), and malnutrition (hypogammaglobulinemia, hypoalbuminemia, leukocytopenia with lymphocytopenia). Accurate diagnostic assessment allowed to diagnose a protein‐losing enteropathy. Conventional oil contrast lymphangiography allowed to accurately assess the case and to establish a proper therapeutic approach. The operation consisted in multiple antigravitational ligatures of dilated and incompetent chylous vessels and chylous vessel‐mesenteric vein microanastomoses. Parameters concerning albumin and leukocytes normalized in 1 week after operation and remained stable with time; there were no more episodes of diarrhoea and the patient recovered weight. An accurate diagnostic assessment and above all lymphangiography allow to diagnose properly difficult cases of immunodeficiency due to intestinal protido‐dispersion and to plan a correct therapeutic functional approach. © 2010 Wiley‐Liss, Inc. Microsurgery 30:401–404, 2010.
Monoterpenoid glucoindole alkaloids and iridoids from Pterocephalus pinardii
Authors: Gülcemal Derya , Masullo Milena , Alankuş‐Çalışkan Ozgen , Karayıldırım Tamer , Şenol Serdar G. , Piacente Sonia , Bedir Erdal
Published: January 2010

A new secondary metabolite, pterocephaline, along with the known cantleyoside, 7α‐morroniside, 3β,5α‐tetrahydrodesoxycordifoline lactam, 5S‐5‐carboxyvincoside, sweroside, and loganin have been isolated from the aerial parts of P. pinardii (Dipsacaceae). Moreover, cantleyoside‐methyl‐hemiacetal and cantleyoside‐dimethyl‐acetal were obtained as seco‐iridoid artifacts. The structures were elucidated by extensive spectroscopic methods including 1D‐(1H, 13C and TOCSY) and 2D‐NMR (DQF‐COSY, HSQC and HMBC). Monoterpenoid glucoindole alkaloids were encountered for the first time in Dipsacaceae family. Copyright © 2010 John Wiley & Sons, Ltd.
Ongoing remission after intensive All‐type chemotherapy in pediatric intestinal T‐cell lymphoma
Authors: Friedrich Carsten , Schrum Johanna , Chott Andreas , Janka‐Schaub Gritta , Kabisch Hartmut
Published: January 2010

A rare case of primary intestinal T‐cell lymphoma (ITL) of an 8‐year‐old boy is reported. Medium‐ to large‐sized tumor cells were βF1+, CD3+, CD8+. TIA‐1+, but CD4−, CD5−, CD30−, CD56−, CD20−, CD79a−, TdT−, consistent with an intraepithelial lymphocyte (IEL) origin. They showed monoclonal rearrangement of the T‐cell receptor γ‐chain and no evidence of EBV infection. No clinical, histologic, laboratory, or genetic evidence of celiac disease was detected. In adults, ITL is often associated with enteropathy and has a very poor outcome. Our patient remains in first remission 30 months after finishing the acute lymphoblastic leukemia protocol COALL‐07‐03 high risk standard. Pediatr Blood Cancer 2010;54:610–612. © 2009 Wiley‐Liss, Inc.
Pre‐B‐cell acute lymphoblastic leukemia with bulk extramedullary disease and chromosome 22 (EWSR1) rearrangement masquerading as Ewing sarcoma
Authors: Jakovljević Gordana , Nakić Melita , Rogošić Srđan , Kardum‐Skelin Ika , Mrsić‐Davidović Sanja , Zadro Renata , Krušlin Božo
Published: January 2010

We report a 2‐year‐old female with a subcutaneous tumor who was initially misdiagnosed as suffering from Ewing sarcoma with a positive EWSR1 rearrangement and EWS/FLI1 transcript. After finding lymphoblasts in peripheral blood, the diagnosis of acute lymphoblastic leukemia was established. This necessitated further analysis of the subcutaneous tumor. The tissue was positive for immature B‐cell markers and an immunoglobulin heavy chain gene rearrangement, which confirmed the final diagnosis of common type acute lymphoblastic leukemia with bulk extramedullary disease. The patient was treated with chemotherapy and was in remission 30 months after the diagnosis. Pediatr Blood Cancer 2010;54:606–609. © 2009 Wiley‐Liss, Inc.