bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in age and physical status prior to total knee and hip replacement surgery: A comparison of centers in Australia and Europe
Authors: Ackerman Ilana N. , Dieppe Paul A. , March Lyn M. , Roos Ewa M. , Nilsdotter Anna K. , Brown Graeme C. , Sloan Karen E. , Osborne Richard H.
Published: January 2009

Objective

To investigate whether variation exists in the preoperative age, pain, stiffness, and physical function of people undergoing total knee replacement (TKR) and total hip replacement (THR) at several centers in Australia and Europe.

Methods

Individual Western Ontario and McMaster Universities Osteoarthritis Index data (range 0–100, where 0 = best and 100 = worst) collected within 6 weeks prior to primary TKR and THR were extracted from 16 centers (n = 2,835) according to specified eligibility criteria. Analysis of covariance was used to evaluate differences in pain, stiffness, and physical function between centers, with adjustment for age and sex.

Results

There was marked variation in the age of people undergoing surgery between the centers (TKR mean age 67–73 years; F[6,1004] = 4.21, P < 0.01, and THR mean age 63–72 years; F[14,1807] = 7.27, P < 0.01). Large differences in preoperative status were observed between centers, most notably for pain (TKR adjusted mean pain 52.5–61.1; F[6,1002] = 4.26, P < 0.01, and THR adjusted mean pain 49.2–65.7; F[14,1802] = 8.44, P < 0.01) and physical function (TKR adjusted mean function 52.7–61.4; F[6,1002] = 5.27, P < 0.01, and THR adjusted mean function 53.3–71.0; F[14,1802] = 6.71, P < 0.01). Large effect sizes (up to 0.98) reflect the magnitude of variation between centers and highlight the clinical relevance of these findings.

Conclusion

The large variations in age and preoperative status indicate substantial differences in the timing of joint replacement across the centers studied, with potential for compromised surgical outcomes due to premature or delayed surgery. Possible contributing factors include patient preferences, the absence of concrete indications for surgery, and the capacity of the health care systems.
Expression, regulation, and signaling of the pattern‐recognition receptor nucleotide‐binding oligomerization domain 2 in rheumatoid arthritis synovial fibroblasts
Authors: Ospelt Caroline , Brentano Fabia , Jüngel Astrid , Rengel Yvonne , Kolling Christoph , Michel Beat A. , Gay Renate E. , Gay Steffen
Published: January 2009

Objective

Since pattern‐recognition receptors (PRRs), in particular Toll‐like receptors (TLRs), were found to be overexpressed in the synovium of rheumatoid arthritis (RA) patients and to play a role in the production of disease‐relevant molecules, we sought to determine the expression, regulation, and function of the PRR nucleotide‐binding oligomerization domain 2 (NOD‐2) in RA.

Methods

Expression of NOD‐2 in synovial tissues was analyzed by immunohistochemistry. Expression and induction of NOD‐2 in RA synovial fibroblasts (RASFs) were measured by conventional and real‐time polymerase chain reaction (PCR) analyses. Levels of interleukin‐6 (IL‐6) and IL‐8 were measured by enzyme‐linked immunosorbent assay (ELISA) and expression of matrix metalloproteinases (MMPs) by ELISA and/or real‐time PCR. NOD‐2 expression was silenced with small interfering RNA. Western blotting with antibodies against phosphorylated and total p38, JNK, and ERK, as well as inhibitors of p38, JNK, and ERK was performed. Activation of NF‐κB was measured by electrophoretic mobility shift assay.

Results

NOD‐2 was expressed by fibroblasts and macrophages in the synovium of RA patients, predominantly at sites of invasion into articular cartilage. In cultured RASFs, no basal expression of messenger RNA for NOD‐2 was detectable, but was induced by poly(I‐C), lipopolysaccharide, and tumor necrosis factor α. After up‐regulation of NOD‐2 by TLR ligands, its ligand muramyl dipeptide (MDP) increased the expression of IL‐6 and IL‐8 via p38 and NF‐κB. Stimulation with MDP further induced the expression of MMP‐1, MMP‐3, and MMP‐13.

Conclusion

Not only TLRs, but also the PRR NOD‐2 is expressed in the synovium of RA patients, and activation of NOD‐2 acts synergistically with TLRs in the production of proinflammatory and destructive mediators. Therefore, NOD‐2 might contribute to the initiation and perpetuation of chronic, destructive inflammation in RA.
Genetic risk factors for rheumatoid arthritis differ in caucasian and Korean populations
Authors: Lee Hye‐Soon , Korman Benjamin D. , Le Julie M. , Kastner Daniel L. , Remmers Elaine F. , Gregersen Peter K. , Bae Sang‐Cheol
Published: January 2009

Objective

Recent studies have identified a number of novel rheumatoid arthritis (RA) susceptibility loci in Caucasian populations. The aim of this study was to determine whether the genetic variants at 4q27, 6q23, CCL21, TRAF1/C5, and CD40 identified in Caucasians are also associated with RA in a Korean case–control collection. We also comprehensively evaluated the genetic variation within PTPN22, a well‐established autoimmune disease–associated gene.

Methods

We designed an experiment to thoroughly evaluate the PTPN22 linkage disequilibrium region, using tag single‐nucleotide polymorphisms (SNPs) and disease‐associated SNPs at 5 RA‐associated loci recently identified in Caucasians, in 1,128 Korean patients with RA and 1,022 ethnically matched control subjects. We also resequenced the PTPN22 gene to seek novel coding variants that might be contributing to disease in this population.

Results

None of the susceptibility loci identified in Caucasian patients with RA contributed significantly to disease in Koreans. Although tag SNPs covering the PTPN22 linkage disequilibrium block were polymorphic, they did not reveal any disease association, and resequencing did not identify any new common coding region variants in this population. The 6q23 and 4q27 SNPs assayed were nonpolymorphic in this population, and the TRAF1/C5, CD40, and CCL21 SNPs did not show any evidence for association with RA in this population of Korean patients.

Conclusion

The genetic risk factors for RA are different in Caucasian and Korean patients. Although patients of different ethnic groups share the HLA region as a major genetic risk locus, most other genes shown to be significantly associated with disease in Caucasians appear not to play a role in Korean patients with RA.
Altered integrin mechanotransduction in human nucleus pulposus cells derived from degenerated discs
Authors: Le Maitre Christine Lyn , Frain Jennie , Millward‐Sadler Jane , Fotheringham Andrew P. , Freemont Anthony John , Hoyland Judith Alison
Published: January 2009

Objective

Several studies have demonstrated biologic responses of intervertebral disc (IVD) cells to loading, although the mechanotransduction pathways have not been elucidated. In articular chondrocytes, which have a phenotype similar to that of IVD cells, a number of mechanoreceptors have been identified, with α5β1 integrin acting as a predominant mechanoreceptor. The purpose of this study was to investigate the role of integrin signaling in IVD cells during mechanical stimulation and to determine whether RGD integrins are involved.

Methods

Human nucleus pulposus (NP) cells derived from nondegenerated and degenerated discs were subjected to dynamic compressive loading in the presence of an RGD inhibitory peptide. Expression of the α5β1 heterodimer in IVD tissue was examined by immunohistochemistry and possible alternative mechanoreceptors by real‐time quantitative polymerase chain reaction.

Results

Aggrecan gene expression was decreased following loading of NP cells from nondegenerated and degenerated discs. This response was inhibited by treatment with an RGD peptide in cells from nondegenerated, but not degenerated, IVDs. Immunohistochemistry demonstrated that expression of the α5β1 heterodimer was unaltered in degenerated IVD tissue as compared with normal IVD tissue.

Conclusion

Our results indicate that the mechanotransduction pathways are altered in cells from degenerated IVDs. Mechanosensing in NP cells from nondegenerated discs occurs via RGD integrins, possibly via the α5β1 integrin, while cells from degenerated discs show a different signaling pathway that does not appear to involve RGD integrins.
Tissue targeting of anti‐RNP autoimmunity: Effects of T cells and myeloid dendritic cells in a murine model
Authors: Greidinger Eric L. , Zang YunJuan , Fernandez Irina , Berho Mariana , Nassiri Mehdi , Martinez Laisel , Hoffman Robert W.
Published: January 2009

Objective

To explore the role of immune cells in anti‐RNP autoimmunity in a murine model of pneumonitis or glomerulonephritis, using adoptive transfer techniques.

Methods

Donor mice were immunized with 50 μg of U1–70‐kd small nuclear RNP fusion protein and 50 μg of U1 RNA adjuvant. Whole splenocytes as well as CD4+ cell and dendritic cell (DC) subsets from the immunized mice were infused into naive syngeneic recipients. Anti‐RNP and T cell responses were assessed by immunoblotting, enzyme‐linked immunosorbent assay, and flow cytometry. Development of renal or lung disease was assessed by histology and urinalysis.

Results

Unfractionated splenocytes from donor mice without proteinuria induced predominantly lung disease in recipients (8 [57%] of 14 versus 2 [14%] of 14 developing renal disease; P = 0.046). However, infusion of CD4+ cells from donors without proteinuria induced renal disease more frequently than lung disease (7 [70%] of 10 versus 2 [20%] of 10; P = 0.01); adoptive transfer of RNP+CD4+ T cells from short‐term culture yielded similar results (renal disease in 8 [73%] of 11 recipients versus lung disease in 3 [27%] of 11). Cotransfer of splenic myeloid DCs and CD4+ T cells from immunized donors prevented induction of renal disease in all 5 recipients (P = 0.026 versus recipients of fresh CD4+ cells alone), although lung disease was still observed in 1 of 5 mice. Transfer of myeloid DCs alone from immunized donors induced lung disease in 3 (60%) of 5 recipients, without evidence of nephritis. Cotransfer of splenocytes from mice with and those without nephritis led to renal disease in 4 of 5 recipients, without evidence of lung disease.

Conclusion

These findings indicate that RNP+CD4+ T cells are sufficient to induce anti‐RNP autoimmunity, tissue targeting in anti‐RNP autoimmunity can be deviated to either a renal or pulmonary phenotype depending on the presence of accessory cells such as myeloid DCs, and DC subsets can play a role in both propagation of autoimmunity and end‐organ targeting.
Increased expression of CD40 on bone marrow CD34+ hematopoietic progenitor cells in patients with systemic lupus erythematosus: Contribution to Fas‐mediated apoptosis
Authors: Pyrovolaki Katerina , Mavroudi Irene , Sidiropoulos Prodromos , Eliopoulos Aristides G. , Boumpas Dimitrios T. , Papadaki Helen A.
Published: January 2009

Objective

Patients with systemic lupus erythematosus (SLE) display increased apoptosis of bone marrow (BM) CD34+ hematopoietic progenitor cells. This study was undertaken to evaluate the expression of CD40 and CD40L in the BM of SLE patients, and to explore the possible involvement of these molecules in apoptosis of CD34+ cells.

Methods

The proportion and survival characteristics of CD40+ cells within the BM CD34+ fraction from SLE patients and healthy controls were evaluated by flow cytometry. The production of CD40L by BM stromal cells was assessed using long‐term BM cultures, and the effect of CD40L on the survival characteristics and clonogenic potential of CD34+ cells was evaluated ex vivo by flow cytometry and clonogenic assays.

Results

SLE patients displayed an increased proportion of CD40+ cells within the CD34+ fraction as compared with controls. The CD34+CD40+ subpopulation contained an increased proportion of apoptotic cells compared with the CD34+CD40− fraction in patients and controls, suggesting that CD40 is involved in the apoptosis of CD34+ cells. Stimulation of patients' CD34+ cells with CD40L increased the proportion of apoptotic cells and decreased the proportion of colony‐forming cells as compared with untreated cultures. The CD40L‐mediated effects were amplified following treatment with recombinant Fas ligand, suggesting that the effects of these ligands are synergistic. CD40L levels were significantly increased in long‐term BM culture supernatants and adherent layers of BM cells from SLE patients as compared with controls.

Conclusion

These data reveal a novel role for the CD40/CD40L dyad in SLE by demonstrating that up‐regulation and induction of CD40 on BM CD34+ cells from patients with SLE contribute to the amplification of Fas‐mediated apoptosis of progenitor cells.
Unmasking of a protective tumor necrosis factor receptor I–mediated signal in the collagen‐induced arthritis model
Authors: Williams‐Skipp Cheryll , Raman Thiagarajan , Valuck Robert J. , Watkins Herschel , Palmer Brent E. , Scheinman Robert I.
Published: January 2009

Objective

To examine the relative importance of tumor necrosis factor receptor I (TNFRI) signaling in the hematopoietic tissue compartment in the progression of collagen‐induced arthritis (CIA), a model of rheumatoid arthritis (RA).

Methods

DBA/1 mice were administered a lethal radiation dose and were then rescued with bone marrow derived from either DBA/1 or TNFRI−/− mice. CIA was then induced, and disease progression was characterized.

Results

Surprisingly, mice with CIA that received TNFRI−/− donor marrow developed increased disease severity as compared with control mice with CIA. This could not be attributed to an increased primary response to collagen or to the contribution of a non‐DBA genetic background. In mice that received TNFRI−/− bone marrow, histologic markers of advanced disease were evident shortly after initiation of the immune response to collagen and long before clinical evidence of disease. Serum TNFα was undetectable, whereas serum interleukin‐12 p40 levels were increased, at the end point of the study in mice that received TNFRI−/− bone marrow.

Conclusion

These data raise the intriguing possibility of the existence of an antiinflammatory, TNFRI‐mediated circuit in the hematopoietic compartment. This circuit bears a resemblance to the switch in TNFα function that has been observed during the resolution of bacterial infections. These data suggest that TNFRI‐mediated signals in the radioresistant tissues contribute to disease progression, whereas TNFRI‐mediated signals in the radiosensitive tissues can contribute to protection from disease. We thus put forward the hypothesis that the degree of response to TNFα blockade in RA is dependent in part on the relative genetic strengths of these 2 pathways.
Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double‐blind, methotrexate‐controlled study of patients with active rheumatoid arthritis
Authors: Cohen Stanley B. , Cheng Tien‐Tsai , Chindalore Vishala , Damjanov Nemanja , Burgos‐Vargas Ruben , DeLora Patricia , Zimany Kathleen , Travers Helen , Caulfield John P.
Published: January 2009

Objective

To determine the efficacy and safety of pamapimod (a selective inhibitor of the α‐isoform of p38 MAP kinase) as monotherapy in comparison with methotrexate (MTX) treatment in adult patients with active rheumatoid arthritis (RA).

Methods

Patients were randomly assigned to 1 of 4 treatment groups and received 12 weeks of double‐blind treatment. One group received MTX (7.5 mg/week with planned escalation to 20 mg/week), and 3 groups received pamapimod (50, 150, or 300 mg) once daily. The primary efficacy end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks. Secondary end points included ACR50 and ACR70 responses, change from baseline in the Disease Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European League Against Rheumatism response, and change from baseline in each parameter of the ACR core set of measures. Safety monitoring included recording of adverse events (AEs), laboratory testing, immunology assessments, administration of electrocardiograms, and assessment of vital signs.

Results

Patients assigned to receive MTX and pamapimod had similar demographics and baseline characteristics. At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and 31% in the 50‐, 150‐, and 300‐mg groups, respectively) compared with patients taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs were typically characterized as mild and included infections, skin disorders, and dizziness. Pamapimod was generally well tolerated, but the 300‐mg dose appeared to be more toxic than either the 2 lower doses or MTX.

Conclusion

The present results showed that pamapimod was not as effective as MTX in the treatment of active RA.
Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration
Authors: Pockert Aneta J. , Richardson Stephen M. , Le Maitre Christine L. , Lyon Malcolm , Deakin Jonathan A. , Buttle David J. , Freemont Anthony J. , Hoyland Judith A.
Published: January 2009

Objective

Intervertebral disc degeneration is linked to loss of extracellular matrix (ECM), particularly the early loss of aggrecan. A group of metalloproteinases called aggrecanases are important mediators of aggrecan turnover. The present study was undertaken to investigate the expression of the recognized aggrecanases and their inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP‐3), in human intervertebral disc tissue.

Methods

Twenty‐four nondegenerated and 30 degenerated disc samples were analyzed for absolute messenger RNA (mRNA) copy number of ADAMTS 1, 4, 5, 8, 9, and 15 and TIMP‐3 by real‐time reverse transcription–polymerase chain reaction. Thirty‐six formalin‐fixed embedded intervertebral disc samples of varying grades of degeneration were used for immunohistochemical analyses. In addition, samples from 8 subjects were analyzed for the presence of matrix metalloproteinase (MMP)– and aggrecanase‐generated aggrecan products.

Results

Messenger RNA for all the aggrecanases other than ADAMTS‐8 was identified in intervertebral disc tissue, as was mRNA for TIMP‐3. Levels of mRNA expression of ADAMTS 1, 4, 5, and 15 were significantly increased in degenerated tissue compared with nondegenerated tissue. All these aggrecanases and TIMP‐3 were also detected immunohistochemically in disc tissue, and numbers of nucleus pulposus cells staining positive for ADAMTS 4, 5, 9, and 15 were significantly increased in degenerated tissue compared with nondegenerated tissue. Aggrecan breakdown products generated by MMP and aggrecanase activities were also detected in intervertebral disc tissue.

Conclusion

The aggrecanases ADAMTS 1, 4, 5, 9, and 15 may contribute to the changes occurring in the ECM during intervertebral disc degeneration. Targeting these enzymes may be a possible future therapeutic strategy for the prevention of intervertebral disc degeneration and its associated morbidity.
Detection of arthritis‐susceptibility loci, including Ncf1, and variable effects of the major histocompatibility complex region depending on genetic background in rats
Authors: Rintisch Carola , Förster Michael , Holmdahl Rikard
Published: January 2009

Objective

To characterize the arthritis‐modulating effects of 3 non–major histocompatibility complex (MHC) quantitative trait loci (QTLs) in rat experimental arthritis in the disease‐resistant E3 strain, and to investigate the disease‐modulating effects of the MHC region (RT1) in various genetic backgrounds.

Methods

A congenic fragment containing Ncf1 along with congenic fragments containing the strongest remaining loci, Pia5/Cia3 and Pia7/Cia13 on chromosome 4, were transferred from the arthritis‐susceptible DA strain into the background of the completely resistant E3 strain. The arthritis‐regulatory potential of the transferred alleles was evaluated by comparing the susceptibility to experimental arthritis in congenic rats with that in E3 rats. The RT1u haplotype from the E3 strain was transferred into the susceptible DA strain (RT1av1), and various F1 and F2 hybrids were generated to assess the effects of RT1 on arthritis susceptibility.

Results

The DA allele of Ncf1 did not break the arthritis resistance of the E3 rats, although it led to enhanced autoimmune B cell responses, as indicated by significantly elevated levels of anticollagen antibodies in congenic rats. Introgressing Pia5 and Pia7 loci on chromosome 4 broke the resistance to arthritis, and the MHC locus on chromosome 20 in DA rats enhanced arthritis when RT1 interacted with E3 genes.

Conclusion

The findings in these congenic lines confirm the existence of 3 major QTLs that regulate the severity of arthritis and are sufficient to induce the transformation of a completely arthritis‐resistant rat strain into an arthritis‐susceptible strain. This study also reveals a dramatic difference in the arthritis‐regulatory potential of the rat MHC depending on genetic background, suggesting that strong epistatic interactions occur between MHC and non‐MHC genes.
Personal exposure to mobile communication networks and well‐being in children—A statistical analysis based on a functional approach
Authors: Kühnlein Anja , Heumann Christian , Thomas Silke , Heinrich Sabine , Radon Katja
Published: January 2009

The MobilEe‐study was the first cross‐sectional population‐based study to investigate possible health effects of mobile communication networks on children using personal dosimetry. Exposure was assessed every second resulting in 86,400 measurements over 24 h for each participant. Therefore, a functional approach to analyze the exposure data was considered appropriate. The aim was to categorize exposure taking into account the course of the measurements over 24 h. The analyses were based on the 480 maxima of each 3 min time interval. Exposure was classified using a nonparametric functional method. Heterogeneity of a sample of functional data was assessed by comparing the functional mode and mean of the distribution of a functional variable. The partition was built within a descending hierarchical method. The resulting exposure groups were compared with categories derived from a standard method, which used the average exposure over 24 h and set the cut‐off at the 90th percentile. The functional classification resulted in a splitting of the exposure data into two groups. Plots of the mean curves showed that the groups could be interpreted as children with “low exposure” (88%) and “higher exposure” (12%). These groups were comparable with categories of the standard method. No association between the categorized exposure and well‐being was observed in logistic regression models. The functional classification approach yielded a plausible partition of the exposure data. The comparability with the standard approach might be due to the data structure and should not be generalized to other exposures. Bioelectromagnetics 30:261–269, 2009. © 2009 Wiley‐Liss, Inc.
Two New Solanapyrone Analogues from the Endophytic Fungus Nigrospora sp. YB‐141 of Azadirachta indica
Authors: Wu Shao‐Hua , Chen You‐Wei , Shao Shi‐Cheng , Wang Li‐Dong , Yu Ying , Li Zhi‐Ying , Yang Li‐Yuan , Li Shao‐Lan , Huang Rong
Published: January 2009

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Two new solanapyrone analogues, solanapyrones N and O (1 and 2, resp.), and three known compounds, solanapyrone C (3), nigrosporalactone (4), and phomalactone (5), were isolated from the fermentation culture of Nigrospora sp. YB‐141, an endophytic fungus isolated from Azadirachta indica A. Juss. The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The antifungal activities of 1–5 towards seven phytopathogenic fungi were tested. Most of the compounds exhibited no or only weak antifungal activities.
Two New Daphniphyllum Alkaloids from the Stems and Leaves of Daphniphyllum calycinum
Authors: Li Zhen‐Yu , Peng Shu‐Ying , Fang Li , Yang Yi‐Ming , Guo Yue‐Wei
Published: January 2009

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Two new Daphniphyllum alkaloids, 9,10‐epoxycalycinine A (1) and homodaphniphyllate (2), together with eight known related alkaloids, were isolated from the stems and leaves of Daphniphyllum calycinum. The structures of the new compounds 1 and 2 were elucidated on the basis of in‐depth spectroscopic‐data analysis, by chemical derivatization, and by comparison of their spectroscopic data with those of known compounds.
Aib and Iva in the Biosphere: Neither Rare nor Necessarily Extraterrestrial
Authors: Brückner Hans , Becker Dieter , Gams Walter , Degenkolb Thomas
Published: January 2009

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Fourty‐nine species and strains of filamentous fungi of the genera Acremonium, Bionectria, Clonostachys, Emericellopsis, Hypocrea/Trichoderma, Lecythophora, Monocillium, Nectriopsis, Niesslia, Tolypocladium, and Wardomyces, deposited with the culture collection of the Centraalbureau voor Schimmelcultures (CBS) in Utrecht, The Netherlands, were grown on nutrient agar plates. Organic extracts of mycelia were analyzed after acidic total hydrolysis and derivatization by GC/SIM‐MS on Chirasil‐L‐Val for the presence of Aib (=α‐aminoisobutyric acid, 2‐methylalanine) and dl‐Iva (=isovaline, 2‐ethylalanine). In 37 of the hydrolysates, Aib was detected, and in several of them D‐Iva or mixtures of D‐ and L‐Iva. Non‐proteinogenic Aib, in particular, is a highly specific marker for a distinctive group of fungal polypeptides named peptaibols or, comprehensively, peptaibiotics, i.e., peptides containing Aib and displaying (anti)biotic activities. The biotic synthesis of these amino acids by filamentous fungi contradicts the still widespread belief that α,α‐dialkyl‐α‐amino acids do not or rarely occur in the biosphere and, if detected, are of extraterrestrial origin. The abundant production of peptaibiotics by cosmopolitan species of microfungi has also to be considered in the discussion on the occurrence of Aib and Iva in ancient and recent sediments. The detection of trace amounts of Aib in ice samples of Antarctica that are devoid of meteorites might also be related to the presence of Aib‐producing microorganisms, being either indigenous psychrophiles, or being transported and localized by mechanisms related to bioaerosols and cryoconites. The presence of microfungi being capable of producing α,α‐dialkyl α‐amino acids in terrestrial samples, and possible contamination of extraterrestrial materials are pointed out to be of relevance for the reliable interpretation of cosmogeochemical data.
Conclusions Drawn from the Buncefield and Naples Incidents Regarding the Utilization of Consequence Models
Authors: Hailwood M. , Gawlowski M. , Schalau B. , Schönbucher A.
Published: January 2009

In both incidents, as a result of overfilling, a very large mass of winter gasoline (mf = 300 t in Buncefield, mf = 700 t in Naples) was released, which in both cases led to a major fire of several days duration and involved 22 of a total of 41 tanks (Buncefield) and 24 of a total of 31 tanks (Naples). Whilst the Buncefield site was unconfined or only slightly confined, the Naples site had a high degree of confinement due to walls, buildings as well as a high embankment. The most important, current consequence models as well as new consequence models for the prediction of the extraordinarily high flame heights, extraordinarily high thermal radiation as well as the extraordinarily high maximum peak overpressure are described and discussed. The analysis of the Buncefield incident so far has shown that the maximum visible relative flame height lies in the region of 2.5 < (H/d)max,Bunc < 6.5 and the predicted value lies in the region 1.8 < (H/d)max,calc < 1.9. For large, black smoky fires the estimation of the critical thermal separation distance is not dependent on the total fire, but on the height of a hot, clear burning zone. In addition, for multiple tank fires there is a considerable increase in the mass burning rate, the flame height, the surface emission power as well as the thermal separation distance. With the new consequence models maximum peak overpressures for an unconfined vapor cloud explosion (UVCE) of ≈ 1.3 bar (Buncefield) and of ≈ 1.5 bar (Naples) are predicted. For a partially confined vapor cloud explosion (VCE) a maximum peak overpressure of ≈ 3 bar for a jet ignition into a corridor is predicted.
Experimental and theoretical studies on high pressure safety valves: sizing and design supported by numerical calculations (CFD)
Authors: Schmidt J. , Peschel W. , Beune A.
Published: January 2009

High‐pressure safety valves with set pressures of more than 200 bar are required in industry, e.g. for polyethylene and synthesis gas applications. They are presently sized according to ISO 4126‐1. Only equations for ideal gases are presented there, and there are no indications as to how the real gas factor and the adiabatic exponent for real gases are to be calculated. For this reason, an equation for the critical mass flow rate of a real gas through a nozzle was derived and compared with the model according to EN‐ISO 4126‐1 and with experimental data. It is recommended that the current ISO‐standard be supplemented by the nozzle flow model for real gases. The first numerical calculations (ANSYS‐CFX) show that the discharge coefficient for a high pressure safety valve measured at moderate pressures can be extrapolated to very high pressures if it is used in conjunction with the nozzle flow model for real gases. However, this numerical result must yet be validated for further valve types by experiment. For this purpose, BASF has set up a high pressure valve test facility in Ludwigshafen.
Influence of the Liquid Phase Physical Properties on the Void Fraction at the Inlet of a Full‐Lift Safety Valve
Authors: Moncalvo D. , Friedel L.
Published: January 2009

This work studies the influence of the physical properties of a liquid on the void fraction at the inlet of a corner valve resembling a full‐lift safety valve. The test media are mixtures of air and aqueous solutions of glycerin. Our own measurements evince a reduction in the void fraction when the relative weight of glycerin in the solution is increased. If the effects of density, viscosity, and surface tension on the void fraction are accounted for by increasing the relative weight of glycerin in the solution, it results that the observed reduction of the void fraction is primarily a consequence of the enhancement of viscosity. On the other hand, the increment of the liquid density is responsible for a modest increase in the void fraction and the effect of the reduction in the surface tension is almost negligible. The enhancement of either the density or the viscosity of the liquid phase increases the relative velocity of the gas in the two‐phase mixture and, therefore, the slip. The impact of the liquid properties on the void fraction in co‐current vertical pipe flows is similar to that at the inlet of the corner valve. Among the most common correlations for pipe flows, the formulation of Rouhani and the homogeneous void fraction accurately reproduce the void fraction at the inlet of the valve only for two‐phase flows with liquids of low viscosity. A new void fraction correlation is proposed here, which reproduces all measurements very well and correctly predicts the impact of the liquid phase properties. Despite numerical coefficients, which can be fitted to additional sets of measurements, the structure of the new correlation is also applicable outside the range of two‐phase flows for which it has been explicitly validated.
Divergent Electronic Structures of Isoelectronic Metalloclusters: Tungsten(II) Halides and Rhenium(III) Chalcogenide Halides
Authors: Gray Thomas G.
Published: January 2009

Same but different: DFT calculations on hexanuclear tungsten(II) halide clusters [W6X8X′6]2− (X, X′=Cl, Br, I) indicate a breakdown in the isoelectronic analogy between themselves and the isostructural rhenium(III) chalcogenide clusters [Re6S8X6]4− (see figure).

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The hexanuclear tungsten(II) halide clusters and the sulfido‐halide clusters of rhenium(III) are subsets of a broad system of 24‐electron metal–metal bonded assemblies that share a common structure. Tungsten(II) halide clusters and rhenium(III) sulfide clusters luminesce from triplet excited states upon ultraviolet or visible excitation; emission from both cluster series has been extensively characterized elsewhere. Reported here are density‐functional theory studies of the nine permutations of [W6X8X′6]2− (X, X′=Cl, Br, I). Ground‐state properties including geometries, harmonic vibrational frequencies, and orbital energy‐level diagrams, have been calculated. Comparison is made to the sulfide clusters of rhenium(III), of which [Re6S8Cl6]4− is representative. [W6X8X′6]2− and [Re6S8Cl6]4− possess disparate electronic structures owing to the greater covalency of the metal–sulfur bond and hence of the [Re6S8]2+ core. Low‐lying virtual orbitals are raised in energy in [Re6S8Cl6]4− with the result that the LUMO+7 (or LUMO+8 in some cases) of tungsten(II) halide clusters is the LUMO of [Re6S8Cl6]4− species. An inversion of the HOMO and HOMO−1 between the two cluster series also occurs. Time‐dependent density‐functional calculations using asymptotically correct functionals do not recapture the experimentally observed periodic trend in [W6X14]2− luminescence (Eem increasing in the order [W6Cl14]2− < [W6Br14]2− < [W6I14]2−), predicting instead that emission energies decrease with incorporation of the heavier halides. This circumstance is either a gross failure of the time‐dependent formalism of DFT or it indicates extensive multistate emission in [W6X8X′6]2− clusters. The inapplicability of isoelectronic analogies between clusters of Group 6 and Group 7 is emphasized.
Reactivity of Thiosemicarbazides with Redox Active Metal Ions: Controlled Formation of Coordination Complexes versus Heterocyclic Compounds
Authors: López‐Torres Elena , Dilworth Jonathan R.
Published: January 2009

Careful metal selection: Control of the reaction conditions of CuII and SnIV with Me2NNHCSNHPh permits the selective synthesis of metal complexes or a range of heterocyclic compounds generated by the oxidative coupling of two thiosemicarbazides (see figure).

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The reactions of 1,1‐dimethyl‐4‐phenylthiosemicarbazide (LH) with CuII and SnIV have been investigated. If THF or methanol is used as solvent with CuII, oxidative cyclisation and coupling are observed, yielding a 1,2,4‐thiadiazole or a 1,3,4‐thiadiazolium salt. SnI4 is also able to induce oxidative coupling of two thiosemicarbazide ligands, yielding 1,2,4‐thiadiazolium or 1,2,4‐triazolium salts, with I3− as the counterion, depending on the reaction conditions. By contrast, reaction of LH with SnI4 in acetone yields a 1,3‐thiazolium salt, with I− as counterion. Reaction with CuII salts or SnI4 in basic media leads to the formation of metal complexes containing two deprotonated thiosemicarbazide ligands. In the reaction of CuCl2 in water in the presence of acid a complex containing two neutral ligands is obtained. Reactions with SnCl4 are not able to induce ligand cyclisation, although a coordination compound with two neutral ligands was isolated from methanol.
A Versatile Methodology for the Synthesis of α,β‐Unsaturated 3‐Iminophosphines
Authors: Shaffer Andrew R. , Schmidt Joseph A. R.
Published: January 2009

Phorteen phine phosphines: Fourteen new α,β‐unsaturated β‐chloroimines were synthesized from inexpensive ketones by using the Vilsmeier–Haack reagent followed by Schiff‐base condensation. Each imine was subsequently converted to an α,β‐unsaturated 3‐iminophosphine through either late‐metal‐catalyzed phosphorus–carbon cross‐coupling or through an addition–elimination sequence (see scheme). This high‐yield protocol serves as a general means to produce α,β‐unsaturated 3‐iminophosphines.

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Fourteen new α,β‐unsaturated β‐chloroimines were synthesized from commercially available ketones using the Vilsmeier–Haack reagent, followed by Schiff‐base condensation. Each imine was subsequently converted to an α,β‐unsaturated 3‐iminophosphine through either late‐metal‐catalyzed phosphorus–carbon cross‐coupling or through an addition–elimination sequence. Depending on the substituents present on the vinyl group, the resultant phosphines were isolated as either E or Z diastereomers with successful isolation of predominately single diastereomers for all fourteen new phosphines investigated. Full synthetic and spectroscopic details, as well as several X‐ray crystal structures of these new imines and phosphines, are reported in addition to X‐ray crystal structures of related palladium complexes.
A Binuclear CuII Metallacycle Capable of Discerning between Pyrazine and Its Different Methyl‐Substituted Derivatives Based on Reversible Intracage Metal–Ligand Binding
Authors: Hou Gui‐Ge , Ma Jian‐Ping , Sun Ting , Dong Yu‐Bin , Huang Ru‐Qi
Published: January 2009

Squashy cage: A flexible, spongelike, and reversible metal‐binding Cu2L2 cage that can adjust its internal space in response to pyrazine and its derivatives based on a recognition sequence of pyrazine, 2,5‐dimethylpyrazine, and 2‐methylpyrazine (see figure) is described.

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Environmentally Benign Production of Biodiesel Using Heterogeneous Catalysts
Authors: Hara Michikazu
Published: January 2009

Fuelling the future: The production of esters of higher fatty acids from plant materials is of great interest for the manufacture of biodiesel. Heterogeneous catalysts can provide new routes for the environmentally benign production of biodiesel. Particulate heterogeneous catalysts can be readily separated from products following reaction allowing the catalyst to be reused, generating less waste, and consuming less energy.

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Diesel engines are simple and powerful, and exhibit many advantages in energy efficiency and cost. Therefore, the production of higher fatty acid esters from plant materials has become of interest in recent years for the manufacture of biodiesel, a clean‐burning alternative fuel. The industrial production of biodiesel mostly proceeds in the presence of “soluble” catalysts such as alkali hydroxides and liquid acids. A considerable amount of energy is required for the purification of products and catalyst separation, and furthermore these catalysts are not reusable. This process results in substantial energy wastage and the production of large amounts of chemical waste. Particulate heterogeneous catalysts can be readily separated from products following reaction, allowing the catalyst to be reused and consuming less energy. This Minireview describes the environmentally benign production of biodiesel using heterogeneous catalysts such as solid bases, acid catalysts, and immobilized enzymes.
Epithelial expression of human papillomavirus type 16 E7 protein results in peripheral CD8 T‐cell suppression mediated by CD4+CD25+ T cells
Authors: Narayan Sharmal , Choyce Allison , Linedale Richard , Saunders Nicholas A. , Dahler Alison , Chan Emily , Fernando Germain J. , Frazer Ian H. , Leggatt Graham R.
Published: January 2009

The role of thymic versus peripheral epithelium in the regulation of the antigen‐specific CD8 T‐cell repertoire is still largely unresolved. We generated TCR‐β chain transgenic mice in which an increased frequency of peripheral CD8 T cells recognizes an epitope from a viral oncoprotein (HPV16E7) in the context of H‐2Db MHC class I. When T cells from these mice developed through the thymus of mice expressing functional E7 protein from a keratin 14 promoter, no major perturbation to transgenic T‐cell development in the thymus was observed in these double‐transgenic mice. In contrast, peripheral CD8 T‐cell responses in the single‐transgenic, K14E7 mice, including those unrelated to E7 antigen, are reduced whereas CD4 T‐cell responses and antibody production are unchanged in these mice. Peripheral non‐responsiveness among CD8 T cells was mediated largely by CD4+CD25+ T cells. This suggested that epithelium expressing HPV16E7 protein induces Treg that specifically down‐regulate CD8 T‐cell responses in the periphery. This may have important consequences for the treatment of cervical pre‐cancers and provides a model for understanding differential suppression of T and B lymphocyte subsets by Treg.
Expression of IL‐15RA or an IL‐15/IL‐15RA fusion on CD8+ T cells modifies adoptively transferred T‐cell function in cis
Authors: Rowley Jesse , Monie Archana , Hung Chien‐Fu , Wu T.‐C.
Published: January 2009

IL‐15 and IL‐15 receptor alpha (IL‐15RA) play a significant role in multiple aspects of T‐cell biology. However, given the evidence that IL‐15RA can present IL‐15 in trans, the functional capacity of IL‐15RA expressed on CD8+ T cells to modify IL‐15 functions in cis is currently unclear. In the current study, we explore the functional consequences of IL‐15RA, expression on T cells using a novel method to transfect naive CD8+ T cells. We observed that RNA nucleofection led to highly efficient, non‐toxic, and rapid manipulation of protein expression levels in unstimulated CD8+ T cells. We found that transfection of unstimulated CD8+ T cells with IL‐15RA RNA led to enhanced viability of CD8+ T cells in response to IL‐15. Transfection with IL‐15RA enhanced IL‐15‐mediated phosphorylation of STAT5 and also promoted IL‐15‐mediated proliferation in vivo of adoptively transferred naïve CD8+ T cells. We demonstrated that IL‐15RA can present IL‐15 via cis‐presentation on CD8+ T cells. Finally, we showed that transfection with a chimeric construct linking IL‐15 to IL‐15RA cell autonomously enhances the viability and proliferation of primary CD8+ T cells and cytotoxic potential of antigen‐specific CD8+ T cells. The clinical implications of the current study are discussed.
Functional islet‐specific Treg can be generated from CD4+CD25− T cells of healthy and type 1 diabetic subjects
Authors: Long S. Alice , Walker Mindi R. , Rieck Mary , James Eddie , Kwok William W. , Sanda Srinath , Pihoker Catherine , Greenbaum Carla , Nepom Gerald T. , Buckner Jane H.
Published: January 2009

CD4+CD25+FOXP3+ Treg cells require TCR engagement for suppressive function, thus ensuring that suppression occurs only in the presence of specific antigens; however, to date no studies have addressed the function of self‐antigen‐specific Treg in humans. These studies were designed to determine whether peripheral generation and function of islet antigen‐specific adaptive Treg are defective in human subjects with type 1 diabetes (T1D). Islet antigen‐specific adaptive Treg were induced in vitro by activation of CD4+FOXP3− T cells with glutamic acid decarboxylase and islet‐specific glucose‐6‐phosphate catalytic subunit‐related protein peptides in the context of T1D‐associated HLA‐DRβ alleles. Antigen‐specific Treg were characterized using flow cytometry for FOXP3 and class II tetramer and assessed for the ability to inhibit proliferation. These adaptive Treg were then compared with influenza‐specific Treg from the same study population. The function of tetramer+ cells that expressed FOXP3 was similar for both influenza and islet antigens generated from control and T1D subjects. In fact, the potency of suppression correlated with FOXP3 expression, not antigen specificity. Thus, these data suggest that development of functional adaptive Treg can occur in response to islet antigens and activation of islet‐specific Treg may potentially be used as a targeted immunotherapy in T1D.
Cover Picture: Eur. J. Immunol. 2/09
Authors: Aoshi Taiki , Carrero Javier A. , Konjufca Vjollca , Koide Yukio , Unanue Emil R. , Miller Mark J.
Published: January 2009

The cover image shows immunohistological staining of the white pulp (WP) and a bridging channel (BC) in the spleen of a BALB/c mouse and is taken from Aoshi et al. (pp. 417–425); CD11b staining is shown in blue, F4/80 in green and CD11c in red. In contrast to other reports, Aoshi et al. identified, by antibody staining, cell location and morphology, five different phagocytic populations (F4/801 macrophages, MARCO1 macrophages, MOMA‐11 macrophages, CD11b1 neutrophils and CD11c1 DC) involved in the splenic uptake of Listeria monocytogenes. In addition, MARCO1 macrophages are shown to be involved only in the very early stages of infection.
Synthesis, Characterization and OFET Properties of Amphiphilic Mixed (Phthalocyaninato)(porphyrinato)europium(III) Complexes
Authors: Ma Pan , Chen Yanli , Sheng Ning , Bian Yongzhong , Jiang Jianzhuang
Published: January 2009

Amphiphilic mixed (phthalocyaninato)(porphyrinato)europium(III) triple‐decker complexes Eu2[Pc(15C5)4]2[T(C10H21)4P] (1) and Eu2[Pc(15C5)4]2[TPOPP] (2) [H2Pc(15C5)4 = 2,3,9,10,16,17,23,24‐tetrakis(15‐crown‐5)phthalocyanine; H2T(C10H21)4P = meso‐5,10,15,20‐tetra‐n‐decylporphyrin, H2TPOPP = meso‐5,10,15,20‐tetrakis(4‐pentyloxyphenyl)porphyrin] were designed and synthesized by the raise‐by‐one‐story method. These novel sandwich triple‐decker complexes were characterized by a wide range of spectroscopic methods, and they were also electrochemically studied. Highly ordered films were fabricated by the Langmuir–Blodgett (LB) technique into organic field‐effect transistors (OFETs). The devices display good OFET performance with a carrier mobility in the range 0.03–0.78 cm2 V–1 s–1. As expected, the devices show a low threshold voltage range from –1.19 to –4.34 V. The mobility of compound 1 reaches 0.78 cm2 V–1 s–1, which is the highest value so far achieved for LB film‐based OFETs, as a result of the narrow energy gap (1.04 eV) of this compound.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Preparation of Triaryl‐ and Triheteroarylmethanes under Ytterbium Triflate Catalysis and Solvent‐Free Conditions
Authors: Genovese Salvatore , Epifano Francesco , Pelucchini Caroline , Curini Massimo
Published: January 2009

Triaryl‐ and triheteroarylmethanes have been synthesized in very good yield under solvent‐free conditions from differently substituted aldehydes and 2‐methylfuran or methoxybenzene in the presence of Yb(OTf)3 as catalyst. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Carbohydrate‐Based Pyridine‐2‐carboxamides for Mo‐Catalyzed Asymmetric Allylic Alkylations
Authors: Del Litto Raffaella , Benessere Vincenzo , Ruffo Francesco , Moberg Christina
Published: January 2009

Bis(pyridine‐2‐carboxamides) were prepared from 1,2‐diamines obtained from α‐D‐glucose and α‐D‐mannose. The ligands were assessed in molybdenum‐catalyzed asymmetric allylic alkylations (AAA) by using both methyl (E)‐3‐phenyl‐2‐propenyl and methyl rac‐1‐phenyl‐2‐propenyl carbonates and dimethyl malonate as nucleophile under microwave irradiation. High enantioselectivity (99 % ee) and high regioselectivity (49:1 in favour of the branched isomer) were observed in reactions of the linear achiral substrate in the presence of 10 mol‐% of a catalyst prepared from a ligand derived from glucose. Somewhat lower enantioselectivity (up to 96 % ee) was observed in reactions with the branched racemic carbonate by using the same ligand.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Comparison of aromatic and alkyl micelles for the electrokinetic determination of phthalates in virgin olive oil
Authors: Morales‐Cid Gabriel , Cárdenas Soledad , Simonet Bartolomé M. , Valcárcel Miguel
Published: January 2009

Two electrokinetic methods for the separation of phthalates are proposed. One uses 25 mM sodium borate and 50 mM sodium taurodeoxycholate adjusted to pH 2.8, and the other uses 15 mM ammonium tetraborate, 100 mM SDS, 0.25% w:v hydroxypropylmethyl cellulose (HPMC) and 5% v:v methanol (MeoH) adjusted to pH 9. The BGE containing SDS micelles as the pseudo‐stationary phase provided better analytical figures of merit, particularly as regards LOD (0.4–1.4 mg/L) and precision (1.1–6.5%). Adding MeoH and HPMC to the BGE proved essential in order to obtain narrow and symmetric peaks. The proposed method was successfully used to determine phthalates in virgin olive oil. Recoveries from spiked samples ranged from 96 to 106%. The precision obtained in the analysis of real samples, as RSD, was better than 6.8%.