bluuebunny/crossref_metadata_2025 huggingface dataset:
Donor demographic and laboratory predictors of allogeneic peripheral blood stem cell mobilization in an ethnically diverse population
Authors: Vasu Sumithira , Leitman Susan F. , Tisdale John F. , Hsieh Matthew M. , Childs Richard W. , Barrett A. John , Fowler Daniel H. , Bishop Michael R. , Kang Elizabeth M. , Malech Harry L. , Dunbar Cynthia E. , Khuu Hanh M. , Wesley Robert , Yau Yu Y. , Bolan Charles D.
Published: June 2008

A reliable estimate of peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF) may identify donors at risk for poor mobilization and help optimize transplantation approaches. We studied 639 allogeneic PBSC collections performed in 412 white, 75 black, 116 Hispanic, and 36 Asian/Pacific adult donors who were prescribed G-CSF dosed at either 10 or 16 μg/kg per day for 5 days followed by large-volume leukapheresis (LVL). Additional LVL (mean, 11 L) to collect lymphocytes for donor lymphocyte infusion (DLI) and other therapies was performed before G-CSF administration in 299 of these donors. Day 5 preapheresis blood CD34+ cell counts after mobilization were significantly lower in whites compared with blacks, Hispanics, and Asian/Pacific donors (79 vs 104, 94, and 101 cells/μL, P < .001). In addition, donors who underwent lymphapheresis before mobilization had higher CD34+ cell counts than donors who did not (94 vs 79 cells/μL, P < .001). In multivariate analysis, higher post–G-CSF CD34+ cell counts were most strongly associated with the total amount of G-CSF received, followed by the pre–G-CSF platelet count, pre–G-CSF mononuclear count, and performance of prior LVL for DLI collection. Age, white ethnicity, and female gender were associated with significantly lower post–G-CSF CD34+ cell counts.
SODa: An Mn/Fe superoxide dismutase prediction and design server
Authors: Kwasigroch Jean Marc , Wintjens René , Gilis Dimitri , Rooman Marianne
Published: June 2008

Background

Superoxide dismutases (SODs) are ubiquitous metalloenzymes that play an important role in the defense of aerobic organisms against oxidative stress, by converting reactive oxygen species into nontoxic molecules. We focus here on the SOD family that uses Fe or Mn as cofactor.

Results

The SODa webtoolhttp://babylone.ulb.ac.be/sodapredicts if a target sequence corresponds to an Fe/Mn SOD. If so, it predicts the metal ion specificity (Fe, Mn or cambialistic) and the oligomerization mode (dimer or tetramer) of the target. In addition, SODa proposes a list of residue substitutions likely to improve the predicted preferences for the metal cofactor and oligomerization mode. The method is based on residue fingerprints, consisting of residues conserved in SOD sequences or typical of SOD subgroups, and of interaction fingerprints, containing residue pairs that are in contact in SOD structures.

Conclusion

SODa is shown to outperform and to be more discriminative than traditional techniques based on pairwise sequence alignments. Moreover, the fact that it proposes selected mutations makes it a valuable tool for rational protein design.
Activation of peroxisome proliferator-activated receptor alpha in human peripheral blood mononuclear cells reveals an individual gene expression profile response
Authors: Bouwens Mark , Afman Lydia A , Müller Michael
Published: June 2008

Background

Peripheral blood mononuclear cells (PBMCs) are relatively easily obtainable cells in humans. Gene expression profiles of PBMCs have been shown to reflect the pathological and physiological state of a person. Recently, we showed that the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) has a functional role in human PBMCs during fasting. However, the extent of the role of PPARα in human PBMCs remains unclear. In this study, we therefore performed gene expression profiling of PBMCs incubated with the specific PPARα ligand WY14,643.

Results

Incubation of PBMCs with WY14,643 for 12 hours resulted in a differential expression of 1,373 of the 13,080 genes expressed in the PBMCs. Gene expression profiles showed a clear individual response to PPARα activation between six healthy human blood donors. Pathway analysis showed that genes in fatty acid metabolism, primarily in β-oxidation were up-regulated upon activation of PPARα with WY14,643, and genes in several amino acid metabolism pathways were down-regulated.

Conclusion

This study shows that PPARα in human PBMCs regulates fatty acid and amino acid metabolism. In addition, PBMC gene expression profiles show individual responses to WY14,643 activation. We showed that PBMCs are a suitable model to study changes in PPARα activation in healthy humans.
Analysis of outer membrane vesicle associated proteins isolated from the plant pathogenic bacterium Xanthomonas campestris pv. campestris
Authors: Sidhu Vishaldeep K , Vorhölter Frank-Jörg , Niehaus Karsten , Watt Steven A
Published: June 2008

Background

Outer membrane vesicles (OMVs) are released from the outer membrane of many Gram-negative bacteria. These extracellular compartments are known to transport compounds involved in cell-cell signalling as well as virulence associated proteins, e.g. the cytolysine from enterotoxic E. coli.

Results

We have demonstrated that Xanthomonas campestris pv. campestris (Xcc) releases OMVs into the culture supernatant during growth. A proteome study identified 31 different proteins that associate with the OMV fraction of which half are virulence-associated. A comparison with the most abundant outer membrane (OM) proteins revealed that some proteins are enriched in the OMV fraction. This may be connected to differences in the LPS composition between the OMVs and the OM. Furthermore, a comparison of the OMV proteomes from two different culture media indicated that the culture conditions have an impact on the protein composition. Interestingly, the proteins that are common to both culture conditions are mainly involved in virulence.

Conclusion

Outer membrane vesicles released from the OM of Xcc contain membrane- and virulence-associated proteins. Future experiments will prove whether these structures can serve as "vehicles" for the transport of virulence factors into the host membrane.
Association between television viewing and the risk of metabolic syndrome in a community-based population
Authors: Chang Pei-Chia , Li Tsai-Chung , Wu Ming-Tsang , Liu Chiu-Shong , Li Chia-Ing , Chen Ching-Chu , Lin Wen-Yuan , Yang Shin-Yuh , Lin Cheng-Chieh
Published: June 2008

Background

As a result of metabolic syndrome becoming an important issue during recent decades, many studies have explored the risk factors contributing to its development. However, less attention has been paid to the risk associated with sedentary behavior, especially television viewing. This study examined the association between television viewing time and the risk of having metabolic syndrome in a population of Taiwanese subjects.

Methods

This community-based cross-sectional study included 2,353 subjects (1,144 men and 1,209 women) aged 40 and over from October, 2004 to September, 2005. Information about the time spent watching TV was obtained using a self-administered questionnaire. The definition of metabolic syndrome was according to the Third Report of the National Cholesterol Education Program's Adult Treatment Panel modified for Asians.

Results

Compared to subjects who viewed TV < 14 hr/week, those who viewed TV > 20 hr/week had a 1.50-fold (95% confidence intervals (CI): 1.10, 2.03) risk for men and a 1.93-fold (95% CI: 1.37, 2.71) risk for women of having metabolic syndrome, after adjusting for physical activity and other covariates. Stratifying by the three categories of total activity levels, TV viewing time > 20 hr/week was found to still hold a significant risk for having metabolic syndrome in the lowest of the three categories of total activity level for men and in all three categories of total activity level for women.

Conclusion

The findings suggest that TV viewing is an independent risk factor associated with metabolic syndrome in Taiwanese people.
Evaluation of the Webler-Brown model for estimating tetrachloroethylene exposure from vinyl-lined asbestos-cement pipes
Authors: Spence Lisa A , Aschengrau Ann , Gallagher Lisa E , Webster Thomas F , Heeren Timothy C , Ozonoff David M
Published: June 2008

Background

From May 1968 through March 1980, vinyl-lined asbestos-cement (VL/AC) water distribution pipes were installed in New England to avoid taste and odor problems associated with asbestos-cement pipes. The vinyl resin was applied to the inner pipe surface in a solution of tetrachloroethylene (perchloroethylene, PCE). Substantial amounts of PCE remained in the liner and subsequently leached into public drinking water supplies.

Methods

Once aware of the leaching problem and prior to remediation (April-November 1980), Massachusetts regulators collected drinking water samples from VL/AC pipes to determine the extent and severity of the PCE contamination. This study compares newly obtained historical records of PCE concentrations in water samples (n = 88) with concentrations estimated using an exposure model employed in epidemiologic studies on the cancer risk associated with PCE-contaminated drinking water. The exposure model was developed by Webler and Brown to estimate the mass of PCE delivered to subjects' residences.

Results

The mean and median measured PCE concentrations in the water samples were 66 and 0.5 μg/L, respectively, and the range extended from non-detectable to 2432 μg/L. The model-generated concentration estimates and water sample concentrations were moderately correlated (Spearman rank correlation coefficient = 0.48, p < 0.0001). Correlations were higher in samples taken at taps and spigots vs. hydrants (ρ = 0.84 vs. 0.34), in areas with simple vs. complex geometry (ρ = 0.51 vs. 0.38), and near pipes installed in 1973–1976 vs. other years (ρ = 0.56 vs. 0.42 for 1968–1972 and 0.37 for 1977–1980). Overall, 24% of the variance in measured PCE concentrations was explained by the model-generated concentration estimates (p < 0.0001). Almost half of the water samples had undetectable concentrations of PCE. Undetectable levels were more common in areas with the earliest installed VL/AC pipes, at the beginning and middle of VL/AC pipes, at hydrants, and in complex pipe configurations.

Conclusion

PCE concentration estimates generated using the Webler-Brown model were moderately correlated with measured water concentrations. The present analysis suggests that the exposure assessment process used in prior epidemiological studies could be improved with more accurate characterization of water flow. This study illustrates one method of validating an exposure model in an epidemiological study when historical measurements are not available.
Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma
Authors: Yang David T , Young Ken H , Kahl Brad S , Markovina Stephanie , Miyamoto Shigeki
Published: June 2008

Background

The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL). However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear.

Results

Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA). Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231) and a breast carcinoma cell line (MDA-MB-468), the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10) displayed bortezomib-resistant constitutive NF-κB activity.

Conclusion

Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.
DNA copy number changes in high-grade malignant peripheral nerve sheath tumors by array CGH
Authors: Kresse Stine H , Skårn Magne , Ohnstad Hege O , Namløs Heidi M , Bjerkehagen Bodil , Myklebost Ola , Meza-Zepeda Leonardo A
Published: June 2008

Background

Malignant peripheral nerve sheath tumors (MPNSTs) are rare and highly aggressive soft tissue tumors showing complex chromosomal aberrations. In order to identify recurrent chromosomal regions of gain and loss, and thereby novel gene targets of potential importance for MPNST development and/or progression, we have analyzed DNA copy number changes in seven high-grade MPNSTs using microarray-based comparative genomic hybridization (array CGH).

Results

Considerable more gains than losses were observed, and the most frequent minimal recurrent regions of gain included 1q24.1-q24.2, 1q24.3-q25.1, 8p23.1-p12, 9q34.11-q34.13 and 17q23.2-q25.3, all gained in five of seven samples. The 17q23.2-q25.3 region was gained in all five patients with poor outcome and not in the two patients with disease-free survival. cDNA microarray analysis and quantitative real-time reverse transcription PCR were used to investigate expression of genes located within these regions. The gene lysyl oxidase-like 2 (LOXL2) was identified as a candidate target for the 8p23.1-p12 gain. Within 17q, the genes topoisomerase II-α (TOP2A), ets variant gene 4 (E1A enhancer binding protein, E1AF) (ETV4) and baculoviral IAP repeat-containing 5 (survivin) (BIRC5) showed increased expression in all samples compared to two benign tumors. Increased expression of these genes has previously been associated with poor survival in other malignancies, and for TOP2A, in MPNSTs as well. In addition, we have analyzed the expression of five micro RNAs located within the 17q23.2-q25.3 region, but none of them showed high expression levels compared to the benign tumors.

Conclusion

Our study shows the potential of using DNA copy number changes obtained by array CGH to predict the prognosis of MPNST patients. Although no clear correlations between the expression level and patient outcome were observed, the genes TOP2A, ETV4 and BIRC5 are interesting candidate targets for the 17q gain associated with poor survival.
A plastome primer set for comprehensive quantitative real time RT-PCR analysis of Zea mays: a starter primer set for other Poaceae species
Authors: Sharpe Richard M , Dunn Sade N , Cahoon A Bruce
Published: June 2008

Background

Quantitative Real Time RT-PCR (q2(RT)PCR) is a maturing technique which gives researchers the ability to quantify and compare very small amounts of nucleic acids. Primer design and optimization is an essential yet time consuming aspect of using q2(RT)PCR. In this paper we describe the design and empirical optimization of primers to amplify and quantify plastid RNAs from Zea mays that are robust enough to use with other closely related species.

Results

Primers were designed and successfully optimized for 57 of the 104 reported genes in the maize plastome plus two nuclear genes. All 59 primer pairs produced single amplicons after end-point reverse transcriptase polymerase chain reactions (RT-PCR) as visualized on agarose gels and subsequently verified by q2(RT)PCR. Primer pairs were divided into several categories based on the optimization requirements or the uniqueness of the target gene. An in silico test suggested the majority of the primer sets should work with other members of the Poaceae family. An in vitro test of the primer set on two unsequenced species (Panicum virgatum and Miscanthus sinensis) supported this assumption by successfully producing single amplicons for each primer pair.

Conclusion

Due to the highly conserved chloroplast genome in plant families it is possible to utilize primer pairs designed against one genomic sequence to detect the presence and abundance of plastid genes or transcripts from genomes that have yet to be sequenced. Analysis of steady state transcription of vital system genes is a necessary requirement to comprehensively elucidate gene expression in any organism. The primer pairs reported in this paper were designed for q2(RT)PCR of maize chloroplast genes but should be useful for other members of the Poaceae family. Both in silico and in vitro data are presented to support this assumption.
The moose throat bot fly Cephenemyia ulrichii larvae (Diptera: Oestridae) found developing in roe deer (Capreolus capreolus) for the first time
Authors: Nilssen Arne C , Isomursu Marja , Oksanen Antti
Published: June 2008

About fifty larvae of Cephenemyia ulrichii Brauer (Diptera: Oestridae), some of them nearly full-grown third instars, were found in the throat of a roe deer (Capreolus capreolus) in June 2007 near Helsinki in Finland. The parasite is considered to be host specific, occurring only in the moose (Alces alces), and this paper is apparently the first report of a successful infestation in an aberrant host.
Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts
Authors: Bruegger Dirk , Rehm Markus , Jacob Matthias , Chappell Daniel , Stoeckelhuber Mechthild , Welsch Ulrich , Conzen Peter , Becker Bernhard F
Published: June 2008

Introduction

Postischemic injury to the coronary vascular endothelium, in particular to the endothelial glycocalyx, may provoke fluid extravasation. Shedding of the glycocalyx is triggered by redox stress encountered during reperfusion and should be alleviated by the radical scavenger nitric oxide (NO). The objective of this study was to investigate the effect of exogenous administration of NO during reperfusion on both coronary endothelial glycocalyx and vascular integrity.

Methods

Isolated guinea pig hearts were subjected to 15 minutes of warm global ischemia followed by 20 minutes of reperfusion in the absence (Control group) and presence (NO group) of 4 μM NO. In further experiments, the endothelial glycocalyx was enzymatically degraded by means of heparinase followed by reperfusion without (HEP group) and with NO (HEP+NO group).

Results

Ischemia and reperfusion severely damaged the endothelial glycocalyx. Shedding of heparan sulfate and damage assessed by electron microscopy were less in the presence of NO. Compared with baseline, coronary fluid extravasation increased after ischemia in the Control, HEP, and HEP+NO groups but remained almost unchanged in the NO group. Tissue edema was significantly attenuated in this group. Coronary vascular resistance rose by 25% to 30% during reperfusion, but not when NO was applied, irrespective of the state of the glycocalyx. Acute postischemic myocardial release of lactate was comparable in the four groups, whereas release of adenine nucleotide catabolites was reduced 42% by NO. The coronary venous level of uric acid, a potent antioxidant and scavenger of peroxynitrite, paradoxically decreased during postischemic infusion of NO.

Conclusion

The cardioprotective effect of NO in postischemic reperfusion includes prevention of coronary vascular leak and interstitial edema and a tendency to forestall both no-reflow and degradation of the endothelial glycocalyx.
Inhibition of casein kinase 1-epsilon induces cancer-cell-selective, PERIOD2-dependent growth arrest
Authors: Yang Wan Seok , Stockwell Brent R
Published: June 2008

Background

Kinases are under extensive investigation as targets for drug development. Discovering novel kinases whose inhibition induces cancer-cell-selective lethality would be of value. Recent advances in RNA interference have enabled the realization of this goal.

Results

We screened 5,760 short hairpin RNA clones targeting the human kinome to detect human kinases on which cancer cells are more dependent than normal cells. We employed a two-step screening strategy using human sarcoma cell lines and human fibroblast-derived isogenic cell lines, and found that short hairpin RNAs targeting CSNK1E, a clock gene that regulates circadian rhythms, can induce selective growth inhibition in engineered tumor cells. Analysis of gene-expression data revealed that CSNK1E is overexpressed in several cancer tissue samples examined compared to non-tumorigenic normal tissue, suggesting a positive role of CSNK1E in neogenesis or maintenance. Treatment with IC261, a kinase domain inhibitor of casein kinase 1-epsilon (CK1ε), a protein product of CSNK1E, showed a similar degree of cancer-cell-selective growth inhibition. In a search for substrates of CK1ε that mediate IC261-induced growth inhibition, we discovered that knocking down PER2, another clock gene involved in circadian rhythm control, rescues IC261-induced growth inhibition.

Conclusion

We identified CK1ε as a potential target for developing anticancer reagents with a high therapeutic index. These data support the hypothesis that circadian clock genes can control the cell cycle and cell survival signaling, and emphasize a central role of CK1ε and PERIOD2 in linking these systems.
Pulmonary eosinophilia requires interleukin-5, eotaxin-1, and CD4+ T cells in mice immunized with respiratory syncytial virus G glycoprotein
Authors: Johnson Teresa R , Rothenberg Marc E , Graham Barney S
Published: June 2008

Severe illness, type 2 cytokine production, and pulmonary eosinophilia are adverse immune responses resulting from respiratory syncytial virus (RSV) challenge of vvGs-immunized mice. We have shown IL-4 and IL-13 activity must be simultaneously inhibited to reduce disease severity. We now address the contributions of IL-5, eotaxin-1, and CD4+ and CD8+ T cells to the induction of disease-enhancing immune responses. Depletion of CD4+ T cells during immunization prevented IL-4, IL-13, and eotaxin-1 production, diminished eosinophilia, and reduced weight loss. Conversely, CD8+ T cell depletion did not decrease eosinophilia, weight loss, or type 2 cytokines but did dramatically reduce mucus production and increase eotaxin production. Anti-IL-5 administration at immunization or challenge significantly decreased pulmonary eosinophilia. Strikingly, there were not concomitant decreases in weight loss. Following RSV challenge eotaxin-1-deficient mice immunized with vvGs exhibited significantly less eosinophilia without decreased weight loss or type 2 cytokine production. We conclude CD4+ T cell production of IL-5 and induction of eotaxin-1 are required for vvGs-induced eosinophilia following RSV challenge, while CD8+ T cells appear to down-regulate eotaxin-1 and mucus production. In summary, we demonstrate that pulmonary eosinophilia 1) is a by-product of memory CD4+ T cell activation, 2) does not necessarily correlate with mucus production, and, most importantly, 3) is not required for the RSV G-induced illness in mice. These findings have important implications for the evaluation of candidate RSV vaccines.
CCR7 regulates B16 murine melanoma cell tumorigenesis in skin
Authors: Fang Lei , Lee Vivian C , Cha Emily , Zhang Hong , Hwang Sam T
Published: June 2008

Tumor cell-associated chemokine receptors play distinct roles in cancer biology, including enhancement of lymph node (LN) metastasis. To determine if CCR7 influences tumor formation in skin, we inoculated B16 cells transduced with CCR7 and luciferase (CCR7-luc-B16) or with retroviral vector and luciferase (pLNCX2-luc-B16) into ear skin and footpads of wild-type (WT) mice. In contrast to pLNCX2-luc-B16 cells, 97% of CCR7-luc-B16 cell-inoculated mice formed skin tumors as well as cervical LN metastases by Day 21 following ear inoculation. CCR7-expressing and control B16 cells, however, formed tumors of similar size and with high-efficiency in SCID-beige mice. Cells from both lines accumulated in the skin of WT mice in similar numbers until Day 7. By Day 11, however, control cells decreased tenfold, whereas CCR7-luc-B16 cells formed small tumor nodules. Tumor cells were infrequently detected in draining cervical LNs up to 11 days after injection of both cell lines, but stable nodal metastases were only observed after CCR7-luc-B16 ear tumors had been established (∼Day 21). ELISPOT assays revealed that IFN-γ-producing cells in draining LNs from CCR7-luc-B16-injected ears were reduced through Day 7. After footpad injection, tumor formation by CCR7-expressing B16 cells was enhanced only with small, initial tumor cell inocula. With larger inocula, tumor formation was equivalent, but the numbers of tumor-infiltrating leukocytes were reduced by approximately sixfold in CCR7-B16 tumors compared with pLNCX2-B16 tumors of equal size. IFN-γ and CXCL10 were reduced 35- and sixfold, respectively, in CCR7-B16 cell tumors (vs. control tumors). Thus, CCR7 expression enhances tumorigenesis in addition to facilitating LN metastasis.
Research Perspectives in Inherited Lymphatic Disease
Authors: Ferrell Robert E. , Finegold David N.
Published: June 2008

Genetic studies of inherited lymphedema have provided the starting point for the molecular dissection of lymphatic development and disease. Here, we update the recent contribution of the study of inherited lymphedema and discuss the parallels between mouse models of lymphedema and inherited lymphedema. That the known mutations leading to lymphatic phenotypes explain fewer than half the cases of lymphedema means that the continued study of these disorders may reveal new pathways in lymphatic biology.
The Clinical Spectrum of Lymphatic Disease
Authors: Radhakrishnan Kavita , Rockson Stanley G.
Published: June 2008

Lymphatic disease is quite prevalent, and often not well clinically characterized. Beyond lymphedema, there is a broad array of human disease that directly or indirectly alters lymphatic structure and function. The symptomatic and objective presentation of these patients can be quite diverse. In this review, we have attempted to provide a systematic overview of the subjective and objective spectrum of lymphatic disease, with consideration of all of the categories of disease that primarily or secondarily impair the functional integrity of the lymphatic system. Lymphedema is discussed, along with chromosomal disorders, lymphangioma, infectious diseases, lymphangioleiomyomatosis, lipedema, heritable genetic disorders, complex vascular malformations, protein‐losing enteropathy, and intestinal lymphangiectasia.
Targeted Treatment for Lymphedema and Lymphatic Metastasis
Authors: Tervala Tomi , Suominen Erkki , Saaristo Anne
Published: June 2008

The presence of lymphatic vessels has been known for centuries, but the key players regulating the lymphatic vessel growth and function have only been discovered during the recent decade. The lymphatic vasculature is essential for maintenance of normal fluid balance and for the immune response. Hypoplasia or dysfunction of the lymphatic vessels can lead to lymphedema. Currently, lymphedema is treated primarily by physiotherapy, compression garments, and occasionally by surgery, but the means to reconstitute the collecting lymphatic vessels and cure the condition are limited. Specific growth factor therapy has been used in experimental models to regenerate lymphatic capillaries and collecting vessels after surgical damage. Recent results provide a new concept of combining growth factor therapy with lymph node transplantation as a rationale for treating secondary lymphedema. Lymphatic vessels are also involved in lymph node and systemic metastasis of cancer cells; our understanding of mechanisms of lymphatic metastasis has increased remarkably.
The 38th David A. Karnofsky Lecture: The Paradoxical Actions of Estrogen in Breast Cancer—Survival or Death?
Authors: Jordan V. Craig
Published: June 2008

During the first David A. Karnofsky Award lecture entitled “Thoughts on Chemical Therapy” in 1970, Sir Alexander Haddow commented about the dramatic regressions observed with estrogen in some breast cancers in postmenopausal women, but regrettably the mechanism was unknown. He was concerned that a cancer-specific target would remain elusive, without tests to predict response to therapy. At that time, I was conducting research for my PhD on an obscure group of estrogen derivatives called nonsteroidal antiestrogens. Antiestrogens had failed to fulfill their promise as postcoital contraceptives and were unlikely to be developed further by the pharmaceutical industry. In 1972, that perspective started to change and ICI 46,474 was subsequently reinvented as the first targeted therapy for breast cancer. The scientific strategy of targeting the estrogen receptor (ER) in the tumor, treating patients with long-term adjuvant therapy, examining active metabolites, and considering chemoprevention all translated through clinical trials to clinical practice during the next 35 years. Hundreds of thousands of women now have enhanced survivorship after their diagnosis of ER-positive breast cancer. However, it was the recognition of selective ER modulation (SERM) that created a new dimension in therapeutics. Nonsteroidal antiestrogens selectively turn on or turn off estrogen target tissues throughout the body. Patient care was immediately affected by the recognition in the laboratory that tamoxifen would potentially increase the growth of endometrial cancer during long-term adjuvant therapy. At that time, a failed breast cancer drug, keoxifene, was found to maintain bone density of rats (estrogenic action) while simultaneously preventing mammary carcinogenesis (antiestrogenic action). Perhaps a SERM used to prevent osteoporosis could simultaneously prevent breast cancer? Keoxifene was renamed raloxifene and became the first SERM for the treatment and prevention of osteoporosis as well as the prevention of breast cancer, but without an increase in endometrial cancer. There the story might have ended had the study of antihormone resistance not revealed a vulnerability of cancer cells that could be exploited in the clinic. The evolution of antihormone resistance over years of therapy reconfigures the survival mechanism of the breast cancer cell, so estrogen no longer is a survival signal but a death signal. Remarkably, remaining tumor tissue is again responsive to continuing antihormone therapy. This new discovery is currently being evaluated in clinical trials but it also solves the mystery mechanism of chemical therapy with estrogen noted by Haddow in the first Karnofsky lecture.
Bolt preload scatter and relaxation behaviour during tightening a 4 in-900# flange joint with spiral wound gasket
Authors: Abid M. , Hussain S.
Published: June 2008

Gasketed bolted flange pipe joints are found prone to leakage during operating conditions. Therefore, performance of a gasketed flange joint is highly dependent on the proper joint assembly with proper gasket, proper gasket seating stress, and proper preloading in the bolts of a joint. For a gasketed flange joint, the two main concerns are the joint strength and the sealing capability. To investigate these, a detailed three-dimensional non-linear finite-element analysis (FEA) of a gasketed joint is carried out using a spiral wound gasket. FEA results are compared with the experimental results and are found to be in good agreement, hence validating the FE model developed. Bolt scatter, bolt bending, and bolt relaxation are considered to be the main factors affecting the joint performance. In addition, the importance of proper bolt tightening sequence and number of passes and the influence of elastic and elasto-plastic material modelling on joint performance are also presented. Stress variation in the flange due to flange rotation highlighted joint strength, and gasket contact/seating stress variation highlighted the sealing performance during bolt up. Modelling the non-linearity of the spiral wound gasket using non-linear elements highlights reduced joint strength and sealing performance. Summarizing, a dynamic mode in a gasketed joint is concluded, which is the main reason for its failure.
Research on cryogenic grinding of plastics with air turbine refrigeration system
Authors: Xing L. , Wang P. , Liu S. , Fang X.
Published: June 2008

Cryogenic grinding has been the development in the field of ultrafine grinding of plastics, especially the ones with low softening temperature. The common refrigeration methods are difficult to apply in engineering production, as liquid nitrogen effects in high operation costs. Freon, lithium bromide, and ammonia show dissatisfactory refrigeration effect and need complex system. The authors chose a kind of typical thermoplastic elastomer, EVA (ethylene vinyl acetate), as their subject for research. Based on thorough study of material properties and grinding mechanism of EVA, the authors accomplished experiments to grind EVA into fine powders, effectively enhancing the fine grinding efficiency of particles at low costs, and creating a new way of recycling renewable plastics on a large scale with high quality and low energy consumption. An engineering approach to analyse the core processes of refrigeration and grinding is introduced with the energy conservation law to guide the improvement of equipment performance during the process. The key issues of the grinding process and effects are discussed in detail.
Experimental and numerical study to predict crack growth in a thick-walled cylinder under fatigue loading
Authors: Malik M A , Salam I , Abid M
Published: June 2008

Experimental and numerical studies were carried out to predict the crack growth rate under fatigue loading in a thick-walled cylinder made of aluminum alloy. Extensive experimental fatigue-crack growth data on middle tension samples was compiled and applied to simulate and predict the crack growth process using detailed two-dimensional parametric finite-element (FE) technique. The fatigue-crack propagation was simulated, based on linear elastic fracture mechanics and stress intensity factor determination. The FE model provided results of crack-growth analysis optimized for stress levels ranging from 40 per cent to 25 per cent of the material yield stress. Fatigue-life analysis of the samples showed that the results obtained from the two techniques were in good agreement up to a stress range of 79 MPa. However, at lower stress ranges, the number of cycles to failure as determined by FE analysis (FEA) was smaller than found experimentally. The experimental results were 13 per cent and 36 per cent higher than FEA results at stress ranges of 63 and 49 MPa, respectively. This disparity was explained in terms of the crack growth rates near the threshold stress intensity factor range.
Computed versus measured force coefficients on a cone in a small arc facility
Authors: Russo G P , Zuppardi G , Esposito A
Published: June 2008

Measurements of the aerodynamic forces acting on a 70° semiangle cone have been made in the small arc facility SPES at the Department of Aerospace Engineering in Naples. Two sets of measurements, with arc electrical currents of 300 and 400A, respectively, are noted; the test gas was argon, the mass flow rate was 1g/s. Because of the existing difficulties in measuring the free stream parameters in an arc wind tunnel, two procedures are proposed to calculate them: the first based on the one-dimensional theory and the second solving the flow field in the nozzle by a two-dimensional direct simulation Monte Carlo method (DSMC) code; the ‘continuum break-down limit’ is overcome just before the exit of the nozzle. The experimental force coefficients have been compared both with other experimental data available in the open literature and with the results from three-dimensional DSMC code. The comparison shows, as expected, some discrepancies among experimental and numerical data due to the uncertainties in the test parameters and to the interference, at high angle of attack, of the sting supporting the model.
Fault detection and isolation in aircraft gas turbine engines. Part 1: Underlying concept
Authors: Gupta S , Ray A , Sarkar S , Yasar M
Published: June 2008

Degradation monitoring is of paramount importance to safety and reliability of aircraft operations and also for timely maintenance of its critical components. This two-part paper formulates and validates a novel methodology of degradation monitoring of aircraft gas turbine engines with emphasis on detection and isolation of incipient faults. In a complex system with multiple interconnected components (e.g. an aircraft engine), fault isolation becomes a crucial task because of possible input—output and feedback interactions among the individual components. This paper, which is the first of two parts, presents the underlying concepts of fault detection and isolation (FDI) in complex dynamical systems. The FDI algorithms are formulated in the setting of symbolic dynamic filtering (SDF) that has been recently reported in literature. The underlying concept of SDF is built upon the principles of symbolic dynamics, statistical pattern recognition, and information theory. In addition to abrupt large faults, the SDF-based algorithms are capable of detecting slowly evolving anomalies (i.e. deviations from the nominal behaviour) based on analysis of time series data of critical process variables of different engine components. The second part, which is a companion paper, validates the concept, laid out in the first part, on the simulation test bed of a generic two-spool turbofan aircraft engine model for detection and isolation of incipient faults.
Investigations on ethylene combustion in a scramjet combustor using resistance heaters
Authors: Xiao Y , Song W , Chen L , Wang D , Le J
Published: June 2008

In this article, the ignition characteristics of the gaseous ethylene hydrocarbon fuel is investigated in a supersonic clean airstream experimental facility with resistance heaters. A generic cavity flame holder is used to create a recirculation region and promote the fuel/air mixing at the lower wall of the combustor. Three different injection concepts are considered in this research: (a) ethylene injection upstream of the cavity; (b) ethylene and hydrogen injection upstream of the cavity simultaneously; and (c) ethylene injection preceded by pilot hydrogen injection. The pilot injection is a supportive tool for holding the flame of the main normal ethylene fuel injection. Therefore, using pilot hydrogen injection and cavity configuration necessitates optimizing the combustor length to ensure complete combustion and full liberation of the chemical energy stored in the fuel before exiting the combustor. This study proved the possibility of igniting the ethylene and maintaining its flame in the supersonic airstreams.
Acute toxicity of acidity in larvae and adults of four stream salamander species (Plethodontidae)
Authors: Green Linda E , Peloquin Jennifer E
Published: June 2008

High levels of acid deposition have severely affected streamwater chemistry in the southern Appalachians. Plethodontid stream salamanders living in and around headwater streams rely on cutaneous respiration and are highly susceptible to changes in water quality. We examined the sensitivity to low pH conditions in four stream salamanders by monitoring the response to six pH treatments ranging from pH 2.75 to 6.5. To quantify acid tolerance, we determined median lethal concentrations (LC50) in 96-h laboratory bioassays. This is the first study to quantify the level of sensitivity of stream salamanders to acidic conditions, indicating that stream salamanders are acid tolerant compared with many other lotic organisms. We found that acid tolerance is a species-specific trait with intraspecific variation shaped by life stage and body size. Mortality occurred at pH levels less than 4.2. The acid sensitivity of Desmognathus quadramaculatus larvae (LC50 = pH 3.95) was highest compared to sensitivity of Eurycea cirrigera larvae (LC50 = 3.6), Gyrinophilus porphyriticus larvae (LC50 = 3.5), and Pseudotriton ruber larvae (LC50 = 3.5). Larval survival was lower than adult survival in low pH treatments for E. cirrigera (adult LC50 = 3.1) and D. quadramaculatus (adult LC50 = 3.5). Salamanders responded to sublethal exposure to acidity with lethargic movements and decreased swimming speed. These results suggest that episodic acid events that cause streamwater pH to drop near 4.2 may cause mortality or induce sublethal effects, such as slower swimming speed. Because salamander larvae are more sensitive to acidic conditions than adults, we recommend that population monitoring programs extend methodology to include reliable estimates of larval population sizes.
Enzyme-linked immunosorbent assay for screening dioxin soil contamination by uncontrolled combustion during informal recycling in slums
Authors: Trindade Mirta , Nording Malin , Nichkova Mikaela , Spinnel Erik , Haglund Peter , Last Michael S , Gee Shirley , Hammock Bruce , Last Jerold A , González-Sapienza Gualberto , Brena Beatriz M
Published: June 2008

Uncontrolled combustion due to garbage recycling is a widespread activity among slum dwellers in distressed economy countries and has been indicated as a major source of dioxin contamination. However, because of the high cost and complexity of gas chromatography/high-resolution mass spectrometry (GC-HRMS) analysis, the magnitude of the problem remains largely unknown. The present study describes a first approach toward the use of a dioxin antibody-based enzyme-linked immunosorbent assay (ELISA) as the basis for a sustainable, simple, and low-cost monitoring program to assess the toxicological impact of uncontrolled combustion in slums. A panel of 16 samples was analyzed by GC-HRMS and ELISA on split extracts. Close to 20% of the analyzed samples showed dioxin concentrations up to almost twice the guidance level for residential soil in several countries, pointing out the need for performing a large-scale monitoring program. Despite the potential for variations in dioxin congener distribution due to the mixed nature of the incinerated material, there was a good correlation between the toxic equivalents as determined by GC-HRMS and ELISA. Furthermore, an interlaboratory ELISA validation showed that the capacity to perform the dioxin ELISA was successfully transferred between laboratories. It was concluded that the ELISA method performed very well as a screening tool to prioritize samples for instrumental analysis, which allows cutting down costs significantly.
Epoxiconazole causes changes in testicular histology and sperm production in the Japanese quail (Coturnix coturnix japonica)
Authors: Grote Konstanze , Niemann Lars , Selzsam Britta , Haider Wolfgang , Gericke Christine , Herzler Matthias , Chahoud Ibrahim
Published: June 2008

The fungicide epoxiconazole (Epox), a triazole, belongs to the group of azole compounds that are extensively used as fungicides in various fruit crops. The frequent use of agricultural lands for wintering by migrating birds can be the source of their increased dietary intake of agricultural pesticides. We investigated whether exposure to Epox causes effects on avian fertility and reproduction, using the Japanese quail (Coturnix coturnix japonica) as a model species for the assessment of reproductive effects of pesticides in wild birds. Epox was administered to adult Japanese quail for three weeks at dietary levels of 10, 50, and 500 ppm, and possible effects on reproduction were investigated. Epox administration resulted in a significantly decreased number of spermatids in the 50- and 500-ppm dose groups. Histopathology showed a reduced number of testicular canaliculi with visible germ cells and a reduction in spermatid number. However, testis weight was not affected up to the highest dose level. No impact was observed on hormone levels, fertility, and reproductive outcome, as laying rate and percentage of fertile eggs were not altered. Likewise, treatment had no influence on the egg or chick parameters evaluated. A time- and dose-related transfer of Epox into the eggs was determined in all treatment groups. We conclude that dietary treatment of Japanese quail with 50 and 500 ppm of the triazole fungicide Epox resulted in a clear impact on the testis. The evaluation of the additional endpoints spermatid count and testicular histology have proven useful and are recommended for future studies on avian reproduction.
A database of fish biotransformation rates for organic chemicals
Authors: Arnot Jon A , Mackay Don , Parkerton Thomas F , Bonnell Mark
Published: June 2008

Biotransformation is a key process that can mitigate the bioaccumulation potential of organic substances and is an important parameter for exposure assessments. A recently published method for estimating whole-body in vivo metabolic biotransformation rate constants (kM) is applied to a database of measured laboratory bioconcentration factors and total elimination rate constants for fish. The method uses a kinetic mass balance model to estimate rates of chemical uptake and elimination when measured values are not reported. More than 5,400 measurements for more than 1,000 organic chemicals were critically reviewed to compile a database of 1,535 kM estimates for 702 organic chemicals. Biotransformation rates range over six orders of magnitude across a diverse domain of chemical classes and structures. Screening-level uncertainty analyses provide guidance for the selection and interpretation of kM values. In general, variation in kM estimates from different routes of exposure (water vs diet) and between fish species is approximately equal to the calculation uncertainty in kM values. Examples are presented of structure–biotransformation relationships. Biotransformation rate estimates in the database are compared with estimates of biodegradation rates from existing quantitative structure–activity relationship models. Modest correlations are found, suggesting some consistency in biotransformation capabilities between fish and microorganisms. Additional analyses to further explore possible quantitative structure–biotransformation relationships for estimating kM from chemical structure are encouraged, and recommendations for improving the database are provided.
Selection and identification of bacterial strains with methyl-tert-butyl ether, ethyl-tert-butyl ether, and tert-amyl methyl ether degrading capacities
Authors: Purswani Jessica , Pozo Clementina , Rodríguez-Díaz Marina , González-López Jesús
Published: June 2008

Nine bacterial strains isolated from two hydrocarbon-contaminated soils were selected because of their capacity for growth in culture media amended with 200 mg/L of one of the following gasoline oxygenates: Methyl-tert-butyl ether (MTBE), ethyl-tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME). These strains were identified by amplification of their 16S rRNA gene, using fD1 and rD1 primers, and were tested for their capacity to grow and biotransform these oxygenates in both mineral and cometabolic media. The isolates were classified as Bacillus simplex, Bacillus drentensis, Arthrobacter sp., Acinetobacter calcoaceticus, Acinetobacter sp., Gordonia amicalis (two strains), Nocardioides sp., and Rhodococcus ruber. Arthrobacter sp. (strain MG) and A. calcoaceticus (strain M10) consumed 100 (cometabolic medium) and 82 mg/L (mineral medium) of oxygenate TAME in 21 d, respectively, under aerobic conditions. Rhodococcus ruber (strain E10) was observed to use MTBE and ETBE as the sole carbon and energy source, whereas G. amicalis (strain T3) used TAME as the sole carbon and energy source for growth. All the bacterial strains transformed oxygenates better in the presence of an alternative carbon source (ethanol) with the exception of A. calcoaceticus (strain M10). The capacity of the selected strains to remove MTBE, ETBE, and TAME looks promising for application in bioremediation technologies.