bluuebunny/crossref_metadata_2025 huggingface dataset:
The Human Placenta Remodels the Uterus by Using a Combination of Molecules That Govern Vasculogenesis or Leukocyte Extravasation
Authors: ZHOU YAN , GENBACEV OLGA , FISHER SUSAN J.
Published: July 2009

Abstract: After fertilization, the next major hurdle for human reproduction is trophoblast differentiation, which is required for implantation, followed in lockstep by rapid assembly of these embryonic cells into a functional placenta. During this process, cytotrophoblast stem cells invade the uterus, anchoring the conceptus to the mother and establishing blood flow to the placenta. Cytotrophoblast invasion is actually a differentiation process that yields cells with many unusual attributes, that is, their tumor‐like ability to invade the uterus and engraft maternal blood vessels. We discovered that once cytotrophoblasts commit to invasion they turn on expression of adhesion receptors characteristic of endothelium. They also begin to express and activate matrix metalloproteinase‐9. Together, these phenotypic changes facilitate invasion while enabling cytotrophoblasts to present an endothelium‐like surface to maternal blood. Currently, we are trying to understand the factors that play a role in cytotrophoblast differentiation/invasion. In keeping with the vascular characteristics that differentiated cytotrophoblasts assume, our recent data suggest that the key regulators include an unusual subset of vascular endothelial growth factor family members that play important roles in conventional vasculogenesis/angiogenesis. Surprisingly, we also discovered that these cells express functional l‐selectin, which mediates neutrophil rolling and tethering, under shear stress, on inflamed endothelium. Trophoblast l‐selectin likely interacts with carbohydrate selectin ligands that are upregulated on uterine glandular epithelium during the window of receptivity. Together, these data suggest that differentiating cytotrophoblasts have co‐opted portions not only of vasculogenesis, but also of the process that facilitates leukocyte emigration from the blood into tissues, additional evidence of these cells' amazing plasticity.
Tissue Involution and the Acute Phase Response
Authors: NILSEN‐HAMILTON MARIT , LIU QUANSHENG , RYON JOEL , BENDICKSON LEE , LEPONT PIERIG , CHANG QING
Published: July 2009

Abstract: After their roles in reproduction are completed, the mass of the uterus and the mammary gland decrease rapidly by the process of involution that involves an ordered series of events including apoptosis, neutrophil entry, the release of degradative enzymes, and phagocytosis of cellular debris. The acute phase proteins are produced by the liver and other tissues in response to inflammation or a toxic challenge. Uterocalin (SIP24/24p3) is one of these proteins. During involution, the mammary gland and uterus express high levels of uterocalin that reach an average of 0.2–0.5% of the total extractable protein at its peak. Uterocalin and its orthologues have been demonstrated in vitro to (1) bind certain fatty acids and (2) specifically induce apoptosis in neutrophils and other leukocytes. The period of uterocalin expression during involution is consistent with the hypothesis that one of its physiological roles is to induce apoptosis of invading neutrophils and delay the entry of neutrophils into the tissue until the second phase of involution. Interestingly, it has been shown that uterocalin expression remains higher in primiparous gland than in virgin glands after the pregnant glands have completely involuted. This observation and the known protective effect of early pregnancy on later development of breast cancer suggest that the ability of uterocalin to induce apoptosis in neutrophils might also decrease oxidative and carcinogenic activity in the gland and result in a lower mutation rate and thus a lower probability of cancer in the primiparous gland.
Differentiation and Morphological Integration of Neural Progenitor Cells Transplanted into the Developing Mammalian Eye
Authors: SAKAGUCHI D. S. , Van HOFFELEN S. J. , YOUNG M. J.
Published: July 2009

Abstract: Transplantation of neural stem/progenitor cells has been proposed as a novel approach for the replacement and repair of damaged CNS tissues. We have evaluated the influence of the host cellular microenvironment upon the survival, differentiation, and integration of neural progenitor cells transplanted into the CNS. Using this approach, we have investigated the fate of neural progenitor cells in vivo following transplantation into the developing mammalian eye. Murine brain progenitor cells (mBPCs) isolated from neonatal mice expressing the green fluorescent protein (GFP) transgene were transplanted into the eyes of Brazilian opossums (Monodelphis domestica). Monodelphis pups are born in an extremely immature, fetal‐like state. The eyes of neonatal pups provide a fetal‐like environment in which to study cellular interactions between host tissues and transplanted neural progenitor cells. mBPCs were transplanted by intraocular injection in hosts ranging in age from 5 days postnatal to adult. The transplanted cells were easily identified because of their GFP fluorescence. Extensive survival, differentiation, and morphological integration of mBPCs within the host tissue was observed. We found that the younger retinas provided a more supportive environment for the morphological integration of the transplanted mBPCs. Cells with morphologies characteristic of specific retinal cell types were observed. Moreover, some transplanted mBPCs were labeled with antibodies characteristic of specific neural/retinal phenotypes. These results suggest that the host environment strongly influences progenitor cell differentiation and that transplantation of neural progenitor cells may be a useful approach aimed at treating degeneration and pathology of the CNS.
Role of Collagen Type II and Perlecan in Skeletal Development
Authors: GUSTAFSSON ERIKA , ASZÓDI ATTILA , ORTEGA NATHALIE , HUNZIKER ERNST B. , DENKER HANS‐WERNER , WERB ZENA , FÄSSLER REINHARD
Published: July 2009

Abstract: The cartilage extracellular matrix is composed of a dense collagen network that entraps a range of other specialized proteins important for the proper formation and function of the tissue. Loss of two abundant cartilage components, type II collagen and perlecan, has drastic effects on skeletal development. Both collagen II and perlecan mutants have severe and lethal chondrodysplasia characterized by disorganized growth plate, lack of collagen network, defective endochondral bone formation, and abnormal intervertebral disk development. To test whether the reduced collagen density in the perlecan‐null cartilage is due to enhanced activity of collagen‐degrading proteinases, we have analyzed gelatinase expression and activity in the mutant tissue. Immunohistochemical analysis revealed a weak, but clear, expansion of MMP‐9 deposition into the hypertrophic zone of the perlecan‐null growth plate. However, in situ and SDS‐PAGE zymography showed that the activity of gelatinases (MMP‐2 and MMP‐9) is not altered in perlecan‐null cartilage, suggesting that they are not primarily linked to the reduced fibrillar network observed in the mutant. Likewise, intercrossing of perlecan mutants onto an MMP‐9‐null background could not rescue the ultrastructural abnormalities of the perlecan‐deficient cartilage.
Notch Signaling in Primary Endothelial Cells
Authors: SHAWBER CARRIE J. , DAS INDRANIL , FRANCISCO ESTHER , KITAJEWSKI JAN
Published: July 2009

Abstract: The Notch family of cell‐surface receptors has been proposed to regulate cell‐fate decisions by modulating the ability of each cell to respond to environmental cues. In vertebrates, gain‐of‐function and loss‐of‐function studies have demonstrated a requirement for Notch signaling for proper patterning of the vasculature during embryogenesis. To examine the molecular mechanisms by which Notch regulates vascular development, we analyzed changes in gene expression in response to Notch signaling. Notch signal transduction and function were assessed in primary human endothelial cells isolated from the dermal microvasculature of neonates, HMVECd. We demonstrate that HMVECd cells express a heterodimeric form of endogenous Notch4 on their cell surface. Using an in vitro coculture assay, we found that Delta4 can function as a ligand for Notch4 in HMVECd cells. Moreover, ectopic expression of an activated allele of Notch4 upregulated the expression of Delta4, suggesting that there may be a regulatory loop between Notch4 and its ligand, Delta4. Notch4 activation also induced the expression of the transcriptional repressors, HES1, HERP1, and HERP2, as well as ephrinB2, an angiogenic factor proposed to be involved in arterial/venous endothelial cell specification.
ADAMTS1: A Matrix Metalloprotease with Angioinhibitory Properties
Authors: IRUELA‐ARISPE M. LUISA , CARPIZO DARREN , LUQUE ALFONSO
Published: July 2009

Abstract: Neovascularization is a hallmark of cancer progression. Suppression of the angiogenic response in tumors has been associated with inhibition and even regression of total tumor mass. Therefore, the derivation of synthetic or natural products that could interfere with proangiogenic signaling pathways can greatly impact cancer therapy. Using the antiangiogenic motifs in thrombospondin‐1, we have recently cloned METH1/ADAMTS1, a secreted metalloproteinase with three thrombospondin‐1, and shown that the protein inhibits endothelial cell proliferation in vitro and blocks the neovascular response induced by growth factors in vivo. The mechanism of action responsible for these events has not been elucidated. In this report, we present evidence to support two effects of METH1/ADAMTS1 that impact proangiogenic signaling events. ADAMTS1 binds to VEGF and dampens VEGFR2 phosphorylation. The ability of ADAMTS1 to bind VEGF and functionally inactivate VEGFR2 is reversible as dissociation of the complex results in active growth factor. A second activity of ADAMTS1 requires the catalytic domain as a single point mutation in the metalloproteinase domain renders the protein inactive in tumor xenograft assays. The emerging theme is that both domains are likely required for the antiangiogenic/antitumor activities of ADAMTS1.
Genetic Analysis of Hypoxia Signaling and Response in C. elegans
Authors: SHEN CHUAN , POWELL‐COFFMAN JO ANNE
Published: July 2009

Abstract: During normal development and homeostasis, animals use cellular and systemic strategies to adapt to changing oxygen levels. In mammals, hypoxic tissues secrete growth factors to induce angiogenesis, and individual cells increase anaerobic metabolism in order to sustain basic cellular functions. Many of these critical responses to decreased oxygen availability are regulated by the hypoxia‐inducible factors, dimeric transcriptional complexes consisting of α and β subunits. HIFα proteins are specialized for hypoxia response, and oxygen levels regulate their stability and activity. The C. elegans hif‐1 gene is orthologous to mammalian HIFα genes, and C. elegans has proven to be a powerful system for the study of hypoxia‐inducible factor regulation and function. Mutants lacking hif‐1 function are viable in normoxic or anoxic conditions, but they cannot adapt to hypoxia. Recent genetic analyses in C. elegans led to the identification of the evolutionarily conserved enzyme that hydroxylates HIFa in an oxygen‐dependent manner. Once modified, HIFα binds the von Hippel‐Lindau tumor suppressor protein and is targeted for proteasomal degradation. Here, we briefly review the characterization of C. elegans hif‐1 and interacting genes, and discuss genetic strategies for studying hypoxia signaling and response.
Comparative Structure‐Function Analysis of VEGFR‐1 and VEGFR‐2
Authors: MEYER ROSANA D. , RAHIMI NADER
Published: July 2009

Abstract: Activation of vascular endothelial growth factor receptor‐1 and ‐2 (VEGFR‐1 and VEGFR‐2) plays a critical role in vasculogenesis and angiogenesis. However, the mechanism by which activation of VEGFRs elicits these cellular events is not fully understood. We recently constructed chimeric receptors containing the extracellular domain of human CSF‐1R/c‐fms fused with the entire transmembrane and cytoplasmic domains of murine VEGFR‐1 and VEGFR‐2. Selective activation of chimeric VEGFR‐2, but not chimeric VEGFR‐1, stimulated endothelial cell growth, migration, and differentiation. Stimulation of cells coexpressing chimeric VEGFR‐1 and VEGFR‐2 suppressed VEGFR‐2‐mediated endothelial cell growth. Site‐directed mutagenesis demonstrated that tyrosines 799 and 1173 are required for VEGFR‐2‐mediated endothelial cell growth and activation of PI3 kinase. Further site‐directed mutagenesis demonstrated that tyrosine 1212, located in the carboxyl tail of VEGFR‐2, is required for the ligand‐dependent autophosphorylation of the receptor and its ability to activate signaling proteins. Collectively, our results suggest that activation of VEGFR‐1 and VEGFR‐2 differentially regulates endothelial cell function and angiogenesis. Second, activation of VEGFR‐2 is associated with many endothelial cell functions, including cell proliferation, migration, and differentiation. Third, activation of PI3 kinase by VEGFR‐2 regulates endothelial cell proliferation.
Genome‐Wide Analysis of Epigenetics in Cancer
Authors: LEE MAXWELL P.
Published: July 2009

Abstract: Human cancers are caused by multiple mechanisms. Research in the last 30 years has firmly established the roles of a group of genes including oncogenes, tumor suppressor genes, and DNA repair genes in human cancers. The activation and inactivation of these cancer genes can be caused by genetic mutations or epigenetic alterations. The epigenetic changes in cancers include methylation of CpG islands, loss of imprinting, and chromatin modification. The completion of the genome sequences of many organisms including the human has transformed the traditional approach to molecular biology research into an era of functional genome research. Traditional research usually involves the study of one or a few genes (proteins) in a particular biological process in normal physiology or disease. Functional genome research takes advantage of newly available genome sequences and high‐throughput genome technologies to study genes and/or proteins to inform the perspective of entire biological processes. I will focus on recent progress in the identification of imprinted genes and methylation of CpG islands through genome‐wide analysis.
Methylation‐Sensitive Representational Difference Analysis and Its Application to Cancer Research
Authors: KANEDA ATSUSHI , TAKAI DAIYA , KAMINISHI MICHIO , OKOCHI ERIKO , USHIJIMA TOSHIKAZU
Published: July 2009

Abstract: Methylation‐sensitive representational difference analysis (MS‐RDA) was previously established to detect differences in the methylation status of two genomes. This method uses the digestion of genomic DNA with a methylation‐sensitive restriction enzyme, HpaII, and PCR to prepare ‘HpaII‐amplicons,’ followed by RDA. An HpaII‐amplicon prepared using betaine and reverse electrophoresis was enriched 3.6‐fold (compared with the HpaII‐amplicon prepared by the original method) with DNA fragments originating from CpG islands (CGIs). As for the specificity of MS‐RDA, it was shown that DNA fragments that are unmethylated in the tester and almost completely methylated in the driver are efficiently isolated. This indicated that genes that are in biallelic methylation or in monoallelic methylation with loss of the other allele are efficiently isolated. Further, by use of two additional methylation‐sensitive six‐base recognition restriction enzymes, SacII and NarI, more DNA fragments were isolated from CGIs in the 5′ regions of genes. After analysis of human lung, gastric, and breast cancers, 12 genes were seen to be silenced and additional genes seen to show decreased expression in association with methylation of genomic regions outside CGIs in the 5′ regions of genes. MS‐RDA is effective in identifying silenced genes in various cancers.
Environmental Exposure, DNA Methylation, and Gene Regulation
Authors: LI SHUANFANG , HURSTING STEPHEN D. , DAVIS BARBARA J. , McLACHLAN JOHN A. , BARRETT J. CARL
Published: July 2009

Abstract: DNA methylation is an epigenetic mechanism that regulates chromosomal stability and gene expression. Abnormal DNA methylation patterns have been observed in many types of human tumors, including those of the breast, prostate, colon, thyroid, stomach, uterus, and cervix. We and others have shown that exposure to a wide variety of xenobiotics during critical periods of mammalian development can persistently alter the pattern of DNA methylation, resulting in potentially adverse biological effects such as aberrant gene expression. Thus, this epigenetic mechanism may underlie the observed increased risk in adulthood of several chronic diseases, including cancer, in response to xenobiotic exposures early in life. We present here the lessons learned from studies on the effects of perinatal diethylstilbesterol (DES) exposure on the methylation pattern of the promoters of several estrogen‐responsive genes associated with the development of reproductive organs. Perinatal DES exposure, which induces epithelial tumors of the uterus in mice and is associated with several reproductive tract abnormalities and increased vaginal and cervical cancer risk in women, provides a clear example of how estrogenic xenobiotic exposure during a critical period of development can abnormally demethylate DNA sequences during organ development and possibly increase cancer risk later in life. In addition, nutritional factors and stress may also alter DNA methylation during early life and modulate the risk of cancer and other chronic diseases in adulthood. We suggest that DNA methylation status may be influenced by environmental exposures in early life, leading to increased risk of cancer in adulthood.
Diet and DNA Methylation Interactions in Cancer Prevention
Authors: ROSS SHARON A.
Published: July 2009

Abstract: Epigenetic events constitute an important mechanism by which gene function is selectively activated or inactivated. Since epigenetic events are susceptible to change they offer potential explanations of how environmental factors, including diet, may modify cancer risk and tumor behavior. Abnormal methylation patterns are a nearly universal finding in cancer, as changes in DNA methylation have been observed in many cancer tissues (e.g., colon, stomach, uterine cervix, prostate, thyroid, and breast). Site‐specific alterations in DNA methylation have also been observed in cancer and may play a significant role in gene regulation and cancer development. This review presents intriguing evidence that part of the anticancer properties attributed to several bioactive food components, encompassing both essential nutrients and non‐essential components, may relate to DNA methylation patterns. Four sites where dietary factors may be interrelated with DNA methylation are discussed. First, dietary factors may influence the supply of methyl groups available for the formation of S‐adenosylmethionine (SAM). Second, dietary factors may modify the utilization of methyl groups by processes including shifts in DNA methyltransferase (Dnmt) activity. A third plausible mechanism may relate to DNA demethylation activity. Finally, the DNA methylation patterns may influence the response to a bioactive food component.
Epigenetics in High‐Grade Astrocytomas
Authors: DEBINSKI WALDEMAR , GIBO DENISE , MINTZ AKIVA
Published: July 2009

Abstract: Human high‐grade astrocytomas (HGA) are the most prevalent incurable brain tumors. We found that the vast majority of HGA patients overexpress a restricted receptor for an immune regulatory cytokine, interleukin 13 (IL‐13). Interestingly, the HGA‐associated restricted receptor protein IL‐13Rα2 is expressed in the testes, and its gene is localized to chromosome X. These mirror the expression pattern and genomic localization of cancer/testes tumor antigens (CTA). Hypothetical considerations and now experimental evidence are beginning to point towards epigenetics, and DNA methylation alterations in particular, as being responsible for the appearance in cancer of CTA, including IL‐13Rα2. In line with our interest in the X chromosome and oncogenesis, we have identified a new ubiquitous angiogenic factor in HGA, a vascular endothelial growth factor‐D (VEGF‐D). We have also demonstrated that the activating protein‐1 (AP‐1) family of transcription factors play a potentially critical role in the progression of gliomas by eliciting uncontrolled upregulation of VEGF‐D and other compounds essential for cancer cell proliferation, tumorigenesis, and infiltration. The possibility exists that an unopposed constitutive increase in AP‐1 activity in HGA is related to epigenetic silencing of the inhibitors of AP‐1 activity. These phenomena offer potential targets for exploitation in either prevention or early detection of brain tumors. For example, anticancer vaccines against shared CTA could help in prevention of HGA development. Furthermore, drugs with anti‐AP‐1 activity could be effective in preventing formation/progression of HGA, or progression from less malignant lower grade gliomas to HGA. Also, circulating antibodies against CTA and factors that are AP‐1 regulated may provide a useful tool in early detection of brain tumors or for monitoring their progression following initial treatment.
Aberrant DNA Methylation in Ovarian Cancer
Authors: WEI SUSAN H. , BROWN ROBERT , HUANG TIM H.‐M.
Published: July 2009

Abstract: Epigenetic regulation of gene expression has been observed in a variety of tumor types. We have used microarray technology to evaluate the predisposition of drug response by aberrant methylation in ovarian cancer. Results indicate that loss of gene activity due to hypermethylation potentially confers a predisposition in certain cancer types and is an early event in disease progression. Methylation profiles of ovarian cancer might be useful for early cancer detection and prediction of chemotherapy outcome in a clinical context.
Early Detection and Risk Assessment Proceedings and Recommendations from the Workshop on Epigenetics in Cancer Prevention
Authors: VERMA MUKESH , DUNN BARBARA K. , ROSS SHARON , JAIN PAWAN , WANG WENDY , HAYES RICHARD , UMAR ASAD
Published: July 2009

Abstract: Recent advances in molecular biology that have provided a greater understanding of multistage carcinogenesis include the use of biomarkers of early detection and risk assessment. Prominent among such biomarkers are epigenetic changes. The field of epigenetics has seen a recent surge of interest among cancer researchers since alterations in DNA methylation have emerged as one of the most consistent molecular alterations in multiple neoplasms. Chromatin condensation, histone deacetylation, and promoter methylation are major steps in the epigenetic regulation of gene expression. Epigenetic changes may occur due to environmental factors, aging, and genomic imprinting. An important distinction between genetic and epigenetic alterations in cancer prevention is that the latter might be more easily reversed using therapeutic interventions. In the workshop the following areas of research were recognized for emphasis in future work: (1) basic epigenetic mechanisms in cancer need further investigation; (2) technology development in the area of epigenetics, such as high‐throughput quantitative assays and increased sensitivity/specificity, is essential for the early detection and risk assessment of cancer; (3) the clinical application of epigenetic changes to cancer prevention and risk assessment needs further investigation. Further research will lead to the identification of new targets for cancer prevention.
Application of Hollow Fiber Membrane Contactors for Catalyst Recovery in the WPO Process
Authors: ORTIZ INMACULADA , URTIAGA ANE , ABELLÁN M. JOSÉ , SAN ROMÁN FRESNEDO
Published: July 2009

Abstract: In this work the use of a membrane based liquid extraction process for recovery of the homogeneous catalyst employed in the wet peroxide oxidation process (WPO) is studied. In the WPO process the oxidation agent is the hydroxyl radical that is obtained by using a combination of hydrogen peroxide and a mixture of Fe(II), Cu(II), and Mn(II) in aqueous solution. The mixture of metallic cations permits the almost total degradation of the refractory organic compounds, but the use of metallic salts as catalysts induces additional pollution. To recover the homogeneous catalyst of the WPO process by means of non‐dispersive solvent extraction (NDSX) two hollow fiber membrane contactors are employed, one for the extraction step and the second for the backextraction step. From the initial assays, the extractant LIX 622N was selected for Cu(II) recovery and Cyanex 272 for Fe(II) and Mn(II) recovery. Selective separation of Fe(II) and Mn(II) can be obtained by adjusting the pH of the feed aqueous phase. The three metals are stripped using sulfuric acid to give concentrated solutions of CuSO4, FeSO4, and MnSO4 that can be recycled to the formulation of the catalyst solution of the WPO process. A mathematical model has been proposed to describe the recovery of Cu. Two design parameters are required: the membrane mass transport coefficient of the extraction and stripping modules (km= 3.07 × 10−7 m/sec) and the equilibrium parameter of the extraction reaction (KEx= 0.0832).
Characteristics and Application of Ceramic Nanofiltration Membranes
Authors: WEBER RALPH , CHMIEL HORST , MAVROV VALKO
Published: July 2009

Abstract: In this paper we report on the characteristic and filtration behavior of a newly developed ceramic nanofiltration membrane and compare it with other commercial ceramic nanofiltration membranes currently available. It is shown that it is possible to produce a ceramic membrane with separation properties in the nanofiltration range and with permeability rates that are clearly superior to those of polymer nanofiltration membranes. The ceramic membrane was used in tests involving the treatment of textile wastewater, alkaline solutions from bottle washing machines, and pickling bath solutions.
Nanocomposite Lithium Ion Conducting Membranes
Authors: CROCE FAUSTO , SCROSATI BRUNO
Published: July 2009

Abstract: This review describes the properties and characteristics of a class of membranes formed by blends of a lithium salt, LiX, where X is preferably a large soft anion, such as ClO4 or N(CF3SO2)2, and a high molecular weight polymer containing Li+‐coordinating group, such as polyethylene oxide (PEO) with the dispersion of selected ceramic powders, such as TiO2, Al2O3, and SiO2, at the nanoscale particle size. These nanocomposite membranes behave as lithium polymer electrolytes, that is, they exhibit a high lithium ion conductivity. Because of this property, the PEO‐LiX nanocomposite electrolytes may find an important application as separators in advanced, rechargeable lithium polymer batteries.
Preparation of Nano‐Structured Polymeric Proton Conducting Membranes for Use in Fuel Cells
Authors: ALBERTI GIULIO , CASCIOLA MARIO , PICA MONICA , DI CESARE GIUSI
Published: July 2009

Abstract:We briefly discuss the state of the art of polymer electrolyte membrane fuel cells and suggest that the main obstacles to the commercial development of these fuel cells are essentially the high costs and poor characteristics of present proton conducting membranes. A strategy for the preparation of improved nanocomposite membranes based on the introduction of proton conducting lamell? in the polymeric matrix of present ionomeric membranes is then discussed. Due to their high proton conductivity (in some cases even higher than 10−1S cm−1), tailor made lamellæ obtained by exfoliation of superacid metal (IV) phosphonates are particularly suitable for the preparation of these hybrid membranes. The expected positive influence of the dispersed lamellæ on important properties of proton conducting membranes, such as swelling, mechanical resistance, proton transport, and diffusion of methanol, are also discussed. The methods used to obtain good lamellar dispersions into ionomeric polymers and the preparation and main characteristics of some hybrid membranes are also briefly described. The presence of nanoparticles of metal phosphonates in the electrodic interfaces Nafion/Pt already considerably improves the electrochemical characteristics of fuel cells in the temperature range 80–130°C. The increased working temperature of the fuel cell considerably reduces CO poisoning of the platinum electrodes and allows better control of the cooling system, thus overcoming important obstacles to the development of medium temperature PEM fuel cells.
High Performance Perfluoropolymer Films and Membranes
Authors: ARCELLA VINCENZO , GHIELMI ALESSANDRO , TOMMASI GIULIO
Published: July 2009

Abstract: Membrane processes are receiving increasing attention in the scientific community and in industry because in many cases they offer a favorable alternative to processes that are not easy to achieve by conventional routes. In this context, membranes made with perfluorinated polymers are of particular interest because of the unique features demonstrated by these materials. Both highly hydrophobic and hydrophilic membranes have been developed from appropriate perfluoropolymers that were, in turn, obtained by copolymerizing TFE with special monomers available on an industrial scale. Highly hydrophobic membranes obtained from the glassy copolymers of TFE and 2,2,4‐trifluoro‐5 trifluoromethoxy‐1,3 dioxole (Hyflon® AD) exhibit properties that make them particularly well suited for use in optical applications, in the field of gas separation, and in gas‐liquid contactors. Conditions for preparing membranes that are adequate for use in various applications are exemplified. Hydrophylic highly conductive proton exchange membranes obtained from the copolymer of TFE and a short‐side‐chain (SSC) perfluorosulfonylfluoridevinylether (Hyflon Ion) find interesting application in the field of fuel cells, especially in view of the current tendency to move to high temperature operation. The advantages offered by these hydrophobic and hydrophylic perfluorinated materials for use in membrane technology are discussed. Comparison of membrane properties and performance is made with other membranes available on the market.
Polysulfone Hollow Fiber Gas Separation Membranes Filled with Submicron Particles
Authors: BHARDWAJ V. , MACINTOSH A. , SHARPE I. D. , GORDEYEV S. A. , SHILTON S. J.
Published: July 2009

Abstract: Three different fillers, carbon black (CB), vapor grown carbon fibers (VGCF), and TiO2, were incorporated into polysulfone spinning solutions with the intention of producing highly selective membranes with enhanced mechanical strength. The effect of filler presence on gas permeation characteristics, mechanical strength (bursting pressure), and morphology was investigated and compared to unfilled membranes. As well as studying filler types, the influence of CB filler concentration on membrane performance was also examined. For all filler types (at a concentration of 5%w/w), the pressure‐normalized flux of O2, N2, and CH4 was greater in the composite than in the unfilled membranes. The CO2 pressure‐normalized flux was only greater in the TiO2 composite membranes. For CB and VGCF, the CO2 pressure‐normalized flux was reduced compared with unfilled membranes. Three CB concentrations were investigated (2, 5, and 10%w/w). For O2, N2, and CH4, pressure‐normalized flux peaked at 5%w/w CB. CO2 exhibited the opposite trend, showing a minimum pressure‐normalized flux at 5%w/w. Considering O2/N2 and CO2/CH4 gas pairs and the various filled membrane categories, only the O2/N2 selectivity of the 2%w/w CB filled membranes was higher than that of the unfilled fibers—all other selectivities were lower. In terms of CB concentration, selectivity was a minimum at the intermediate concentration of 5%w/w. All the filled membrane types exhibited greater mechanical strength (bursting pressure) than unfilled fibers apart from the 5%w/w VGCF composites. The 2%w/w CB composites were the strongest. Electron microscopy showed no visible differences in general morphology between the various filled and unfilled membranes.
Carbon Molecular Sieve Membranes
Authors: HÄGG MAY‐BRITT , LIE JON A. , LINDBRÅTHEN ARNE
Published: July 2009

Abstract: Carbon molecular sieve (CMS) membranes (hollow fibers) have been studied for application as possible separation units for selected industrial gas streams. Gas streams at petrochemical plants (polypropene and polyethene) and upgrading of biogas to fuel specifications have been in focus. Gases present in biogas (N2, CO2, H2Ovap, and CH4) and gas streams at polyolefin plants (C2H4, C3H6, and C3H8) have been measured; both as pure gases and in mixtures. Aging of the CMS‐membranes as a function of humidity and pore blocking is discussed; likewise, possible regeneration methods when flux decrease is experienced. Transport mechanisms depending on pore size and molecular properties are also discussed. Excellent separation properties were documented for these applications, but also the need for frequent regeneration of the membrane in order to maintain permeability flux. The mixed gas experiments documented clearly the need for careful pore tailoring in order to optimize selectivity when the membranes were used for alkane‐alkene separation.
CO2 Capture by Means of an Enzyme‐Based Reactor
Authors: COWAN R. M. , GE J. ‐J. , QIN Y. ‐J. , McGREGOR M. L. , TRACHTENBERG M. C.
Published: July 2009

Abstract: We report a means for efficient and selective extraction of carbon dioxide (CO2) at low to medium concentration from mixed gas streams. CO2 capture was accomplished by use of a novel enzyme‐based, facilitated transport contained liquid membrane (EBCLM) reactor. The parametric studies we report explore both structural and operational parameters of this design. The structural parameters include carbonic anhydrase (CA) concentration, buffer concentration and pH, and liquid membrane thickness. The operational parameters are temperature, humidity of the inlet gas stream, and CO2 concentration in the feed stream. The data show that this system effectively captures CO2 over the range 400 ppm to at least 100,000 ppm, at or around ambient temperature and pressure. In a single pass across this homogeneous catalyst design, given a feed of 0.1% CO2, the selectivity of CO2 versus N2 is 1,090 : 1 and CO2 versus O2 is 790 :1. CO2 permeance is 4.71 × 10−8 molm−2 Pa−1 sec−1. The CLM design results in a system that is very stable even in the presence of dry feed and sweep gases.
Affinity Membranes as a Tool for Life Science Applications
Authors: BORCHERDING HEIKE , HICKE HANS‐GEORG , JORCKE DIERK , ULBRICHT MATHIAS
Published: July 2009

Abstract: As a matrix for affinity membrane technology we chose a flat‐sheet microfiltration membrane based on polypropylene. Using photopolymerization to graft epoxy groups onto the pore surface, we worked with glycidylmethacrylate as a monomer. We developed optimized, efficient, and mild UV irradiation conditions for the two‐step photografting process practically preserving the given pore structure of the base membrane. A grafting degree of up to 1.2 mg/cm2 per surface area of the membrane was obtained. The poly‐propylene membrane surface became significantly more hydrophilic. Introduction of epoxy groups allowed a stable covalent immobilization of the protein streptavidin serving as receptor for affinity ligand binding. A relatively high streptavidin immobilization capacity of about 65 μg/cm2 per surface area of the membrane was obtained. Apparently, only about two of the binding sites of the immobilized streptavidin were available for biotin recognition. We also found that the oriented immobilization of biotinylated alkaline phosphatase onto the surface via a streptavidin bridge increased the specific enzymatic activity about sixfold compared with random immobilization of this enzyme.
Membrane Evaporative Cooling to 30°C or Less
Authors: LOEB SIDNEY
Published: July 2009

Abstract: Microporous hydrophobic membranes were examined for use in steady state membrane evaporative air cooling. The examination consisted of calculating membrane performance as a function of overall heat and mass transfer coefficients already obtained and reported in Part 1 (previous paper, this volume). This performance was compared with that obtained by similar calculations made on existing evaporative air coolers. It was found that the cooling performance of the membrane evaporative air cooler was not as good as that of the existing evaporative air cooler. This is to be expected since the existing cooler has only one resistance, the air boundary layer (ABL), whereas the membrane cooler has the ABL and the membrane resistance. However, the membrane air cooler has advantages, such as appreciably lower water consumption and operation under more sanitary conditions, that is, without intimate conjunction of flowing air and liquid water on solid surfaces.
B Cell Immunity Regulated by the Protein Kinase C Family
Authors: SAIJO KAORU , MECKLENBRÄUKER INGRID , SCHMEDT CHRISTIAN , TARAKHOVSKY ALEXANDER
Published: July 2009

Abstract: Protein kinase C (PKC) is a family of serine/threonine kinases which mediate essential cellular signals required for activation, proliferation, differentiation, and survival. Several PKC members are expressed in B lineage cells and activated by stimulation of the B cell receptor (BCR), thus suggesting a contribution of PKCs to the B cell‐mediated immune response. To understand the individual roles of PKCs for B cell immunity, mice deficient for PKCβI/II (PKCβ) or PKCδ were analyzed. PKCβ and PKCδ play essential but distinctive roles in B cell immunity. In addition to its role in B cell activation and humoral immunity, PKCβ was recently shown to control NF‐κB activation and survival of mature B cells. PKCδ on the other hand specifically regulates the induction of tolerance in self‐reactive B cells. Thus, individual PCKs regulate B cell immunity specifically.
A Modified Digestion‐Circularization PCR (DC‐PCR) Approach to Detect Hypermutation‐Associated DNA Double‐Strand Breaks
Authors: DICKERSON SARAH K. , PAPAVASILIOU F. NINA
Published: July 2009

Abstract: Hypermutation of immunoglobulin variable region genes occurs in B cells during an immune response, and is vital for the development of high‐affinity antibodies. The molecular mechanism of the hypermutation reaction is unknown, but it seems to correlate with the generation of locus‐specific, double‐strand breaks. These DNA breaks have been measured by ligation‐mediated polymerase chain reaction (LM‐PCR), a technique that relies upon the ligation of a small linker to DNA breaks followed by the specific amplification of such breaks using combinations of locus‐ and linker‐specific primers. Here, we describe a modified version of the digestion‐circularization PCR (DC‐PCR) technique, which can be used to amplify and measure DNA breaks directly.
Using Single‐Gene Deletions to Identify Checkpoints in the Progression of Systemic Autoimmunity
Authors: POLLARD K. MICHAEL , HULTMAN PER , KONO DWIGHT H.
Published: July 2009

Abstract: Systemic lupus erythematosus is a multigenic disorder of unknown etiology. To investigate the roles that specific genes play in lupus, we have examined the disease profiles in mice with single‐gene deletions. In total, some 17 genes have been studied. Absence of certain genes, such as CD40L, CD28, or Igh6, abrogated induction of autoimmunity. Other genes, such as Igh5, IL‐4, or ICAM‐1, had little effect on the development of disease. Intermediate effects were observed in IL‐6‐deficient mice, while absence of β2‐microglobulin resulted in loss of hypergammaglobulinemia and IgG1 autoantibodies, but produced little change in anti‐chromatin antibodies or glomerular deposits. The most interesting observations were obtained with genes related to the expression or function of interferon‐γ (IFN‐γ). Reductions in IFN‐γ levels in murine lupus are associated with reductions in both autoantibody levels and immune‐complex‐ mediated pathology. Genes involved in up‐regulation of IFN‐γ expression, such as IL‐12, STAT‐4, or ICE, did not significantly influence autoimmunity, whereas absence of IFN‐γ or IFN‐γ receptor led to greatly reduced autoantibody response and immunopathology. Absence of IRF‐1, a gene ex‐pressed in response to IFN‐γ, resulted in selective retention of anti‐chromatin antibodies but little glomerular pathology. These studies suggest that the presence of a baseline level of IFN‐γ, rather than increased expression, is important for autoimmunity. Furthermore, as the IRF‐1 knockout demonstrates, specific defects in signaling pathways and gene expression subsequent to IFN‐γ/IFN‐γ receptor interaction may influence only certain disease parameters. It has not escaped our attention that IFN‐γ influences the expression and function of other immunologically relevant genes, such as IL‐4, IL‐6, and β2‐microglobulin. Thus, these genes may be part of the downstream events following IFN‐γ/IFN‐γ receptor interaction that promote the development of autoimmunity.
Activation of the Ets Transcription Factor Elf‐1 Requires Phosphorylation and Glycosylation
Authors: TSOKOS GEORGE C. , NAMBIAR MADHUSOODANA P. , JUANG YUANG‐TAUNG
Published: July 2009

Abstract: Elf‐1, a member of the Ets transcription factor family with an estimated molecular mass of 68 kDa, is involved in the transcriptional regulation of several hematopoietic cell genes. It is shown that following O‐GlcNAc glycosylation and phosphorylation by PKC ϑ, the cytoplasm‐located, 80‐kDa Elf‐1 translocates to the nucleus as a 98‐kDa protein. In the nucleus, Elf‐1 binds to the promoter of the TCRζ gene and promotes its transcription in Jurkat and fresh human T cells. It is also shown that in the majority of patients with systemic lupus erythematosus (SLE), who are known to express decreased levels of T cell receptor (TCR) ζ chain and mRNA, the 80‐kDa Elf‐1 protein does not undergo proper post‐transcriptional modification, which results in low levels of the 98‐kDa protein, lack of Elf‐binding to the TCR ζ promoter, and decreased gene transcription. Therefore, a novel activation pathway for a member of the Ets family of transcription factors, which is defective in patients with systemic autoimmunity, has been revealed.
Molecular Mechanism of Serial VH Gene Replacement
Authors: ZHANG ZHIXIN , WANG YUI‐HSI , ZEMLIN MICHAEL , FINDLEY HARRY W. , BRIDGES S. LOUIS , BURROWS PETER D. , COOPER MAX D.
Published: July 2009

Abstract: The molecular mechanism of serial VH replacement was analyzed using a human B cell line, EU12, that undergoes continuous spontaneous differentiation from pro‐B to pre‐B and then to B cell stage. In earlier studies, we found that this cell line undergoes intraclonal V(D)J diversification. Analysis of the IgH gene sequences in EU12 cells predicted the occurrence of serial VH replacement involving the cryptic recombination signal sequences (cRSS) embedded within framework 3 regions and concurrent extension of the CDR3 region. Detection of double‐stranded DNA breaks at the cRSS site and different VH replacement excision circles confirm the ongoing nature of this diversification process in the EU12 cells. In vitro binding and cleavage assays using recombinant RAG‐1 and RAG‐2 proteins further validated the cRSS participation in this RAG‐mediated recombination process. Serial VH replacements may represent an additional mechanism for diversification of the primary B cell repertoire.
Oligoclonal Expansions of Antigen‐Specific CD8+ T Cells in Aged Mice
Authors: POSNETT DAVID N. , YARILIN DMITRY , VALIANDO JENNIFER R. , LI FANG , LIEW FOO Y , WEKSLER MARC E. , SZABO PAUL
Published: July 2009

Abstract: Oligoclonal T cell expansions (TCE) are common in old humans and mice. It is not known whether an Ag‐specific response becomes more oligoclonal with age, and, if so, how this might alter biological responses or compromise the immune response, thus contributing to the immunodeficiency of aging. We used a tumor antigen response to study these questions. Early on, antigen reactive T cell numbers at the site of tumor injection were lower and clonally more restricted in old mice. Subsequently, long‐term oligoclonal TCE emerged in the blood and spleen of old mice. IL‐15 was not necessary for development of TCE in the blood. Overall, the data pointed to a dysregulated immune response in old mice, perhaps due to lack of optimal IL‐2 and CD4 help at the earliest stages and a lack of an efficient local peritoneal CTL response. This was associated with a deficient humoral response and, likely, persistence of tumor cells or tumor antigens. Perhaps the spleen is the site of persistence which explains clonal TCE observed primarily in PBL and spleen. The TCE appear to be inefficient as they are often anergic. As a result an occasional peritoneal or splenic tumor may arise in old mice.
Explaining Explanation in Chemistry
Authors: FISHER GRANT
Published: July 2009

Abstract: The notion that explanations are arguments, central to the covering law account, persists in developments of accounts of explanation in general philosophy of science. I argue that these developments fail to capture chemical explanation—motivating the explanatory autonomy of chemistry requires the investigation of alternative accounts. Ubiquitous use of models in chemistry is indicative of their importance to explanation. I argue that contemporary accounts of models that emphasize their partial autonomy from fundamental physical laws provide a basis for investigating explanation in chemistry. Furthermore, I sketch the importance of the semantic view of theories in articulating model autonomy, and thus why the semantic view might fulfill a significant role in explicating the explanatory autonomy of chemistry.
Autonomy, Explanation, and Theoretical Values
Authors: HENDRY ROBIN FINDLAY
Published: July 2009

Abstract: The emergence of quantum chemistry in the early twentieth century was an international as well as an interdisciplinary affair, involving dialogue between physicists and chemists in Germany, the United States, and Britain. Historians of science have recently documented both the causes and effects of this internationalism and interdisciplinarity. Chemists and physicists involved in the development of quantum chemistry in its first few decades tended to argue for opposing views on acceptable standards of explanation in their field, although the debate did not divide along disciplinary lines. The purpose of this paper is to investigate these different positions, through the methodological reflections of John Clarke Slater, Linus Pauling, and Charles Coulson. Slater tended to argue for quantum‐mechanical rigor and the application of fundamental principles as the values guiding models of molecular bonding. Although they were on different sides of the debate between the valence‐bond and molecular‐orbital approaches, Pauling and Coulson both emphasized the recovery of traditional chemical explanations and systematic explanatory power within chemistry.