bluuebunny/crossref_metadata_2025 huggingface dataset:
ORIGINAL ARTICLE: Effect of Leukocyte Therapy on Tumor Necrosis Factor‐Alpha and Interferon‐Gamma Production in Patients with Recurrent Spontaneous Abortion
Authors: Gharesi‐Fard Behrouz , Zolghadri Jaleh , Kamali‐Sarvestani Eskandar
Published: February 2008

Problem

Considering the deleterious role of T helper1 (Th1) cells in pregnancy outcome, a successful treatment for recurrent spontaneous abortion (RSA) should be able to make a significant shift away from Th1 responses. Although paternal leukocyte immunization has been used for treatment of RSA for years, because of methodological differences there is no consensus on the mechanism of action and effectiveness of this method.

Method of study

Twenty‐five Iranian non‐pregnant women with RSA and 16 non‐pregnant control women with at least two successful pregnancies were included in this study. All cases were followed up after leukocyte therapy for pregnancy outcome. Mononuclear cells from women were co‐cultured with the husband’s mononuclear cells before and after immunotherapy. The levels of tumor necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ) were checked on culture supernatant by enzyme‐linked immunosorbent assay method.

Results

The mean concentration of TNF‐α was significantly higher in patients compared with that in normal controls (P = 0.0001). After immunotherapy, the TNF‐α level was only significantly decreased in women with successful outcome (P = 0.0001). Immunotherapy also induced a significant reduction in the IFN‐γ level (P = 0.009).

Conclusion

The results of this investigation confirm the role of TNF‐α in RSA and propose the assessment of TNF‐α production as a valuable prognostic parameter for the prediction of abortion after leukocyte therapy.
REVIEW ARTICLE: Guilty As Charged: All Available Evidence Implicates Complement’s Role in Fetal Demise
Authors: Girardi Guillermina
Published: February 2008

Appropriate complement inhibition is an absolute requirement for normal pregancy. Uncontrolled complement activation in the maternal‐fetal interface leads to fetal death. Here we show that complement activation is a crucial and early mediator of pregnancy loss in two different mouse models of pregnancy loss.

Using a mouse model of fetal loss and growth restriction (IUGR) induced by antiphospholipid antibodies (aPL), we examined the role of complement activation in fetal loss and IUGR. We found that C5a‐C5aR interaction and neutrophils are key mediators of fetal injury. Treatment with heparin, the standard therapy for pregnant patients with aPL, prevents complement activation and protects mice from pregnancy complications induced by aPL, and anticoagulants that do not inhibit complement do not protect pregnancies.

In an antibody‐independent mouse model of spontaneous miscarriage and IUGR (CBA/J×DBA/2) we also identified C5a as an essential mediator. Complement activation caused dysregulation of the angiogenic factors required for normal placental development. In CBA/J×DBA/2 mice, we observed inflammatory infiltrates in placentas, functional deficiency of free vascular endothelial growth factor (VEGF), elevated levels of soluble VEGF receptor‐1 (sVEGFR‐1, also known as sFlt‐1; a potent anti‐angiogenic molecule), and defective placental development. Inhibition of complement activation blocked the increase in sVEGFR‐1 and rescued pregnancies.

Our studies in antibody‐dependent and antibody‐independent models of pregnancy complications identified complement activation as the key mediator of damage and will allow development of new interventions to prevent pregnancy loss and IUGR.
ORIGINAL ARTICLE: N‐glycosylation is Required for Binding of Murine Pregnancy‐Specific Glycoproteins 17 and 19 to the Receptor CD9
Authors: Ha Cam T. , Waterhouse Roseann , Warren James , Zimmermann Wolfgang , Dveksler Gabriela S.
Published: February 2008

Problem

Murine pregnancy‐specific glycoproteins (PSGs) are encoded by 17 different genes. Different family members have different expression levels at different stages of embryonic development. It is currently unknown whether all members of this family of placentally secreted proteins have the same function and bind to the same receptor. Furthermore, the requirement of post‐translational modifications for the activity of these highly glycosylated proteins remains undetermined.

Method of study

Recombinant PSG17 and PSG19 were generated and purified by affinity chromatography. An expression library was screened to identify the receptor for mouse PSG19. Binding to the receptor by proteins generated in different expression systems and mapping of the binding domain were analyzed by pull‐down assays. Analysis of the carbohydrate composition of the receptor‐binding domain was performed with the DIG glycan differentiation kit.

Results

PSG19 binds to the tetraspanin CD9, specifically to extra cellular loop 2 and can induce secretion of TGFβ1 by a macrophage cell line. The receptor‐binding domain of PSG17 and PSG19 is post‐translationally modified by the addition of N‐linked carbohydrates and, when expressed in CHO cells, terminal sialic acids are detected. PSGs produced in bacteria do not bind CD9.

Conclusion

PSG19, as previously determined for PSG17, binds to the second extracellular loop 2 of the tetraspanin CD9. The first immunoglobulin variable‐like domain of PSG19 is sufficient for receptor binding and function. Analysis of receptor usage by the remaining 15 murine PSGs will most likely require that the proteins be generated in eukaryotic expression systems, as we have demonstrated that the addition of carbohydrates is essential for PSG‐receptor interaction.
ORIGINAL ARTICLE: The Association of RCAS1 Serum Concentration with the Reversibility or Irreversibility of the Process of Immune Cytotoxic Activity Restriction During Normal Menstrual Cycle, Cancer Relapse, and Surgical Treatment for Various Types of Squamous Cell Carcinomas and Adenocarcinomas
Authors: Dutsch‐Wicherek Magda , Wicherek Lukasz
Published: February 2008

Problem

The selective suppression phenomenon of the cytotoxic immune response may be brought about by an increase in sRCAS1 serum concentration during the progression of cancer.

Method of study

We studied sRCAS1 serum concentration levels in patients with adenocarcinomas and squamous cell carcinomas. The healthy control consisted of patients who were in the mid‐proliferative or mid‐secretory phases of their cycles.

Results

Statistically, significantly higher sRCAS1 blood serum concentration levels were found in patients experiencing a recurrence of cancer in comparison to those patients who had undergone radical surgical treatment. For patients in the early stages of cancer, sRCAS1 blood serum concentration levels were statistically, significantly higher than those found in patients who were in the proliferative cycle phase and who were comparable to the levels found in patients in the secretory cycle phase.

Conclusion

The blood serum concentration level of RCAS1 seems to determine the level of immune system activity restriction that accompanies all three processes—decidualization, cancer development, and cancer relapse.
Polymorphism in ADH and MTHFR genes in oral squamous cell carcinoma of Indians
Authors: Solomon PR , Selvam GS , Shanmugam G
Published: February 2008

Objectives:  Alcohol consumption is known to increase the risk for several cellular disorders like oral cancer. The risk may be reinforced by polymorphism in genes like alcohol dehydrogenase. Therefore, this study is designed to asses the polymorphic status in ADH1B (formerly ADH2), ADH1C (formerly ADH3) and MTHFR genes in order to correlate the susceptibility to oral squamous cell carcinoma (OSCC).

Subjects and methods:  DNA from 126 OSCC samples were amplified using primers for ADH1B, ADH1C and MTHFR genes. The amplicons were analyzed for ADH1B*1, ADH1C*2 and MTHFR C677T allelic polymorphism by restriction digestion using appropriate enzymes.

Results:  ADH1B*1/*1 genotype in cancer patients who were heavy drinkers showed a negligible risk association with an odds ratio of 1.62; 95% CI = 1.08–2.14. In OSCC patients, ADH1C*2/*2 genotypes showed a relatively higher risk (odds ratio 2.65; 95% CI = 1.78–3.53) in heavy drinkers and a less significant risk (1.6; 95% CI = 1.15–2.03) in moderate drinkers and negligible risk in light drinkers (1.23; 95% CI = 0.77–1.63). In contrast, MTHFR 677TT genotype showed a high risk association for OSCC in heavy drinkers (odds ratio 3.0; 95% CI = 2.02–4.0). Interestingly, the combination of ADH1B*1/*1/ MTHFR 677TT genotypes in alcoholic cancer patients showed a high risk (odds ratio 4.16; 95% CI = 2.78–5.53). A similar risk (odds ratio 4.16; 95% CI = 1.18–5.53) was shown by ADH1B*1/*2/*2/*2MTHFR 677TT genotype combination. The ADH1C*2/*2 /MTHFR 677TT genotype combination showed the maximum risk (odds ratio 20; 95% CI = 13.45–26.64) in the heavy drinker group. This combination showed a high risk in moderate drinkers (odds ratio 5.88; 95% CI = 4.24–7.50) and relatively lower risk in light drinkers (odds ratio 2.77; 95% CI = 1.74–3.68).

Conclusions:  The ADH1C*2/*2/MTHFR 677TT genotype combination appears to be more susceptible for OSCC, since it showed a 20‐fold increase in risk in heavy drinkers and a 5.9‐ and 2.8‐fold increase in risk respectively in moderate drinkers and light drinkers. This study suggests the association of ADH1C*2/*2/MTHFR 677TT genotype combination as a risk factor for OSCC in alcoholics.
Behavioral characterization of mice lacking GIRK/Kir3 channel subunits
Authors: Pravetoni M. , Wickman K.
Published: February 2008

G protein‐gated inwardly rectifying K+ (GIRK/Kir3) channels mediate the postsynaptic inhibitory effects of many neurotransmitters and drugs of abuse. The lack of drugs selective for GIRK channels has hindered our ability to study their contributions to behavior. Here, we assessed the impact of GIRK subunit ablation on several behavioral endpoints. Mice were evaluated with respect to open‐field motor activity and habituation, anxiety‐related behavior, motor co‐ordination and ataxia and operant performance. GIRK3 knockout (−/−) mice behaved indistinguishably from wild‐type mice in this panel of tests. GIRK1−/− mice and GIRK2−/− mice, however, showed elevated motor activity and delayed habituation to an open field. GIRK2−/− mice, and to a lesser extent GIRK1−/− mice, also displayed reduced anxiety‐related behavior in the elevated plus maze. Both GIRK1−/− mice and GIRK2−/− mice displayed marked resistance to the ataxic effects of the GABAB receptor agonist baclofen in the rotarod test. All GIRK−/− mice were able to learn an operant task using food as the reinforcing agent. Within‐session progressive ratio scheduling, however, showed elevated lever press behavior in GIRK2−/− mice and, to a lesser extent, in GIRK1−/− mice. Phenotypic differences between mice lacking GIRK1, GIRK2 and GIRK3 correlate well with the known impact of GIRK subunit ablation on neurotransmitter‐gated GIRK currents, arguing that most neuronal GIRK channels contain GIRK1 and/or GIRK2. Altogether, our data suggest that GIRK channels make important contribution to a range of behaviors and may represent points of therapeutic intervention in disorders of anxiety, spasticity and reward.
Erythema elevatum diutinum with unusual clinical appearance
Authors: Soubeiran Evelyn , Wacker Jörg , Haußer Ingrid , Hartschuh Wolfgang
Published: February 2008

Erythema elevatum diutinum is a rare chronic inflammatory skin disease of unknown etiology with a histopathology of a leukocytoclastic vasculitis. Clinical findings involve symmetrical livid‐erythematous to red‐brown papules and plaques or nodules which are initially soft but become firmer. The skin lesions are located over extensor surfaces and often over joints. Early treatment with dapsone, corticosteroids and antibiotics is sometimes effective. A patient with multiple myeloma displayed unusual lesions of erythema elevatum diutinum.
Anaphylaxis after mouse bite
Authors: Leng Katharina , Wiedemeyer Katharina , Hartmann Martin
Published: February 2008

Allergic sensitivity to laboratory animals is an occupational risk for all workers in contact with small animals. In rare cases, life‐threatening reactions can occur. We describe a laboratory worker who after six years contact with mice developed an anaphylactic reaction after a mouse bite. Testing revealed positive reactions to all components of the mouse. The greatest risk for development of allergy is in the first three years and is usually an immediate hypersensitivity to inhalant allergens.
C‐mannosylation in the hypertrehalosaemic hormone from the stick insect Carausius morosus
Authors: Munte Claudia E. , Gäde Gerd , Domogalla Barbara , Kremer Werner , Kellner Roland , Kalbitzer Hans R.
Published: February 2008

The hypertrehalosaemic hormone from the stick insect Carausius morosus (Cam‐HrTH) contains a hexose covalently bound to the ring of the tryptophan, which is in the eighth position in the molecule. We show by solution NMR spectroscopy that the tryptophan is modified at its Cδ1(C2) by an α‐mannopyranose. It is the first insect hormone to exhibit C‐glycosylation whose exact nature has been determined experimentally. Chemical shift analysis reveals that the unmodified as well as the mannosylated Cam‐HrTH are not completely random‐coil in aqueous solution. Most prominently, C‐mannosylation strongly influences the average orientation of the tryptophan ring in solution and stabilizes it in a position clearly different from that found in the unmodified peptide. NMR diffusion measurements indicate that mannosylation reduces the effective hydrodynamic radius. It induces a change of the average peptide conformation that also diminishes the propensity for aggregation of the peptide.
Characterization and expression analysis of an interleukin‐7 homologue in the Japanese pufferfish, Takifugu rubripes
Authors: Kono Tomoya , Bird Steve , Sonoda Kohei , Savan Ram , Secombes Christopher J. , Sakai Masahiro
Published: February 2008

An interleukin‐7 (IL‐7) gene has been cloned and sequenced within the Japanese pufferfish, Takifugu rubripes (Fugu), providing the first conclusive evidence for the existence of IL‐7 in teleosts. The IL‐7 cDNA was composed of 1438 bp, with a 117 bp 5′‐UTR, an 826 bp 3′‐UTR containing two mRNA instability motifs, and a 498 bp ORF which translates into a peptide of 166 amino acid residues. The Fugu IL‐7 peptide contained a predicted signal peptide of 19 amino acid residues and the IL‐7/9 family signature (Arg140–Val149). Homology analysis of Fugu IL‐7 with other known IL‐2 family members showed some similarity to the known mammalian IL‐7 and Fugu IL‐21 molecules, and phylogenetic tree analysis showed that the Fugu IL‐7 clustered with the chicken and mammalian IL‐7 and mammalian IL‐9, away from other IL‐2 family members (IL‐2, IL‐4, IL‐15 and IL‐21). The organization of the Fugu IL‐7 gene was the same as in mouse, and consisted of five exons and four introns, but differed from the human gene, which is composed of six exons and five introns. Comparison of the Fugu and human genomes showed that some synteny existed around the IL‐7 gene, with the presence of both the protein kinase inhibitor‐α and chromosome 8 ORF 70 (C8orf70) genes, with IL‐7 and C8orf70 having the same transcriptional orientation. The Fugu IL‐7 gene was expressed within unstimulated tissues, such as the head kidney, spleen, liver, intestine, gill and muscle. Stimulation of head kidney cells with lipopolysaccharide, polyinosinic polycytidylic acid or phytohaemagglutinin increased this expression. This discovery of IL‐7 in Fugu will allow a more complete analysis of fish immune responses in the future.
The Vps4 C‐terminal helix is a critical determinant for assembly and ATPase activity and has elements conserved in other members of the meiotic clade of AAA ATPases
Authors: Vajjhala Parimala R. , Nguyen Chau H. , Landsberg Michael J. , Kistler Carol , Gan Ai‐Lin , King Glenn F. , Hankamer Ben , Munn Alan L.
Published: February 2008

Sorting of membrane proteins into intralumenal endosomal vesicles, multivesicular body (MVB) sorting, is critical for receptor down regulation, antigen presentation and enveloped virus budding. Vps4 is an AAA ATPase that functions in MVB sorting. Although AAA ATPases are oligomeric, mechanisms that govern Vps4 oligomerization and activity remain elusive. Vps4 has an N‐terminal microtubule interacting and trafficking domain required for endosome recruitment, an AAA domain containing the ATPase catalytic site and a β domain, and a C‐terminal α helix positioned close to the catalytic site in the 3D structure. Previous attempts to identify the role of the C‐terminal helix have been unsuccessful. Here, we show that the C‐terminal helix is important for Vps4 assembly and ATPase activity in vitro and function in vivo, but not endosome recruitment or interactions with Vta1 or ESCRT‐III. Unlike the β domain, which is also important for Vps4 assembly, the C‐terminal helix is not required in vivo for Vps4 homotypic interaction or dominant‐negative effects of Vps4–E233Q, carrying a mutation in the ATP hydrolysis site. Vta1 promotes assembly of hybrid complexes comprising Vps4–E233Q and Vps4 lacking an intact C‐terminal helix in vitro. Formation of catalytically active hybrid complexes demonstrates an intersubunit catalytic mechanism for Vps4. One end of the C‐terminal helix lies in close proximity to the second region of homology (SRH), which is important for assembly and intersubunit catalysis in AAA ATPases. We propose that Vps4 SRH function requires an intact C‐terminal helix. Co‐evolution of a distinct Vps4 SRH and C‐terminal helix in meiotic clade AAA ATPases supports this possibility.
Cadmium phytoextraction capacity in eight C3 herbage grass species
Authors: Sabreen Shamima , Sugiyama Shu‐ichi
Published: February 2008

Grasses are excellent candidates for phytoremediation because of their high biomass production, high adaptability and low management cost. This study assesses interspecific variation of cadmium (Cd) phytoextraction capabilities in eight C3 grass species. Populations of 30‐day‐old C3 grass species – namely, Agrostis alba, Anthoxanthum odoratum, Dactylis glomerata, Festuca arundinacea, Festuca pratensis, Lolium multiflorum, Lolium perenne and Poa pratensis– were grown hydroponically for 15 days with different concentrations of Cd (0, 5, 10 and 50 µM). For each species, shoot biomass, the proportion of growth inhibition (GI, %), shoot Cd concentration and accumulation, shoot nutrient uptake, and the proportion of uptake inhibition (UI, %) of nutrient minerals were evaluated. Effects of Cd application included stunted growth. The GI increased from 5% to 70% with an increase in Cd concentrations. For all Cd treatments, L. multiflorum showed the highest shoot dry biomass. Shoot Cd concentrations negatively affected mineral nutrient uptake. The highest Cd treatment caused UI of various elements of 37–95%. Under 50‐µM Cd treatment, Cd accumulation varied by 20 times among species, and L. multiflorum showed the highest Cd accumulation (116.46 µg plant−1). Our results indicate that L. multiflorum exhibited high degrees of both Cd tolerance and Cd phytoextraction capacity among grass species.
Forage selection by beef cows grazed on a dwarf bamboo (Pleioblastus argenteostriatus f. glaber)‐dominant pasture
Authors: Yayota Masato , Nakano Miwa , Karashima Jun , Ohtani Shigeru
Published: February 2008

This study investigated the influence of forage selection on the quality of the diet ingested by beef cows grazed on a dwarf bamboo‐dominated pasture. For 13 days each in spring, summer and autumn, eight Japanese Black cows were grazed on a 1.8‐ha dwarf bamboo (Pleioblastus argenteostriatus f. glaber)‐dominant pasture during the day. The plant species and number of bites of each species ingested by the cows were recorded, and plant samples were hand plucked to imitate the behavior of the cows during the grazing time on the seventh and 13th days of each period. The botanical and chemical compositions of the available pasture were systematically estimated by sampling 28 plots. The cows slightly avoided dwarf bamboo and preferred grasses on the seventh day of each period. On the 13th day, the cows ate any available forage in the pasture. The selected forages were higher in crude protein and in vitro digestibility and had lower insoluble protein, neutral detergent fiber and lignin contents than the forages available in the pasture during a season. The frequency of the botanical groups selected by the cows was different in autumn from that in spring and summer, and a substantial increase in grasses and a decrease in P. argenteostriatus f. glaber among the selected forages were observed. Although the botanical groups selected by the cows were relatively different between the seasons, an increase in the levels of unavailable fractions such as lignin and insoluble protein and a decrease in in vitro digestibility were observed as the seasons progressed. Thus, the cows could not avoid a decrease in their diet quality in autumn. The selection of forage improved the nutrient intake of the beef cows in terms of chemical and digestible components; however, in a dwarf bamboo‐dominated pasture, there is a substantial limitation in the effectiveness of forage selection.
Effects of chemical composition on the rate and temporal pattern of decomposition in grassland species leaf litter
Authors: Hossain M. Zabed , Sugiyama Shu‐ichi
Published: February 2008

We examined the effects of the chemical composition of leaf litter on the rate and temporal pattern of decomposition for 15 grassland plant species. Respiration rates (CO2 flux) of soil treated with leaf sections of each species were measured periodically at 15 days, 30 days, 45 days and 60 days after incubation under laboratory conditions to monitor temporal changes in decomposition. Results showed that soil respiration rates of the plant species differed significantly at all four measurement times. The soil respiration rate at the earliest measurement (15 days) was positively correlated with the leaf N content, but the rates at the later measurements (30–60 days) were significantly correlated with the phenol : N ratios of litter types, indicating that contribution of litter chemicals changes with progression of decomposition processes. The one‐phase exponential decay curve well represented the temporal changes in the soil respiration rate. The relative rate of decline in soil respiration with time differed significantly among the plant species, and it was correlated significantly and positively with litter N content and negatively with the litter tannin content, indicating importance of litter chemical composition on temporal pattern of decomposition. These results indicate the importance of soil CO2 flux measurements at temporal scale.
Effect of aerobic training on 99mTc‐methoxy isobutyl isonitrile (99mTc‐sestamibi) uptake by myocardium and skeletal muscle: implication for noninvasive assessment of muscle metabolic profile
Authors: Kyparos D. , Arsos G. , Kyparos A. , Georga S. , Petridou A. , Sotiriadou S. , Mougios V. , Matziari C.
Published: February 2008

Aim:  The effect of long‐term endurance training on skeletal muscle and myocardial uptake of 99mTc‐sestamibi, a radiopharmaceutical accumulating in the mitochondria, was investigated.

Methods:  Twenty‐six Wistar rats were divided into a trained (5 days week−1 endurance running for 14 weeks) and an untrained group. On completion of training, 99mTc‐sestamibi was administered and, 2 h post‐injection, the myocardium and the soleus, extensor digitorum longus (EDL) and medial gastrocnemius (MG) muscles were removed for the measurement of cytochrome c oxidase (CCO) activity and 99mTc‐sestamibi uptake. Tissue 99mTc‐sestamibi kinetics was preliminarily studied in 16 other rats for up to 2 h post‐injection.

Results:  Two hours post‐injection 99mTc‐sestamibi uptake was either stable (myocardium) or still rising (skeletal muscles). Both CCO activity and 99mTc‐sestamibi uptake decreased in the same order (myocardium, soleus, EDL, MG) in the tissues examined. The CCO activity of the EDL and MG muscles was higher (P < 0.05) in the trained compared to the untrained group. 99mTc‐sestamibi uptake in the soleus and EDL muscles was higher (P < 0.05) in the trained compared to the untrained rats, whereas the difference in MG was marginally significant (P = 0.06) in favour of the trained group.

Conclusions:  Long‐term endurance training, resulting in elevated skeletal muscle CCO activity, is also associated with a similar increase in 99mTc‐sestamibi uptake. This finding suggests that 99mTc‐sestamibi could be used in imaging assessment of skeletal muscle metabolism with possible applications in both clinical and sports medicine settings.
Angiotensin II‐induced contractions in human jejunal wall musculaturein vitro
Authors: Spak E. , Casselbrant A. , Olbers T. , Lönroth H. , Fändriks L.
Published: February 2008

Aim: Angiotensin II is well known for its contractile effects on smooth muscle cells. This effect is also present in the gut previously shown in animal models. The aim of this study was to clarify expression and localization of angiotensin II receptors in the human small intestine and to explore the pharmacological profile of angiotensin II effectsin vitro.

Methods: Strips of jejunal muscle wall from 32 patients undergoing bariatric surgery were used to record isometric tensionin vitroin response to angiotensin II (10−10–10−5 m) alone and in the presence of PD123319 (10−7 m), losartan (10−7 m), PD123319 (10−7 m) and losartan (10−7 m) in combination, tetrodotoxin (TTX) (10−6 m), atropine (10−6 m) and guanethidine (3 × 10−6 m). Western blot, immunohistochemistry and RT‐PCR were performed on corresponding muscle samples to identify expression and localization of key components of the renin–angiotensin system.

Results: Angiotensin II elicited concentration‐dependent contraction in both longitudinal and circular jejunal muscle wall strips; neither TTX, atropine nor guanethidine affected this action. Losartan alone and in combination with PD123319 shifted the concentration–response curve to the right. Transcription of angiotensinogen, ACE and angiotensin II types 1 and 2 receptor RNA was detected in all patients. Immunohistochemistry detected angiotensin II type 1 receptors in the musculature; both angiotensin II types 1 and type 2 receptors were found in the myenteric plexus.

Conclusion: This pharmacological analysis indicates that the contractile action elicited by angiotensin II on jejunal wall musculature is primarily mediated through the angiotensin II type 1 receptor located on the musculature.
Regulatory innovation in the governance of human subjects research: A cautionary tale and some modest proposals
Authors: Burris Scott
Published: February 2008

Under US regulations known as the “Common Rule,” federally‐supported human‐subject research must be reviewed by an Institutional Review Board (IRB). The Common Rule system from a distance looks like an innovative instantiation of prescriptions for constitutive regulation and soft law, but in practice has grown into a self‐referential, unresponsive, and legalistic bureaucracy. This article reviews criticism of the Common Rule. It also discusses why the system fails to regulate in an efficient and effective way, pointing in particular to the poor fit between the IRB and its assigned tasks. Turning to reforms, the article uses the heuristic of “regulatory space” to describe the range of actual and potential regulators with the capacity to set standards, monitor compliance, and discipline violators. Regulatory reform is framed by three conceptual changes: recognizing the limitations of the IRB as an oversight body; narrowing the range of risks the system is tasked to control; and disentangling the conflicting regulatory logics of behavioral standard‐setting and virtue promotion. The article concludes with a roster of possible changes that would make the IRB a more responsive regulator, enroll a wider range of actors in the promotion of virtue, focus resources on more serious risks, and address the structural causes of researcher misconduct.
Thinking about how to avoid thought: Deep norms, shallow rules, and the structure of attention
Authors: Heimer Carol A.
Published: February 2008

If the core problem for decision making is the limited capacity of people and organizations to collect and process information, it is their limited capacity to pay attention that poses the challenge for regulation. Much regulatory activity is thus focused on devising methods for ensuring that organizations and their staff pay attention to the “right” things. Yet outsiders’ claims on attention often are trivialized by insiders because outsiders make those claims without understanding what will be displaced. Drawing on a study of how rules are used in five HIV clinics, this article analyzes forms, training and meetings, and delegation to new occupations as devices for conserving attention. In asking how much thought is required, what should be thought about, and who should do the thinking, people argue about the moral priority of treatment, research, and administration. Allocation of attention is not just about using a scarce resource efficiently, but is also about the right to decide for oneself what is important.
The European Union’s governance of health care and the welfare modernization agenda
Authors: Hervey Tamara K
Published: February 2008

In the face of “permanent welfare austerity,” the European Union (EU) is increasingly involved in the governance of health care through various “new governance” tools. This development coincides with a growing interest in modernization of welfare, including health care. One of the fundamental critiques of new governance in the EU context concerns the (perceived) inability of new governance to protect the “social” against the “market” in Europe’s constitutional settlement. Using multi‐level governance and constructivist approaches, this article considers whether the EU’s governance of health care via the “Open Method of Coordination” advances a neo‐liberal agenda of health care modernization.
Challenges of democratic experimentalism: A case study of the National Quality Forum in health care
Authors: Hoflund A. Bryce , Farquhar Marybeth
Published: February 2008

Networks are an increasingly common aspect of administrative life in almost any public policy arena. In health care, networks have emerged in order to address “wicked” quality problems. One such network organization, the National Quality Forum (NQF), was created as a response to the fragmentation and information deficit that have plagued the health care industry’s efforts to improve health care quality. Its purpose is to bring diverse health care stakeholders from the public and private sectors together to discuss and debate quality and performance measurement issues. Democratic experimentalism offers one way of assessing the NQF’s efforts. The purpose of this article is to examine the NQF’s efforts through the lens of democratic experimentalism and to explore some of the virtues and shortcomings of applying a democratic experimentalist approach to health care regulation.
Hybrid design, systemic rigidity: Institutional dynamics in human research oversight
Authors: Halpern Sydney
Published: February 2008

New governance scholars see hybrid regulation as a means for achieving regulatory flexibility and responsiveness. The US system for overseeing human subjects research embodies three dimensions of hybridity: it brings together governmental and non‐governmental controls; it combines central and local authority; and it engages a multiplicity of policy actors. Yet this system became rigid 20 years into its development. Sources of rigidity included shifts in the regulatory environment, temporal constriction in the range policy participants, and risk aversion on the part of non‐governmental institutions charged with implementing federally mandated controls. This article explores the implications of these institutional dynamics for the relationship between hybridity and regulatory responsiveness. It also examines possibilities for renewed flexibility generated by the recent advent of both accreditation and regulatory innovation by university research administrators.
Yttrium-Doped Barium Zirconates as Ceramic Conductors in the Intermediate Temperature Range
Authors: Higgins S. , Sammes N. M. , Smirnova A. , Kilner J. A. , Tompsett G.
Published: February 2008

A modified Pechini process has been used to synthesize perovskite-structured yttrium-doped barium zirconate of the form BaZr0.85Y0.15O3-δ (BZY15). The X-ray diffraction pattern for the sintered material (5h at 1500°C) confirms a cubic structure with unit cell parameter of 8.424Å. Scanning electron microscopy images reveal a dense electrolyte structure. Thermal analysis (TGA/DTA) was also conducted on the material to determine possible endothermic and exothermic peaks and phase transformations. Raman spectroscopy data indicated that the most intense band in the spectrum of BZY15 occurs at 616cm−1, which suggests that cubic zirconia (Zr-O) vibrations are present. No bands were observed for secondary oxides, such as BaO, which would have a characteristic sharp band at 949cm−1, or Y2O3, whose characteristic band occurs at 376cm−1. AC-impedance measurements at 600°C indicate that the conductivity of the sample is higher in humidified gases compared to dry ones and has the lowest value in humidified air.
Ag–Cu–Ti Braze Materials for Sealing SOFCs
Authors: Kobsiriphat Worawarit , Barnett Scott
Published: February 2008

Two Ag–Cu–Ti brazing alloy compositions were studied as gas seals for solid oxide fuel cells (SOFCs). Yttria-stabilized zirconia pellets were bonded using Ag–35.25Cu–1.75Ti (Cusil-ABA) or Ag–20.1Cu–1.0Ti (average composition; Ag-Cusil). Both as-brazed filler metals contained metallic Ag and Cu phases, along with continuous titanium oxide layers at the filler metal-zirconia interfaces. The brazed joints were then aged at 700°C for up to 100h in air or while separating H2 and air atmospheres. After annealing in air for 100h at 700°C, degradation in microstructure and hermeticity was more pronounced in Cusil-ABA. However, in H2-air atmosphere, Cusil-ABA performed better than Ag-Cusil. Ag-Cusil aged in H2 air delaminated from zirconia and its microstructure showed large interconnected pores in Ag-rich regions. The results were confirmed by single-cell tests using each filler metal as a gas seal. Observations of the post-test Cusil-ABA microstructure revealed little degradation. These results indicate that Cusil-ABA is better suited than Ag-Cusil as a SOFC gas seal.
Experimental Results of a PEM System Operated on Hydrogen and Reformate
Authors: Minutillo M. , Jannelli E. , Tunzio F.
Published: February 2008

The main objective of this study is to evaluate the performance of a proton exchange membrane (PEM) fuel cell generator operating for residential applications. The fuel cell performance has been evaluated using the test bed of the University of Cassino. The experimental activity has been focused to evaluate the performance in different operating conditions: stack temperature, feeding mode, and fuel composition. In order to use PEM fuel cell technology on a large scale, for an electric power distributed generation, it could be necessary to feed fuel cells with conventional fuel, such as natural gas, to generate hydrogen in situ because currently the infrastructure for the distribution of hydrogen is almost nonexistent. Therefore, the fuel cell performance has been evaluated both using pure hydrogen and reformate gas produced by a natural gas reforming system.
Modeling and Study of the Influence of Sealing on a Solid Oxide Fuel Cell
Authors: Wuillemin Zacharie , Autissier N. , Nakajo A. , Luong M. , Van herle J. , Favrat D.
Published: February 2008

The properties of sealing materials are important for the performance and reliability of solid oxide fuel cells (SOFCs). Even if the properties of a sealing material can be studied separately, it remains difficult to quantify the effect of an imperfect seal on the repeat-element behavior. In this study, simulation is used to investigate the effects of an imperfect seal behavior on the performance and reliability of SOFCs. Diffusion through the sealing material and inherent local combustion of fuel are added to the computational fluid dynamics (CFD) repeat-element model, which also allows us to compute the flow field, the electrochemical reactions, and the energy equations. The results are in good agreement with experiments. The zones of parasitic combustion and local overheating are well reproduced. Furthermore, the model predicts a risk of reoxidation under polarization that is well observed. The model also shows the necessity to take into account the diffusion transport for the development of compressive seal materials, hence verifying the hypotheses made by other groups. The modeling approach presented here, which includes the imperfections of components, allows us to reproduce experiments with good accuracy and gives a better understanding of degradation processes. With its reasonable computational cost, it is a powerful tool for a design of SOFC based on reliability.
Measuring Open Circuit Voltage in a Glucose Alkaline Fuel Cell Operated as a Continuous Stirred Tank Reactor
Authors: Mor Lea , Rubin Zeev , Schechner Pinchas
Published: February 2008

Open circuit voltage is an important parameter of fuel cells. Prior works have demonstrated that open cell voltages of alkaline fuel cells fueled with glucose reach saturation at high glucose concentrations (0.1M–1M). At low concentrations, this voltage should increase logarithmically, according to the Nernst law. To study this reaction in the said fuel cells, open circuit voltages were measured over a wide concentration range. The fuel cell was operated as a continuous tank reactor undergoing a transient. During this transient, the concentration (either of glucose or KOH) of the solution in the fuel cell was decreased by several orders of magnitude. Measurements of voltage and concentration taken at different times tested their interdependence. Though no stirring was applied, the fuel cell behaves like a continuous stirred tank reactor. This was established by measuring concentration (either of glucose or KOH) versus time. The effect of concentration on the open circuit voltage was examined from 1.4M down to 0.001M for glucose and from 1M to 10−6M for KOH. The open cell voltage depends logarithmically on the glucose concentration at low glucose concentrations, up to 0.1M. From the Nernst law, it may be deduced that one electron is transferred by one glucose molecule to the anode. The open cell voltage is constant, 0.83V, at KOH concentrations from 1M down to 0.017M, dropping down to 0.52V at 10−6M KOH. Operating a fuel cell as a continuous stirred tank reactor is an efficient way of measuring fuel cell performance over a wide range of fuel and electrolyte concentrations. Analyzing the effect of concentration on cell voltage provides insight into the reaction mechanism.
Influence of the Temperature on Oxygen Reduction on SOFC Composite Electrodes: Theoretical and Experimental Analysis
Authors: Nicolella C. , Reverberi A. P. , Carpanese P. , Viviani M. , Barbucci A.
Published: February 2008

Experimental data on half-cells consisting of YSZ electrolyte pellets and slurry-coated cathodes, and a simplified theoretical model were used to give an insight into the kinetics of oxygen reduction in solid electrolyte composite cathodes. Electrochemical impedance spectroscopy and potentiodynamic polarizations were used to evaluate the main electrochemical parameters of the cathodic process in a temperature range between 500°C and 900°C. The experimental results show that the oxygen reaction is not under activation control at low temperatures, and other phenomena, such as the transfer of oxygen ions to and through the solid electrolyte in the composite cathode, occur and retard the overall rate of oxygen reduction. This working hypothesis was assessed using a simplified theoretical model of the cathode that accounts for charge transfer, mass transfer, and conduction. The model simulations compared satisfactorily with the experimental data, and they show that, at low temperatures, the reaction zone in the cathode is confined to the electrolyte interface. When the temperature is increased, the retarding effects of mass transfer and conduction in the electrolyte become negligible, and the reaction zone progressively extends through the electrode.
Development of a Cylindrical Shape Self-Breathing Mini Fuel Cell Stack
Authors: Xia Zetao , Chan Siew Hwa
Published: February 2008

This paper presents the work on the development of a self-breathing mini fuel cell stack. The diameter of the five-cell stack is same as that of a D-size battery, but the length is half of it. The maximum power could reach 1.02W when operating at 2.4V. The stabilized operating temperature was 305K at 3V after 1h of operation. The cylindrical structure design makes the cathode more accessible to the ambient air and easier for the heat to be dissipated away. To assemble the fuel cell, only a single bolt was mounted through the centerline of the fuel cell, which reduced the overall weight of the stack. A mathematical 3D model based on the finite element method was developed for the cylindrical structure. The validation of the model was carried out by comparing the measured bulk performance with the predicted performance of the mini fuel cell. The current distribution was calculated and the improved design was suggested.
A Detailed Three-Dimensional Simulation of an IP-SOFC Stack
Authors: Haberman B. A. , Young J. B.
Published: February 2008

A typical integrated-planar solid oxide fuel cell (IP-SOFC) consists of modules with series connected electrochemical cells printed on their outer surfaces. Oxygen is supplied to the cathodes from air flowing over the outside of the module and hydrogen diffuses from the internal fuel channels to the anodes through the porous module support structure. The IP-SOFC is intended for use in medium scale stationary power applications, and such a system will use a fuel cell stack containing many thousands of modules housed inside a pressure vessel. For certain purposes, the geometry of this stack can be adequately described using a computational domain that considers just two modules. A computer code has been developed to simulate the many physical and chemical processes occurring within the stack, including fluid flow, heat transfer, water gas shift, and electrochemical reactions. The simulation results show how the performance of the IP-SOFC stack is strongly affected by these physical processes, the geometry of the stack, and the operating conditions. The temperature distribution, which is difficult to predict using a less realistic geometric model, is almost uniform within each fuel channel and rises steadily in the air flow direction. The shift reaction, which is catalyzed by the anodes, is of great importance, and as the fuel flow becomes depleted of hydrogen it enables the electrochemical cells to make increasing use of carbon monoxide. Overall it was found that the operating voltage produced by the fuel cells is typically 0.74V and the component efficiency, the ratio of the actual power output to the maximum available from the fuels consumed, is around 59%.
A Nonisothermal PEM Fuel Cell Model Including Two Water Transport Mechanisms in the Membrane
Authors: Steinkamp K. , Schumacher J. O. , Goldsmith F. , Ohlberger M. , Ziegler C.
Published: February 2008

A dynamic two-phase flow model for proton exchange membrane fuel cells is presented. The two-dimensional model includes the two-phase flow of water (gaseous and liquid) in the gas diffusion layers (GDLs) and in the catalyst layers (CLs), as well as the transport of the species in the gas phase. The membrane model describes water transport in a perfluorinated-sulfonic-acid-ionomer-based membrane. Two transport modes of water in the membrane are considered, and appropriate coupling conditions to the porous CLs are formulated. Water transport through the membrane in the vapor equilibrated transport mode is described by a Grotthus mechanism, which is included as a macroscopic diffusion process. The driving force for water transport in the liquid equilibrated mode is due to a gradient in the hydraulic water pressure. Moreover, electro-osmotic drag of water is accounted for. The discretization of the resulting flow equations is done by a mixed finite element approach. Based on this method, the transport equations for the species in each phase are discretized by a finite volume scheme. The coupled mixed finite element/finite volume approach gives the spatially resolved water and gas saturation and the species concentrations. In order to describe the charge transport in the fuel cell, the Poisson equations for the electrons and protons are solved by using Galerkin finite element schemes. The electrochemical reactions in the catalyst layer are modeled with a simple Tafel approach via source/sink terms in the Poisson equations and in the mass balance equations. Heat transport is modeled in the GDLs, the CLs, and the membrane. Heat transport through the solid, liquid, and gas phases is included in the GDLs and the CLs. Heat transport in the membrane is described in the solid and liquid phases. Both heat conduction and heat convection are included in the model.
Coupling of Lattice Boltzmann and Finite Element Methods for Fluid-Structure Interaction Application
Authors: Kwon Y. W.
Published: February 2008

In order to analyze the fluid-structure interaction between a flow and a flexible structure, an algorithm was presented to couple the lattice Boltzmann method (LBM) and the finite element method (FEM). The LBM was applied to the fluid dynamics while the FEM was applied to the structural dynamics. The two solution techniques were solved in a staggered manner, i.e., one solver after another. Continuity of the velocity and traction was applied at the interface boundaries between the fluid and structural domains. Furthermore, so as to make the fluid-structure interface boundary more flexible in terms of the computational modeling perspective, a technique was also introduced for the LBM so that the interface boundary might not coincide with the fluid lattice mesh. Some example problems were presented to demonstrate the developed techniques.
Influence of the Interaction on Stress Intensity Factor of Semielliptical Surface Cracks
Authors: Kamaya Masayuki
Published: February 2008

The interaction between multiple surface cracks is an important consideration in the cracking behavior due to thermal fatigue and stress corrosion cracking. However, it is difficult to evaluate the intensity of the interaction quantitatively because there are many factors, such as the relative position, size, and geometry of the cracks. Furthermore, the influence of the interaction differs with the crack tip position along the front. In this study, to investigate the intensity of interaction, the stress intensity factor (SIF) of interacting semielliptical surface cracks was evaluated by the finite element method and finite element alternating method. These methods enable us to evaluate the SIF of interacting cracks for various conditions. The analysis results reveal that the change in the averaged SIF along the crack front caused by coalescence of two cracks can be estimated from the change in the area size. The maximum interaction can be estimated by a simple addition of the area size of two cracks regardless of the loading condition and relative crack size. To exclude the conservativeness caused by the current combination rule, new criteria are shown.