bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphodiesterase inhibition with tadalafil provides longer and sustained protection of stem cells
Authors: Haider Husnain Kh , Lee Yun-Jung , Jiang Shujia , Ahmed Rafeeq P. H. , Ryon Mok , Ashraf Muhammad
Published: September 2010

We hypothesized that inhibition of the cGMP-specific enzyme phosphodiesterase 5A (PDE5A) promoted cGMP/protein kinase G (PKG) activity to condition stem cells for enhanced survival and proliferation. One-time tadalafil treatment (1 μM for 30 min) of mesenchymal stem cells (TadaMSCs) provided sustained protection of cells for 36 h. Higher cGMP activity with concomitantly increased PKG1 activity was observed inTadaMSCs, which peaked within 12 h after tadalafil treatment. Pretreatment with PKG1 blockers (1 μM KT-5823 or 20 nM K-252a) or transduction with adenoviral PKG1-short-hairpin RNA abolished tadalafil-induced cytoprotection of the cells. A higher proliferation rate was observed inTadaMSCs compared with nontreated MSCs (ContMSCs). In a rat model of acute myocardial infarction,TadaMSCs transplanted 0 and 24 h after tadalafil treatment showed higher survival compared withContMSCs on day 2 and day 4 after engraftment.TadaMSCs transplanted 48 h after tadalafil treatment lost their protection on both day 2 and day 4 after engraftment, and their rate of survival was similar toContMSCs. Reduced terminal dUTP nick end-labeling positivity ( P < 0.01 vs.ContMSCs) and higher proliferation ofTadaMSCs ( P < 0.01 vs.ContMSCs) was observed in the infarcted heart. Fluorescence immunostaining revealed neomyogenesis in both the infarct and peri-infarct areas. Blood vessel density was significantly increased in group 2 compared with group 1. Transthoracic echocardiographic heart function revealed significant preservation of the indexes of left ventricle contractility and attenuation of remodeling inTadaMSC-engrafted animal hearts ( group 2) compared withContMSCs ( group 1). PDE5A inhibition using long-acting tadalafil is an innovative approach to promote stem cell survival and proliferation in the infarcted heart.
Local angiotensin II aggravates cardiac remodeling in hypertension
Authors: Xu Jiang , Carretero Oscar A. , Liao Tang-Dong , Peng Hongmei , Shesely Edward G. , Xu Junxiao , Liu Thomas S. , Yang James J. , Reudelhuber Timothy L. , Yang Xiao-Ping
Published: September 2010

Angiotensin II (ANG II) contributes to hypertension, cardiac hypertrophy, fibrosis, and dysfunction; however, it is difficult to separate the cardiac effect of ANG II from its hemodynamic action in vivo. To overcome the limitations, we used transgenic mice with cardiac-specific expression of a transgene fusion protein that releases ANG II from cardiomyocytes (Tg-ANG II) and treated them with deoxycorticosterone acetate (DOCA)-salt to suppress their systemic renin-angiotensin system. Using this unique model, we tested the hypothesis that cardiac ANG II, acting on the angiotensin type 1 receptor (AT1R), increases inflammation, oxidative stress, and apoptosis, accelerating cardiac hypertrophy and fibrosis. Male Tg-ANG II mice and their nontransgenic littermates (n-Tg) were uninephrectomized and divided into the following three groups: 1) vehicle-treated normotensive controls; 2) DOCA-salt; and 3) DOCA-salt + valsartan (AT1R blocker).Under basal conditions, systolic blood pressure (SBP) and cardiac phenotypes were similar between strains. In DOCA-salt hypertension, SBP increased similarly in both n-Tg and Tg-ANG II, and cardiac function did not differ between strains; however, Tg-ANG II had 1) greater ventricular hypertrophy as well as interstitial and perivascular fibrosis; 2) a higher number of deoxynucleotidyl-transferase-mediated dUTP nick end labeling-positive cells and infiltrating macrophages; 3) increased protein expression of NADPH oxidase 2 and transforming growth factor-β1; and 4) downregulation of phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase B (Akt) phosphorylation. Valsartan partially reversed these effects in Tg-ANG II but not in n-Tg. We conclude that, when hemodynamic loading conditions remain unchanged, cardiac ANG II does not alter heart size or cardiac functions. However, in animals with hypertension, cardiac ANG II, acting via AT1R, enhances inflammation, oxidative stress, and cell death (most likely via downregulation of PI 3-kinase and Akt), contributing to cardiac hypertrophy and fibrosis.
Understanding exercise-induced hyperemia: central and peripheral hemodynamic responses to passive limb movement in heart transplant recipients
Authors: Hayman Melissa A. , Nativi Jose N. , Stehlik Josef , McDaniel John , Fjeldstad Anette S. , Ives Stephen J. , Walter Wray D. , Bader Feras , Gilbert Edward M. , Richardson Russell S.
Published: September 2010

To better characterize the contribution of both central and peripheral mechanisms to passive limb movement-induced hyperemia, we studied nine recent (<2 yr) heart transplant (HTx) recipients (56 ± 4 yr) and nine healthy controls (58 ± 5 yr). Measurements of heart rate (HR), stroke volume (SV), cardiac output (CO), and femoral artery blood flow were recorded during passive knee extension. Peripheral vascular function was assessed using brachial artery flow-mediated dilation (FMD). During passive limb movement, the HTx recipients lacked an HR response (0 ± 0 beats/min, Δ0%) but displayed a significant increase in CO (0.4 ± 0.1 l/min, Δ5%) although attenuated compared with controls (1.0 ± 0.2 l/min, Δ18%). Therefore, the rise in CO in the HTx recipients was solely dependent on increased SV (5 ± 1 ml, Δ5%) in contrast with the controls who displayed significant increases in both HR (6 ± 2 beats/min, Δ11%) and SV (5 ± 2 ml, Δ7%). The transient increase in femoral blood volume entering the leg during the first 40 s of passive movement was attenuated in the HTx recipients (24 ± 8 ml) compared with controls (93 ± 7 ml), whereas peripheral vascular function (FMD) appeared similar between HTx recipients (8 ± 2%) and controls (6 ± 1%). These data reveal that the absence of an HR increase in HTx recipients significantly impacts the peripheral vascular response to passive movement in this population and supports the concept that an increase in CO is a major contributor to exercise-induced hyperemia.
Short-term exercise training protects against doxorubicin-induced cardiac mitochondrial damage independent of HSP72
Authors: Kavazis Andreas N. , Smuder Ashley J. , Min Kisuk , Tümer Nihal , Powers Scott K.
Published: September 2010

Doxorubicin (Dox) is an antitumor agent used in cancer treatment, but its clinical use is limited due to cardiotoxicity. Although exercise training can defend against Dox-mediated cardiac damage, the means for this cardioprotection remain unknown. To investigate the mechanism(s) responsible for exercise training-induced cardioprotection against Dox-mediated cardiotoxicity, we tested a two-pronged hypothesis: 1) exercise training protects against Dox-induced cardiotoxicity by preventing Dox-mediated mitochondrial damage/dysfunction and increased oxidative stress and 2) exercise training-induced cardiac expression of the inducible isoform of the 70-kDa heat shock protein 72 (HSP72) is essential to achieve exercise training-induced cardioprotection against Dox toxicity. Animals were randomly assigned to sedentary or exercise groups and paired with either placebo or Dox treatment (i.e., 20 mg/kg body wt ip Dox hydrochloride 24 h before euthanasia). Dox administration resulted in cardiac mitochondrial dysfunction, activation of proteases, and apoptosis. Exercise training increased cardiac antioxidant enzymes and HSP72 protein abundance and protected cardiac myocytes against Dox-induced mitochondrial damage, protease activation, and apoptosis. To determine whether exercise-induced expression of HSP72 in the heart is required for this cardioprotection, we utilized an innovative experimental strategy that successfully prevented exercise-induced increases in myocardial HSP72 levels. However, prevention of exercise-induced increases in myocardial HSP72 did not eliminate the exercise-induced cardioprotective phenotype that is resistant to Dox-mediated injury. Our results indicate that exercise training protects against the detrimental side effects of Dox in cardiac myocytes, in part, by protecting mitochondria against Dox-mediated damage. However, this exercise-induced cardioprotection is independent of myocardial HSP72 levels. Finally, our data are consistent with the concept that increases in cardiac mitochondrial antioxidant enzymes may contribute to exercise-induced cardioprotection.
Cardiac myosin heavy chain gene regulation by thyroid hormone involves altered histone modifications
Authors: Haddad F. , Jiang W. , Bodell P. W. , Qin A. X. , Baldwin K. M.
Published: September 2010

The antithetical regulation of cardiac α- and β-myosin heavy chain (MHC) genes by thyroid hormone (T3) is not well understood but appears to involve thyroid hormone interaction with its nuclear receptor and MHC promoters as well as cis-acting noncoding regulatory RNA (ncRNA). Both of these phenomena involve epigenetic regulations. This study investigated the extent that altered thyroid state induces histone modifications in the chromatin associated with the cardiac MHC genes. We hypothesized that specific epigenetic events could be identified and linked to cardiac MHC gene switching in response to a hypothyroid or hyperthyroid state. A hypothyroid state was induced in rats by propylthiouracil treatment (PTU), whereas a hyperthyroid (T3) was induced by T3treatment. The left ventricle was analyzed after 7 days for MHC pre-mRNA expression, and the chromatin was assessed for enrichment in specific histone modifications using chromatin immunoprecipitation quantitative PCR assays. At both the α-MHC promoter and the intergenic region, the enrichment in acetyl histone H3 at K9/14 (H3K9/14ac) and trimethyl histone H3 at K4 (H3K4me3) changed in a similar fashion. They were both decreased with PTU treatment but did not change under T3, except at a location situated 5′ to the antisense intergenic transcription start site. These same marks varied differently on the β-MHC promoter. For example, H3K4me3 enrichment correlated with the β-promoter activity in PTU and T3groups, whereas H3K9/14ac was repressed in the T3group but did not change under PTU. Histone H3K9me was enriched in chromatin of both the intergenic and α-MHC promoters in the PTU group, whereas histone H4K20me1 was enriched in chromatin of β-MHC promoter in the normal control and T3groups. Collectively, these findings provide evidence that specific epigenetic phenomena modulate MHC gene expression in altered thyroid states.
Preexposure to hyperoxia causes increased lung injury and epithelial apoptosis in mice ventilated with high tidal volumes
Authors: Makena Patrudu S. , Luellen Charlean L. , Balazs Louisa , Ghosh Manik C. , Parthasarathi Kaushik , Waters Christopher M. , Sinclair Scott E.
Published: September 2010

Both high tidal volume mechanical ventilation (HV) and hyperoxia (HO) have been implicated in ventilator-induced lung injury. However, patients with acute lung injury are often exposed to HO before the application of mechanical ventilation. The potential priming of the lungs for subsequent injury by exposure to HO has not been extensively studied. We provide evidence that HO (90%) for 12 h followed by HV (25 μl/g) combined with HO for 2 or 4 h (HO-12h+HVHO-2h or -4h) induced severe lung injury in mice. Analysis of lung homogenates showed that lung injury was associated with cleavage of executioner caspases, caspases-3 and -7, and their downstream substrate poly(ADP-ribose) polymerase-1 (PARP-1). No significant lung injury or caspase cleavage was seen with either HO for 16 h or HV for up to 4 h. Ventilation for 4 h with HO (HVHO) did not cause significant lung injury without preexposure to HO. Twelve-hour HO followed by lower tidal volume (6 μl/g) mechanical ventilation failed to produce significant injury or caspase cleavage. We also evaluated the initiator caspases, caspases-8 and -9, to determine whether the death receptor or mitochondrial-mediated pathways were involved. Caspase-9 cleavage was observed in HO-12h+HVHO-2h and -4h as well as HO for 16 h. Caspase-8 activation was observed only in HO-12h+HVHO-4h, indicating the involvement of both pathways. Immunohistochemistry and in vitro stretch studies showed caspase cleavage in alveolar epithelial cells. In conclusion, preexposure to HO followed by HV produced severe lung injury associated with alveolar epithelial cell apoptosis.
Tenascin-C deficiency attenuates TGF-β-mediated fibrosis following murine lung injury
Authors: Carey William A. , Taylor Glen D. , Dean Willow B. , Bristow James D.
Published: September 2010

Tenascin-C (TNC) is an extracellular matrix glycoprotein of unknown function that is highly expressed in adult lung parenchyma following acute lung injury (ALI). Here we report that mice lacking TNC are protected from interstitial fibrosis in the bleomycin model of ALI. Three weeks after exposure to bleomycin, TNC-null mice had accumulated 85% less lung collagen than wild-type mice. The lung interstitium of TNC-null mice also appeared to contain fewer myofibroblasts and fewer cells with intranuclear Smad-2/3 staining, suggesting impaired TGF-β activation or signaling. In vitro, TNC-null lung fibroblasts exposed to constitutively active TGF-β expressed less α-smooth muscle actin and deposited less collagen I into the matrix than wild-type cells. Impaired TGF-β responsiveness was correlated with dramatically reduced Smad-3 protein levels and diminished nuclear translocation of Smad-2 and Smad-3 in TGF-β-exposed TNC-null cells. Reduced Smad-3 in TNC-null cells reflects both decreased transcript abundance and enhanced ubiquitin-proteasome-mediated protein degradation. Together, these studies suggest that TNC is essential for maximal TGF-β action after ALI. The clearance of TNC that normally follows ALI may restrain TGF-β action during lung healing, whereas prolonged or exaggerated TNC expression may facilitate TGF-β action and fibrosis after ALI.
Hyaluronan Inhibits Postchemotherapy Tumor Regrowth in a Colon Carcinoma Xenograft Model
Authors: Mueller Barbara M. , Schraufstatter Ingrid U. , Goncharova Valentina , Povaliy Tatiana , DiScipio Richard , Khaldoyanidi Sophia K.
Published: September 2010

Bone marrow hypoplasia and pancytopenia are among the most undesirable sequelae of chemotherapy for the treatment of cancer. We recently showed that hyaluronan (HA) facilitates hematopoietic recovery in tumor-free animals receiving chemotherapeutic agents. However, following a chemotherapeutic regimen in tumor-bearing animals, it is possible that residual tumor cells might respond to systemic injections of HA. Thus, in this study, we investigated the effect of HA on the regrowth of residual tumor cells following chemotherapy. As a model, we used the HCT-8 human colon carcinoma cell line, which expresses the HA receptor CD44, binds exogenous HA, and is susceptible to a chemotherapy protocol containing irinotecan and 5-fluorouracil in a human/mouse xenograft model. HCT-8 cells were implanted in severe combined immunodeficient mice, followed by irinotecan/5-fluorouracil treatment. After three rounds of chemotherapy, residual tumors were allowed to regrow in the presence or absence of HA. The dynamics of tumor regrowth in the group treated with HA was slower compared with the control group. By week 5 after tumor implantation, the difference in the size of regrown tumors was statistically significant and correlated with lower proliferation and higher apoptosis in HA-treated tumors as compared with controls. This finding provides evidence that HA treatment does not stimulate but delays the growth of residual cancer cells, which is an important parameter in establishing whether the use of HA can enhance current chemotherapeutic strategies. Mol Cancer Ther; 9(11); 3024–32. ©2010 AACR.
Nanaomycin A Selectively Inhibits DNMT3B and Reactivates Silenced Tumor Suppressor Genes in Human Cancer Cells
Authors: Kuck Dirk , Caulfield Thomas , Lyko Frank , Medina-Franco Jose L.
Published: September 2010

Enzymes involved in the epigenetic regulation of the genome represent promising starting points for therapeutic intervention by small molecules, and DNA methyltransferases (DNMT) are emerging targets for the development of a new class of cancer therapeutics. In this work, we present nanaomycin A, initially identified by a virtual screening for inhibitors against DNMT1, as a compound inducing antiproliferative effects in three different tumor cell lines originating from different tissues. Nanaomycin A treatment reduced the global methylation levels in all three cell lines and reactivated transcription of the RASSF1A tumor suppressor gene. In biochemical assays, nanaomycin A revealed selectivity toward DNMT3B. To the best of our knowledge, this is the first DNMT3B-selective inhibitor identified to induce genomic demethylation. Our study thus establishes the possibility of selectively inhibiting individual DNMT enzymes. Mol Cancer Ther; 9(11); 3015–23. ©2010 AACR.
An Earlier Sunnī Version of Khomeini’s Rule of the Jurist: Mustafā l-Sibāī on Ulamā and Politics
Authors: Meir Hatina
Published: September 2010

The notion of “the rule of the jurist” is identified exclusively with Ayatollah Khomeini, and was implemented politically following the Islamic revolution in Iran in 1979. What was perceived as a revolutionary innovation in Šia Islam, however, was seen as alien in Sunnī Islam. Traditionally, Sunnī Ulamā were identified as “men of the pen”, whose task was to preserve religious knowledge but not to assume state authority. Sunnī Islamic movements of the twentieth century did not alter this traditional viewpoint. Most of their leaders actually criticized the Ulamās submission to secular rulers. Indeed, Sunnī circles—as Khomeini himself—spoke of the urgent need to establish an Islamic government to combat imperialism and Westernization, but did not assign any political function to the religious scholars.The paper focuses on a different view, that of Šayh Mustafā l-Sibāī (d. 1964), of Syrian origin, who asserted in the late 1930s that Ulamā are the best guardians of the nation’s rights. Their entry into politics is neither improper nor deviant, he held, but rather a confirmation of the historic reality in the formative period of Islam. Al-Sibāī’s perception was put into practice with the establishment of the Muslim Brethren in Syria in 1946, but this perception failed to gain momentum.The paper illuminates an interesting episode in modern Sunnī political thought: an early Sunnī version of Khomeini’s “the rule of the jurist”. While the Sunnī version remained a textual idea, the Šīite version turned into living political reality, exposing the asymmetry between the status of Sunnī and Šīite Ulamā in modern times.
Pious Muslims in the Making: A Closer Look at Narratives of Ascetic Conversion
Authors: Sirry Munim
Published: September 2010

This article examines conversion narratives of some Sufi ascetics by looking closely at their life-stories as expounded in Sufi biographical traditions. How is the ascetic conversion told in the Sufi biographical sources? What kind of purpose do the ascetic conversion narratives serve? In what sense can we see the ascetic practices as an intentional language of protest and opposition? and against whom/what? These questions form the major concern of this article. Different narratives of ascetic conversion will be discussed with the intention of demonstrating the larger context of setting the boundaries of an Islamic piety within which the portrait of idealized pious Muslims is framed in the main traditions of Sufi hagiography. It is, therefore, hoped that this article will shed light on the transformation of individuals from ordinary people to idealized pious Muslims.
The Facts of Inequality
Authors: O'Neill Martin
Published: September 2010

This review essay looks at two important recent books on the empirical social science of inequality, Richard Wilkinson and Kate Pickett's The Spirit Level and John Hills et al.'s Towards a More Equal Society?, situating these books against the important work of Michael Marmot on epidemiology and health inequalities. I argue that political philosophy can gain a great deal from careful engagement with empirical research on the nature and consequences of inequality, especially in regard to empirical work on the relationship between socioeconomic inequality, status, self-respect, domination, autonomy, the quality of social relations, and societal health outcomes. The essay also raises some methodological questions about the approach taken by Wilkinson and Pickett, as well as questioning the ways in which their argument is (or is not) best understood as being fundamentally egalitarian in character. It concludes with some reflections, prompted by Hills et al., on the lessons that should be learned by egalitarians from the experience of the Blair and Brown governments in the UK.
A Horse in the Basement Nietzschean Reflections on Political Philosophy
Authors: Bittner Rüdiger
Published: September 2010

Political philosophers often see their task in providing a justification of states, with 'justification' understood, in analogy to the theological use of the term, as an argument showing states to be right, or unobjectionable. Political philosophers disagree on what property of a state it is that is required for its being right. In fact, it is difficult to see what could give this or that property of a state its right-making power. Since there is nothing that states as such are called upon to be or to do, claims to the effect that some property or other is right-making are unfounded. The task of justification falling away, then, political philosophers should rather ask what should be done now with states.
Does Value Pluralism Entail Liberalism?
Authors: Talisse Robert
Published: September 2010

Isaiah Berlin repeatedly attempted to derive liberalism from value pluralism. It is generally agreed that Berlin's arguments fail; however, neo-Berlinians have taken up the project of securing the entailment. This paper begins with an account of why the Berlinian project seems attractive to contemporary theorists. I then examine Berlin's argument. With this background in place, I argue that recent attempts by William Galston and George Crowder to rescue the Berlinian project do not succeed.
Motivating Cosmopolitanism? A Skeptical View
Authors: Lenard Patti Tamara
Published: September 2010

We are not cosmopolitans, if by cosmopolitan we mean that we are willing to prioritize equally the needs of those near and far. Here, I argue that cosmopolitanism has yet to wrestle with the motivational challenges it faces: any good moral theory must be one that well-meaning people will be motivated to adopt. Some cosmopolitans suggest that the principles of cosmopolitanism are themselves sufficient to motivate compliance with them. This argument is flawed, for precisely the reasons that motivate this paper – we are cosmopolitan neither in our attitudes nor in our behaviors towards others. Other cosmopolitans suggest that 'global solidarity' is sufficient to generate a commitment to carrying out duties towards others. These latter efforts implicitly rely on insights best captured by the nationalist thesis, that is, that national communities are the best vehicles, morally speaking, through which individuals can carry out their obligations to others. I consider, and refute, two objections to my argument: first, that it is guilty of a 'time-lag fallacy' and, second, that it ignores an emergent cosmopolitan attitude among global citizens.
Cognitive Biases and Moral Luck
Authors: Guttel Ehud , Enoch David
Published: September 2010

Some of the recent philosophical literature on moral luck attempts to make headway in the moral-luck debate by employing the resources of empirical psychology, in effect arguing that some of the intuitive judgments relevant to the moral-luck debate are best explained – and so presumably explained away – as the output of well-documented cognitive biases. We argue that such attempts are empirically problematic, and furthermore that even if they were not, it is still not at all clear what philosophical significance they would have.
Moral Status, Speciesism, and Liao's Genetic Account
Authors: Grau Christopher
Published: September 2010

This paper offers several criticisms of the account of rightholding laid out in S. Matthew Liao's recent paper 'The Basis of Human Moral Status'. I argue that Liao's account both does too much and too little: it grants rightholder status to those who may not deserve it, and it does not provide grounds for offering such status to those who arguably do deserve it. Given these troubling aspects of his approach, I encourage Liao to abandon his 'physical basis of moral agency' account of moral status and instead adopt a position closer to a traditional 'speciesist' view.
What branches grow out of this stony rubbish? Christian Origins and the Study of Religion
Authors: Arnal William
Published: September 2010

The following paper argues for the potential relevance of scholarship on New Testament/Christian origins to the study of religion generally, in response to recent institutional developments that have driven the Society of Biblical Literature and American Academy of Religion to hold separate meetings. The paper claims that Christian Origins scholarship suggests a series of cautions — about originary stories, the boundaries of traditions, and the predictability of historical developments — as well as some substantive contributions — regarding the desultory character of ‘‘religious’’ interventions, the role of narrative, and the input of intellectuals — to our views of religion that should be of interest to students of other data-sets. At the same time, and in some ways more to the point, it is incumbent upon those scholars of Christian Origins who aim to situate their scholarship within the larger field of the study of religion to be willing to generalize and not only to draw broad conclusions about the development and origins of ancient Christianity, but also to ensure that their own analyses and conclusions are, at least potentially, formulatable in terms of expansive generalizations about human behavior. Thus not only does the incorporation of Christian origins into the study of religion potentially add at least to the relevant data-set of the latter, but it may also be a way to enhance the responsibility and intelligibility of the former.
To Err in their Ways: The Attribution Biases of the New Atheists
Authors: Amarasingam Amarnath
Published: September 2010

The term ‘‘new atheism’’ has been given to the recent barrage of anti-religion and anti-God books written by Richard Dawkins (2006), Sam Harris (2004, 2008), Christopher Hitchens (2007), Daniel Dennett (2006), and others. This paper contends that one of the fundamental arguments put forth by the new atheists — that religion poisons everything or that religion is responsible for much of the evil in the world — falls victim to one of the best established theories of interpersonal and intergroup relations in social psychology: the fundamental attribution error. Insights gleaned from social psychology are especially useful for critiquing the new atheism. Instead of simply arguing that the new atheists ‘‘over-generalize,’’ social psychological studies on the nature of individual and group attribution provide the tools needed to launch a more substantive critique.
The True Covenant People: Ethnic Reasoning in the Epistle of Barnabas
Authors: Kok Michael
Published: September 2010

There was no abstract conception of religion in antiquity, but religious beliefs and practices were closely intertwined with ethnicity in the Graeco-Roman period. Building on the groundbreaking studies of Denise Kimber Buell, I investigate the use of ethnic reasoning in centrist Christian identity formation with the epistle of Barnabas as a specific case study. The epistle of Barnabas utilizes ethnic reasoning to construct a distinct Christian ethnic identity and to manufacture sharp differences between Christian and Judaean social praxis. In order to promote the idea of a homogeneous Christian ethnic identity with pure origins, Barnabas re-appropriates the legacy of Israel while representing the ‘‘Judaean’’ as an adversaral foil.

Il n’y avait pas de conception abstraite de la religion dans l’antiquité, mais les croyances et pratiques religieuses étaient étroitement entrelacées à l’ethnicité dans la période gréco-romaine. En me basant sur les études innovantes de Denise Kimber Buell, je recherche l’utilisation du raisonnement ethnique dans la formation de l’identité chrétienne avec l’épitre de Barnabas comme étude de cas. L’épitre de Barnabas utilise le raisonnement ethnique pour construire une identité chrétienne distincte et pour créer une nette différence entre les coutumes chrétiennes et judaïques. Afin de promouvoir l’idée d’une identité chrétienne homogène avec des origines pures, Barnabas rétablit l’héritage d’Israël tout en représentant le christianisme et le judaïsme comme des adversaires.
The Book of Job as Metaprophecy
Authors: Harding James Edward
Published: September 2010

This article argues that the conventional definition of the book of Job as an example of a ‘‘wisdom’’ text unhelpfully closes off other possibilities. In particular, the book may be read as a penetrating critique of the idea, central to the prophetical books of the Hebrew Bible, that knowledge of the justice of Israel’s god is authentically revealed by ‘‘true’’ prophets standing in the divine council. The book of Job is thus best read as ‘‘metaprophecy.’’
Lost in interpretation: The use of interpreters in research on mental ill health
Authors: Ingvarsdotter Karin , Johnsdotter Sara , Östman Margareta
Published: September 2010

Background: The literature concerning interpretation in research primarily concentrates on rigorous techniques to eliminate bias. This article analyses other significant issues that arise when interpreters participate in research.

Material: Empirical examples are drawn from a research project concerning mental ill health in a multicultural neighbourhood.

Discussion: Interpreters influence interview data in ways commonly unnoticed by researchers. One often-overlooked factor is that languages are dynamic and interpreters are not instruments.

Conclusion: Research conducted with an interpreter is a complex undertaking. Solely relying on checklists to improve methodological rigour can result in a false sense of the material’s validity.
Free Vibrations of Thick Rectangular Composite Plate with Uniformly Distributed Attached Mass Including Stiffness Effect
Authors: Malekzadeh K. , Tafazoli S. , Khalili S.M.R.
Published: September 2010

In this article, free vibrations of rectangular composite plate with and without a uniformly distributed attached mass are analyzed using the standard Galerkin procedure. The results of free vibrations without distributed attached mass are validated by some common literatures. The stiffness effect of the distributed attached mass is taken into account and the results are compared with those well-known published results in which this effect is not considered. Various results for isotropic and composite rectangular plates under a variety of conditions such as variation in thickness of the plate, variation in thickness of the distributed attached mass, fiber orientations and layup, and various elastic moduli for the distributed attached mass are presented in this article. In simple cases, to verify the results, other theories such as first-order shear deformation theory and classical lamination plate theory are used. Adding the stiffness of the attached mass increases the natural frequencies of the system.
AC Electrical and Structural Properties of Polymethylmethacrylate/Aluminum Composites
Authors: Singh Dolly , Singh N.L. , Kulriya P. , Tripathi A. , Phase D.M.
Published: September 2010

Different concentrations (i.e., 10, 20, 30, and 40 wt%) of Al metal are dispersed in polymethylmethacrylate (PMMA) matrix and the composite films are prepared by solution casting method. The frequency and temperature dependence of dielectric constant, dielectric loss, and conductivity of pure polymer and polymer composites filled with Al-metal filler are studied in the broad frequency range from 100 Hz to 10 MHz and in the temperature range 25—80°C. It is observed that the dielectric constant, dielectric loss, and electrical conductivity gradually increase with filler concentration and also with temperature and is explained in terms of hopping conduction mechanism. The electrical conductivity of the composites obeys universal power law model (i.e., σ = Af n), where n is power exponent. A comparison of dielectric constant values of PMMA/Al composites is made with predictions of theoretical models and it is observed that an empirical power equation gives a better fit to our results. Structural property of the composites is studied by means of X-ray diffraction. The results show that the crystallinity and crystalline size increase with increasing concentration of aluminum filler. Average surface roughness is observed to change with filler concentration as obtained from atomic force microscopy and scanning electron microscopy analysis.
Synthesis of New Cu-based Self-lubricating Composites with Great Mechanical Properties
Authors: Chen Suiyuan  , Wang Jing  , Liu Yijie  , Liang Jing  , Liu Changsheng
Published: September 2010

New copper-based self-lubricating composites consisting of different quantities of graphite are prepared by means of powder metallurgy using a designed atomizing Cu-10Ni-3Sn-3Pb (wt.%) alloy with 0.5 wt.% Y2O3 as the matrix. Microstructures and properties of the composites are studied by scanning electron microscopy, X-ray diffraction, a hardness tester, and a wear tester. The results indicate that the composites sintered at 910°C for 4 h have the best mechanical properties. The composites prepared under such a condition are mainly composed of α-solid solution together with some CuNi 2Sn, Pb, and graphite phases. Here, Ni and Sn play the reinforcing role in the materials by either dissolving into the Cu matrix or forming the second phase with Cu, while Pb and graphite as inclusions act as the lubricating phases. The composites have hardness but deteriorated wear and self-lubricating performance with the increasing graphite content. The composite with 1 wt.% graphite possesses better mechanical and frictional properties, while the composite with 2% graphite possesses better self-lubricating properties. These Cu-based composites with low friction coefficient and enough strength are suitable for the application as surface lubricating film to run under a dry friction condition.
On the Compliance and Energy Release Rate of Generically-unified Beam-type Fracture Specimens
Authors: Pizhong Qiao  , Fangliang Chen
Published: September 2010

A unified approach is proposed to evaluate the compliance and energy release rate (ERR) of generic beam-type interface fracture specimens. Based on a sub-layer Timoshenko beam theory, the classic composite (rigid joint), shear deformable (semi-rigid joint), and interface deformable (flexible joint) bi-layer beam models are revisited, from which the compliance and ERR of the generic beam-type fracture specimens are determined. According to specific combinations of loading conditions and material properties of each sub-layer, the generic fracture specimens are reduced to the conventional fracture specimens for actual applications. The effects of the crack tip deformation on the ERR of the interface crack are compared among the three different joint models, from which the evolving accuracy of the joint models to the ERR predictions of beam-type fracture specimens is manifested. The derived explicit formulas and improved solution for the compliance and ERR of the common beam-type fracture specimens can be effectively used to reduce data in interface fracture experiments and increase accuracy of fracture toughness evaluation of dissimilar material interfaces.
Modeling Corrosion Initiation of Reinforcing Steel in Concrete: Effect of Non-diffusive Coarse Aggregate
Authors: Hui Yu  , Hartt William H.
Published: September 2010

The exposure time at which a threshold Cl— concentration, Ct, is initially achieved at the reinforcement depth in concrete, Ti, is an important service life determinant for reinforced concrete structures. However, there is no consensus in the literature of a value for Ct, as reported concentrations extend over one order of magnitude; and it has become increasingly apparent that Ct is distributed even for apparently identical specimens. In this research, models of randomly arranged coarse aggregate (CA) particles in concrete cover were generated for different aggregate types (particle size and size distribution), CA volume fraction, and cover; and, by finite element analysis, the effect of these factors on the time and location along the reinforcement at which Ct is initially achieved was investigated as a function of Ct. The results are discussed within the context of factors that contribute to the reported variability in Ct.
Development and Material Properties of Chitosan and Phosphomolybdic Acid-based Composites
Authors: Bhat A.H. , Bhat Irshad-Ul-Haq , Khalil H.P.S. Abdul , Mishra R.K. , Datt M. , Banthia Ajit K.
Published: September 2010

This work reports the development and characterization of chitosan/ phosphomolybdic acid-based composite membranes. The prepared composite membranes were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), tensile strength test, and thermogravimetric analysis (TGA). FTIR spectroscopy indicated the proper molecular interactions between chitosan and PMA. XRD spectroscopy indicated the semi crystalline nature of the composite membranes. DSC study showed the presence of single glass transition temperature (Tg) at 156°C in the 20% PMA-doped membrane, which indicates the miscible nature of chitosan and PMA blend. TGA study indicates increase in thermal stability of the composite membranes as compared to pure chitosan. Mechanical properties of the composite membranes were found to be enhanced significantly.
An Examination of the Compressive Cyclic Loading Aspects of Damage Tolerance for Polymer Matrix Launch Vehicle Hardware
Authors: Nettles Alan , Hodge Andrew , Jackson Justin
Published: September 2010

The issue of fatigue loading of structures composed of composite materials is considered in a requirements document that is currently in place for manned launch vehicles. By taking into account the short lives of these parts, coupled with design considerations, it is demonstrated that the necessary coupon level fatigue data collapse to a static case. Data from a literature review of past studies that examined compressive fatigue loading after impact and data generated from this experimental study are presented to support this finding. In other studies from the literature, a stress amplitude of about 60% of the static compression after impact (CAI) strength was found to exist, below which fatigue had no deleterious effects up to one million cycles. In this study, a stress amplitude of about 80% of the static (CAI) strength was found to exist, below which fatigue had no deleterious effects up to 10,000 cycles. A launch vehicle structure should never experience one cycle above 61.4% of static CAI strength, much less 10,000 at 80%. Despite utilizing severe fatigue amplitude loading in impact damaged coupons, residual strength after fatigue was consistently higher than expected. Unrealistically high fatigue stress amplitudes were needed to fail 5 of 15 specimens, before 10,000 cycles was reached. Since a typical launch vehicle structure, such as the ARES I interstage, only experiences a few cycles near limit load, it is concluded that static CAI strength data will suffice for most launch vehicle structures.
Agglomeration of Knowledge
Authors: Gabe Todd , Abel Jaison R.
Published: September 2010

This paper examines the agglomeration of people working in jobs with similar knowledge requirements, ranging from groups of artists and scientists to service providers and low-skilled labourers. Empirical results from the US suggest that agglomeration enhances earnings in innovation- and creative-based occupations such as artists, engineers, financial executives and information technology workers. In contrast, medical workers, personal service providers and low-skilled labourers do not appear to benefit from agglomeration. Positive agglomeration effects, however, need not lead to a high geographical concentration of economic activity. Rather, an occupation’s ability to concentrate in a few places also depends on the way in which knowledge is disseminated to people outside the occupational cluster.
Bilbao and Barcelona ‘in Motion’. How Urban Regeneration ‘Models’ Travel and Mutate in the Global Flows of Policy Tourism
Authors: González Sara
Published: September 2010

This paper explores how the so-called Bilbao effect and Barcelona Model are diffused internationally through what may be called urban policy tourism: short trips made to Bilbao and Barcelona by policy-makers to learn from their regeneration in the past 15 years. The paper reveals for the first time the substantial extent of this practice and contextualises it within a wider phenomenon of urban policy transfer and the international ‘motion’ of urban policies. Although both models are internationally known for a set of elements, this research shows that in fact the messages mutate and shift as they circulate through the policy circuits. Ultimately, however, the popularity of the Bilbao and Barcelona models suggests a process of global urban policy convergence.
The Fluctuating Record of Economic Regeneration in England’s Second-order City-regions, 1984–2007
Authors: Champion Tony , Townsend Alan
Published: September 2010

Within the context of theoretical and policy debates about the new economic geography and an urban renaissance, this paper examines how far and in what way ‘Our cities are back’, as claimed by England’s Core Cities Group. It focuses on 1984–2007 employment changes for the eight Core Cities and their city-regions: Birmingham, Bristol, Leeds, Liverpool, Manchester, Newcastle, Nottingham and Sheffield. These provincial city-regions are found to have suffered from the early 1990s recession relatively less than London, but then recovered more slowly. While they continued to gain jobs until 2007, their growth rate relative to the national average peaked in 1998–2002, which was also the only time that Core Cities themselves outpaced the rest of their city-regions.
‘I’m a Normal Person’1
Authors: McCarthy Deborah
Published: September 2010

This paper analyses 41 qualitative interviews with utilitarian cyclists in Charleston South Carolina to explore their understanding of cycling-related risks. The utilitarian cyclists list a number of risks related to motorist behaviour, such as cars passing too closely, which make them feel unsafe. Thirty-nine out of 41 of the respondents reveal the sentiment that often the risky behaviour of motorists is part of an anti-bicycle culture. This paper concludes that cyclists, in their attempt to make sense of these risks, perceive that the anti- bicycle culture is based on a system of exclusion in which drivers are insiders who belong on the road and treat cyclists as outsiders who do not belong.
Interactive Visualization and Communication for Increased Impact of Pharmacometrics
Authors: Krause Andreas , Gieschke Ronald
Published: September 2010

The art of pharmacometric activities (also called modeling and simulation) is in developing the appropriate model to describe the data at hand. In a subsequent step, outputs from the model are frequently used for quantitative decision making: what is the appropriate dose and dosing regimen, should the dose be individualized, what percentage of patients can be expected to reach therapeutic levels of exposure, and more. However, a good model does not automatically lead to a good decision‐making process, which implies clinical team decisions on the population to be treated, the clinical end point, the dose, and the dosing regimen. The authors argue that seeing is believing: interactive visualization helps the communication process of clinical teams substantially. A flow of arguments guided by visualization of the model‐predicted consequences of choosing a particular setup makes the discussion transparent and enhances quantitative decision making. The use of interactive visualization tools (such as the Berkeley Madonna software system) for pharmacometric results facilitates effective communication, enhanced quantitative decision making, and thus increases the impact of pharmacometrics in drug development.
Population Pharmacokinetic‐Pharmacodynamic Modeling of Biological Agents: When Modeling Meets Reality
Authors: Mould Diane R. , Frame Bill
Published: September 2010

The pharmacokinetics (PK) and pharmacodynamics (PD) of many biological agents (biologics) have inherent complexities requiring specialized approaches to develop reliable, unbiased models. Three cases are covered: preponderance of zero values, nonresponder subpopulations, and adaptive dosing. Engineered biologics exhibit high affinity for target receptors. Biologics can saturate receptors, abolishing free receptor levels for protracted periods. Consequently, the distribution of observations can be heavy at, and near, the boundary. A 2‐part model (ie, a truncated δ log‐normal distribution) may be appropriate. Mixture models identify subpopulations based on bimodal or multimodal distributions of η values. With biologics, PD may be compromised because of lack of receptors, or the PD may be affected because of other events resulting in erratic excursions. Nonresponders exhibit a random walk‐around placebo trajectory, resulting in high residual variability. The distributions of etas are often badly skewed or polymodal. An indescribable mixture model separates subjects who are nonresponders, providing diagnostic pharmacologic information on the drug. Many biologics use PD‐based adaptive dosing. During model development, data used for model development include adaptive dosing. For simulation, adaptive dosing must be implemented. Failure to account for dose adjustments results in biased or inflated prediction intervals because subjects in the simulated data undergo inappropriate dose adjustments.
Population Modeling of Filgrastim PK‐PD in Healthy Adults Following Intravenous and Subcutaneous Administrations
Authors: Krzyzanski Wojciech , Wiczling Pawel , Lowe Phil , Pigeolet Etienne , Fink Martin , Berghout Alexander , Balser Sigrid
Published: September 2010

Filgrastim is a recombinant human granulocyte colony stimulating factor (G‐CSF) that stimulates production of neutrophils. The objective of this analysis was to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model to account for an increase in G‐CSF clearance on multiple dosing because of an increase of the G‐CSF receptor‐mediated endocytosis. Data from 4 randomized studies involving healthy volunteers were used for analysis. Subjects received filgrastim (Neupogen) via subcutaneous (SC) and intravenous (IV) routes. Filgrastim was administered SC daily for 1 week at 2.5, 5, and 10 μg/kg doses and as single IV infusions (5 μg/kg over 0.5 hours) and SC (1 μg/kg) doses. PK data comprised serum concentration‐time measurements and the blood absolute neutrophil count (ANC) was used for PD evaluations. Population nonlinear mixed‐effect modeling was done using NONMEM VI (Version 6.1.0, Icon Development Solutions, Ellicott City, Maryland). The model depicted the decaying trend in Cmax values with repeated doses and an increase in ANCmax values consistently with an increase in the G‐CSF receptor pool. Simulated time courses of the total clearance exhibited an increasing pattern. The increase in filgrastim clearance on multiple dosing was attributed to the increased neutrophil count in the bone marrow and blood paralleled by an increase in the total G‐CSF receptor density.