bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal Cell Fate Decisions Within Periosteum and Bone Marrow During Bone Regeneration
Authors: Colnot Céline
Published: October 2008

Bone repair requires the mobilization of adult skeletal stem cells/progenitors to allow deposition of cartilage and bone at the injury site. These stem cells/progenitors are believed to come from multiple sources including the bone marrow and the periosteum. The goal of this study was to establish the cellular contributions of bone marrow and periosteum to bone healing in vivo and to assess the effect of the tissue environment on cell differentiation within bone marrow and periosteum. Results show that periosteal injuries heal by endochondral ossification, whereas bone marrow injuries heal by intramembranous ossification, indicating that distinct cellular responses occur within these tissues during repair. Next, lineage analyses were used to track the fate of cells derived from periosteum, bone marrow, and endosteum, a subcompartment of the bone marrow. Skeletal progenitor cells were found to be recruited locally and concurrently from periosteum and/or bone marrow/endosteum during bone repair. Periosteum and bone marrow/endosteum both gave rise to osteoblasts, whereas the periosteum was the major source of chondrocytes. Finally, results show that intrinsic and environmental signals modulate cell fate decisions within these tissues. In conclusion, this study sheds light into the origins of skeletal stem cells/progenitors during bone regeneration and indicates that periosteum, endosteum, and bone marrow contain pools of stem cells/progenitors with distinct osteogenic and chondrogenic potentials that vary with the tissue environment.
Association Between Change in BMD and Fragility Fracture in Women and Men
Authors: Berger Claudie , Langsetmo Lisa , Joseph Lawrence , Hanley David A , Davison K Shawn , Josse Robert G , Prior Jerilynn C , Kreiger Nancy , Tenenhouse Alan , Goltzman David
Published: October 2008

Our objective was to estimate the relationship between longitudinal change in BMD and fragility fractures. We studied 3635 women and 1417 men 50–85 yr of age in the Canadian Multicentre Osteoporosis Study who had at least two BMD measurements (lumbar spine, femoral neck, total hip, and trochanter) within the first 5 yr of the study and fragility fractures (any, main, forearm/wrist, ribs, hip) within the first 7 yr. Multiple logistic regression was used to model the relationship between baseline BMD, BMD change, and fragility fractures. We found that, among nonusers of antiresorptives, independent of baseline BMD, a decrease of 0.01 g/cm2/yr in total hip BMD was associated with an increased risk of fragility fracture with ORs of 1.15 (95% CI: 1.01; 1.32) in women and 1.34 (95% CI: 1.02; 1.78) in men. The risk of fragility fractures in subgroups such as fast losers and those with osteopenia was better estimated by models that included BMD change than by models that included baseline BMD but excluded BMD change. Although the association between baseline BMD and fragility fractures was similar in users and nonusers of antiresorptives, the association was stronger in nonusers compared with users. These results show that BMD change in both men and women is an independent risk factor for fragility fractures and also predicts fracture risk in those with osteopenia. The results suggest that BMD change should be included with other variables in a comprehensive fracture prediction model to capture its contribution to osteoporotic fracture risk.
Activation of Renin-Angiotensin System Induces Osteoporosis Independently of Hypertension
Authors: Asaba Yutaro , Ito Masako , Fumoto Toshio , Watanabe Ken , Fukuhara Ryoji , Takeshita Sunao , Nimura Yuji , Ishida Junji , Fukamizu Akiyoshi , Ikeda Kyoji
Published: October 2008

Hypertension and osteoporosis are two major age-related disorders; however, the underlying molecular mechanism for this comorbidity is not known. The renin-angiotensin system (RAS) plays a central role in the control of blood pressure and has been an important target of antihypertensive drugs. Using a chimeric RAS model of transgenic THM (Tsukuba hypertensive mouse) expressing both the human renin and human angiotensinogen genes, we showed in this study that activation of RAS induces high turnover osteoporosis with accelerated bone resorption. Transgenic mice that express only the human renin gene were normotensive and yet exhibited a low bone mass, suggesting that osteoporosis occurs independently of the development of hypertension per se. Ex vivo cultures showed that angiotensin II (AngII) acted on osteoblasts and not directly on osteoclast precursor cells and increased osteoclastogenesis-supporting cytokines, RANKL and vascular endothelial growth factor (VEGF), thereby stimulating the formation of osteoclasts. Knockdown of AT2 receptor inhibited the AngII activity, whereas silencing of the AT1 receptor paradoxically enhanced it, suggesting a functional interaction between the two AngII receptors on the osteoblastic cell surface. Finally, treatment of THM mice with an ACE inhibitor, enalapril, improved osteoporosis and hypertension, whereas treatment with losartan, an angiotensin receptor blockers specific for AT1, resulted in exacerbation of the low bone mass phenotype. Thus, blocking the synthesis of AngII may be an effective treatment of osteoporosis and hypertension, especially for those afflicted with both conditions.
Muscle Cross-Sectional Area and Structural Bone Strength Share Genetic and Environmental Effects in Older Women
Authors: Mikkola Tuija M , Sipilä Sarianna , Rantanen Taina , Sievänen Harri , Suominen Harri , Tiainen Kristina , Kaprio Jaakko , Koskenvuo Markku , Kauppinen Markku , Heinonen Ari
Published: October 2008

The purpose of this study was to estimate to what extent muscle cross-sectional area of the lower leg (mCSA) and tibial structural strength are influenced by common and trait-specific genetic and environmental factors. pQCT scans were obtained from both members of 102 monozygotic (MZ) and 113 dizygotic (DZ) 63- to 76-yr-old female twin pairs to estimate the mCSA of the lower leg, structural bending strength of the tibial shaft (BSIbend), and compressive strength of the distal tibia (BSIcomp). Quantitative genetic models were used to decompose the phenotypic variances into common and trait-specific additive genetic (A), shared environmental (C), and individual environmental (E) effects. The age-adjusted trivariate independent pathway model showed that the total relative contributions of A, C, and E were, respectively, 75%, 0%, and 25% for mCSA, 55%, 20%, and 25% for BSIbend, and 40%, 37%, and 23% for BSIcomp. In addition, the model showed that all three traits shared genetic and individual environmental factors. BSIbend and BSIcomp had common shared environmental factors and were also influenced by trait-specific genetic factors. In conclusion, the association between muscle cross-sectional area and structural bone strength has its origins in both genetic and environmental effects in older women. These results suggest that in older women the same genetic and environmental factors may predispose to or, conversely, protect from both sarcopenia and bone fragility.
Ethanol Impairs Estrogen Receptor Signaling Resulting in Accelerated Activation of Senescence Pathways, Whereas Estradiol Attenuates the Effects of Ethanol in Osteoblasts
Authors: Chen Jin-Ran , Lazarenko Oxana P , Haley Rani Lynn , Blackburn Michael L , Badger Thomas M , Ronis Martin J
Published: October 2008

Epidemiological and animal studies have suggested that chronic alcohol consumption is a major risk factor for osteoporosis. Using bone from cycling female rats infused chronically with ethanol (EtOH) in vivo and osteoblastic cells in vitro, we found that EtOH significantly increased estrogen receptor α (ERα) and β (ERβ) mRNA and ERα protein levels. Treatment with 17β-estradiol (E2) in vivo and in vitro interfered with these effects of EtOH on bone and osteoblastic cells. ERα agonist propylpyrazoletriol (PPT) and ERβ agonist diarylpropionitrile (DPN) attenuated EtOH-induced ERα and ERβ gene overexpression, respectively. Similar to the ER antagonist ICI 182780, EtOH blocked nuclear translocation of ERα-ECFP in the presence of E2 in UMR-106 osteoblastic cells. EtOH also downregulated ERE-luc reporter activity. On the other hand, EtOH by itself upregulated some common ERα- and ERβ-mediated genes apparently by an ER-independent pathway. EtOH also transactivated the luciferase activity of the p21 promoter region independent of additional exogenous ERα, activated p21 and p53, and stimulated senescence-associated β-galactosidase activity in rat stromal osteoblasts. E2 treatment attenuated these EtOH actions. We conclude that inhibitory cross-talk between EtOH and E2 in osteoblasts on ERs, p53/p21, and cell senescence provides a pathophysiologic mechanism underlying bone loss and the protective effects of estrogens in alcohol-exposed females.
Simplified System for Absolute Fracture Risk Assessment: Clinical Validation in Canadian Women
Authors: Leslie William D , Tsang James F , Lix Lisa M
Published: October 2008

Absolute 10-yr fracture risk based on multiple factors is the preferred method for risk assessment. A simplified risk assessment system from sex, age, DXA, and two clinical risk factors (CRFs)—prior fracture and systemic corticosteroid (CS) use-has been used in Canada since 2005. This study was undertaken to evaluate this system in the Canadian female population. A total of 16,205 women ≥50 yr of age at the time of baseline BMD (1998–2002) were identified in a database containing all clinical DXA test results for the Province of Manitoba, Canada. Basal 10-yr fracture risk from age and minimum T-score (lumbar spine, femur neck, trochanter, total hip) was categorized as low (<10%), moderate (10–20%), or high (>20%). Health service records since 1987 were assessed for prior fracture codes (N = 5224), recent major CS use (N = 616), and fracture codes after BMD testing (mean, 3.1 yr of follow-up) for the hip, vertebrae, forearm, or humerus (designated osteoporotic, N = 757). Fracture risk predicted from age and minimum T-score alone showed a significant gradient in observed fracture rates (low 5.1 [95% CI, 4.1–6.4], moderate 11.5 [95% CI, 10.1–13.0], high 25.4 [95% CI, 23.2–27.9] per 1000 person-years; p-for-trend <0.0001). There was an incremental increase in incident fracture rates from a prior fracture (13.9 [95% CI, 11.3–16.4] per 1000 person-years) or major CS use (11.2 [95% CI, 4.1–18.2] per 1000 person-years). This simplified fracture risk assessment system provides an assessment of fracture risk that is consistent with observed fracture rates.
Carboxypeptidase Z (CPZ) Links Thyroid Hormone and Wnt Signaling Pathways in Growth Plate Chondrocytes
Authors: Wang Lai , Shao Yvonne Y , Ballock R Tracy
Published: October 2008

Carboxypeptidase Z (CPZ) removes carboxyl-terminal basic amino acid residues, particularly arginine residues, from proteins. CPZ contains a cysteine-rich domain (CRD) similar to the CRD found in the frizzled family of Wnt receptors. We have previously shown that thyroid hormone regulates terminal differentiation of growth plate chondrocytes through activation of Wnt-4 expression and Wnt/β-catenin signaling. The Wnt-4 protein contains a C-terminal arginine residue and binds to CPZ through the CRD. The objective of this study was to determine whether CPZ modulates Wnt/β-catenin signaling and terminal differentiation of growth plate chondrocytes. Our results show that CPZ and Wnt-4 mRNA are co-expressed throughout growth plate cartilage. In primary pellet cultures of rat growth plate chondrocytes, thyroid hormone increases both Wnt-4 and CPZ expression, as well as CPZ enzymatic activity. Knockdown of either Wnt-4 or CPZ mRNA levels using an RNA interference technique or blocking CPZ enzymatic activity with the carboxypeptidase inhibitor GEMSA reduces the thyroid hormone effect on both alkaline phosphatase activity and Col10a1 mRNA expression. Adenoviral overexpression of CPZ activates Wnt/β-catenin signaling and promotes the terminal differentiation of growth plate cells. Overexpression of CPZ in growth plate chondrocytes also removes the C-terminal arginine residue from a synthetic peptide consisting of the carboxyl-terminal 16 amino acids of the Wnt-4 protein. Removal of the C-terminal arginine residue of Wnt-4 by site-directed mutagenesis enhances the positive effect of Wnt-4 on terminal differentiation. These data indicate that thyroid hormone may regulate terminal differentiation of growth plate chondrocytes in part by modulating Wnt signaling pathways through the induction of CPZ and subsequent CPZ-enhanced activation of Wnt-4.
Atorvastatin May Have No Effect on Acute Phase Reaction in Children After Intravenous Bisphosphonate Infusion
Authors: Srivastava Tarak , Haney Connie J , Alon Uri S
Published: October 2008

Intravenous bisphosphonate therapy is associated with acute phase reaction characterized by fever and musculoskeletal pain. Bisphosphonates have been shown in vitro to activate γδT-cells to proliferate and produce cytokines, suggesting a role in acute phase reaction, which can be effectively blocked by statins. We conducted a double-blind randomized crossover placebo controlled study in 12 children (12.1 ± 4.2 yr; 10 girls and 2 boys) receiving intravenous bisphosphonates to evaluate whether statins can be used to prevent acute phase reaction associated with therapy. Children received two cycles given 3–4 mo apart of intravenous bisphosphonate given on 2 consecutive days in each cycle. Atorvastatin 10 mg or placebo was given orally once a day for 3 days, starting the day before intravenous bisphosphonate therapy and on the 2 infusion days. We measured pain using a visual analog pain scale at five time points in 0–48 h, oxycodone use for pain, acetaminophen for fever, C-reactive protein (CRP), and total and percent γδT-cells. There was a nonsignificant decrease in pain, oxycodone use, and acetaminophen use with Atorvastatin compared with placebo. There was no difference in CRP and total or percent γδT-cells between the two groups. The results remained unchanged after adjustment for Atorvastatin versus placebo given with the first cycle. We conclude that in vivo Atorvastatin may not be as effective in modulating the acute phase reaction associated with intravenous bisphosphonate as would have been anticipated from in vitro studies.
Quantification of Methylmalonic Acid in Human Plasma with Hydrophilic Interaction Liquid Chromatography Separation and Mass Spectrometric Detection
Authors: Lakso Hans-Åke , Appelblad Patrik , Schneede Jörn
Published: October 2008

Background: Measurement of methylmalonic acid (MMA) in serum or plasma is useful for diagnosing cobalamin deficiency. We developed a method for quantifying MMA in plasma based on hydrophilic interaction liquid chromatography (HILIC) and single-stage negative electrospray ionization (ESI) mass spectrometry.

Methods: We deproteinized plasma samples (200 μL) with 800 μL acidified acetonitrile containing 0.17 μmol/L deuterated MMA (D3-MMA) internal standard, centrifuged the samples, and injected 4 μL of the supernatant into the LC-MS instrument. Separation was achieved within 3 min on a Merck SeQuant ZIC®-HILIC column with a mobile phase consisting of 4 volumes acetonitrile plus 1 volume 100 mmol/L ammonium acetate buffer, pH 4.5, at a flow rate of 400 μL/min. Subsequent column washing and reconditioning contributed to a total run time of 10 min. MMA and D3-MMA were quantified by single-ion monitoring (m/z 117.2 and 120.2, respectively) in negative ESI mode at a drying-gas flow rate of 10 L/min, 300 °C, and a capillary voltage of 3.0 kV.

Results: The estimated limits of MMA quantification and detection were 0.09 μmol/L and 0.03 μmol/L, respectively, in plasma. The assay was linear to 200 μmol/L. Interassay and intraassay CVs were ≤5% at all tested concentrations. Recoveries were 90%–93%.

Conclusions: This robust assay allows analysis of MMA in human plasma without derivatization. Sample preparation is simple and suitable for automation.
Simultaneous Measurement of Plasma Concentrations of Proinsulin and C-Peptide and Their Ratio with a Trefoil-Type Time-Resolved Fluorescence Immunoassay
Authors: De Pauw Pieter E M , Vermeulen Ilse , Ubani Ogonnaya C , Truyen Inge , Vekens Evilien M F , van Genderen Farah T , De Grijse Joeri W , Pipeleers Daniel G , Van Schravendijk Chris , Gorus Frans K
Published: October 2008

Background: When the concentrations of 2 or more substances are measured separately, their molar ratios are subject to the additive imprecisions of the different assays. We hypothesized that the cumulative error for concentration ratios of peptides containing a common sequence might be minimized by measuring the peptides simultaneously with a “trefoil-type” immunoassay.

Methods: As a model of this approach, we developed a dual-label time-resolved fluorescence immunoassay (TRFIA) to simultaneously measure proinsulin, C-peptide, and the proinsulin–C-peptide ratio (PI/C). A monoclonal antibody captures all C-peptide–containing molecules, and 2 differently labeled antibodies distinguish between proinsulin-like molecules and true C-peptide.

Results: The trefoil-type TRFIA was capable of measuring plasma C-peptide and proinsulin simultaneously without mutual interference at limits of quantification of 48 and 8125 pmol/L, and 2.1 and 197 pmol/L, respectively. Within-laboratory imprecision values for the trefoil-type TRFIA ranged between 8.4% and 12% for the hormone concentrations. Unlike the hormone results obtained with separate assays, imprecision did not increase when PI/C was calculated from trefoil assay results (P < 0.05). Peptide concentrations were highly correlated with results obtained in individual comparison assays (r2 ≥ 0.965; P < 0.0001). The total error for PI/C obtained with the trefoil-type TRFIA remained ≤25% over a broader C-peptide range than with separate hormone assays (79–7200 pmol/L vs 590–4300 pmol/L C-peptide). Preliminary data indicate little or no interference by heterophile antibodies.

Conclusions: The developed trefoil-type TRFIA is a reliable method for simultaneous measurement of proinsulin, C-peptide, and PI/C and provides proof of principle for the development of other trefoil-type multiple-label immunoassays.
Water shortages in Queensland: are businesses ready to meet the challenge?
Authors: Hyland Paul , Miles Bob
Published: October 2008

Water shortages are often viewed as a problem facing emerging economies, but with changes in weather patterns developed economies are discovering that the water supply infrastructure that was designed to meet their needs is failing to provide an adequate supply of water for consumers.
In regions were an adequate supply of water was taken for granted households and businesses are ill-prepared to manage water shortages. Many businesses are able to manage changing resource availability however responding to changes requires that they understand the risks associated with water
shortages and they have sufficient time to implement operational changes to meet the scarcity of water. The article reports on the approach taken by an association of businesses in Australia to understand and manage the risks associated with ongoing water shortages.
Traumatized masculinity and American national identity in Hollywood's Gulf War
Authors: Straw Mark
Published: October 2008

The main question of this article is how traumatic male subjectivity and American national identity are rendered explicitly in contemporary Hollywood war films, the latter through encounter with the enemy, who is inevitably figured as other. I deal with this question by referring to an emergent critical discourse surrounding the aesthetics and technologies (and politics/economics) involved in constructing millennial or 1990s American cinema; what Jon Lewis has described as the end of cinema. This form of cinema contains persistent themes of trauma, memory, nostalgia, endings, terminations, death and apocalyptic images. I use this and contemporary theorizations of masculinity and film in order to look at Hollywood Gulf War films such as Courage Under Fire (Edward Zwick 1996) and The Jacket (John Maybury 2005). I argue that encounters with the usually abstract and obscured enemy appear to present a challenge to American dominance and paternalism, a challenge which has to be worked through and rebuffed if the film is to be successful in achieving what Marita Sturken has dubbed making way for the next war. Contemporary Hollywood cinema is crucial in this regard, since the conservative ideology of making way for the next war in order to reinforce and fortify US foreign policy, becomes fraught with ambiguities. I also argue that contemporary war films which engage with recent US foreign policy exhibit many slippages and imbrications regarding identity and memory, and hence national identity is formulated in an inter-subjective and inter-relational manner. The value of this exploration is that it shows how recent US foreign policy is worked through in the context of contemporary cinema, and how American national identity is founded upon mythical constructions of victimhood, perceived emasculation and the centralization of male crisis in representation.
Identities and oppressions: Jean-Claude Lauzon's Lolo (1992)
Authors: Larrive Pierre
Published: October 2008

This article approaches the fragmentation of identities characteristic of contemporary Western societies through the 1992 film Lolo by Jean-Claude Lauzon. Although it does explore linguistic, social, religious and ethnic divisions, this major piece of the Quebec repertoire recasts the sociolinguistic conflict between vernacular and formal practices (Labov 1972; Blanche-Benveniste 2002), raising questions of status and choice. This conflict is subsumed by the dialectics between primary and secondary culture. The cultural and linguistic opposition finds a primary metaphor in the film's central motif of the duality of dream and reality. No more than the cultural and linguistic can this opposition find a synthesis. This impossible reconciliation defines the constitutive rupture of the human psyche itself.
De-essentializing the Banlieues, reframing the nation: documentary cinema in France in the late 1990s
Authors: Levasseur Bruno
Published: October 2008

This article considers the part played by recent documentary cinema in France in constructing an integrated rather than a fragmented image of the French nation. Suggesting that this may be part of an international trend in documentary-making, it starts from the observation that dominant
media discourse in France, along with the critically acclaimed fiction film movement of the cinma de banlieue, has perpetuated an image of these cits peripheral to many French cities as threatening spaces adrift of the national community and emblematic of France's postmodern crisis of identity.
Focusing on three documentaries about La Courneuve, a typically pilloried cit to the northeast of Paris, it argues that the ordinariness of the lives they convey, along with the documentarists' emphasis on the continuing penetration of cit space by State institutions and processes, and their
insertion of supposedly alien spaces into a continuous narrative of memory and culture, effectively treats geography, history and culture in a way that calls into question the externalizing dominant discourse. Although limited by their lack of appeal to a mass audience that prefers the violence
and spectacle of narrative cinema complicit with dominant representations of the banlieues as violent, dangerous spaces, these documentaries and French documentary cinema of the late 1990s in general offer images that de-essentialize the banlieue myth and challenge the image of a French nation
in continuous crisis.
N-terminal polyglutamine-containing fragments inhibit androgen receptor transactivation function
Authors: Schiffer Niclas W. , Céraline Jocelyn , Hartl F. Ulrich , Broadley Sarah A.
Published: October 2008

Several neurodegenerative diseases, including Kennedy's disease (KD), are associated with misfolding and aggregation of polyglutamine (polyQ)-expansion proteins. KD is caused by a polyQ-expansion in the androgen receptor (AR), a key player in male sexual differentiation. Interestingly, KD patients often show signs of mild-to-moderate androgen insensitivity syndrome (AIS) resulting from AR dysfunction. Here, we used the yeast Saccharomyces cerevisiae to investigate the molecular mechanism behind AIS in KD. Upon expression in yeast, polyQ-expanded N-terminal fragments of AR lacking the hormone binding domain caused a polyQ length-dependent growth defect. Interestingly, while AR fragments with 67 Q formed large, SDS-resistant inclusions, the most pronounced toxicity was observed upon expression of 102 Q fragments which accumulated exclusively as soluble oligomers in the 100–600 kDa range. Analysis using a hormone-dependent luciferase reporter revealed that full-length polyQ-expanded AR is fully functional in transactivation, but becomes inactivated in the presence of the corresponding polyQ-expanded N-terminal fragment. Furthermore, the greatest impairment of AR activity was observed upon interaction of full-length AR with soluble AR fragments. Taken together, our results suggest that soluble polyQ-containing fragments bind to full-length AR and inactivate it, thus providing insight into the mechanism behind AIS in KD and possibly other polyglutamine diseases, such as Huntington's disease.
Role of tissue kallikrein-related peptidases in cervical mucus remodeling and host defense
Authors: Shaw Julie L.V. , Petraki Constantina , Watson Carole , Bocking Alan , Diamandis Eleftherios P.
Published: October 2008

Human tissue kallikrein-related peptidases (KLKs) are 15 hormonally regulated genes on chromosome 19q13.4 encoding secreted serine proteases. Many KLKs are expressed throughout the female reproductive system and found in cervico-vaginal fluid (CVF). Immunohistochemistry was performed to determine KLK localization in the female reproductive system (fallopian tube, endometrium, cervix and vagina tissues). KLK levels were measured in CVF and saliva over the menstrual cycle to study whether KLKs are regulated by hormonal changes during the cycle.In vitrocleavage analysis was performed to establish whether KLKs may play a role in vaginal epithelial desquamation, mucus remodeling or processing of antimicrobial proteins. KLKs were localized in the glandular epithelium of the fallopian tubes and endometrium, the cervical mucus-secreting epithelium and vaginal stratified squamous epithelium. KLK levels peaked in CVF and saliva after ovulation.In vitrocleavage analysis confirmed KLKs 5 and 12 as capable of digesting desmoglein and desmocollin adhesion proteins and cervical mucin proteins 4 and 5B. KLK5 can digest defensin-1α, suggesting it may aid in cervico-vaginal host defense. We provide evidence of potential physiological roles for KLKs in cervico-vaginal physiology: in desquamation of vaginal epithelial cells, remodeling of cervical mucus and processing of antimicrobial proteins.
Reduction of myocardial infarction by postischemic administration of the calpain inhibitor A-705253 in comparison to the Na+/H+exchange inhibitor Cariporide®in isolated perfused rabbit hearts
Authors: Neuhof Christiane , Fabiunke Verena , Speth Maria , Möller Achim , Fritz Hans , Tillmanns Harald , Neuhof Heinz , Erdogan Ali
Published: October 2008

The calpain inhibitor A-705253 and the Na+/H+-exchange inhibitor Cariporide®were studied in isolated perfused rabbit hearts subjected to 60 min occlusion of the ramus interventricularis of the left coronary artery (below the origin of the first diagonal branch), followed by 120 min of reperfusion. The inhibitors were added to the perfusion fluid solely or in combination at the beginning of reperfusion. Hemodynamic monitoring and biochemical analysis of perfusion fluid from the coronary outflow were performed. Myocardial infarct size and area at risk (transiently not perfused myocardium) were determined from left ventricular slices after a special staining procedure with Evans blue and 2,3,5-triphenyltetrazolium chloride. The infarcted area (dead myocardium) was 72.7±4.0% of the area at risk in untreated controls, but was significantly smaller in the presence of the inhibitors. The largest effect was observed with 10-6 M A-705253, which reduced the infarcted area to 49.2±4.1% of the area at risk, corresponding to a reduction of 33.6%. Cariporide®at 10-6 M reduced the infarct size to the same extent. The combination of both inhibitors, however, did not further improve cardioprotection. No significant difference was observed between the experimental groups in coronary perfusion, left ventricular pressure, heart rate, or in the release of lactate dehydrogenase and creatine kinase from heart muscle.
Rethinking low genus hyperelliptic Jacobian arithmetic over binary fields: interplay of field arithmetic and explicit formulæ
Authors: Avanzi R. , Thériault N. , Wang Z.
Published: October 2008

In this paper, we present several improvements on the best known explicit formulæ for hyperelliptic curves of genus three and four in characteristic two, including the issue of reducing memory requirements.

To show the effectiveness of these improvements and to allow a fair comparison of the curves of different genera, we implement all formulæ using a highly optimized software library for arithmetic in binary fields. This library was designed to minimize the impact of a whole series of overheads which have a larger significance as the genus of the curves increases. The current state of the art in attacks against the discrete logarithm problem is taken into account for the choice of the field and group sizes. Performance tests are done on two personal computers with very different architectures.

Our results can be shortly summarized as follows: Curves of genus three provide performance similar, or better, to that of curves of genus two, and these two types of curves can perform faster than elliptic curves – indeed on some processors often twice as fast. Curves of genus four attain a performance level comparable to elliptic curves. A large choice of curves is therefore available for the deployment of curve-based cryptography, with curves of genus three and four providing their own advantages as larger cofactors can be allowed for the group order.
Reaction of rhenium and carbon at high pressures and temperatures
Authors: Juarez-Arellano Erick A. , Winkler Björn , Friedrich Alexandra , Wilson Dan J. , Koch-Müller Monika , Knorr Karsten , Vogel Sven C. , Wall James J. , Reiche Helmut , Crichton Wilson , Ortega-Aviles Mayahuel , Avalos-Borja Miguel
Published: October 2008

A study of the reaction of rhenium with carbon at high-(P, T) conditions up to P
max = 67 GPa and T
max = 3800 K is presented. A hexagonal ReC
x
was identified as the stable phase at high-(P, T) conditions. A composition of ReC0.5 is proposed. No evidence for a cubic ReC polymorph with rocksalt structure, as suggested in the literature, or for any other phase was found at the P-T conditions explored. A preliminary P-T rhenium-carbon phase diagram has been derived and properties such as bulk moduli and elastic stiffness coefficients were obtained.
Electron density of a new EGFR Tyrokinase-inhibitor at 100 K, consideration of different models
Authors: Mebs Stefan , Lüth Anja , Löwe Wolfgang , Paulmann Carsten , Luger Peter
Published: October 2008

The electron density (ED) of a substituted 4-(indol-3-yl)-quinazoline, a newly developed anti-cancer drug, was determined from a high resolution X-ray data set measured at 100 K using synchrotron radiation. Because the structure contains a chlorine atom, which has a diffuse outer electron shell and is therefore beyond standard modeling, the influence of the model on the bond topological and atomic properties was studied following Bader's approach of ‘Atoms In Molecules’ (AIM). The expansion/contraction parameters κ and κ′ of the four atoms being constitutive for the Cl—C-bond and the F—C-bond were obtained by calculation of theoretical structure factors of a model compound and assigned in subsequent multipole refinements. The κ and κ′-values for all other non H-atoms atoms were taken from the literature. The effect of two different sets of κ and κ′ (1.20/1.20 and 1.13/1.29) for the hydrogen atoms was evaluated for the topological properties at bonds to hydrogen atoms (including hydrogen bonds) and to the atomic properties of the hydrogen atoms. Furthermore the effect of particular n

l
-sets for the chlorine atom to bond topological descriptors of the Cl—C-bond was investigated for the theoretical structure factors and compared with experiment. All results were compared with corresponding theoretical findings from a single point calculation at experimental geometry.
Solid state molecular assemblies of five bile acid derivatives
Authors: Bertolasi Valerio , Ferretti Valeria , Fantin Giancarlo , Fogagnolo Marco
Published: October 2008

The crystal structures of five bile acid derivatives are reported: 1: 6α,7α-Dihydroxy-5β-cholan-24-oic acid; 2: 3α,6α-Dihydroxy-5β-cholan-24-oic acid (Hyodeoxycholic acid); 3: 3α,7α,12α-Trihydroxy-5β-cholan-24-hydrazide hemihydrate; 4: 3-Dimethyl ketal,7,12-dioxo-5β-cholan-24-oic acid and 5: 3α,7α-Di-O-acetyl-12-oxo-5β-cholan-24-oic acid methyl ester. In all the structures the four saturated cycles, forming the common alicyclic steroidal skeleton, have the same conformation, while the flexible side chain adopts different conformations. Whereas all the crystal structures of Cholic Acid inclusion compounds are characterized by the formation of a bilayer-type structure with channels within the lipophilic layers, the chemical variations of the substituents on the cholanic framework induce remarkable changes in the H-bond scheme and in the crystal packing arrangements. For instance, the structures 1, 2, having a different number and position of the hydroxyl groups on the rigid skeleton, display a variety of supramolecular architectures dominated by networks of cooperative …O—H…O… H-bonds which do not produce typical molecular layers and channels of Cholic Acid inclusion compounds. Cholic hydrazide hemihydrate, 3, where both the hydrazide group and water molecule are strongly involved in the H-bond system, forms an overall structural motif similar to that observed in CA inclusion compounds containing hydrophilic and lipophilic layers and small channels. Compound 4, containing only the carboxylic OH group as H-bond donor, makes simple antiparallel chains of molecules, while compound 5, lacking of H-bond donors, forms a crystal aggregation dominated by weak C—H…O contacts and van der Waals interactions leading to a crystal packing where neither molecular layers nor channels are recognizable.
Ascending notions of Personhood in the Bhagavata Purana Dedicated to Professor Klaus K. Klostermaier on the occasion of his Seventy-fifth Anniversary
Authors: Theodor Ithamar
Published: October 2008

The paper looks at one of the main themes of the Bhagavata Purana, which is the theme of ascending notions of Divine Personhood; these sequential notions are arranged in hierarchical order, resembling a ladder. they evoke various emotional states, each more complex and more intense then the previous one, beginning with a state that evokes santa and culminating in a state that evokes srngara.
Why the Monks took no Delight in the Buddha’s Words
Authors: Gombrich Richard
Published: October 2008

Records of the Buddha’s sermons in the Pali Canon often end with a statement that the monks delighted in the Buddha’s words. However, the first sermon in one collection, the Majjhima Nikaya, says that they did not delight in them. though this reading is ancient, most modern editors have emended by removing the negative. this article argues that a careful study of the preceding text reveals why the negative is correct.
Interpretations of the Bhagavad-Gita and Images of the Hindu Tradition: The Song of the Lord, by Catherine A. Robinson
Authors: Johnson William John
Published: October 2008

Interpretations of the Bhagavad-Gita and Images of the Hindu Tradition: The Song of the Lord, by Catherine A. Robinson. Abingdon, Oxon and New York: Routledge, 2006. x + 192 pp., £85 (hb). ISBN 0-415-346711.
The Socially Involved Renunciate: Guru Nanak’s Discourse to the Nath Yogis, by Kamala Elizabeth Nayar and Jaswinder Singh Sandhu
Authors: Johnson Will
Published: October 2008

The Socially Involved Renunciate: Guru Nanak’s Discourse to the Nath Yogis, by Kamala Elizabeth Nayar and Jaswinder Singh Sandhu. Albany, NY: State University of New York Press, 2007. xvi + 181 pp., $60 (hb), $18.95 (pb). ISBN-13 978-0-7914-7213-2 (hb), ISBN-13 978-0-7914-7214-9 (pb; June 2008).
Fish Assemblages in a Western Iowa Stream Modified by Grade Control Structures
Authors: Litvan Mary E. , Pierce Clay L. , Stewart Timothy W. , Larson Chris J.
Published: October 2008

Over 400 riprap grade control structures (GCSs) have been built in streams of western Iowa to reduce erosion and protect bridges, roads, and farmland. In conjunction with a companion study evaluating fish passage over GCSs in Turkey Creek, we evaluated the differences in fish assemblage and habitat characteristics in reaches immediately downstream from GCSs (GCS sites) and reaches at least 1 km from any GCS (non-GCS sites). The GCS sites were characterized by greater proportions of pool habitat, maximum depths, fish biomass, and abundance of juvenile largemouth bass Micropterus salmoides than were non-GCS sites. Index of biotic integrity (IBI) scores were poor or fair (<43 on a 0–100 scale) and not significantly different between the GCS and non-GCS sites. Additionally, we investigated both the longitudinal changes in fish assemblages in this GCS-fragmented stream and the changes in fish assemblages after slope modifications of three GCSs to facilitate fish passage. Thirteen fish species were present throughout the study area, whereas another 15 species exhibited truncated distributions not extending to the most upstream sampling location. After modification of the GCSs, IBI scores increased at seven of nine sites (mean increase = 4.6 points). Also, channel catfish Ictalurus punctatus were detected 7.3 km upstream at sites where, 2 years before GCS modification, they had been absent from collections. Given the number and distribution of GCSs in western Iowa streams, understanding the effects of these structures is vital to the conservation and management of fish assemblages in this and other regions where GCSs or similar structures are used.
A Novel Approach for the Derivation of Putative Primordial Germ Cells and Sertoli Cells from Human Embryonic Stem Cells
Authors: Bucay Nathan , Yebra Mayra , Cirulli Vincenzo , Afrikanova Ivka , Kaido Thomas , Hayek Alberto , Montgomery Anthony M.P.
Published: October 2008

Using human embryonic stem cells (hESCs), we describe a novel method for the rapid derivation and enrichment of cells that are comparable to primordial germ cells (PGCs) and Sertoli cells. The methodology described is based on modest changes to the growth conditions commonly used to expand hESCs and does not require genetic manipulation or complex three-dimensional culture. Remarkably, we have determined that simply reducing the size of cultured ESC colonies and manipulating the number of feeding cycles, results in the rapid emergence of cells that are comparable to migratory PGCs. Importantly, these cells can be monitored and purified on the basis of the expression of the chemokine receptor CXCR4. Under more stringent differentiating conditions these cells mature and upregulate the expression of specific germ cell markers. Importantly, this process is accompanied by the development of Sertoli-like support cells. Such cells normally provide trophic support and immunoprotection to developing germ cells and may have significant clinical utility in the prevention of graft rejection. The putative Sertoli-germ cell cocultures generated in this study may ultimately be developed to study and manipulate interactions and processes involved in human gametogenesis.
Skeletal Muscle Differentiation of Embryonic Mesoangioblasts Requires Pax3 Activity
Authors: Messina Graziella , Sirabella Dario , Monteverde Stefania , Galvez Beatriz G. , Tonlorenzi Rossana , Schnapp Esther , De Angelis Luciana , Brunelli Silvia , Relaix Frederic , Buckingham Margaret , Cossu Giulio
Published: October 2008

Mesoangioblasts have been characterized as a population of vessel-associated stem cells able to differentiate into several mesodermal cell types, including skeletal muscle. Here, we report that the paired box transcription factor Pax3 plays a crucial role in directing mouse mesoangioblasts toward skeletal myogenesis in vitro and in vivo. Mesoangioblasts isolated from the aorta of Pax3 null embryos are severely impaired in skeletal muscle differentiation, whereas most other differentiation programs are not affected by the absence of Pax3. Moreover, Pax3−/− null mesoangioblasts failed to rescue the myopathic phenotype of the α-sarcoglycan mutant mouse. In contrast, mesoangioblasts from Pax3 gain of function, Pax3PAX3-FKHR/+, mice display enhanced myogenesis in vitro and are more efficient in regenerating new muscle fibers in this model of muscular dystrophy. These data demonstrate that Pax3 is required for the differentiation of mesoangioblast stem cells into skeletal muscle, in keeping with its role in orchestrating entry into the myogenic program.
FOXO3a: a novel player in thyroid carcinogenesis?
Authors: Karger Stefan , Weidinger Carl , Krause Kerstin , Sheu Sien-Yi , Aigner Thomas , Gimm Oliver , Schmid Kurt-Werner , Dralle Henning , Fuhrer Dagmar
Published: October 2008

The forkhead box transcription factor FOXO3a has recently been identified as central mediator of the cellular response to oxidative stress inducing cell cycle arrest or apoptosis. The aim of our study was to investigate the regulation of FOXO3a in the thyroid and to determine whether alterations in FOXO3a activity occur in thyroid carcinogenesis. In vitro, we demonstrate that FOXO3a activity is negatively regulated by the PI3K/Akt cascade promoting increased phosphorylation and cytoplasmatic accumulation of FOXO3a with decreased transcription of the target genes p27kip (CDKN1B) and Bim (BCL2L11), but increased expression of GADD45A. By contrast, we show that H2O2 exposure activates FOXO3a in thyrocytes with JNK (MAPK8)-mediated nuclear accumulation of FOXO3a and increased expression of the cell cycle arrest genes p27kip and GADD45A. In vivo, we observed a marked cytoplasmatic accumulation of FOXO3a in differentiated thyroid cancers versus an exclusive nuclear accumulation in follicular adenoma and normal thyroid tissue. Moreover, this cytosolic accumulation of FOXO3a correlated with an increased phospho-Akt expression in thyroid malignancies and was accompanied by decreased expression of the FOXO targets p27kip and Bim and an increase in GADD45A mRNA expression in the thyroid cancers. Our data suggest FOXO3a as a novel player of cellular stress response in the thyroid, mediating the thyrocyte's fate either to survive or to undergo apoptosis. Furthermore, PI3K-dependent FOXO3a inactivation may be a novel pathomechanism for the escape from apoptosis in thyroid cancer cells, in particular in follicular thyroid carcinoma.
Tunnelling and geotechnics: new horizons
Authors: Mair R. J.
Published: October 2008

New developments in both the theory and the practice of tunnelling are covered in the lecture. The important relationship between tunnelling and geotechnics is highlighted, and recent advances in research and practice are described, drawing on model studies, theoretical developments and field measurements from case histories from around the world. Simplified plasticity models are presented that can be used by designers to assess ground movements and tunnel lining loads in complex ground conditions. The important role of pilot tunnels and in situ measurements to validate such models, drawing on a case history from Bolu, Turkey, and on other tunnelling projects, is described. Recent technical advances in earth pressure balance tunnelling are considered, illustrated by measurements from the Channel Tunnel Rail Link project, with emphasis on key factors influencing volume loss, such as face pressure, soil conditioning and effective screw conveyor operation. A recent case history in Bologna is described, in which the innovative use of directional drilling to install curved grout tubes was employed for a compensation grouting project in granular soils. Time-dependent ground movements and tunnel lining distortions occurring after tunnelling are discussed, their magnitude depending on the relative permeability of the tunnel lining and soil, the degree of anisotropy of the soil permeability, and the initial pore pressure prior to tunnelling. The effects of tunnelling-induced settlements on pipelines are considered, drawing on centrifuge tests and analytical solutions, and a new design approach is presented, taking into account the reduction of soil stiffness with increasing shear strain as a result of tunnel volume loss. The lecture concludes with a description of a distributed strain sensing technique using fibre optic technology, based on Brillouin optical time domain reflectometry (BOTDR), and its innovative application to field monitoring of a masonry tunnel subjected to new tunnel construction beneath it.
Anisotropy of a shear zone
Authors: Comegna L. , Picarelli L.
Published: October 2008

The behaviour of landslides in clay is essentially governed by a shear zone located at the base of the soil mass. While some data regarding the shear zones of slides are available, information is rather poor about the shear zones of mudslides. The paper reports some results of investigations on the shear zone located at the base of a mudslide, showing the strong hydraulic and mechanical anisotropy of the material.
Reliability analysis of building serviceability problems caused by excavation
Authors: Schuster M. J. , Juang C. H. , Roth M. J. S. , Rosowsky D. V.
Published: October 2008

Based on previously developed evaluation criteria, a serviceability limit state is established for reliability analysis of building damage caused by excavation. The term damage is defined herein as the violation of serviceability requirements such as exceeding the threshold principal strain in the building. In this paper the model uncertainty or model bias, characterised by applying Bayesian mapping and reliability techniques, and its relationship to prior knowledge of damage potential (probability) are analysed. The concept of apparent model bias factor is introduced, and an iterative procedure is developed to tackle the issue of prior probability in the calibration of apparent model bias factor. Satisfactory results are obtained with the developed iterative procedure for estimating the probability of damage of buildings caused by excavation.
Designing marine protected area networks to address the impacts of climate change
Authors: McLeod Elizabeth , Salm Rodney , Green Alison , Almany Jeanine
Published: October 2008

Principles for designing marine protected area (MPA) networks that address social, economic, and biological criteria are well established in the scientific literature. Climate change represents a new and serious threat to marine ecosystems, but, to date, few studies have specifically considered how to design MPA networks to be resilient to this emerging threat. Here, we compile the best available information on MPA network design and supplement it with specific recommendations for building resilience into these networks. We provide guidance on size, spacing, shape, risk spreading (representation and replication), critical areas, connectivity, and maintaining ecosystem function to help MPA planners and managers design MPA networks that are more robust in the face of climate‐change impacts.