bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational investigation of the effect of up-armouring on the reduction in occupant injury or fatality in a prototypical high-mobility multi-purpose wheeled vehicle subjected to mine blast
Authors: Grujicic M , Arakere G , Bell W C , Haque I
Published: May 2009

A comprehensive finite-element-based computational investigation of the ability of different measures (e.g. up-armouring, seat cushion, or seat belt restraint system) to protect the occupant(s) of a prototypical high-mobility multi-purpose wheeled vehicle in the event of an anti-vehicle mine detonation under the vehicle's front right wheel is carried out. While assessing the effectiveness of these protective measures, different injury criteria had to be defined and/or employed, their values calculated (during the initial response stage of the blast event), and compared with the limiting values corresponding to the critical levels of injury. The efficacies are compared both when these measures are implemented in isolation and in the presence of other protective measures with respect to specific injuries.
Predicted performance of integrated power plants based on diesel engines and steam cycles fuelled with a rapeseed oil chain
Authors: Cocco D
Published: May 2009

This work focuses attention on the evaluation of global energy balances of an agro-energy system based on a diesel engine fuelled with rapeseed oil integrated with a steam plant fuelled with the residues of rape cultivation. The agro-energy system has been separated into the stages of in-the-field cultivation, transport of products to the industrial plant, and conversion into electric power. For each stage, inputs (fuels, electric power, fertilizers, and so on) and energy outputs (oil, electricity, residues, and by-products) are evaluated. Integration between the engine and the steam plant is implemented through thermal recovery of the engine exhaust gases and cooling fluids (supercharging air, lubricating oil, engine jacket cooling water) to preheat the boiler feed water.

The results of the study show that the recovery of thermal energy made available by the diesel engine leads to an increase in steam plant conversion efficiency of more than three per cent (from 25.1 per cent to 28.4 per cent). In other words, energy recovery leads to an equivalent efficiency of the engine over 56 per cent, which is more than nine points above the efficiency of the diesel engine alone. In addition to the sole use of vegetable oil for energy production, the use of straw makes it possible to double net energy production per unit of cultivated area. Implementation of this agro-energy chain provides a net energy production of 55–60 GJ/ha, an energy output—input ratio around 3.0–3.3, and a primary energy saving of about 65–70 per cent compared to the use of fossil fuels.
Hybrid-cooling, combined cooling, heating, and power systems
Authors: Fumo N , Mago P J , Chamra L M
Published: May 2009

Combined cooling, heating, and power (CCHP) systems have the ability to optimize fuel consumption by recovering thermal energy from the prime mover of the power generation unit (PGU). Design of a CCHP system requires consideration, among other variables, of CCHP system components size and type. This study focuses on the analysis of hybrid-cooling, heating, and power (hybrid-cooling CCHP) systems that have an absorption chiller (CH) and a vapour compression system to handle the cooling load. The effect of the size of both cooling mechanisms is analysed in conjunction with the PGU size and efficiency. For better energy performance analysis simulations, results are presented based on the building-CCHP system primary energy consumption (PEC). Hybrid-cooling CCHP systems yield higher primary energy reduction than CCHP systems with an absorption CH alone. To account for the effect of climate conditions, hot and cold climates were considered by performing simulations for Tampa and Chicago weather conditions. The results are presented in tabular form to show the value of the PEC reduction as a function of the PGU size and efficiency, and the size of the absorption CH.
In-stream tidal energy potential of Puget Sound, Washington
Authors: Polagye B , Kawase M , Malte P
Published: May 2009

The far-field, barotropic effects of in-stream tidal energy extraction from Puget Sound are quantified using a one-dimensional channel model. In-stream turbines are modelled in regions of energetic flow in northern Admiralty Inlet and Tacoma Narrows. The far-field extraction effects include changes to the tide (amplitude and phase), transport, power dissipation, and kinetic power density. These effects are observed throughout Puget Sound and are dependent on the magnitude and location of extraction. The model indicates that a 5 per cent reduction in transport in the South Sound would correspond to either 260 MW of dissipation by in-stream turbines in Admiralty Inlet, 120 MW in Tacoma Narrows, or an intermediate level of dissipation in both locations. The environmental and economic limits on future developments are discussed. For pilot-scale development, this modelling indicates that the barotropic, far-field extraction effects on Puget Sound will be immeasurably small.
Optimum mean power output of a point-absorber wave energy converter in irregular waves
Authors: McCabe A P , Aggidis G A
Published: May 2009

This article presents an assessment of the optimum mean power output of a point-absorber wave energy converter (PAWEC) in irregular wave climates. A first-order method is used to calculate the mean power spectrum of the device in waves of dissimilar spectra. JONSWAP spectra with different peak enhancement parameters are used to show the effect of energy concentration within the wave spectrum on the device mean power spectrum. A comparison of the optimum mean power output of a PAWEC in an irregular wave climate with that in an energy-equivalent regular wave climate is made to show the influence of the combination of wave spectrum and power output characteristics on the former. The principle is demonstrated by results obtained with the simulation of a PAWEC collector. An evaluation is made of the difference between the optimum mean power output of the device and the mean power output achieved using a simple, standard control method. The resulting difference in energy output with measured data from a possible site is also assessed. The implications of the results on the appraisal of device performance are considered.
Influence of Surface Energy and Roughness of Substrate on Thin Pentacene and C60 Films Prepared by Vacuum Deposition
Authors: Yan Hu , Uchida Takuya , Kagata Tsubasa , Iriyama Yu , Okuzaki Hidenori
Published: May 2009

Substrate surface roughness predominantly influenced grain size of pentacene in vacuum-deposited thin films while surface energy of the substrate did not, i.e., larger pentacene grain was obtained on a substrate with lower roughness instead of lower surface energy. On the other hand, grain size of C60 deposited in the same manner was influenced by both surface energy and roughness, i.e., large C60 grain was obtained on substrates with lower surface roughness and energy.
Review Paper: Implications of the “Cancer Stem Cell” Hypothesis on Murine Models of Colon Cancer and Colitis-associated Cancer
Authors: Hynes M. J. , Huang K. M. , Huang E. H.
Published: May 2009

The use of murine models to investigate human diseases has been an invaluable tool. In the areas of inflammation and oncogenesis, such models have provided unique insights into pathogenesis and mechanisms to evaluate potential therapy. As such, one facet of these disease processes links inflammation and cancer. Inflammation is associated with at least 15% of the world's malignancies. One example of this relationship is documented in the association between colitis and colorectal cancer. To date, the precise molecular events linking inflammation and cancer remain unclear. A new paradigm that may bridge these processes includes the cancer stem cell hypothesis. In this review, murine models of colitis, colon cancer, and colitis-associated cancer are discussed in reference to the potential of this paradigm to clarify the relationship of these devastating diseases.
A Retrospective Study of Eyelid Tumors from 43 Cats
Authors: Newkirk K. M. , Rohrbach B. W.
Published: May 2009

Submissions to the University of Tennessee pathology service from June 1999 to June 2008 were searched for feline cases of tumors involving the eyelids or nictitans. Forty-three tumors were identified. The average age at diagnosis was 10.4 years. Significantly more males than females had eyelid tumors. There were 12 squamous cell carcinomas (SCCs), 11 mast cell tumors (MCTs), 6 hemangiosarcomas (HSAs), 4 adenocarcinomas (ACAs), 3 peripheral nerve sheath tumors (PNSTs), 3 lymphomas, 3 apocrine hidrocystomas (AHCs), and 2 hemangiomas. Cats with MCTs were significantly younger than cats with all other tumor types combined. In contrast, cats with SCCs were significantly older than cats with other tumor types. The HSAs and SCCs were significantly more likely than other tumors to occur in nonpigmented areas. The MCTs, HSAs, AHCs, and hemangiomas did not recur after surgical excision. In contrast, the lymphomas, ACAs, SCCs, and PNSTs frequently recurred and/or resulted in death or euthanasia of the cat. The SCCs were significantly more likely to recur than the MCTs. The average survival time for cats with SCCs was 7.4 months. Although eyelid MCTs have been reported in cats, the prevalence in this study is much higher than previously described.
Immunohistochemical Expression of c-KIT Protein in Feline Soft Tissue Fibrosarcomas
Authors: Smith A. J. , Njaa B. L. , Lamm C. G.
Published: May 2009

C-KIT is the cellular homolog of the feline sarcoma viral oncogene v-KIT, which encodes the tyrosine kinase receptor protein KIT. Mutations and varied expression of this gene have been demonstrated within multiple neoplasms in people and domestic animals. The purpose of this study was to determine if KIT protein is expressed in feline soft tissue fibrosarcomas (ST FSA) using immunohistochemistry (IHC). The computer database at the Oklahoma Animal Disease Diagnostic Laboratory was searched from January 1, 2006, to December 31, 2007, for any domestic cat with an ST FSA. Routinely stained slides from 46 feline ST FSAs were reviewed and graded based on the scale outlined by Kuntz et al. Immunohistochemistry for KIT protein was performed on one representative section from each cat. There were a total of 12/46 (26%) cats that were immunoreactive for KIT. Immunoreactivity was detected in greater than 80% of the neoplastic cells in 4/46 (9%) cats. Immunoreactivity was detected in less than 10% of the neoplastic cells in 8/46 (17%) cats. Immunoreactivity was characterized by evenly distributed cytoplasmic stippling within the neoplastic spindle-shaped cells and/or multinucleated giant cells. Based on these results, KIT immunoreactivity can be detected within feline ST FSAs using IHC. The results of this study also indicate that KIT immunoreactivity in feline ST FSA does not correlate with the histologic grade ( P = .141, X 2 = 2.166), survivability ( P = .241, X 2 = 1.373), or whether the neoplasm was a spontaneous or an injection site FSA ( P = .074, X 2 = 3.184).
Expression of Tumor Invasion Factors Determines Systemic Engraftment and Induction of Humoral Hypercalcemia in a Mouse Model of Adult T-cell Leukemia
Authors: Parrula C. , Zimmerman B. , Nadella P. , Shu S. , Rosol T. , Fernandez S. , Lairmore M. , Niewiesk S.
Published: May 2009

Infection with human T-cell leukemia virus type 1 (HTLV-1) leads sometimes to the development of adult T-cell lymphoma/leukemia (ATL), which is invariably fatal and often associated with humoral hypercalcemia of malignancy. The transformation of infected CD4 T cells and the pathogenesis of leukemia have been studied with great limitation in tissue culture and patients. To better understand the pathogenesis and perform preclinical drug studies, animal models of ATL are urgently needed. In mice, inoculation of HTLV-1 cell lines mostly leads to development of localized lymphomas. To develop an ATL animal model with leukemic spread of ATL cells, mouse strains with different well-defined immune deficiencies were inoculated intraperitoneally with different HTLV-1infected cell lines (ACH.2, C8166, MT-2, MET-1). Inoculation of MET-1 cells into NOD/SCID mice provided the best model system for slowly developing T-cell leukemia with multiple organ involvement. In leukemic mice, an increase in serum calcium levels correlated with expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand on leukemic cells and secretion of parathyroid hormone-related protein and interleukin-6. In contrast to the other cell lines that did not spread systemically, MET-1 expressed both the adhesion molecules CDlla (LFA-lot) and CD49d (VLA-4ot) and produced or induced expression of matrix metalloproteinases 1, 2, 3, and 9, thus underlining the importance of these molecules in the spread of adult T-cell leukemia cells. The MET-1/NOD/SCID model will be useful for developing interventions against invasion and spread of leukemic cells and subsequent humoral hypercalcemia of malignancy.
Review Paper: Host-Pathogen Interactions in the Kidney during Chronic Leptospirosis
Authors: Monahan A. M. , Callanan J. J. , Nally J. E.
Published: May 2009

Pathogenic species of Leptospira cause leptospirosis, a global zoonotic disease. Leptospira colonize renal tubules of chronically infected maintenance hosts, from where they are shed in urine to the environment and survive in suitable moist conditions. Transmission of disease to new hosts is facilitated by contact with contaminated urine or water sources, because Leptospira can penetrate broken skin or mucosal surfaces of new hosts. Infection of new hosts may be asymptomatic, as with chronically infected maintenance hosts, or may result in an acute disease process in which clinical signs can include fever, jaundice, renal failure, and pulmonary hemorrhage. Those factors that determine if an animal will suffer an acute or a chronic infection are not fully understood but include host animal species, infecting serovar, and infecting dose. During chronic infection, renal colonization and leptospiruria persist despite cellular and humoral responses by the host. Tubulointerstitial nephritis is the most common lesion associated with chronic infection, and this may progress to fibrosis and subsequent renal failure. This review aims to address how Leptospira cause tubulointerstitial nephritis during chronic leptospirosis and to summarize the mechanisms by which Leptospira might evade host immune responses during chronic colonization of the renal tubule.
Immunohistochemical Evaluation of GATA-4 in Canine Testicular Tumors
Authors: Ramos-Vara J. A. , Miller M. A.
Published: May 2009

GATA-4 is a transcription factor expressed in Sertoli cells and less commonly in Leydig (interstitial) cells but not germ cells in adult human beings, cattle, pigs, and mice. We examined GATA-4 in 76 formalin-fixed, paraffin-embedded canine testicular tumors, including 21 Sertoli cell tumors (SCT), 28 Leydig (interstitial) cell tumors (LCT), 24 seminomas (GCT), and 3 mixed germ cell sex cord-stromal tumors (MGSCT). Our hypothesis was that immunohistochemistry for GATA-4 could discriminate between germ cell and sex cord-stromal tumors of the canine testis. SCTs (21/21) had strong diffuse nuclear and weak and inconsistent cytoplasmic staining. LCTs (27/28) also had strong diffuse nuclear staining and much weaker and granular cytoplasmic staining. GCTs were negative for this marker. Sex cord-stromal cells of MGSCT were also positive. These results indicate that GATA-4 is mainly expressed in sex cord-stromal tumors and not in germ cell tumors of the canine testis.
Detection of Group C Rotavirus in Juvenile Ferrets (Mustela putorius furo) with Diarrhea by Reverse Transcription Polymerase Chain Reaction: Sequencing and Analysis of the Complete Coding Region of the VP6 Gene
Authors: Wise A. G. , Smedley R. C. , Kiupel M. , Maes R. K.
Published: May 2009

Nine juvenile ferrets ( Mustela putorius furo) with a history of diarrhea were severely dehydrated and had distended abdomens and thin-walled small intestines that contained gas and fluid. Histologically, small intestines exhibited acute superficial atrophic enteritis. Transmission electron microscopy of the small intestine showed rotavirus-like particles within apical vacuoles. Reverse transcription polymerase chain reaction (RT-PCR) was negative for group A rotavirus. A group C rotavirus-specific RT-PCR assay was developed using consensus primers designed from the alignment of VP6 gene sequences of porcine, bovine, and human strains. A 182-bp product of the VP6 gene was sequenced and showed significant similarity to group C rotavirus VP6 sequences. This strain was designated “Ferret Rota C-MSU.” The entire coding sequence of VP6 was determined and compared with other rotaviruses. Ferret Rota C-MSU virus was found to be most closely related to Shintoku group C rotavirus. This is the first definitive identification of a group C rotavirus in ferrets, based upon RT-PCR, sequencing, and genetic analysis.
DVD Reviews
Authors: Spring Katherine , von Logue Newth Tom
Published: May 2009

Distant Voices, Still Lives, (1988) UK Director Terence Davies Screenplay Terence Davies Producer Jennifer Howarth, Colin MacCabe Cinematography William Diver, Patrick Duval Editor William Diver Production Design Jocelyn James,
Miki Van Zwanenberg Art Direction Miki Van Zwanenberg, Jocelyn James Costume Design Monica Howe Make-up Lesley Rouvray Sound Alex Mackie, Aad Wirtz Camera Operator Harriet Cox Title Designer Richard Morrison With Freda Dowie (Mother), Pete Postlethwaite
(Father), Angela Walsh (Eileen), Dean Williams (Tony), Lorraine Ashbourne (Maisie), Sally Davies (Eileen as a child), Nathan Walsh (Tony as a child), Susan Flanagan (Maisie as a child), Michael Starke (Dave), Vincent Maguire (George), Antonia Mallen (Rose), Debi Jones (Micky), Chris Darwin
(Red), Marie Jelliman (Jingles), Andrew Schofield (Les) Production Companies British Film Institute, Channel Four Films Runtime 80 minutes DVD UK, 2007 Distributed by BFI Video (region 2, PAL) Aspect Ratio 1.78:1 Sound Mix Dolby Digital 2.0 English Extras
English subtitles. Full-feature commentary by Terence Davies. Filmed interviews with Terence Davies, Miki van Zwanenberg. Original trailer. 20-page illustrated booklet including film stills, storyboard frames, essays by Beryl Bainbridge and Adrian Danks, and an original review by Adam Barker
for Monthly Film Bulletin. DVD Producer Caroline Millar Technical Production James White Production Manager Marianthi Makra

A Cottage On Dartmoor (1929) UK, black and white, silent with music Director Anthony Asquith Based on the story
by Herbert C. Price Producer Bruce H. Woolfe Director of photography Stanley Rodwell, Axel Lindblom Art Direction Ian Campbell-Gray, Arthur Woods with Uno Henning, Norah Baring, Hans Schlettow Runtime 84 minutes DVD UK (2008) Produced and Distributed by
BFI (Region 2) Aspect Ratio 1.33:1 OAR Sound Mix Dolby Digital 2.0 stereo Extras Correct frame rate of 22fps. New musical accompaniment composed and performed by Stephen Horne. Insight, onset study of Asquith (Lee, UK, 1960, 15m). Rush Hour (Asquith, UK,
1941, 6m). Illustrated booklet with original press photographs and new essays by Geoffrey Macnab and Briony Dixon.
Unsuccessful alterity? The pursuit of otherness in Nina Bouraoui's autobiographical writing
Authors: Vassallo Helen
Published: May 2009

This article examines Nina Bouraoui's three autobiographical texts (Garon Manqu, 2000; Poupe Bella, 2004; Mes Mauvaises Penses, 2005), and the semi-autobiographical La Vie Heureuse (2002). It argues that despite an apparent desire to affirm and assert her
alterity, Bouraoui frequently falls prey to the trappings of homogenous notions of sexual and cultural identity that she purports to subvert. By using two seminal texts which aim to expose and deconstruct such binary paradigms, Frantz Fanon's Peau Noire, Masques Blancs (1952) and Simone
de Beauvoir's Le Deuxime Sexe (1949), the analysis suggests that in the first two of her autobiographical narratives Bouraoui often conforms to outmoded tropes of racial and sexual collusion with the norm and that, while initially appearing to carve out a new post-colonial identity,
she frequently confirms existing stereotypes of racial and sexual otherness and/or inferiority complexes. The article then proposes that it is only in Mes Mauvaises Penses that Bouraoui begins to reclaim her sexual and cultural identity in the negotiation of a new alterity.
Community, identity and the dynamics of borders in Yasmina Yahiaoui's Rue des Figuiers (2005) and Karin Albou's La Petite Jrusalem (2006)
Authors: Tarr Carrie
Published: May 2009

In the context of Republican universalism, the perceived communitarianism of diasporic postcolonial communities in France is considered a threat to the unity and cohesion of the nation. Most films by minority film-makers stress their protagonists' hybrid identity and aspirations towards
a form of integration which would recognize the multicultural nature of contemporary postcolonial French society. However, two recent films by minority women film-makers, Yasmina Yahiaoui's Rue des Figuiers and Karin Albou's La Petite Jrusalem, focus on the representation of
particular, bounded, postcolonial communities in France, one of Arab/Berber Maghrebi origin, the other of Jewish Maghrebi (and other) origin. This article contrasts the films' representations of the various physical and mental, real and imagined borders which delimit the lives of the inhabitants
of these communities, particularly those of the female protagonists, and investigates the extent to which they promote or assuage majority fears about the alterity of its citizens from postcolonial minorities. It suggests that, whereas the young women in La Petite Jrusalem can only
negotiate their identities by either accepting or completely abandoning their family and community, the women in Rue des Figuiers are able to negotiate new gender roles and identities within the diasporic Maghrebi community itself. Yet this situation is only possible because the community
is constructed as a secular rather than a religious community, indicating that there are still limits to the way in which the postcolonial immigrant community can be represented in French cinema.
Unpacking the discursive and social links in BBC, CNN and Al-Jazeera's Middle East reporting
Authors: Barkho Leon
Published: May 2009

To understand the language of journalism in relation to the moments of why and how news is differently structured and patterned, English online stories tackling the IsraeliPalestinian conflict, issued by the BBC, CNN and Al-Jazeera, were critically analysed following Fowler and Fairclough's
seminal texts. The results of the findings were discussed in interviews with the editors of the three international networks in order to see what links these linguistic features have with the interviewees' social assumptions, ideologies and economic conditions. The article finds first that
the discourse within the news pyramid is composed of four major layers: quoting, paraphrasing, background and comment. Second, it demonstrates that there are marked differences in the discourse structures and layers that the three networks employ in the production of the news stories they
issue in English. Third, Al-Jazeera English exhibits marked differences in the discursive features and their social implications at the four layers of discourse to report the conflict when compared with both the BBC and CNN. Fourth, the article shows that the differences in linguistic patterns
largely reflect and respond to each network's social and political assumptions and practices as well as economic conditions.
The US media, Camp David and the Oslo peace process
Authors: Piner Andrew
Published: May 2009

This article examines US mainstream press coverage given to the aftermath of the Camp David negotiations in July 2000, offering a critical perspective on the events and reactions to the failed summit. In doing so the article is able to identify and highlight the detrimental effects of inaccurate reporting of the IsraeliPalestinian conflict in the US press. It demonstrates how this misrepresentation of failure at Camp David has contributed to the ever-decreasing prospects for a just and viable solution to the conflict. This important snapshot of the long-standing IsraeliPalestinian conflict, it argues, accurately encapsulates the flawed nature of many dominant truths of the debate over the conflict. Consequently it can provide a critical lens through which to draw broader conclusions about the issues that continue to impede and undermine the prospects for balanced negotiations and peace in the region.

The conclusions reached through the analysis of mainstream US press reactions to the Camp David summit are subsequently contextualized through an exploration of the largely neglected issue of water sharing in the Palestinian Territories. The celebrated water-sharing agreements in the Oslo period are shown to have failed to bring about any meaningful change from the discriminatory water-distribution policies pursued by Israel in the occupied territories between 1967 and 1993.

The article thus demonstrates how US mainstream press reactions to the failed Camp David summit simply reinforced the misleading impression of Israeli cooperation and compromise which masks a historically grounded policy of domination over the Palestinians. It concludes that only an approach grounded in critical theory, emphasizing different conceptions of security in the region, can offer its people a brighter and more peaceful future.
Book Reviews
Authors: Allison Olivia , Syed Shabana
Published: May 2009

New Media and the New Middle East, Philip Seib (ed.), (2007) New York: Palgrave Macmillan, 284 pp., Hardcover, ISBNs: 1403979731, 978-1403979735, Price: 42.50.

Reading the Mohammed Cartoons Controversy: An International Analysis of Press Discourses on Free Speech
and Political Spin, Risto Kunelius, Elizabeth Eide, Oliver Hahn and Roland Schroeder (eds.), (2007) Germany: Projektverlag, 218 pp., (pbk), ISBN: 978-3-89733-167-9, Price: 35
A study of Egyptian and American young adult parasocial relationships with music video personae
Authors: Auter Philip J , Ashton Erica , Soliman Mohamed R
Published: May 2009

Approximately 360 undergraduate students in the U.S. and Egypt were surveyed regarding their consumption of music videos, affinity for them, and perception of them as reality. Respondent's parasocial interaction with their favorite music video performers was also assessed. Results showed that Egyptian young adults consume significantly greater amounts of music videos than their American counterparts. A similar effect was noted with Muslims versus Christians. Furthermore, Egyptian students scored significantly higher on all other measures than their U.S. counterparts. Affinity was positively correlated with perceptions of reality, and consumption. PSI showed positive correlations with consumption on overall PSI, and subsets of identification with the favorite persona and interest in favorite persona. Limited correlations were also evident between PSI and affinity on overall PSI, and subsets of problem solving abilities, group identification and interaction, and identification with favorite persona. Implications and suggestions for future research are discussed.
Regulative interactions of the osmosensing C-terminal domain in the trimeric glycine betaine transporter BetP from Corynebacterium
glutamicum
Authors: Krämer Reinhard , Ziegler Christine
Published: May 2009

Activation of the osmoregulated trimeric betaine transporter BetP from Corynebacterium glutamicum was shown to depend mainly on the correct folding and integrity of its 55 amino acid long, partly α-helical C-terminal domain. Reorientation of the three C-terminal domains in the BetP trimer indicates different lipid-protein and protein-protein interactions of the C-terminal domain during osmoregulation. A regulation mechanism is suggested where this domain switches the transporter from the inactive to the active state. Interpretation of recently obtained electron and X-ray crystallography data of BetP led to a structure-function based model of C-terminal molecular switching involved in osmoregulation.
The peptide-loading complex – antigen translocation and MHC class I loading
Authors: Schölz Christian , Tampé Robert
Published: May 2009

A large and dynamic membrane-associated machinery orchestrates the translocation of antigenic peptides into the endoplasmic reticulum (ER) lumen for subsequent loading onto major histocompatibility complex (MHC) class I molecules. The peptide-loading complex ensures that only high-affinity peptides, which guarantee long-term stability of MHC I complexes, are presented to T-lymphocytes. Adaptive immunity is dependent on surface display of the cellular proteome in the form of protein fragments, thus allowing efficient recognition of infected or malignant transformed cells. In this review, we summarize recent findings of antigen translocation by the transporter associated with antigen processing and loading of MHC class I molecules in the ER, focusing on the mechanisms involved in this process.
Tumor-associated MUC1 glycopeptide epitopes are not subject to self-tolerance and improve responses to MUC1 peptide epitopes in MUC1 transgenic mice
Authors: Ryan Sean O. , Vlad Anda M. , Islam Kazi , Gariépy Jean , Finn Olivera J.
Published: May 2009

Human adenocarcinomas overexpress a hypoglycosylated, tumor-associated form of the mucin-like glycoprotein MUC1 containing abnormal mono- and disaccharide antigens, such as Tn, sialyl-Tn, and TF, as well as stretches of unglycosylated protein backbone in the variable number of tandem repeats (VNTR) region. Both peptide and glycopeptide epitopes generated from the VNTR are candidates for cancer vaccines and we performed experiments to evaluate their relative potential to elicit tumor-MUC1-specific immunity. We show here that immunization with the 100 amino acid-long VNTR peptide (MUC1p) elicits weaker responses in MUC1 transgenic mice compared to wild type mice suggesting self-tolerance. In contrast, when glycosylated with tumor-associated Tn antigen (GalNAc-O-S/T), TnMUC1 induces glycopeptide-specific T cell and antibody responses in both strains of mice and helps enhance responses to MUC1p in MUC1 transgenic mice. Using newly derived MUC1-specific mouse T cell hybridomas we show that the only antigen-presenting cells able to cross-present TnMUC1 glycopeptide are dendritic cells (DCs). This is likely due to their exclusive expression of receptors capable of binding TnMUC1. We conclude that MUC1 glycopeptides induce stronger immunity in MUC1-Tg mice because they are recognized as `foreign' rather than `self' and because they are cross-presented preferentially by DCs.
Carbohydrate microarrays: key developments in glycobiology
Authors: Liu Yan , Palma Angelina S. , Feizi Ten
Published: May 2009

Carbohydrate chains of glycoproteins, glycolipids, proteoglycans, and polysaccharides mediate processes of biological and medical importance through their interactions with complementary proteins. The unraveling of these interactions is therefore a priority in biomedical sciences. Carbohydrate microarray technology is a new development at the frontier of glycomics that is revolutionizing the study of carbohydrate-protein interactions and the elucidation of their specificities in endogenous biological processes, microbe-host interactions, and immune defense mechanisms. In this review, we briefly refer to the principles of numerous platforms since the introduction of carbohydrate microarrays in 2002, and we highlight platforms that are beyond proof-of-concept and have provided new biological information.
From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans
Authors: André Sabine , Kožár Tibor , Kojima Shuji , Unverzagt Carlo , Gabius Hans-Joachim
Published: May 2009

Glycan epitopes of cellular glycoconjugates act as versatile biochemical signals (sugar coding). Here, we test the hypothesis that the common N-glycan modifications by core fucosylation and introduction of the bisecting N-acetylglucosamine moiety have long-range effects with functional consequences. Molecular dynamics simulations indicate a shift in conformational equilibria between linear extension or backfolding of the glycan antennae upon substitution. We also present a new fingerprint-like mode of presentation for this multi-parameter system. In order to delineate definite structure-function relationships, we strategically combined chemoenzymatic synthesis with bioassaying cell binding and the distribution of radioiodinated neoglycoproteins in vivo. Of clinical relevance, tailoring the core region affects serum clearance markedly, e.g., prolonging circulation time for the neoglycoprotein presenting the N-glycan with both substitutions. α2,3-Sialylation is another means toward this end, similarly seen for type II branching in triantennary N-glycans. This discovery signifies that rational glycoengineering along the given lines is an attractive perspective to optimize pharmacokinetic behavior of glycosylated pharmaproteins. Of general importance for the concept of the sugar code, the presented results teach the fundamental lesson that N-glycan core substitutions convey distinct characteristics to the concerned oligosaccharide relevant for cis and trans biorecognition processes. These modifications are thus molecular switches.
Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis
Authors: Reinke Stefan O. , Lehmer Gerhard , Hinderlich Stephan , Reutter Werner
Published: May 2009

The key enzyme for the biosynthesis of N-acetylneuraminic acid, from which all other sialic acids are formed, is the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). GNE is a highly conserved protein found throughout the animal kingdom. Its highest expression is seen in the liver and placenta. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac, which is defect in the human disease sialuria. GNE knock-out in mice leads to embryonic lethality, emphasizing the crucial role of this key enzyme for sialic acid biosynthesis. The metabolic capacity to synthesize sialic acid and CMP-sialic acid upon ManNAc loads is amazingly high. An additional characteristic of GNE is its interaction with proteins involved in the regulation of development, which might play a crucial role in the hereditary inclusion body myopathy. Due to the importance of increased concentrations of tumor-surface sialic acid, first attempts to find inhibitors of GNE have been successful.
Protein-lipid interactions: paparazzi hunting for snap-shots
Authors: Haberkant Per , van Meer Gerrit
Published: May 2009

Photoactivatable groups meeting the criterion of minimal perturbance allow the investigation of interactions in biological samples. Here, we review the application of photoactivatable groups in lipids enabling the study of protein-lipid interactions in (biological) membranes. The chemistry of various photoactivatable groups is summarized and the specificity of the interactions detected is discussed. The recent introduction of ‘click chemistry’ in photocrosslinking of membrane proteins by photo-activatable lipids opens new possibilities for the analysis of crosslinked products and will help to close the gap between proteomics and lipidomics.
Glycosylation pattern of brush border-associated glycoproteins in enterocyte-like cells: involvement of complex-type N-glycans in apical trafficking
Authors: Morelle Willy , Stechly Laurence , André Sabine , Seuningen Isabelle Van , Porchet Nicole , Gabius Hans-Joachim , Michalski Jean-Claude , Huet Guillemette
Published: May 2009

We have previously reported that galectin-4, a tandem repeat-type galectin, regulates the raft-dependent delivery of glycoproteins to the apical brush border membrane of enterocyte-like HT-29 cells. N-Acetyllactos-amine-containing glycans, known as galectin ligands, were found enriched in detergent-resistant membranes. Here, we analyzed the potential contribution of N- and/or O-glycans in this mechanism. Structural studies were carried out on the brush border membrane-enriched fraction using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and nano-ESI-QTOF-MS/MS. The pattern of N-glycans was very heterogeneous, with the presence of high mannose- and hybrid-type glycans as well as a multitude of complex-type glycans. In contrast, the pattern of O-glycans was very simple with the presence of two major core type 1 O-glycans, sialylated and bisialylated T-antigen structures [Neu5Acα2–3Galβ1–3GalNAc-ol and Neu5Acα2– 3Galβ1–3(Neu5Acα2–6)GalNAc-ol]. Thus, N-glycans rather than O-glycans contain the N-acetyllactosamine recognition signals for the lipid raft-based galectin-4-dependent apical delivery. In the presence of 1-deoxymannojirimycin, a drug which inhibits the generation of hybrid-type or complex type N-glycans, the extensively O-glycosylated mucin-like MUC1 glycoprotein was not delivered to the apical brush border but accumulated inside the cells. Altogether, our data demonstrate the crucial role of complex N-glycans in the galectin-4-dependent delivery of glycoproteins to the apical brush border membrane of enterocytic HT-29 cells.
Impact of glycosylation and detergent-resistant membranes on the function of intestinal sucrase-isomaltase
Authors: Wetzel Gabi , Heine Martin , Rohwedder Arndt , Naim Hassan Y.
Published: May 2009

Sucrase-isomaltase (SI) is a highly N- and O-glycosylated intestinal brush border membrane protein. SI is sorted with high fidelity to the apical membrane via O-linked glycans that mediate its association with lipid rafts or detergent-resistant membranes (DRMs). Here, we show that N- and O-glycosylation and DRMs are implicated in the regulation of the function of SI in intestinal Caco-2 cells. The activities of sucrase (SUC) and isomaltase (IM) increase substantially in DRMs when N- and O-glycosylation patterns are intact. Disruption of DRMs by solubilization with Triton X-100 at 37°C substantially reduces the activities of SUC and IM. Furthermore, modulation of O-glycosylation by benzyl-2-acetamido-2-deoxy-α-d-galactopyranoside and N-glycosylation by deoxymannojirimycin is linked to a decreased capacity of SI to associate with DRMs, with a subsequent reduction of the enzymatic activities of SUC and IM. This is the first report that reveals a direct role of N- and O-glycans in association with DRMs in regulating the function of a membrane glycoprotein.
Solubility of plutonium in MgCl2 and CaCl2 solutions in contact with metallic iron
Authors: Altmaier Marcus , Neck Volker , Lützenkirchen J. , Fanghänel Thomas
Published: May 2009

The solubility of Pu(IV) hydrous oxide is studied at 22±2 °C under Ar atmosphere in 0.25 and 3.5 M MgCl2 (pHc≈9) and 3.5 M CaCl2 (pHc=11–12) solutions in contact with iron powder. In alkaline 3.5–4.0 M CaCl2 ternary Ca-Pu-OH complexes are formed and the solubility of PuO2·xH2O(s) increases from about 10-10 M at pHc=11 to 10-8–10-7 M at pHc=12, both in the presence and absence of Fe powder. In the presence of iron the aqueous speciation is dominated by Pu(III) at pHc<10 and by Pu(IV) complexes at pHc>10. In the absence of reducing agents the aqueous speciation is dominated by Pu(V), with significant contributions of Pu(IV) complexes at pHc>10. The effect of ternary Ca-Pu(III,IV,V)-OH complexes in alkaline CaCl2 solutions can be described by assuming complex stoichiometries and experimental data from the oxidation state analogs Cm(III)/Nd(III), Th(IV) and Np(V). The ion interaction Pitzer approach is used for model calculations.
Redox equilibria of Pu4+/Pu3+ and PuO2
2+/Pu4+ couples in molten NaCl-CsCl eutectic as measured by absorption spectrophotometry
Authors: Nagai Takayuki , Uehara Akihiro , Fujii Toshiyuki , Shirai Osamu , Myochin Munetaka , Yamana Hajimu
Published: May 2009

In order to enhance the understanding of redox reactions of plutonium ions in molten NaCl-CsCl eutectic, absorption spectrophotometry was performed for Pu3+, Pu4+, and PuO2
2+ in molten NaCl-CsCl at 923 K by controlling the flow-rate ratio of Cl2 and Ar or O2 in the ventilating mixture gas. Based upon the relations of the measured rest potentials to the concentration ratios of [Pu4+]/[Pu3+] and [PuO2
2+]/[Pu4+], the redox potentials of Pu4+/Pu3+ and PuO2
2+/Pu4+ couples in molten NaCl-CsCl eutectic at 923 K were estimated.
Effect of oxide ions on separation factors of actinides from lanthanides in reductive extraction
Authors: Moriyama Hirotake , Moritani K. , Toda T. , Hayashi H.
Published: May 2009

The distribution coefficients of Am, Ce, and Eu between the salt and metal phases were measured at 1073 K in a reductive extraction system of equimolar NaCl-KCl melt and liquid Ga. By changing the solute concentrations, it was observed that the distribution coefficients were dependent on the oxide ion concentration in the system, possibly due to the formation of such compounds as AmO+. In addition, the mass balance of Am was possibly affected by the formation and precipitation of its oxychlorides and/or oxides in some runs. Taking these observations into consideration, the separation factor between Am and Ce was found to be around 30 in the present system.
Plutonium in the environment: key factors related to impact assessment in case of an accidental atmospheric release
Authors: Guétat Philippe , Moulin Valérie , Reiller Pascal E. , Vercouter T. , Bion Lionel , Fritsch P. , Monfort M. , Flüry-Herard A. , Comte A. , Menetrier F. , Ansoborlo Eric , et al.
Published: May 2009

This paper deals with plutonium and key factors related to impact assessment. It is based on recent work performed by CEA which summarize the main features of plutonium behaviour from sources inside installations to the environment and man, and to report current knowledge on the different parameters used in models for environmental and radiological impact assessment. These key factors are illustrated through a case study based on an accidental atmospheric release of Pu in a nuclear facility.
The King's Two Buckets: Kantorowicz, Richard II, and Fiscal Trauerspiel
Authors: Halpern Richard
Published: May 2009

The King's Two Bodies critiques Carl Schmitt's version of political theology by way of form as well as content. Shakespeare's Richard II provides a formal model (Trauerspiel) that allows Kantorowicz to carry out this project.
Political Theology and Fiction in The King's Two Bodies
Authors: Kahn Victoria
Published: May 2009

This essay argues that Ernst Kantorowicz's The King's Two Bodies is intended as a contribution to twentieth-century debates about political theology and that modern students of political theology can learn from Kantorowicz's association of political theology with legal fiction.
Abnormalities of cAMP signaling are present in adrenocortical lesions associated with ACTH-independent Cushing syndrome despite the absence of mutations in known genes
Authors: Bimpaki Eirini I , Nesterova Maria , Stratakis Constantine A
Published: May 2009

Context

Bilateral adrenal hyperplasias (BAHs) may be caused by mutations of genes that code for molecules that participate in cAMP signaling. Little is known about cAMP signaling in adrenal lesions associated with ACTH-independent Cushing syndrome (AICS) that do not harbor mutations in known genes.

Objective

We assessed the cAMP-signaling pathway by enzymatic and molecular studies.

Design

Samples from 27 patients (ages 5–60 years) were studied and compared with normal adrenocortical tissue (n=4) and aldosterone-producing adenomas (APA, n=5). All samples were sequenced for GNAS, PRKAR1A, PDE11A, and PDE8B sequencing defects. cAMP levels and binding, protein kinase A, and phosphodiesterase (PDE) activities were assayed. Immunohistochemistry was used for certain studies and the phosphorylation status of CREB was studied.

Patients

A total of 36 samples from patients were used.

Results

Cortisol-producing adenomas (CPAs) and other lesions that were GNAS, PRKAR1A, PDE11A, and PDE8B gene mutation-negative were compared with PRKAR1A mutation-positive lesions, normal tissue, and APAs; abnormalities of the cAMP-signaling pathway were found in both BAHs and CPAs. Interestingly, mutation-negative CPAs had significantly decreased PDE activity.

Conclusion

Lesions of the adrenal associated with AICS, independently of their GNAS, PRKAR1A, PDE11A, and PDE8B mutation status, have functional abnormalities of cAMP signaling. It is probable that epigenetic events or additional defects of genes involved in this pathway are responsible for this phenomenon.
Evaluation of insulin sensitivity with a new lipid-based index in non-diabetic postmenopausal overweight and obese women before and after a weight loss intervention
Authors: Antuna-Puente Barbara , Disse Emmanuel , Faraj May , Lavoie Marie-Eve , Laville Martine , Rabasa-Lhoret Rémi , Bastard Jean-Philippe
Published: May 2009

Objective

To evaluate the validity of a new lipid-based index (Disse index) in assessing insulin sensitivity (IS) compared with the hyperinsulinemic-euglycemic (HIEG) clamp in overweight and obese, non-diabetic, postmenopausal women, before and after a weight loss intervention.

Research design and methods

Association between Disse index and the HIEG clamp was evaluated in 86 non-diabetic postmenopausal overweight and obese women before and after weight loss. Percentage changes (%Δ) were calculated for several fasting indices and compared with %Δ of HIEG clamp.

Results

We observed a strong correlation between Disse index and HIEG clamp (r=0.69, P<0.001). This association was higher than those of homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), and McAuley indices while no significant difference was observed with Revised-QUICKI. Percent change of Disse index (pre- versus post-weight loss program) was significantly correlated with %Δ of HIEG clamp (r=0.34, P<0.01). This correlation was similar to those observed for the other indices tested.

Conclusions

We validated the reliability of Disse index in assessing IS in non-diabetic post-menopausal overweight and obese women, before and after weight loss intervention. Disse index may be useful not only for insulin resistant diagnostics in this type of population, but also for the IS follow-up after a weight-loss program and weight stabilization. The presence of lipid elements in this fasting index improves the estimation of IS in overweight and obese non-diabetic post-menopausal women and could add more information about peripheral IS.