bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure-Function Approach Identifies a COOH-Terminal Domain That Mediates Heparanase Signaling
Authors: Fux Liat , Feibish Nir , Cohen-Kaplan Victoria , Gingis-Velitski Svetlana , Feld Sari , Geffen Chen , Vlodavsky Israel , Ilan Neta
Published: February 2009

Heparanase is an endo-β-d-glucuronidase capable of cleaving heparan sulfate, activity that is strongly implicated in cellular invasion associated with tumor metastasis, angiogenesis, and inflammation. In addition, heparanase was noted to exert biological functions apparently independent of its enzymatic activity, enhancing the phosphorylation of selected protein kinases and inducing gene transcription. A predicted three-dimensional structure of constitutively active heparanase clearly delineates a TIM-barrel fold previously anticipated for the enzyme. Interestingly, the model also revealed the existence of a COOH-terminal domain (C-domain) that apparently is not an integral part of the TIM-barrel fold. We provide evidence that the C-domain is critical for heparanase enzymatic activity and secretion. Moreover, the C-domain was found to mediate nonenzymatic functions of heparanase, facilitating Akt phosphorylation, cell proliferation, and tumor xenograft progression. These findings support the notion that heparanase exerts enzymatic activity-independent functions, and identify, for the first time, a protein domain responsible for heparanase-mediated signaling. Inhibitors directed against the C-domain, combined with inhibitors of heparanase enzymatic activity, are expected to neutralize heparanase functions and to profoundly affect tumor growth, angiogenesis, and metastasis. [Cancer Res 2009;69(5):1758–67]
Rat Umbilical Cord Stem Cells Completely Abolish Rat Mammary Carcinomas with No Evidence of Metastasis or Recurrence 100 Days Post–Tumor Cell Inoculation
Authors: Ganta Chanran , Chiyo Doi , Ayuzawa Rie , Rachakatla Rajashekar , Pyle Marla , Andrews Gordon , Weiss Mark , Tamura Masaaki , Troyer Deryl
Published: February 2009

Genetically engineered stem cells efficiently deliver therapeutic proteins to cancer and other sites of inflammation. However, a major advantage would be realized if tumor-trafficking stem cells that have not been genetically modified exhibit an inherent antitumor effect, thus circumventing the necessity of the expression of exogenous genes by the cells. We transplanted Fisher 344 rat–derived mammary adenocarcinoma cells (Mat B III) orthotopically into syngeneic F344 rats with an intact immune system. Rat umbilical cord matrix stem (rUCMS) cells derived from Wharton's jelly were then administered intratumoral (i.t) or i.v. 4 days later. The tumor attenuation effect was significantly evident starting from day 14 in i.v. and i.t. rUCMS cell–transplanted rats compared with sham-transplanted rats. In addition, unmodified rUCMS cell–transplanted rats showed complete regression of tumors to undetectable levels by 34 to 38 days with no evidence of metastasis or recurrence 100 days post–tumor cell inoculation. Dye-loaded rUCMS cells were identified within tumors only 4 days after their i.v. transplantation. In vitro colony assays with rUCMS cells as feeder layers markedly reduced Mat B III colony size and number. Growth attenuation of Mat B III cells exposed to either rUCMS cells directly or to the conditioned medium derived from rUCMS cells was associated with apoptosis indicators, including increased activated caspase-3. In addition, rUCMS cells cocultured with Mat B III cells had a dose-dependent antiproliferative effect on Mat B III cells. These findings suggest that unmodified human UCMS cells could be used for targeted cytotherapy for breast cancer. [Cancer Res 2009;69(5):1815–20]
Interleukin-27 Activates Natural Killer Cells and Suppresses NK-Resistant Head and Neck Squamous Cell Carcinoma through Inducing Antibody-Dependent Cellular Cytotoxicity
Authors: Matsui Masahiro , Kishida Tsunao , Nakano Hiroshi , Yoshimoto Koichiro , Shin-Ya Masaharu , Shimada Taketoshi , Nakai Shigeru , Imanishi Jiro , Yoshimoto Takayuki , Hisa Yasuo , Mazda Osam
Published: February 2009

Interleukin (IL)-27 is an IL-12 family cytokine playing a pivotal role in the induction of Th1 immune responses, although its action on natural killer (NK) cells has not been fully elucidated. Here, we show that IL-27 is capable of inducing phosphorylation of signal transducers and activators of transcription 1 and 3, as well as expression of T-bet and granzyme B in murine DX-5+ NK cells. IL-27 also enhances cytotoxic activity of NK cells both in vitro and in vivo, while the in vitro viability of NK cells is also improved by this cytokine. Therapeutic administration of the IL-27 gene drastically suppressed the growth of NK-unsusceptible SCCVII tumors that had been preestablished in syngenic mice, resulting in significant prolongation of the survival of the animals. This can likely be ascribed to the antibody-dependent cellular cytotoxicity machinery because IL-27 successfully induced tumor-specific IgG in the sera of the tumor-bearing mice, and supplementation of the sera enabled IL-27–activated NK cells to kill SCCVII cells in an Fcγ receptor III–dependent manner. These findings strongly suggest that IL-27 may offer a powerful immunotherapeutic tool to eradicate head and neck squamous cell carcinoma and other poorly immunogenic neoplasms through activating NK cells and inducing tumor-specific immunoglobulin that may cooperatively elicit antibody-dependent cellular cytotoxicity activity. [Cancer Res 2009;69(6):2523–30]
Androgen-Stimulated UDP-Glucose Dehydrogenase Expression Limits Prostate Androgen Availability without Impacting Hyaluronan Levels
Authors: Wei Qin , Galbenus Robert , Raza Ashraf , Cerny Ronald L. , Simpson Melanie A.
Published: February 2009

UDP-glucose dehydrogenase (UGDH) oxidizes UDP-glucose to UDP-glucuronate, an essential precursor for production of hyaluronan (HA), proteoglycans, and xenobiotic glucuronides. High levels of HA turnover in prostate cancer are correlated with aggressive progression. UGDH expression is high in the normal prostate, although HA accumulation is virtually undetectable. Thus, its normal role in the prostate may be to provide precursors for glucuronosyltransferase enzymes, which inactivate and solubilize androgens by glucuronidation. In this report, we quantified androgen dependence of UGDH, glucuronosyltransferase, and HA synthase expression. Androgen-dependent and androgen-independent human prostate cancer cell lines were used to test the effects of UGDH manipulation on tumor cell growth, HA production, and androgen glucuronidation. Dihydrotestosterone (DHT) increased UGDH expression ∼2.5-fold in androgen-dependent cells. However, up-regulation of UGDH did not affect HA synthase expression or enhance HA production. Mass spectrometric analysis showed that DHT was converted to a glucuronide, DHT-G, at a 6-fold higher level in androgen-dependent cells relative to androgen-independent cells. The increased solubilization and elimination of DHT corresponded to slower cellular growth kinetics, which could be reversed in androgen-dependent cells by treatment with a UDP-glucuronate scavenger. Collectively, these results suggest that dysregulated expression of UGDH could promote the development of androgen-independent tumor cell growth by increasing available levels of intracellular androgen. [Cancer Res 2009;69(6):2332–9]
Rnd3 Regulation of the Actin Cytoskeleton Promotes Melanoma Migration and Invasive Outgrowth in Three Dimensions
Authors: Klein R. Matthew , Aplin Andrew E.
Published: February 2009

The depth of cell invasion into the dermis is a clinical determinant for poor prognosis in cutaneous melanoma. The signaling events that promote the switch from a noninvasive to invasive tumor phenotype remain obscure. Activating mutations in the serine/threonine kinase B-RAF are prevalent in melanoma. Mutant B-RAF is required for melanoma cell invasion. The expression of Rnd3, a Rho family GTPase, is regulated by mutant B-RAF, although its role in melanoma progression is unknown. In this study, we determined the functional contribution of Rnd3 to invasive melanoma. Endogenous Rnd3 was targeted for knockdown using a doxycycline-inducible short hairpin RNA system in invasive human melanoma cells. Depletion of Rnd3 promoted prominent actin stress fibers and enlarged focal adhesions. Mechanistically, stress fiber formation induced by Rnd3 knockdown required the specific involvement of RhoA and ROCK1/2 activity but not RhoB or RhoC. Rnd3 expression in human melanoma cell lines was strongly associated with elevated extracellular signal–regulated kinase phosphorylation and invasive behavior in a three-dimensional dermal-like environment. A functional role for Rnd3 was shown in the invasive outgrowth of melanoma tumor spheroids. Knockdown of Rnd3 reduced the invasive outgrowth of spheroids embedded in collagen gels. Additionally, Rnd3 depletion inhibited collective and border cell movement out from spheroids in a ROCK1/2-dependent manner. Collectively, these findings implicate Rnd3 as a major suppressor of RhoA-mediated actin cytoskeletal organization and in the acquisition of an invasive melanoma phenotype. [Cancer Res 2009;69(6):2224–33]
Mdm2 Affects Genome Stability Independent of p53
Authors: Bouska Alyssa , Eischen Christine M.
Published: February 2009

Mdm2 is a critical negative regulator of the p53 tumor suppressor and is frequently overexpressed in human cancers. However, reports, including our own studies, suggest that Mdm2 has both p53-dependent and p53-independent functions that contribute to genomic instability and transformation when deregulated. We recently elucidated a p53-independent role for Mdm2 in the regulation of the DNA double-strand break repair response, genomic stability, and transformation through interaction with Nbs1, a member of the Mre11/Rad50/Nbs1 DNA double-strand break repair complex. In light of these findings, targeting Mdm2 in human malignancies may have effects other than activating p53. [Cancer Res 2009;69(5):1697–701]
Mitogen-Activated Protein Kinase Inhibition Induces Translocation of Bmf to Promote Apoptosis in Melanoma
Authors: VanBrocklin Matthew W. , Verhaegen Monique , Soengas Maria S. , Holmen Sheri L.
Published: February 2009

Constitutive activation of the mitogen-activated protein kinase (MAPK) pathway is implicated in the development and progression of many human cancers, including melanoma. Mutually exclusive activating mutations in NRAS or BRAF have been identified in ∼85% of melanomas, and components of this pathway have been developed as molecular targets for therapeutic intervention. We and others have shown that inhibition of this pathway with specific small molecule MAPK/extracellular signal-regulated kinase kinase (MEK) inhibitors induces a wide range of apoptotic responsiveness in human melanoma cells both in vitro and in vivo. To define the molecular mechanism underlying variable apoptotic sensitivity of melanoma cells to MEK inhibition, we examined the expression and subcellular localization of Bcl-2 family members in a comprehensive set of human melanoma cell lines. Whereas the proapoptotic protein Bim was activated and localized to the mitochondrial membrane in all cell lines regardless of apoptotic sensitivity, Bmf activation and cytosolic translocation was exclusive to sensitive cells. In resistant cells, Bmf remained sequestered to the cytoskeleton through dynein light chain 2 (DLC2) binding. Overexpression of Bmf in resistant cells did not enhance apoptosis, whereas expression of mutant BmfA69P, which has decreased binding to DLC2, promoted cell death. Expression of BmfA69P mutants possessing the Bcl-2 homology 3 (BH3) domain mutation L138A, which impairs BH3 interactions, did not enhance apoptosis in resistant cells. RNA interference targeting Bim and Bmf provided protection from apoptosis induced by MEK inhibition. These results show a novel role for Bmf in promoting apoptosis and provide insight into the mechanism of apoptotic resistance to MEK inhibition in melanoma. [Cancer Res 2009;69(5):1985–94]
Immune Effector Cells Produce Lethal DNA Damage in Cells Treated with a Thiopurine
Authors: Daehn Ilse , Karran Peter
Published: February 2009

Azathioprine, a widely used immunosuppressant, is also used in the control of inflammatory disorders. These are characterized by the local accumulation of immune effector cells that produce reactive oxygen species (ROS). The DNA of azathioprine-treated patients contains 6-thioguanine (6-TG), a base analogue that is particularly susceptible to oxidation. Here, we show that 6-TG is vulnerable to ROS produced by chemical oxidants and that cells containing DNA 6-TG are hypersensitive to these oxidants. We also show that 6-TG incorporated into the DNA of macrophages sensitizes them to killing by endogenously produced ROS. ROS generated by macrophages are also a hazard for cocultured nonmacrophage cells containing DNA 6-TG. This bystander vulnerability of cells containing DNA 6-TG to oxidation by ROS generated by immune effector cells has implications for the long-term use of azathioprine in the management of inflammatory disorders. [Cancer Res 2009;69(6):2393–9]
Biodistributions, Myelosuppression, and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the α-Emitting Radionuclides Bismuth-213 or Astatine-211
Authors: Nakamae Hirohisa , Wilbur D. Scott , Hamlin Donald K. , Thakar Monica S. , Santos Erlinda B. , Fisher Darrell R. , Kenoyer Aimee L. , Pagel John M. , Press Oliver W. , Storb Rainer , Sandmaier Brenda M.
Published: February 2009

We previously investigated the potential of targeted radiotherapy using a bismuth-213 (213Bi)–labeled anti-CD45 antibody to replace total body irradiation as conditioning for hematopoietic cell transplantation in a canine model. Although this approach allowed sustained marrow engraftment, limited availability, high cost, and short half-life of 213Bi induced us to investigate an alternative α-emitting radionuclide, astatine-211 (211At), for the same application. Biodistribution and toxicity studies were conducted with conjugates of the anti-murine CD45 antibody 30F11 with either 213Bi or 211At. Mice were injected with 2 to 50 μCi on 10 μg or 20 μCi on 2 or 40 μg of 30F11 conjugate. Biodistribution studies showed that the spleen contained the highest concentration of radioactivity, ranging from 167 ± 23% to 417 ± 109% injected dose/gram (% ID/g) after injection of the 211At conjugate and 45 ± 9% to 166 ± 11% ID/g after injection of the 213Bi conjugate. The higher concentrations observed for 211At-labeled 30F11 were due to its longer half-life, which permitted better localization of isotope to the spleen before decay. 211At was more effective at producing myelosuppression for the same quantity of injected radioactivity. All mice injected with 20 or 50 μCi 211At, but none with the same quantities of 213Bi, had lethal myeloablation. Severe reversible acute hepatic toxicity occurred with 50 μCi 213Bi, but not with lower doses of 213Bi or with any dose of 211At. No renal toxicity occurred with either radionuclide. The data suggest that smaller quantities of 211At-labeled anti-CD45 antibody are sufficient to achieve myelosuppression and myeloablation with less nonhematologic toxicity compared with 213Bi-labeled antibody. [Cancer Res 2009;69(6):2408–15]
Coordination of DNA Mismatch Repair and Base Excision Repair Processing of Chemotherapy and Radiation Damage for Targeting Resistant Cancers
Authors: Kinsella Timothy J.
Published: February 2009

DNA damage processing by mismatch repair (MMR) and/or base excision repair (BER) can determine the therapeutic index following treatment of human cancers using radiation therapy and several classes of chemotherapy drugs. Over the last decade, basic and translational cancer research in DNA repair has led to an increased understanding of how these two DNA repair pathways can modify cytotoxicity to chemotherapy and/or ionizing radiation treatments in both normal and malignant tissues. This Molecular Pathways article provides an overview of the current understanding of mechanisms involved in MMR and BER damage processing, including insights into possible coordination of these two DNA repair pathways after chemotherapy and/or ionizing radiation damage. It also introduces principles of systems biology that have been applied to better understand the complexities and coordination of MMR and BER in processing these DNA damages. Finally, it highlights novel therapeutic approaches to target resistant (or DNA damage tolerant) human cancers using chemical and molecular modifiers of chemotherapy and/or ionizing radiation including poly (ADP-ribose) polymerase inhibitors, methoxyamine and iododeoxyuridine (and the prodrug, 5-iodo-2-pyrimidinone-2'-deoxyribose).
Systemic Administration of a Conditionally Replicating Adenovirus, Targeted to Angiogenesis, Reduced Lung Metastases Burden in Cotton Rats
Authors: Peled Michael , Shaish Aviv , Katav Avi , Greenberger Shoshana , Barshack Iris , Tal Reshef , Bangio Livnat , Breitbart Eyal , Harats Dror
Published: February 2009

Purpose: Angiogenesis is an essential process for solid tumor development. To interfere with angiogenesis, AdPPE3x-E1, an adenovirus that is transcriptionally targeted to replicate in angiogenic endothelial cells, was constructed, by replacing the E1 promoter with the modified preproendothelin-1 promoter, PPE-1-3x, previously shown to induce specific transcription in angiogenic endothelial cells.

Experimental Design: The specificity of AdPPE3x-E1 to endothelial cells was shown by quantitative PCR and immunostaining, and its antiangiogenic effect was evaluated in Matrigel models. The in vivo efficacy of AdPPE3x-E1 was also tested in a cotton rat lung metastases model.

Results: The replication rate of AdPPE3x-E1 in endothelial cells was similar to that of AdCMV-E1, a nonselective replicating adenovector, but the replication rate was reduced up to 60-fold in nonendothelial cells. Moreover, AdPPE3x-E1 reduced endothelial cell viability by 90% whereas nonendothelial cells were not affected. In in vitro and in vivo Matrigel models, endothelial cells infected with AdPPE3x-E1 did not develop capillary-like structures. The systemic administration of AdPPE3x-E1 reduced the lung metastases burden in a cotton rat model by 55%, compared with saline-treated rats, without significant evidence of toxicity. Quantitative PCR analysis showed that the viral copy number of AdPPE3x-E1 was increased 3-fold in the lung metastases but not in the liver, compared with a nonreplicating adenovector control.

Conclusions: We have shown here for the first time an antimetastatic effect induced by an angiogenesis-transcriptionally targeted adenovirus following systemic administration. Because adenovirus replication is more efficient in humans than in cotton rats, we assume a significant effect for AdPPE3x-E1 treatment in fighting human solid tumors and metastases.
Polymorphisms in the FAS and FASL Genes and Survival of Early Stage Non–small Cell Lung Cancer
Authors: Park Jae Yong , Lee Won-Kee , Jung Duk-Ku , Choi Jin-Eun , Park Tae-In , Lee Eung-Bae , Cho Sukki , Park Ji-Young , Cha Sung-Ick , Kim Chang-Ho , Kam Sin , Jung Tae Hoon , Jheon Sanghoon
Published: February 2009

Purpose: This study was conducted to investigate the impact of functional polymorphisms in the FAS and FASL genes on the survival of early stage non–small cell lung cancer (NSCLC) patients.

Experimental Design: Three hundred and thirty-eight consecutive patients with surgically resected NSCLC were enrolled. The FAS -1377G>A (rs2234767) and -670A>G (rs1800682) and FASL -844C>T (rs763110) polymorphisms were investigated. Immunohistochemistry was used to assess FAS protein expression in tumors. The genotype and haplotype associations with survival were analyzed using Cox proportional hazards model, Kaplan-Meier method, and the log-rank test.

Results: Patients with the GG and combined AG + GG genotypes of the FAS -670A>G locus had a significantly decreased survival when compared with patients with the AA genotype [adjusted hazard ratio = 1.71, 95% confidence interval (95% CI) = 1.06-2.77, and P = 0.03; and adjusted hazard ratio = 1.48, 95% CI = 1.01-2.20, and P = 0.047, respectively]. In addition, the FAS -1377G/-670G and -1377A/-670G haplotypes exhibited a significantly lower survival compared with the -1377G/-670A haplotype (adjusted hazard ratio = 1.87, 95% CI = 1.20-2.91, and P = 0.006; and adjusted hazard ratio = 1.31, 95% CI = 1.05-1.65, P = 0.02, respectively). Strongly positive FAS immunostaining was significantly less frequent in patients with the FAS -670 AG + GG genotype than in patients with the -670 AA genotype (4.5% versus 10.8%; P = 0.04).

Conclusion: The FAS -670A>G polymorphism may affect survival in early-stage NSCLC. The analysis of the FAS -670A>G polymorphism can help identify patients at high risk for a poor disease outcome.
Treatment of Mammary Carcinomas in HER-2 Transgenic Mice through Combination of Genetic Vaccine and an Agonist of Toll-Like Receptor 9
Authors: Aurisicchio Luigi , Peruzzi Daniela , Conforti Antonella , Dharmapuri Sridhar , Biondo Antonella , Giampaoli Saverio , Fridman Arthur , Bagchi Ansu , Winkelmann Christopher T. , Gibson Raymond , Kandimalla Ekambar R. , Agrawal Sudhir , Ciliberto Gennaro , La Monica Nicola
Published: February 2009

Purpose: Oligodeoxynucleotides containing unmethylated CpG dinucleotides induce innate and adaptive immunity through Toll-like receptor 9 (TLR9). In the present study, we have examined the ability of a novel agonist of TLR9, called immunomodulatory oligonucleotide (IMO), to enhance effects of a HER-2/neu plasmid DNA electroporation/adenovirus (DNA-EP/Ad) vaccine.

Experimental Design: BALB/NeuT mice were treated with DNA-EP vaccine alone, IMO alone, or the combination of two agents starting at week 13, when all mice showed mammary neoplasia. Tumor growth and survival were documented. Antibody and CD8+ T-cell responses were determined. Peptide microarray analysis of sera was carried out to identify immunoreactive epitopes. Additionally, microCT and microPET imaging was carried out in an advanced-stage tumor model starting treatment at week 17 in BALB/NeuT mice.

Results: The combination of DNA-EP and IMO resulted in significant tumor regression or delay to tumor progression. 2-Deoxy-2-[18F]fluoro-d-glucose microPET and microCT imaging of mice showed reduced tumor size in the DNA-EP/IMO combination treatment group. Mice treated with the combination produced greater antibody titers with IgG2a isotype switch and antibody-dependent cellular cytotoxicity activity than did mice treated with DNA-EP vaccine. An immunogenic B-cell linear epitope, r70, within the HER-2 dimerization domain was identified through microarray analysis. Heterologous DNA-EP/Ad vaccination combined with IMO increased mice survival.

Conclusion: The combination of HER-2/neu genetic vaccine and novel agonist of TLR9 had potent antitumor activity associated with antibody isotype switch and antibody-dependent cellular cytotoxicity activities. These results support possible clinical trials of the combination of DNA-EP/Ad-based cancer vaccines and IMO.
Hypoxia Enhances Sphingosine Kinase 2 Activity and Provokes Sphingosine-1-Phosphate-Mediated Chemoresistance in A549 Lung Cancer Cells
Authors: Schnitzer Steffen E. , Weigert Andreas , Zhou Jie , Brüne Bernhard
Published: February 2009

Hypoxia and signaling via hypoxia-inducible factor-1 (HIF-1) is a key feature of solid tumors and is related to tumor progression as well as treatment failure. Although it is generally accepted that HIF-1 provokes tumor cell survival and induces chemoresistance under hypoxia, HIF-1-independent mechanisms operate as well. We present evidence that conditioned medium obtained from A549 cells, incubated for 24 h under hypoxia, protected naive A549 cells from etoposide-induced cell death. Lipid extracts generated from hypoxia-conditioned medium still rescued cells from apoptosis induced by etoposide. Specifically, the bioactive lipid sphingosine-1-phosphate (S1P) not only was essential for cell viability of A549 cells but also protected cells from apoptosis. We noticed an increase in sphingosine kinase 2 (SphK2) protein level and enzymatic activity under hypoxia, which correlated with the release of S1P into the medium. Knockdown of SphK2 using specific small interfering RNA relieved chemoresistance of A549 cells under hypoxia and conditioned medium obtained from SphK2 knockdown cells was only partially protective. Coincubations of conditioned medium with VPC23019, a S1P1/S1P3 antagonist, reduced protection of conditioned medium, with the further notion that p42/44 mitogen-activated protein kinase transmits autocrine or paracrine survival signaling downstream of S1P1/S1P3 receptors. Our data suggest that hypoxia activates SphK2 to promote the synthesis and release of S1P, which in turn binds to S1P1/S1P3 receptors, thus activating p42/44 mitogen-activated protein kinase to convey autocrine or paracrine protection of A549 cells. (Mol Cancer Res 2009;7(3):393–401)
Adolescents with Skin Disease Have Specific Quality of Life Issues
Authors: Golics C.J. , Basra M.K.A. , Finlay A.Y. , Salek M.S.
Published: February 2009

Background: Adolescence is a period of life with its own unique characteristics. Objectives: To provide an in-depth understanding of the impact of skin disease on different aspects of adolescents’ health-related quality of life (HRQoL). Methods: Semi-structured qualitative interviews were conducted with a sample of dermatology patients between 12 and 19 years of age, attending the dermatology outpatient clinic of a secondary referral centre. Participants were invited to talk in detail about all the ways their lives had been affected by their skin disease. Interviews were transcribed verbatim. Results: Thirty-two adolescents (males = 10, females = 22) with a mean age of 15.7 years (range = 12–18 years) participated in the interviews. Twenty-eight HRQoL themes adversely affected by skin diseases were identified from the interviews which were grouped under 6 main HRQoL domains – psychological impact (91% of patients), physical impact (81%), social impact (81%), impact on lifestyle (63%), need for support (41%) and education and employment (34%). The number of HRQoL themes affected in each individual varied between 1 and 23 (mean = 8.1). Conclusions: The results of this study revealed the extent and nature of the impact of skin diseases on adolescents’ HRQoL. A number of issues identified were specific to adolescents, highlighting the need for specific HRQoL assessment.
Postdramatic Stress Syndrome: Dood Paard's medEia at P.S. 122
Authors: Gallagher-Ross Jacob
Published: February 2009

Art—or at least the kind we most like to write about—is almost always political, whether it is inter/national or personal; and though TDR has already taken this up in its “War and Other Bad Shit” issue, the topic remains center stage. In his review of Dutch theatre troupe Dood Paard's medEia, Jacob Gallagher-Ross notes the emergence of “a new age of the chorus” in which spectatorship becomes inseparable from paralyzed witnessing and Medea's tragedy is reconceived as a metaphor for the West's tragic relations with the East. Laurietz Seda explores Guillermo Gómez-Peña's recent performance/installation Mapa/Corpo 2: Interactive Rituals for the New Millennium, a fluid piece that, like much of the artist's recent work, addresses the xenophobia and “war on difference” that underlies the US's ongoing War on Terror. The Burmese stand-up trio the Moustache Brothers is the subject of Xan Colman and Tamara Searle's personal account of how performance can be both art and resistance in a contradictory and charged political regime.
Decolonizing the Body Politic: Guillermo Gómez-Peña's Mapa/Corpo 2: Interactive Rituals for the New Millennium
Authors: Seda Laurietz
Published: February 2009

Art—or at least the kind we most like to write about—is almost always political, whether it is inter/national or personal; and though TDR has already taken this up in its “War and Other Bad Shit” issue, the topic remains center stage. In his review of Dutch theatre troupe Dood Paard's medEia, Jacob Gallagher-Ross notes the emergence of “a new age of the chorus” in which spectatorship becomes inseparable from paralyzed witnessing and Medea's tragedy is reconceived as a metaphor for the West's tragic relations with the East. Laurietz Seda explores Guillermo Gómez-Peña's recent performance/installation Mapa/Corpo 2: Interactive Rituals for the New Millennium, a fluid piece that, like much of the artist's recent work, addresses the xenophobia and “war on difference” that underlies the US's ongoing War on Terror. The Burmese stand-up trio the Moustache Brothers is the subject of Xan Colman and Tamara Searle's personal account of how performance can be both art and resistance in a contradictory and charged political regime.
Concerning Theory for Performance Studies
Authors: Schechner Richard , Beal Timothy K. , Deal William E. , Rodgers Talia , L'Enfant Claire , Butler Judith , Carlson Marvin , Davis Tracy C. , Savran David , Jackson Shannon , Jakovljevic Branislav , Dolan Jill , Zarrilli Phillip , Worthen W.B. , Roach Joseph , Phelan Peggy
Published: February 2009

In 2007, Routledge published Theory for Performance Studies as part of its Theory 4 series, listing Philip Auslander as author. When, in August, The Chronicle of Higher Education revealed that much of the book was lifted word-for-word from the template for the series, Theory for Religious Studies by Timothy K. Beal and William E. Deal, TDR editor Richard Schechner convened via email and phone conversations a “TDR Forum,” asking leaders in the field to respond to the book and the series. Schechner and other respondents address issues of plagiarism, corporate takeovers of academic publishing, and the dumbing down of performance studies, asking why a notable scholar such as Auslander would undertake such an egregious piece of “scholarship.” Deal and Beal answer some questions put to them by Schechner, and Routledge's Claire L'Enfant and Talia Rodgers offer their perspectives.
Remote Sensing of Cloud-Top Pressure Using Moderately Resolved Measurements within the Oxygen A Band—A Sensitivity Study
Authors: Preusker Rene , Lindstrot Rasmus
Published: February 2009

Reflected solar radiation measured by the Medium Resolution Imaging Spectrometer (MERIS) on the Environmental Satellite (Envisat) is currently used within the European Space Agency’s ground segment for the retrieval of cloud-top pressure. The algorithm is based on the analysis of the gaseous absorption of solar radiation in the oxygen A band at 761 nm. The strength of absorption is directly related to the average photon pathlength, which is mainly determined by the cloud-top pressure. However, it additionally depends on surface and cloud properties, like cloud thickness and microphysics. The interpretation of the measurements is further complicated by the temperature dependence of the absorption line shapes and the sensitivity to the spectral properties of the spectrometer like spectral position and width. This paper is focused on results of sensitivity studies using the Matrix Operator Model (MOMO) radiative transfer model that examine the most important parameters affecting the measurements of MERIS or similar instruments. The cloud-top pressure retrieval scheme is briefly presented. An analysis of the information content and the degrees of freedom of measurements within the oxygen A band is included in this study.
A Method of Successive Corrections of the Control Subspace in the Reduced-Order Variational Data Assimilation*
Authors: Yaremchuk Max , Nechaev Dmitri , Panteleev Gleb
Published: February 2009

A version of the reduced control space four-dimensional variational method (R4DVAR) of data assimilation into numerical models is proposed. In contrast to the conventional 4DVAR schemes, the method does not require development of the tangent linear and adjoint codes for implementation. The proposed R4DVAR technique is based on minimization of the cost function in a sequence of low-dimensional subspaces of the control space. Performance of the method is demonstrated in a series of twin-data assimilation experiments into a nonlinear quasigeostrophic model utilized as a strong constraint. When the adjoint code is stable, R4DVAR’s convergence rate is comparable to that of the standard 4DVAR algorithm. In the presence of strong instabilities in the direct model, R4DVAR works better than 4DVAR whose performance is deteriorated because of the breakdown of the tangent linear approximation. Comparison of the 4DVAR and R4DVAR also shows that R4DVAR becomes advantageous when observations are sparse and noisy.
Ensemble Data Assimilation Applied to RAINEX Observations of Hurricane Katrina (2005)
Authors: Torn Ryan D. , Hakim Gregory J.
Published: February 2009

An ensemble Kalman filter (EnKF) based on the Weather Research and Forecasting model is applied to generate ensemble analyses and forecasts of Hurricane Katrina (2005) and the surrounding area every 6 h over the lifetime of the storm on a nested domain. Analyses are derived from assimilating conventional in situ observations, reconnaissance dropsondes, including data taken during the Hurricane Rainband and Intensity Exchange Experiment (RAINEX), and tropical cyclone position estimates. Observation assimilation at individual times consistently reduces errors in tropical cyclone position, but not necessarily in intensity; however, withholding observations leads to significantly larger errors in both quantities. Analysis increments for observations near the tropical cyclone are dominated by changes in vortex position, and these increments increase the asymmetric structure of the storm. Data denial experiments indicate that dropsondes deployed in the synoptic environment provide minimal benefit to the outer domain; however, dropsondes deployed within the tropical cyclone lead to significant reductions in position and intensity errors on the inner domain. Specifically, errors in the inner domain ensemble-mean 6-h forecasts of minimum pressure are 70% larger when dropsonde data is not assimilated. Precipitation fields are qualitatively similar to Tropical Rainfall Measuring Mission (TRMM) satellite estimates, although model values are double the values of the satellite estimate. Moreover, the spinup period and initial imbalance in EnKF-initialized WRF forecasts is less than starting the model from a GFS analysis. Ensemble-mean 48-h forecasts initialized with EnKF analyses have track and intensity errors that are 50% smaller than GFS and NHC official forecasts.
Evaluation of a Mesoscale Model with Different Surface Parameterizations and Vertical Resolutions for the Bay of Valencia
Authors: Ries Hinnerk , Schlünzen K. Heinke
Published: February 2009

Two different setups of the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) are used and the results of 71 forecasts are evaluated with a focus on the accuracy of meteorological surface data including wind, temperature, dewpoint temperature, and pressure. The forecasts, which cover the Valencia coastal region with a 3-km grid, are nested into two coarser grids of 9- and 27-km mesh size. The integration time is 18 h. The ability to correctly simulate the sea breeze plays a major role for this area. Different model setups are used: in the M1 simulations 34 atmospheric vertical sigma levels combined with a five-layer land surface model (5L LSM) are applied for the first half of the year 2006. In total, 52 atmospheric vertical sigma levels and the Noah LSM are used for the second half of 2006 (setup M2). The accuracy improves for all meteorological parameters except pressure with the M2 setup. However, negative biases of temperature, dewpoint temperature, and wind speed worsen. Detailed analysis of results for 4 days simulated with all combinations of vertical resolutions and LSMs shows that the increase of vertical resolution is responsible for the improved forecast performance. The Noah LSM generally improves temperature performance, but reduces the performance of all other parameters, especially for days with sea-breeze conditions. The Noah LSM performs better than the 5L LSM scheme only for a day driven by synoptic changes.
An Examination of the Interactions of Race and Gender on Sentencing Decisions Using a Trichotomous Dependent Variable
Authors: Freiburger Tina L. , Hilinski Carly M.
Published: February 2009

This study examined how race, gender, and age interact to affect defendants’ sentences using a trichotomized dependent variable. The findings indicate that the racial and gender disparity found in sentencing decisions was largely due to Black men’s increased likelihood of receiving jail as opposed to probation. The results also show that being young resulted in increased odds of receiving probation over jail for White men and for women but resulted in decreased odds for Black men. Separate analysis of incarceration terms to jail and prison further reveal that legal factors had a greater impact on prison than on jail sentence length. Overall, the results strongly support the argument that sentencing research needs to consider sentences to jail and prison separately.
Analysis of Boron Carbide Aluminum Matrix Composites
Authors: Gómez L. , Busquets-Mataix D. , Amigó V. , Salvador M.D.
Published: February 2009

This study deals with the feasibility of using boron carbide (B4C) as reinforcement for aluminum matrix composites (AMCs) obtained by solid-state processes (powder metallurgy and extrusion). Two different reinforcements were considered: B4C as the object of this study and SiC for direct comparison of results. Aluminum alloy AA6061 was used as matrix in all cases. Comparative analysis between both SiC and B4C composites was focused on mechanical and tribological properties and correlated to microstructural features. Hardness and strength increased for composites together with volume fraction of reinforcement, reaching its maximum value to 10% B4C. Regarding tribology, composites showed an increased dynamic friction coefficient but a lower wear rate than the unreinforced aluminum alloy. Applications as brake disks for automotive industry are foreseen.
A Panel Data Analysis of the Military Expenditure-External Debt Nexus: Evidence from Six Middle Eastern Countries
Authors: Smyth Russell , Kumar Narayan Paresh
Published: February 2009

While a number of studies examine the nexus between military expenditure and economic growth, little consideration has been give to the effect of military expenditure on external debt. This article examines the impact of military expenditure and income on external debt for a panel of six Middle Eastern countries - Oman, Syria, Yemen, Bahrain, Iran, and Jordan - over the period 1988 to 2002. The Middle East represents an interesting study of the effect of military expenditure on external debt because it has one of the highest rates of arms imports in the world and it is one of the most indebted regions in the world. The study first establishes whether there is a long-run relationship between military expenditure, income, and external debt in the six countries using a panel unit root and panel cointegration framework and then proceeds to estimate the long-run and short-run effects of military expenditure and income on external debt. The study finds that external debt is elastic with respect to military expenditure in the long run and inelastic with respect to military expenditure in the short run. For the panel of six Middle Eastern countries, in the long run a 1% increase in military expenditure results in between a 1.1 % and 1.6% increase in external debt, while a 1% increase in income reduces external debt by between 0.6% and 0.8%, depending on the specific estimator employed. In the short run, a 1% increase in military expenditure increases external debt by 0.2%, while the effect of income on external debt is statistically insignificant.
`The German of caricature, the real German, the fellow we were up against'
Authors: Storer Colin
Published: February 2009

At first glance Greenmantle , John Buchan's 1916 novel of war and high adventure, seems a fairly conventional Boy's Own tale of wartime daring and heroism, in which a plucky band of British patriots attempt to foil a dastardly German plan to topple the British Empire. But a closer reading of the text reveals a much more complex set of themes and attitudes, especially regarding the Germans. Far from conforming with the negative stereotypes of the Germans prevalent in wartime, Buchan presents his readers with a complex set of representations of German characters which can be read as challenging and undermining established prewar and wartime conceptions of the Germans in British popular culture. This essay examines the ways in which the Germans are represented in Greenmantle in order to assess to what extent these representations conform to or challenge contemporary stereotypes, and indeed to what extent Buchan's German characters are typically or specifically German.
Costs and Benefits Associated With Diabetes Education A Review of the Literature
Authors: Boren Suzanne A. , Fitzner Karen A. , Panhalkar Pallavi S. , Specker James E.
Published: February 2009

Purpose The purpose of this article was to review the published literature and evaluate the economic benefits and costs associated with diabetes education.

Methods The Medline database (1991-2006) and Google were searched. Articles that addressed the economic and/or financial outcomes of a diabetes-related self-care or educational intervention were included. The study aim, population, design, intervention, financial and economic outcomes, results, and conclusions were extracted from eligible articles.

Results Twenty-six papers were identified that addressed diabetes self-management training and education. Study designs included meta-analysis (1); randomized controlled trials (8); prospective, quasi-experimental, and pre-post studies (8); and retrospective database analyses (9). The studies conducted cost analyses (6), cost-effectiveness analyses (13), cost-utilization analyses (7), and number needed to treat analyses (2). More than half (18) of the 26 papers identified by the literature review reported findings that associated diabetes education (and disease management) with decreased cost, cost saving, cost-effectiveness, or positive return on investment. Four studies reported neutral results, 1 study found that costs increased, and 3 studies did not fit into these categories.

Conclusions The findings indicate that the benefits associated with education on self-management and lifestyle modification for people with diabetes are positive and outweigh the costs associated with the intervention. More research is needed to validate that diabetes education provided by diabetes educators is cost-effective.
Health of Gullah Families in South Carolina With Type 2 Diabetes
Authors: Johnson-Spruill Ida , Hammond Pamela , Davis Bertha , McGee Zina , Louden Delroy
Published: February 2009

Purpose The purpose of this study was to describe diabetes self-management practices and service utilization among Gullah families in South Carolina.

Methods Data were obtained from 1276 persons with type 2 diabetes through interviews using the Family Health History Questionnaire. This was a primary analysis of a project conducted in conjunction with a parent study (Project SuGar) which focused on the molecular aspects of diabetes. Descriptive statistics were used for data analysis.

Results Diabetes self-management behaviors were not consistent with recommendations from the American Diabetes Association. Over half (55.6%) reported exercising, but only 27.7% reported self-glucose monitoring. Service utilization was poor, less than half, (41.1%) reported referral to a diabetic class/diet, 32.8% reported making yearly visits to the ophthalmologist, 22.3% reported visiting the dentist, and only 12.8% reported visiting the podiatrist.

Conclusions Although some self-management behaviors were identified, Gullah family members remain at risk for preventable diabetes complications. Education must reflect behaviors and beliefs valued by Gullah individuals. Culturally appropriate educational programs may increase use of health care services aimed at decreasing preventable complications of type 2 diabetes in the Gullah population.
Gender and Friendship Norms Among Older Adults
Authors: Felmlee Diane , Muraco Anna
Published: February 2009

The authors examined same- and cross-gender friendship norms in a sample of 135 adults (average age 73 years). Participants evaluated a friend's behavior, quantitatively and qualitatively, in vignettes in which the friend's gender was experimentally manipulated. Gender often significantly, though modestly, influenced normative evaluations. Women frequently had higher expectations of friends than men and placed a greater emphasis on intimacy. Women were more disapproving of violations of friendship rules, such as betraying a confidence, paying a surprise visit, and failing to stand up for a friend in public. However, both men and women were less approving of a man than a woman who greets another friend with a kiss or who requests to stay overnight. Respondents' open-ended comments reflected positive attitudes regarding cross-gender friendships. Most findings demonstrated that men and women across a wide age range held similar cultural norms for close ties, norms of trust, commitment, and respect.
Serious further offences: An exploration of risk and typologies
Authors: Craissati Jackie , Sindall Oliver
Published: February 2009

This study examined 94 serious further offences (SFOs) committed by offenders managed by the London Probation Area over a 14-month period between 2004 and 2006. Data was collated on background and criminogenic variables for the sample, as well as retrospectively administering a range of validated actuarial measures of risk prediction. The predictive validity of key variables embedded within the probation OASys tool were also examined, specifically the utility of the DSPD variables and the OGRS and OGRS-2. The SFO offender characteristics — in keeping with previous studies — were wide ranging, as were the risk profiles of the offenders, the majority of whom fell into the medium risk range. The risk assessment and personality-based assessment tools routinely available to the probation service — that is, DSPD and OGRS scores — were found to be at least as accurate as other actuarially based methods of risk prediction. There were no clear identifying features of this sample of offenders which seemed to differentiate them from a much wider sample of the probation caseload, although the research was not designed to provide a comparison study. However, examination of the nature of the SFOs suggested there were some key situational contexts which were associated with serious harm to others (rather than simply likelihood of re-offending). These contexts included pervasive weapon use, unexpected victim responses during acquisitive crimes, and disputes occurring within an anti-social male subculture. Recommendations included a greater emphasis on harm reduction approaches to probation interventions in terms of risky lifestyles and weapon use.