bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urban Governance for Adaptation: Assessing Climate Change Resilience in Ten Asian Cities
Authors: Tanner Thomas , Mitchell Tom , Polack Emily , Guenther Bruce 
Published: May 2009

SummaryRapidly expanding urban settlements in the developing world face severe climatic risks in light of climate change. Urban populations will increasingly be forced to cope with increased incidents of flooding, air and water pollution, heat stress and vector‐borne diseases. This research, undertaken with a set of partner research institutes, examines how to manage climate‐related impacts in an urban context by promoting planned and autonomous adaptation in order to by improve resilience in a changing climate. It investigates the linkages between the characteristics of pro‐poor good urban governance, climate adaptation and resilience, and poverty and sustainable development concerns. The paper develops an analytical framework by combining governance literature with rapid climate resilience assessments conducted in ten Asian cities. Based on this empirical data, we argue that a number of key characteristics can be identified to assess and build urban resilience to climate change in a way that reduces the vulnerability of the citizens most at risk from climate shocks and stresses. These characteristics form the basis of a climate resilient urban governance assessment framework, and include (1) decentralisation and autonomy, (2) accountability and transparency, (3) responsiveness and flexibility, (4) participation and inclusion and (5) experience and support. This framework can help to assist in the planning, design and implementation of urban climate change resilience‐building programmes in the future.
The category of toric stacks
Authors: Iwanari Isamu 
Published: May 2009

AbstractIn this paper, we show that there is an equivalence between the 2-category of smooth Deligne–Mumford stacks with torus embeddings and actions and the 1-category of stacky fans. To this end, we prove two main results. The first is related to a combinatorial aspect of the 2-category of toric algebraic stacks defined by I. Iwanari [Logarithmic geometry, minimal free resolutions and toric algebraic stacks, Preprint (2007)]; we establish an equivalence between the 2-category of toric algebraic stacks and the 1-category of stacky fans. The second result provides a geometric characterization of toric algebraic stacks. Logarithmic geometry in the sense of Fontaine–Illusie plays a central role in obtaining our results.
Cluster structures for 2-Calabi–Yau categories and unipotent groups
Authors: Buan A. B. , Iyama O. , Reiten I. , Scott J. 
Published: May 2009

AbstractWe investigate cluster-tilting objects (and subcategories) in triangulated 2-Calabi–Yau and related categories. In particular, we construct a new class of such categories related to preprojective algebras of non-Dynkin quivers associated with elements in the Coxeter group. This class of 2-Calabi–Yau categories contains, as special cases, the cluster categories and the stable categories of preprojective algebras of Dynkin graphs. For these 2-Calabi–Yau categories, we construct cluster-tilting objects associated with each reduced expression. The associated quiver is described in terms of the reduced expression. Motivated by the theory of cluster algebras, we formulate the notions of (weak) cluster structure and substructure, and give several illustrations of these concepts. We discuss connections with cluster algebras and subcluster algebras related to unipotent groups, in both the Dynkin and non-Dynkin cases.
Rigid subsets of symplectic manifolds
Authors: Entov Michael , Polterovich Leonid 
Published: May 2009

AbstractWe show that there is an hierarchy of intersection rigidity properties of sets in a closed symplectic manifold: some sets cannot be displaced by symplectomorphisms from more sets than the others. We also find new examples of rigidity of intersections involving, in particular, specific fibers of moment maps of Hamiltonian torus actions, monotone Lagrangian submanifolds (following the works of P. Albers and P. Biran-O. Cornea) as well as certain, possibly singular, sets defined in terms of Poisson-commutative subalgebras of smooth functions. In addition, we get some geometric obstructions to semi-simplicity of the quantum homology of symplectic manifolds. The proofs are based on the Floer-theoretical machinery of partial symplectic quasi-states.
q-series and weight 3/2 Maass forms
Authors: Bringmann Kathrin , Folsom Amanda , Ono Ken 
Published: May 2009

AbstractDespite the presence of many famous examples, the precise interplay between basic hypergeometric series and modular forms remains a mystery. We consider this problem for canonical spaces of weight 3/2 harmonic Maass forms. Using recent work of Zwegers, we exhibit forms that have the property that their holomorphic parts arise from Lerch-type series, which in turn may be formulated in terms of the Rogers–Fine basic hypergeometric series.
Algebraic and topological aspects of the schematization functor
Authors: Katzarkov L. , Pantev T. , Toën B. 
Published: May 2009

AbstractWe study some basic properties of schematic homotopy types and the schematization functor. We describe two different algebraic models for schematic homotopy types, namely cosimplicial Hopf alegbras and equivariant cosimplicial algebras, and provide explicit constructions of the schematization functor for each of these models. We also investigate some standard properties of the schematization functor that are helpful for describing the schematization of smooth projective complex varieties. In a companion paper, these results are used in the construction of a non-abelian Hodge structure on the schematic homotopy type of a smooth projective variety.
Costimulation as a Platform for the Development of Vaccines: A Peptide-Based Vaccine Containing a Novel Form of 4-1BB Ligand Eradicates Established Tumors
Authors: Sharma Rajesh K. , Elpek Kutlu G. , Yolcu Esma S. , Schabowsky Rich-Henry , Zhao Hong , Bandura-Morgan Laura , Shirwan Haval 
Published: May 2009

Abstract
Vaccines represent an attractive treatment modality for the management of cancer primarily because of their specificity and generation of immunologic memory important for controlling recurrences. However, the efficacy of therapeutic vaccines may require formulations that not only generate effective immune responses but also overcome immune evasion mechanisms employed by progressing tumor. Costimulatory molecules play critical roles in modulating innate, adaptive, and regulatory immunity and have potential to serve as effective immunomodulatory components of therapeutic vaccines. In this study, we tested the function of a novel soluble form of 4-1BB ligand (4-1BBL) costimulatory molecule in modulating innate, adaptive, and regulatory immunity and assessed its therapeutic efficacy in the HPV-16 E7-expressing TC-1 cervical cancer and survivin-expressing 3LL lung carcinoma mouse models. Vaccination with 4-1BBL activated dendritic cells and enhanced antigen uptake, generated CD8+ T-cell effector/memory responses, and endowed T effector cells refractory to suppression by CD4+CD25+FoxP3+ T regulatory cells. Immunization with 4-1BBL in combination with an E7 peptide or survivin protein resulted in eradication of TC-1 and 3LL tumors, respectively. 4-1BBL was more effective than TLR agonists LPS, MPL, and CpG and an agonistic 4-1BB antibody as a component of E7 peptide-based therapeutic vaccine for the generation of immune responses and eradication of TC-1 established tumors in the absence of detectable toxicity. Therapeutic efficacy was associated with reversal of tumor-mediated nonresponsiveness/anergy as well as establishment of long-term CD8+ T-cell memory. Potent pleiotropic immunomodulatory activities combined with lack of toxicity highlight the potential of 4-1BBL molecule as an effective component of therapeutic cancer vaccines. [Cancer Res 2009;69(10):4319–26]
Role of MUTYH and MSH2 in the Control of Oxidative DNA Damage, Genetic Instability, and Tumorigenesis
Authors: Russo Maria Teresa , De Luca Gabriele , Casorelli Ida , Degan Paolo , Molatore Sara , Barone Flavia , Mazzei Filomena , Pannellini Tania , Musiani Piero , Bignami Margherita 
Published: May 2009

Abstract
Mismatch repair is the major pathway controlling genetic stability by removing mispairs caused by faulty replication and/or mismatches containing oxidized bases. Thus, inactivation of the Msh2 mismatch repair gene is associated with a mutator phenotype and increased cancer susceptibility. The base excision repair gene Mutyh is also involved in the maintenance of genomic integrity by repairing premutagenic lesions induced by oxidative DNA damage. Because evidence in bacteria suggested that Msh2 and Mutyh repair factors might have some overlapping functions, we investigated the biological consequences of their single and double inactivation in vitro and in vivo. Msh2−/− mouse embryo fibroblasts (MEF) showed a strong mutator phenotype at the hprt gene, whereas Mutyh inactivation was associated with a milder phenotype (2.9 × 10−6 and 3.3 × 10−7 mutation/cell/generation, respectively). The value of 2.7 × 10−6 mutation/cell/generation in Msh2−/−Mutyh−/− MEFs did not differ significantly from Msh2−/− cells. When steady-state levels of DNA 8-oxo-7,8-dihydroguanine (8-oxoG) were measured in MEFs of different genotypes, single gene inactivation resulted in increases similar to those observed in doubly defective cells. In contrast, a synergistic accumulation of 8-oxoG was observed in several organs of Msh2−/−Mutyh−/− animals, suggesting that in vivo Msh2 and Mutyh provide separate repair functions and contribute independently to the control of oxidative DNA damage. Finally, a strong delay in lymphomagenesis was observed in Msh2−/−Mutyh−/− when compared with Msh2−/− animals. The immunophenotype of these tumors indicate that both genotypes develop B-cell lymphoblastic lymphomas displaying microsatellite instability. This suggests that a large fraction of the cancer-prone phenotype of Msh2−/− mice depends on Mutyh activity. [Cancer Res 2009;69(10):4372–9]
Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response
Authors: Szokalska Angelika , Makowski Marcin , Nowis Dominika , Wilczyński Grzegorz M. , Kujawa Marek , Wójcik Cezary , Młynarczuk-Biały Izabela , Salwa Pawel , Bil Jacek , Janowska Sylwia , Agostinis Patrizia , Verfaillie Tom , Bugajski Marek , Gietka Jan , Issat Tadeusz , Głodkowska Eliza , Mrówka Piotr , Stoklosa Tomasz , Hamblin Michael R. , Mróz Paweł , Jakóbisiak Marek , Golab Jakub 
Published: May 2009

Abstract
Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity toward tumor cells by inducing production of reactive oxygen species such as singlet oxygen. PDT leads to oxidative damage of cellular macromolecules, including proteins that undergo multiple modifications such as fragmentation, cross-linking, and carbonylation that result in protein unfolding and aggregation. Because the major mechanism for elimination of carbonylated proteins is their degradation by proteasomes, we hypothesized that a combination of PDT with proteasome inhibitors might lead to accumulation of carbonylated proteins in endoplasmic reticulum (ER), aggravated ER stress, and potentiated cytotoxicity toward tumor cells. We observed that Photofrin-mediated PDT leads to robust carbonylation of cellular proteins and induction of unfolded protein response. Pretreatment of tumor cells with three different proteasome inhibitors, including bortezomib, MG132, and PSI, gave increased accumulation of carbonylated and ubiquitinated proteins in PDT-treated cells. Proteasome inhibitors effectively sensitized tumor cells of murine (EMT6 and C-26) as well as human (HeLa) origin to PDT-mediated cytotoxicity. Significant retardation of tumor growth with 60% to 100% complete responses was observed in vivo in two different murine tumor models (EMT6 and C-26) when PDT was combined with either bortezomib or PSI. Altogether, these observations indicate that combination of PDT with proteasome inhibitors leads to potentiated antitumor effects. The results of these studies are of immediate clinical application because bortezomib is a clinically approved drug that undergoes extensive clinical evaluations for the treatment of solid tumors. [Cancer Res 2009;69(10):4235–43]
NORE1A Tumor Suppressor Candidate Modulates p21CIP1 via p53
Authors: Calvisi Diego F. , Donninger Howard , Vos Michele D. , Birrer Michael J. , Gordon Laura , Leaner Virna , Clark Geoffrey J. 
Published: May 2009

Abstract
NORE1A (RASSF5) is a proapoptotic Ras effector that is frequently inactivated by promoter methylation in human tumors. It is structurally related to the RASSF1A tumor suppressor and is itself implicated as a tumor suppressor. In the presence of activated Ras, NORE1A is a potent inducer of apoptosis. However, when expressed at lower levels in the absence of activated Ras, NORE1A seems to promote cell cycle arrest rather than apoptosis. The mechanisms underlying NORE1A action are poorly understood. We have used microarray analysis of an inducible NORE1A system to screen for physiologic signaling targets of NORE1A action. Using this approach, we have identified several potential signaling pathways modulated by NORE1A. In particular, we identify the cyclin-dependent kinase inhibitor p21CIP1 as a target for NORE1A activation and show that it is a vital component of NORE1A-mediated growth inhibition. In primary human hepatocellular carcinomas (HCC), loss of NORE1A expression is frequent and correlates tightly with loss of p21CIP1 expression. NORE1A down-regulation in HCC also correlates with poor prognosis, enhanced proliferation, survival, and angiogenic tumor characteristics. Experimental inactivation of NORE1A results in the loss of p21CIP1 expression and promotes proliferation. The best characterized activator of p21CIP1 is the p53 master tumor suppressor. Further experiments showed that NORE1A activates p21CIP1 via promoting p53 nuclear localization. Thus, we define the molecular basis of NORE1A-mediated growth inhibition and implicate NORE1A as a potential component of the ill-defined connection between Ras and p53. [Cancer Res 2009;69(11):4629–37]
The CD4+ T-Cell Response of Melanoma Patients to a MAGE-A3 Peptide Vaccine Involves Potential Regulatory T Cells
Authors: François Violaine , Ottaviani Sabrina , Renkvist Nicolina , Stockis Julie , Schuler Gerold , Thielemans Kris , Colau Didier , Marchand Marie , Boon Thierry , Lucas Sophie , van der Bruggen Pierre 
Published: May 2009

AbstractMelanoma patients were injected with various vaccines containing a MAGE-A3 peptide presented by HLA-DP4. Anti–MAGE-A3.DP4 T cells were not detectable in the blood before vaccination, but their frequencies after vaccination ranged from 2 × 10−6 to 2 × 10−3 among the CD4+ blood T lymphocytes of the patients. The CD4+ blood T lymphocytes that stained ex vivo with HLA-DP4 tetramers folded with the MAGE-A3 peptide were selected by flow cytometry and amplified under clonal conditions. About 5% of the CD4+ T-cell clones that recognized the MAGE-A3.DP4 antigen had a CD25+ phenotype in the resting state. These CD25+ clones had a high capacity to suppress the proliferation of another T-cell clone after peptide stimulation in vitro. Most of them had high FOXP3 expression in the resting state and an unmethylated FOXP3 intron 1. They produced active transforming growth factor-β but none of cytokines IFN-γ, interleukin-2 (IL-2), IL-4, IL-5, and IL-10. About 20% of CD25− clones had a significant but lower suppressive activity. Most of the CD25− clonal populations contained cells that expressed FOXP3 in the resting state, but FOXP3 demethylation was not observed. We conclude that MAGE-A3.DP4 vaccination can produce CD4+ T cells that may exert regulatory T-cell function in vivo. [Cancer Res 2009;69(10):4335–45]
Epigenetic Silencing of the Tumor Suppressor MicroRNAHsa-miR-124aRegulates CDK6 Expression and Confers a Poor Prognosis in Acute Lymphoblastic Leukemia
Authors: Agirre Xabier , Vilas-Zornoza Amaia , Jiménez-Velasco Antonio , Martin-Subero José Ignacio , Cordeu Lucia , Gárate Leire , San José-Eneriz Edurne , Abizanda Gloria , Rodríguez-Otero Paula , Fortes Puri , Rifón José , Bandrés Eva , Calasanz María José , Martín Vanesa , Heiniger Anabel , Torres Antonio , Siebert Reiner , Román-Gomez José , Prósper Felipe 
Published: May 2009

AbstractWhereas transcriptional silencing of genes due to epigenetic mechanisms is one of the most important alterations in acute lymphoblastic leukemia (ALL), some recent studies indicate that DNA methylation contributes to down-regulation of miRNAs during tumorigenesis. To explore the epigenetic alterations of miRNAs in ALL, we analyzed the methylation and chromatin status of the miR-124a loci in ALL. Expression of miR-124a was down-regulated in ALL by hypermethylation of the promoter and histone modifications including decreased levels of 3mk4H3 and AcH3 and increased levels of 2mK9H3, 3mK9H3, and 3mK27H3. Epigenetic down-regulation of miR-124a induced an up-regulation of its target, CDK6, and phosphorylation of retinoblastoma (Rb) and contributed to the abnormal proliferation of ALL cells both in vitro and in vivo. Cyclin-dependent kinase 6 (CDK6) inhibition by sodium butyrate or PD-0332991 decreased ALL cell growth in vitro, whereas overexpression of pre-miR124a led to decreased tumorigenicity in a xenogeneic in vivo Rag2−/−γc−/− mouse model. The clinical implications of these findings were analyzed in a group of 353 patients diagnosed with ALL. Methylation of hsa-miR-124a was observed in 59% of the patients, which correlated with down-regulation of miR-124a (P &lt; 0.001). Furthermore, hypermethylation of hsa-miR-124a was associated with higher relapse rate (P = 0.001) and mortality rate (P &lt; 0.001), being an independent prognostic factor for disease-free survival (P &lt; 0.001) and overall survival (P = 0.005) in the multivariate analysis. These results provide the grounds for new therapeutic strategies in ALL either targeting the epigenetic regulation of microRNAs and/or directly targeting the CDK6-Rb pathway. [Cancer Res 2009;69(10):4443–53]
Haploinsufficiency of Krüppel-Like Factor 5 Rescues the Tumor-Initiating Effect of the ApcMin Mutation in the Intestine
Authors: McConnell Beth B. , Bialkowska Agnieszka B. , Nandan Mandayam O. , Ghaleb Amr M. , Gordon Frank J. , Yang Vincent W. 
Published: May 2009

Abstract
Inactivation of the tumor suppressor adenomatous polyposis coli, with the resultant activation of β-catenin, is the initiating event in the development of a majority of colorectal cancers. Krüppel-like factor 5 (KLF5), a proproliferative transcription factor, is highly expressed in the proliferating intestinal crypt epithelial cells. To determine whether KLF5 contributes to intestinal adenoma formation, we examined tumor burdens in ApcMin/+ mice and ApcMin/+/Klf5+/− mice. Compared with ApcMin/+ mice, ApcMin/+/Klf5+/− mice had a 96% reduction in the number of intestinal adenomas. Reduced tumorigenicity in the ApcMin/+/Klf5+/− mice correlated with reduced levels and nuclear localization of β-catenin as well as reduced expression of two β-catenin targets, cyclin D1 and c-Myc. In vitro studies revealed a physical interaction between KLF5 and β-catenin that enhanced the nuclear localization and transcriptional activity of β-catenin. Thus, KLF5 is necessary for the tumor-initiating activity of β-catenin during intestinal adenoma formation in ApcMin/+ mice, and reduced expression of KLF5 offsets the tumor-initiating activity of the ApcMin mutation by reducing the nuclear localization and activity of β-catenin. [Cancer Res 2009;69(10):4125–33]
VEGF-A Induces Angiogenesis by Perturbing the Cathepsin-Cysteine Protease Inhibitor Balance in Venules, Causing Basement Membrane Degradation and Mother Vessel Formation
Authors: Chang Sung-Hee , Kanasaki Keizo , Gocheva Vasilena , Blum Galia , Harper Jay , Moses Marsha A. , Shih Shou-Ching , Nagy Janice A. , Joyce Johanna , Bogyo Matthew , Kalluri Raghu , Dvorak Harold F. 
Published: May 2009

Abstract
Tumors initiate angiogenesis primarily by secreting vascular endothelial growth factor (VEGF-A164). The first new vessels to form are greatly enlarged, pericyte-poor sinusoids, called mother vessels (MV), that originate from preexisting venules. We postulated that the venular enlargement necessary to form MV would require a selective degradation of their basement membranes, rigid structures that resist vascular expansion. To identify the specific proteases responsible for MV formation, we induced angiogenesis in mouse tissues with an adenoviral vector expressing VEGF-A164 (Ad-VEGF-A164) or with VEGF-A–secreting TA3/St mammary tumors. We found that MV formation resulted from greatly increased activity of cathepsins (B&gt;S&gt;L) in venules transitioning into MV, as well as from a reciprocal decrease in the expression of several cysteine protease inhibitors (CPI), stefin A and cystatins B and C, by these same venules. Using a fluorescence probe that selectively binds cellular sites of cathepsin protease activity in vivo, we showed that increased cathepsin activity was localized exclusively to perivenular cells, not to venule endothelial cells. CPI strikingly inhibited angiogenesis in the Matrigel assay, and Ad-VEGF-A164–induced angiogenesis was reduced by ∼50% in cathepsin B–null mice. Thus, VEGF-A, whether expressed by interstitial cells infected with an adenoviral vector or by tumor cells, upsets the normal cathepsin-CPI balance in nearby venules, leading to degradation of their basement membranes, an important first step in angiogenesis. [Cancer Res 2009;69(10):4537–44]
The Vascular Endothelial Growth Factor Receptor Inhibitor PTK787/ZK222584 Inhibits Aromatase
Authors: Banerjee Susana , Zvelebil Marketa , Furet Pascal , Mueller-Vieira Ursula , Evans Dean B. , Dowsett Mitch , Martin Lesley-Ann 
Published: May 2009

Abstract
Endocrine therapy is well established for the treatment of breast cancer, and antiangiogenic agents are showing considerable promise. Targeting the vascular endothelial growth factor (VEGF) and estrogen receptor (ER) signaling pathways concomitantly may provide enhanced therapeutic benefit in ER-positive breast cancer. Therefore, the effects of the VEGF receptor (VEGFR) tyrosine kinase inhibitor PTK787/ZK222584 (PTK/ZK) were investigated using human breast cancer cell lines engineered to express aromatase. As expected in this system, estrogen (E2) or androstenedione induced a proliferative response and increased ER-mediated transcription in ER-positive cell lines expressing aromatase. However, surprisingly, in the presence of androstenedione, PTK/ZK suppressed both the androstenedione-stimulated proliferation and ER-mediated transcription. PTK/ZK alone and in the presence of E2 had no observable effect on proliferation or ER-mediated transcription. These effects result from PTK/ZK having previously unrecognized antiaromatase activity and PTK/ZK being a competitive aromatase inhibitor. Computer-assisted molecular modeling showed that PTK/ZK could potentially bind directly to aromatase. The demonstration that PTK/ZK inhibits aromatase and VEGFR indicates that agents cross-inhibiting two important classes of targets in breast cancer could be developed. [Cancer Res 2009;69(11):4716–23]