176 research outputs found

    Public value creation : exploring partnerships in value capture projects in China : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Resource and Environmental Planning at Massey University, Manawatu, New Zealand

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    The urban planning literature has identified a positive relationship between public transport investment and the land value of adjacent properties. In many cities worldwide, the increase in land value has been captured (called value capture (VC)) to fund public transport infrastructure and services. However, the key issue for the planning and implementation of VC is the complexity of the multiple stakeholders’ collaboration and coordination in the process, and few studies have investigated this complexity. This research aimed to fill this gap and explore how different stakeholders have worked together to plan and implement VC policies and projects in China. This research developed a theoretical framework based on public value and partnership theories. These theories provide a comprehensive strategic triangle framework to explore interdependent processes of enabling environment, operational capabilities, and goals to create public value of VC development. Based on the framework, this research proposed three types of partnerships for investigating the VC process. The political–institutional partnership analysed how government organisations and local transport agencies create an enabling political and institutional environment to take the initiative and plan for VC projects. The financial partnership focused on how local transport agencies develop partnerships with other public and private organisations to share the risks, responsibilities, and benefits of developing real estate in VC projects. The social partnership examined what role culturally sensitive communication and trust play in building relationships between local government and local communities. This research used a qualitative research approach by applying the case study method. Two Chinese VC projects, the Qianhai project in Shenzhen and the Luxiao project in Chengdu, were selected as case studies in this research. Data were collected from 55 semi-structured interviews with relevant stakeholders, and from policy and planning documents produced at the central, provincial, and local government levels, supplemented by enterprise reports, media information, and research papers. Firstly, the research found that stable and sustained political–institutional support is crucial to the initiation planning, and implementation of a VC project. Because of continuous political support, Shenzhen initially adopted the Hong Kong model but later developed its own model and institutional capacity for VC projects. In contrast, VC projects in Chengdu suffered as a result of uncertain political support, a fragmented planning framework, an insufficient land exchange market, and a lack of experience and knowledge of VC projects. Both case studies showed that creating a partnership between local government and local transport agency is vital for mobilising land resources, sharing planning power, and generating institutional innovation in land transactions. Secondly, the research illustrated that a financial partnership between local transport agencies and developers is fundamental for implementing VC projects. In Shenzhen, the local transport agency established proactive working relationships with developers, creating a flow of the resources necessary for implementing the projects. In contrast, the local transport agency in Chengdu ignored developers and worked directly with the district-level government without a competitive selection process. This process created concerns for real estate development in the later stages of implementation. Thirdly, the research identified that developing a trustworthy social partnership between the local government and the local communities is beneficial for enhancing the legitimacy of VC projects. Shenzhen adopted both top-down and bottom-up public participation processes to engage local communities. In comparison, weak communication in Chengdu led to limited community involvement and a lack of public awareness of the VC project. Both case studies showed a strong emphasis on expert opinions and little contact with non-governmental organisations in China’s VC projects. This research concluded that political–institutional, financial, and social partnerships have contributed significantly to VC planning and implementation in China. These partnerships worked together and developed an enabling environment, promoted legitimacy, and established operational capacities to deliver the VC projects. However, these partnerships were not developed in a vacuum, and macro and contextual factors played an essential part in the planning and implementation of the VC projects

    Tetrazole-containing STAT5 Inhibitors Derived from Furazan-based Phosphate Mimetics

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    Signal transducers and activators of transcription (STAT) are a family of proteins that regulate gene transcription. Seven members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6) have been identified in human STAT family since two decades ago. As a member of the STAT family, STAT5 plays a central role in transmitting signals from transmembrane receptors such as cytokine receptors and growth factor receptors to the nucleus. It has been found that STAT5 is constitutively phosphorylated at a conserved tyrosine residue located at the end of SH2 domain by various activated tyrosine kinases in a broad range of human cancer cells. Inhibiting STAT5 has been considered as a promising approach for cancer therapy. However, STATs have been described as difïŹcult pharmacological targets and small-molecule inhibitors of STAT5 are poorly investigated. The subject of this work is the investigation of small-molecule inhibitors targeting STAT5b-SH2. The tetrazole-containing active compounds discovered in this work are derived from the furazan-based phosphate mimetics. In the first section of this work, a structurally stable scaffold was designed. The aim is to improve the binding affinity of the existing inhibitors and to avoid the instability. For this purpose, four different methods were tried to synthesize the new structures. The main problem, low reactivity of the amino group in fragment 1 in the formation of a linkage between the furazan ring and the 5-position in the tetrazole ring, was solved in the N-cyanomethyl amine synthetic method. The obtained compounds showed expected stability under acidic conditions. However, these compounds were surprisingly inactive in a FP binding assay. In the second section of this work, a series of 1-aminomethyl tetrazoles based on the structures with different substituents at the 5-position of the tetrazole ring was synthesized via Mannich ligation reaction. Most of them displayed binding affinity to STAT5b-SH2 in low micromolar range in the FP-based competitive binding assay, in which compound 24 was the most active one with a Ki value of 1.8 ”M. To investigate how different substituents at the 5-position of the tetrazole ring influence the stability of the scaffold, a systematic stability analysis was carried out on LC-MS and compounds 19, 22, 24, and 25 were found to possess better stability in contrast with the lead compounds 2 and 3. Furthermore, the binding of compound 24 to STAT5b-SH2 and the pivotal role of Asn642 were proven in the binding assays. Finally, the inhibitory activity of compounds 3 and 24 on leukemic cell proliferation was determined by the Alamar Blue assay.STAT (signal transducers and activators of transcription) sind eine Familie von Proteinen, die die Gentranskription regulieren. Sieben Mitglieder (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6) wurden vor zwei Jahrzehnten in der menschlichen STAT-Familie identifiziert. Als Mitglied der STAT-Familie spielt STAT5 eine zentrale Rolle bei der Übertragung von Signalen von Transmembranrezeptoren wie Zytokinrezeptoren und Wachstumsfaktorrezeptoren zum Zellkern. Es wurde gefunden, dass STAT5 an einem konservierten Tyrosinrest, der sich am Ende der SH2-DomĂ€ne befindet, durch verschiedene aktivierte Tyrosinkinasen in einem breiten Bereich menschlicher Krebszellen konstitutiv phosphoryliert wird. Die Hemmung von STAT5 gilt als vielversprechender Ansatz fĂŒr die Krebstherapie. STAT-Proteine wurden jedoch als schwierige pharmakologische Ziele beschrieben, und niedermolekulare Inhibitoren von STAT5 sind nur unzureichend untersucht. Gegenstand dieser Arbeit ist die Untersuchung von niedermolekularen Inhibitoren, die auf STAT5b-SH2 abzielen. Die in dieser Arbeit entdeckten Tetrazol-haltigen Verbindungen leiten sich von den Furazan-basierten Phosphat-Mimetika ab. Im ersten Teil dieser Arbeit wurde ein strukturelles stabiles GerĂŒst entworfen. Ziel ist es, die BindungsaffinitĂ€t der vorhandenen Inhibitoren zu verbessern und die InstabilitĂ€t zu vermeiden. Zu diesem Zweck wurden vier verschiedene Methoden zur Synthese der neuen Strukturen ausprobiert. Das Hauptproblem, die geringe ReaktivitĂ€t der Aminogruppe in Fragment 1 bei der Bildung einer Bindung zwischen dem Furazanring und der 5-Position im Tetrazolring, wurde mit der N-Cyanomethylamin-Synthesemethode gelöst. Die erhaltenen Verbindungen zeigten erwartete StabilitĂ€t unter sauren Bedingungen. Diese Verbindungen waren jedoch in einem FP-Bindungsassay ĂŒberraschend inaktiv. Im zweiten Teil dieser Arbeit wurde eine Reihe von 1-Aminomethyltetrazolen basierend auf den Strukturen mit unterschiedlichen Substituenten an der 5-Position des Tetrazolrings durch Mannich-Ligation synthetisiert. Die meisten von ihnen zeigten im FP-basierten kompetitiven Bindungstest, in dem Verbindung 24 die aktivste Verbindung mit einem Ki-Wert von 1,8 ”M war, eine BindungsaffinitĂ€t zu STAT5b-SH2 im niedrigen mikromolaren Bereich. Um zu untersuchen, wie unterschiedliche Substituenten an der 5-Position des Tetrazolrings die StabilitĂ€t des GerĂŒsts beeinflussen, wurde eine systematische StabilitĂ€tsanalyse an LC-MS durchgefĂŒhrt und festgestellt, dass die Verbindungen 19, 22, 24 und 25 im Gegensatz dazu eine bessere StabilitĂ€t aufweisen mit den Bleiverbindungen 2 und 3. Weiterhin wurden die Bindung von Verbindung 24 an STAT5b-SH2 und die SchlĂŒsselrolle von Asn642 in den Bindungsassays nachgewiesen. Schließlich wurde die Hemmwirkung der Verbindungen 3 und 24 auf die LeukĂ€miezellproliferation durch den Alamar Blue-Assay bestimmt

    A predictive distributed congestion metric with application to technology mapping

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    Capacity Expansion of High Renewable Penetrated Energy Systems Considering Concentrating Solar Power for Seasonal Energy Balance

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    With the increasing proportion of variable renewable energy which owns fluctuation characteristics and the promotion of the Clean Heating policy, the seasonal energy imbalance of the system has been more and more challenging. There is a lack of effective means to mitigate this challenge under the background of gradual compression of the traditional thermal unit construction. Concentrating solar power (CSP) is a promising technology to replace thermal units by integrating emergency boilers to cope with extreme weather, and can meet long-time energy balance as a seasonal peak regulation source. In this paper, we propose a long-term high-resolution expansion planning model of the energy system under high renewable penetration which integrates CSP technology for seasonal energy balance. With the projection to 2050, by taking the energy system in Xinjiang province which is a typical area of the Clean Heating project with rich irradiance as a case study, it shows that the optimal deployment of CSP and electric boiler (EB) can reduce the cost, peak-valley difference of net load and renewable curtailment by 8.73%, 19.72% and 58.24% respectively at 65% renewable penetration compared to the base scenario.Comment: 17 pages, 13 figure

    Wave-resistance computation via CFD and IGA-BEM solvers : a comparative study

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    This paper delivers a preliminary comparative study on the computation of wave resistance via a commercial CFD solver (STAR-CCM+Âź) versus an in-house developed IGA-BEM solver for a pair of hulls, namely the parabolic Wigley hull and the KRISO container ship (KCS). The CFD solver combines a VOF (Volume Of Fluid) free-surface modelling technique with alternative turbulence models, while the IGA-BEM solver adopts an inviscid flow model that combines the Boundary Element approach (BEM) with Isogeometric Analysis (IGA) using T-splines or NURBS. IGA is a novel and expanding concept, introduced by Hughes and his collaborators (Hughes et al, 2005), aiming to intrinsically integrate CAD with Analysis by communicating the CAD model of the geometry (the wetted ship hull in our case) to the solver without any approximation

    A Video-Based Augmented Reality System for Human-in-the-Loop Muscle Strength Assessment of Juvenile Dermatomyositis

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    As the most common idiopathic inflammatory myopathy in children, juvenile dermatomyositis (JDM) is characterized by skin rashes and muscle weakness. The childhood myositis assessment scale (CMAS) is commonly used to measure the degree of muscle involvement for diagnosis or rehabilitation monitoring. On the one hand, human diagnosis is not scalable and may be subject to personal bias. On the other hand, automatic action quality assessment (AQA) algorithms cannot guarantee 100% accuracy, making them not suitable for biomedical applications. As a solution, we propose a video-based augmented reality system for human-in-the-loop muscle strength assessment of children with JDM. We first propose an AQA algorithm for muscle strength assessment of JDM using contrastive regression trained by a JDM dataset. Our core insight is to visualize the AQA results as a virtual character facilitated by a 3D animation dataset, so that users can compare the real-world patient and the virtual character to understand and verify the AQA results. To allow effective comparisons, we propose a video-based augmented reality system. Given a feed, we adapt computer vision algorithms for scene understanding, evaluate the optimal way of augmenting the virtual character into the scene, and highlight important parts for effective human verification. The experimental results confirm the effectiveness of our AQA algorithm, and the results of the user study demonstrate that humans can more accurately and quickly assess the muscle strength of children using our system

    Human EVI2B acts as a Janus-faced oncogene/antioncogene by differently affecting as per cancer type neoplastic cells growth and immune infiltration

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    Objectives: The EVI2B (Ecotropic Viral Integration Site 2B) gene encodes a transmembrane glycoprotein pivotal in immunocytes maturation. Recent evidence implicated EV12B’s expression with human colon cancer progression. However, EVI2B’s downstream pathways affecting tumor growth and tumor-infiltrating cells remain unclear. Methods: We first studied the diagnostic and prognostic value of EVI2B in pan-cancers by utilizing a series of in silico tools and clinical samples. Then we identified the modulated transcriptional expression and DNA methylation in high EVI2B’s expression groups of the same three cancers. We verified via RT-PCR the effect of stable EVI2B knock-down on the expression of JAK/STAT-related genes in two immune cell lines and the acceleration of proliferation in four cancer cell lines. Finally, the regulation of leukocyte infiltration was studied using TIMER. Results: In SKCM and LUAD a heightened EVI2B’s expression promoted a better prognosis. Conversely, in LGG EVI2B’s upregulation concurred with a worse prognosis. EVI2B silencing enhanced the proliferation of the tumor cell lines. The hypermethylated genome strengthened EVI2B’s Janus-like effect in high EVI2B expressing SKCM and LUAD tumors. While the total DNA methylation was lower in high EVI2B expressing LGG. Further analysis revealed that multiple EVI2B-involved down-stream JAK-STAT genes also exhibited the Janus-like feature in SKCM, LUAD and LGG progression. Correspondingly, anti-tumor leukocytes infiltrated EVI2B high expressing SKCM and LUAD while more pro-tumor ones penetrated into EVI2B heightened LGG. Conclusions: EVI2B acts as a Janus-faced oncogene/antioncogene by differently affecting neoplastic cell proliferation rates and tumor-promoting or tumor-hindering immunocytes’ infiltration
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