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Remedies for breach of contract in the international sale of goods – a comparative study between the CISG, Chinese Law and English law with reference to Chinese cases
No full textThe United Nations Convention on Contracts for the International Sale of Goods (CISG) is one of the most successful international instruments that provide uniformity in the rules for international trade. It has been adopted by seventy-three countries and has been in force for twenty-one years. The People’s Republic of China (PRC) signed the CISG on 30th September 1981 and many international sales of goods cases have been resolved under the CISG in China. The author will investigate these Chinese cases to examine the effectiveness of the CISG in order to establish whether the application of the CISG has been successful in leading to predictable judgments. This thesis focuses on remedies for breach of contract in the international sale of goods. Remedies are the main reason why claims are made in the international sale of goods and as such they are fundamental to that trade. The main remedies considered in this thesis are the avoidance of contract, damages and specific performance. In addition, mitigation and the categorisation of the breach of contract are discussed where the former is an important means to restrict the recoverable damages and the latter constitutes the foundation for the study of remedies for breach of contract. Furthermore, the provisions related to the remedial rule of the CISG are those that the Chinese tribunals have applied most in their judgments. Research in this area provides the author with sufficient sources of cases for the examination of the Chinese decisions. Two other alternative national regimes are compared with the CISG to assess the predictability of decisions under these systems. These are the old Chinese law, i.e., the PRC Foreign-Related Economic Contract Law (FECL) and English law, i.e., Sale of Goods Act 1979 (SGA) together with English case law. The FECL was the governing law of the international sale contract before China acceded to the CISG. The SGA is the present statute of English international sale contract law. The similarities and differences of the remedial rules between the CISG, FECL and English law are compared in this thesis. Analysis of the Chinese cases tried under the rules of the CISG shows that the outcomes of these cases are not predictable. The author will apply the remedial rules of the FECL and English law to the Chinese cases examined here to find out whether the application of either of these two alternative regimes could have led to outcomes that are more predictable. The conclusion of this thesis summarizes the results of the author’s examination with regard to the Chinese tribunals’ difficulties in making predictable judgments, the causes of difficulty where judgments have been unpredictable and the author’s proposals as to how to resolve such difficultie
CUHK electronic theses & dissertations collection
No full textLi, Yan Hei.Thesis M.Phil. Chinese University of Hong Kong 2015.Includes bibliographical references (leaves 58-68).Abstracts also in Chinese.Title from PDF title page (viewed on 11, November, 2016)
CUHK electronic theses & dissertations collection
No full textLi, Yan Kit.Thesis M.Phil. Chinese University of Hong Kong 2014.Includes bibliographical references (leaves 83-89).Abstracts also in Chinese.Title from PDF title page (viewed on 30, November, 2016)
Evaluation of Mortality prediction model from Li Yan et al. on an Indian cohort.
No full textEvaluation of Mortality prediction model from Li Yan et al. on an Indian cohort.</p
Studies on the molecular basis for activation of phospholipase A2 found in inflammatory exudates
No full textImproved therapeutic efficacy of decorin expressing oncolytic adenovirus driven by cancer- and tumor microenvironment-specific promoter in pancreatic cancer
Full text linkGraduate Program for Nanomedical Science/박사Pancreatic cancer is a leading cause of cancer-related death. Desmoplastic pancreatic tumors exhibit excessive extracellular matrix (ECM) and are thus highly resistant to anticancer therapeutics, since the ECM restricts drug penetration and dispersion. Here, we designed and generated two hypoxia-responsive and cancer-specific hybrid promoters, HmTE and HEmT. Transgene expression driven by each hybrid promoter was markedly higher under hypoxic conditions than normoxic conditions. Moreover, HEmT-driven transgene expression was highly cancer-specific and was superior to that of HmTE-driven expression. A decorin-expressing oncolytic adenovirus (Ad; oHEmT-DCN) replicating under the control of the HEmT promoter induced more potent and highly cancer-specific cell death compared with its cognate control oncolytic Ad, which harbored the endogenous Ad E1A promoter. Moreover, oHEmT-DCN exhibited enhanced antitumor efficacy compared with both the clinically approved oncolytic Ad ONYX-015 and its cognate control oncolytic Ad lacking DCN. oHEmT-DCN treatment also attenuated the expression of major ECM components, such as collagen I/III, elastin, and fibronectin, and induced tumor cell apoptosis, leading to extensive viral dispersion within orthotopic pancreatic tumors and pancreatic cancer patient-derived tumor spheroids. Collectively, these findings demonstrate that oHEmT-DCN exhibits potent antitumor efficacy by degrading the ECM and inducing apoptosis in a multifunctional process. This process facilitates the dispersion and replication of oncolytic Ad, making it an attractive candidate for the treatment of aggressive and desmoplastic pancreatic cancer.
2013년 말 발표된 국가 암 등록통계 자료에 따르면, 췌장암은 한국인 암 사망원인의 5위로 조사된 암종 중 5년 생존율이 가장 낮은 5%, 중앙생존기간은 5개월에 불과한 가장 치명적 종양질환이다. 췌장암 환자의 90% 정도는 이미 근치적 수술을 시행할 수 없는 상태에서 발견되어 인체 암 중 예후가 가장 불량한 것으로 보고되었다. 또한 췌장암 환자의 항암제 반응률은 20% 내외에 불과할 뿐 아니라 조기에 항암제 내성이 발생하는 것으로 알려져 있다. 결합조직증식 반응(desmoplasia)이 활발하게 일어나는 췌장암 조직은 조직 내 증가된 저산소 조건과 과도하게 분포된 세포외기질(extracellular matrix)로 인해 종양의 악성도가 크게 증가될 뿐 아니라 약물의 침투 및 확산이 저해되고 이러한 췌장암 조직의 독특한 특성은 항암 치료제의 치료효과를 감소시키는 원인으로 작용한다. 그러므로 이러한 췌장암의 종양 미세환경을 표적할 수 있는 새로운 패러다임의 췌장암 치료제의 개발이 절실히 요구되는 실정이다.
따라서 본 연구에서는, 종양 특이적 살상 아데노바이러스의 저산소 조건에서의 복제능을 증가시키기 위해, 종양 살상 아데노바이러스인 Rd19-k35에 종양 선택성을 높이고 저산소 조건에서 바이러스의 복제를 조절할 수 있는 HmTE와 HEmT 프로모터를 도입하여 oHmTE(HmTE-Rd19-k35)와 oHEmT(HEmT-Rd19-k35)를 제작하였다. 췌장암 세포주에서 제작된 oHmTE와oHEmT의 암세포 살상능 및 바이러스 증식능을 검증하여, oHmTE에 비해 oHEmT가 우수한 프로모터 활성을 나타내는 것을 확인하였다. 이러한 결과를 바탕으로, oHEmT 바이러스에 세포고사를 유도하고 세포외기질을 분해할 수 있는 데코린(DCN)유전자를 삽입하여 oHEmT-DCN을 제작하고 이를 이용하여 췌장암 동소이식 동물모델 및 췌장암 환자 유래 종양조직에서 항종양 효과를 확인하였다. oHEmT-DCN를 투여한 그룹에서 현재 시판되고 있는 종양 특이적 살상 아데노바이러스인 ONYX-015 또는 대조군인 oHEmT를 투여한 그룹에 비해 현저히 향상된 항종양 효과가 나타남을 확인하였다. 뿐만 아니라 췌장암 조직에서 HEmT 프로모터에 의해 바이러스가 저산소 환경을 효과적으로 표적하여 저산소 조건에서의 바이러스 복제저하가 개선됨을 확인하였고, 종양조직 내에서 oHEmT-DCN에 의한 치료유전자 DCN의 발현 증가, TGF-β의 발현 감소, 바이러스 분포 및 복제 증가, 췌장암 조직 내의 세포외기질 분해 증가, 그리고 종양조직 특이적 세포고사의 증가 등을 통해 결과적으로 우수한 항종양 효과가 유도됨을 확인하였다. 따라서 데코린을 발현하는 종양 선택적 살상 아데노바이러스는 종양 미세환경의 저산소 조건 및 세포외기질을 효과적으로 표적하고 증대된 항종양 효과를 유도하므로 안전하고 효과적인 췌장암 치료제로 적용될 수 있을 것으로 사료된다.ope
Identification and investigation of cellular factors associated with HIV replication
No full textHuman immunodeficiency virus type-1 (HIV-1) is a member of the lentivirus subfamily of the retroviridae family. Currently, HIV infection is considered incurable. Combinations of antiretroviral therapies will limit HIV replication and is able to extend the patients’ lives. However, HIV-1 multi-drug resistance continues to rise. Therefore, novel HIV inhibitors are needed. Like all viruses, HIV-1 requires host cellular factors for productive replication. Identification of these factors may lead to the development of novel cell-based inhibitors.
The first study of this dissertation is based on a previous proteomic screening in our laboratory that identified nuclear factor 45 (NF45) and nuclear factor 90 (NF90) as potential cellular factors involved in HIV-1 replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1, which is required for Tat-dependent trans-activation of viral gene expression. In this study, the roles of NF45 and NF90 in HIV replication were investigated through over-expression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 and NF90 diminished the enhancement of HIV infection and gene expression. Both proteins were found to interact with the HIV RNA in a sequence independent manner. RNA decay assays demonstrated that NF90, but not NF45, increased the half-life of the HIV RNA. Overall, these studies demonstrate that both NF45 and NF90 potentiate HIV infection through their RNA binding activities.
In the next study described in this dissertation, I constructed a labelled virus to perform affinity purification-mass spectrometry and identify the host factors which interact with the matrix (MA) protein of HIV. A Strep affinity tag was inserted into the C-terminus of the MA protein. The resultant virus was replication competent and used to infect Jurkat T-cells. Matrix complexes were affinity purified with Strep-Tactin agarose. Protein identification was performed by sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry. The data was log2 transformed and student t-tests with Bonferroni correction used to determine proteins associated with matrix. A total of 17 proteins were found to be statistically different between the infected versus uninfected and untagged control samples. Several candidate proteins were validated by immunoblot and investigated for their role in virus infection by siRNA knockdown assays. Ku70, Ku80 and YB-1 were confirmed to interact with matrix by immunoblot. Knockdown of two candidates, EZRIN and YB-1, enhanced HIV infection in vitro. These data further increased our understanding of HIV-host cell interactions.
For the final study, we investigated the effects of deletions in the C-terminal alpha helix (α5) of MA on virus assembly release. Deletion of the N-terminus of α5 as small as three amino acids impaired virus release. Electron microscopy of one deletion mutant (MA∆96-120) showed that its particles were tethered to the surface of cells by membranous stalks. Immunoblots indicated all mutants were processed completely, but mutants with large deletions had alternative processing intermediates. Consistent with the EM data, MA∆96-120 retained membrane association and multimerization capability. Co-expression of this mutant inhibited wild type particle release. Alanine scanning mutation in this region did not affect virus release, although the progeny virions were poorly infectious. Combined, these data demonstrate that structural ablation of the α5 of MA inhibits virus release.ProQuest Traditional Publishing Optionxvi, 220 page
Digitalisation and labour productivity in the tourism sector: a micro-enterprise level analysis
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