Synchrotron x-ray and electrochemical studies of pitting corrosion of iron

Pitting corrosion of iron has been studied via artificial pits. Solid corrosion products were observed within the pit, which was characterised as disordered-carbon and Fe$_3$C, acted as diffusion barriers for metal ions and slightly increased the solution resistance. Its formation depends upon the interfacial potential. High purity iron was used to calculate an effective diffusion coefficient for metal ions (a combination of self-diffusion and electrical migration) in different MgCl$_2$ concentrations. The contribution of self-diffusion increases with increasing MgCl$_2$ concentration if Mg$^2$$^+$ depletion in the pit is considered. The Tafel kinetics of iron dissolution in metal ion saturated solutions was studied in different MgCl$_2$ concentrations. The Tafel slope (56 to 70 mV/decade) was independent of MgCl$_2$ and FeCl$_2$ concentration when FeCl$_2$ is saturated. The effect of nitrate on the composition/structure of salt layers was characterised. The salt layer is composed of FeCl$_2$.4H$_2$O in chloride-based solutions (isotropic in HCl and anisotropic in HCl with trace nitrate), and Fe(NO$_3$)$_2$.6H$_2$O in nitrate-based solutions. The dissolution behaviour of iron in chloride/nitrate solutions was studied. Dissolution is uniform under a salt layer, but crevice formation and surface roughening. Potentiodynamic measurements can induce abrupt dissolution/ passivation transitions, resulting in deep and localised attack

Peptide-based biosensors and light-activatable proteins: tools for studying cell signaling and developing cancer diagnosis

Protein kinases play central roles in almost all aspects of normal and abnormal cell functions. Therefore, methods that provide sensitive, selective and controllable measurement of kinase activity should prove useful for studying cell signaling events. Moreover, easy to operate, generalizable strategies are in high demand for disease diagnosis. This dissertation described the development and application of peptide-based kinase biosensors and strategies to control enzyme activities by light. First, we developed a highly sensitive peptide-based biosensor that employs capillary electrophoresis to measure Src activity in prostate cell lysates as well as in single living cells. Our studies revealed that there is a direct correlation between cell aggressiveness and the fraction of cellular Src that is in the active state. We also determined that pTyr-527 level of Src is a poor indicator of inactive Src. In addition, we have demonstrated that two or more kinases can be simultaneously monitored using this technique. Second, aimed at unraveling the distinct roles of the Src family kinases Fyn and Lck in T cell activation, we developed a highly selective, potent, and light-deactivatable Fyn inhibitor. This inhibitor provides a way of selectively activating Fyn kinase by light. We have also discovered that attaching a profluorescent dye rendered this peptide cell permeable. Third, we described a new strategy for the construction of a profluorescent light-activatable cAMP-dependent protein kinase (PKA) via active site-directed peptide-based affinity labeling. This modified PKA displays minimum catalytic activity and low fluorescence. Light illumination restored enzymatic activity and induced stress fibers lose in living cells. A 6.2-fold fluorescence enhancement was also observed. The strategies developed in these studies provided powerful tools to elucidate the relationship of kinase activity with disease stages and the complex cell signaling networks. With these tools in hand, we are hoping to advance our knowledge of a basic biological phenomenon as well as providing future diagnostic tool for cancer patients.Doctor of Philosoph

The Supreme People\u27s Court Annual Report on Intellectual Property Cases (2017) (China)

The Supreme People’s Court of China began publishing its Annual Report on Intellectual Property Cases in 2008. The Annual Report summarizes intellectual property cases, such as patent, trademark, trade secrets, copyright, and unfair competition cases. This 2017 Annual Report examines 42 cases and includes general guidelines for legal application. This summary reflects the Supreme People’s Court’s thoughts and approaches for ruling on new and complex IP and competition cases

Towards Arbitrary Text-driven Image Manipulation via Space Alignment

The recent GAN inversion methods have been able to successfully invert the real image input to the corresponding editable latent code in StyleGAN. By combining with the language-vision model (CLIP), some text-driven image manipulation methods are proposed. However, these methods require extra costs to perform optimization for a certain image or a new attribute editing mode. To achieve a more efficient editing method, we propose a new Text-driven image Manipulation framework via Space Alignment (TMSA). The Space Alignment module aims to align the same semantic regions in CLIP and StyleGAN spaces. Then, the text input can be directly accessed into the StyleGAN space and be used to find the semantic shift according to the text description. The framework can support arbitrary image editing mode without additional cost. Our work provides the user with an interface to control the attributes of a given image according to text input and get the result in real time. Ex tensive experiments demonstrate our superior performance over prior works.Comment: 8 pages, 12 figure

Conversion therapy with immunotherapy plus chemotherapy achieves a pathological complete response in stage IIIC NSCLC

As stage IIIC non-small cell lung cancer (NSCLC) is not recommended for surgical resection, the survival and prognosis for stage IIIC NSCLC remain poor. More powerful and individualized therapies are urgently needed to improve the prognosis of stage IIIC NSCLC. Recently, immunotherapeutics have been increasingly considered in the neoadjuvant therapy of NSCLC. This study presents a patient with stage IIIC NSCLC achieving a pathological complete response (pCR) following conversion therapy with immunotherapy plus chemotherapy. This case also presents a histologic transformation from squamous cell carcinoma to adenocarcinoma after prolonged progression-free survival (PFS) following surgery. Collectively, this case suggests that conversion immunotherapy with chemotherapy and subsequent surgery can be considered and benefits a subset of unresectable stage IIIC NSCLC

Construction of a Photoactivatable Profluorescent Enzyme Via Propinquity Labeling

A strategy for the construction of a profluorescent caged enzyme is described. An active site-directed peptide-based affinity label was designed, synthesized, and employed to covalently label a non-active site residue in the cAMP-dependent protein kinase. The modified kinase displays minimal catalytic activity and low fluorescence. Photolysis results in partial cleavage of the enzyme-bound affinity label, restoration of enzymatic activity (60 – 80%) and a strong fluorescent response (10 – 20 fold). The caged kinase displays analogous behavior in living cells, inducing a light-dependent loss of stress fibers that is characteristic of cAMP action. This strategy furnishes molecularly engineered enzymes that can be remotely controlled in time, space, and total activity

Molecular Docking of Potential Inhibitors for Influenza H7N9

As a new strain of virus emerged in 2013, avian influenza A (H7N9) virus is a threat to the public health, due to its high lethality and pathogenicity. Furthermore, H7N9 has already generated various mutations such as neuraminidase R294K mutation which could make the anti-influenza oseltamivir less effective or ineffective. In this regard, it is urgent to develop new effective anti-H7N9 drug. In this study, we used the general H7N9 neuraminidase and oseltamivir-resistant influenza virus neuraminidase as the acceptors and employed the small molecules including quercetin, chlorogenic acid, baicalein, and oleanolic acid as the donors to perform the molecular docking for exploring the binding abilities between these small molecules and neuraminidase. The results showed that quercetin, chlorogenic acid, oleanolic acid, and baicalein present oseltamivir-comparable high binding potentials with neuraminidase. Further analyses showed that R294K mutation in neuraminidase could remarkably decrease the binding energies for oseltamivir, while other small molecules showed stable binding abilities with mutated neuraminidase. Taken together, the molecular docking studies identified four potential inhibitors for neuraminidase of H7N9, which might be effective for the drug-resistant mutants

Applications of functional nucleic acids in imaging, sensing and drug delivery and investigations of DNAzyme-metal interactions

Functional nucleic acids (FNA), including nucleic acids catalysts (ribozymes and DNAzymes) and ligands (aptamers), have been discovered in nature or isolated in a laboratory through a process called in vitro selection. They are nucleic acids with functions similar to protein enzymes or antibodies. They have been developed into sensors with high sensitivity and selectivity; it is realized by converting the reaction catalyzed by a DNAzyme/ribozyme or the binding event of an aptamer to a fluorescent, colorimetric or electrochemical signal. While a number of studies have been reported for in vitro sensing using DNAzymes or aptamers, there are few reports on in vivo sensing or imaging. MRI is a non-invasive imaging technique; smart MRI contrast agents were synthesized for molecular imaging purposes. However, their rational design remains a challenge due to the difficulty to predict molecular interactions. Chapter 2 focuses on rational design of smart T1-weighted MRI contrast agents with high specificity based on DNAzymes and aptamers. It was realized by changing the molecular weight of the gadolinium conjugated DNA strand with the analytes, which lead to analyte-specific water proton relaxation responses and contrast changes on an MRI image. The designs are general; the high selectivity of FNA was retained. Most FNA-based fluorescent sensors require covalent labeling of fluorophore/quencher to FNAs, which incurrs extra expenses and could interfere the function of FNAs. Chapter 3 describes a new sensor design avoiding the covalent labeling of fluorophore and quencher. The fluorescence of malachite green (MG) was regulated by the presence of adenosine. Conjugate of aptamers of MG and adenosine and a bridge strand were annealed in a solution containing MG. The MG aptamer did not bind MG because of its hybridization to the bridge strand, resulting in low fluorescence signal of MG. The hybridization was weakened in the presence of adenosine, leading to the binding of MG to its aptamer and a fluorescence increase. The sensor has comparable detection limit (20 micromolar) and specificity to its labeled derivatives. Enzymatic activity of most DNAzymes requires metal cations. The research on the metal-DNAzyme interaction is of interest and challenge to scientists because of the lack of structural information. Chapters 4 presents the research on the characterization of the interaction between a Cu2+-dependent DNAzyme and Cu2+. Electron paramagnetic resonance (EPR) and UV-Vis spectroscopy were used to probe the binding of Cu2+ to the DNAzyme; circular dichroism was used to probe the conformational change of the DNAzyme induced by Cu2+. It was proposed that the conformational change by the Cu2+ binding is important for the activity of the DNAzyme. Chapter 5 reports the dependence of the activity of 8-17 DNAzyme on the presence of both Pb2+ and other metal cations including Zn2+, Cd2+ and Mg2+. It was discovered that presence of those metal cations can be cooperative or inhibitive to 8-17 activity. It is hypothesized that the 8-17 DNAzyme had multiple binding sites for metal cations based on the results. Cisplatin is effective killing tumor cells, but with significant side effects, which can be minimized by its targeted delivery. Chapter 6 focuses on the effort to functionalize liposomes encapsulating cisplatin by an aptamer that selectively bind nucleolin, an overexpressed protein by breast cancer cells. The study proved the selective cytotoxicity to breast cancer cells of the aptamer-functionalized liposome