Site specific cross-linking of thio-nucleosides

Cancer is a devastating disease. Numerous drugs have been synthesised over the years aiming to cure cancer. Significant new advancements in anti-cancer therapy have been achieved over the past few years. This was made possible by the molecular level understanding of the cancer disease, which has led to the synthesis of various targeted drugs. The targets within the cancer cells are very limited for anti-cancer drug design because cancerous cells resemble normal cells in most of their molecular aspects. This makes it extremely difficult for cell specific incorporation of drugs or cell killing. So, alternative approaches have been followed for specific cell killing. However, such approaches are still at an early stage and a great deal of work needs to be done. Various DNA-targeted approaches, such as photo cross-linking and chemical cross-linking; have been developed for killing cancerous cells. These approaches have not completely solved the problem of specificity. Like traditional anti cancer drugs, these agents also indiscriminately cross-link DNA in both normal cells, cancerous cells leading to cell death. In this thesis, two modified nucleosides were chosen which can be incorporated into the DNA of the cells easily. These thio-modified nucleosides were proven to have more affinity towards the DNA of the cancerous cells. Such modified nucleosides have previously been exploited for anti-cancer activity, especially UVA cell killing. In this thesis the thio-modified nucleosides have been explored for their site specific cross-linking activity. The first modified nucleoside 4-thiothymidine was synthesised and reported in 1959. 4-Thiothymidine resembles thymidine, except for a modification at position 4 with sulphur instead of oxygen. Previous studies have shown that 4-thiothymidine behaves like thymidine when incorporated into the cells. Like thymidine, this is base-paired with adenine in DNA. In this thesis, at first the thiol group of 4-thiothymidine has been specifically activated by a stable and readily replaceable group. This group was then replaced by various thio-nucleophiles which lead to the cross-linking of the nucleoside. The standards of these cross-linked nucleosides were successfully synthesised and characterised. In the quest to improve specificity of incorporation into cancer cells a novel pro-drug, 4-thio-5-bromodeoxyuridine (S4-BrdU) was synthesised by members of our group in 2003. This nucleoside is another thymidine analogue which is modified by replacing oxygen at position 4 with sulphur and methyl at position 5 with bromine. The thiol group of S4-BrdU nucleoside was chosen for the purpose of cross-linking. Successful cross-linking of the nucleoside with various thiol nucleophiles has been explored. Firstly S4-BrdU was converted into a DNP derivative. The DNP was then replaced with mercaptoethanol, thioethanethiol and natural thiols such as cysteine (the only amino acid containing a thiol group in the molecule) and glutathione (a natural peptide which helps in detoxification pathways in the body). These cross-linked products have been characterised by various methods. After successfully cross-linking the nucleosides, oligomers containing 4-thiothymidine were synthesised. The oligomers were characterised and 4-thiothymidine was successfully incorporated into the oligomers

Gate Driver Circuit Design, PWM signal generation using FEZ Panda III and Arduino for Inverter

This paper presents the gate driver circuit design and PWM signal generation using FEZ panda III and Arduino boards for Inverter. FEZ panda III works on .net micro framework and all its programming, debugging features are available through Microsoft’s Visual studio whereas Arduino features are available through Arduino software. Inverters are used in various applications like in motor drives and solar and wind power applications. This paper is commenced by basic understanding of need of gate driver circuit for inverter and different types of PWM techniques for generating gate signals for inverter. Simulation of SPWM inverter in both open loop and closed loop operation is done and its respective gate voltage waveforms are studied and later hardware implementation of gate driver circuit using TLP250H IC is carried out and gate voltages at different duty cycles is studied with the help of FEZ Panda III and Arduino boards

JTEC Panel report on electronic manufacturing and packaging in Japan

This report summarizes the status of electronic manufacturing and packaging technology in Japan in comparison to that in the United States, and its impact on competition in electronic manufacturing in general. In addition to electronic manufacturing technologies, the report covers technology and manufacturing infrastructure, electronics manufacturing and assembly, quality assurance and reliability in the Japanese electronics industry, and successful product realization strategies. The panel found that Japan leads the United States in almost every electronics packaging technology. Japan clearly has achieved a strategic advantage in electronics production and process technologies. Panel members believe that Japanese competitors could be leading U.S. firms by as much as a decade in some electronics process technologies

High loading of nanostructured ceramics in polymer composite thick films by aerosol deposition

Low temperature fabrication of Al2O3-polyimide composite substrates was carried out by an aerosol deposition process using a mixture of Al2O3 and polyimide starting powders. The microstructures and dielectric properties of the composite thick films in relation to their Al2O3 contents were characterized by X-ray diffraction analysis. As a result, the crystallite size of α-Al2O3 calculated from Scherrer's formula was increased from 26 to 52 nm as the polyimide ratio in the starting powders increased from 4 to 12 vol.% due to the crushing of the Al2O3 powder being reduced by the shock-absorbing effect of the polyimide powder. The Al2O3-polyimide composite thick films showed a high loss tangent with a large frequency dependence when a mixed powder of 12 vol.% polyimide was used due to the nonuniform microstructure with a rough surface. The Al2O3-polyimide composite thick films showed uniform composite structures with a low loss tangent of less than 0.01 at 1 MHz and a high Al2O3 content of more than 75 vol.% when a mixed powder of 8 vol.% polyimide was used. Moreover, the Al2O3-polyimide composite thick films had extremely high Al2O3 contents of 95 vol.% and showed a dense microstructure close to that of the Al2O3 thick films when a mixed powder of 4 vol.% polyimide was used

Next-generation microvia and global wiring technologies for SOP

© 2004 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.DOI: 10.1109/TADVP.2004.831890As microsystems continue to move toward higher speed and microminiaturization, the demand for interconnection density both on the IC and the package levels increases tremendously. The 2002 ITRS roadmap update identifies the need for sub-100-µm area array pitch and data rates of 10 Gb/s in the package or board by the year 2010, requiring much finer lines and vias than the current microvias of 50 µm diameter and lines and spaces of 25 µm. After a brief description of the future need for high-density substrates, the historical evolution of microvia technologies worldwide is summarized. With the move toward highly integrated and higher performance system-on-a-package (SOP) technology, the demand for microvia wiring density in the package is increasing dramatically requiring new innovations in fine line, ultralow-loss, and ultrathin-film dielectrics. The low-cost needs of this technology are driving research in high throughput and large area processes in dielectric and conductor deposition. The third section of this paper describes in detail some of the key emerging global microvia research and development in the fabrication of microminiaturized, multifunction SOP packages including rapid curing of low-loss dielectric thin films on organic substrates, environmentally friendly high-speed electroless copper plating, ultrafine lines, and spaces down to 5 µm and low-cost stacked via structures without chemical-mechanical polishing. This paper concludes with a perspective on future directions in dielectrics and conductor materials and processes leading to ultrahigh-density and low-cost microvia technologies for build-up SOP implementation

New System for the Acceleration of the Airflow in Wind Turbines

Background: This patent is based on the wind industry technology called Diffuser Augmented Wind Turbines (DAWTs). This technology consists of a horizontal axis wind turbine, which is housed inside a duct with diverging section in the direction of the free air stream. In this paper, a review of preceding patents related to this technology is carried out. Objective: This paper presents an innovative patent to improve the performance of horizontal axis wind turbines. In particular, this system is aimed at improving the performance of those turbines that otherwise might not be installed due to the low wind resource existing at certain locations. Methods: The most innovative elements of this patent are: (1) the semi-spherical grooves, which are mechanized on the surface of the two diffusers in order to guarantee a more energetic boundary layer; (2) the coaxial diffuser, which is located downwind following the first diffuser in order to increase the suction effect on the air mass close to the inlet; (3) the coaxial rings located around the first diffuser outlet, which are used to deflect the external airflow toward the turbine wake; and (4), the selforientating system to orientate the system by the prevailing wind direction. Results: An application of the patent for increasing the power generated by a horizontal axis wind turbine with three blades is presented. The patent is designed and its performance is evaluated by using a Computational Fluid Dynamics code. The numerical results show that this system rises the airflow going through the rotor of the turbine. Conclusion: The patented device is an original contribution aimed at enabling a more profitable installation of wind turbines in places where the wind resource is insufficient because of the wind shear caused both by the proximity of the earth and the obstacles on the earth surface.This work was supported by the OASIS Research Project that was cofinanced by CDTI (Spanish Science and Innovation Ministry) and developed with the Spanish companies: Iridium, OHL Concesiones, Abertis, Sice, Indra, Dragados, OHL, Geocisa, GMV, Asfaltos Augusta, Hidrofersa, Eipsa, PyG, CPS, AEC and Torre de Comares Arquitectos S.L and 16 research centres. The authors also acknowledge the partial funding with FEDER funds under the Research Project FC-15-GRUPIN14-004. Finally, we also thank Swanson Analysis Inc. for the use of ANSYS University Research programs as well as the Workbench simulation environment

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011