DESIGN METHODOLOGIES AND SOME ASPECTS OF VLSI AND ULSI

This is a review and considers first technical aspects and drawbacks for realizing very large scale and wafer scale integrated circuits. Among these are small geometry effects and interconnection delay. Some solutions are considered. Next, design methodologies for VLSI are discussed, considering the hierarchy of VLSI systems. Finally the influences for students education are remarked and a design system consisting of CAD tools for logic synthesis and simulation, network-and device simulation, automated layout generation and layout-verification are described

Advanced modification of drug nanocrystals by using novel fabrication and downstream approaches for tailor-made drug delivery

Drug nanosuspensions/nanocrystals have been recognized as one useful and successful approach for drug delivery. Drug nanocrystals could be further decorated to possess extended functions (such as controlled release) and designed for special in vivo applications (such as drug tracking), which make best use of the advantages of drug nanocrystals. A lot of novel and advanced size reduction methods have been invented recently for special drug deliveries. In addition, some novel downstream processes have been combined with nanosuspensions, which have highly broadened its application areas (such as targeting) besides traditional routes. A large number of recent research publication regarding as nanocrystals focuses on above mentioned aspects, which have widely attracted attention. This review will focus on the recent development of nanocrystals and give an overview of regarding modification of nanocrystal by some new approaches for tailor-made drug delivery

SOME ASPECTS OF MICROPROGRAMMED CONTROL OF PROCESSORS

After a short review of general feat ures of microprogrammed control units some design problems are treated. especially optimization of control store by means of compacting and coding

Synthesis of guanidine amino acids and investigation of their interactions with nucleic acid

Certain amino acids have a high propensity to be found at the intermolecular contact regions in protein-nucleic acid complexes. One of them is arginine whose side chain commonly makes contact through electrostatic interactions with phosphates and hydrogen bonding to nucleobases. Rigidified arginine analogues in which the side chain is cyclised would reduce torsional entropy loss occurring on binding. In this project amino acids were synthesised with cyclic guanidine side chains as modular arginine analogue building blocks for preparation of nucleic acid binding peptides. The synthetic strategies to prepare the amino acids involve Grignard reactions and Heck coupling reactions with iodo-pyrimidines. The Heck coupling is followed by a catalytic asymmetric hydrogenation to generate the stereo centre. An enzymatic kinetic resolution is essential after the Grignard coupling to provide stereoselectivity. Small molecule interactions with nucleic acids can be used as a tool for modulating processes like transcription and translation. Ultimately peptide binding screens against the mRNA of TGF-β1 may be undertaken to study the role of protein binding in regulation of translation. Within this thesis a peptide library was prepared via the split and recombine method using macro-beads which provides valuable groundwork for the aim of continuing research. This would be the synthesis of peptides containing rigidified arginine mimetics that interact with mRNA of TGF-β1 or other nucleic acids

Nanosizing techniques for improving bioavailability of drugs

The poor solubility of significant number of Active Pharmaceutical Ingredients (APIs) has become a major challenge in the drug development process. Drugs with poor solubility are difficult to formulate by conventional methods and often show poor bioavailability. In the last decade, attention has been focused on developing nanocrystals for poorly water soluble drugs using nanosizing techniques. Nanosizing is a pharmaceutical process that changes the size of a drug to the sub-micron range in an attempt to increase its surface area and consequently its dissolution rate and bioavailability. The effectiveness of nanocrystal drugs is evidenced by the fact that six FDA approved nanocrystal drugs are already on the market. The bioavailabilities of these preparations have been significantly improved compared to their conventional dosage forms. There are two main approaches for preparation of drug nanocrystals; these are the top-down and bottom-up techniques. Top-down techniques have been successfully used in both lab scale and commercial scale manufacture. Bottom-up approaches have not yet been used at a commercial level, however, these techniques have been found to produce narrow sized distribution nanocrystals using simple methods. Bottom-up techniques have been also used in combination with top-down processes to produce drug nanoparticles. The main aim of this review article is to discuss the various methods for nanosizing drugs to improve their bioavailabilities

Controlled Crystallization of the Lipophilic Drug Fenofibrate During Freeze-Drying: Elucidation of the Mechanism by In-Line Raman Spectroscopy

We developed a novel process, “controlled crystallization during freeze-drying” to produce drug nanocrystals of poorly water-soluble drugs. This process involves freeze-drying at a relatively high temperature of a drug and a matrix material from a mixture of tertiary butyl alcohol and water, resulting in drug nanocrystals incorporated in a matrix. The aim of this study was to elucidate the mechanisms that determine the size of the drug crystals. Fenofibrate was used as a model lipophilic drug. To monitor the crystallization during freeze-drying, a Raman probe was placed just above the sample in the freeze-dryer. These in-line Raman spectroscopy measurements clearly revealed when the different components crystallized during freeze-drying. The solvents crystallized only during the freezing step, while the solutes only crystallized after the temperature was increased, but before drying started. Although the solutes crystallized only after the freezing step, both the freezing rate and the shelf temperature were critical parameters that determined the final crystal size. At a higher freezing rate, smaller interstitial spaces containing the freeze-concentrated fraction were formed, resulting in smaller drug crystals (based on dissolution data). On the other hand, when the solutes crystallized at a lower shelf temperature, the degree of supersaturation is higher, resulting in a higher nucleation rate and consequently more and therefore smaller crystals. In conclusion, for the model drug fenofibrate, a high freezing rate and a relatively low crystallization temperature resulted in the smallest crystals and therefore the highest dissolution rate