• Genomics & Informatics
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• v.21 no.3
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• Steel and Composite Structures
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• v.49 no.5
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• pp.487-502
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• 2023

In the realm of nanotechnology, the nonlocal strain gradient theory takes center stage as it scrutinizes the behavior of spinning cantilever nanobeams and nanotubes, pivotal components supporting various mechanical movements in sport structures. The dynamics of these structures have sparked debates within the scientific community, with some contending that nonlocal cantilever models fail to predict dynamic softening, while others propose that they can indeed exhibit stiffness softening characteristics. To address these disparities, this paper investigates the dynamic response of a nonlocal cantilever cylindrical beam under the influence of external discontinuous dynamic loads. The study employs four distinct models: the Euler-Bernoulli beam model, Timoshenko beam model, higher-order beam model, and a novel higher-order tube model. These models account for the effects of functionally graded materials (FGMs) in the radial tube direction, giving rise to nanotubes with varying properties. The Hamilton principle is employed to formulate the governing differential equations and precise boundary conditions. These equations are subsequently solved using the generalized differential quadrature element technique (GDQEM). This research not only advances our understanding of the dynamic behavior of nanotubes but also reveals the intriguing phenomena of both hardening and softening in the nonlocal parameter within cantilever nanostructures. Moreover, the findings hold promise for practical applications, including drug delivery, where the controlled vibrations of nanotubes can enhance the precision and efficiency of medication transport within the human body. By exploring the multifaceted characteristics of nanotubes, this study not only contributes to the design and manufacturing of rotating nanostructures but also offers insights into their potential role in revolutionizing drug delivery systems.

• Korean Journal of Pharmacognosy
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• v.8 no.4
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• pp.139-148
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• 1977

It is the purpose of this article to present a brief and systematical behavioral methods in recent developed behavioral pharmacology. Specifically, the present review has been organized around three major topics reflecting both current research emphasis in behavioral pharmacology and methodological applications to the study of psychopharmacological actions of crude drug or herb medicine. The first major topic focuses upon the appropriate experimental design especially in the study of psychopharmacology. A large number of factors should be controlled to have a bearing on design of studies reflecting to psychological effects of drugs. The second section presents several recent methodological developments in behavioral pharmacology involving Turner's screening methods and several types of conditioning techniques. The last section calls specific attention to the observation of behavioral development processes in relation to the activity of pharmacological agents and emphasizes critical period of drug treatment.

• Journal of KIISE:Computing Practices and Letters
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• v.9 no.1
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• pp.25-32
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• 2003

As one of a new generation of industries, biotechnology is currently spotlighted, and is creating new research and industrial areas that can be readily combined with information technology. Among them, virtual screening is a method for new drug design which uses computer simulation to virtually design active drug candidates for special disease. In this paper, we present a distributed system for virtual screening, called DVSF(Distributed Virtual Screening Facilities). DVSF is designed and developed to perform virtual screening efficiently on logically distributed idle or strategic resources in a small or medium scale laboratory.

• Archives of Pharmacal Research
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• v.22 no.6
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• pp.533-541
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• 1999

Many conventional anticancer drugs display relatively poor selectivity for neoplastic cells, in particular for solid tumors. Furthermore, expression or development of drug resistance, increased glutathione transferases as well as enhanced DNA repair decrease the efficacy of these drugs. Research efforts continue to overcome these problems by understanding these mechanisms and by developing more effective anticancer drugs. Cyclophosphamide is one of the most widely used alkylating anticancer agents. Because of its unique activation mechanism, numerous bioreversible prodrugs of phosphramide mustard, the active species of cyclophosphamide, have been investigated in an attempt to improve the therapeutic index. Solid tumors are particularly resistant to radiation and chemotherapy. There has been considerable interest in designing drugs selective for hypoxic environments prevalent in solid tumors. Much of the work had been centered on nitroheterocyclics that utilize nitroreductase enzyme systems for their activation. In this article, recent developments of anticancer prodrug design are described with a particular emphasis on exploitation of selective metabolic processes for their activation.

• Journal of Pharmaceutical Investigation
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• v.10 no.1
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• pp.24-33
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• 1980

Drug product design of phenylbutazone tablets by direct compressing was investigated. Weight variation, hardness, friability, disintegration time, apparent volume and dissolution rate for experimental tablets of nine formulations which were considered to be the effect of the additive concentration were measured. It was found out that direct compressing by the formulation No. 5 was the most suitable condition (phenylbutazone 16.7%, lactose 25%, calcium phosphate dibasic 15%, $Avicel^{\circledR}$ 41.83% and magnesium stearate 1.5%). The coefficient of correlation between disintegration time and dissolution rate, r, was = -0.97 (P<0.01).

• Proceedings of the KIEE Conference
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• 2007.07a
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• pp.1526-1527
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• 2007

This paper presents the design, fabrication and experimental results of an electromagnetic microvalve for drug delivery systems. The microvalve consists of two silicon substrates with a silicone rubber diaphragm and a flow channel, a PDMS layer, and an electromagnetic actuator. Each substrate is fabricated by using the silicon wet etch, SU-8 mold process and $O_2$ plasma bonding.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.91-91
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• 2003

The beta-turn has been implicated as an important conformation for biological recognition of peptides or proteins. We adapted the concept of general Ca atom positioning from the cluster analysis and recombination of each ideal beta-turn conformation pattern by Garland and Dean (1. Computer-Aided Molecular Design, 1999, 13, 469) as one strategy of designing non-peptide beta-turn scaffolds. (omitted)

• Journal of Integrative Natural Science
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• v.5 no.1
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• pp.1-5
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• 2012

Quantitative structure-activity relationship (QSAR) methodologies have been applied for many years, to correlate the relationship between physicochemical properties of chemical substances and their biological activities to generate a statistical model for prediction of the activities of new chemical entities. The basic principle behind the QSAR models is that, how structural variation is responsible for the difference in biological activities of the compounds. 3D-QSAR has emerged as a natural extension to the classical Hansch and Free-Wilson approaches, which develops the 3D properties of the ligands to predict their biological activities using various chemometric techniques (PLS, G/PLS, ANN etc). It has served as a valuable predictive tool in the design of pharmaceuticals and agrochemicals. This review seeks to provide different 3D-QSAR approaches involved in drug designing process to develop structure-activity relationships and also discussed the fundamental limitations, as well as those that might be overcome with the improved methodologies.

• Communications for Statistical Applications and Methods
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• v.6 no.2
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• pp.601-610
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• 1999

Crossover design is officially except for special occasions recommended by KFDA and FDA for assessing Bioequivalence between two drugs one for reference and the other for innovator. Such design is regarded as a special case of latin square split-polt or repeated measurement design and its main difference with other designing methods is that each subject in an experiment is exposed two drugs in sequence. Therefore general statistical analysis is not suitable since the model for this experiment includes carryover effect in addition to period and sequence effect. in this paper analysis for crossover model with two drugs and its interpretation are mainly discussed and an example is given for illustration.