Search results for: drug target selection

Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

Abstract:

Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

Procedia PDF Downloads 376

Authors: Courtney Evans, Yuto Morimitsu, Tsubasa Hisadome, Futo Inomoto, Masahiro Yoshida, Takayuki Takei

Abstract:

Hydrogels are useful biomaterials due to their highly biocompatible nature and their ability to absorb large quantities of liquid and mimic soft tissue. They are often used as therapeutic drug delivery systems. However, it is sometimes difficult to sustain controlled release when using hydrophobic medicines, as hydrogels are frequently hydrophilic. As such, this research shows the success of chitosan hydrogels modified through hydrophobic interaction. This was done through the imide bonding of the alkyl groups in fatty aldehydes and the amino groups in chitosan, followed by reductive animation. The resulting cryogels could be optimized for strength as well as sorption and desorption (of a hydrophobic dye used to mimic hydrophobic medicine) by varying the alkyl chain length and the substitution degree of the fatty aldehyde. Optimized cryogels showed potential as biomedical materials, particularly as drug delivery systems.

Keywords: biomedical materials, chitosan, drug carriers, hydrophobic modification

Procedia PDF Downloads 203

Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

Abstract:

In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

Procedia PDF Downloads 274

Authors: Maryam Beiranvand

Abstract:

Multi-drug resistance in various microorganisms has increased globally in many healthcare facilities. Less effective antimicrobial activity of drug therapies for infection control becomes trouble. Since 1980, no new type of antimicrobial drug has been identified, even though combinations of antibiotic drugs have been discovered almost every decade. Between 1981 and 2006, over 70% of novel pharmaceuticals and chemical agents came from natural sources. Microorganisms have yielded almost 22,000 natural compounds. The identification of antimicrobial components from endophytes bacteria could help overcome the threat posed by multi-drug resistant strains. The project aims to analyze and identify antimicrobial peptides isolated from entophytic bacteria and their activity against multidrug-resistant Gram-negative bacteria in South Korea. Endophytic Paenibacillus polymyxa. 4G3 isolated from the plant, Gynura procumbery exhibited considerable antimicrobial activity against Methicillin-resistant Staphylococcus aureus, and Escherichia coli. The Rapid Annotations using Subsystems Technology showed that the total size of the draft genome was 5,739,603bp, containing 5178 genes with 45.8% G+C content. Genome annotation using antiSMASH version 6.0.0 was performed, which predicted the most common types of non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS). In this study, diethyl aminoethyl cellulose (DEAEC) resin was used as the first step in purifying for unknown peptides, and then the target protein was identified using hydrophilic and hydrophobic solutions, optimal pH, and step-by-step tests for antimicrobial activity. This crude was subjected to C18 chromatography and elution with 0, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% methanol, respectively. Only the fraction eluted with 20% -60% methanol demonstrated good antimicrobial activity against MDR E. coli. The concentration of the active fragment was measured by the Brad-ford test, and Protein A280 - Thermo Fisher Scientific at the end by examining the SDS PAGE Resolving Gel, 10% Acrylamide and purity were confirmed. Our study showed that, based on the combined results of the analysis and purification. P polymyxa. 4G3 has a high potential exists for producing novel functions of polymyxin E and bacitracin against bacterial pathogens.

Keywords: endophytic bacteria, antimicrobial activity, antimicrobial peptide, whole genome sequencing analysis, multi -drug resistance gram negative bacteria

Procedia PDF Downloads 46

Authors: Nilubon Kurubanjerdjit, Nattakarn Iam-On, Ka-Lok Ng

Abstract:

MicroRNAs are small non-coding RNA found in many different species. They play crucial roles in cancer such as biological processes of apoptosis and proliferation. The identification of microRNA-target genes can be an essential first step towards to reveal the role of microRNA in various cancer types. In this paper, we predict miRNA-target genes for lung cancer by integrating prediction scores from miRanda and PITA algorithms used as a feature vector of miRNA-target interaction. Then, machine-learning algorithms were implemented for making a final prediction. The approach developed in this study should be of value for future studies into understanding the role of miRNAs in molecular mechanisms enabling lung cancer formation.

Keywords: microRNA, miRNAs, lung cancer, machine learning, Naïve Bayes, SVM

Procedia PDF Downloads 366

Authors: Eylem Koç, Hasan Arda Burhan

Abstract:

Location selection presents a crucial decision problem in today’s business world where strategic decision making processes have critical importance. Thus, location selection has strategic importance for companies in boosting their strength regarding competition, increasing corporate performances and efficiency in addition to lowering production and transportation costs. A right choice in location selection has a direct impact on companies’ commercial success. In this study, a store location selection problem of Carglass Turkey which operates in vehicle glass branch is handled. As this problem includes both tangible and intangible criteria, Analytic Network Process (ANP) was accepted as the main methodology. The model consists of control hierarchy and BOCR subnetworks which include clusters of actors, alternatives and criteria. In accordance with the management’s choices, five different locations were selected. In addition to the literature review, a strict cooperation with the actor group was ensured and maintained while determining the criteria and during whole process. Obtained results were presented to the management as a report and its feasibility was confirmed accordingly.

Keywords: analytic network process (ANP), BOCR, multi-actor decision making, multi-criteria decision making, real-life problem, location selection

Procedia PDF Downloads 444

Authors: Nirupama Dixit, Anyaa Mittal, Neeru Sood

Abstract:

Alzheimer’s disease (AD) is a progressive form of dementia, contributing to up to 70% of cases, mostly observed in elderly but is not restricted to old age. The pathophysiology of the disease is characterized by specific pathological changes in brain. The changes (i.e. accumulation of metal ions in brain, formation of extracellular β-amyloid (Aβ) peptide aggregates and tangle of hyper phosphorylated Tau protein inside neurons) damage the neuronal connections irreversibly. The current issues in improvement of life quality of Alzheimer's patient lies in the fact that the diagnosis is made at a late stage of the disease and the medications do not treat the basic causes of Alzheimer's. The targeted delivery of drug through the blood brain barrier (BBB) poses several limitations via traditional approaches for treatment. To overcome these drug delivery limitation, nanoparticles provide a promising solution. This review focuses on current strategies for efficient targeted drug delivery using nanoparticles and improving the quality of therapy provided to the patient. Nanoparticles can be used to encapsulate drug (which is generally hydrophobic) to ensure its passage to brain; they can be conjugated to metal ion chelators to reduce the metal load in neural tissue thus lowering the harmful effects of oxidative damage; can be conjugated with drug and monoclonal antibodies against BBB endogenous receptors. Finally this review covers how the nanoparticles can play a role in diagnosing the disease.

Keywords: Alzheimer's disease, β-amyloid plaques, blood brain barrier, metal chelators, nanoparticles

Procedia PDF Downloads 463

Authors: Wadha Alqahtani

Abstract:

In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

Procedia PDF Downloads 91

Authors: G. C. Tikkiwal, Mukesh Upadhyay

Abstract:

During the surveillance operations at war or peace time, the Radar operator gets a scatter of targets over the screen. This may be a tracked vehicle like tank vis-à-vis T72, BMP etc, or it may be a wheeled vehicle like ALS, TATRA, 2.5Tonne, Shaktiman or moving army, moving convoys etc. The Radar operator selects one of the promising targets into Single Target Tracking (STT) mode. Once the target is locked, the operator gets a typical audible signal into his headphones. With reference to the gained experience and training over the time, the operator then identifies the random target. But this process is cumbersome and is solely dependent on the skills of the operator, thus may lead to misclassification of the object. In this paper we present a technique using mathematical and statistical methods like Fast Fourier Transformation (FFT) and Principal Component Analysis (PCA) to identify the random objects. The process of classification is based on transforming the audible signature of target into music octave-notes. The whole methodology is then automated by developing suitable software. This automation increases the efficiency of identification of the random target by reducing the chances of misclassification. This whole study is based on live data.

Keywords: radar target, fft, principal component analysis, eigenvector, octave-notes, dsp

Procedia PDF Downloads 320

Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

Abstract:

Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

Procedia PDF Downloads 78

Authors: Purnima Rawat, Divya Vohora, Sarika Gupta, Farhan J. Ahmad, Sushama Talegaonkar

Abstract:

Nanoparticles (NPs) that target bone tissue were developed using PLGA–mPEG (poly(lactic-co-glycolic-acid)–polyethylene glycol) diblock copolymers by using pamidronate as a bone-targeting moieties. These NPs are expected to enable the transport of hydrophilic drugs. The NP was prepared by in situ polymerization method, and their in- vitro characteristics were evaluated using dynamic light scattering, transmission electron microscopy (TEM) and in phosphate-buffered solution. The bone targeting potential of the NP was also evaluated on in-vitro pre-osteoblast MCT3E1 cell line using ALP activity, degree of mineralization and RT-PCR assay. The average particle size of the NP was 101.6 ± 3.7nm, zeta potential values were negative (-25±0.34mV) of the formulations and the entrapment efficiency was 93± 3.1 % obtained. The moiety of the PLGA–mPEG–pamidronate NPs exhibited the best apatite mineral binding ability in-vitro MCT3E1 pre-osteoblast cell line. Our results suggested that the developed nanoparticles may use as a delivery system for Pamidronate in bone repair and regeneration, warranting further evaluation of the treatment of bone disease.

Keywords: nanoparticle, pamidronate, in-situ polymerization, osteoblast

Procedia PDF Downloads 457

Authors: Ailing Yang, Penghan Song, Aihua Cai

Abstract:

The nonlinear maneuvering target tracking problem is mainly a state estimation problem when the target motion model is uncertain. Traditional solutions include Kalman filtering based on Bayesian filtering framework and extended Kalman filtering. However, these methods need prior knowledge such as kinematics model and state system distribution, and their performance is poor in state estimation of nonprior complex dynamic systems. Therefore, in view of the problems existing in traditional algorithms, a convolution LSTM target state estimation (SAConvLSTM-SE) algorithm based on Self-Attention memory (SAM) is proposed to learn the historical motion state of the target and the error distribution information measured at the current time. The measured track point data of airborne radar are processed into data sets. After supervised training, the data-driven deep neural network based on SAConvLSTM can directly obtain the target state at the next moment. Through experiments on two different maneuvering targets, we find that the network has stronger robustness and better tracking accuracy than the existing tracking methods.

Keywords: maneuvering target, state estimation, Kalman filter, LSTM, self-attention

Procedia PDF Downloads 112

Authors: Uswah Khairuddin, Rubiyah Yusof, Nenny Ruthfalydia Rosli

Abstract:

This paper presents a comparative study between k-Nearest Neighbour (k-NN) and Multi-Layer Perceptron Neural Network (MLP-NN) classifier using Genetic Algorithm (GA) as feature selector for wood recognition system. The features have been extracted from the images using Grey Level Co-Occurrence Matrix (GLCM). The use of GA based feature selection is mainly to ensure that the database used for training the features for the wood species pattern classifier consists of only optimized features. The feature selection process is aimed at selecting only the most discriminating features of the wood species to reduce the confusion for the pattern classifier. This feature selection approach maintains the ‘good’ features that minimizes the inter-class distance and maximizes the intra-class distance. Wrapper GA is used with k-NN classifier as fitness evaluator (GA-kNN). The results shows that k-NN is the best choice of classifier because it uses a very simple distance calculation algorithm and classification tasks can be done in a short time with good classification accuracy.

Keywords: feature selection, genetic algorithm, optimization, wood recognition system

Procedia PDF Downloads 511

Authors: Ashley R. Logsdon, Becky F. Antle, Cynthia M. Kamer

Abstract:

This study examines the cost and benefits of a family treatment drug court in an urban county in a southeastern state. Additionally, this cost analysis will provide a detailed description of the type and cost of activities to produce the services provided to child welfare families. This study utilized return-on-investment analysis, which uses child welfare practices, disaggregates them into separate activities and estimates costs for these activities including child-level placement data for total cost of care for the child. Direct and indirect costs were considered as well as saving calculations what costs would be associated with child welfare outcomes both short and long term. The costs included were general program costs (salaries, drug screens, transportation, childcare, parent education, program evaluation, visitation, incentives) or personnel costs for other team members (judges, court administrators, child welfare workers, child welfare supervisors, and community mental health provider). The savings that were used in the study were length of time in out of home care, Medicaid costs, substance exposed births, emergency room utilization and jail/probation costs. This study documents an overall savings of between $168,993.30 and $837,993.30. The total savings per family divided by the 40 families who have participated in the program was between $4,224.83 to $20,949.83 per family. The results of this cost benefit analysis are consistent with prior research documenting savings associated with out of home care and jail/probation; however, there are also unique contributions of this study to the literature on cost effectiveness of family treatment drug courts. We will present recommendations for further utilization of family treatment drug courts and how to expand the current model.

Keywords: child welfare, cost analysis, family drug court, family treatment drug court

Procedia PDF Downloads 138

Authors: Gupta Amit, Kumar Ramesh, P. C. Tewari

Abstract:

Globalization is putting enormous pressure on the business organizations specially manufacturing one to rethink the supply chain in innovative manners. Inventory consumes major portion of total sale revenue. Effective and efficient inventory management plays a vital role for the successful functioning of any organization. Selection of inventory policy is one of the important purchasing activities. This paper focuses on selection and ranking of alternative inventory policies. A deterministic quantitative model-based on Distance Based Approach (DBA) method has been developed for evaluation and ranking of inventory policies. We have employed this concept first time for this type of the selection problem. Four inventory policies Economic Order Quantity (EOQ), Just in Time (JIT), Vendor Managed Inventory (VMI) and monthly policy are considered. Improper selection could affect a company’s competitiveness in terms of the productivity of its facilities and quality of its products. The ranking of inventory policies is a multi-criteria problem. There is a need to first identify the selection criteria and then processes the information with reference to relative importance of attributes for comparison. Criteria values for each inventory policy can be obtained either analytically or by using a simulation technique or they are linguistic subjective judgments defined by fuzzy sets, like, for example, the values of criteria. A methodology is developed and applied to rank the inventory policies.

Keywords: inventory policy, ranking, DBA, selection criteria

Procedia PDF Downloads 355

Authors: Shringika Soni, Utkarsh Jain, Nidhi Chauhan

Abstract:

Aptamers are recently discovered ~80-100 bp long artificial oligonucleotides that not only demonstrated their applications in therapeutics; it is tremendously used in diagnostic and sensing application to detect different biomarkers and drugs. Synthesizing aptamers for proteins or genomic template is comparatively feasible in laboratory, but drugs or other chemical target based aptamers require major specification and proper optimization and validation. One has to optimize all selection, amplification, and characterization steps of the end product, which is extremely time-consuming. Therefore, we performed asymmetric PCR (polymerase chain reaction) for random oligonucleotides pool synthesis, and further use them in Systematic evolution of ligands by exponential enrichment (SELEX) for anti-psychotic drugs based aptamers synthesis. Anti-psychotic drugs are major tranquilizers to control psychosis for proper cognitive functions. Though their low medical use, their misuse may lead to severe medical condition as addiction and can promote crime in social and economical impact. In this work, we have approached the in-vitro SELEX method for ssDNA synthesis for anti-psychotic drugs (in this case ‘target’) based aptamer synthesis. The study was performed in three stages, where first stage included synthesis of random oligonucleotides pool via asymmetric PCR where end product was analyzed with electrophoresis and purified for further stages. The purified oligonucleotide pool was incubated in SELEX buffer, and further partition was performed in the next stage to obtain target specific aptamers. The isolated oligonucleotides are characterized and quantified after each round of partition, and significant results were obtained. After the repetitive partition and amplification steps of target-specific oligonucleotides, final stage included sequencing of end product. We can confirm the specific sequence for anti-psychoactive drugs, which will be further used in diagnostic application in clinical and forensic set-up.

Keywords: anti-psychotic drugs, aptamer, biosensor, ssDNA, SELEX

Procedia PDF Downloads 108

Authors: M. S. Deshpande, Snehal D. Bomble

Abstract:

Tuberculosis (TB) is a deadly contagious disease that is caused by a bacterium called Mycobacterium tuberculosis. More than sixty years ago, the introduction of the first anti-TB drugs for the treatment of TB (streptomycin (STR), p-aminosalcylic acid (PAS), isoniazid (INH), and then later ethambutol (EMB) and rifampicin (RIF)) gave optimism to the medical community, and it was believed that the disease would be completely eradicated soon. Worldwide, the number of TB cases has continued to increase, but the incidence rate has decreased since 2003. Recently, highly drug-resistant forms of TB have emerged worldwide. The prolonged use of classical drugs developed a growing resistance and these drugs have gradually become less effective and incapable to meet the challenges, especially those of multi drug resistant (MDR)-TB, extensively drug resistant (XDR)-TB, and HIV-TB co-infections. There is an unmet medical need to discover newer synthetic molecules and new generation of potent drugs for the treatment of tuberculosis which will shorten the time of treatment, be potent and safe while effective facing resistant strains and non-replicative, latent forms, reduce adverse side effect and not interfere in the antiretroviral therapy. This paper attempts to bring out the review of anti-TB drugs, and presents a novel method of synthesizing new anti-tuberculosis drugs and potential compounds to overcome the bacterial resistance and combat the re-emergence of tuberculosis.

Keywords: tuberculosis, mycobacterium, multi-drug resistant (MDR)-TB, extensively drug resistant (XDR)-TB

Procedia PDF Downloads 353

Authors: Anita, Sari Septiani Tangke, Rusdina Bte Ladju, Nasrum Massi

Abstract:

New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P<0.001) compare with the reference methods. A lower and same concentration of isoniazid and rifampin can be used to detect MDR-TB. Operational cost and application can be more efficient and easier in resource-limited environments. However, additional studies evaluating the MODS using lower and same concentration of isoniazid and rifampin must be conducted with a larger number of clinical isolates.

Keywords: isoniazid, MODS assay, MDR-TB, rifampin

Procedia PDF Downloads 286

Authors: Zainab S. Mahmood, Aisha H. Hashim, Wan Haslina Hassan, Farhat Anwar

Abstract:

The wide use of the internet-based applications bring many challenges to the researchers to guarantee the continuity of the connections needed by the mobile hosts and provide reliable Internet access for them. One of proposed solutions by Internet Engineering Task Force (IETF) is to connect the local, multi-hop, and infrastructure-less Mobile Ad hoc Network (MANET) with Internet structure. This connection is done through multi-interface devices known as Internet Gateways. Many issues are related to this connection like gateway discovery, hand off, address auto-configuration and selecting the optimum gateway when multiple gateways exist. Many studies were done proposing gateway selection schemes with a single selection criterion or weighted multiple criteria. In this research, a review of some of these schemes is done showing the differences, the features, the challenges and the drawbacks of each of them.

Keywords: Internet Gateway, MANET, mobility, selection criteria

Procedia PDF Downloads 392

Authors: Jaehoon Ha, Byungmo Kang, Kilho Hong, Jungsoo Park

Abstract:

Electro-optical (EO) stabilized platforms have been widely used for surveillance and reconnaissance on various types of vehicles, from surface ships to unmanned air vehicles (UAVs). EO stabilized platforms usually consist of an assembly of structure, bearings, and motors called gimbals in which a gyroscope is installed. EO elements such as a CCD camera and IR camera, are mounted to a gimbal, which has a range of motion in elevation and azimuth and can designate and track a target. In addition, a laser range finder (LRF) can be added to the gimbal in order to acquire the precise slant range from the platform to the target. Recently, a versatile functionality of target localization is needed in order to cooperate with the weapon systems that are mounted on the same platform. The target information, such as its location or velocity, needed to be more accurate. The accuracy of the target information depends on diverse component errors and alignment errors of each component. Specially, the type of moving platform can affect the accuracy of the target information. In the case of flying platforms, or UAVs, the target location error can be increased with altitude so it is important to measure altitude as precisely as possible. In the case of surface ships, target location error can be increased with obliqueness of the elevation angle of the gimbal since the altitude of the EO stabilized platform is supposed to be relatively low. The farther the slant ranges from the surface ship to the target, the more extreme the obliqueness of the elevation angle. This can hamper the precise acquisition of the target information. So far, there have been many studies on EO stabilized platforms of flying vehicles. However, few researchers have focused on ship-borne EO stabilized platforms of the surface ship. In this paper, we deal with a target localization method when an EO stabilized platform is located on the mast of a surface ship. Especially, we need to overcome the limitation caused by the obliqueness of the elevation angle of the gimbal. We introduce a well-known approach for target localization using Unscented Kalman Filter (UKF) and present the problem definition showing the above-mentioned limitation. Finally, we want to show the effectiveness of the approach that will be demonstrated through computer simulations.

Keywords: target localization, ship-borne electro-optical stabilized platform, unscented kalman filter

Procedia PDF Downloads 491

Authors: Sarita Pinmanee, Saipan Krapbia, Rataya Yanaphan

Abstract:

Hemp (Cannabis sativa L.) is multi-purpose crop delivering fibers, shives, and seed. The fiber is used today for special paper, insulation material, and biocomposites. This research was to improve low delta-9 Tetrahydrocannabinol (THC) hemp variety for high fiber contents. Mass selection for increased fiber content in four low THC Thai cultivars (including RPF1, RPF2, RPF3, and RPF4) was carried out in highland areas in the northern Thailand. Research work was conducted for three consecutive growing seasons during 2012 to 2014 at Pangda Royal Agricultural Station, Samoeng District, Chiang Mai Province, Thailand. Results of selection indicated that after selecting for three successive generations, the average fiber content of four low THC Thai cultivars increased to 28-36 %. The resulted of selection was found that fiber content of RPF1, RPF2, RPF3 and RPF4 increased to 20.6, 19.1, 19.9 and 22.8%, respectively. In addition, THC contents of these four varieties were 0.07, 0.138, 0.08 and 0.072 % respectively. As well, mass selection method was considered as an effective and suitable method for improving this fiber content.

Keywords: Hemp, mass selection, fiber content, low THC content

Procedia PDF Downloads 382

Authors: Saniye Çeşmecioğlu

Abstract:

The importance of project sustainability and success has become increasingly significant due to the proliferation of external environmental factors that have decreased project resistance in contemporary times. The primary approach to forestall the failure of projects is to ensure their long-term viability through the strategic selection of projects as creating judicious project selection framework within the organization. Decision-makers require precise decision contexts (models) that conform to the company's business objectives and sustainability expectations during the project selection process. The establishment of a rational model for project selection enables organizations to create a distinctive and objective framework for the selection process. Additionally, for the optimal implementation of this decision-making model, it is crucial to establish a Project Management Office (PMO) team and Project Steering Committee within the organizational structure to oversee the framework. These teams enable updating project selection criteria and weights in response to changing conditions, ensuring alignment with the company's business goals, and facilitating the selection of potentially viable projects. This paper presents a multi-criteria decision model for selecting project sustainability and project success criteria that ensures timely project completion and retention. The model was developed using MACBETH (Measuring Attractiveness by a Categorical Based Evaluation Technique) and was based on broadcaster companies’ expectations. The ultimate results of this study provide a model that endorses the process of selecting the appropriate project objectively by utilizing project selection and sustainability criteria along with their respective weights for organizations. Additionally, the study offers suggestions that may ascertain helpful in future endeavors.

Keywords: project portfolio management, project selection, multi-criteria decision making, project sustainability and success criteria, MACBETH

Procedia PDF Downloads 36

Authors: Prakash Singh

Abstract:

Schools throughout the world are facing increasing challenges in dealing with school violence and drug abuse by pupils. Therefore, the question of the fear of failure to meet the aims and objectives of education inevitably surfaces as it places increasing and challenging demands on educators and all other stakeholders to address this malaise. Multiple studies on the construct tobephobia (TBP) simply define TBP as the fear of failure in education. This study is a continuation of the exploratory studies on the manifestation of fear in education. The primary purpose of this study was to establish how TBP, caused by school violence and drug abuse affects teaching and learning in our schools. The qualitative research method was used for this study. Teachers admitted that they fear for their safety at school. Working in a fearful situation places a high rate of stress and anxiety on them. Tobephobic educators spend most of their time worrying about their fear of violence and drug abuse by pupils and are too frightened to carry out their normal duties. They prefer to stay in familiar surroundings for fear of being attacked by inebriated learners. This study, therefore, contributes to our understanding of the effects of TBP in our schools caused by school violence and drug abuse. Also, this study supplements the evidence accumulated over the past fifteen years that TBP is not a figment of someone’s imagination; it is a gruesome reality affecting the very foundation of our educational system globally to provide quality and equal education to all our learners in a harmonious, collegial school environment.

Keywords: tobephobia, tobephobic educators, fear of failure in education, school violence, drug abuse

Procedia PDF Downloads 457

Authors: Mehdi Assefi, Keihan Hataminezhad

Abstract:

One of the efficient architectures for exploring the resources in wireless ad-hoc networks is contact-based architecture. In this architecture, each node assigns a unique zone for itself and each node keeps all information from inside the zone, as well as some from outside the zone, which is called contact. Reducing the overlap between different zones of a node and its contacts increases its performance, therefore Edge Method (EM) is designed for this purpose. Contacts selected by EM do not have any overlap with their sources, but for choosing the contact a vast amount of information must be transmitted. In this article, we will offer a new protocol for contact selection, which is called PEM. The objective would be reducing the volume of transmitted information, using Non-Uniform Dissemination Probabilistic Protocols. Consumed energy for contact selection is a function of the size of transmitted information between nodes. Therefore, by reducing the content of contact selection message using the PEM will decrease the consumed energy. For evaluation of the PEM we applied the simulation method. Results indicated that PEM consumes less energy compared to EM, and by increasing the number of nodes (level of nodes), performance of PEM will improve in comparison with EM.

Keywords: wireless ad-hoc networks, contact selection, method for CARD, energy-efficient

Procedia PDF Downloads 261

Authors: Maryam Vaezjalali, Koroush Rahimian, Maryam Asli, Tahmineh Kandelouei, Foad Davoodbeglou, Amir H. Kashi

Abstract:

Objectives: The present study was conducted to assess the HBV molecular profiles including genotypes, subgenotypes, subtypes & mutations in hepatitis B genes. Materials/Patients and Methods: This study was conducted on 229 intravenous drug users who referred to three Drop- in-Centers and a hospital in Tehran. HBV DNA was extracted from HBsAg positive serum samples and amplified by Nested PCR. HBV genotype, subgenotypes, subtype and genes mutation were determined by direct sequencing. Phylogenetic tree was constructed using neighbor- joining (NJ) method. Statistical analyses were carried out by SPSS 20. Results: HBV DNA was found in 3 HBsAg positive cases. Phylogenetic tree of derived HBV DNAs showed the existence of genotype D (subgenotype D1, subtype ayw2). Also immune escape mutations were determined in S gene. Conclusion: There were a few variations and genotypes and subtypes among infected intravenous drug users. This study showed the predominance of genotype D among intravenous drug users. Our study concurs with other reports from Iran, that all showing currently only genotype D is the only detectable genotype in Iran.

Keywords: drug users, genotype, HBV, phylogenetic tree

Procedia PDF Downloads 292

Authors: Brian W. Mandikiana

Abstract:

Homestead food production has the potential to alleviate hunger, improve health and nutrition for children and adults. This article examines the relationship between self-reported hunger and homestead food production using the ordered probit model. A sample of households participating in homestead food production was drawn from the first wave of the South African National Income Dynamics Survey, a nationally representative cross-section. The sample selection problem was corrected using an ordered probit model with sample selection approach. The findings show that homestead food production exerts a positive and significant impact on children and adults’ ability to cope with hunger and malnutrition. Yet, on the contrary, potential gains of homestead food production are threatened by shocks such as crop failure.

Keywords: agriculture, hunger, nutrition, sample selection

Procedia PDF Downloads 306

Authors: Ragaa T. Darwish, Maha A. Demellawy, Haidy M. Megahed, Doreen N. Younan, Wael S. Kholeif

Abstract:

The testing of drug abuse is authentic in order to affirm the misuse of drugs. Several analytical approaches have been developed for the detection of drugs of abuse in pharmaceutical and common biological samples, but few methodologies have been created to identify them from fingerprints. Liquid Chromatography-Mass Spectrometry (LC-MS) plays a major role in this field. The current study aimed at assessing the possibility of detection of some drugs of abuse (tramadol, clonazepam, and phenobarbital) from fingerprints using LC-MS in drug abusers. The aim was extended in order to assess the possibility of detection of the above-mentioned drugs in fingerprints of drug handlers till three days of handling the drugs. The study was conducted on randomly selected adult individuals who were either drug abusers seeking treatment at centers of drug dependence in Alexandria, Egypt or normal volunteers who were asked to handle the different studied drugs (drug handlers). An informed consent was obtained from all individuals. Participants were classified into 3 groups; control group that consisted of 50 normal individuals (neither abusing nor handling drugs), drug abuser group that consisted of 30 individuals who abused tramadol, clonazepam or phenobarbital (10 individuals for each drug) and drug handler group that consisted of 50 individuals who were touching either the powder of drugs of abuse: tramadol, clonazepam or phenobarbital (10 individuals for each drug) or the powder of the control substances which were of similar appearance (white powder) and that might be used in the adulteration of drugs of abuse: acetyl salicylic acid and acetaminophen (10 individuals for each drug). Samples were taken from the handler individuals for three consecutive days for the same individual. The diagnosis of drug abusers was based on the current Diagnostic and Statistical Manual of Mental disorders (DSM-V) and urine screening tests using immunoassay technique. Preliminary drug screening tests of urine samples were also done for drug handlers and the control groups to indicate the presence or absence of the studied drugs of abuse. Fingerprints of all participants were then taken on a filter paper previously soaked with methanol to be analyzed by LC-MS using SCIEX Triple Quad or QTRAP 5500 System. The concentration of drugs in each sample was calculated using the regression equations between concentration in ng/ml and peak area of each reference standard. All fingerprint samples from drug abusers showed positive results with LC-MS for the tested drugs, while all samples from the control individuals showed negative results. A significant difference was noted between the concentration of the drugs and the duration of abuse. Tramadol, clonazepam, and phenobarbital were also successfully detected from fingerprints of drug handlers till 3 days of handling the drugs. The mean concentration of the chosen drugs of abuse among the handlers group decreased when the days of samples intake increased.

Keywords: drugs of abuse, fingerprints, liquid chromatography–mass spectrometry, tramadol

Procedia PDF Downloads 90

Authors: Delband Yekta Moazami

Abstract:

Background: For proper care and treatment of HIV patients and drug users, the medical staff and physicians must have a correct and positive attitude and knowledge towards such patients. We aimed to assess the attitudes in a sample of health care workers (HCW) working in different hospitals and clinics and medical students in Georgia towards HIV infected people and drug users in Tbilisi. Method: We conducted a cross-sectional study to assess attitudes of health care workers towards people living with HIV and drug users in hospitals and clinics in Tbilisi. The study was carried out from 1st of May 2020 till 30th of September 2020. Data were collected using a self-administered structured online questionnaire. With this tool we evaluated four facets of attitudes: Discrimination, Acceptance of HIV/AIDS patients, Acceptance of drug users and Fear. All data were imported and analyzed with the software SPSS 22 for windows. Results: In total data was collected from168 respondents, that among them 107 (65%) were women and majority of the participants were medical doctors. Women had more acceptance attitudes rather than men towards drug abusers. We found significant differences regarding expressing negative attitudes among HCW who were more than 50 years old comparing with other age groups in all four aspects. Medical doctors expressed more acceptances towards people with HIV and drug users comparing two other groups. Also our study revealed that the group with working experience 21 years and more, showed more discriminatory attitudes comparing other groups. Conclusion: Based on our study findings, there are significant differences regarding respondent’s attitudes based on gender, medical specialty and working experience in health care system. People struggling with HIV and drug use need nonjudgmental and positive behaviors from health care workers and physicians in order to help them for harm reduction and receiving appropriate treatment.

Keywords: hiv, addiction, attitudes, healthcare workers

Procedia PDF Downloads 52

Authors: Samah Benmerbi, Kamal Amroun, Abdelkamel Tari

Abstract:

The increasing number of Web service (WS)providers throughout the globe, have produced numerous Web services providing the same or similar functionality. Therefore, there is a need of tools developing the best answer of queries by selecting and composing services with total transparency. This paper reviews various QoS based Web service selection mechanisms and architectures which facilitate qualitatively optimal selection, in other fact Web service composition is required when a request cannot be fulfilled by a single web service. In such cases, it is preferable to integrate existing web services to satisfy user’s request. We introduce an automatic Web service composition method based on hypergraph decomposition using hypertree decomposition method. The problem of selection and the composition of the web services is transformed into a resolution in a hypertree by exploring the relations of dependency between web services to get composite web service via employing an execution order of WS satisfying global request.

Keywords: web service, web service selection, web service composition, QoS, hypergraph decomposition, BE hypergraph decomposition, hypertree resolution

Procedia PDF Downloads 480

Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

Abstract:

Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

Procedia PDF Downloads 73