Search results for: drug target

Authors: K. N. Seetharamu, Naveen Teggi, Kiranakumar Dhavalagi, Narayana Kamath

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A method of temperature calculations is developed to study the conditions leading to hot spot occurrence on multicore chips. A physical model which has salient features of multicore chips is incorporated for the analysis. The model consists of active and background cell laid out in a checkered pattern, and this pattern repeats itself in each fine grain active cells. The die has three layers i) body ii) buried oxide layer iii) wiring layer, stacked one above the other with heat source placed at the interface between wiring and buried oxide layer. With this model we propose analytical method to calculate the target hotspot temperature, heat flow to top and bottom layers of the die and thermal resistance components at each granularity level, assuming appropriate values of die dimensions and parameters. Finally we attempt to find an easier method for the calculation of the target hotspot temperature using graph.

Keywords: checkered pattern, granularity level, heat conduction, multicore chips, target hotspot temperature

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Authors: Camilla G. Goncalves, Benedito Christ, Walter Miyakawa, Antonio J. Abdalla

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This work aims to investigate the properties and microstructure of diamond-like carbon film deposited by pulsed laser deposition by ablation of a graphite target in a vacuum chamber on a steel substrate. The equipment was mounted to provide one laser beam. The target of high purity graphite and the steel substrate were polished. The mechanical and tribological properties of the film were characterized using Raman spectroscopy, nanoindentation test, scratch test, roughness profile, tribometer, optical microscopy and SEM images. It was concluded that the pulsed laser deposition (PLD) technique associated with the low-pressure chamber and a graphite target provides a good fraction of sp3 bonding, that the process variable as surface polishing and laser parameter have great influence in tribological properties and in adherence tests performance. The optical microscopy images are efficient to identify the metallurgical bond.

Keywords: characterization, DLC, mechanical properties, pulsed laser deposition

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Authors: Sarah P. Wuebbolt, Ashlee N. Sawyer-Mays

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Non-medical prescription and other drug (NMPOD) use has been a significant public health issue for the last few decades, with problematic use increasing among university students more recently. The current study focused on associations between NMPOD use and mental health, well-being, and world beliefs among young adults. Young adults (N=513) completed online questionnaires assessing stress, demographic characteristics, self-esteem, NMPOD use, coping mechanisms, and anxiety. A substantial portion of participants reported using cannabis (48.5%, n=249), while smaller portions of participants reported using stimulants (26.7%, n = 137), sedatives (17.2%, n=88), opioids (10.8%, n=55), and hallucinogens (14.4%, n=74). Five hierarchical logistic regressions were performed to determine the independent relationships between mental health, well-being, and world belief factors and NMPOD use for the five classes of substances. After controlling for demographic factors (age, gender, race/ethnicity, sexual orientation, and religious affiliation), depression was associated with increased non-medical stimulant, opioid, and cannabis use; coping self-efficacy was associated with increased hallucinogen use, and attendance of worship services was associated with decreased non-medical cannabis and hallucinogen use. Results suggest that depression was strongly associated with non-medical stimulant, opioid, and cannabis use, and attendance of worship services was protective against cannabis and hallucinogen use. To the best of our knowledge, this is one of the first studies to investigate the relationships between mental health, well-being, world beliefs, and NMPOD use among young adults. The present study illuminates future targets for intervention, such as increased access to mental health diagnosis and treatment and the exploration of the roles of religion and shared community in the prevention of drug use among young adults.

Keywords: cannabis, mental health, non-medical prescription and other drug use, world beliefs

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Authors: Krutika K. Sawant, Anil Solanki

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The present study deals with the preparation and optimization of ethyl cellulose-containing disopyramide phosphate loaded microspheres using solvent evaporation technique. A central composite design consisting of a two-level full factorial design superimposed on a star design was employed for optimizing the preparation microspheres. The drug:polymer ratio (X1) and speed of the stirrer (X2) were chosen as the independent variables. The cumulative release of the drug at a different time (2, 6, 10, 14, and 18 hr) was selected as the dependent variable. An optimum polynomial equation was generated for the prediction of the response variable at time 10 hr. Based on the results of multiple linear regression analysis and F statistics, it was concluded that sustained action can be obtained when X1 and X2 are kept at high levels. The X1X2 interaction was found to be statistically significant. The drug release pattern fitted the Higuchi model well. The data of a selected batch were subjected to an optimization study using Box-Behnken design, and an optimal formulation was fabricated. Good agreement was observed between the predicted and the observed dissolution profiles of the optimal formulation.

Keywords: disopyramide phosphate, ethyl cellulose, microspheres, controlled release, Box-Behnken design, factorial design

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Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim

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Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.

Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion

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Authors: Mani Mofidi, Neda Valizadeh, Ali Hashemaghaee, Mona Hashemaghaee, Soudabeh Shafiee Ardestani

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Background: Acute pain and its management remained the most complaint of emergency service admission. Diagnostic and therapeutic procedures add to patients’ pain. Diminishing the pain increases the quality of patient’s feeling and improves the patient-physician relationship. Aim: The aim of this study was to evaluate the outcomes and side effects of opioid administration in emergency patients. Material and Methods: patients admitted to ward II emergency service of Imam Khomeini hospital, who received one of the opioids: morphine, pethidine, methadone or fentanyl as an analgesic were evaluated. Their vital signs and general condition were examined before and after drug injection. Also, patient’s pain experience were recorded as numerical rating score (NRS) before and after analgesic administration. Results: 268 patients were studied. 34 patients were addicted to opioid drugs. Morphine had the highest rate of prescription (86.2%), followed by pethidine (8.5%), methadone (3.3%) and fentanyl (1.68). While initial NRS did not show significant difference between addicted patients and non-addicted ones, NRS decline and its score after drug injection were significantly lower in addicted patients. All patients had slight but statistically significant lower respiratory rate, heart rate, blood pressure and O2 saturation. There was no significant difference between different kind of opioid prescription and its outcomes or side effects. Conclusion: Pain management should be always in physicians’ mind during emergency admissions. It should not be assumed that an addicted patient complaining of pain is malingering to receive drug. Titration of drug and close monitoring must be in the curriculum to prevent any hazardous side effects.

Keywords: numerical rating score, opioid, pain, emergency department

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Authors: Feng Tao, Han Ye, Shaoyi Liao

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City constructions collapse after earthquake and people will be buried under ruins. Search and rescue should be conducted as soon as possible to save them. Therefore, according to the complicated environment, irregular aftershocks and rescue allow of no delay, a kind of target localization method based on RSSI (Received Signal Strength Indication) is proposed in this article. The target localization technology based on RSSI with the features of low cost and low complexity has been widely applied to nodes localization in WSN (Wireless Sensor Networks). Based on the theory of RSSI transmission and the environment impact to RSSI, this article conducts the experiments in five scenes, and multiple filtering algorithms are applied to original RSSI value in order to establish the signal propagation model with minimum test error respectively. Target location can be calculated from the distance, which can be estimated from signal propagation model, through improved centroid algorithm. Result shows that the localization technology based on RSSI is suitable for large-scale nodes localization. Among filtering algorithms, mixed filtering algorithm (average of average, median and Gaussian filtering) performs better than any other single filtering algorithm, and by using the signal propagation model, the minimum error of distance between known nodes and target node in the five scene is about 3.06m.

Keywords: signal propagation model, centroid algorithm, localization, mixed filtering, RSSI

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Authors: W. P. Hu, J. V. Kumar, Jeffrey J. P. Tsai

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The inhibition of SH2 domain regulated protein-protein interactions is an attractive target for developing an effective chemotherapeutic approach in the treatment of disease. Molecular simulation is a useful tool for developing new drugs and for studying molecular recognition. In this study, we searched potential drug compounds for the inhibition of SH2 domain by performing structural similarity search in PubChem Compound Database. A total of 37 compounds were screened from the database, and then we used the LibDock docking program to evaluate the inhibition effect. The best three compounds (AP22408, CID 71463546 and CID 9917321) were chosen for MD simulations after the LibDock docking. Our results show that the compound CID 9917321 can produce a more stable protein-ligand complex compared to other two currently known inhibitors of Src SH2 domain. The compound CID 9917321 may be useful for the inhibition of SH2 domain based on these computational results. Subsequently experiments are needed to verify the effect of compound CID 9917321 on the SH2 domain in the future studies.

Keywords: nonpeptide inhibitor, Src SH2 domain, LibDock, molecular dynamics simulation

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Authors: Kalaumari Mayoral-Peña, Ana I. Montejano-Montelongo, Josué Reyes-Muñoz, Gonzalo A. Ortiz-Mancilla, Mayrin Rodríguez-Cruz, Víctor Hernández-Villalobos, Jesús A. Guzmán-López, Santiago García-Jacobo, Iván Licona-Vázquez, Grisel Fierros-Romero, Rosario Flores-Vallejo

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The group B-lactamic antibiotics include some of the most frequently used small drug molecules against bacterial infections. Nevertheless, an alarming decrease in their efficacy has been reported due to the emergence of antibiotic-resistant bacteria. Infections caused by bacteria expressing extended Spectrum B-lactamases (ESBLs) are difficult to treat and account for higher morbidity and mortality rates, delayed recovery, and high economic burden. According to the Global Report on Antimicrobial Resistance Surveillance, it is estimated that mortality due to resistant bacteria will ascend to 10 million cases per year worldwide. These facts highlight the importance of developing low-cost and readily accessible detection methods of drug-resistant ESBLs bacteria to prevent their spread and promote accurate and fast diagnosis. Bacterial detection is commonly done using molecular diagnostic techniques, where PCR stands out for its high performance. However, this technique requires specialized equipment not available everywhere, is time-consuming, and has a high cost. Loop-Mediated Isothermal Amplification (LAMP) is an alternative technique that works at a constant temperature, significantly decreasing the equipment cost. It yields double-stranded DNA of several lengths with repetitions of the target DNA sequence as a product. Although positive and negative results from LAMP can be discriminated by colorimetry, fluorescence, and turbidity, there is still a large room for improvement in the point-of-care implementation. DNA origami is a technique that allows the formation of 3D nanometric structures by folding a large single-stranded DNA (scaffold) into a determined shape with the help of short DNA sequences (staples), which hybridize with the scaffold. This research aimed to generate DNA origami structures using LAMP products as scaffolds to improve the sensitivity to detect ESBLs in point-of-care diagnosis. For this study, the coding sequence of the CTM-X-15 ESBL of E. coli was used to generate the LAMP products. The set of LAMP primers were designed using PrimerExplorerV5. As a result, a target sequence of 200 nucleotides from CTM-X-15 ESBL was obtained. Afterward, eight different DNA origami structures were designed using the target sequence in the SDCadnano and analyzed with CanDo to evaluate the stability of the 3D structures. The designs were constructed minimizing the total number of staples to reduce costs and complexity for point-of-care applications. After analyzing the DNA origami designs, two structures were selected. The first one was a zig-zag flat structure, while the second one was a wall-like shape. Given the sequence repetitions in the scaffold sequence, both were able to be assembled with only 6 different staples each one, ranging between 18 to 80 nucleotides. Simulations of both structures were performed using scaffolds of different sizes yielding stable structures in all the cases. The generation of the LAMP products were tested by colorimetry and electrophoresis. The formation of the DNA structures was analyzed using electrophoresis and colorimetry. The modeling of novel detection methods through bioinformatics tools allows reliable control and prediction of results. To our knowledge, this is the first study that uses LAMP products and DNA-origami in combination to delect ESBL-producing bacterial strains, which represent a promising methodology for diagnosis in the point-of-care.

Keywords: beta-lactamases, antibiotic resistance, DNA origami, isothermal amplification, LAMP technique, molecular diagnosis

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Authors: Frida C. Jaime Franco, C. Paulina Navarro Núñez, R. Jacob Sánchez Nájera

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The importance of developing multi-language abilities in our global society is noteworthy. However, the necessity, interest, and consciousness of the significance that the development of another language represents, apart from the mother tongue, is not always the same in all contexts as it is in multicultural communities, especially in rural higher education institutions immersed in small communities. Leading opportunities for digital interaction among learners from Mexico and abroad partners represents scaffolding towards, not only language skills development but also intercultural communicative competences (ICC). This study leads us to consider what should be the best approach to work while applying a program of ICC integrated into the practice of EFL. While analyzing the roots of the language, it is possible to obtain the main objective of learning another language, to communicate with a functional purpose, as well as attaching social practices to the learning process, giving a result of functionality and significance to the target language. Hence, the collateral impact that collaborative learning leads to, aims to contribute to a better global understanding as well as a means of self and other cultural awareness through intercultural communication. While communicating through the target language by online collaboration among students in platforms of long-distance communication, language is used as a tool of interaction to broaden students’ perspectives reaching a substantial improvement with the help of their differences. This process should consider the application of the target language in the inquiry of sociocultural information, expecting the learners to integrate communicative skills to handle cultural differentiation at the same time they apply the knowledge of their target language in a real scenario of communication, despite being through virtual resources.

Keywords: collaborative learning, communicative approach, culture, interaction, interculturalism, target language, virtual partnership

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Authors: Saima Nazir, Mustansar Ali Ghazanfar, Sanay Muhammad Umar Saeed, Muhammad Awais Azam, Saad Ali Alahmari

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Terrorism is an important and challenging concern. The entire world is threatened by only few sophisticated terrorist groups and especially in Gulf Region and Pakistan, it has become extremely destructive phenomena in recent years. Predicting the pattern of attack type, attack group and target type is an intricate task. This study offers new insight on terrorist group’s attack type and its chosen target. This research paper proposes a framework for prediction of terrorist attacks using the historical data and making an association between terrorist group, their attack type and target. Analysis shows that the number of attacks per year will keep on increasing, and Al-Harmayan in Saudi Arabia, Al-Qai’da in Gulf Region and Tehreek-e-Taliban in Pakistan will remain responsible for many future terrorist attacks. Top main targets of each group will be private citizen & property, police, government and military sector under constant circumstances.

Keywords: data mining, counter terrorism, machine learning, SVM

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Authors: Gagan Dhawan

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Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.

Keywords: drug resistance, efflux pump, molecular docking, virtual screening

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Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: Reynaldo Esquivel, Pedro Hernandez, Aaron Martinez-Higareda, Sergio Tena-Cano, Enrique Alvarez-Ramos, Armando Lucero-Acuna

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Stimuli-responsive nanomaterials play an essential role in loading, transporting and well-distribution of anti-cancer compounds in the cellular surroundings. The outstanding properties as the Lower Critical Solution Temperature (LCST), hydrolytic cleavage and protonation/deprotonation cycle, govern the release and delivery mechanisms of payloads. In this contribution, we experimentally determine the load efficiency and release of antineoplastic Vincristine Sulfate into PNIPAM-Interpenetrated-Chitosan (PIntC) nanoparticles. Structural analysis was performed by Fourier Transform Infrared Spectroscopy (FT-IR) and Proton Nuclear Magnetic Resonance (1HNMR). ζ-Potential (ζ) and Hydrodynamic diameter (DH) measurements were monitored by Electrophoretic Mobility (EM) and Dynamic Light scattering (DLS) respectively. Mathematical analysis of the release pharmacokinetics reveals a three-phase model above LCST, while a monophasic of Vincristine release model was observed at 32 °C. Cytotoxic essays reveal a noticeable enhancement of Vincristine effectiveness at low drug concentration on HeLa cervix cancer and MDA-MB-231 breast cancer.

Keywords: nanoparticles, vincristine, drug delivery, PNIPAM

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

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The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

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Authors: Shweta Sinha, Mukesh Doble, Manju S. L.

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Pyrazole scaffold is an important group of compound in heterocyclic chemistry and is found to possess numerous uses in chemistry. Pyrazole derivatives are also known to possess important biological activities including antitumor, antimicrobial, antiviral, antifungal, anticancer and anti-inflammatory. Inflammation is associated with pain, allergy and asthma. Leukotrienes are mediators of various inflammatory and allergic disorders. 5-Lipoxygenase (5-LOX) is an important enzyme involved in the biosynthesis of leukotrienes and metabolism of arachidonic acid (AA) and thus targeted for anti-inflammation. In vitro inhibitory activity of pyrazol-3-yl thiazole 4-carboxylic acid derivatives is tested against enzyme 5-LOX. Most of these compounds exhibit good inhibitory activity against this enzyme. Binding mode study of these compounds is determined by computational tool. Further experiments are being done to understand the mechanism of action of these compounds in inhibiting this enzyme. To conclude, these compounds appear to be a promising target in drug design against 5-LOX.

Keywords: inflammation, inhibition, 5-lipoxygenase, pyrazole

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Authors: Esra Turker, Umit Hakan Yildiz, Ahu Arslan Yildiz

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The key of regenerative medicine is mimicking natural three dimensional (3D) microenvironment of tissues by utilizing appropriate biomaterials. In this study, a synthetic biodegradable polymer; poly (L-lactide-co-ε-caprolactone) (PLLCL) and a natural polymer; collagen was used to mimic the biochemical structure of the natural extracellular matrix (ECM), and by means of electrospinning technique the real physical structure of ECM has mimicked. PLLCL/Collagen biocomposite scaffolds enables cell attachment, proliferation and nutrient transport through fabrication of micro to nanometer scale nanofibers. Biocomposite materials are commonly preferred due to limitations of physical and biocompatible properties of natural and synthetic materials. Combination of both materials improves the strength, degradation and biocompatibility of scaffold. Literature studies have shown that collagen is mostly solved with heavy chemicals, which is not suitable for cell culturing. To overcome this problem, a new approach has been developed in this study where polyvinylpyrrolidone (PVP) is used as co-electrospinning agent. PVP is preferred due to its water solubility, so PLLCL/collagen biocomposite scaffold can be easily and rapidly produced. Hydrolytic and enzymatic biodegradation as well as mechanical strength of scaffolds were examined in vitro. Cell adhesion, proliferation and cell morphology characterization studies have been performed as well. Further, on-chip drug screening analysis has been performed over 3D tumor models. Overall, the developed biocomposite scaffold was used for 3D tumor model formation and obtained results confirmed that developed model could be used for drug screening studies to predict clinical efficacy of a drug.

Keywords: biomaterials, 3D cell culture, drug screening, electrospinning, lab-on-a-chip, tissue engineering

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Authors: Shukri Dughman, Anthony Rossiter

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This paper builds on earlier work which demonstrated that Model Predictive Control (MPC) may give a poor choice of default feed forward compensator. By first demonstrating the impact of future information of target changes on the performance, this paper proposes a pragmatic method for identifying the amount of future information on the target that can be utilised effectively in both finite and infinite horizon algorithms. Numerical illustrations in MATLAB give evidence of the efficacy of the proposal.

Keywords: model predictive control, tracking control, advance knowledge, feed forward

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Authors: Tegan H. Emerson, Colin C. Olson, George Stantchev, Jason A. Edelberg, Michael Wilson

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Detecting small targets at range is difficult because there is not enough spatial information present in an image sub-region containing the target to use correlation-based methods to differentiate it from dynamic confusers present in the scene. Moreover, this lack of spatial information also disqualifies the use of most state-of-the-art deep learning image-based classifiers. Here, we use characteristics of target tracks extracted from video sequences as data from which to derive distinguishing topological features that help robustly differentiate targets of interest from confusers. In particular, we calculate persistent homology from time-delayed embeddings of dynamic statistics calculated from motion tracks extracted from a wide field-of-view video stream. In short, we use topological methods to extract features related to target motion dynamics that are useful for classification and disambiguation and show that small targets can be detected at range with high probability.

Keywords: motion tracks, persistence images, time-delay embedding, topological data analysis

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Authors: Lin Po-Hsi, Sheu Ming-Thau

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Urea cycle disorders (UCD) are rare genetic metabolic disorders that compromise the body's urea cycle. Sodium phenylbutyrate (SPB) is a medication commonly administered in tablet or powder form to lower ammonia levels. Nonetheless, its high sodium content poses risks to sodium-sensitive UCD patients. This necessitates the creation of an alternative drug formulation to mitigate sodium load and optimize drug delivery for UCD patients. This study focused on crafting a novel oral drug formulation for UCD, leveraging choline bicarbonate and phenylbutyric acid. The active pharmaceutical ingredient-ionic liquids (API-ILs) and therapeutic deep eutectic systems (THEDES) were formed by combining these with choline chloride. These systems display characteristics like maintaining a liquid state at room temperature and exhibiting enhanced solubility. This in turn amplifies drug dissolution rate, permeability, and ultimately oral bioavailability. Incorporating choline-based phenylbutyric acid as a substitute for traditional SPB can effectively curtail the sodium load in UCD patients. Our in vitro dissolution experiments revealed that the ILs and DESs, synthesized using choline bicarbonate and choline chloride with phenylbutyric acid, surpassed commercial tablets in dissolution speed. Pharmacokinetic evaluations in SD rats indicated a notable uptick in the oral bioavailability of phenylbutyric acid, underscoring the efficacy of choline salt ILs in augmenting its bioavailability. Additional in vitro intestinal permeability tests on SD rats authenticated that the ILs, formulated with choline bicarbonate and phenylbutyric acid, demonstrate superior permeability compared to their sodium and acid counterparts. To conclude, choline salt ILs developed from choline bicarbonate and phenylbutyric acid present a promising avenue for UCD treatment, with the added benefit of reduced sodium load. They also hold merit in formulation engineering. The sustained-release capabilities of DESs position them favorably for drug delivery, while the low toxicity and cost-effectiveness of choline chloride signal potential in formulation engineering. Overall, this drug formulation heralds a prospective therapeutic avenue for UCD patients.

Keywords: phenylbutyric acid, sodium phenylbutyrate, choline salt, ionic liquids, deep eutectic systems, oral bioavailability

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Authors: Amos Sunday Onikanni, Bashir Lawal, Babatunji Emmanuel Oyinloye, Gomaa Mostafa-Hedeab, Mohammed Alorabi, Simona Cavalu, Augustine O. Olusola, Chih-Hao Wang, Gaber El-Saber Batiha

Abstract:

The increasing global burden of diabetes mellitus has called for the search for a therapeutic alternative that offers better activities and safety than conventional chemotherapy. Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in a significant reversal of the biochemical alteration and improved the neurocognitive deficit in STZ-induced diabetic rats. However, the ethyl-acetate fraction demonstrated higher activities than the other fractions and was characterized for its phytoconstituents, revealing the presence of Gallic acid (713.00 ppm), catechin (0.91 ppm), ferulic acid (0.98 ppm), rutin (59.82 ppm), quercetin (3.22 ppm) and kaempferol (4.07 ppm). Our molecular docking analysis revealed that these compounds exhibited different binding affinities and potentials for targeting BChE/AChE/ IL-1 β/Na+-K+-ATPase. However, only Kampferol and ferulic exhibited good drug-like, ADMET, and permeability properties suitable for use as a neuronal drug target agent. Hence, the ethyl-acetate fraction of C. pubescent leaves could be considered a source of promising bioactive metabolite for the treatment and management of cognitive impairments related to type II diabetes mellitus.

Keywords: diabetes mellitus, neuroprotective, antioxidant, pro-inflammatory cytokines

Procedia PDF Downloads 98

Authors: Eitan Elaad

Abstract:

The present study's purpose was to examine lyingand pretend fairness by police interrogators in sharing situations. Forty police officers and 40 laypeople from the community, all males, self-assessed their lie-telling ability, rated the frequency of their lies, evaluated the acceptability of lying, and indicated using rational and intuitive thinking while lying. Next, according to the ultimatum game procedure, participants were asked to share 100 points with a virtual target, either a male police interrogator or a male layman. Participantsallocated points to the target person bearing in mind that the other person must accept their offer. Participants' goal was to retain as many points as possible, and to this end, they could tell the target person that fewer than 100 points were available for distribution. The difference between the available 100 points and the sum of points designated for sharing defines lying. The ratio of offered and designated points defines pretend fairness. Results indicate that those police officers lied more than laypeople. Similar results emergedeven when the target person was a police interrogator. However, police interrogators presented higher pretend fairness than laypeople. The higher pretend fairness may be in line with interrogation tactics of persuasion used in the criminal interrogation. Higher-lying frequency reported by police interrogators compared with laypeople support the present results. Finally, lie acceptability predicted lying in the ultimatum game. Specifically, participants who rated lying as more acceptable tended to lie more than low acceptability raters.

Keywords: lying, police interrogators, lie acceptability, ultimatum game, pretend fairness

Procedia PDF Downloads 139

Authors: Lorico D. S. Lapitan Jr., Yihan Xu, Yuan Guo, Dejian Zhou

Abstract:

The ability of ultrasensitive detection of specific genes and discrimination of single nucleotide polymorphisms is important for clinical diagnosis and biomedical research. Herein, we report the development of a new ultrasensitive approach for label-free DNA detection using magnetic nanoparticle (MNP) assisted rapid target capture/separation in combination with signal amplification using poly-enzyme tagged polymer nanobead. The sensor uses an MNP linked capture DNA and a biotin modified signal DNA to sandwich bind the target followed by ligation to provide high single-nucleotide polymorphism discrimination. Only the presence of a perfect match target DNA yields a covalent linkage between the capture and signal DNAs for subsequent conjugation of a neutravidin-modified horseradish peroxidase (HRP) enzyme through the strong biotin-nuetravidin interaction. This converts each captured DNA target into an HRP which can convert millions of copies of a non-fluorescent substrate (amplex red) to a highly fluorescent product (resorufin), for great signal amplification. The use of polymer nanobead each tagged with thousands of copies of HRPs as the signal amplifier greatly improves the signal amplification power, leading to greatly improved sensitivity. We show our biosensing approach can specifically detect an unlabeled DNA target down to 10 aM with a wide dynamic range of 5 orders of magnitude (from 0.001 fM to 100.0 fM). Furthermore, our approach has a high discrimination between a perfectly matched gene and its cancer-related single-base mismatch targets (SNPs): It can positively detect the perfect match DNA target even in the presence of 100 fold excess of co-existing SNPs. This sensing approach also works robustly in clinical relevant media (e.g. 10% human serum) and gives almost the same SNP discrimination ratio as that in clean buffers. Therefore, this ultrasensitive SNP biosensor appears to be well-suited for potential diagnostic applications of genetic diseases.

Keywords: DNA detection, polymer beads, signal amplification, single nucleotide polymorphisms

Procedia PDF Downloads 240

Authors: Neha Singh

Abstract:

Background: Nowadays, the nanoparticle is gaining unexceptional attention in targeted drug delivery. But before proceeding to this episode of accomplishment, the journey and closure of these nanoparticles inside the cells should be disentangle. Being foreign for the cells, nanoparticles will easily getcleared off without any effective outcome. As the cancer cells withhold these nanoparticles for a longer period of time, more will be the drug’s effect. Chlorpromazine is a cationic amphiphilic drug which is believed to inhibit clathrin-coated pit formation by a reversible translocation of clathrin and its adapter proteins from the plasma membrane to intracellular vesicles. Chlorpromazine has a role in increasing the retention of nanoparticles in cancer cells. The mechanism of action how this small molecule increases the retention of nanoparticles is still uncovered. Method: Polymeric nanoparticle (PLGA) with Cyanine3.5 dye were synthesized by solvent evaporation method and characterized for size and zeta potential. FTIR was also done. Pulse and chase studies with and without inhibitor were done to check the retention of nanoparticle using fluorescence microscopy. Mean fluorescence intensity was measured by ImageJ software. Results: Increased retention of nanoparticle with inhibitor was observed in both pulse and chase studies. Conclusion: Our results demonstrate that by repurposing these small molecule inhibitor, we can increase the retention of nanoparticle at the targeted site.

Keywords: nanoparticle, endocytosis, clathrin inhibitor, cancer cell

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Authors: Damola O. Lawal, David W. Gresty, Diane E. Gan, Louise Hewitt

Abstract:

This paper investigates the feasibility of using a programmable USB such as the O.MG Cable to perform a file tampering attack. Here, the O.MG Cable, an apparently harmless mobile device charger, is used in an unauthorized way to alter the content of a file (accounts record-January_Contributions.xlsx). The aim is to determine if a forensics analyst can reliably determine who has altered the target file; the O.MG Cable or the user of the machine. This work highlights some of the traces of the O.MG Cable left behind on the target computer itself, such as the Product ID (PID) and Vendor ID (ID). Also discussed is the O.MG Cable’s behavior during the experiments. We determine if a forensics analyst could identify if any evidence has been left behind by the programmable device on the target file once it has been removed from the computer to establish if the analyst would be able to link the traces left by the O.MG Cable to the file tampering. It was discovered that the forensic analyst might mistake the actions of the O.MG Cable for the computer users. Experiments carried out in this work could further the discussion as to whether an innocent user could be punished for the unauthorized changes made by a programmable device.

Keywords: O.MG cable, programmable USB, file tampering attack, digital evidence credibility, miscarriage of justice, cyber fraud

Procedia PDF Downloads 140

Authors: Sarah Nasr, Maha M. A. Nasra, Ossama Y. Abdallah

Abstract:

The present work aimed to prepare Silymarin loaded MCM-41 type mesoporous silica nanoparticles (MSNs) and to assess the system’s solubility enhancement ability on the pharmacodynamic performance of Silymarin as a hepatoprotective agent. MSNs prepared by soft-templating technique, were loaded with Silymarin, characterized for particle size, zeta potential, surface properties, DSC and XRPD. DSC and specific surface area data confirmed deposition of Silymarin in an amorphous state in MSNs’ pores. In-vitro drug dissolution testing displayed enhanced dissolution rate of Silymarin upon loading on MSNs. High dose Acetaminophen was then used to inflict hepatic injury upon albino male Wistar rats simultaneously receiving either free Silymarin, Silymarin loaded MSNs or blank MSNs. Plasma AST, ALT, albumin and total protein and liver homogenate content of TBARs or LDH as measures of antioxidant drug action were assessed for all animal groups. Results showed a significant superiority of Silymarin loaded MSNs to free drug in almost all parameters. Meanwhile prolonged administration of blank MSNs had no evident toxicity on rats.

Keywords: mesoporous silica nanoparticles, safety, solubility enhancement, silymarin

Procedia PDF Downloads 319

Authors: Chen Bo, Wen Zengping

Abstract:

Based on the results of previous studies, we focus on the research of real ground motion selection and scaling method for structural performance-based seismic evaluation using nonlinear dynamic analysis. The input of earthquake ground motion should be determined appropriately to make them compatible with the site-specific hazard level considered. Thus, an optimized selection and scaling method are established including the use of not only Monte Carlo simulation method to create the stochastic simulation spectrum considering the multivariate lognormal distribution of target spectrum, but also a spectral shape parameter. Its applications in structural fragility analysis are demonstrated through case studies. Compared to the previous scheme with no consideration of the uncertainty of target spectrum, the method shown here can make sure that the selected records are in good agreement with the median value, standard deviation and spectral correction of the target spectrum, and greatly reveal the uncertainty feature of site-specific hazard level. Meanwhile, it can help improve computational efficiency and matching accuracy. Given the important infection of target spectrum’s uncertainty on structural seismic fragility analysis, this work can provide the reasonable and reliable basis for structural seismic evaluation under scenario earthquake environment.

Keywords: ground motion selection, scaling method, seismic fragility analysis, spectral shape

Procedia PDF Downloads 279

Authors: Mohab Magdy Mostafa Mohamed

Abstract:

The objective of this paper is to introduce a vertical handover (VHO) algorithm between wireless LANs (WLANs) and LTE mobile networks. The proposed algorithm is based on the fuzzy control theory and takes into consideration power level, subscriber velocity, and target cell load instead of only power level in traditional algorithms. Simulation results show that network performance in terms of number of handovers and handover occurrence distance is improved.

Keywords: vertical handover, fuzzy control theory, power level, speed, target cell load

Procedia PDF Downloads 332

Authors: Jeena Gupta

Abstract:

In the today’s world of pharmaceutical products, one should not forget the healing properties of inexpensive food materials especially spices. They are known to possess hidden pharmaceutical ingredients, imparting them the qualities of being anti-microbial, anti-oxidant, anti-inflammatory and anti-carcinogenic. Further aberrant epigenetic regulatory mechanisms like DNA methylation, histone modifications or altered microRNA expression patterns, which regulates gene expression without changing DNA sequence, contribute significantly in the development of various diseases. Changing lifestyles and diets exert their effect by influencing these epigenetic mechanisms which are thus the target of dietary phytochemicals. Bioactive components of plants have been in use since ages but their potential to reverse epigenetic alterations and prevention against diseases is yet to be explored. Spices being rich repositories of many bioactive constituents are responsible for providing them unique aroma and taste. Some spices like curcuma and garlic have been well evaluated for their epigenetic regulatory potential, but for others, it is largely unknown. We have evaluated the biological activity of phyto-active components of Fennel, Cardamom and Fenugreek by in silico molecular modeling, in vitro and in vivo studies. Ligand-based similarity studies were conducted to identify structurally similar compounds to understand their biological phenomenon. The database searching has been done by using Fenchone from fennel, Sabinene from cardamom and protodioscin from fenugreek as a query molecule in the different small molecule databases. Moreover, the results of the database searching exhibited that these compounds are having potential binding with the different targets found in the Protein Data Bank. Further in addition to being epigenetic modifiers, in vitro study had demonstrated the antimicrobial, antifungal, antioxidant and cytotoxicity protective effects of Fenchone, Sabinene and Protodioscin. To best of our knowledge, such type of studies facilitate the target fishing as well as making the roadmap in drug design and discovery process for identification of novel therapeutics.

Keywords: epigenetics, spices, phytochemicals, fenchone

Procedia PDF Downloads 144