Search results for: slow drug release

Authors: Mulubrhan Berihu

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Due to the design versatility, availability, and cost efficiency, concrete continues to be the most used construction material on earth. However, the production of Portland cement, the primary component of concrete mix is causing to have a serious effect on environmental and economic impacts. This shows there is a need to study using of supplementary cementitious materials (SCMs). The most commonly used supplementary cementitious materials are wastes, and the use of these industrial waste products has technical, economic, and environmental benefits besides the reduction of CO2 emission from cement production. This paper aims to document the effect on the strength property of concrete due to the use of low cement by maximizing supplementary cementitious materials like fly ash. The amount of cement content was below 250 kg/m3, and in all the mixes, the quantity of powder (cement + fly ash) is almost kept at about 500 kg. According to this, seven different cement content (250 kg/m3, 195 kg/m3, 150 kg/m3, 125 kg/m3, 100 kg/m3, 85 kg/m3, 70 kg/m3) with different amount of replacement of SCMs was conducted. The mix proportion was prepared by keeping the water content constant and varying the cement content, SCMs, and water-to-binder ratio. Based on the different mix proportions of fly ash, a range of mix designs was formulated. The test results showed that using up to 85 kg/m3 of cement is possible for plain concrete works like hollow block concrete to achieve 9.8 Mpa, and the experimental results indicate that strength is a function of w/b. The experiment result shows a big difference in gaining of compressive strength from 7 days to 28 days and this obviously shows the slow rate of hydration of fly ash concrete. As the w/b ratio increases, the strength decreases significantly. At the same time, higher permeability was seen in the specimens which were tested for three hours than one hour.

Keywords: efficiency factor, cement content, compressive strength, mix proportion, w/c ratio, water permeability, SCMs

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Authors: Nurgul Senol, Melda Azman

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In this study, the rate of release of gastrointestinal peptides heavy metal compounds applied to a certain extent (gastrin/CCK) on immunohistochemical aimed to determine the effect. This study was supported by TÜBİTAK. Subjects were randomly grouped into three. Group I; iron (Fe), Group II; zinc (Zn), Group III; control; gavage technique was applied to each group once a day throughout 30 days. At the end of the experiment, rats were decapitated and their stomach-intestine tissues removed, Peroxidase anti peroxidase method was applied following the routine histological follow-ups. According to the control group, in the stomach, had more positive cell density of gastrin in Fe groups, it was observed that group followed by Zn. It was found between the groups in the stomach and intestinal gastrin, gastrin-positive cell density decreases towards the intestines from the stomach. Although CCK differences in staining were observed in the control group, the intensity of staining intensity between the two groups in positive cells was determined to be more than the stomach. The group in the intestines, there is no change in terms of positivity CCK. Consequently, there is no significant effect on gastrointestinal peptides in Zn application. It has been identified Fe application has a significant effect on the releasing of CCK/gastrin peptides.

Keywords: alimentary canal, CCK, iron, gastrin, zinc

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Authors: Nafdha Thajudeen

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Hijamah therapy is one of the leading alternative & complementary modalities in the World. It is a kind of detoxification, rejuvenation, and blood purification method. It comes under Ilaj bil Tadbeer (Regimental therapy) in the Unani medical system. In diabetes, hands and foot care in people is very important because of slow blood circulation, where blood sometimes is not able to fully penetrate the capillaries. Hijamah therapy works upon the following two principles- Tanqiyae Mawad (Evacuation of morbid humor) and Imalae Mawad (Diversion of humor). The aim of this study was to find out the effectiveness of hijamah therapy on the numbness of legs in a diabetic patient. This case study was carried out in Ayurvedic Research Hospital (Non-Communicable Diseases), Ninthavur, Sri Lanka. A 63 years old female diabetic patient came to the clinic with the complain of numbness in both feet for one year. The treatment history of the patient revealed that she had taken western medicine for her complaints for 7 months. In her first visit, wet cupping was done on local and distal points. The patient said there was a remarkable improvement; internal medicines were given to keep the sugar level in normal with some external applications. Every week, wet cupping was done on the same points, with repeating the same medicines. Foot numbness was fully cured within one month. The finding of this study shows that the complaint of numbness in the diabetic patient was treated with hijamah therapy with internal & external medicine. This case study can be concluded as hijamah therapy is very effective in treating diabetic numbness. This single case study may be the entrance for future clinical studies

Keywords: Hijamah therapy, Ilaj bil thadbeer, diabetes, numbness

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Authors: Patcharawalai Jaisamut, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee

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Supersaturation of drugs in the gastrointestinal tract is one approach to increase the absorption of poorly water-soluble drugs. The stabilization of a supersaturated state was achieved by adding precipitation inhibitors that may act through a variety of mechanisms.In this study, the effect of the natural gums, acacia, gelatin, pectin and tragacanth on curcumin supersaturation in simulated gastric fluid (SGF) (pH 1.2), fasted state simulated gastric fluid (FaSSGF) (pH 1.6), and simulated intestinal fluid (SIF) (pH 6.8)was investigated. The results indicated that all natural gums significantly increased the curcum insolubility (about 1.2-6-fold)when compared to the absence of gum, and assisted in maintaining the supersaturated drug solution. Among the tested gums, pectin at 3% w/w was the best precipitation inhibitor with a significant increase in the degree of supersaturation about 3-fold in SGF, 2.4-fold in FaSSGF and 2-fold in SIF.

Keywords: curcumin, solubility, supersaturation, precipitation inhibitor

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Authors: Jiahui Song, Ravindra Joshi

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High-intensity, nanosecond, pulsed electric fields have been shown to be useful non-thermal tools capable of producing a variety of specific cellular responses. While reversible and temporary changes are often desired based on electromanipulation, irreversible effects can also be important objectives. These include elimination of tumor cells and bacterial decontamination. A simple model-based rate-equation treatment of the various cellular biochemical processes was used to qualitatively predict the pulse number-dependent caspase activation and cell survival trends. The model incorporated the caspase-8 associated extrinsic pathway, the delay inherent in its activation, cytochrome c release, and the internal feedback mechanism between caspase-3 and Bid. Results were roughly in keeping with the experimental cell-survival data. A pulse-number threshold was predicted followed by a near-exponential fall-off. The intrinsic pathway was shown to be much weaker as compared to the extrinsic mechanism for electric pulse induced cell apoptosis. Also, delays of about an hour are predicted for detectable molecular concentration increases following electrical pulsing.

Keywords: apoptosis, cell survival, model, pathway

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Authors: N. Naga Subrahmanyeswara Rao, Parag Arvind Deshpande

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Understanding nucleotide synthesis reaction of any organism is beneficial to know the growth of it as in Mycobacterium tuberculosis to design anti TB drug. One of the reactions of de novo pathway which takes place in all organisms was considered. The reaction takes places between phosphoribosyl pyrophosphate and orotate catalyzed by orotate phosphoribosyl transferase and divalent metal ion gives orotdine monophosphate, a nucleotide. All the reaction steps of three experimentally proposed mechanisms for this reaction were considered to develop kinetic rate expression. The model was validated using the data for four organisms. This model could successfully describe the kinetics for the reported data. The developed model can serve as a reliable model to describe the kinetics in new organisms without the need of mechanistic determination. So an organism-independent model was developed.

Keywords: mechanism, nucleotide, organism, tuberculosis

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Authors: Ilham Ihoume, Rachid Tadili, Nora Arbaoui

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Recent innovations in economical heating systems have significantly boosted ‎agricultural production by effectively managing temperature drops in greenhouse ‎microclimates. These advancements enhance product profitability in terms of quality, ‎quantity, and growth duration. This study experimentally investigates the impact of a ‎solar heating system on the microclimate of an agricultural greenhouse, focusing on ‎zucchini (Cucurbita pepo). The System comprises a copper tube placed between double ‎roof glazing and a sensible heat storage system, converting solar energy during the day ‎and storing it for night-time release. A second control greenhouse without heating ‎allows for comparative analysis at various growth stages. During the cold season, the ‎experimental greenhouse showed a temperature increase of 3°C compared to the ‎control greenhouse and 5°C above external ambient air. The relative humidity in the ‎experimental greenhouse ranged from 69% to 70%, whereas the control greenhouse recorded 68% to 86%, and ambient air ‎was between 94% to 99%. The heating systems achieved an efficiency of 73%, and ‎zucchini plants in the experimental greenhouse developed fruit 13 days earlier than ‎those in the control greenhouse.‎

Keywords: solar energy, storage, energy managment, heating system

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Authors: Diala Bitar, Emmanuel Gourdon, Claude H. Lamarque, Manuel Collet

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Acoustic absorber devices play an important role reducing the noise at the propagation and reception paths. An electroacoustic absorber consists of a loudspeaker coupled to an electric shunt circuit, where the membrane is playing the role of an absorber/reflector of sound. Although the use of linear shunt resistors at the transducer terminals, has shown to improve the performances of the dynamical absorbers, it is nearly efficient in a narrow frequency band. Therefore, and since nonlinear phenomena are promising for their ability to absorb the vibrations and sound on a larger frequency range, we propose to couple a nonlinear electric shunt circuit at the loudspeaker terminals. Then, the equivalent model can be described by a 2 degrees of freedom system, consisting of a primary linear oscillator describing the dynamics of the loudspeaker membrane, linearly coupled to a cubic nonlinear energy sink (NES). The system is analytically treated for the case of 1:1 resonance, using an invariant manifold approach at different time scales. The proposed methodology enables us to detect the equilibrium points and fold singularities at the first slow time scales, providing a predictive tool to design the nonlinear circuit shunt during the energy exchange process. The preliminary results are promising; a significant improvement of acoustic absorption performances are obtained.

Keywords: electroacoustic absorber, multiple-time-scale with small finite parameter, nonlinear energy sink, nonlinear passive shunt

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Authors: Blair D. Macdonald

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After nearly one hundred years of its origin, foundational quantum mechanics remains one of the greatest unexplained mysteries in physicists today. Within this time, chaos theory and its geometry, the fractal, has developed. In this paper, the propagation behaviour with an iteration of a simple fractal, the Koch Snowflake, was described and analysed. From an arbitrary observation point within the fractal set, the fractal propagates forward by oscillation—the focus of this study and retrospectively behind by exponential growth from a point beginning. It propagates a potentially infinite exponential oscillating sinusoidal wave of discrete triangle bits sharing many characteristics of light and quantum entities. The model's wave speed is potentially constant, offering insights into the perception and a direction of time where, to an observer, when travelling at the frontier of propagation, time may slow to a stop. In isolation, the fractal is a superposition of component bits where position and scale present a problem of location. In reality, this problem is experienced within fractal landscapes or fields where 'position' is only 'known' by the addition of information or markers. The quantum' measurement problem', 'uncertainty principle,' 'entanglement,' and the classical-quantum interface are addressed; these are a problem of scale invariance associated with isolated fractality. Dual forward and retrospective perspectives of the fractal model offer the opportunity for unification between quantum mechanics and cosmological mathematics, observations, and conjectures. Quantum and cosmological problems may be different aspects of the one fractal geometry.

Keywords: measurement problem, observer, entanglement, unification

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Authors: Mebruka Mohammed, Daniel Bisrat, Asfaw Debella, Tarekegn Birhanu

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Lack of quality control standards for medicinal plants and their preparations is considered major barrier to their integration in to effective primary health care in Ethiopia. Poor quality herbal preparations led to countless adverse reactions extending to death. Denial of penetration for the Ethiopian medicinal plants in to the world’s booming herbal market is also another significant loss resulting from absence of herbal quality control system. Thus, in the present study, Gnidia stenophylla Gilg (popular antimalarial plant of south eastern Ethiopia), is standardized and a full monograph is produced that can serve as a guideline in quality control of the crude drug. Morphologically, the roots are found to be cylindrical and tapering towards the end. It has a hard, corky and friable touch with saddle brown color externally and it is relatively smooth and pale brown internally. It has got characteristic pungent odor and very bitter taste. Microscopically it has showed lignified xylem vessels, wider medullary rays with some calcium oxalate crystals, reddish brown secondary metabolite contents and slender shaped long fibres. Physicochemical standards quantified and resulted: foreign matter (5.25%), moisture content (6.69%), total ash (40.80%), acid insoluble ash (8.00%), water soluble ash (2.30%), alcohol soluble extractive (15.27%), water soluble extractive (10.98%), foaming index (100.01 ml/g), swelling index (7.60 ml/g). Phytochemically: Phenols, flavonoids, steroids, tannins and saponins were detected in the root extract; TLC and HPLC fingerprints were produced and an analytical marker was also tentatively characterized as 3-(3,4-dihydro-3,5-dihydroxy-2-(4-hydroxy-5-methylhex-1-en-2-yl)-7-methoxy-4-oxo-2H-chromen-8-yl)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one. Residue wise pesticides (i.e. DDT, DDE, g-BHC) and radiochemical levels fall below the WHO limit while Heavy metals (i.e. Co, Ni, Cr, Pb, and Cu), total aerobic count and fungal load lie way above the WHO limit. In conclusion, the result can be taken as signal that employing non standardized medicinal plants could cause many health risks of the Ethiopian people and Africans’ at large (as 80% of inhabitants in the continent depends on it for primary health care). Therefore, following a more universal approach to herbal quality by adopting the WHO guidelines and developing monographs using the various quality parameters is inevitable to minimize quality breach and promote effective herbal drug usage.

Keywords: Gnidia stenophylla Gilg, standardization/monograph, pharmacognostic, residue/impurity, quality

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Authors: Raquel C. A. G. Mota, Livia R. Menezes, Emerson O. da Silva

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Both silver nanoparticles and titanium dioxide have been extensively used in tissue engineering since they’ve been approved by the Food and Drug Administration (FDA), and present a bactericide effect when added to a polymeric matrix. In this work, the focus is on fabricating binary systems with both nanoparticles so that the synergistic effect can be investigated. The systems were tested by Nuclear Magnetic Resonance (NMR), Thermogravimetric Analysis (TGA), Fourier-Transformed Infrared (FTIR), and Differential Scanning Calorimetry (DSC), and X-ray Diffraction (XRD), and had both their bioactivity and bactericide effect tested. The binary systems presented different properties than the individual systems, enhancing both the thermal and biological properties as was to be expected. The crystallinity was also affected, as indicated by the finding of the DSC and XDR techniques, and the NMR showed a good dispersion of both nanoparticles in the polymer matrix. These findings indicate the potential of combining TiO₂ and silver nanoparticles in biomedicine.

Keywords: metallic nanoparticles, nanotechnology, polymer nanocomposites, polymer science

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Authors: Joel Weymouth, Ramesh K. Karne, Alexander L. Wijesinha

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Bare Machine Internet is part of the Bare Machine Computing (BMC) paradigm. It is used in programming application ns to run directly on a device. It is software that runs directly against the hardware using CPU, Memory, and I/O. The software application runs without an Operating System and resident mass storage. An important part of the BMC paradigm is the Bare Machine Internet. It utilizes an Application Development model software that interfaces directly with the hardware on a network server and file server. Because it is “bare,” it is a powerful teaching and research tool that can readily display the internals of the network protocols, software, and hardware of the applications running on the Bare Server. It was also demonstrated that the bare server was accessible by laptop and by smartphone/android. The purpose was to show the further practicality of Bare Internet in Computer Engineering and Computer Science Education and Research. It was also to show that an undergraduate student could take advantage of a bare server with any device and any browser at any release version connected to the internet. This paper presents the Bare Web Server as an educational tool. We will discuss possible applications of this paradigm.

Keywords: bare machine computing, online research, network technology, visualizing network internals

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Authors: R. Fegas, S. Zerkout, S. Taberkokt, M. Righezza

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The present work demonstrate the potential of Betacyclodextrine (BCD) for the chiral analysis of a drug .Various separation mechanisms were applied and several parameters affecting the separation were studied, including the type and concentration of chiral selector, and pH of buffer. A simple and sensitive high-performance liquid chromatography (HPLC) method was developed as an assay for fexofenadine enantiomers in pharmaceutical preparation. Fexofenadine enantiomers were separated using a mobile phase of 0.25mM NaH2PO4–acetonitrile (65:35, v/v) – Betacyclodextrine on achiral phenyl-urea column at a flow rate of 1ml/min and measurement at 220nm. The chiral mechanism of separation was mainly based on specific interaction between the solute and the stationary phase. The retention was directly controlled by mobile phase composition but not the selectivity which results of the two mechanisms, electrostatic interactions and partition mechanism.

Keywords: fexofenadine enantiomer, HPLC, achiral phenyl-urea column

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Authors: Aliaksei Patsekha, Michael Hohenberger, Harald Raupenstrauch

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An effective emergency response to accidents with chemical, biological, radiological, nuclear, or explosive materials (CBRNE) that represent highly dynamic situations needs immediate actions within limited time, information and resources. The aim of the study is to provide the foundation for division of unsafe area into risk zones according to the impact of hazardous parameters (heat radiation, thermal dose, overpressure, chemical concentrations). A decision on the boundary values for three risk zones is based on the vulnerability analysis that covered a variety of accident scenarios containing the release of a toxic or flammable substance which either evaporates, ignites and/or explodes. Critical values are selected for the boundary definition of the Red, Orange and Yellow risk zones upon the examination of harmful effects that are likely to cause injuries of varying severity to people and different levels of damage to structures. The obtained results provide the basis for creating a comprehensive real-time risk map for a decision support at CBRNE operations.

Keywords: boundary values, CBRNE threats, decision making process, hazardous effects, vulnerability analysis, risk zones

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Authors: Kun Chun, Jin-Chun Heo, Sang-Han Lee

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Asthma is a chronic airway inflammatory disease characterized by the infiltration of inflammatory cells and tissue remodeling. In this study, we examined the anti-asthmatic activity of a derivative of L-allo threonine by in vitro and in vivo anti-asthmatic assays. Ovalbumin (OVA)-induced C57BL/6 mice were used to analyze lung inflammation and cytokine expressions for exhibiting anti-atopic activity of the derivative. LX519290, a derivative of L-allo threonine, induced an increased IFN-γ and a decreased IL-10 mRNA level. This compound exhibited potent anti-asthmatic activity by decreasing immune cell infiltration in the lung, and IL-4 and IL-13 cytokine levels in the serum of OVA-induced mice. These results indicated that chronic airway injury was decreased by LX519290. We also assessed that LX519290 inhibits infiltration of immune cell, mucus release and cytokine expression in an in vivo model. Our results collectively suggest that the L-allo threonine is effective in alleviating asthmatic symptoms by treating inflammatory factors in the lung.

Keywords: asthma, L -allo threonine, LX519290, mice

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Authors: Theo Welch

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Background: Gamma-hydroxybutyrate (GHB) is a depressant of the central nervous system with euphoric effects. It is being increasingly used recreationally in the United Kingdom (UK) despite associated morbidity and mortality. Due to the lack of evidence, healthcare professionals remain unsure as to the optimum management of GHB acute toxicity. Methods: A literature review was undertaken of its pharmacology and the emergency management of its acute toxicity.Findings: GHB is inexpensive and readily available over the Internet. Treatment of GHB acute toxicity is supportive. Clinicians should pay particular attention to the airway as emesis is common. Intubation is required in a minority of cases. Polydrug use is common and worsens prognosis. Conclusion: An inexpensive and readily available drug, GHB acute toxicity can be difficult to identify and treat. GHB acute toxicity is generally treated conservatively. Further research is needed to ascertain the indications, benefits, and risks of intubating patients with GHB acute toxicity. instructions give you guidelines for preparing papers for the conference.

Keywords: GHB, gamma-hydroxybutyrate, prehospital, emergency, toxicity, management

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Authors: Giacomo Rossi, Bernardo Favini, Eugenio Giacomazzi, Franca Rita Picchia, Nunzio Maria Salvatore Arcidiacono

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A numerical technique for mesh refinement in the HeaRT (Heat Release and Transfer) numerical code is presented. In the CFD framework, Large Eddy Simulation (LES) approach is gaining in importance as a tool for simulating turbulent combustion processes, also if this approach has an high computational cost due to the complexity of the turbulent modeling and the high number of grid points necessary to obtain a good numerical solution. In particular, when a numerical simulation of a big domain is performed with a structured grid, the number of grid points can increase so much that the simulation becomes impossible: this problem can be overcame with a mesh refinement technique. Mesh refinement technique developed for HeaRT numerical code (a staggered finite difference code) is based on an high order reconstruction of the variables at the grid interfaces by means of a least square quasi-ENO interpolation: numerical code is written in modern Fortran (2003 standard of newer) and is parallelized using domain decomposition and message passing interface (MPI) standard.

Keywords: LES, multi-resolution, ENO, fortran

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Authors: Kuei-Ling Sun, Emily Chia-Yu Su

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Allergy is a hypersensitive overreaction of the immune system to environmental stimuli, and a major health problem. These overreactions include rashes, sneezing, fever, food allergies, anaphylaxis, asthmatic, shock, or other abnormal conditions. Allergies can be caused by food, insect stings, pollen, animal wool, and other allergens. Their development of allergies is due to both genetic and environmental factors. Allergies involve immunoglobulin E antibodies, a part of the body’s immune system. Immunoglobulin E antibodies will bind to an allergen and then transfer to a receptor on mast cells or basophils triggering the release of inflammatory chemicals such as histamine. Based on the increasingly serious problem of environmental change, changes in lifestyle, air pollution problem, and other factors, in this study, we both collect allergens and non-allergens from several databases and use several machine learning methods for classification, including logistic regression (LR), stepwise regression, decision tree (DT) and neural networks (NN) to do the model comparison and determine the permutations of allergen amino acid’s sequence.

Keywords: allergy, classification, decision tree, logistic regression, machine learning

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Authors: Kai Chun Yang, Shao-Wen Chen, Jong-Rong Wang, Chunkuan Shih, Jung-Hua Yang, Hsiung-Chih Chen, Wen-Sheng Hsu

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In this study, we build RADionuclide Transport, Removal And Dose Estimation/Symbolic Nuclear Analysis Package (SNAP/RADTRAD) model of Kuosheng Nuclear Power Plant which is based on the Final Safety Evaluation Report (FSAR) and other data of Kuosheng Nuclear Power Plant. It is used to estimate the radiation dose of the Exclusion Area Boundary (EAB), the Low Population Zone (LPZ), and the control room following ‘release from the containment’ case in Loss Of Coolant Accident (LOCA). The RADTRAD analysis result shows that the evaluation dose at EAB, LPZ, and the control room are close to the FSAR data, and all of the doses are lower than the regulatory limits. At last, we do a sensitivity analysis and observe that the evaluation doses increase as the intake rate of the control room increases.

Keywords: RADTRAD, radionuclide transport, removal and dose estimation, snap, symbolic nuclear analysis package, boiling water reactor, NPP, kuosheng

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Authors: D. Ravinder

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Nickel ferrites and Ni doped Lithium nano ferrites [Li0.5Fe0.5]1-xNixFe2O4 with x= 0.8 and 1.0 synthesized by citrate-gel auto combustion method. The broad peaks in the X-ray diffraction pattern (XRD) indicate a crystalline behavior of the prepared samples. Low temperature magnetization studies i,e Field Cooled (FC) and Zero Field Cooled (ZFC) magnetic studies of the investigated samples are measured by using vibrating sample magnetometer (VSM). The magnetization of the prepared samples as a function of an applied magnetic field 10 T was measured at two different temperatures 5 K and 310 K. Field Cooled (FC) and Zero Field Cooled (ZFC) magnetization measurements under an applied field of 100 Oe and 1000 Oe in the temperature range of 5–375 K were carried out.

Keywords: ferro-spinels, field cooled (FC), Zero Field Cooled (ZFC) and blocking temperature, superpara magnetism, drug delivery applications

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Authors: Niv Papo

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Characterizing the binding selectivity landscape of interacting proteins is crucial both for elucidating the underlying mechanisms of their interaction and for developing selective inhibitors. However, current mapping methods are laborious and cannot provide a sufficiently comprehensive description of the landscape. Here, we introduce a distinct and efficient strategy for comprehensively mapping the binding landscape of proteins using a combination of experimental multi-target selective library screening and in silico next-generation sequencing analysis. We map the binding landscape of a non-selective trypsin inhibitor, the amyloid protein precursor inhibitor (APPI), to each of four human serine proteases (kallikrein-6, mesotrypsin, and anionic and cationic trypsins). We then use this map to dissect and improve the affinity and selectivity of APPI variants toward each of the four proteases. Our strategy can be used as a platform for the development of a new generation of target-selective probes and therapeutic agents based on selective protein–protein interactions.

Keywords: drug design, directed evolution, protein engineering, protease inhibition.

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Authors: Ferjani Hanen, El Arem Amira, Boussema Ayed Imen, Bacha Hassen

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Tacrolimus (TAC), a calcineurin inhibitor, is clinically used as an immunosuppressive agent in the transplant recipient, but its use associated-hepatotoxicity. Mycophenolate mofetil (MMF), an anti-metabolite, is a potent immunosuppressive drug. MMF is not hepatotoxic and is the most common adjunctive immunosuppressant for TAC. The effects of TAC and MMF combination in the liver is still not well understood. This work aimed to investigate their combined effect against in liver in rats Wistar after 24 h. The oral median lethal doses (LD50) of TAC and MMF alone were evaluated in rats are 240 mg/kg and 500 mg/kg respectively. Oral administration of the MMF at 50 mg/kg to male Wistar intoxicated with TAC at 60 mg/kg, demonstrated a significant protective effect by lowering the levels of hepatic markers enzymes (AST, ALT) in the serum rat. MMF attenuated oxidative stress by restoring the activities of SOD, CAT and by reducing the malondialdehyde (MDA) and protein carbonyl levels liver. This study provided evidence that MMF protects rat liver from TAC-induced injury and suggests a most combination use for organ transplantation.

Keywords: tacrolimus, mycophenolate mofetil, combination, liver, rat

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Authors: A. N.Ukwuani, A. K. Abdulfatah

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G. crenata is used locally for the treatment of fractured bones, wound healing and inflammatory conditions. In vitro and in vivo antioxidant activity of hydromethanolic extracts of the leaves of G. crenata were assessed. The phytochemical analysis shows the presence of phenols, flavonoids, saponins, cardiac glycosides and tannins. An in vitro quantitative analysis of phenols, flavonoids and tannins respectively were (164±1.20, 199±0.88 and 88.67±0.88 mg/100g FW). In vivo studies of hydromethanolic extract demonstrated a dose dependent increase in hepatic superoxide dismutase (1.14±0.14, 2.13±0.11, 2.55±0.11 U/mg Protein) with improvement in hepatic glutathione (6.98±0.42, 8.91±0.37, 11.07±0.46 µM/mg Protein) and Catalase (4.47±0.05, 6.24±0.02, 7.17±0.04 U/mg Protein) and Total protein (6.18±0.08, 6.69±0.18, 7.27±0.16 mg/ml) respectively at 100-300mg/kg body weight Grewia crenata leaves when compared to the control and standard drug. It can be concluded from the present findings of that G. crenata leaves possess antioxidant potential.

Keywords: Grewia crenata, antioxidant, hydromethanolic extract, in vivo, in vitro

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Authors: Yun Ma, Jiajun Lu

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President Xi Jinping has clearly stated the need to more effectively advance the process of urbanization centered on people, striving to shape cities into spaces that are healthier, safer, and more livable. However, during the development and construction of mountainous cities, numerous uncertain disruptive factors have emerged, one after another, posing severe challenges to the city's overall development. Therefore, building resilient cities and creating high-quality urban ecosystems and safety systems have become the core and crux of achieving sustainable urban development. This paper takes the central urban area of Chongqing as the research object and establishes an urban resilience assessment indicator system from four dimensions: society, economy, ecology, and infrastructure. It employs the entropy weight method and TOPSIS model to assess the urban resilience level of the central urban area of Chongqing from 2019 to 2022. The results indicate that i. the resilience level of the central urban area of Chongqing is unevenly distributed, showing a spatial pattern of "high in the middle and low around"; it also demonstrates differentiation across different dimensions; ii. due to the impact of the COVID-19 pandemic, the overall resilience level of the central urban area of Chongqing has declined significantly, with low recovery capacity and slow improvement in urban resilience. Finally, based on the four selected dimensions, this paper proposes optimization strategies for urban resilience in mountainous cities, providing a basis for Chongqing to build a safe and livable new city.

Keywords: mountainous urban areas, central urban area of chongqing, entropy weight method, TOPSIS model, ArcGIS

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Authors: A. Nusrath Unissa, Sameer Hassan, Luke Elizabeth Hanna

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Altered drug binding may be an important factor in isoniazid (INH) resistance, rather than major changes in the enzyme’s activity as a catalase or peroxidase (KatG). The identification of structural or functional defects in the mutant KatGs responsible for INH resistance remains as an area to be explored. In this connection, the differences in the binding affinity between wild-type (WT) and mutants of KatG were investigated, through the generation of three mutants of KatG, Ser315Thr [S315T], Ser315Asn [S315N], Ser315Arg [S315R] and a WT [S315]) with the help of software-MODELLER. The mutants were docked with INH using the software-GOLD. The affinity is lower for WT than mutant, suggesting the tight binding of INH with the mutant protein compared to WT type. These models provide the in silico evidence for the binding interaction of KatG with INH and implicate the basis for rationalization of INH resistance in naturally occurring KatG mutant strains of Mycobacterium tuberculosis.

Keywords: Mycobacterium tuberculosis, KatG, INH resistance, mutants, modelling, docking

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Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

Abstract:

Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the study of pathogenesis, biological characteristics and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, LipoDox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using Magnetic Resonance Imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thigh were classified into three groups: control group (untreated), Dox-treated group and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, Three-Dimensional (3D) Fast Spin Echo (FSE) T2-Weighted Images (T2WI) was used for tumor volumetric quantification. And Two-Dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic Contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbits. Afterwards, a series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Keywords: doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model

Procedia PDF Downloads 460

Authors: Sudhanshu Sharma

Abstract:

Lisinopril, 1-[N-{(s)-I-carboxy-3 phenyl propyl}-L-proline dehydrate is a lysine analog of enalaprilat, the active metabolite of enalapril. It is long-acting, non-sulhydryl angiotensin-converting enzyme (ACE) inhibitor that is used for the treatment of hypertension and congestive heart failure in daily dosage 10-80 mg. Pharmacological activity of lisinopril has been proved in various experimental and clinical studies. Owing to its importance and widespread use, efforts have been made towards the development of simple and reliable analytical methods. As per our literature survey, lisinopril in pharmaceutical formulations has been determined by various analytical methodologies like polaragraphy, potentiometry, and spectrophotometry, but most of these analytical methods are not too suitable for the Identification of lisinopril from clinical samples because of the interferences caused by the amino acids and amino groups containing metabolites present in biological samples. This report is an attempt in the direction of developing a simple and reliable method for on plate identification and quantification of lisinopril in pharmaceutical formulations as well as from human urine samples using silica gel H layers developed with a new mobile phase comprising of micellar solutions of N-cetyl-N, N, N-trimethylammonium bromide (CTAB). Micellar solutions have found numerous practical applications in many areas of separation science. Micellar liquid chromatography (MLC) has gained immense popularity and wider applicability due to operational simplicity, cost effectiveness, relatively non-toxicity and enhanced separation efficiency, low aggressiveness. Incorporation of aqueous micellar solutions as mobile phase was pioneered by Armstrong and Terrill as they accentuated the importance of TLC where simultaneous separation of ionic or non-ionic species in a variety of matrices is required. A peculiarity of the micellar mobile phases (MMPs) is that they have no macroscopic analogues, as a result the typical separations can be easily achieved by using MMPs than aqueous organic mobile phases. Previously MMPs were successfully employed in TLC based critical separations of aromatic hydrocarbons, nucleotides, vitamin K1 and K5, o-, m- and p- aminophenol, amino acids, separation of penicillins. The human urine analysis for identification of selected drugs and their metabolites has emerged as an important investigation tool in forensic drug analysis. Among all chromatographic methods available only thin layer chromatography (TLC) enables a simple fast and effective separation of the complex mixtures present in various biological samples and is recommended as an approved testing for forensic drug analysis by federal Law. TLC proved its applicability during successful separation of bio-active amines, carbohydrates, enzymes, porphyrins, and their precursors, alkaloid and drugs from urine samples.

Keywords: lisnopril, surfactant, chromatography, micellar solutions

Procedia PDF Downloads 370

Authors: Abdelkader Mohamed Abdelkader Mohamed Gaballah

Abstract:

This study addresses advancements in veterinary health and their significance in enhancing animal care. The primary objective is to meet the increasing needs of veterinarians and farmers by offering sustainable and effective veterinary medicines that comply with safety and efficacy standards. The methodology involves a comprehensive selection process to source high-quality veterinary products from trusted manufacturers while ensuring adherence to environmental sustainability principles. The findings demonstrate that these products significantly contribute to improving animal health, reducing the prevalence of diseases, and supporting sustainable farming practices. In conclusion, the study emphasizes the importance of collaborative efforts within the veterinary pharmaceutical industry to meet global demands and promote sustainable practices in animal care.

Keywords: veterinary medicine, animal health, veterinary pharmaceuticals, livestock management, animal science and care, veterinary drug development, animal nutrition, wellness

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Authors: Stavros Poulopoulos, Aphrodite Tetorou, Constantine Philippopoulos

Abstract:

Day after day more pharmaceutical compounds that are not efficiently removed by conventional treatment methods are found in treated wastewaters and drinking waters. Due to their refractory nature, they escape conventional wastewater treatment facilities, and thus advanced oxidation processes have to be utilized to effectively eliminate them. In the present study, the removal of Ibuprofen from aqueous solutions containing the commercial drug Algofren (non-steroidal, anti-inflammatory) using UV irradiation, hydrogen peroxide, titanium dioxide and ferric ions was examined. All experiments were conducted in a batch photoreactor operated for 120 min. The main target was to select the most effective operating conditions for the mineralization of the solutions treated. The combination of Fe(III)/ H₂O₂/UV proved to be very efficient in terms of total organic carbon removal and ibuprofen conversion. For solutions containing 5 mg/L ibuprofen and initial total carbon 51.1 mg/L, complete mineralization was achieved by means of 2.2 ppm Fe(III) and 333 mg/L H₂O₂.

Keywords: pharmaceuticals, photocatalytic, photo-Fenton, TiO₂

Procedia PDF Downloads 156