Search results for: selective targeting

Authors: G. Wagner, R. Herrmann

Abstract:

Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: cytotoxicity, mesoporous silica, nanoparticles, platinum compounds

Procedia PDF Downloads 319

Authors: Xavier Lorang, Ahmadali Tahmasebimoradi, Chetra Mang, Sylvain Girard

Abstract:

The additive manufacturing processes (e.g. selective laser melting) allow us to produce lattice structures which have less weight, higher impact absorption capacity, and better thermal exchange property compared to the classical structures. Unfortunately, geometric imperfections (defects) in the lattice structures are by-products results of the manufacturing process. These imperfections decrease the lifetime and the strength of the lattice structures and alternate their mechanical responses. The objective of the paper is to present a simulation strategy which allows us to take into account the effect of the geometric imperfections on the mechanical response of the lattice structure. In the first part, an identification method of geometric imperfection parameters of the lattice structure based on point clouds is presented. These point clouds are based on tomography measurements. The point clouds are fed into the platform LATANA (LATtice ANAlysis) developed by IRT-SystemX to characterize the geometric imperfections. This is done by projecting the point clouds of each microbeam along the beam axis onto a 2D surface. Then, by fitting an ellipse to the 2D projections of the points, the geometric imperfections are characterized by introducing three parameters of an ellipse; semi-major/minor axes and angle of rotation. With regard to the calculated parameters of the microbeam geometric imperfections, a statistical analysis is carried out to determine a probability density law based on a statistical hypothesis. The microbeam samples are randomly drawn from the density law and are used to generate lattice structures. In the second part, a finite element model for the lattice structure with the simplified geometric imperfections (ellipse parameters) is presented. This numerical model is used to simulate the generated lattice structures. The propagation of the uncertainties of geometric imperfections is shown through the distribution of the computed mechanical responses of the lattice structures.

Keywords: additive manufacturing, finite element model, geometric imperfections, lattice structures, propagation of uncertainty

Procedia PDF Downloads 180

Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai

Abstract:

Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.

Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis

Procedia PDF Downloads 133

Authors: Ibrahim Hakeem

Abstract:

Biosolids are stabilised sewage sludge produced from wastewater treatment processes. Biosolids contain valuable plant nutrient which facilitates their beneficial reuse in agricultural land. However, the increasing levels of legacy and emerging contaminants such as heavy metals (HMs), PFAS, microplastics, pharmaceuticals, microbial pathogens etc., are restraining the direct land application of biosolids. Pyrolysis of biosolids can effectively degrade microbial and organic contaminants; however, HMs remain a persistent problem with biosolids and their pyrolysis-derived biochar. In this work, we demonstrated the integrated processing of biosolids involving the acid pre-treatment for HMs removal and selective reduction of ash-forming elements followed by the bench-scale pyrolysis of the treated biosolids to produce quality biochar and bio-oil enriched with valuable platform chemicals. The pre-treatment of biosolids using 3% v/v H₂SO₄ at room conditions for 30 min reduced the ash content from 30 wt% in raw biosolids to 15 wt% in the treated sample while removing about 80% of limiting HMs without degrading the organic matter. The preservation of nutrients and reduction of HMs concentration and mobility via the developed hydrometallurgical process improved the grade of the treated biosolids for beneficial land reuse. The co-removal of ash-forming elements from biosolids positively enhanced the fluidised bed pyrolysis of the acid-treated biosolids at 700 ℃. Organic matter devolatilisation was improved by 40%, and the produced biochar had higher surface area (107 m²/g), heating value (15 MJ/kg), fixed carbon (35 wt%), organic carbon retention (66% dry-ash free) compared to the raw biosolids biochar with surface area (56 m²/g), heating value (9 MJ/kg), fixed carbon (20 wt%) and organic carbon retention (50%). Pre-treatment also improved microporous structure development of the biochar and substantially decreased the HMs concentration and bioavailability by at least 50% relative to the raw biosolids biochar. The integrated process is a viable approach to enhancing value recovery from biosolids.

Keywords: biosolids, pyrolysis, biochar, heavy metals

Procedia PDF Downloads 72

Authors: M. G. Murtaza, E. E. Tzirtzilakis, M. Ferdows

Abstract:

Biomagnetic fluid dynamics is an interdisciplinary field comprising engineering, medicine, and biology. Bio fluid dynamics is directed towards finding and developing the solutions to some of the human body related diseases and disorders. This article describes the flow and heat transfer of two dimensional, steady, laminar, viscous and incompressible biomagnetic fluid over a non-linear stretching sheet in the presence of magnetic dipole. Our model is consistent with blood fluid namely biomagnetic fluid dynamics (BFD). This model based on the principles of ferrohydrodynamic (FHD). The temperature at the stretching surface is assumed to follow a power law variation, and stretching velocity is assumed to have a nonlinear form with signum function or sign function. The governing boundary layer equations with boundary conditions are simplified to couple higher order equations using usual transformations. Numerical solutions for the governing momentum and energy equations are obtained by efficient numerical techniques based on the common finite difference method with central differencing, on a tridiagonal matrix manipulation and on an iterative procedure. Computations are performed for a wide range of the governing parameters such as magnetic field parameter, power law exponent temperature parameter, and other involved parameters and the effect of these parameters on the velocity and temperature field is presented. It is observed that for different values of the magnetic parameter, the velocity distribution decreases while temperature distribution increases. Besides, the finite difference solutions results for skin-friction coefficient and rate of heat transfer are discussed. This study will have an important bearing on a high targeting efficiency, a high magnetic field is required in the targeted body compartment.

Keywords: biomagnetic fluid, FHD, MHD, nonlinear stretching sheet

Procedia PDF Downloads 154

Authors: Chi-Hsuan Cheng

Abstract:

This research aims to evaluate public-private partnerships against cyberattacks by comparing the UK and Taiwan. First, the study analyses major cyberattacks and factors influencing cybersecurity in both countries. Second, it assesses the effectiveness of current cyber defence strategies in combating cyberattacks by comparing the approaches taken in the UK and Taiwan, while also evaluating the cyber resilience of both nations. Lastly, the research evaluates existing public-private partnerships by comparing those in the UK and Taiwan, and proposes recommendations for enhancing cooperation and collaboration mechanisms in tackling cyberattacks. Grounded theory serves as the core research method. Theoretical sampling is used to recruit participants in both the UK and Taiwan, including investigators, police officers, and professionals from cybersecurity firms. Semi-structured interviews are conducted in English in the UK and Mandarin in Taiwan, recorded with consent, and pseudonymised for privacy. Data analysis involves open coding, grouping excerpts into codes, and categorising codes. Axial coding connects codes into categories, leading to the development of a codebook. The process continues iteratively until theoretical saturation is reached. Finally, selective coding identifies the core topic, evaluating public-private cooperation against cyberattacks and its implications for social and policing strategies in the UK and Taiwan, which highlights the current status of the cybersecurity industry, governmental plans for cybersecurity, and contributions to cybersecurity from both government sectors and cybersecurity firms, with a particular focus on public-private partnerships. In summary, this research aims to offer practical recommendations to law enforcement, private sectors, and academia for reflecting on current strategies and tailoring future approaches in cybersecurity

Keywords: cybersecurity, cybercrime, public private partnerships, cyberattack

Procedia PDF Downloads 67

Authors: Kashan Bashir, Salah Naji Ahmed Sufyan, Mirza Umar Baig

Abstract:

In this study, n-dodecane, tetralin, decalin, and tetramethybenzene (TMBE) were used as model compounds of alkanes, naphthenic-aromatic, cycloalkanes and alkyl-benzenes presented in hydro-diesel. The catalytic cracking properties of four model compounds over Y zeolite catalyst (Y-Cat.) and ZSM-5 zeolite catalysts (ZSM-5-Cat.) were probed. The experiment results revealed that high conversion of macromolecular paraffin and naphthenic aromatics were achieved over Y-Cat, whereas its low cracking activity of intermediate products micromolecules paraffin and olefin and high activity of hydride transfer reaction goes against the production of value-added products (light olefin and gasoline). In contrast, despite the fact that the hydride transfer reaction was greatly inhabited over ZSM-5-Cat, the low conversion of macromolecules was observed attributed to diffusion limitations. Interestingly, the mixed catalyst compensates for the shortcomings of the two catalysts, and a “relay reaction” between Y-Cat and ZSM-5-Cat was proposed. Specifically, the added Y-Cat acts as a “pre-cracking booster site” and promotes macromolecules conversion. The addition of ZSM-5-Cat not only significantly suppresses the hydride transfer reaction but also contributes to the cracking of immediate products paraffin and olefin into ethylene and propylene, resulting in a high yield of alkyl-benzene (gasoline), ethylene, and propylene with a low yield of naphthalene (LCO) and coke. The catalytic cracking evaluation experiments of mixed hydro-LCO were also performed to further clarify the “relay reaction” above, showing the highest yield of LPG and gasoline over mixed catalyst. The results indicate that the Y-cat and ZSM-5-cat have a synergistic effect on the conversion of hydro-diesel and corresponding value-added product yield and selective coke yield.

Keywords: synergistic effect, hydro-diesel cracking, FCC, zeolite catalyst, ethylene and propylene

Procedia PDF Downloads 61

Authors: Khawaja A. Wahaj Wani, Aykut Erkal

Abstract:

Pakistan's construction industry, a key player in economic development, has experienced remarkable growth. However, the surge in activities has been accompanied by dangerous working conditions, attributed to legislative gaps and flaws. Unhealthy construction practices, uncertain site conditions, and hazardous environments contribute to a concerning rate of injuries and fatalities. The principal aim of this research study is to undertake a thorough evaluation based on the assessment of the current situation of Health & Safety policies and the surveys performed by stakeholders of Pakistan with the aim of providing solution-centric methodologies for the enforcement of health and safety regulations within construction companies operating on project sites. Recognizing the pivotal role that the construction industry plays in bolstering a nation's economy, it is imperative to address the pressing need for heightened awareness among site engineers and laborers. The study adopts a robust approach, utilizing questionnaire surveys and interviews. As an exclusive investigative study, it encompasses all stakeholders: clients, consultants, contractors, and subcontractors. Targeting PEC-registered companies. Safety performance was assessed through the examination of sixty safety procedures using SPSS-18. A high Cronbach's alpha value of 0.958 ensures data reliability, and non-parametric tests were employed due to the non-normal distribution of data. The safety performance evaluation revealed significant insights. "Using Hoists and Cranes" and "Precautionary Measures (Shoring and Excavation)" exhibited commendable safety levels. Conversely, "Trainings on Safety" displayed a lower safety performance, alongside areas such as "Safety in Contract Documentation," "Meetings for Safety," and "Worker Participation," indicating room for improvement. These findings provide stakeholders with a detailed understanding of current safety measures within Pakistan's construction industry.

Keywords: construction industry, health and safety regulations, Pakistan, risk management

Procedia PDF Downloads 51

Authors: André C. Silva, Izabela L. A. Moraes, Elenice M. S. Silva, Carlos M. Silva Filho

Abstract:

In Brazil, most soils are acidic and low in essential nutrients required for the growth and development of plants, making fertilizers essential for agriculture. As the biggest producer of soy in the world and a major producer of coffee, sugar cane and citrus fruits, Brazil is a large consumer of phosphate. Brazilian’s phosphate ores are predominantly from igneous rocks showing a complex mineralogy, associated with carbonites and oxides, typically iron, silicon and barium. The adopted industrial concentration circuit for this type of ore is a mix between magnetic separation (both low and high field) to remove the magnetic fraction and a froth flotation circuit composed by a reverse flotation of apatite (barite’s flotation) followed by direct flotation circuit (rougher, cleaner and scavenger circuit). Since the 70’s fatty acids obtained from vegetable oils are widely used as lower-cost collectors in apatite froth flotation. This is a very effective approach to the apatite family of minerals, being that this type of collector is both selective and efficient (high recovery). This paper presents Jatropha curcas L. oil (JCO) as a renewable and sustainable source of fatty acids with high selectivity in froth flotation of apatite. JCO is considerably rich in fatty acids such as linoleic, oleic and palmitic acid. The experimental campaign involved 216 tests using a modified Hallimond tube and two different minerals (apatite and quartz). In order to be used as a collector, the oil was saponified. The results found were compared with the synthetic collector, Fotigam 5806 produced by Clariant, which is composed mainly by soy oil. JCO showed the highest selectivity for apatite flotation with cold saponification at pH 8 and concentration of 2.5 mg/L. In this case, the mineral recovery was around 95%.

Keywords: froth flotation, jatropha curcas, microflotation, selectivity

Procedia PDF Downloads 425

Authors: Barry Aifesehi Aiworo, Henry Oriakhi

Abstract:

This paper, examines the analysis of access pattern to school and travel risks among school children in Benin City, Edo State, Nigeria. The risk includes accident, molestation (sexually) and kidnapping. The objective of this paper are to examine the various means (modes) of transport to school; determine the type and incidences of risk experienced by school children in the study area; examine the risk incidences and ages of school children in the study area. Hypothesis which states that the types of risks encountered by school children are independent of means of transport was tested using the chi-square test (X2). A sampling ratio of twelve percent (12%) was taken from 396 schools in Benin City. By implication, 49 schools were randomly selected in Benin City for this research. A total of 42,053 students in the 49 schools constitute the sample frame for the research. Two percent (2%), 841 students were taken as the sample size. The use of stratified sampling method was applied by stratifying the study area (Benin City) into local governments- Egor, Ikpoba-Okha and Oredo. Thereafter, the lists of schools in the various local governments were obtained from the Ministry of Education before the schools for research were randomly chosen from each local government area. The analysis revealed that 6.7% of the total students interviewed have been involved in road accidents. 1.04% of the total respondents said at one time or the other that they have been kidnapped. Finally, the research found that travel is comparatively safe and believes this may be partly attributable to safer route to schools and school children being more familiar with the school journey. The research indicates that children aged between eleven and fifteen are most at risk of hit or knocked down on Benin City’s roads. These findings may help in planning and targeting road safety initiative (education, campaigns) in Benin City.

Keywords: accident, molestation (sexually), kidnapping, pedophile, pedestrian

Procedia PDF Downloads 205

Authors: Nagui A. Abdel-Khalek, Khaled A. Selim, Ahmed Hamdy

Abstract:

Kaolin is naturally occurring ore predominantly containing kaolinite mineral in addition to some gangue minerals. Typical impurities present in kaolin ore are quartz, iron oxides, titanoferrous minerals, mica, feldspar, organic matter, etc. The main coloring impurity, particularly in the ultrafine size range, is titanoferrous minerals. Kaolin is used in many industrial applications such as sanitary ware, table ware, ceramic, paint, and paper industries, each of which should be of certain specifications. For most industrial applications, kaolin should be processed to obtain refined clay so as to match with standard specifications. For example, kaolin used in paper and paint industries need to be of high brightness and low yellowness. Egyptian kaolin is not subjected to any beneficiation process and the Egyptian companies apply selective mining followed by, in some localities, crushing and size reduction only. Such low quality kaolin can be used in refractory and pottery production but not in white ware and paper industries. This paper aims to study the amenability of beneficiation of an Egyptian kaolin ore of El-Teih locality, Sinai, to be suitable for different industrial applications. Attrition scrubbing and classification followed by magnetic separation are applied to remove the associated impurities. Attrition scrubbing and classification are used to separate the coarse silica and feldspars. Wet high intensity magnetic separation was applied to remove colored contaminants such as iron oxide and titanium oxide. Different variables affecting of magnetic separation process such as solid percent, magnetic field, matrix loading capacity, and retention time are studied. The results indicated that substantial decrease in iron oxide (from 1.69% to 0.61% ) and TiO2 (from 3.1% to 0.83%) contents as well as improving iso-brightness (from 63.76% to 75.21% and whiteness (from 79.85% to 86.72%) of the product can be achieved.

Keywords: Kaolin, titanoferrous minerals, beneficiation, magnetic separation, attrition scrubbing, classification

Procedia PDF Downloads 350

Authors: Elitsa Kolentsova, Dimitar Dimitrov, Vasko Idakiev, Tatyana Tabakova, Krasimir Ivanov

Abstract:

Formaldehyde production by selective oxidation of methanol is an important industrial process. The main by-products in the waste gas are CO and dimethyl ether (DME). The idea of this study is to combine the advantages of both Cu-Mn and Cu-Co catalytic systems by obtaining a new mixed Cu-Mn-Co catalyst with high activity and selectivity at the simultaneous oxidation of CO, methanol, and DME. Two basic Cu-Mn samples with high activity were selected for further investigation: (i) manganese-rich Cu-Mn/γ–Al2O3 catalyst with Cu/Mn molar ratio 1:5 and (ii) copper-rich Cu-Mn/γ-Al2O3 catalyst with Cu/Mn molar ratio 2:1. Manganese in these samples was replaced by cobalt in the whole concentration region, and catalytic properties were determined. The results show a general trend of decreasing the activity toward DME oxidation and increasing the activity toward CO and methanol oxidation with the increase of cobalt up to 60% for both groups of catalyst. This general trend, however, contains specific features, depending on the composition of the catalyst and the nature of the oxidized gas. The catalytic activity of the sample with Cu/(Mn+Co) molar ratio of 2:1 is gradually changed with increasing the cobalt content. The activity of the sample with Cu/(Mn+Co) molar ratio of 1: 5 passes through a maximum at 60% manganese replacement by cobalt, probably due to the formation of highly dispersed Co-based spinel structures (Co3O4 and/or MnCo2O4). In conclusion, the present study demonstrates that the Cu-Mn-Co/γ–alumina supported catalysts have enhanced activity toward CO, methanol and DME oxidation. Cu/(Mn+Co) molar ratio 1:5 and Co/Mn molar ratio 1.5 in the active component can ensure successful oxidation of CO, CH3OH and DME. The active component of the mixed Cu-Mn-Co/γ–alumina catalysts consists of at least six compounds - CuO, Co3O4, MnO2, Cu1.5Mn1.5O4, MnCo2O4 and CuCo2O4, depending on the Cu/Mn/Co molar ratio. Chemical composition strongly influences catalytic properties, this effect being quite variable with regards to the different processes.

Keywords: Cu-Mn-Co catalysts, oxidation, carbon oxide, VOCs

Procedia PDF Downloads 214

Authors: Ricardo Pinto Mario Covele, Patricio V. Langa, Patrick Swanzy

Abstract:

The English language has been recognized as a universal medium of instruction in academia, especially in Higher Education Institutions (HEIs) hence exerting enormous influence within the context of research and publication. By extension, the English Language has been embraced by scholars from non-English speaking countries. The purpose of this review was to synthesize the discussions using four databases. Discussion in the English language in the career development of academics, particularly in non-English speaking universities, is largely less visible. This paper seeks to fill this gap and to improve the visibility of the English language in the career development of academics focusing on non-English language speaking universities by undertaking a systematic literature review. More specifically, the paper addresses the language policy, English language learning model as a second language, sociolinguistic field and career development, methods, as well as its main findings. This review analyzed 75 relevant resources sourced from Western Cape’s Library, Scopus, Google scholar, and web of science databases from November 2020 to July 2021 using the PQRS framework as an analytical lens. The paper’s findings demonstrate that, while higher education continues to be under-challenges of English language usage, literature targeting non-English speaking universities remains less discussed than it is often described. The findings also demonstrate the dominance of English language policy, both for knowledge production and dissemination of literature challenging emerging scholars from non-English speaking HEIs. Hence, the paper argues for the need to reconsider the context of non-English language speakers in the English language in the career development of academics’ research, both as empirical fields and as emerging knowledge producers. More importantly, the study reveals two bodies of literature: (1) the instrumentalist approach to English Language learning and (2) Intercultural approach to the English Language for career opportunities, classified as the appropriate to explain the English language learning process and how is it perceived towards scholars’ academic careers in HEIs.

Keywords: English language, public and private universities, language policy, career development, non-English speaking countries

Procedia PDF Downloads 146

Authors: Nour S. Abdelrahman, Seunghyun Hong, Hassan A. Arafat, Daniel Choi, Faisal Al Marzooqi

Abstract:

Abstract—The advancement of lithium extraction methods from water sources, particularly saltwater brine, is gaining prominence in the lithium recovery industry due to its cost-effectiveness. Traditional techniques like recrystallization, chemical precipitation, and solvent extraction for metal recovery from seawater or brine are energy-intensive and exhibit low efficiency. Moreover, the extensive use of organic solvents poses environmental concerns. As a result, there's a growing demand for environmentally friendly lithium recovery methods. Membrane-based separation technology has emerged as a promising alternative, offering high energy efficiency and ease of continuous operation. In our study, we explored the potential of lithium-selective sieve channels constructed from layers of 2D graphene oxide and MXene (transition metal carbides and nitrides), integrated with surface – SO₃₋ groups. The arrangement of these 2D sheets creates interplanar spacing ranging from 0.3 to 0.8 nm, which forms a barrier against multivalent ions while facilitating lithium-ion movement through nano capillaries. The introduction of the sulfonate group provides an effective pathway for Li⁺ ions, with a calculated binding energy of Li⁺ – SO³⁻ at – 0.77 eV, the lowest among monovalent species. These modified membranes demonstrated remarkably rapid transport of Li⁺ ions, efficiently distinguishing them from other monovalent and divalent species. This selectivity is achieved through a combination of size exclusion and varying binding affinities. The graphene oxide channels in these membranes showed exceptional inter-cation selectivity, with a Li⁺/Mg²⁺ selectivity ratio exceeding 104, surpassing commercial membranes. Additionally, these membranes achieved over 94% rejection of MgCl₂.

Keywords: ion permeation, lithium extraction, membrane-based separation, nanotechnology

Procedia PDF Downloads 66

Authors: Mitra Assadi, Md. Faan

Abstract:

Background: Autism Spectrum Disorder (ASD) in a common neurodevelopmental disorder with limited pharmacological interventions. Transcranial Magnetic Stimulation (rTMS) has produced promising results in ASD, although there is no consensus regarding optimal targets or stimulation paradigms. A prevailing theory in ASD attributes the core deficits to dysfunction of the mirror neurons located in the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Methods: Thus far, 11 subjects with ASD, 10 boys and 1 girl with the mean age of 13.36 years have completed the study by receiving 10 session of high frequency rTMS to the IPL. The subjects were randomized to receive stimulation on the left or right IPL and sham stimulation to the opposite side. The outcome measures included the Social Responsiveness Scale – Second Edition (SRS-2) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency task. Results: None of the 11 subjects experienced any adverse effects. The rTMS did not produce any improvement in verbal fluency, nor there was any statistically significant difference between the right versus left sided stimulation. Analysis of social awareness on SRS-2 (SRS-AWR) indicated a close to significant effect of the treatment with a small to medium effect size. After removing a single subject with Level 3 ASD, we demonstrated a close to significant improvement on SRS-AWR with a large effect size. The analysis of the data 3-month post TMS demonstrated return of the SRS-AWR values to baseline. Conclusion: This preliminary analysis of the 11 subjects who have completed our study thus far shows a favorable response to high frequency rTMS stimulation of the mirror neurons/IPL on social awareness. While the decay of the response noted during the 3-month follow-up may be considered a limitation of rTMS, the presence of the improvement, especially the effect size despite the small sample size, is indicative of the efficacy of this technique.

Keywords: rTMS, autism, scoial cognition, mirror neurons

Procedia PDF Downloads 61

Authors: Kalkidan Worku, Eniyew Tegegne, Menichil Amsalu, Samuel Derbie Habtegiorgis

Abstract:

Introduction: Because of the seasonal nature of the work, day laborers are exposed to risky sexual practices. Since the majority of them are living far away from their birthplace and family, they engage in unplanned and multiple sexual practices. These unplanned and unprotected sexual experiences are a risk for different types of sexual-related health crises. This study aimed to assess the pooled prevalence of risky sexual practices and its determinants among day laborers in Ethiopia. Methods: Online databases, including PubMed, Google Scholar, Science Direct, African Journal of Online, Academia Edu, Semantic Scholar, and university repository sites, were searched from database inception until March 2023. PRISMA 2020 guideline was used to conduct the review. Among 851 extracted studies, ten articles were retained for the final quantitative analysis. To identify the source of heterogeneity, a sub-group analysis and I² test were performed. Publication bias was assessed by using a funnel plot and the Egger and Beg test. The pooled prevalence of risky sexual practices was calculated. Besides, the association between determinant factors and risky sexual practice was determined using a pooled odds ratio (OR) with a 95% confidence interval. Result: The pooled prevalence of risky sexual practices among day laborers was 46.00% (95% CI: 32.96, 59.03). Being single (OR: 2.49; 95% CI: 1.29 to 4.83), substance use (OR: 1.79; 95% CI: 1.40 to 2.29), alcohol intake (OR: 4.19; 95% CI: 2.19 to 8.04), watching pornographic (OR: 5.49; 95% CI: 2.99 to 10.09), discussion about SRH (OR: 4.21; 95% CI: 1.34 to 13.21), visiting night clubs (OR: 2.86 95% CI: 1.79 to 4.57) and risk perception (OR: 0.37 95% CI: 0.20 to 0.70) were the possible factors for risky sexual practice of day laborers in Ethiopia. Conclusions: A large proportion of day laborers engaged in risky sexual practices. Interventions targeting creating awareness of sexual and reproductive health for day laborers should be implemented. Continuous peer education on sexual health should be given to day laborers. Sexual and reproductive health services should be accessible in their workplaces to maximize condom utilization and to facilitate sexual health education for all day laborers.

Keywords: day laborers, sexual health, risky sexual practice, unsafe sex, multiple sexual partners

Procedia PDF Downloads 66

Authors: Sung-Jun Yoo, Kazuhide Ito

Abstract:

In this study, a comprehensive computer simulated person (CSP) that integrates computational human model (virtual manikin) and respiratory tract model (virtual airway), was applied for estimation of indoor environmental quality. Moreover, an inclusive prediction method was established by integrating computational fluid dynamics (CFD) analysis with advanced CSP which is combined with physiologically-based pharmacokinetic (PBPK) model, unsteady thermoregulation model for analysis targeting micro-climate around human body and respiratory area with high accuracy. This comprehensive method can estimate not only the contaminant inhalation but also constant interaction in the contaminant transfer between indoor spaces, i.e., a target area for indoor air quality (IAQ) assessment, and respiratory zone for health risk assessment. This study focused on the usage of the CSP as an air/thermal quality sensor in indoors, which means the application of comprehensive model for assessment of IAQ and thermal environmental quality. Demonstrative analysis was performed in order to examine the applicability of the comprehensive model to the heating, ventilation, air conditioning (HVAC) control scheme. CSP was located at the center of the simple model room which has dimension of 3m×3m×3m. Formaldehyde which is generated from floor material was assumed as a target contaminant, and flow field, sensible/latent heat and contaminant transfer analysis in indoor space were conducted by using CFD simulation coupled with CSP. In this analysis, thermal comfort was evaluated by thermoregulatory analysis, and respiratory exposure risks represented by adsorption flux/concentration at airway wall surface were estimated by PBPK-CFD hybrid analysis. These Analysis results concerning IAQ and thermal comfort will be fed back to the HVAC control and could be used to find a suitable ventilation rate and energy requirement for air conditioning system.

Keywords: CFD simulation, computer simulated person, HVAC control, indoor environmental quality

Procedia PDF Downloads 357

Authors: Simmi Chopra

Abstract:

In the last few years, there has been a surge of Autoimmune diseases that have become more like an epidemic all over the world. The reasons vary from stress, insufficient sleep, smoking, genetics, environmental pollution, adulterated foods, and a diet full of “the deadly white,” which is white sugar and white flour. Most of the people diagnosed with these diseases are given steroids, opioids, supplements, or elimination diets to manage their lives, but most of them continue suffering to varying degrees. On the other hand, Ayurveda can help manage autoimmune problems effectively. Ayurveda is a 5000 years old holistic medical system from India that has an individualistic approach where health problems are looked at from the lens of balancing body and mind and by targeting the root cause of the problem. A combination of diet and lifestyle according to Ayurvedic principles, Ayurvedic herbal formulations and Ayurvedic therapies can help in the management of autoimmune and other chronic diseases. Panchkarma, which is an intense six weeks detox method, helps balance our body and mind, and has been very effective in managing autoimmune problems. The paper will introduce the basic concepts of Ayurveda and describe the terminologies- doshas, agni and ama. The paper will discuss the importance of diet and lifestyle according to the individual’s imbalance in the three functional parameters - doshas, which govern every aspect of our body and mind, our cells and tissues. The significance of agni, which can be correlated to digestive strength and ama, which can be correlated to toxins that are formed in our body leading to health problems, will be outlined. The Ayurvedic pathophysiology of autoimmune diseases will be discussed with emphasis on Rheumatoid arthritis, Multiple sclerosis and Psoriasis. Ayurvedic management will be discussed for these autoimmune conditions. As Ayurveda is an individualistic system, one protocol will not work for everyone. Therefore, case studies with Ayurvedic protocols for the above autoimmune disease will be presented. Conclusion: Ayurveda can help in managing as well as arresting the progression of autoimmune problems. Ayurveda is an ancient medical system, is much more needed today than ever. It is a tried and tested holistic system which has been practiced for the past many generations in India.

Keywords: ayurveda, autoimmune, diseases, nutrition

Procedia PDF Downloads 60

Authors: Beatrice Wamuyu Muchiri, Monika M. L. Dos Santos

Abstract:

An increasingly recognised prevention approach for substance use entails reduction in risk factors and enhancement of promotive or protective factors in individuals and the environment surrounding them during their growth and development. However, in order to enhance the effectiveness of this approach, continuous study of risk aspects targeting different cultures, social groups and mixture of society has been recommended. This study evaluated the impact of potential risk and protective factors associated with family management and relations on adolescent substance abuse in South Africa. Exploratory analysis and cumulative odds ordinal logistic regression modelling was performed on the data while controlling for demographic and socio-economic characteristics on adolescent substance use. The most intensely used substances were tobacco, cannabis, cocaine, heroin and alcohol in decreasing order of use intensity. The specific protective or risk impact of family management or relations factors varied from substance to substance. Risk factors associated with demographic and socio-economic factors included being male, younger age, being in lower education grades, coloured ethnicity, adolescents from divorced parents and unemployed or fully employed mothers. Significant family relations risk and protective factors against substance use were classified as either family functioning and conflict or family bonding and support. Several family management factors, categorised as parental monitoring, discipline, behavioural control and rewards, demonstrated either risk or protective effect on adolescent substance use. Some factors had either interactive risk or protective impact on substance use or lost significance when analysed jointly with other factors such as controlled variables. Interaction amongst risk or protective factors as well as the type of substance should be considered when further considering interventions based on these risk or protective factors. Studies in other geographical regions, institutions and with better gender balance are recommended to improve upon the representativeness of the results. Several other considerations to be made when formulating interventions, the shortcomings of this study and possible improvements as well as future studies are also suggested.

Keywords: risk factors, protective factors, substance use, adolescents

Procedia PDF Downloads 196

Authors: Patrick Oehler, Nicholas Folger

Abstract:

Following a new public management approach, Germany has widely reformed its higher education system around the turn of the millennium. Aimed at preparing the country’s publicly funded universities and applied science colleges for a century of glory, the reforms led to the introduction of rigid performance measurement and management practices, which disrupted the inert system on all levels. Yet, many of the new policies met significant resistance, and some of them had to be reversed over time. Ever since Germany has struggled to find a balance between its pre- and its post-millennial approach to performance measurement and management. This contribution combines insights of a joint research project, which was created and funded by the German Federal Ministry of Education and Research with the aim to better understand the effects of its performance measurement and management policies, including those the ministry had implemented over the previous decades. The research project combines researchers from 17 German research institutions who employed a wide range of theories from various disciplines and very diverse research methods to explain performance measurement and management and their consequences on the behavior of various stakeholders in higher education systems. In these projects, performance measurement and management have been researched from three angles—education, research, and third mission. The collaborative project differentiated functional and dysfunctional elements of common performance measurement and management practices, and identified key problems with these practices, such as (1) oversimplification of performance indicators, (2) ‘overmeasurement’ of performance in general, (3) excessive use of quantitative indicators, and (4), a myopic focus on research-focused indicators and a negligence of measures targeting education and third mission. To address these issues, the collaborative project developed alternative approaches to performance measurement and management, including suggestions for qualitative performance measures, improved supervision, review, and evaluations methods, and recommendations how to better balance education, research, and third mission. The authors would like to share the rich findings of the joint research project with an international audience and discuss their implications for alternative higher education systems.

Keywords: performance measurement, performance management, new public management, performance evaluation

Procedia PDF Downloads 265

Authors: Malay K. Das, Bhupen Kalita

Abstract:

The poor oral bioavailability of resveratrol (RSV) due to presystemic metabolism can be avoided via dermal route of administration. The hydrophilic-lipophilic nature of resveratrol-phospholipid complex (RSVPs) favors the delivery of resveratrol via the skin. The RSVPs embedded polymeric patch with moderate adhesiveness was developed for dermal application for sustained anti-inflammatory effect. The prepared patches were evaluated for various physicochemical properties, surface morphology by SEM, TEM, and compatibility of patch components by FT-IR and DSC studies. The dermal flux of the optimized patch formulation was found to be at 4.28 ± 0.48 mg/cm2/24 h. The analysis of skin extract after permeation study revealed the presence of resveratrol, which confirmed the localization of RSVPs in the skin. The stability of RSVPs in the polymeric patch and the physiologic environment was confirmed by FE-SEM studies on the patches after drug release and skin permeation studies. The RSVPs particles released from the polymer matrix maintaining the structural integrity and permeate the keratinized horney layer of skin. The optimized patch formulation showed sustained anti-inflammatory effect (84.10% inhibition of inflammation at 24 h) in carrageenan-induced rat paw edema model compared to marketed diclofenac sodium gel (39.58% inhibition of inflammation at 24 h). The CLSM study confirmed the localization of RSVPs for a longer period, thus enabling drug targeting to the dermis for sustained anti-inflammatory effect. Histological studies with phase contrast trinocular microscope suggested no alteration of skin integrity and no evidence of the presence of inflammatory cells after exposure to the permeants. The patch was found to be safe for skin application as evaluated by Draize method for skin irritation scoring in a rabbit model. These results suggest the therapeutic efficacy of the developed patch in both acute and chronic inflammatory diseases.

Keywords: resveratrol-phospholipid complex, skin delivery, sustained anti-inflammatory effect, inflammatory diseases, dermal patch

Procedia PDF Downloads 228

Authors: Baburao Ganpat Apte, Gajodhar

Abstract:

Introduction: diopathic Parkinson’s disease (PD) is the most common neurodegenerative disorder. Early PD may present a diagnostic challenge with broad differential diagnoses that are not associated with striatal dopamine deficiency. This test was performed by using special type of radioactive precursor which was made available through our logistics. 131I-TOPA L-6-[131I] Iodo-3,4-Trihydroxyphenylalnine (131I -TOPA) is a positron emission tomography (PET) agent that measures the uptake of dopamine precursors for assessment of presynaptic dopaminergic integrity and has been shown to accurately reflect the sign of nervous mind going in patients suffers from monoaminergic disturbances in PD. Both qualitative and quantitative analyses of the scans were performed. Therefore, the early clinical diagnosis alone may be accurate and this reinforces the importance of functional imaging targeting the patholigically of the disease process. The patient’s medical records were then assessed for length of follow-up, response to levotopa, clinical course of sickness, and usually though of symptoms at time of 131I -TOPA PET. A respective analysis was carried out for all patients that gone through 131I -TOPA PET brain scan for motor symptoms suspicious for PD between 2000 - 2006. The eventual diagnosis by the referring neurologist, movement therapist, physiotherapist, was used as the accurate measurements in standard for further analysis. In this study, our goal to illustrate our local experience to determine the accuracy of 131I -TOPA PET for diagnosis of PD. We studied a total of 48 patients. Of the 25 scans, it found that one was a false negative, 40 were true positives, and 7 were true negatives. The resultant values are Sensitivity 90.4% (95% CI: 100%-71.3%), Specificity 100% (92% CI: 100%-58.0%), PPV 100% (91% CI 100%-75.7%), and NPV 80.5% (95% CI: 92.5%-48.5%). Result: Twenty-three patients were found in the initial query, and 1 were excluded (2 uncertain diagnosis, 2 inadequate follow-up). Twenty-eight patients (28 scans) remained with 15 males (62%) and 8 females (30%). All the patients had a clinical follow-up of at least 3 years, however the median length of follow-up was 5.5 years (range: 2-8 years). The median age at scan time was 51.2 years (range: 35-75)

Keywords: 18F-TOPA, petct, parkinson’s disease, cardiac

Procedia PDF Downloads 12

Authors: Maria Francesca Scannone, Martina Bochicchio

Abstract:

One of the major environmental problems today is hydrocarbon contamination. The promising sustainable technologies for the treatment of these contaminated sites involves the use of biological organisms. In Agri Valley (Basilicata Region) there is a living laboratory (natural oil seeps) where the selective pressure has enriched the environmental matrices with microorganisms, fungi and plant species able to use the hydrocarbons as a source of metabolic energy, to degrade or tolerate hydrocarbons. Observers visiting this area are fascinated by its unspoiled nature, and the condition of the ecosystem does not appear to has been damaged. The amazing resiliency observed in Tramutola site is of key importance to try to bring green remediation technologies, but no research has been done to identify high-performing native species. The aim of this research was to study how natural processes affect the fate of released oil or how individual species or communities of plants and animals are capable of dealing with the burden of otherwise toxic chemicals. The survey of vegetation was carried out, more than 60 species have been identified and divided into tree, shrub and herb layer. Plant data sheets have been completed only for the species that showed the most appropriate properties for phytoremediation. In general, members of the Salicales, Cyperales, Poales, Fagales, Cornales, Equisetales orders were the most commonly identified orders. They are pioneer plants with high adaptive capacity and vegetative propagation. The literature review has highlighted the existence of rhizosphere effect and a green liver model on selected plants. The study provides significant information on the environmental stress adaptation processes of many indigenous plants that are living and growing on a natural leak of crude oil and gas that migrates up through subsurface.

Keywords: green liver, hydrocarbon degradation, oil seeps, phytoremediation

Procedia PDF Downloads 170

Authors: Christine Fräulin, Daniela Schurr, Hamed Shahidi Rad, Gerrit Waters, Günter Rinke, Roland Dittmeyer, Michael Nilles

Abstract:

The reaction mechanisms of many liquid-phase reactions in organic chemistry have not yet been sufficiently clarified. Process conditions of several hundred degrees celsius and pressures to ten megapascals complicate the sampling and the determination of kinetic data. Space resolved in-situ measurements promises new insights. A non-invasive in-situ measurement technique has the advantages that no sample preparation is necessary, there is no change in sample mixture before analysis and the sampling do no lead to interventions in the flow. Thus, the goal of our research was the development of a contact-free spatially resolved measurement technique for kinetic studies of liquid phase reaction under process conditions. Therefore we used laser Raman spectroscopy combined with an optical transparent microchannel reactor. To show the performance of the system we choose the oxidation of cyclohexane as sample reaction. Cyclohexane oxidation is an economically important process. The products are intermediates for caprolactam and adipic acid, which are starting materials for polyamide 6 and 6.6 production. To maintain high selectivities of 70 to 90 %, the reaction is performed in industry at a low conversion of about six percent. As Raman spectroscopy is usually very selective but not very sensitive the detection of the small product concentration in cyclohexane oxidation is quite challenging. To meet these requirements, an optical experimental setup was optimized to determine the concentrations by laser Raman spectroscopy with respect to good detection sensitivity. With this measurement technique space resolved kinetic studies of uncatalysed and homogeneous catalyzed cyclohexane oxidation were carried out to obtain details about the reaction mechanism.

Keywords: in-situ laser raman spectroscopy, space resolved kinetic measurements, homogeneous catalysis, chemistry

Procedia PDF Downloads 327

Authors: Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Demet Sinem Guden, Sefika Pinar Kucukkavruk, Bahar Tunctan, Ayse Nihal Sari, Zumrut Kocak

Abstract:

We hypothesized that mTOR inhibition may prevent the multiple organ failures following severe multiple tissue injury associated with increased NADPH oxidase system activity occur in zymosan-induced systemic inflammation. Therefore, we investigated the role of mTOR in oxidative/nitrosative stress associated with increase in NADPH oxidase activity in zymosan-induced systemic inflammation model in rats. Male Wistar rats received saline (4 ml/kg, i.p.) and zymosan (500 mg/kg, i.p.) at time 0. Saline, or zymosan-treated rats were given rapamycin (1 mg/kg, i.p.) 1 h after saline or zymosan injections. Rats were sacrified 4 h after zymosan challenge and kidney, heart, thoracic aorta, and superior mesenteric artery were collected. NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels were measured in tissue samples. Zymosan administration caused an increase in NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels in kidney, heart, thoracic aorta, and superior mesenteric artery. These changes caused by zymosan reversed by rapamycin, a selective mTOR inhibitor. Rapamycin alone had no effect on the parameters measured. Our results demonstrated that zymosan-induced oxidative/nitrosative stress presumably due to enhanced activity of NADPH oxidase, expression of p22phox, gp91phox, and p47phox and production of peroxynitrite were mediated by mTOR. [This work was financially supported by Research Foundation of Mersin University (2016-2-AP3-1900)].

Keywords: oxidative stress, mTOR, nitrosative stress, zymosan

Procedia PDF Downloads 310

Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

Abstract:

One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

Procedia PDF Downloads 96

Authors: In-Hwan Baek

Abstract:

Valsartan is a potent and highly selective antagonist of the angiotensin II type 1 receptor, and is widely used for the treatment of hypertension. The aim of this study was to investigate the pharmacokinetic properties of the valsartan in dogs following oral administration of a single dose using quantitative modeling approaches. Forty beagle dogs were randomly divided into two group. Group A (n=20) was administered a single oral dose of valsartan 80 mg (Diovan® 80 mg), and group B (n=20) was administered a single oral dose of valsartan 160 mg (Diovan® 160 mg) in the morning after an overnight fast. Blood samples were collected into heparinized tubes before and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 h following oral administration. The plasma concentrations of the valsartan were determined using LC-MS/MS. Non-compartmental pharmacokinetic analyses were performed using WinNonlin Standard Edition software, and modeling approaches were performed using maximum-likelihood estimation via the expectation maximization (MLEM) algorithm with sampling using ADAPT 5 software. After a single dose of valsartan 80 mg, the mean value of maximum concentration (Cmax) was 2.68 ± 1.17 μg/mL at 1.83 ± 1.27 h. The area under the plasma concentration-versus-time curve from time zero to the last measurable concentration (AUC24h) value was 13.21 ± 6.88 μg·h/mL. After dosing with valsartan 160 mg, the mean Cmax was 4.13 ± 1.49 μg/mL at 1.80 ± 1.53 h, the AUC24h was 26.02 ± 12.07 μg·h/mL. The Cmax and AUC values increased in proportion to the increment in valsartan dose, while the pharmacokinetic parameters of elimination rate constant, half-life, apparent of total clearance, and apparent of volume of distribution were not significantly different between the doses. Valsartan pharmacokinetic analysis fits a one-compartment model with first-order absorption and elimination following a single dose of valsartan 80 mg and 160 mg. In addition, high inter-individual variability was identified in the absorption rate constant. In conclusion, valsartan displays the dose-dependent pharmacokinetics in dogs, and Subsequent quantitative modeling approaches provided detailed pharmacokinetic information of valsartan. The current findings provide useful information in dogs that will aid future development of improved formulations or fixed-dose combinations.

Keywords: dose-dependent, modeling, pharmacokinetics, valsartan

Procedia PDF Downloads 293

Authors: Nadine Wiesmann, Melanie Viel, Christoph Buhr, Rachel Tanner, Wolfgang Tremel, Juergen Brieger

Abstract:

Recidivation of tumors and the development of resistances against the classical anti-tumor approaches represent a major challenge we face when treating cancer. In order to master this challenge, we are in desperate need of new treatment options beyond the beaten tracks. Zinc oxide nanoparticles (ZnO NPs) represent such an innovative approach. Zinc oxide is characterized by a high level of biocompatibility, concurrently ZnO NPs are able to exert anti-tumor effects. By concentration of the nanoparticles at the tumor site, tumor cells can specifically be exposed to the nanoparticles while low zinc concentrations at off-target sites are tolerated well and can be excreted easily. We evaluated the toxicity of ZnO NPs in vitro with the help of immortalized tumor cell lines and primary cells stemming from healthy tissue. Additionally, the Chorioallantoic Membrane Assay (CAM Assay) was employed to gain insights into the in vivo behavior of the nanoparticles. We could show that ZnO NPs interact with tumor cells as nanoparticulate matter. Furthermore, the extensive release of zinc ions from the nanoparticles nearby and within the tumor cells results in overload with zinc. Beyond that, ZnO NPs were found to further the generation of reactive oxygen species (ROS). We were able to show that tumor cells were more prone to the toxic effects of ZnO NPs at intermediate concentrations compared to fibroblasts. With the help of ZnO NPs covered by a silica shell in which FITC dye was incorporated, we were able to track ZnO NPs within tumor cells as well as within a whole organism in the CAM assay after injection into the bloodstream. Depending on the applied concentrations, selective tumor cell killing seems feasible. Furthermore, the combinational treatment of tumor cells with radiotherapy and ZnO NPs shows promising results. Still, further investigations are needed to gain a better understanding of the interaction between ZnO NPs and the human body to be able to pave the way for their application as an innovative anti-tumor agent in the clinics.

Keywords: metal oxide nanoparticles, nanomedicine, overcome resistances against classical treatment options, zinc oxide nanoparticles

Procedia PDF Downloads 123

Authors: Anna Lierova, Jitka Kasparova, Marcela Jelicova, Lucie Korecka, Zuzana Bilkova, Zuzana Sinkorova

Abstract:

Hyaluronic acid (HA) is a simple linear, unbranched polysaccharide with a lot of exceptional physiological and chemical properties such as high biocompatibility and biodegradability, strong hydration and viscoelasticity that depend on the size of the molecule. It plays the important role in a variety of molecular events as tissue hydration, mechanical protection of tissues and as well as during inflammation, leukocyte migration, and extracellular matrix remodeling. Also, HA-based biomaterials, including HA scaffolds, hydrogels, thin membranes, matrix grafts or nanoparticles are widely use in various biomedical applications. Our goal is to determine the radioprotective effect of hyaluronic acid nanoparticles (HA NPs). We are investigating effect of ionizing radiation on stability of HA NPs, in vitro relative toxicity of nanoscale as well as effect on cell lines and specific surface receptors and their response to ionizing radiation. An exposure to ionizing radiation (IR) can irreversibly damage various cell types and may thus have implications for the level of the whole tissue. Characteristic manifestations are formation of over-granulated tissue, remodeling of extracellular matrix (ECM) and abortive wound healing. Damages are caused by either direct interaction with DNA and IR proteins or indirectly by radicals formed during radiolysis of water Accumulation and turnover of ECM are a hallmark of radiation induces lung injury, characterized by inflammation, repair or remodeling health pulmonary tissue. HA is a major component of ECM in lung and plays an important role in regulating tissue injury, accelerating tissue repair, and controlling disease outcomes. Due to that, HA NPs were applied to in vivo model (C57Bl/6J mice) before total body or partial thorax irradiation. This part of our research is targeting on effect of exogenous HA on the development and/or mitigating acute radiation syndrome and radiation induced lung injuries.

Keywords: hyaluronic acid, ionizing radiation, nanoparticles, radiation induces lung damages

Procedia PDF Downloads 162

Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

Abstract:

Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

Procedia PDF Downloads 440