Search results for: therapeutic response

Authors: Phill-Seung Jung, Dae-Yeon Kim

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Objectives: In young, especially nulliparous women, it is not easy to decide on excisional therapy for cervical intraepithelial neoplasia (CIN). We aimed to evaluate how effective topical imiquimod is in the treatment of high-grade CIN so that excisional therapy can be avoided in young women. Methods: Patients with CIN were allocated to this pilot study. They did not want excisional therapy and agreed with topical imiquimod therapy, which required once-a-week hospital visit for 8 weeks for the application of imiquimod to the cervix by a gynecologic oncologist. If the lesion got worse during treatment, it was decided to convert imiquimod therapy to excisional therapy. Results: A total of 36 patients with a median age of 29 years (range, 22–41 years) agreed to receive topical imiquimod therapy. Of these, 32 patients (88.9%) were positive for high-risk human papillomavirus (HR HPV). Twenty-five patients (69.4%) had low-grade squamous intraepithelial lesion (LSIL), and 11 (30.6%) had high-grade squamous intraepithelial lesion (HSIL) on their initial LBC. Twenty-eight patients underwent punch biopsy, which showed CIN 1 in 7 (19.4%), CIN 2 in 11 (30.6%), and CIN 3 in 10 (27.8%) patients. Twenty patients finished the 8-week imiquimod therapy. Among them, 14 patients had CIN 2 or 3, and 6 patients had CIN 1. HR HPV was positive in 12 patients. On the last examination, 14 patients (70.0%) had negative intraepithelial lesions, 3 (15.0%) had atypical squamous cells of undetermined significance, and 1 (5.0%) had LSIL. Two patients had persistent HSIL: 1 patient underwent loop electrosurgical excision procedure, resulting in CIN 3 with positive resection margin, and the other patient underwent punch biopsy, resulting in intermediate cells and restarted imiquimod therapy. Only 7 patients were negative for HR HPV. Conclusions: This study showed that topical imiquimod therapy was effective for the treatment of high-grade CIN, with a histologic regression rate of 85.7% (14/20) and HPV eradication rate of 25.0% (8/32). Based on our findings, topical imiquimod therapy might have a successful therapeutic effect in young women with CIN 2-3 so that they can avoid excisional therapy. In addition, it could be a more reassuring treatment option for CIN 1 than just follow-up after few months. To confirm its efficacy, a phase II study with larger cohort would be needed.

Keywords: Imiquimod, Cervical Intraepthelial Neoplasia, Cervical Dysplasia, Human Papillomavirus

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Authors: Simone F. Medeiros, Jessica M. Fonseca, Gizelda M. Alves, Danilo M. Santos, Sérgio P. Campana-Filho, Amilton M. Santos

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Stimuli responsive and biocompatible hydrogel nanoparticles have gained special attention as systems for potential applications in controlled release of drugs to improve their therapeutic efficacy while minimizing side effects. In this work, novel solid dispersions based on thermo- and pH-responsive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate) hydrogel nanoparticles embedded in chitosan matrices were prepared via spray drying for controlled release of ketoprofen. Firstly, the hydrogel nanoparticles containing ketoprofen were prepared via precipitation polymerization and their stimuli-responsive behavior, thermal properties, chemical composition, encapsulation efficiency and morphology were characterized. Then, hydrogel nanoparticles with different particles size were embedded into chitosan matrices via spray-drying. Scanning electron microscopy (SEM) analyses were performed to investigate the particles size, dispersity and morphology. Finally, ketoprofen release profiles were studied as a function of pH and temperature. Chitosan/poly(NVCL-co-IA-co-EGDMA)-ketoprofen microparticles presented spherical shape, rough surface and pronounced agglomeration, indicating that hydrogels nanoparticles loaded with ketoprofen modified the surface of chitosan matrix. The maximum encapsulation efficiency of ketoprofen into hydrogel nanoparticles was 57.8% and the electrostatic interactions between amino groups from chitosan and carboxylic groups from hydrogel nanoparticles were able to control ketoprofen release. The hydrogel nanoparticles themselves were capable to retard the release of ketoprofen-loaded until 48h of in vitro release tests, while their incorporation into chitosan matrix achieved a maximum percentage of drug release of 45%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 10:7, and 69%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 5:2.

Keywords: hydrogel nanoparticles, poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate), chitosan, ketoprofen, spray-drying

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Authors: T. V. Dinh, I. Y. Choi, J. W. Ahn, Y. H. Oh, G. Bo, J. Y. Lee, J. C. Kim

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A Non-Dispersive Infrared (NDIR) multi-gas analyzer has been developed to monitor the emission of carbon monoxide (CO) and sulfur dioxide (SO2) from various industries. The NDIR technique for gas measurement is based on the wavelength absorption in the infrared spectrum as a way to detect particular gasses. NDIR analyzers have popularly applied in the Tele-Monitoring System (TMS). The advantage of the NDIR analyzer is low energy consumption and cost compared with other spectroscopy methods. However, zero/span drift and interference are its urgent issues to be solved. Multi-pathway technique based on optical White cell was employed to improve the sensitivity of the analyzer in this work. A pyroelectric detector was used to detect the Infrared radiation. The analytical range of the analyzer was 0 ~ 200 ppm. The instrument response time was < 2 min. The detection limits of CO and SO2 were < 4 ppm and < 6 ppm, respectively. The zero and span drift of 24 h was less than 3%. The linearity of the analyzer was less than 2.5% of reference values. The precision and accuracy of both CO and SO2 channels were < 2.5% of relative standard deviation. In general, the analyzer performed well. However, the detection limit and 24h drift should be improved to be a more competitive instrument.

Keywords: analyzer, CEMS, monitoring, NDIR, TMS

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Authors: I. Toumi, Y. Abed, A. Bouafia

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This paper presents a methodology for identifying the cohesive soil parameters that takes into account different constitutive equations. The procedure, applied to identify the parameters of generalized Prager model associated to the Drucker & Prager failure criterion from a pressuremeter expansion curve, is based on an inverse analysis approach, which consists of minimizing the function representing the difference between the experimental curve and the simulated curve using a simplex algorithm. The model response on pressuremeter path and its identification from experimental data lead to the determination of the friction angle, the cohesion and the Young modulus. Some parameters effects on the simulated curves and stresses path around pressuremeter probe are presented. Comparisons between the parameters determined with the proposed method and those obtained by other means are also presented.

Keywords: cohesive soils, cavity expansion, pressuremeter test, finite element method, optimization procedure, simplex algorithm

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Authors: Shanker Kalakotla, Krishna Mohan Gottumukkala

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Diabetes is a metabolic disorder characterized by hyperglycemia, carbohydrates, altered lipids and proteins metabolism. In recent research nanotechnology is a blazing field for the researchers; latterly there has been prodigious excitement in the nanomedicine and nano pharmacological area for the study of silver nanoparticles synthesis using natural products. Biological methods have been used to synthesize silver nanoparticles in presence of medicinally active antidiabetic plants, and this intention made us assess the biologically synthesized silver nanoparticles from the seed extract of Psoralea corylfolia using 1 mM silver nitrate solution. The synthesized herbal mediated silver nanoparticles (HMSNP’s) then subjected to various characterization techniques such as XRD, SEM, EDX, TEM, DLS, UV and FT-IR respectively. In current study, the silver nanoparticles tested for in-vitro anti-diabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Herbal mediated silver nanoparticles were successfully obtained from bioreduction of silver nitrate using Psoralea corylifolia plant extract. Silver nanoparticles have been appropriately characterized and confirmed using different types of equipment viz., UV-vis spectroscopy, XRD, FTIR, DLS, SEM and EDX analysis. From the behavioral observations of the study, the female albino mice did not show sedation, respiratory arrest, and convulsions. Test compounds did not cause any mortality at the dose level tested (i.e., 2000 mg/kg body weight) doses till the end of 14 days of observation and were considered safe. It may be concluded that LD50 of the HMSNPs was 2000mg/kg body weight. Since LD50 of the HMSNPs was 2000mg/kg body weight, so the preferred dose range for HMSNPs falls between the levels of 200 and 400 mg/kg. Further In-vivo pharmacological models and biochemical investigations will clearly elucidate the mechanism of action and will be helpful in projecting the currently synthesized silver nanoparticles as a therapeutic target in treating chronic ailments.

Keywords: herbal mediated silver nanoparticles, HMSNPs, toxicity of silver nanoparticles, PTP1B in-vitro anti-diabetic assay female albino mice, 425 OECD guidelines

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Authors: Leyli Hashemi Rafsanjani, Hoda Mortazavi Alavi, Amirhossein Habibzadeh

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At present, the atmospheric and environmental factors impose massive damages to buildings. Thus, to reduce these damages, researchers pay more attention on qualitative and quantitative characteristic of buildings materials. Condensation is one of the problems in Contemporary Sustecture Design. It could cause serious damages to the frontage, interior and structural elements of buildings. As a result, taking preventative steps to avoid condensation from occurring in buildings will help prevent avoidable and costly problems in the future. Hence, the aim of this paper is to answer the question: “Does the use of advanced materials cause the reduction of condensation formed on the walls?" In response to those flaws, this paper considered similar articles and selected 20 buildings randomly from contemporary architecture of developing countries which have been built in recent decade from 2002 to 2012, to find out the mutual relation between the usage of advanced materials and level of condensation damages. This consideration shows that by using advanced materials, we will have fewer damages.

Keywords: condensation, advanced materials, contemporary sustecture, moisture

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Authors: Lata Shakya, Toshio Otsuki, Saori Imoto, Bijaya Krishna Shrestha, Umesh Bahadur Malla

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2015 Gorkha Nepal earthquake have damaged the human settlements in 14 districts of Nepal. Historic core areas of three principal cities namely Kathmandu, Lalitpur and Bhaktapur including numerous traditional ‘newari’ settlements in the peripheral areas have been either collapsed or severely damaged. Despite Government of Nepal and (international) non-government organisations’ attempt towards disaster risk management through the preparation of policies and guidelines and implementation of community-based activities, the recent ‘Gorkha’ earthquake has demonstrated the inadequate preparedness, poor implementation of a legal instrument, resource constraints, and managerial weakness. However, the social capital through community based institutions, self-help attitude, and community bond has helped a lot not only in rescue and relief operation but also in a post-disaster temporary shelter living thereby exhibiting the resilient power of the local community. Conducting a detailed case study of ‘Kaminani’ community with 42 houses at ward no. 16 of Bhaktapur municipality, this paper analyses the local community’s response and activities on the Gorkha earthquake in rescue and relief operation as well as in post disaster work. Leadership, the existence of internal/external aid, physical and human support are also analyzed. Social resource and networking are also explained through critical review of the existing community organisation and their activities. The research methodology includes literature review, field survey, and interview with community leaders and residents based on a semi-structured questionnaire. The study reveals that community carried their recovery process in four different phases: (i) management of emergency evacuation, (ii) constructing community owed temporary shelter for individuals, (iii) demolishing upper floors of the damaged houses, and (iv) planning for collaborative housing reconstruction. As territorial based organization, religion based agency and aim based institution exist in the survey area from pre-disaster time, it can be assumed that the community activists including leaders are well experienced to create aim-based group and manage teamwork to deal with various issues and problems collaboratively. Physical and human support including partial financial aid from external source as a result of community leader’s personal networking is extended to the community members. Thus, human/social resource and personal/social network play a crucial role in the recovery process. And to build such social capital, community should have potential from pre-disaster time.

Keywords: Gorkha Nepal earthquake, local community, recovery process, social resource, social network

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Authors: Manjinder Bajwa, Mahipal Singh, Manish Nagpal

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This research paper aims to propose a novel approach using ANOVA technique for the strategic investigation of process parameters and their effects on the mechanical properties of Aluminium alloy cast. The two process parameters considered here were permeability of sand and pouring temperature of aluminium alloy. ANOVA has been employed for the first time to determine the effects of these selected parameters on the impact strength of alloy. The experimental results show that this proposed technique has great potential for analyzing sand casting process. Using this approach we have determined the treatment mean square, response mean square and mean square of error as 8.54, 8.255 and 0.435 respectively. The research concluded that at the 5% level of significance, permeability of sand is the more significant parameter influencing the impact strength of cast alloy.

Keywords: aluminium alloy, pouring temperature, permeability of sand, impact strength, ANOVA

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Authors: Regina Connolly, Justin Connolly

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Despite the benefits which they confer, Information & Communication Technologies (ICT) also have the potential to be used negatively. This paper focuses on one of those negative social effects - adolescent cyberbullying. Although early research in this field has pointed to the fact that the successful intervention and resolution of bullying incidents is to a large degree dependent on such incidents being reported to an adult caregiver, the literature consistently shows that adolescents who have been bullied tend not to inform others of their experiences. However, the reasons underlying such reluctance to seek adult intervention remain undetermined. Similarly, the degree to which gender, age or other variables apply in the case of adolescents’ resistance to report cyberbullying experiences has yet to be established. Understanding the factors that influence this resistance to communicate on the part of adolescents will assist caregivers, teachers and those involved in the formulation of school anti-bullying policies in their attempts to counter the cyberbullying phenomenon.

Keywords: information and Communication technologies, technology-enabled bullying, cyberbullying

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Authors: Changgil Lee, Seunghee Park

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Although vehicle driving test for the development of BWIM system is necessary, but it needs much cost and time in addition application of various driving condition. Thus, we need the numerical-simulation method resolving the cost and time problems of vehicle driving test and the way of measuring response of bridge according to the various driving condition. Using the precision analysis model reflecting the dynamic characteristic is contributed to increase accuracy in numerical simulation. In this paper, we conduct a numerical simulation to apply precision analysis model, which reflects the dynamic characteristic of bridge using Bridge Weigh-in-Motion technique and suggest overload vehicle enforcement technology using precision analysis model.

Keywords: bridge weigh-in-motion(BWIM) system, precision analysis model, dynamic characteristic of bridge, numerical simulation

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Authors: Sena Park

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Background: The concurrent presentation with colorectal cancer in the inguinal hernia has been extremely rare. Due to its rarity, its presentation may lead to diagnostic and therapeutic dilemmas. We aim to review all the reported cases on colorectal cancer incarcerated in the inguinal hernia in the last 20 years, and discuss the operative approaches. Methods: We identified all case reports on colorectal cancer within inguinal hernia using PUBMED (2002-2022) and MEDLINE (2002-2022). The search strategy included the following keywords: colorectal cancer (title/abstract) AND inguinal hernia (title/abstract) OR incarceration (title/abstract). The search did not include letters, book chapters, systemic reviews, meta-analysis and editorials. Results: In the last 20 years, a total of 19 cases on colorectal cancer within the inguinal hernia were identified. The age of the patients ranged between 48 and 89. Majority of the patients were male (95%). Most commonly involved part of the large intestine was sigmoid colon (79%). Of all the cases, 79 percent of patients received open procedure and 21 percent had laparoscopic procedure. Discussion: Inguinal hernias are common with an incidence of approximately 1.7 percent. Colorectal cancer is the one of the leading causes of cancer-related mortality worldwide. However, their concurrent presentation has been extremely rare. In the last 20 years, 19 cases on concurrent presentation of colorectal cancer and inguinal hernia have been reported. Most patients who had open procedures had two incisions of groin incision and a midline laparotomy. There were 4 cases where the oncological resection was performed laparoscopically. The advantages of laparoscopic resection include reduced blood lost, reduced post-operative pain, reduced length of hospital stay and similar number of lymph nodes taken. From the review of the cases in the last 20 years, both open and laparoscopic approaches seemed to be safe and achieve adequate oncological resections. Conclusion: This is a brief overview of reported cases of colorectal cancer presenting with inguinal hernia concurrently. Due to its rarity, there are no current guidelines on operative approach in clinical practice. The experience in the last 20 years supports both open and laparoscopic approach.

Keywords: colorectal cancer, inguinal hernia, incarceration, operative approach

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Authors: S. C. Kattimani

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This article deals with the analysis of active constrained layer damping (ACLD) of smart multiferroic or magneto-electro-elastic doubly curved shells. The kinematics of deformations of the multiferroic doubly curved shell is described by a layer-wise shear deformation theory. A three-dimensional finite element model of multiferroic shells has been developed taking into account the electro-elastic and magneto-elastic couplings. A simple velocity feedback control law is employed to incorporate the active damping. Influence of layer stacking sequence and boundary conditions on the response of the multiferroic doubly curved shell has been studied. In addition, for the different orientation of the fibers of the constraining layer, the performance of the ACLD treatment has been studied.

Keywords: active constrained layer damping (ACLD), doubly curved shells, magneto-electro-elastic, multiferroic composite, smart structures

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Authors: Zakaria S. G. Hegazy, Walid M. A. Ahmed

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This paper examines the dependence structure of Islamic stock markets on Bitcoin’s realized volatility components in bear, normal, and bull market periods. A quantile regression approach is employed, after adjusting raw returns with respect to a broad set of relevant global factors and accounting for structural breaks in the data. The results reveal that upside volatility tends to exert negative influences on Islamic developed-market returns more in bear than in bull market conditions, while downside volatility positively affects returns during bear and bull conditions. For emerging markets, we find that the upside (downside) component exerts lagged negative (positive) effects on returns in bear (all) market regimes. By and large, the dependence structures turn out to be asymmetric. Our evidence provides essential implications for investors.

Keywords: cryptocurrency markets, bitcoin, realized volatility measures, asymmetry, quantile regression

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Authors: C. Makwana, S. R. Dave

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Arsenic is toxic to almost all living cells. Its contamination in natural sources affects the growth of microorganisms. The presence of arsenic is associated with various human disorders also. The attempt of this sort of study provides information regarding the performance of our isolated microorganisms in the presence of Arsenic, which have ample scope for bioremediation. Six isolates were selected from the polluted sample of industrial zone Vatva, Ahmedabad, Gujarat, India, out of which two were Thermophilic organisms. The thermophilic exopolysaccharide (EPS) producing Bacillus was used for microbial enhance oil recovery (MEOR) and in the bio beneficiation. Inorganic arsenic primarily exists in the form of arsenate or arsenite. This arsenic resistance isolate was capable of transforming As +3 to As+5. This isolate would be useful for arsenic remediation standpoint from aquatic systems. The study revealed that the thermophilic microorganism was growing at 55 degree centigrade showed considerable remediation property. The results on the growth and enzyme catalysis would be discussed in response to Arsenic remediation.

Keywords: aquatic systems, thermophilic, exopolysacchride, arsenic

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Authors: Eszter Repasi, Akos Koller

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Our genetic information determines our look, physiology, sports performance and all our features. Maximizing the performances of athletes have adopted a science-based approach to the nutritional support. Nowadays genetics studies have blended with nutritional sciences, and a dynamically evolving, new research field have appeared. Nutritional genomics is needed to be used by nutritional experts. This is a recent field of nutritional science, which can provide a solution to reach the best sport performance using correlations between the athlete’s genome, nutritions, molecules, included human microbiome (links between food, microbiome and epigenetics), nutrigenomics and nutrigenetics. Nutritional genomics has a tremendous potential to change the future of dietary guidelines and personal recommendations. Experts need to use new technology to get information about the athletes, like nutritional genomics profile (included the determination of the oral and gut microbiome and DNA coded reaction for food components), which can modify the preparation term and sports performance. The influence of nutrients on the genes expression is called Nutrigenomics. The heterogeneous response of gene variants to nutrients, dietary components is called Nutrigenetics. The human microbiome plays a critical role in the state of health and well-being, and there are more links between food or nutrition and the human microbiome composition, which can develop diseases and epigenetic changes as well. A nutritional genomics-based profile of athletes can be the best technic for a dietitian to make a unique sports nutrition diet plan. Using functional food and the right food components can be effected on health state, thus sports performance. Scientists need to determine the best response, due to the effect of nutrients on health, through altering genome promote metabolites and result changes in physiology. Nutritional biochemistry explains why polymorphisms in genes for the absorption, circulation, or metabolism of essential nutrients (such as n-3 polyunsaturated fatty acids or epigallocatechin-3-gallate), would affect the efficacy of that nutrient. Controlled nutritional deficiencies and failures, prevented the change of health state or a newly discovered food intolerance are observed by a proper medical team, can support better sports performance. It is important that the dietetics profession informed on gene-diet interactions, that may be leading to optimal health, reduced risk of injury or disease. A special medical application for documentation and monitoring of data of health state and risk factors can uphold and warn the medical team for an early action and help to be able to do a proper health service in time. This model can set up a personalized nutrition advice from the status control, through the recovery, to the monitoring. But more studies are needed to understand the mechanisms and to be able to change the composition of the microbiome, environmental and genetic risk factors in cases of athletes.

Keywords: gene-diet interaction, multidisciplinary team, microbiome, diet plan

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Authors: Ahmed A. D. Sarhan, S. R. Besharaty, Javad Akbaria, M. Hamdi

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The capability of CNC gantry milling machines in manufacturing long components has caused the expanded use of such machines. On the other hand, the machines’ gantry rigidity can reduce under severe loads or vibration during operation. Indeed, the quality of machining is dependent on the machine’s dynamic behavior throughout the operating process. For this reason, this type of machines has always been used prudently and are non efficient. Therefore, they can usually be employed for rough machining and may not produce adequate surface finishing. In this paper, a CNC gantry milling machine with the potential to produce good surface finish has been designed and analyzed. The lowest natural frequency of this machine is 202 Hz at all motion amplitudes with a full range of suitable frequency responses. Meanwhile, the maximum deformation under dead loads for the gantry machine is 0.565µm, indicating that this machine tool is capable of producing higher product quality.

Keywords: frequency response, finite element, gantry machine, gantry design, static and dynamic analysis

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Authors: Saeed Ullah Jan, Shafaq, Sumbul

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Anxiety is one of the most common emotions and is a normal reaction to danger or a threat. It is a normal reaction to stress and can be beneficial in some situations. It can alert us to dangers and help us prepare and pay attention. The prime aim of this study was to examine the level of anxiety of Library and Information Science students at the Department of Library and Information Science, Khushal Khan Khattak University Karak. A survey method was used for the completion of this study. The response of male respondents was better than female LIS students at the Department of Library and Information Science, Khushal Khan Khattak University Karak. The librarians should have to focus on the information needs of the university students. Special training needs to be arranged for female students to improve their library usage and readership rate.

Keywords: library-anxiety, library anxiety-students, library anxiety -students-Pakistan, stress

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Authors: Eric Lacoste

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Laboratory animals are currently widely used as a model of human pathologies in dermatology such as atopic dermatitis (AD). These models provide a better understanding of the pathophysiology of this complex and multifactorial disease, the discovery of potential new therapeutic targets and the testing of the efficacy of new therapeutics. However, confirmation of the correct development of AD is mainly based on histology from skin biopsies requiring invasive surgery or euthanasia of the animals, plus slicing and staining protocols. However, there are currently accessible imaging technologies such as Optical Coherence Tomography (OCT), which allows non-invasive visualization of the main histological structures of the skin (like stratum corneum, epidermis, and dermis) and assessment of the dynamics of the pathology or efficacy of new treatments. Briefly, female immunocompetent hairless mice (SKH1 strain) were sensitized and challenged topically on back and ears for about 4 weeks. Back skin and ears thickness were measured using calliper at 3 occasions per week in complement to a macroscopic evaluation of atopic dermatitis lesions on back: erythema, scaling and excoriations scoring. In addition, OCT was performed on the back and ears of animals. OCT allows a virtual in-depth section (tomography) of the imaged organ to be made using a laser, a camera and image processing software allowing fast, non-contact and non-denaturing acquisitions of the explored tissues. To perform the imaging sessions, the animals were anesthetized with isoflurane, placed on a support under the OCT for a total examination time of 5 to 10 minutes. The results show a good correlation of the OCT technique with classical HES histology for skin lesions structures such as hyperkeratosis, epidermal hyperplasia, and dermis thickness. This OCT imaging technique can, therefore, be used in live animals at different times for longitudinal evaluation by repeated measurements of lesions in the same animals, in addition to the classical histological evaluation. Furthermore, this original imaging technique speeds up research protocols, reduces the number of animals and refines the use of the laboratory animal.

Keywords: atopic dermatitis, mouse model, oxzolone model, histology, imaging

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Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

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Authors: Zhengrong Wu, Haibo Yang

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In the context of escalating global climate change and environmental degradation, the complexity and frequency of natural disasters are continually increasing. Confronted with an abundance of information regarding natural disasters, traditional knowledge graph construction methods, which heavily rely on grammatical rules and prior knowledge, demonstrate suboptimal performance in processing complex, multi-source disaster information. This study, drawing upon past natural disaster reports, disaster-related literature in both English and Chinese, and data from various disaster monitoring stations, constructs question-answer templates based on large language models. Utilizing the P-Tune method, the ChatGLM2-6B model is fine-tuned, leading to the development of a disaster knowledge graph based on large language models. This serves as a knowledge database support for disaster emergency response.

Keywords: large language model, knowledge graph, disaster, deep learning

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Authors: Nasibeh Azizi Khereshki

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Olive leaf (OL) extract as a green reductant agent was utilized for the biogenic synthesis of silver nanoparticles (Ag NPs) for the first time in this study, and then its performance was evaluated for colorimetric detection of Fe3+ in different media. Some analytical methods were used to characterize the nanosensor. The effective sensing parameters were optimized by central composite design (CCD) combined with response surface methodology (RSM) application. Then, the prepared material's applicability in antibacterial and optical chemical sensing for naked-eye detection of Fe3+ ions in aqueous solutions were evaluated. Furthermore, OL-Ag NPs-loaded paper strips were successfully applied to the colorimetric visualization of Fe3+. The colorimetric probe based on OL-AgNPs illustrated excellent selectivity and sensitivity towards Fe3+ ions, with LOD and LOQ of 0.81 μM and 2.7 μM, respectively. In addition, the developed method was applied to detect Fe3+ ions in real water samples and validated with a 95% confidence level against a reference spectroscopic method.

Keywords: Ag NPs, colorimetric detection, Fe(III) ions, green synthesis, olive leaves

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Authors: Nooraneda Mutalip Laidey

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Computer Crimes Act 1997 (CCA 1997) was conceded by Malaysia’s legislative body in 1997 and the Act was enforced in June 2000. The purpose of CCA 1997 is to provide for offences related to misuse of computers such as hacking, cracking and phishing. CCA 1997 was modelled after United Kingdom’s Computer Misuses Act 1990 as a response to the emerging computer crimes. This legislation is divided into three parts and 12 Sections. The first part outlines preliminary matters that include short title and relevant definitions, second part provides for the offenses related to misuse of computers and specifies penalties for each offences, and the last part deals with ancillary provisions such as jurisdictional and investigational issues of cybercrime. The main objective of this paper is to discuss the development of computer crimes and its deterrence in Malaysia. Specific sections of CCA 1997 will be analysed in details and detail assessment on the prevention and prosecution of computer crimes in Malaysia will be accessed to determine whether CCA 1997 is so far adequate in preventing computer crimes in Malaysia.

Keywords: computer, computer crimes, CCA 1997, circumvention, deterrence

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Authors: Maria Isabel Garcia-Planas, Maria Victoria Garcia-Camba

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The use of brain stem auditory evoked potential (BAEP) is a common way to study the auditory function of people, a way to learn the functionality of a part of the brain neuronal groups that intervene in the learning process by studying the behaviour of wave VI. The latest advances in neuroscience have revealed the existence of different brain activity in the learning process that can be highlighted through the use of innocuous, low-cost, and easy-access techniques such as, among others, the BAEP that can help us to detect early possible neurodevelopmental difficulties for their subsequent assessment and cure. To date and to the authors' best knowledge, only the latency data obtained, observing the first to V waves and mainly in the left ear, were taken into account. This work shows that it is essential to take into account both ears; with these latest data, it has been possible had diagnosed more precise some cases than with the previous data had been diagnosed as 'normal' despite showing signs of some alteration that motivated the new consultation to the specialist.

Keywords: ear, neurodevelopment, auditory evoked potentials, intervals of normality, learning disabilities

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Authors: Faris Mohsin Alabeedi

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Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by the presence of autoantibodies directed against the epidermis's surface proteins. There are two forms of PV, mucocutaneous and mucosal-dominant PV. Disruption of the cell junctions is a hallmark of PV due to the autoantibodies targeting the desmosomal cadherins, desmoglein-3 (Dsg3) and desmoglein-1, leading to acantholysis in the skin and mucous membrane. Although the pathogenesis of PV is known, the detailed molecular events remain not fully understood. Our recent study has shown that both the PV sera and pathogenic anti-Dsg3 antibody AK23 can induce ROS and cause oxidative stress in cultured keratinocytes. In line with our finding, other independent studies also demonstrate oxidative stress in PV. Since Nrf2 plays a crucial role in cellular anti-oxidative stress response, we hypothesize that the expression of Nrf2 may alter in PV. Thus, treatment of cells with PV sera or AK23 may cause changes in Nrf2 expression and distribution. The purpose of this study was to examine the effect of AK23 and PV sera on Nrf2 in a normal human keratinocyte cell line, such as NTERT cells. Both a time-course and dose-dependent experiments with AK23, alongside the matched isotype control IgG, were performed in keratinocyte cultures and analysed by immunofluorescence for Nrf2 and Dsg3. Additionally, the same approach was conducted with the sera from PV patients and healthy individuals that served as a control in this study. All the fluorescent images were analysed using ImageJ software. Each experiment was repeated twice. In general, variations were observed throughout this study. In the dose-response experiments, although enhanced Dsg3 expression was consistently detected in AK23 treated cells, the expression of Nrf2 showed no consistent findings between the experiments, although changes in its expression were noticeable in cells treated with AK23. In the time-course study, a trend with induction of Nrf2 over time was shown in control cells treated with mouse isotype IgG. Treatment with AK23 showed a reduction of Nrf2 in a time-dependent manner, especially at the 24-hour time point. However, the earlier time points, such as 2 hours and 6 hours with AK23 treatments, detected somewhat variations. Finally, PV sera caused a decrease of Dsg3, but on the other hand, variations were observed in Nrf2 expression in PV sera treated cells. In general, PV sera seemed to cause a reduction of Nrf2 in the majority of PV sera treated samples. In addition, more pronounced cytoplasmic expression of Nrf2 has been observed in PV sera treated cells than those treated with AK23, suggesting that polyclonal and monoclonal IgG might induce a different effect on Nrf2 expression and distribution. Further experimental studies are crucial to obtain a more coincide global view of Nrf2-mediated gene regulation. In particular, Pemphigus Voulgaris studies assessing how the Nrf2-dependent network changes from a physiological to a pathological condition can provide insight into disease mechanisms and perhaps initiate further treatment approaches.

Keywords: pemphigus vulgaris, monoclonal antibody against desmoglein-3, Nrf2 oxidative stress, keratinocyte cultures

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Authors: B. Razmi, F. Rafiee, M. Baziar, A. Saeedi Azizkandi

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In the present research, a series of 3-D finite element numerical modeling was performed to study the effect of system frequency and excitation specifications on the internal forces of the piled raft (PR) system in a dry sand layer. The results of numerical simulations were first compared with those associated with centrifuge tests. The natural frequency of superstructure, modeled on the piled raft foundation, was smaller than the natural frequency of the fixed-base super-structure. This difference was greater for super-structures with higher frequencies. In PR systems, the excitation with a frequency close to the system frequency produced the largest responses. Furthermore, based on the results of presented numerical analyses, ignoring the interactions and characteristics of all components of a pile-raft-structure, may lead to highly uneconomical design.

Keywords: centrifuge test, excitation frequency, natural frequency of super-structure, piled raft foundation, 3-D finite element model

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Authors: Misty Attwood, Helgi Schioth

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Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.

Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein

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Authors: Sharad Kumar Kulshreshtha

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India is a great land of cultural and traditional diversity. Its spectrums create a unique ambiance in all over the country. Specially, fairs and festivals are ancient phenomena in Indian culture. In India, there are thousands of such religious, spiritual, cultural fairs organized on auspicious occasions. These fairs reflect the effective and efficient role of social governance and responsibility of Indian society. In this context a mega event known as ‘Kumbha Mela’ literally mean ‘Kumbha Fair’ which is organize after every twelve years at (Prayaag) Allahabad an ancient city of India, now is in the state of Uttar Pradesh. Kumbh Mela is one of the largest human congregations on the Earth. The Kumbha Mela that is held here is considered to be the largest and holiest city among the four cities where Kubha fair organize. According to the Hindu religious scripture a dip for possessing the holy confluence, known as Triveni Sangam, which is a meeting point of the three sacred rivers of India i.e., –Ganges, Yamuna and Saraswati (mythical). During the Kumbha fair the River Ganges is believed to turn to nectar, bringing great blessing to everyone who bathes in it. Other activities include religious discussions, devotional singings and mass feedings pilgrims and poor. The venue for Kumbh Mela (fair) depends on the position Sun, Moon, and Jupiter which holds in that period in different zodiac signs. More than 120 Millions (12 Crore) people visited in the Kumbha Fair-2013 in Allahabad. A temporary tented city was set up for the pilgrims over an area of 2 hectares of the land along the river of Ganges. As many as 5 power substations, temporary police stations, hospitals, bus terminals, stalls were set up for providing various facilities to the visitors and thousands of volunteers participated for assistance of this event. All efforts made by fair administration to provide facility to visitors, such security and sanitation, medical care and frequent water and power supply. The efficient and timely arrangement at the Kumbha Mela attracted the attention of many government and institutions. The Harvard University of USA conducted research to find out how it was made possible. This paper will focuses on effective and efficient planning and preparation of Kumbha Fair which includes facilitation process, role of various coordinating agencies. risk management crisis management strategies Prevention, Preparedness, Response, and Recovery (PPRR Approach), emergency response plan (ERP), safety and security issues, various environmental aspects along with health hazards and hygiene crowd management, evacuation, monitoring, control and evaluation.

Keywords: event planning and facility arrangement, risk management, crowd management, India

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Authors: Donatello Cardone

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Bilinear hysteresis models are usually used to describe the cyclic behavior of high damping rubber bearings. However, they neglect a number of phenomena (such as the interaction between axial load and shear force, buckling and post-buckling behavior, cavitation, scragging effects, etc.) that can significantly influence the dynamic behavior of such isolation devices. In this work, an advanced hysteresis model is examined and properly calibrated using consolidated procedures. Results of preliminary numerical analyses, performed in OpenSees, are shown and compared with the results of experimental tests on high damping rubber bearings and simulation analyses using alternative nonlinear models. The findings of this study can provide an useful tool for the accurate evaluation of the seismic response of structures with rubber-based isolation systems.

Keywords: seismic isolation, high damping rubber bearings, numerical modeling, axial-shear force interaction

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Authors: Mohammed Alkiyumi

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Educational systems are currently paying special attention to developing learners' higher thinking skills to develop the capabilities of human resources to deal with contemporary challenges. Although psychologists disagree about the concept of higher-order thinking skills and the skills they include, there is unlimited effort in designing them and building strategies for their implementation. The most important factor helping to develop these skills is their classification according to specific criteria, and the most important of these classifications is Bloom's classification, which is dominant in most educational systems at all levels. Previous classifications have many limitations, including the comprehensiveness of the skills they contain, the logical structure of their hierarchy, and classification criteria. Therefore, this article puts another step in this area by providing a new classification of higher-order thinking skills that includes five categories: the first response stage, transformative stage, application, reasoning stage, and the production stage with a logical justification for this classification, with some techniques to developing it among learners.

Keywords: high-order thinking skills, classification, teaching, education

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Authors: William Elnemer, Nauman Hussain, Samir Al-Ali, Henry Shu, Diane Ghanem, Babar Shafiq

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Introduction: The incidence of infection in open tibial shaft injuries varies depending on the severity of the injury, with rates ranging from 1.8% for Gustilo-Anderson type I to 42.9% for type IIIB fractures. The timely administration of antibiotics upon presentation to the emergency department (ED) is an essential component of fracture management, and evidence indicates that prompt delivery of antibiotics is associated with improved outcomes. The objective of this study is to identify factors that contribute to the expedient administration of antibiotics. Methods: This is a retrospective study of open tibial shaft fractures at an academic Level I trauma center. Current Procedural Terminology (CPT) codes identified all patients treated for open tibial shaft fractures between 2015 and 2021. Open fractures were identified by reviewing ED and provider notes, and with ballistic fractures were considered open. Chart reviews were performed to extract demographics, fracture characteristics, postoperative outcomes, time to operative room, time to antibiotic order, and delivery. Univariate statistical analysis compared patients who received early antibiotics (EA), which were delivered within one hour of ED presentation, and those who received late antibiotics (LA), which were delivered outside of one hour of ED presentation. A multivariate analysis was performed to investigate patient, fracture, and transport/ED characteristics contributing to faster delivery of antibiotics. The multivariate analysis included the dependent variables: ballistic fracture, activation of Delta Trauma, Gustilo-Andersen (Type III vs. Type I and II), AO-OTA Classification (Type C vs. Type A and B), arrival between 7 am and 11 pm, and arrival via Emergency Medical Services (EMS) or walk-in. Results: Seventy ED patients with open tibial shaft fractures were identified. Of these, 39 patients (55.7%) received EA, while 31 patients (44.3%) received LA. Univariate analysis shows that the arrival via EMS as opposed to walk-in (97.4% vs. 74.2%, respectively, p = 0.01) and activation of Delta Trauma (89.7% vs. 51.6%, respectively, p < 0.001) was significantly higher in the EA group vs. the LA group. Additionally, EA cases had significantly shorter intervals between the antibiotic order and delivery when compared to LA cases (0.02 hours vs. 0.35 hours, p = 0.007). No other significant differences were found in terms of postoperative outcomes or fracture characteristics. Multivariate analysis shows that a Delta Trauma Response, arrival via EMS, and presentation between 7 am and 11 pm were independent predictors of a shorter time to antibiotic administration (Odds Ratio = 11.9, 30.7, and 5.4, p = 0.001, 0.016, and 0.013, respectively). Discussion: Earlier antibiotic delivery is associated with arrival to the ED between 7 am and 11 pm, arrival via EMS, and a coordinated Delta Trauma activation. Our findings indicate that in cases where administering antibiotics is critical to achieving positive outcomes, it is advisable to employ a coordinated Delta Trauma response. Hospital personnel should be attentive to the rapid administration of antibiotics to patients with open fractures who arrive via walk-in or during late-night hours.

Keywords: antibiotics, emergency department, fracture management, open tibial shaft fractures, orthopaedic surgery, time to or, trauma fractures

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