Search results for: therapeutic response

Authors: Woei-Shyan Lee, Hao-Chien Kao

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The impact deformation and fracture behaviour of cobalt-based Haynes 188 superalloy are investigated by means of a split Hopkinson pressure bar. Impact tests are performed at strain rates ranging from 1×103 s-1 to 5×103 s-1 and temperatures between 25°C and 800°C. The experimental results indicate that the flow response and fracture characteristics of cobalt-based Haynes 188 superalloy are significantly dependent on the strain rate and temperature. The flow stress, work hardening rate and strain rate sensitivity all increase with increasing strain rate or decreasing temperature. It is shown that the impact response of the Haynes 188 specimens is adequately described by the Zerilli-Armstrong fcc model. The fracture analysis results indicate that the Haynes 188 specimens fail predominantly as the result of intensive localised shearing. Furthermore, it is shown that the flow localisation effect leads to the formation of adiabatic shear bands. The fracture surfaces of the deformed Haynes 188 specimens are characterised by dimple- and / or cleavage-like structure with knobby features. The knobby features are thought to be the result of a rise in the local temperature to a value greater than the melting point.

Keywords: Haynes 188 alloy, impact, strain rate and temperature effect, adiabatic shearing

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Authors: Cheng Zeng, Xia Luo

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Passenger organization has always been an essential part of China's metro operation and management. Facing the massive passenger flow, stations need to improve their intelligence and automation degree by an appropriate integrated system. Based on the existing integrated supervisory control system (ISCS) and simulation software (Anylogic), this paper designs an intelligent passenger organization system (IPOS) for metro stations. Its primary function includes passenger information acquisition, data processing and computing, visualization management, decision recommendations, and decision response based on interlocking equipment. For this purpose, the logical structure and intelligent algorithms employed are particularly devised. Besides, the structure diagram of information acquisition and application module, the application of Anylogic, the case library's function process are all given by this research. Based on the secondary development of Anylogic and existing technologies like video recognition, the IPOS is supposed to improve the response speed and address capacity in the face of emergent passenger flow of metro stations.

Keywords: anylogic software, decision-making support system, intellectualization, ISCS, passenger organization

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Authors: Danna Jia, Bin Li

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Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

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Authors: Shohreh Rahimi Lascokalayeh, Hasan Yousefnia, Mojtaba Tajik, Samaneh Zolghadri, Bentehoda Abdolhosseini

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In this study, the production of terbium-161 as new therapeutic radionuclide was investigated using TALYS1.6& EMPIRE 3.2 codes. For this purpose, cross section for the reactions reactor to produce 161Tb were extracted by mean of this code In the following step, stopping power of the reactions reactor was calculated by SRIM code. The best reaction in the production of 161Tb is160 Gd(d,n)161Tb Production yield of the 161Tb was obtained by utilization of MATLAB calculation code and based on the charged particle reaction formalism.The results showed that Production yield of the 161Tb was obtained 0.8 (mci/ A*h).

Keywords: terbium161, TALYS1.6, EMPIRE3.2, yield, cross-section

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Authors: K. J. Keerthi, Vasundhara Kamineni, A. Ravi Shanker, T. Rammurthy, A. Vijaya Lakshmi, Q. Hasan

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Pancreatic β-cells are the predominant insulin-producing cell types within the Islets of Langerhans and insulin is the primary hormone which regulates carbohydrate and fat metabolism. Apoptosis of β-cells or insufficient insulin production leads to Diabetes Mellitus (DM). Current therapy for diabetes includes either medical management or insulin replacement and regular monitoring. Replacement of β- cells is an attractive treatment option for both Type-1 and Type-2 DM in view of the recent paper which indicates that β-cells apoptosis is the common underlying cause for both the Types of DM. With the development of Edmonton protocol, pancreatic β-cells allo-transplantation became possible, but this is still not considered as standard of care due to subsequent requirement of lifelong immunosuppression and the scarcity of suitable healthy organs to retrieve pancreatic β-cell. Fetal pancreatic cells from abortuses were developed as a possible therapeutic option for Diabetes, however, this posed several ethical issues. Hence, in the present study Mesenchymal stem cells (MSCs) were differentiated into insulin producing cells which were isolated from Human Umbilical cord (HUC) tissue. MSCs have already made their mark in the growing field of regenerative medicine, and their therapeutic worth has already been validated for a number of conditions. HUC samples were collected with prior informed consent as approved by the Institutional ethical committee. HUC (n=26) were processed using a combination of both mechanical and enzymatic (collagenase-II, 100 U/ml, Gibco ) methods to obtain MSCs which were cultured in-vitro in L-DMEM (Low glucose Dulbecco's Modified Eagle's Medium, Sigma, 4.5 mM glucose/L), 10% FBS in 5% CO2 incubator at 37°C. After reaching 80-90% confluency, MSCs were characterized with Flowcytometry and Immunocytochemistry for specific cell surface antigens. Cells expressed CD90+, CD73+, CD105+, CD34-, CD45-, HLA-DR-/Low and Vimentin+. These cells were differentiated to β-cells by using H-DMEM (High glucose Dulbecco's Modified Eagle's Medium,25 mM glucose/L, Gibco), β-Mercaptoethanol (0.1mM, Hi-Media), basic Fibroblast growth factor (10 µg /L,Gibco), and Nicotinamide (10 mmol/L, Hi-Media). Pancreatic β-cells were confirmed by positive Dithizone staining and were found to be functionally active as they released 8 IU/ml insulin on glucose stimulation. Isolating MSCs from usually discarded, abundantly available HUC tissue, expanding and differentiating to β-cells may be the most feasible cell therapy option for the millions of people suffering from DM globally.

Keywords: diabetes mellitus, human umbilical cord, mesenchymal stem cells, differentiation

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Authors: B. McGovern, J. F. Luck, A. Gade, I. V. Lake, D. O’Connell, H. C. Cutcliffe, K. P. Shah, E. E. Ginalis, C. M. Lambert, N. Christian, J. R. Kait, A. W. Yu, C. P. Eckersley, C. R. Bass

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Mild traumatic brain injury (mTBI) in the form of post-concussive injuries and attention deficit / hyperactivity disorder (ADHD) share similar cognitive impairments, including impaired working memory and executive function. The memory-guided oculomotor task separates working memory and inhibitory components to provide further information on the nature of these deficits in each pathology. Eleven subjects with ADHD, fifteen control subjects, and ten subjects with recent concussive injury were matched on age, gender, and education (all high school-age males). Eye movements were recorded during memory-guided oculomotor tasks with varying delays using EyeLink 1000 (SR Research). The percentage of premature saccades and the latency of correct response are the analyzed measures for response inhibition and working memory, respectively. No significant differences were found in latencies between controls subjects and subjects with ADHD or post-concussive injuries, in accordance with previous studies. Subjects with ADHD and post-concussive injuries both demonstrated a trend of increased percentages of premature saccades compared to control subjects in the same oculomotor task. This trend reached statistical significance between the post-concussive and control groups (p < 0.05). These findings support the primary nature of the executive function deficits in response inhibition in ADHD and mTBI. The interpretation of results is limited by the small sample size and the exploratory nature of the study. Further investigation into oculomotor performance differences in mTBI and ADHD may help in differentiating these pathologies in consequent diagnoses and provide insight into the interaction of these deficits in mTBI.

Keywords: attention deficit / hyperactivity disorder (ADHD), concussion, diagnosis, oculomotor, pediatrics

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Authors: Vanessa L. Haro

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Beginning with a historical foundation of Mexico, this marks the start of a close examination of this major Latin American country by providing the context needed to understand the reasons for Mexico’s strengths and struggles today, specific to their response to the issue of gender violence. Responding to the challenge of combating gender violence and inequality, Mexico has created social programs and initiatives in hopes of addressing these issues and modernizing their gender norms, which currently disempower and dehumanize women, while simultaneously denying women the necessary tools needed to fight back or bring balance to the gender scales. Nevertheless, women in Mexico have made their voices heard with the most salient image of that of the mothers protesting while holding the photos of their young daughters who lost their lives. This case study on gender issues in Mexico works to acknowledge the diverse forces that contribute to the issue of gender violence, and to make a statement that this is a crisis that requires a more dynamic response within Mexico’s social welfare policies, and should not be allowed to continue to progress as a normative phenomenon. As the advocacy groups and protesters cry out, “Ni una menos! (Not one less), meaning we will not lose one more woman and making the statement that all women’s lives matter.

Keywords: gender issues, Mexico, poverty, social welfare

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Authors: Luis E. Zapata, Sergio Ruiz, María F. Mantilla, Jhon A. Villamizar

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Sand as fine aggregate for concrete production needs a feasible substitute due to several environmental issues. In this work, a study of the behavior of self-compacting concrete mixtures under replacement of sand by iron slag from 0.0% to 50.0% of weight and variations of water/cementitious material ratio between 0.3 and 0.5 is presented. Control fresh state tests of Slump flow, T500, J-ring and L-box were determined. In the hardened state, compressive strength was determined and optimization from response surface analysis was performed. The study of the variables in the hardened state was developed based on inferential statistical analyses using central composite design methodology and posterior analyses of variance (ANOVA). An increase in the compressive strength up to 50% higher than control mixtures at 7, 14, and 28 days of maturity was the most relevant result regarding the presence of iron slag as replacement of natural sand. Considering the obtained result, it is possible to infer that iron slag is an acceptable alternative replacement material of the natural fine aggregate to be used in structural concrete.

Keywords: ANOVA, iron slag, response surface analysis, self-compacting concrete

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Authors: Naznin Sultana Daisy, Mohammad Hesam Hafezi, Lei Liu

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Nowadays, oily solid waste management has become an important issue for many countries due to frequent oil spill accidents and the increase of industrial oily wastewater. The historical oil spill data show that marine oil spills that affect the shoreline can, in extreme cases, produce up to 30 or 40 times more waste than the volume of oil initially released. Hence, responsive authorities aim to develop the most effective oily waste management solution in a timely manner to manage and minimize the waste generated. In this study initially, we tried to develop the roadmap of oily waste management for three-tiered spill scenarios for Atlantic Canada. For that purpose, three oily waste disposal scenarios are evaluated via six criteria which are determined according to the opinions of the experts from the field. Consequently, through sustainable response strategies, the most appropriate and feasible scenario is determined. The results of this study will assist to develop an integrated oily waste management system for identifying the optimal waste-generation-allocation-disposal schemes and generating the optimal management alternatives based on the holistic consideration of environmental, technological, economic, social, and regulatory factors.

Keywords: oily waste management, marine oil spill, multi-criteria decision making, oil spill response

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Authors: Julian Donovan, Jessica Brealey, Matthew Bowker, Marianne Feghali, Gregory Smith, Lee Thompson, Deborah Henderson

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This article details the development of the X-ray response team (XRT), a service that utilises innovative technology to safely deliver acute and elective imaging and medical assessment service in the pre-hospital and community setting. This involves a partnership between Northumbria Healthcare NHS Foundation Trust’s Radiology and Emergency Medicine departments and the North East Ambulance Service to create a multidisciplinary prehospital team. The team committed to the delivery of a two-day acute service every week, alongside elective referrals, starting in November 2020. The service was originally made available to a 15-mile radius surrounding the Northumbria Hospital. Due to demand, this was expanded to include the North Tyneside and Northumberland regions. The target population was specified as frail and vulnerable patients, as well as those deemed to benefit from staying in their own environment. Within the first two months, thirty-six percent of patients assessed were able to stay at home due to the provision of off-site imaging. In the future, this service aims to allow patient transfer directly to an appropriate ward or clinic, bypassing the emergency department to improve the patient journey and reduce emergency care pressures.

Keywords: frailty, imaging, pre-hospital, X-ray

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Authors: Sujatha Edla

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Introduction: New compounds and possible uses for the bioactive substances produced by freshwater cyanobacteria are constantly being discovered through research. Certain molecules are hazardous to the environment and human health, but others have potential applications in industry, biotechnology, and pharmaceuticals. These discoveries advance our knowledge of the varied functions these microbes perform in different ecosystems. Cyanobacterial silver nanoparticles (AgNPs) have special qualities and possible therapeutic advantages, which make them very promising for a range of medicinal uses. Aim: In our study; the attention was focused on the analysis and characterization of bioactive compounds extracted from freshwater cyanobacteria Planktothricoides raciorskii and its comparative study on Cyanobacteria-mediated silver nanoparticles synthesized by cell-free extract of Planktothricoides raciorskii. Material and Methods: A variety of bioactive secondary metabolites have been extracted, purified, and identified from cyanobacterial species using column chromatography, FTIR, and GC-MS/MS chromatography techniques and evaluated for antibacterial and cytotoxic studies, where the Cyanobacterial silver nanoparticles (CSNPs) were characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) analysis and were further tested for antibacterial and cytotoxic efficiency. Results: The synthesis of CSNPs was confirmed through visible color change and shift of peaks at 430–445 nm by UV-Vis spectroscopy. The size of CSNPs was between 22 and 34 nm and oval-shaped which were confirmed by SEM and TEM analyses. The FTIR spectra showed a new peak at the range of 3,400–3,460 cm−1 compared to the control, confirming the reduction of silver nitrate. The antibacterial activity of both crude bioactive compound extract and CSNPs showed remarkable activity with Zone of inhibition against E. coli with 9.5mm and 10.2mm, 13mm and 14.5mm against S. paratyphi, 9.2mm and 9.8mm zone of inhibition against K. pneumonia by both crude extract and CSNPs, respectively. The cytotoxicity as evaluated by extracts of Planktothricoides raciorskii against MCF7-Human Breast Adenocarcinoma cell line and HepG2- Human Hepatocellular Carcinoma cell line employing MTT assay gave IC50 value of 47.18ug/ml, 110.81ug/ml against MCF7cell line and HepG2 cell line, respectively. The cytotoxic evaluation of Planktothricoides raciorskii CSNPs against the MCF7cell line was 43.37 ug/ml and 20.88 ug/ml against the HepG2 cell line. Our ongoing research in this field aims to uncover the full therapeutic potential of cyanobacterial silver nanoparticles and address any associated challenges.

Keywords: cyanobacteria, silvernanoparticles, pharmaceuticals, bioactive compounds, cytotoxic

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Authors: Faghihnia Torshizi Mostafa, Saitoh Masato

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An efficient method is developed for the response of a group of vertical, cylindrical fixed-head, finite length piles embedded in a homogeneous elastic stratum, subjected to harmonic force atop the pile group cap. Pile to pile interaction is represented through simplified beam-on-dynamic-Winkler-foundation (BDWF) with realistic frequency-dependent springs and dashpots. Pile group effect is considered through interaction factors. New closed-form expressions for interaction factors and curvature ratios atop the pile are extended by considering different boundary conditions at the tip of the piles (fixed, hinged). In order to investigate the fundamental characteristics of inertial bending strains in pile groups, inertial bending strains at the head of each pile are expressed in terms of slenderness ratio. The results of parametric study give valuable insight in understanding the behavior of fixed head pile groups in fundamental natural frequency of soil stratum.

Keywords: Winkler-foundation, fundamental frequency of soil stratum, normalized inertial bending strain, harmonic excitation

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Authors: Avigail Moor, Michal Otmazgin, Hagar Tsiddon, Avivit Mahazri

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The goal of the present study was to refine sexual assault therapy through the examination of the level of agreement between survivor and therapist assessments of key recovery-promoting therapeutic interventions. This is the first study to explore the level of agreement between those who partake in the treatment process from either position. Semi structured interviews were conducted in this qualitative study with 10 survivors and 10 experienced therapists. The results document considerable concurrence between them regarding relational and trauma processing treatment components alike. Together, these reports outline key effective interventions, both common and specific in nature, concomitantly supported by both groups.

Keywords: sexual assault, rape treatment, therapist training, psychotherapy

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Authors: María José Núñez-Ruiz, Luis Álvarez-González, Cristian Olivares-Rodriguez, Benjamin Lazo-Letelier

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This paper begins with some concept of formative assessment and the relationship with learning objective: contents objectives, processes objectives, and metacognitive objectives. Two methodologies are describes Evidence-Based teaching and Question Drive Instruction. To do formative assessments in larges classes a Classroom Response System (CRS) is needed. But most of CRS use only Multiple Choice Questions (MCQ), True/False question, or text entry; however, this is insufficient to formative assessment. To do that a new CRS, call FAMA was developed. FAMA support six types of questions: Choice, Order, Inline choice, Text entry, Associated, and Slider. An experiment participated in 149 students from four engineering careers. For results, Kendall's Range Correlation Analysis and descriptive analysis was done. In conclusion, there is a strong relation between contents question, process questions (ask in formative assessment without a score) and metacognitive questions, asked in summative assessment. As future work, the lecturer can do personalized teaching, because knows the behavior of all students in each formative assessment

Keywords: Python language, formative assessment, classroom response systems, evidence-Based teaching, question drive instruction

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Authors: Lucian Stefanita Grigore, Damian Gorgoteanu, Cristian Molder, Amado Stefan, Daniel Constantin

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The purpose of this article is to present an analytical-numerical study on the structural behavior of a sunken autonomous underwater vehicle (AUV) for emergency intervention. The need for such a study was generated by the key objective of the ERL-Emergency project. The project aims to develop a system of collaborative robots for emergency response. The system consists of two robots: unmanned ground vehicles (UGV) on tracks and the second is an AUV. The system of collaborative robots, AUV and UGV, will be used to perform missions of monitoring, intervention, and rescue. The main mission of the AUV is to dive into the maritime space of an industrial port to detect possible leaks in a pipeline transporting petroleum products. Another mission is to close and open the valves with which the pipes are provided. Finally, you will need to be able to lift a manikin to the surface, which you can take to land. Numerical analysis was performed by the finite element method (FEM). The conditions for immersing the AUV at 100 m depth were simulated, and the calculations for different fluid flow rates were repeated. From a structural point of view, the stiffening areas and the enclosures in which the command-and-control elements and the accumulators are located have been especially analyzed. The conclusion of this research is that the AUV meets very well the established requirements.

Keywords: analytical-numerical, emergency, FEM, robotics, underwater

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Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios

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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.

Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition

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Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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Authors: Yu Chen

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Auricular-magnet therapy is the development of auricular acupuncture. It is a powerful, convenient, and quick result-achieving therapeutic method. This therapy works by using magnetic discs to be placed on acupuncture points on the ears to treat diseases and improve health. In this study, the fundamental principles, indications, and contraindications of this therapy are discussed. Five examples, including reducing blood glucose levels, healing gangrene for diabetes patients, and treating Bell's palsy, are presented. Auricular-magnet therapy is a powerful development in acupuncture.

Keywords: auricular-magnet therapy, Bell’s palsy, diabetes mellitus, food craving, insomnia, nausea, obesity

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Authors: Nouf M. Al-Ourfi, A. S. Bashammakh, M. S. El-Shahawi

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The redox behavior of dianabol steroid (DS) on Nafion Multiwalled Carbon nano -tubes (MWCNT) composite film modified glassy carbon electrode (GCE) in various buffer solutions was studied using cyclic voltammetry (CV) and differential pulse- adsorptive cathodic stripping voltammetry (DP-CSV) and successfully compared with the results at non modified bare GCE. The Nafion-MWCNT composite film modified GCE exhibited the best electrochemical response among the two electrodes for the electro reduction of DS that was inferred from the EIS, CV and DP-CSV. The modified sensor showed a sensitive, stable and linear response in the concentration range of 5 – 100 nM with a detection limit of 0.08 nM. The selectivity of the proposed sensor was assessed in the presence of high concentration of major interfering species. The analytical application of the sensor for the quantification of DS in pharmaceutical formulations and biological fluids (urine) was determined and the results demonstrated acceptable recovery and RSD of 5%. Statistical treatment of the results of the proposed method revealed no significant differences in the accuracy and precision. The relative standard deviations for five measurements of 50 and 300 ng mL−1 of DS were 3.9 % and 1.0 %, respectively.

Keywords: dianabol steroid, determination, modified GCE, urine

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Authors: Saad M. Algharib

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The major concern of planners when placing fire stations is finding their optimal locations such that the fire companies can reach fire locations within reasonable response time or distance. Planners are also concerned with the numbers of fire stations that are needed to cover all service areas and the fires, as demands, with standard response time or distance. One of the tools for such analysis is location-allocation models. Location-allocation models enable planners to determine the optimal locations of facilities in an area in order to serve regional demands in the most efficient way. The purpose of this study is to examine the geographic distribution of the existing fire stations in Kuwait City. This study utilized location-allocation models within the Geographic Information System (GIS) environment and a number of statistical functions to assess the current locations of fire stations in Kuwait City. Further, this study investigated how well all service areas are covered and how many and where additional fire stations are needed. Four different location-allocation models were compared to find which models cover more demands than the others, given the same number of fire stations. This study tests many ways to combine variables instead of using one variable at a time when applying these models in order to create a new measurement that influences the optimal locations for locating fire stations. This study also tests how location-allocation models are sensitive to different levels of spatial dependency. The results indicate that there are some districts in Kuwait City that are not covered by the existing fire stations. These uncovered districts are clustered together. This study also identifies where to locate the new fire stations. This study provides users of these models a new variable that can assist them to select the best locations for fire stations. The results include information about how the location-allocation models behave in response to different levels of spatial dependency of demands. The results show that these models perform better with clustered demands. From the additional analysis carried out in this study, it can be concluded that these models applied differently at different spatial patterns.

Keywords: geographic information science, GIS, location-allocation models, geography

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Authors: Lee Tasker, Ali Karrech, Jeffrey Shragge, Matthew Josh

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Monitoring for the deterioration of concrete infrastructure is an important assessment tool for an engineer and difficulties can be experienced with monitoring for deterioration within an infrastructure. If a failure crack, or fluid seepage through such a crack, is observed from the surface often the source location of the deterioration is not known. Geophysical methods are used to assist engineers with assessing the subsurface conditions of materials. Techniques such as Ground Penetrating Radar (GPR) provide information on the location of buried infrastructure such as pipes and conduits, positions of reinforcements within concrete blocks, and regions of voids/cavities behind tunnel lining. This experiment underlines the application of GPR as an infrastructure-monitoring tool to highlight and monitor regions of possible deterioration within a concrete test wall due to an increase in the generation of fractures; in particular, during a time period of applied load to a concrete wall up to and including structural failure. A three-point load was applied to a concrete test wall of dimensions 1700 x 600 x 300 mm³ in increments of 10 kN, until the wall structurally failed at 107.6 kN. At each increment of applied load, the load was kept constant and the wall was scanned using GPR along profile lines across the wall surface. The measured radar amplitude responses of the GPR profiles, at each applied load interval, were reconstructed into depth-slice grids and presented at fixed depth-slice intervals. The corresponding depth-slices were subtracted from each data set to compare the radar amplitude response between datasets and monitor for changes in the radar amplitude response. At lower values of applied load (i.e., 0-60 kN), few changes were observed in the difference of radar amplitude responses between data sets. At higher values of applied load (i.e., 100 kN), closer to structural failure, larger differences in radar amplitude response between data sets were highlighted in the GPR data; up to 300% increase in radar amplitude response at some locations between the 0 kN and 100 kN radar datasets. Distinct regions were observed in the 100 kN difference dataset (i.e., 100 kN-0 kN) close to the location of the final failure crack. The key regions observed were a conical feature located between approximately 3.0-12.0 cm depth from surface and a vertical linear feature located approximately 12.1-21.0 cm depth from surface. These key regions have been interpreted as locations exhibiting an increased change in pore-space due to increased mechanical loading, or locations displaying an increase in volume of micro-cracks, or locations showing the development of a larger macro-crack. The experiment showed that GPR is a useful geophysical monitoring tool to assist engineers with highlighting and monitoring regions of large changes of radar amplitude response that may be associated with locations of significant internal structural change (e.g. crack development). GPR is a non-destructive technique that is fast to deploy in a production setting. GPR can assist with reducing risk and costs in future infrastructure maintenance programs by highlighting and monitoring locations within the structure exhibiting large changes in radar amplitude over calendar-time.

Keywords: 4D GPR, engineering geophysics, ground penetrating radar, infrastructure monitoring

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Authors: Yang Zhong, Mei-Jie Xu

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To study the dynamic mechanics response of asphalt pavement under the temperature load and vehicle loading, asphalt pavement was regarded as multilayered elastic half-space system, and theory analysis was conducted by regarding dynamic modulus of asphalt mixture as the parameter. Firstly, based on the dynamic modulus test of asphalt mixture, function relationship between the dynamic modulus of representative asphalt mixture and temperature was obtained. In addition, the analytical solution for thermal stress in the single layer was derived by using Laplace integral transformation and Hankel integral transformation respectively by using thermal equations of equilibrium. The analytical solution of calculation model of thermal stress in asphalt pavement was derived by transfer matrix of thermal stress in multilayer elastic system. Finally, the variation of thermal stress in pavement structure was analyzed. The result shows that there is an obvious difference between the thermal stress based on dynamic modulus and the solution based on static modulus. Therefore, the dynamic change of parameter in asphalt mixture should be taken into consideration when the theoretical analysis is taken out.

Keywords: asphalt pavement, dynamic modulus, integral transformation, transfer matrix, thermal stress

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Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

Abstract:

As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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Authors: Gabriel Sunday Ayayia

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The paper argues that Ubuntu, as a philosophy that emphasizes the interconnectedness of all living things and importance of community and mutual support, can be used as a social framework to address the problems of climate change and promote environmental sustainability. The research demonstrate that Ubuntu is an ideological concept that encourages collective action on climate change, with the emphasis on individual and collective commitment to taking concrete action to address the problems of climate change. The paper shows that Ubuntu can be employed as a social tool that would enhance the cultivation of shared identity and promote the sense of shared response responsibility to develop the resilience to cope with climate change. Using qualitative and quantitative methodologies, the study establishes the imperativeness of mutual support and cooperation through the lens of Ubuntu as a human-centered scalable response to the debacle of climate change. It recommends that we can build a society that values the environment and promotes sustainable practices by encouraging community involvement in sustainable initiatives by integrating Ubuntu-based principles to our decision-making processes, collaboration, leadership, human agency and governance.

Keywords: ubuntu, climate change, humanity, collective actions, community-based

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Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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Authors: Soniya Nityanand, Ekta Minocha, Manali Jain, Rohit Anthony Sinha, Chandra Prakash Chaturvedi

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Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: amniotic fluid stem cells, acute renal failure, autophagy, cisplatin

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Authors: Dianelys Vega, Carlos Magluta, Ney Roitman

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The simulation of loads induced by walking people in civil engineering structures is still challenging It has been the focus of considerable research worldwide in the recent decades due to increasing number of reported vibration problems in pedestrian structures. One of the most important key in the designing of slender structures is the Human-Structure Interaction (HSI). How moving people interact with structures and the effect it has on their dynamic responses is still not well understood. To rely on calibrated pedestrian models that accurately estimate the structural response becomes extremely important. However, because of the complexity of the pedestrian mechanisms, there are still some gaps in knowledge and more reliable models need to be investigated. On this topic several authors have proposed biodynamic models to represent the pedestrian, whether these models provide a consistent approximation to physical reality still needs to be studied. Therefore, this work comes to contribute to a better understanding of this phenomenon bringing an experimental validation of a pedestrian walking model and a Human-Structure Interaction model. In this study, a bi-dimensional bipedal walking model was used to represent the pedestrians along with an interaction model which was applied to a prototype footbridge. Numerical models were implemented in MATLAB. In parallel, experimental tests were conducted in the Structures Laboratory of COPPE (LabEst), at Federal University of Rio de Janeiro. Different test subjects were asked to walk at different walking speeds over instrumented force platforms to measure the walking force and an accelerometer was placed at the waist of each subject to measure the acceleration of the center of mass at the same time. By fitting the step force and the center of mass acceleration through successive numerical simulations, the model parameters are estimated. In addition, experimental data of a walking pedestrian on a flexible structure was used to validate the interaction model presented, through the comparison of the measured and simulated structural response at mid span. It was found that the pedestrian model was able to adequately reproduce the ground reaction force and the center of mass acceleration for normal and slow walking speeds, being less efficient for faster speeds. Numerical simulations showed that biomechanical parameters such as leg stiffness and damping affect the ground reaction force, and the higher the walking speed the greater the leg length of the model. Besides, the interaction model was also capable to estimate with good approximation the structural response, that remained in the same order of magnitude as the measured response. Some differences in frequency spectra were observed, which are presumed to be due to the perfectly periodic loading representation, neglecting intra-subject variabilities. In conclusion, this work showed that the bipedal walking model could be used to represent walking pedestrians since it was efficient to reproduce the center of mass movement and ground reaction forces produced by humans. Furthermore, although more experimental validations are required, the interaction model also seems to be a useful framework to estimate the dynamic response of structures under loads induced by walking pedestrians.

Keywords: biodynamic models, bipedal walking models, human induced loads, human structure interaction

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Authors: Roya Yumul, Ofelia Loani Elvir-Lazo, Sevan Komshian, Ruby Wang, Jun Tang

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BACKGROUND: An objective means for monitoring the anti-nociceptive effects of perioperative medications has long been desired as a way to provide anesthesiologists information regarding a patient’s level of antinociception and preclude any untoward autonomic responses and reflexive muscular movements from painful stimuli intraoperatively. To this end, electroencephalogram (EEG) based tools including BIS and qCON were designed to provide information about the depth of sedation while qNOX was produced to inform on the degree of antinociception. The goal of this study was to compare the reliability of qCON/qNOX to BIS as specific indicators of response to nociceptive stimulation. METHODS: Sixty-two patients undergoing general anesthesia with LMA were included in this study. Institutional Review Board (IRB) approval was obtained, and informed consent was acquired prior to patient enrollment. Inclusion criteria included American Society of Anesthesiologists (ASA) class I-III, 18 to 80 years of age, and either gender. Exclusion criteria included the inability to consent. Withdrawal criteria included conversion to the endotracheal tube and EEG malfunction. BIS and qCON/qNOX electrodes were simultaneously placed on all patients prior to induction of anesthesia and were monitored throughout the case, along with other perioperative data, including patient response to noxious stimuli. All intraoperative decisions were made by the primary anesthesiologist without influence from qCON/qNOX. Student’s t-distribution, prediction probability (PK), and ANOVA were used to statistically compare the relative ability to detect nociceptive stimuli for each index. Twenty patients were included for the preliminary analysis. RESULTS: A comparison of overall intraoperative BIS, qCON and qNOX indices demonstrated no significant difference between the three measures (N=62, p> 0.05). Meanwhile, index values for qNOX (62±18) were significantly higher than those for BIS (46±14) and qCON (54±19) immediately preceding patient responses to nociceptive stimulation in a preliminary analysis (N=20, * p= 0.0408). Notably, certain hemodynamic measurements demonstrated a significant increase in response to painful stimuli (MAP increased from 74 ±13 mm Hg at baseline to 84 ± 18 mm Hg during noxious stimuli [p= 0.032] and HR from 76 ± 12 BPM at baseline to 80 ± 13 BPM during noxious stimuli [p=0.078] respectively). CONCLUSION: In this observational study, BIS and qCON/qNOX provided comparable information on patients’ level of sedation throughout the course of an anesthetic. Meanwhile, increases in qNOX values demonstrated a superior correlation to an imminent response to stimulation relative to all other indices

Keywords: antinociception, BIS, general anesthesia, LMA, qCON/qNOX

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: Yunusa Audu, Alona Cuevas Linatoc, Aisha Idris

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The maximum carboxylation rate of Rubisco (Vcmax) and the maximum electron transport rate (Jmax), light compensation point (LCP), light saturation point (LSP), maximum photosynthesis (Amax), and apparent quantum yield (Aqy) are gas exchange characteristics that are derived from the carbon dioxide (CO2) and light response curves. This characteristics can be affected by the level of CO2 and light received by the plant. Moreover, the characteristics determines the photosynthetic capacity of the plant. The objective of the study is to evaluate the gas exchange characteristics of selected plant species of UTHM. Photosynthetic carbon dioxide (A\Ci) and light (A/Q) response curves were measured using portable photosynthesis system (LICOR). The results shows that both A/Ci and A/Q curves increases as CO2 and light increases, but reach to a certain point where the curves will become saturated. Spathodea campanulata was having the highest Vcmax (52.14±0.005 µmolCO2 m-2s-1), Jmax (104.461±0.011 µmolCO2 m-2s-1) and Aqy (0.072±0.001 mol CO2 mol-1 photons). The highest LCP was observed in Rhaphis excelsa (69.60±0.067 µmol photons m-2s-1) while the highest LSP was recorded for Costus spicatus (1576.69±0.173 µmol photons m-2s-1). It was concluded that the plants need high light intensity and CO2 for their maximum assimilation rate.

Keywords: Gas, Co2, Exchange, Plants

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