Search results for: intracellular mechanisms

Authors: Fatin H. Mohamad, Jia H. Wong, Muhammad Bilal, Abdul A. Mohamed Yusoff, Jafri M. Abdullah, Jingli Zhang

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Kv1.4 is a Shaker-related member of voltage-gated potassium channel which can be associated with cardiac action potential but can also be found in Schaffer collateral and dentate gyrus. It has two inactivation mechanisms; the fast N-type and slow C-type. Kv1.4 produces rapid current inactivation. This A type potential of Kv1.4 makes it as a target in antiepileptic drugs (AEDs) selection. In this study, 4-hydroxybenzoic acid, which can be naturally found in bamboo shoots, were tested on its enhancement effect on potassium current of Kv1.4 channel expressed in Xenopus laevis oocytes using the two-microelectrode voltage clamp method. Current obtained were recorded and analyzed with pClamp software whereas statistical analysis were done by student t-test. The ratio of final / peak amplitude is an index of the activity of the Kv1.4 channel. The less the ratio, the greater the function of Kv1.4. The decrease of ratio of which by 1µM 4-hydroxybenzoic acid (n= 7), compared with 0.1% DMSO (vehicle), was mean= 47.62%, SE= 13.76%, P= 0.026 (statistically significant). It indicated more opening of Kv1.4 channels under 4-hydroxybenzoic acid. In conclusion, 4-hydroxybenzoic acid can enhance the function of Kv1.4 potassium channels, which is regarded as one of the mechanisms of antiepileptic treatment.

Keywords: antiepileptic, Kv1.4 potassium channel, two-microelectrode voltage clamp, Xenopus laevis oocytes, 4-hydroxybenzoic acid

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Authors: Olena Grygorieva

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Nowadays mechanisms of thymocytes emigration from the thymus to the periphery are investigated actively. We have proposed a hypothesis of thymocytes’ migration from the thymus through lymphatic vessels during periodical short-term local edema. By morphological, hystochemical methods we have examined quantity of lymphocytes, epitelioreticulocytes, mast cells, blood and lymphatic vessels in morpho-functional areas of rats’ thymuses during the first week after birth in 4 hours interval. In newborn and beginning from 8 hour after birth every 12 hours specific density of the thymus, absolute quantity of microcirculatory vessels, especially of lymphatic ones, lymphcyte-epithelial index, quantity of mast cells and their degranulative forms increase. Structure of extracellular matrix, intrathymical microenvironment and lymphocytes’ adhesive properties change. Absolute quantity of small lymphocytes in thymic cortex changes wavy. All these changes are straightly expressed from 0 till 2, from 12 till 16, from 108 till 120 hours of postnatal life. During this periods paravasal lymphatic vessels are stuffed with lymphocytes, i.e. discrete migration of lymphocytes from the thymus occurs. After rapid edema reduction, quantity of lymphatic vessels decrease, they become empty. Therefore, in the thymus of newborn periodical short-term local edema is observed, on its top discrete migration of lymphocytes from the thymus occurs.

Keywords: lymphocytes, lymphatic vessels, mast cells, thymus

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Authors: Wenqiu Cao

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Suicide prevention is a global problem that needs to be taken seriously. Investigating the mechanisms of suicide in major depressive disorder (MDD) separately through neuroimaging technology is essential for effective suicide prevention. And it’s particularly urgent in geriatric depressive patients since older adults are more likely to use rapidly deadly means, and suicidal behavior is more lethal for older adults. The current study reviews five studies related to suicide in geriatric MDD that uses neuroimaging methodology in order to analyze the relevant neurobiological mechanisms. The majority of the studies found significant white matter and grey matter reduction or lesion widespread in multiple brain regions, including the frontal and parietal regions, the midbrain, the external capsule, and the cerebellum. Regarding the cognitive impairment in geriatric MDD, the reward signals were found weakened in the paralimbic cortex. The functional magnetic resonance imaging (fMRI) studies also found hemodynamic changes in the right dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and right frontopolar cortex (FPC) regions in late-life MDD patients with suicidal ideation. Future studies should consider the age of depression onset, more accurate measurements of suicide, larger sample size, and longitudinal design.

Keywords: brain imaging, geriatric major depressive disorder, suicidality, suicide

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Authors: L. Grinis

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Turbulent flow in complex geometries receives considerable attention due to its importance in many engineering applications. It has been the subject of interest for many researchers. Some of these interests include the design of storm water channels. The design of these channels requires testing through physical models. The main practical limitation of physical models is the so called “scale effect”, that is, the fact that in many cases only primary physical mechanisms can be correctly represented, while secondary mechanisms are often distorted. These observations form the basis of our study, which centered on problems associated with the design of storm water channels near the Dead Sea, in Israel. To help reach a final design decision we used different physical models. Our research showed good coincidence with the results of laboratory tests and theoretical calculations, and allowed us to study different effects of fluid flow in an open channel. We determined that problems of this nature cannot be solved only by means of theoretical calculation and computer simulation. This study demonstrates the use of physical models to help resolve very complicated problems of fluid flow through baffles and similar structures. The study applies these models and observations to different construction and multiphase water flows, among them, those that include sand and stone particles, a significant attempt to bring to the testing laboratory a closer association with reality.

Keywords: open channel, physical modeling, baffles, turbulent flow

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Authors: Jessica Hemberg, Anna K. Forsman, Johanna Nordmyr

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With a considerable increase in the aging population in the Nordic countries there is a call for a deeper understanding of healthy aging and its underlying mechanisms. The aim of this study is to uncover health and well-being for older adults according to their own views and understand what role the existential dimension play? The study uses a hermeneutical approach. Material was collected through focus group interviews with 18 older adults. The texts were interpreted through hermeneutical reading. The underlying mechanisms of health among older adults are described, illustrating the key prerequisites for health as being in the present. This implies ‘living on the continuums of life and death’ and in this field of forces also ‘living on the continuum of the past and the future’. Important aspects for being in the present was balancing ambivalent emotions, considering existential issues, and being in connectedness. Health for older adults may be understood in the light of the metaphor of taking it one day at a time. Being in the present was emphasized as a health potential for older adults highlighting the existential health dimension. From a societal point of view, this implies that health promotion should focus on highlighting the importance of the existential dimension of health since it holds health-promoting potentials for older adults. Optimal health for older adults requires awareness of one’s attitude to life through being in the present as a basis for a positive and healthy outlook on life.

Keywords: focus group interviews, hermeneutics, life experiences, older adults

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Authors: Hasmik V. Zanginyan, Gayane S. Ghazaryan, Laura M. Hovsepyan

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Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system that is induced in laboratory animals by developing an immune response against myelin epitopes. The typical clinical course is ascending palsy, which correlates with inflammation and tissue damage in the thoracolumbar spinal cord, although the optic nerves and brain (especially the subpial white matter and brainstem) are also often affected. With multiple sclerosis, there is a violation of lipid metabolism in myelin. When membrane lipids (glycosphingolipids, phospholipids) are disturbed, metabolites not only play a structural role in membranes but are also sources of secondary mediators that transmit multiple cellular signals. The purpose of this study was to investigate the effect of ganglioside as a therapeutic agent in experimental multiple sclerosis. The biological activity of a ganglioside-containing medicinal preparation (Cronassial) was evaluated in an experimental model of multiple sclerosis in laboratory animals. An experimental model of multiple sclerosis in rats was obtained by immunization with myelin basic protein (MBP), as well as homogenization of the spinal cord or brain. EAE was induced by administering a mixture of an encephalitogenic mixture (EGM) with Complete Freund’s Adjuvant. Mitochondrial fraction was isolated in a medium containing 0,25 M saccharose and 0, 01 M tris buffer, pH - 7,4, by a method of differential centrifugation on a K-24 centrifuge. Glutathione peroxidase activity was assessed by reduction reactions of hydrogen peroxide (H₂O₂) and lipid hydroperoxides (ROOH) in the presence of GSH. LPO activity was assessed by the amount of malondialdehyde (MDA) in the total homogenate and mitochondrial fraction of the spinal cord and brain of control and experimental autoimmune encephalomyelitis rats. MDA was assessed by a reaction with Thiobarbituric acid. For statistical data analysis on PNP, SPSS (Statistical Package for Social Science) package was used. The nature of the distribution of the obtained data was determined by the Kolmogorov-Smirnov criterion. The comparative analysis was performed using a nonparametric Mann-Whitney test. The differences were statistically significant when р ≤ 0,05 or р ≤ 0,01. Correlational analysis was conducted using a nonparametric Spearman test. In the work, refrigeratory centrifuge, spectrophotometer LKB Biochrom ULTROSPECII (Sweden), pH-meter PL-600 mrc (Israel), guanosine, and ATP (Sigma). The study of the process of lipid peroxidation in the total homogenate of the brain and spinal cord in experimental animals revealed an increase in the content of malonic dialdehyde. When applied, Cronassial observed normalization of lipid peroxidation processes. Reactive oxygen species, causing lipid peroxidation processes, can be toxic both for neurons and for oligodendrocytes that form myelin, causing a violation of their lipid composition. The high content of lipids in the brain and the uniqueness of their structure determines the nature of the development of LPO processes. The lipid layer of cellular and intracellular membranes performs two main functions -barrier and matrix (structural). Damage to the barrier leads to dysregulation of intracellular processes and severe disorders of cellular functions.

Keywords: experimental autoimmune encephalomyelitis, multiple sclerosis, neuroinflammation, therapy

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Authors: Preston Nabors, Nasseh Tabrizi

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Portable Document Format (PDF) files have gained significant popularity for sharing and distributing documents due to their universal compatibility. However, the widespread use of PDF files has made them attractive targets for cybercriminals, who exploit vulnerabilities to deliver malware and compromise the security of end-user systems. This paper reviews notable contributions in PDF malware detection, including static, dynamic, signature-based, and hybrid analysis. It presents a comprehensive examination of PDF malware detection techniques, focusing on the emerging threat of adversarial sampling and the need for robust defense mechanisms. The paper highlights the vulnerability of machine learning classifiers to evasion attacks. It explores adversarial sampling techniques in PDF malware detection to produce mimicry and reverse mimicry evasion attacks, which aim to bypass detection systems. Improvements for future research are identified, including accessible methods, applying adversarial sampling techniques to malicious payloads, evaluating other models, evaluating the importance of features to malware, implementing adversarial defense techniques, and conducting comprehensive examination across various scenarios. By addressing these opportunities, researchers can enhance PDF malware detection and develop more resilient defense mechanisms against adversarial attacks.

Keywords: adversarial attacks, adversarial defense, adversarial machine learning, intrusion detection, PDF malware, malware detection, malware detection evasion

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Authors: Estefanya Vazquez-Casaubon, Veroline Cauberghe, Dieneke Van de Sompel, Hayley Pearce

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Working together to reduce the anthropogenic impact should be a collective action, including effort within the household. In the matter, children are considered to have an important role in influencing the household to reduce the environmental impact through reversed socialization where children motivate and increase the concern of the parents towards environmental protection. Previous studies reveal that communication between parents and kids is key for effective reversed socialization. However, multiple barriers have been identified in the literature, such as the acceptance of the influence from the kids, the properties of the communication, among other factors. Based on the previous evidence, the present study aims to assess barriers and facilitators of communication at the household level that have an impact on reversed socialization. More precisely, the study examines how parents’ climate change coping strategy (problem-focused, meaning-focused, disregarding) influences the valence and the type of the communication related to climate change, and eventually the extent to which they report their beliefs and behaviours to be influenced by the pro-environmental perspectives of their children; i.e. reversed socialization. Via an online survey, 723 Belgian parents self-reported on communication about environmental protection and risk within their household (such as the frequency of exchange about topics related to climate change sourced from school, the household rules, imparting knowledge to the children, and outer factors like media or peer pressure, the emotional valence of the communication), their perceived socialization, and personal factors (coping mechanisms towards climate change). The results, using structural equation modelling, revealed that parents applying a problem-solving coping strategy related to climate change, appear to communicate more often in a positive than in a negative manner. Parents with a disregarding coping style towards climate change appear to communicate less often in a positive way within the household. Parents that cope via meaning-making of climate change showed to communicate less often in either a positive or negative way. Moreover, the perceived valence of the communication (positive or negative) influenced the frequency and type of household communication. Positive emotions increased the frequency of the communication overall. However, the direct effect of neither of the coping mechanisms on the reversed socialization was significant. High frequency of communication about the media, environmental views of the household members among other external topics had a positive impact on the perceived socialization, followed by discussions school-related; while parental instructing had a negative impact on the perceived socialization. Moreover, the frequency of communication was strongly affected by the perceived valence of the communication (positive or negative). The results go in line with previous evidence that a higher frequency of communication facilitates reversed socialization. Hence the results outstand how the coping mechanisms of the parents can be either a facilitator when they cope via problem-solving, while parents that disregard might avert frequent communication about climate change at the household.

Keywords: communication, parents’ coping mechanisms, environmental protection, household, perceived socialization

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Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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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: Bhagwant Singh, Sikander Singh Cheema

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This paper examines firewall mechanisms routinely implemented for network security in depth. A firewall can't protect you against all the hazards of unauthorized networks. Consequently, many kinds of infrastructure are employed to establish a secure network. Firewall strategies have already been the subject of significant analysis. This study's primary purpose is to avoid unnecessary connections by combining the capability of the firewall with the use of additional firewall mechanisms, which include packet filtering and NAT, VPNs, and backdoor solutions. There are insufficient studies on firewall potential and combined approaches, but there aren't many. The research team's goal is to build a safe network by integrating firewall strength and firewall methods. The study's findings indicate that the recommended concept can form a reliable network. This study examines the characteristics of network security and the primary danger, synthesizes existing domestic and foreign firewall technologies, and discusses the theories, benefits, and disadvantages of different firewalls. Through synthesis and comparison of various techniques, as well as an in-depth examination of the primary factors that affect firewall effectiveness, this study investigated firewall technology's current application in computer network security, then introduced a new technique named "tight coupling firewall." Eventually, the article discusses the current state of firewall technology as well as the direction in which it is developing.

Keywords: firewall strategies, firewall potential, packet filtering, NAT, VPN, proxy services, firewall techniques

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Authors: Jiahui Song

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The use of high-intensity, nanosecond electric pulses has been a recent development in biomedical. High-intensity (∼100 kV/cm), nanosecond duration-pulsed electric fields have been shown to induce cellular electroporation. This will lead to an increase in transmembrane conductivity and diffusive permeability. These effects will also alter the electrical potential across the membrane. The applications include electrically triggered intracellular calcium release, shrinkage of tumors, and temporary blockage of the action potential in nerves. In this research, the dynamics of pore formation with the presence of an externally applied electric field is studied on the basis of molecular dynamics (MD) simulations using the GROMACS package. MD simulations show pore formation occurs for a pulse with the amplitude of 0.5V/nm at 1ns at temperature 316°K. Also increasing temperatures facilitate pore formation. When the temperature is increased to 323°K, pore forms at 0.75ns with the pulse amplitude of 0.5V/nm. For statistical significance, a total of eight MD simulations are carried out with different starting molecular velocities for each simulation. Also, actual experimental observations are compared against MD simulation results.

Keywords: molecular dynamics, high-intensity, nanosecond, electroporation

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Authors: Van Tran Thi Thuy, Cheol Won Lim, Dukjoon Kim

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A series of biodegradable copolymers based on polyaspartamide (PASPAM) were synthesized by grafting hydrophilic O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) (MPEG), hydrophobic cholic acid (CA), and pH-sensitive hydrazine (Hyd) segments on a PASPAM backbone. The hydrazine group was effectively cleaved to release doxorubicin (DOX) conjugated on PASPAM in an acidic environment. The chemical structure of the polymer and the degree of substitution of each graft segment were analyzed using FT-IR and 1H-NMR spectroscopy. The size of the MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates was examined by dynamic light scattering (DLS) and transmission electron microscope (TEM). The mean diameter of the self - aggregates increased from 125 to 200 nm at pH 7.4, as the degree of substitution of CA increased from 10 to 20 %. The release kinetics of DOX was strongly affected by the pH of the releasing medium. While less than 30% of the DOX-loaded was released in about 30 h at pH 7.4, more than 60% was released at pH 5.0 within the same time. The viability tests of human breast cancer cells (MCF-7) and human embryonic kidney cells (293T) show the potential application of MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates in the controlled intracellular delivery for cancer treatments.

Keywords: pH-sensitive, drug delivery, polyaspartamide, self-assembly, nano-aggregates

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Authors: Xize Dai, Jian Hao, Claus Leth Bak, Gian Carlo Montanari, Huai Wang

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Printed Circuit Board (PCB) is a critical component applicable to power electronics systems, especially for high-voltage applications involving several high-voltage and high-frequency SiC/GaN devices. The insulation system of PCB is facing more challenges from high-voltage and high-frequency stress that can alter the dielectric properties. Dielectric properties of the PCB insulation system also determine the electrical field distribution that correlates with intrinsic and extrinsic aging mechanisms. Hence, investigating the dielectric properties in the frequency domain of the PCB insulation system is a must. The paper presents the frequency-dependent, temperature-dependent, and voltage-dependent dielectric properties, permittivity, conductivity, and dielectric loss tangents of PCB insulation systems. The dielectric properties mechanisms associated with frequency, temperature, and voltage are revealed from the design perspective. It can be concluded that the dielectric properties of PCB in the frequency domain show a strong dependence on voltage, frequency, and temperature. The voltage-, frequency-, and temperature-dependent dielectric properties are associated with intrinsic conduction behavior and polarization patterns from the perspective of dielectric theory. The results may provide some reference for the PCB insulation system design in high voltage, high frequency, and high-temperature power electronics applications.

Keywords: electrical insulation system, dielectric properties, high voltage and frequency, printed circuit board

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Authors: Ali Taher Othman Ali

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The aim of this research is to provide a draft proposal for the professional development of mathematics teachers in accordance with the orientation of science, technology, engineering and mathematics which is known by the abbreviation STEM, as a modern and contemporary orientation in the teaching and learning of mathematics and in order to achieve the objective of the research, the researcher used the theoretical descriptive method through the induction of the literature of education and the previous studies and experiments related to the topic. The researcher concluded by providing the proposal according to five basic axes, the first axe: professional development as a system, and its requirements include: development of educational systems, and allocate sufficient budgets to support the requirements of teaching STEM, identifying mechanisms for incentives and rewards for teachers attending professional development programs based on STEM; the second: development of in-depth knowledge content and its requirements include: basic sciences content development for STEM, linking the scientific understanding of teachers with real-world issues and problems, to provide the necessary resources to expand teachers' knowledge in this area; the third: the necessary pedagogical skills of teachers in the field of STEM, and its requirements include: identification of the required training and development needs and the mechanism of determining these needs, the types of professional development programs and the mechanism of designing it, the mechanisms and places of execution, evaluation and follow-up; the fourth: professional development strategies and mechanisms in the field of STEM, and its requirements include: using a variety of strategies to enable teachers to design and transfer effective educational experiences which reflect their scientific mastery in the fields of STEM, provide learning opportunities, and developing the skills of procedural research to generate new knowledge about the STEM; the fifth: to support professional development in the area of STEM, and its requirements include: support leadership within the school, provide a clear and appropriate opportunities for professional development for teachers within the school through professional learning communities, building partnerships between the Ministry of education and the local and international community institutions. The proposal includes other factors that should be considered when implementing professional development programs for mathematics teachers in the field of STEM.

Keywords: professional development, mathematics teachers, the orientation of science, technology, engineering and mathematics (STEM)

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Authors: Yantao Li, Jun Zheng

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Food poison caused by consumption of contaminated food, especially seafood, is one of most serious public health threats worldwide. Vibrio parahaemolyticus is emerging bacterial pathogen and the leading cause of human gastroenteritis associated with food poison, especially in the southern coastal region of China. To successfully cause disease in host, bacterial pathogens need to overcome the host-derived stresses encountered during infection. One of the toxic chemical species elaborated by the host is nitric oxide (NO). NO is generated by acidified nitrite in the stomach and by enzymes of the inducible NO synthase (iNOS) in the host cell, and is toxic to bacteria. Bacterial pathogens have evolved some mechanisms to battle with this toxic stress. Such mechanisms include genes to sense NO produced from immune system and activate others to detoxify NO toxicity, and genes to repair the damage caused by toxic reactive nitrogen species (RNS) generated during NO toxic stress. However, little is known about the NO resistance in V. parahaemolyticus. In this study, a transposon coupled with next generation sequencing (Tn-seq) technology will be utilized to identify genes for NO resistance in V. parahaemolyticus. Our strategy will include construction the saturating transposon insertion library, transposon library challenging with NO, next generation sequencing (NGS), bioinformatics analysis and verification of the identified genes in vitro and in vivo.

Keywords: vibrio parahaemolyticus, nitric oxide, tn-seq, virulence

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: Eman Ismail, Adnan Masri

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Energy dissipation in ductile moment frames occurs mainly through plastic hinge rotations in its members (beams and columns). Generally, plastic hinge locations are pre-determined and limited to the beam ends, where columns are designed to remain elastic in order to avoid premature instability (aka story mechanisms) with the exception of column bases, where a base is 'fixed' in order to provide higher stiffness and stability and to form a plastic hinge. Plastic hinging at steel column bases in ductile moment frames using conventional base connection details is accompanied by several complications (thicker and heavily stiffened connections, larger embedment depths, thicker foundation to accommodate anchor rod embedment, etc.). An encased composite base connection is proposed where a segment of the column beginning at the base up to a certain point along its height is encased in reinforced concrete with headed shear studs welded to the column flanges used to connect the column to the concrete encasement. When the connection is flexurally loaded, stresses are transferred to a reinforced concrete encasement through the headed shear studs, and thereby transferred to the foundation by reinforced concrete mechanics, and axial column forces are transferred through the base-plate assembly. Horizontal base reactions are expected to be transferred by the direct bearing of the outer and inner faces of the flanges; however, investigation of this mechanism is not within the scope of this research. The inelastic and cyclic behavior of the connection will be investigated where it will be subjected to reversed cyclic loading, and rotational ductility will be observed in cases of yielding mechanisms where yielding occurs as flexural yielding in the beam-column, shear yielding in headed studs, and flexural yielding of the reinforced concrete encasement. The findings of this research show that the connection is capable of achieving satisfactory levels of ductility in certain conditions given proper detailing and proportioning of elements.

Keywords: seismic design, plastic mechanisms steel structure, moment frame, composite construction

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Authors: Xinli Chi, Xiaoqi Wei

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Background: Body-mind theory refers to the concept that the mind and body are interconnected; in this case, combining aerobic exercise and mindfulness-based training may be beneficial for mind-body health; however, there is limited evidence regarding their effects and potential mechanisms among Chinese university students. Therefore, the current study aims to examine the preliminary effects and feasibility of the combined intervention on depressive and insomnia symptoms, as well as to explore the underlying mechanisms. Methods: This is a two-arm pilot study of a randomized, controlled trial. Sixty-one Chinese university students were randomly allocated to 8-week combined intervention group (aerobic exercise plus mindfulness, N = 36) or control group (N = 36). In addition, 8 participants in combined intervention group were later volunteer to engage in semi-structured interview. The Self-Rating Depression Scale (SDS) and the Youth Self-Rating Insomnia Scales (YSIS) were used to measure depressive and insomnia symptoms, respectively. The intervention outcome and feasibility were tested by repeated-measures ANOVA, mediation model, and qualitative analysis. Results: The study included 31 participants in the intervention group and 30 participants in the control group, all of whom completed pre-test and post-test questionnaires. The results of the repeated-measures ANOVA showed that the combined intervention was effective in reducing depressive and insomnia symptoms among university students. Moreover, the mediation analysis suggested that improvement in insomnia symptoms might be a significant mechanism for the combined intervention. Qualitative analysis identified two main themes: “Helpful aspects of mind-body state” (including 7 sub-themes) and “Factors that influence the training effects” (including 3 sub-themes). Conclusions: The study confirmed the preliminary effect and feasibility of the combined intervention of mindfulness and aerobic exercise, while also exploring the potential mechanisms underlying this effect. Additionally, qualitative data provided valuable insights for optimizing future protocols.

Keywords: combined intervention, mindfulness, aerobic exercise, depressive symptoms, insomnia symptoms

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Authors: Shahla Ali

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In the context of promoting green infrastructure development, new opportunities are emerging to re-examine sustainable development practices. This paper presents an initial exploration of the development of community-investor dispute prevention and facilitation mechanisms in the context of the Belt and Road Initiative (BRI) spanning Asia, Africa, and Europe. Given the widescale impact of China’s multi-jurisdictional development initiative, learning how to coordinate with local communities is vital to realizing inclusive and sustainable growth. In the 20 years since the development of the first multilateral community-investor dispute resolution mechanism developed by the International Finance Centre/World Bank, much has been learned about public facilitation, community engagement, and dispute prevention during the early stages of major infrastructure development programs. This paper will explore initial findings as they relate to initiatives underway along the BRI within the Asian Infrastructure Investment Bank and the Asian Development Bank. Given the borderless nature of sustainability concerns, insights from diverse regions are critical to deepening insights into best practices. Drawing on a case-based methodology, this paper will explore the achievements, challenges, and lessons learned in community-investor dispute prevention and resolution for major infrastructure projects in the greater China region.

Keywords: law and development, dispute prevention, sustainable development, mitigation

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Authors: Victor Arokia Doss, Kuberapandian Dharaniyambigai, K. Julia Rose Mary

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Advanced Glycation End (AGE) products are the end products due to the reaction between excess reducing sugar present in diabetes and free amino group in protein lipids and nucleic acids. Thus, non-enzymic glycation of molecules such as hemoglobin, collagen, and other structurally and functionally important proteins add to the pathogenic complications such as diabetic retinopathy, neuropathy, nephropathy, vascular changes, atherosclerosis, Alzheimer's disease, rheumatoid arthritis, and chronic heart failure. The most common non-cross linking AGE, carboxymethyl lysine (CML) is formed by the oxidative breakdown of fructosyllysine, which is a product of glucose and lysine. CML is formed in a wide variety of tissues and is an index to assess the extent of glycoxidative damage. Thus we have constructed a mathematical and computational model that predicts the effect of temperature differences in vivo, on the formation of CML, which is now being considered as an important intracellular milieu. This hybrid model that had been tested for its parameter fitting and its sensitivity with available experimental data paves the way for designing novel laboratory experiments that would throw more light on the pathological formation of AGE adducts and in the pathophysiology of diabetic complications.

Keywords: advanced glycation end-products, CML, mathematical model, computational model

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Authors: Andrey Makarov

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This article will focus on the development of antitrust policy in transition economies in the context of preventing explicit and tacit collusion. Experience of BRICS, CIS (Ukraine, Kazakhstan) and CEE countries (Bulgaria, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, Slovenia, Czech Republic, Estonia) in the creation of antitrust institutions was analyzed, including both legislation and enforcement practice. Most of these countries in the early 90th were forced to develop completely new legislation in the field of protection of competition and it is important to compare different ways of building antitrust institutions and policy results. The article proposes a special approach to evaluation of preventing collusion mechanisms. This approach takes into account such enforcement problems as: classification problems (tacit vs explicit collusion, vertical vs horizontal agreements), flexibility of prohibitions (the balance between “per se” vs “rule of reason” approaches de jure and in practice), design of sanctions, private enforcement challenge, leniency program mechanisms, the role of antitrust authorities etc. The analysis is conducted using both official data, published by competition authorities, and expert assessments. The paper will show how the integration process within the EU predetermined some aspects of the development of antitrust policy in CEE countries, including the trend of the use of "rule of reason" approach. Simultaneously was analyzed the experience of CEE countries in special mechanisms of government intervention. CIS countries in the development of antitrust policy followed more or less original ways, without such a great impact from the European Union, more attention will be given to Russian experience in this field, including the analysis of judicial decisions in antitrust cases. Main problems and challenges for transition economies in this field will be shown, including: Legal uncertainty problem; Problem of rigidity of prohibitions; Enforcement priorities of the regulator; Interaction of administrative and criminal law, limited effectiveness of criminal sanctions in the antitrust field; The effectiveness of leniency program design; Private enforcement challenge.

Keywords: collusion, antitrust policy, leniency program, transition economies, Russia, CEE

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Authors: Stephen Eyije Abechi, Casimir Emmanuel Gimba, Zaharaddeen Nasiru Garba, Sani Shamsudeen, David Ebuka Authur

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The mechanisms of corrosion inhibition of mild steel in acid medium using Acalypha chamaedrifolia leaves extract as potential green inhibitor were investigated. Gravimetric (weight loss) technique was used for the corrosion studies. Mild steel coupons of 2cm × 1cm × 0.27 cm dimensions were exposed for varying durations of between 24 to 120 hours, in 1M HCl medium containing a varying concentrations of the leaves extract (0.25g/L, - 1.25g/L). The results show that corrosion rates dropped from a value of 0.49 mgcm-2hr-1 for the uninhibited medium to a value of 0.15 mgcm-2hr-1 for the inhibited medium of 1M HCl in 0.25 g/l of the extract. Values of corrosion inhibition efficiencies of 70.38-85.11% were observed as the concentration of the inhibitor were increased from 0.25g/L, - 1.25g/L. Corrosion Inhibition was found to increase with increase in immersion time and temperature. The magnitude of the Ea indicates that the interaction between the metal surface and the inhibitor was chemisorptions. The Adsorption process fit into the Langmuir isotherm model with a correlation coefficient of 0.97. Evidence from molecular dynamics model shows that Methyl stearate (Line 5) and (3Z, 13Z)-2-methyloctadeca-3,13-dien-1-ol (line 11) were found to have the highest binding energy of -197.69 ± 3.12 and-194.56 ± 10.04 in kcal/mol respectively. The binding energy of these compounds indicates that they would be a very good corrosion inhibitor for mild steel and other Fe related materials.

Keywords: binding energy, corrosion, inhibitor, Langmuir isotherm, mild steel.

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Authors: Samantha Shallop, Hakinya Karra, Tytus Bernas, Gladys Shaw, Gretchen Neigh, Jeffrey Dupree, Mathula Thangarajh

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Abnormal neuronal homeostasis is considered a structural correlate of cognitive deficits in Duchenne Muscular Dystrophy. Neurons are highly polarized cells with multiple dendrites but a single axon. Trafficking of cellular organelles are highly regulated, with the cargo in the somatodendritic region of the neuron not permitted to enter the axonal compartment. We investigated the molecular mechanisms that regular organelle trafficking in neurons using a multimodal approach, including high-resolution structural illumination, proteomics, immunohistochemistry, and computational modeling. We investigated the expression of ankyrin-G, the master regulator controlling neuronal polarity. The expression of ankyrin G and the morphology of the axon initial segment was profoundly abnormal in the CA1 hippocampal neurons in the mdx52 animal model of DMD. Ankyrin-G colocalized with kinesin KIF5a, the anterograde protein transporter, with higher levels in older mdx52 mice than younger mdx52 mice. These results suggest that the functional trafficking from the somatodendritic compartment is abnormal. Our data suggests that dystrophin deficiency compromised neuronal homeostasis via ankyrin-G-based mechanisms.

Keywords: neurons, axonal transport, duchenne muscular dystrophy, organelle transport

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Authors: David Broussard

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This review article delves into the realm of marine conservation finance, addressing the inadequacies in current financial streams from the private sector and the underutilization of existing financing mechanisms. The study emphasizes the emerging field of “blue finance”, which contributes to economic growth, improved livelihoods, and marine ecosystem health. The financial burden of marine conservation projects typically falls on philanthropists and governments, contrary to the polluter-pays principle. However, the private sector’s increasing commitment to NetZero and growing environmental and social responsibility goals prompts the need for alternative funding sources for marine conservation initiatives like marine protected areas. The article explores the potential of utilizing several financing mechanisms like carbon credits and other forms of payment for ecosystem services in the marine context, providing a solution to the lack of private funding for marine conservation. The methodology employed involves a systematic and quantitative approach, combining traditional review methods and elements of meta-analysis. A comprehensive search of the years 2000 - 2023, using relevant keywords on the Scopus platform, resulted in a review of 252 articles. The temporal evolution of blue finance studies reveals a significant increase in annual articles from 2010 to 2022, with notable peaks in 2011 and 2022. Marine Policy, Ecosystem Services, and Frontiers in Marine Science are prominent journals in this field. While the majority of articles focus on payment for ecosystem services, there is a growing awareness of the need for holistic approaches in conservation finance. Utilizing bibliometric techniques, the article showcases the dominant share of payment for ecosystem services in the literature with a focus on blue carbon. The classification of articles based on various criteria, including financing mechanisms and conservation types, aids in categorizing and understanding the diversity of research objectives and perspectives in this complex field of marine conservation finance.

Keywords: biodiversity offsets, carbon credits, ecosystem services, impact investment, payment for ecosystem services

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Authors: A. V. Belousov, Yakushenko

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One of the main problems of modern dentistry is development a reliable method to detect inflammation in the gums on the stages of diagnosis and assessment of treatment efficacy. We have proposed a method of gingival fluid intake, which successfully combines accessibility, excluding the impact of the annoying and damaging the gingival sulcus factors and provides reliable results (patent of RF№ 2342956 Method of gingival fluid intake). The objects of the study were students - volunteers of Dentistry Faculty numbering 75 people aged 20-21 years. Cellular composition of gingival fluid was studied using microscope "Olympus CX 31" (Japan) with the calculation of epithelial leukocyte index (ELI). Assessment of gingival micro circulation was performed using the apparatus «LAKK–01» (Lazma, Moscow). Cytological investigation noted the highly informative of epithelial leukocyte index (ELI), which demonstrated changes in the mechanisms of protection gums. The increase of ELI occurs during inhibition mechanisms of phagocytosis and activation of epithelial desquamation. The cytological data correlate with micro circulation indicators obtained by laser Doppler flowmetry. We have identified and confirmed the correlations between parameters laser Doppler flowmetry and data cytology gingival fluid in patients with gingivitis.

Keywords: gingivitis, laser doppler flowmetry, gingival fluid cytology, epithelial leukocyte index (ELI)

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Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

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Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

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Authors: Ezequiel Garcia-Rodriguez, Lenin Hernandez-Ferreyra, Luis Ochoa-Franco

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The Sustainable Sewer Urban Systems (SSUS) are mechanisms integrated into the cities for manage rain water, reducing its runoff volume and velocity, enhancing the rain water quality and preventing flooding and other catastrophes associated to the rain, as well as improving the energy efficiency. The objective of SSUS is to mimic or to equal the runoff and infiltration natural conditions of the land before its urbanization, reducing runoff that may cause troubles within the houses, as well as flooding. At the same time, energy for warming homes and for pumping and treating water is reduced, contributing to the reduction of CO₂ emissions and therefore contributing to reduce the climate change. This paper contains an evaluation of the advantages that SSUS may offer within a zone of Morelia City, Mexico, applying support tools for decision making. The hydrological conditions prior to and after the urbanization of the study area were analyzed to propose the recommended SSUS. Different types of SSUS were proposed in this case study, assessing their effect on the rainwater flow behavior within the study area. SSUS usage in this case resulted, positively, in an important reduction of the magnitude and velocity of runoff, reducing therefore the risk of flooding. So that, it is recommended the implementation of SSUS in this case.

Keywords: energy efficiency, morelia, sustainablesewer, urban systems

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Authors: Anubhav Kumar Dwivedi, Arshad Khan, S. N. Tripathi, Manish Joshi, Gaurav Mishra, Dinesh Nath, Naveen Tiwari, B. K. Sapra

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In a nuclear reactor accident scenario, a large number of fission products may release to the piping system of the primary heat transport. The released fission products, mostly in the form of the aerosol, get deposited on the inner surface of the piping system mainly due to gravitational settling and thermophoretic deposition. The removal processes in the complex piping system are controlled to a large extent by the thermal-hydraulic conditions like temperature, pressure, and flow rates. These parameters generally vary with time and therefore must be carefully monitored to predict the aerosol behavior in the piping system. The removal process of aerosol depends on the size of particles that determines how many particles get deposit or travel across the bends and reach to the other end of the piping system. The released aerosol gets deposited onto the inner surface of the piping system by various mechanisms like gravitational settling, Brownian diffusion, thermophoretic deposition, and by other deposition mechanisms. To quantify the correct estimate of deposition, the identification and understanding of the aforementioned deposition mechanisms are of great importance. These mechanisms are significantly affected by different flow and thermodynamic conditions. Thermophoresis also plays a significant role in particle deposition. In the present study, a series of experiments were performed in the piping system of the National Aerosol Test Facility (NATF), BARC using metal aerosols (zinc) in dry environments to study the spatial distribution of particles mass and number concentration, and their depletion due to various removal mechanisms in the piping system. The experiments were performed at two different carrier gas flow rates. The commercial CFD software FLUENT is used to determine the distribution of temperature, velocity, pressure, and turbulence quantities in the piping system. In addition to the in-built models for turbulence, heat transfer and flow in the commercial CFD code (FLUENT), a new sub-model PBM (population balance model) is used to describe the coagulation process and to compute the number concentration along with the size distribution at different sections of the piping. In the sub-model coagulation kernels are incorporated through user-defined function (UDF). The experimental results are compared with the CFD modeled results. It is found that most of the Zn particles (more than 35 %) deposit near the inlet of the plenum chamber and a low deposition is obtained in piping sections. The MMAD decreases along the length of the test assembly, which shows that large particles get deposited or removed in the course of flow, and only fine particles travel to the end of the piping system. The effect of a bend is also observed, and it is found that the relative loss in mass concentration at bends is more in case of a high flow rate. The simulation results show that the thermophoresis and depositional effects are more dominating for the small and larger sizes as compared to the intermediate particles size. Both SEM and XRD analysis of the collected samples show the samples are highly agglomerated non-spherical and composed mainly of ZnO. The coupled model framed in this work could be used as an important tool for predicting size distribution and concentration of some other aerosol released during a reactor accident scenario.

Keywords: aerosol, CFD, deposition, coagulation

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Authors: Bharat Kumar, Deepak Kumar, Vijay Chaudhry

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Zirconium alloys are used as core components of nuclear reactors due to their high wear resistance, good corrosion properties, and good mechanical stability at high temperatures. Water flows inside the pressure tube through fuel claddings, which produces vibration of these core components and results in the wear of some components. Some components are subjected to the environment of coolant water containing LiOH which results in the corrosion of these components. The present work simulates some of these conditions to determine the failure mechanisms under these conditions and the effect of various parameters on them. Friction and wear experiments were performed varying the surrounding environment (room temperature, high temperature, and water submerged), duration, frequency, and displacement amplitude. Electrochemical corrosion experiments were performed by varying the concentration of LiOH in water. The worn and corroded surfaces were analyzed using scanning electron microscopy (SEM) to analyze the wear and corrosion mechanism and energy dispersive x-ray spectroscopy (EDS) and Raman spectroscopy to analyze the tribo-oxide layer formed during the wear and oxide layer formed during the corrosion. Wear increases with frequency and amplitude, and corrosion increases with LiOH concentration in water.

Keywords: zirconium alloys, wear, oxide layer, corrosion, EIS, linear polarization

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