Search results for: Limbal Stem Cells

Authors: Laila H. Abdel-Rahman, Mohamed Shaker S. Adam, Ahmed M. Abu-Dief, Hanan El-Sayed Ahmed

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In this investigation, Cu(II), Pd(II) and Ag(I) complexes with the tetra-dentate DSPH Schiff base ligand were synthesized. The DSPH Schiff base and its complexes were characterized by using different physicochemical and spectral analysis. The results revealed that the metal ions coordinated with DSPH ligand through azomethine nitrogen and phenolic oxygen. Cu(II), Pd(II) and Ag(I) complexes are present in a 1:1 molar ratio. Pd(II) and Ag(I) complexes have square planar geometries while, Cu(II) has a distorted octahedral (Oh) geometry. All investigated complexes are nonelectrolytes. The investigated compounds were tested against different strains of bacteria and fungi. Both prepared compounds showed good results of inhibition against the selected pathogenic microorganism. Moreover, the interaction of investigated complexes with CT-DNA was studied via various techniques and the binding modes are mainly intercalative and grooving modes. Operating Environment MOE package was used to do docking studies for the investigated complexes to explore the potential binding mode and energy. Furthermore, the growth inhibitory effect of the investigated compounds was examined on some cancer cells lines.

Keywords: tetradentate, antimicrobial, CT-DNA interaction, docking, anticancer

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Authors: Nabila N. El-Maraghy, Amany Essa, Yousra Abdel–Mottaleb, Nada Ismail

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The use of combination of chemotherapy and natural products to influence the cell death with low doses of chemotherapeutic agents and few side effects has recently emerged as a new method of cancer therapy. Aim: Evaluation the modulatory effect of Thymoquinone on HepG2 cells treated with Sorafenib. Methods: Hepatocellular Carcinoma HepG2 cell line was treated with Sorafenib and TQ individually and in combination. The effect of these treatments on cell viability (MTT assay), apoptosis (Expression of Caspase-3) and oxidative markers (GSH content and extent of lipid peroxidation) was determined. Results: When compared the effect of both agents alone and the combination of the IC50 of Sorafenib and the IC50 TQ, the combination resulted in reduction of cell inhibition and apoptosis and antagonize their actions on GSH content and extent of lipid peroxidation which are increased. This study showed potent anti-tumor activity of both TQ and Sorafenib separately on HepG2 but upon combination surprisingly they interacted and give antagonistic effect. Conclusion: Co-treatment resulted in antagonistic interaction between Sorafenib and Thymoquinone.

Keywords: antagonism, hepatocellular carcinoma, sorafenib, thymoquinone

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Authors: Turky Al-Qahtani, Roustem Miftahof

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Introduction: Under common assumptions of excitabi-lity, morphological (cellular) homogeneity, and spatial structural anomalies added as required, it has been shown that biological systems are able to display travelling wave dynamics. Being not self-sustainable, existence depends on the electrophysiological state of transmembrane ion channels and it requires an extrinsic/intrinsic periodic source. However, organs in the body are highly multicellular, heterogeneous, and their functionality is the outcome of electro-mechanical conjugation, rather than excitability only. Thus, peristalsis in the gut relies on spatiotemporal myoelectrical pattern formations between the mechanical, represented by smooth muscle cells (SM), and the control, comprised of a chain of primary sensory and motor neurones, components. Synaptically linked through the afferent and efferent pathways, they form a functional unit (FU) of the gut. Aims: These are: i) to study numerically the complex dynamics, and ii) to investigate the possibility of self-sustained myoelectrical activity in the FU. Methods: The FU recreates the following sequence of physiological events: deformation of mechanoreceptors of located in SM; generation and propagation of electrical waves of depolarisation - spikes - along the axon to the soma of the primary neurone; discharge of the primary neurone and spike propagation towards the motor neurone; burst of the motor neurone and transduction of spikes to SM, subsequently producing forces of contraction. These are governed by a system of nonlinear partial and ordinary differential equations being a modified version of the Hodgkin-Huxley model and SM fibre mechanics. In numerical experiments; the source of excitation is mechanical stretches of SM at a fixed amplitude and variable frequencies. Results: Low frequency (0.5 < v < 2 Hz) stimuli cause the propagation of spikes in the neuronal chain and, finally, the generation of active forces by SM. However, induced contractions are not sufficient to initiate travelling wave dynamics in the control system. At frequencies, 2 < v < 4 Hz, multiple low amplitude and short-lasting contractions are observed in SM after the termination of stretching. For frequencies (0.5 < v < 4 Hz), primary and sensory neurones demonstrate strong connectivity and coherent electrical activity. Significant qualitative and quantitative changes in dynamics of myoelectical patterns with a transition to a self-organised mode are recorded with the high degree of stretches at v = 4.5 Hz. Increased rates of deformation lead to the production of high amplitude signals at the mechanoreceptors with subsequent self-sustained excitation within the neuronal chain. Remarkably, the connection between neurones weakens resulting in incoherent firing. Further increase in a frequency of stimulation (v > 4.5 Hz) has a detrimental effect on the system. The mechanical and control systems become disconnected and exhibit uncoordinated electromechanical activity. Conclusion: To our knowledge, the existence of periodic activity in a multicellular, functionally heterogeneous biological system with mechano-electrical dynamics, such as the FU, has been demonstrated for the first time. These findings support the notion of possible peristalsis in the gut even in the absence of intrinsic sources - pacemaker cells. Results could be implicated in the pathogenesis of intestinal dysrythmia, a medical condition associated with motor dysfunction.

Keywords: complex dynamics, functional unit, the gut, dysrythmia

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Authors: Lukasz Szydlowski, Jiri Ehlich, Igor Goryanin

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We demonstrate a single chamber, 96-well-plated based Microbial Fuel Cell (MFC) with printed, electronic components. This invention is aimed at robust selection of electrogenic microbial community under specific conditions, e.g., electrode potential, pH, nutrient concentration, salt concentration that can be altered within the 96 well plate array. This invention enables robust selection of electrogenic microbial community under the homogeneous reactor, with multiple conditions that can be altered to allow comparative analysis. It can be used as a standalone technique or in conjunction with other selective processes, e.g., flow cytometry, microfluidic-based dielectrophoretic trapping. Mobile conductive elements, like carbon paper, carbon sponge, activated charcoal granules, metal mesh, can be inserted inside to increase the anode surface area in order to collect electrogenic microorganisms and to transfer them into new reactors or for other analytical works. An array of 96-well plate allows this device to be operated by automated pipetting stations.

Keywords: bioengineering, electrochemistry, electromicrobiology, microbial fuel cell

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Authors: Min Liu, Jirui Gong, Qinpu Luo, Lili Yang, Bo Yang, Zihe Zhang, Yan Pan, Zhanwei Zhai

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Grazing disturbance is one of the important land-use types that affect plant growth and ecosystem processes. In order to study the responses of dominant species to grazing in the semiarid temperate grassland of Inner Mongolia, we set five grazing intensity plots: a control and four levels of grazing (light (LG), moderate (MG), heavy (HG) and extreme heavy grazing (EHG)) to test the morphological and physiological responses of Stipa grandis, Leymus chinensis at the individual levels. With the increase of grazing intensity, Stipa grandis and Leymus chinensis both exhibited reduced plant height, leaf area, stem length and aboveground biomass, showing a significant dwarf phenomenon especially in HG and EHG plots. The photosynthetic capacity decreased along the grazing gradient. Especially in the MG plot, the two dominant species have lowest net photosynthetic rate (Pn) and water use efficiency (WUE). However, in the HG and EHG plots, the two species had high light saturation point (LSP) and low light compensation point (LCP), indicating they have high light-use efficiency. They showed a stimulation of compensatory photosynthesis to the remnant leaves as compared with grasses in MG plot. For Leymus chinensis, the lipid peroxidation level did not increase with the low malondialdehyde (MDA) content even in the EHG plot. It may be due to the high enzymes activity of superoxide dismutase (SOD) and peroxidase (POD) to reduce the damage of reactive oxygen species. Meanwhile, more carbohydrate was stored in the leaf of Leymus chinensis to provide energy to the plant regrowth. On the contrary, Stipa grandis showed the high level of lipid peroxidation especially in the HG and EHG plots with decreased antioxidant enzymes activity. The soluble protein content did not change significantly in the different plots. Therefore, with the increase of grazing intensity, plants changed morphological and physiological traits to defend themselves effectively to herbivores. Leymus chinensis is more resistant to grazing than Stipa grandis in terms of tolerance traits, particularly under heavy grazing pressure.

Keywords: antioxidant enzymes activity, grazing density, morphological responses, photosynthesis

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Authors: Siddhartha Paul, Aman Harlalka, Ashim K. Dey

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Soft clayey soil possesses poor bearing capacity and high compressibility because of which foundations cannot be directly placed over soft clay. Normally pile foundations are constructed to carry the load through the soft soil up to the hard stratum below. Pile construction is costly and time consuming. In order to increase the properties of soft clay, many ground improvement techniques like stone column, preloading with and without sand drains/band drains, etc. are in vogue. Time is a constraint for successful application of these improvement techniques. Another way to improve the bearing capacity of soft clay and to reduce the settlement possibility is to apply geocells below the foundation. The geocells impart rigidity to the foundation soil, reduce the net load intensity on soil and thus reduce the compressibility. A well designed geocell reinforced soil may replace the pile foundation. The present paper deals with the applicability of geocells on improvement of the bearing capacity. It is observed that a properly designed geocell may increase the bearing capacity of soft clay up to two and a half times.

Keywords: bearing capacity, geo-cell, ground improvement, soft clay

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Authors: Seyed Mehdi Razavi Khosroshahi

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In recent years a great deal of efforts has been made to find natural derivative compounds to replace it's with synthetic drugs, herbicides or pesticides for management of human health and agroecosystem programs. This process can lead to a reduction in environmental harmful effects of synthetic chemicals. Xanthotoxin, as a furanocoumarin compound, found in some genera of the Apiaceae family of plants. The current work focuses on some xanthotoxin cytotoxicity and antipathogenic activities. The results indicated that xanthotoxin showed strong cytotoxic effects against LNCaP cell line with the IC₅₀ value of 0.207 mg/ml in a dose-dependent manner. After treatments of the cell line with 0.1 mg/ml of the compound, the viability of the cells was reached to zero. The current study revealed that xanthotoxin displayed strong antifungal activity against human or plant pathogen fungi, Aspergillus fumigatus, Aspegillusn flavus and Fusarum graminearum with minimum inhibitory concentration values of 52-68 µg/ml. The compound exhibited antibacterial effects on some Erwinia and Xanthomonas species of bacteria, as well

Keywords: Xanthomonas, cytotoxic, antipathogen, LNCaP, Aspergillus fumigatus, spegillusn flavus

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Authors: Bedilu A. Ejigu, Eshetu Wencheko, Kiros Berhane

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Anaemia is a condition in which the haemoglobin concentration falls below an established cut-off value due to a decrease in the number and size of red blood cells. The current study aimed to assess the spatial pattern and identify predictors related to anaemia using the third Ethiopian demographic health survey which was conducted in 2010. To achieve this objective, this study took into account the clustered nature of the data. As a result, multilevel modeling has been used in the statistical analysis. For analysis purpose, only complete cases from 15,909 females, and 13,903 males were considered. Among all subjects who agreed for haemoglobin test, 5.49 %males, and 19.86% females were anaemic. In both binary and ordinal outcome modeling approaches, educational level, age, wealth index, BMI and HIV status were identified to be significant predictors for anaemia prevalence. Furthermore, it was noted that pregnant women were more anaemic than non-pregnant women. As revealed by Moran's I test, significant spatial autocorrelation was noted across clusters. The risk of anaemia was found to vary across different regions, and higher prevalence was observed in Somali and Affar region.

Keywords: anaemia, Moran's I test, multilevel models, spatial pattern

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Authors: Tanu Khanuja, Harikrishnan N. Unni

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Head is the most vulnerable part of human body and may cause severe life threatening injuries. As the in vivo brain response cannot be recorded during injury, computational investigation of the head model could be really helpful to understand the injury mechanism. Majority of the physical damage to living tissues are caused by relative motion within the tissue due to tensile and shearing structural failures. The present Finite Element study focuses on investigating intracranial pressure and stress/strain distributions resulting from impact loads on various sites of human head. This is performed by the development of the 3D model of a human head with major segments like cerebrum, cerebellum, brain stem, CSF (cerebrospinal fluid), and skull from patient specific MRI (magnetic resonance imaging). The semi-automatic segmentation of head is performed using AMIRA software to extract finer grooves of the brain. To maintain the accuracy high number of mesh elements are required followed by high computational time. Therefore, the mesh optimization has also been performed using tetrahedral elements. In addition, model validation with experimental literature is performed as well. Hard tissues like skull is modeled as elastic whereas soft tissues like brain is modeled with viscoelastic prony series material model. This paper intends to obtain insights into the severity of brain injury by analyzing impacts on frontal, top, back, and temporal sites of the head. Yield stress (based on von Mises stress criterion for tissues) and intracranial pressure distribution due to impact on different sites (frontal, parietal, etc.) are compared and the extent of damage to cerebral tissues is discussed in detail. This paper finds that how the back impact is more injurious to overall head than the other. The present work would be helpful to understand the injury mechanism of traumatic brain injury more effectively.

Keywords: dynamic impact analysis, finite element analysis, intracranial pressure, MRI, traumatic brain injury, von Misses stress

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Authors: Abdelghani Boucheham, Djoudi Bouhafs, Nabil Khelifati, Baya Palahouane

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The main aim of this study is to investigate the low temperature internal gettering of manganese and chromium transition metals content in p-type multicrystalline silicon grown by Heat Exchanger Method (HEM). The minority carrier lifetime variation, the transition metal elements behavior, the sheet resistivity and the interstitial oxygen concentration after different temperatures annealing under N2 ambient were investigated using quasi-steady state photoconductance technique (QSSPC), secondary ion mass spectroscopy (SIMS), four-probe measurement and Fourier transform infrared spectrometer (FTIR), respectively. The obtained results indicate in the temperature range of 300°C to 700°C that the effective lifetime increases and reaches its maximum values of 28 μs at 500 °C and decreasing to 6 μs at 700 °C. This amelioration is due probably to metallic impurities internal gettering in the extended defects and in the oxygen precipitates as observed on SIMS profiles and the FTIR spectra. From 300 °C to 500 °C the sheet resistivity values rest unchanged at 30 Ohm/sq and rises significantly to reach 45 Ohm/sq for T> 500 °C.

Keywords: mc-Si, low temperature annealing, internal gettering, minority carrier lifetime, interstitial oxygen, resistivity

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Authors: Dheepshika Kodieswaran

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The persisting problem in the world that continuously impose our planet at risk is the increasing amounts of recalcitrant. One such issue is the disposal of the Petroleum Refinery Sludge (PRS) which constitutes hydrocarbons that are hazardous to terrestrial and aquatic life. The comparatively safe approach to handling these wastes is by microbial degradation, while the other chemical and physical methods are either expensive and/or produce secondary pollutants. The bacterial and algal systems have different pathways for the degradation of hydrocarbons, and their growth rates vary. This study shows how different bacterial and microalgal strains degrade the polyaromatic hydrocarbon PAHs individually and their symbiotic influence on degradation as well. In this system, the metabolites and gaseous exchange help each other in growth. This method using also aids in the accumulation of lipids in microalgal cells and from which bio-oils can also be extracted. The bacterial strains used in this experiment are reported to be indigenous strains isolated from PRS. The target PAH studied were anthracene and pyrene for a period of 28 days. The PAH degradation kinetics best fitted the Gompertz model, and the order of the kinetics, rate constants, and half-life was determined.

Keywords: petroleum refinery sludge, co-culturing, polycyclic hydrocarbons, microalgal-bacterial consortia

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Authors: Riffat Kalsoom, Qurat-Ul-Ain Javed

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Optical and dielectric properties of lithium niobates have made them the fascinating materials to be used in optical industry for device formation such as Q and optical switching. Synthesis of lithium niobates was carried out by solvothermal process with and without temperature fluctuation at 200°C for 4 hrs, and behavior of properties for different durations was also examined. Prepared samples of LiNbO₃ were examined in a way as crystallographic phases by using XRD diffractometer, morphology by scanning electron microscope (SEM), absorption by UV-Visible Spectroscopy and dielectric measurement by impedance analyzer. A structural change from trigonal to spherical shape was observed by changing the time of reaction. Crystallite size decreases by the temperature fluctuation and increasing reaction time. Band gap decreases whereas dielectric constant and dielectric loss was increased with increasing time of reaction. Trend of AC conductivity is explained by Joschner’s power law. Due to these significant properties, it finds its applications in devices, such as cells, Q switching and optical switching for laser and gigahertz frequencies, respectively and these applications depend on the industrial demands.

Keywords: lithium niobates, renewable energy devices, controlled structure, temperature fluctuations

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Authors: E.A. Kuchma

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Photodynamic therapy (PDT) is considered an alternative and minimally invasive cancer treatment modality compared to chemotherapy and radiation therapy. PDT includes three main components: a photosensitizer (PS), oxygen, and a light source. PS is injected into the patient's body and then selectively accumulates in the tumor. However, the light used in PDT (spectral range 400–700 nm) is limited to superficial lesions, and the light penetration depth does not exceed a few cm. The problem of PDT (poor visible light transmission) can be solved by using X-rays. The penetration depth of X-rays is ten times greater than that of visible light. Therefore, X-ray radiation easily penetrates through the tissues of the body. The aim of this work is to develop universal nanocomposites for X-ray photodynamic therapy of deep and superficial tumors using scintillation nanoparticles of gadolinium fluoride (GdF3), doped with Tb3+, coated with a biocompatible coating (PEG) and photosensitizer RB (Rose Bengal). PEG@GdF3:Tb3+(15%) – RB could be used as an effective X-ray, UV, and photoluminescent mediator to excite a photosensitizer for generating reactive oxygen species (ROS) to kill tumor cells via photodynamic therapy. GdF3 nanoparticles can also be used as contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI).

Keywords: X-ray induced photodynamic therapy, scintillating nanoparticle, radiosensitizer, photosensitizer

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Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

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Authors: Ali A. A. Alqarni, Gamal A. Mohamed, Hossam M. Abdallah, Sabrin R. M. Ibrahim

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Phytochemical investigation of the methanolic extract of aerial parts of Tagetes minuta L. (Family: Asteraceae) using different chromatographic techniques led to the isolation of five compounds; ecliptal (1), scopoletin (2), P-hydroxy benzoic acid (3), patuletin (4), and patuletin-7-O-β-D-glucopyranoside (5) (Figure 1). Their structures were established based on physical, chemical, and spectral data [Ultraviolet (UV), Proton ¹H, Carbon thirteen ¹³C, and Heteronuclear Multiple Bond Correlation (HMBC) NMR], as well as Electrospray Ionization Mass Spectroscopy (ESIMS) and comparison with literature data. Their cytotoxic activity was assessed towards human liver hepatocellular carcinoma (HepG2), human breast cancer (MCF-7), and human colon cancer (HCT116) cancer cell lines using sulphorhodamine B (SRB) assay. It is noteworthy that compound 1 demonstrated a significant cytotoxic potential towards HepG2, MCF7, and HCT116 cells with IC₅₀s ranging from 2.74 to 7.01 μM, compared to doxorubicin (IC₅₀ 0.18, 0.60, and 0.20 μM, respectively), whereas compounds 2, 4, and 5 showed moderate cytotoxic potential with IC50s ranging from 11.71 to 35.64 μM. However, 3 was inactive up to a concentration of 100 μM towards the three tested cancer cell lines.

Keywords: Asteraceae, cytotoxicity, metabolites, Tagetes minuta

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Authors: Gabriel Dolabella, Henrique Rangel, Stella Araújo, Carlos Bolonha, Igor de Lazari

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Public security is a common subject on the Brazilian political agenda. The seventh largest economy in the world has high crime and insecurity rates. Specialists try to explain this social picture based on poverty, inequality or public policies addressed to drug trafficking. This excerpt approaches State measures to handle that picture. Therefore, the public security - law enforcement institutions - is at the core of this paper, particularly the relationship among federal and state law enforcement agencies, mainly ruled by a system of urgency. The problems are informal changes on law enforcement management and public opinion collaboration to these changes. Whenever there were huge international events, Brazilian armed forces occupied streets to assure law enforcement - ensuring the order. This logic, considered in the long time, could impact the federal structure of the country. The post-madisonian theorists verify that urgency is often associated to delegation of powers, which is true for Brazilian law enforcement, but here there is a different delegation: States continuously delegate law enforcement powers to the federal government throughout the use of Armed Forces. Therefore, the hypothesis is: Brazil is under a political process of federalization of public security. The political framework addressed here can be explained by the disrespect of legal constraints and the failure of rule of law theoretical models. The methodology of analysis is based on general criteria. Temporally, this study investigates events from 2003, when discussions about the disarmament statute begun. Geographically, this study is limited to Brazilian borders. Materially, the analysis result from the observation of legal resources and political resources (pronouncements of government officials). The main parameters are based on post-madisonianism and federalization of public security can be assessed through credibility and popularity that allow evaluation of this political process of constitutional change. The objective is to demonstrate how the Military Forces are used in public security, not as a random fact or an isolated political event, in order to understand the political motivations and effects that stem from that use from an institutional perspective.

Keywords: public security, governability, rule of law, federalism

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Authors: Vural Erdogan

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We created two-dimensional hexagonal cellular automata to obtain complexity by using simple rules same as Conway’s game of life. Considering the game of life rules, Wolfram's works about life-like structures and John von Neumann's self-replication, self-maintenance, self-reproduction problems, we developed 2-states and 3-states hexagonal growing algorithms that reach large populations through random initial states. Unlike the game of life, we used six neighbourhoods cellular automata instead of eight or four neighbourhoods. First simulations explained that whether we are able to obtain sort of oscillators, blinkers, and gliders. Inspired by Wolfram's 1D cellular automata complexity and life-like structures, we simulated 2D synchronous, discrete, deterministic cellular automata to reach life-like forms with 2-states cells. The life-like formations and the oscillators have been explained how they contribute to initiating self-maintenance together with self-reproduction and self-replication. After comparing simulation results, we decided to develop the algorithm for another step. Appending a new state to the same algorithm, which we used for reaching life-like structures, led us to experiment new branching and fractal forms. All these studies tried to demonstrate that complex life forms might come from uncomplicated rules.

Keywords: hexagonal cellular automata, self-replication, self-reproduction, self- maintenance

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Authors: Mohammad Zahidul Islam Bhuiyan, Shanyong Wang, Scott William Sloan, Daichao Sheng

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Nowadays soil pressure transducers are widely used to measure the soil stress states in laboratory and field experiments. The soil pressure transducers, investigated here, are traditional diaphragm-type earth pressure cells (DEPC) based on strain gauge principle. It is found that the output of these sensors varies with the soil conditions as well as the position of a sensor. Therefore, it is highly recommended to calibrate the pressure sensors based on the similar conditions of their intended applications. The factory calibration coefficients of the EPCs are not reliable to use since they are normally calibrated by applying fluid (a special type of oil) pressure only over load sensing zone, which does not represent the actual field conditions. Thus, the calibration of these sensors is utmost important, and they play a pivotal role for assessing earth pressures precisely. In the present study, TML soil pressure sensor is used to compare its sensitivity under different calibration systems, for example, fluid calibration, and static load calibration with or without soil. The results report that the sensor provides higher sensitivity (more accurate results) under soil calibration system.

Keywords: calibration, soil pressure, earth pressure cell, sensitivity

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Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

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Authors: M. Y. Ismail, M. Inam

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This paper presents the design and analysis of Liquid Crystal (LC) based tunable reflect array antenna with different design configurations within X-band frequency range. The effect of LC volume used for unit cell element on frequency tunability and reflection loss performance has been investigated. Moreover different slot embedded patch element configurations have been proposed for LC based tunable reflect array antenna design with enhanced performance. The detailed fabrication and measurement procedure for different LC based unit cells has been presented. The waveguide scattering parameter measured results demonstrated that by using the circular slot embedded patch elements, the frequency tunability and dynamic phase range can be increased from 180 MHz to 200 MHz and 120° to 124° respectively. Furthermore the circular slot embedded patch element can be designed at 10 GHz resonant frequency with a patch volume of 2.71 mm3 as compared to 3.47 mm3 required for rectangular patch without slot.

Keywords: liquid crystal, tunable reflect array, frequency tunability, dynamic phase range

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Authors: S. Ghalem, M. Mesmoudi, I. Daoudand, H. Allali

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The nitrogen-containing bisphosphonates (N-BPs) are well established as the treatments of choice for disorders of excessive bone resorption, myeloma and bone metastases, and osteoporosis. They inhibit farnesyl pyrophosphate synthase (FFPS), a key enzyme in the mevalonate pathway, resulting in inhibition of the prenylation of small GTP-binding proteins in osteoclasts and disruption of their cytoskeleton, adhesion/spreading, and invasion of cancer cells. A very few examples for synthesis of α-amino bisphosphonates based on several amino acids are known from the literature. In the present work, esters of aminoacid react with ketophsophonate (or their analog acid or acyl) to afford the desired products, α-iminophosphonates. The reaction of imine with dimethyl phosphate in the presence of catalytic amount of I2 give ester of α-aminobisphosphonate as sole product in good yield. Finally, we used computational docking methods to predict how several α-aminobisphosphonates bind to FPPS and how R and X influence. Pamidronate, β-aminobisphosphonate already marketed, was used as reference. These results are of interest since they represent a new and simple way to sythesize α-aminobisphosphonates with a free COOH group increased by R2 functionalisable and opening up the possibility of using the molecular docking to facilitate the design of other, novel FFPS inhibitors.

Keywords: drug research, cancer, α-amino bisphosphonates, molecular docking

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Authors: Mike T. Wei, Douglas N. Mintz, Lisa A. Mandl, Arielle W. Fein, Jayme C. Burket, Yuo-Yu Lee, Wei-Ti Huang, Vivian P. Bykerk, Mark P. Figgie, Edward F. Di Carlo, Bruce N. Cronstein, Susan M. Goodman

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Background/Purpose: Rheumatoid arthritis (RA) patients have excellent total hip arthroplasty (THA) survival, and methotrexate (MTX), an anti-inflammatory disease modifying drug which may affect bone reabsorption, may play a role. The purpose of this study is to determine the diagnosis leading to revision THA (rTHA) in RA patients and to assess the association of radiographic lucency with MTX use. Methods: All patients with validated diagnosis of RA in the institution’s THA registry undergoing rTHA from May 2007 - February 2011 were eligible. Diagnosis leading to rTHA and medication use was determined by chart review. Osteolysis was evaluated on available radiographs by measuring maximum lucency in each Gruen zone. Differences within RA patients with/without MTX in osteolysis, demographics, and medications were assessed with chi-squared, Fisher's exact tests or Mann-Whitney U tests as appropriate. The error rate for multiple comparisons of lucency in the different Gruen zones was corrected via false discovery rate methods. A secondary analysis was performed to determine differences in diagnoses leading to revision between RA and matched OA controls (2:1 match by sex age +/- 5 years). OA exclusion criteria included presence of rheumatic diseases, use of MTX, and lack of records. Results: 51 RA rTHA were identified and compared with 103 OA. Mean age for RA was 57.7 v 59.4 years for OA (p = 0.240). 82.4% RA were female v 83.5% OA (p = 0.859). RA had lower BMI than OA (25.5 v 28.2; p = 0.166). There was no difference in diagnosis leading to rTHA, including infection (RA 3.9 v OA 6.8%; p = 0.719) or dislocation (RA 23.5 v OA 23.3%; p = 0.975). There was no significant difference in the length of time the implant was in before revision: RA 11.0 v OA 8.8 years (p = 0.060). Among RA with/without MTX, there was no difference in use of biologics (30.0 v 43.3%, p = 0.283), steroids (47.6 v 50.0%, p = 0.867) or bisphosphonates (23.8 v 33.3%, p = 0.543). There was no difference in rTHA diagnosis with/without MTX, including loosening (52.4 v 56.7%, p = 0.762). There was no significant difference in lucencies with MTX use in any Gruen zone. Patients with MTX had femoral stem subsidence of 3.7mm v no subsidence without MTX (p = 0.006). Conclusion: There was no difference in the diagnosis leading to rTHR in RA and OA, although RA trended longer prior to rTHA. In this small retrospective study, there were no significant differences associated with MTX exposure or radiographic lucency among RA patients. The significance of subsidence is not clear. Further study of arthroplasty survival in RA patients is warranted.

Keywords: hip arthroplasty, methotrexate, revision arthroplasty, rheumatoid arthritis

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Authors: Zeyu Zhou, Ziyu Zhao, Xiaochen Yang, Ling AI, Heng Zhai, Stuart Holmes

Abstract:

As a promising sustainable alternative to traditional fossil fuels, fuel cell technology is highly favoured due to its enhanced working efficiency and reduced emissions. In the context of high-temperature fuel cells (operating above 100 °C), the most commonly used proton exchange membrane (PEM) is the Polybenzimidazole (PBI) doped phosphoric acid (PA) membrane. Grafting is a promising strategy to advance PA-doped PBI PEM technology. The existing grafting modification on PBI PEMs mainly focuses on grafting phosphate-containing or alkaline groups onto the PBI molecular chains. However, quaternary ammonium-based grafting approaches face a common challenge. To initiate the N-alkylation reaction, deacidifying agents such as NaH, NaOH, KOH, K2CO3, etc., can lead to ionic crosslinking between the quaternary ammonium group and PBI. Polyvinylpyrrolidone (PVP) is another widely used polymer, the N-heterocycle groups within PVP endow it with a significant ability to absorb PA. Recently, PVP has attracted substantial attention in the field of fuel cells due to its reduced environmental impact and impressive fuel cell performance. However, due to the the poor compatibility of PVP in PBI, few research apply PVP in PA-doped PBI PEMs. This work introduces an innovative strategy to graft PVP onto PBI to form a network-like polymer. Due to the absence of quaternary ammonium groups, PVP does not pose issues related to crosslinking with PBI. Moreover, the nitrogen-containing functional groups on PVP provide PBI with a robust phosphoric acid retention ability. The nuclear magnetic resonance (NMR) hydrogen spectrum analysis results indicate the successful completion of the grafting reaction where N-alkylation reactions happen on both sides of the grafting agent 1,4-bis(chloromethyl)benzene. On one side, the reaction takes place with the hydrogen atoms on the imidazole groups of PBI, while on the other side, it reacts with the terminal amino group of PVP. The XPS results provide additional evidence from the perspective of the element. On synthesized PBI-g-PVP surfaces, there is an absence of chlorine (chlorine in grafting agent 1,4-bis(chloromethyl)benzene is substituted) element but a presence of sulfur element (sulfur element in terminal amino PVP appears in PBI), which demonstrates the occurrence of the grafting reaction and PVP is successfully grafted onto PBI. Prepare these modified membranes into MEA. It was found that during the fuel cell operation, all the grafted membranes showed substantial improvement in maximum current density and peak power density compared to unmodified one. For PBI-g-PVP 30, with a grafting degree of 22.4%, the peak power density reaches 1312 mW cm⁻², marking a 59.6% enhancement compared to the pristine PBI membrane. The improvement is caused by the improved PA binding ability of the membrane after grafting. The AST test result shows that the grafting membranes have better long-term durability and performance than unmodified membranes attributed to the presence of added PA binding sites, which can effectively prevent the PA leaching caused by proton migration. In conclusion, the test results indicate that grafting PVP onto PBI is a promising strategy which can effectively improve the fuel cell performance.

Keywords: fuel cell, grafting modification, PA doping ability, PVP

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Authors: R. A. Lahmer, A. P. Williams, S. Townsend, S. Baker, D. L. Jones

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Chitosan-arginine (Ch-arg) has been proposed as an anti-microbial agent to reduce the proliferation of spoilage and pathogenic bacteria within meat products destined for human consumption. In the current experiment its use as an antimicrobial packaging material was examined. Two different concentrations of chitosan-arginine (0.05 and 0.15 % w/w) were blended into a cellulose film (Ch-arg film). When placed in contact with chicken and beef juice inoculated with a lux-marked strain of E. coli O157, the film incorporating the highest Ch-arg concentration resulted in a small reduction of E. coli O157 in chicken juice; however, there was no effect of the Ch-arg film on E. coli O157 in beef juice. The lack of observed effect in the beef juice experiment we ascribe to insufficient surface-to-surface contact between the film and the bacteria in the beef juice and the greater presence of other Ch-arg reactive components in the juice (e.g. fats, blood cells). Results suggest that, in combination with other anti microbials, Ch-arg packaging may offers some potential for limiting the growth of pathogenic bacteria in foodstuffs; however, further research is needed to enhance their anti-microbial performance.

Keywords: cross-contamination, foodborne pathogen, polymer film, shelf life

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Authors: Daniel J. Patricio Jiménez

Abstract:

Digital reality demands new ways of thinking, flexibility in learning, acquisition of new competencies, visualizing reality under new approaches, generating open spaces, understanding dimensions in continuous change, etc. We need inclusive growth, where colors are not lacking, where lights do not give a distorted reality, where science is not half-truth. In carrying out this study, the documentary or bibliographic collection has been taken into account, providing a reflective and analytical analysis of current reality. In this context, deductive and inductive methods have been used on different multidisciplinary information sources. Women today and tomorrow are a strategic element in science and arts, which, under the umbrella of sustainability, implies ‘meeting current needs without detriment to future generations’. We must build new scenarios, which qualify ‘the feminine and the masculine’ as an inseparable whole, encouraging cooperative behavior; nothing is exclusive or excluding, and that is where true respect for diversity must be based. We are all part of an ecosystem, which we will make better as long as there is a real balance in terms of gender. It is the time of ‘the lifting of the veil’, in other words, it is the time to discover the pseudonyms, the women who painted, wrote, investigated, recorded advances, etc. However, the current reality demands much more; we must remove doors where they are not needed. Mass processing of data, big data, needs to incorporate algorithms under the perspective of ‘the feminine’. However, most STEM students (science, technology, engineering, and math) are men. Our way of doing science is biased, focused on honors and short-term results to the detriment of sustainability. Historically, the canons of beauty, the way of looking, of perceiving, of feeling, depended on the circumstances and interests of each moment, and women had no voice in this. Parallel to science, there is an under-representation of women in the arts, but not so much in the universities, but when we look at galleries, museums, art dealers, etc., colours impoverish the gaze and once again highlight the gender gap and the silence of the feminine. Art registers sensations by divining the future, science will turn them into reality. The uniqueness of the so-called new normality requires women to be protagonists both in new forms of emotion and thought, and in the experimentation and development of new models. This will result in women playing a decisive role in the so-called "5.0 society" or, in other words, in a more sustainable, more humane world.

Keywords: art, digitalization, gender, science

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Authors: Elmira Davasaz Tabrizi, Müşteba Sevil, Ercan Arican

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In recent decades, there has been a sharp increase in the prevalence of several unrelated chronic diseases. The use of long-term antibiotics for chronic illnesses is increasing. The antibiotic resistance occurrence and its relationship with host microbiomes are still unclear. Properties of the identifying antibodies have been the focus of chronic disease research, such as prostatitis or autoimmune. The immune system is made up of a complicated but well-organized network of cell types that constantly monitor and maintain their surroundings. The regulated homeostatic interaction between immune system cells and their surrounding environment shapes the microbial flora. Researchers believe that the disappearance of special bacterial species from our ancestral microbiota might have altered the body flora that can cause a rise in disease during the human life span. This unpleasant pattern demonstrates the importance of focusing on discovering and revealing the root causes behind the disappearance or alteration of our microbiota. In this review, we gathered the results of some studies that reveal changes in the diversity and quantity of microorganisms that may affect chronic and autoimmune diseases. Additionally, a Ph.D. thesis that is still in process as Metagenomic studies in chronic prostatitis samples is mentioned.

Keywords: metagenomic, autoimmune, prostatitis, microbiome

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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: Rory Anthony Hutagalung, Leonardus Widjaja

Abstract:

Microalgae Meyerella planktonica is a potential biofuel source because it can grow in bulk in either autotrophic or heterotrophic condition. However, the quantitative growth of this algal type is still low as it tends to precipitates on the bottom. Beside, the lipid concentration is still low when grown in autotrophic condition. In contrast, heterotrophic condition can enhance the lipid concentration. The combination of autotrophic condition and agitation treatment was conducted to increase the density of the culture. On the other hand, a heterotrophic condition was set up to raise the lipid production. A two-stage experiment was applied to increase the density at the first step and to increase the lipid concentration in the next step. The autotrophic condition resulted higher density but lower lipid concentration compared to heterotrophic one. The agitation treatment produced higher density in both autotrophic and heterotrophic conditions. The two-stage experiment managed to enhance the density during the autotrophic stage and the lipid concentration during the heterotrophic stage. The highest yield was performed by using 0.4% v/v glycerol as a carbon source (2.9±0.016 x 106 cells w/w) attained 7 days after the heterotrophic stage began. The lipid concentration was stable starting from day 7.

Keywords: agitation, glycerol, heterotrophic, lipid productivity, Meyerella planktonica

Procedia PDF Downloads 334

Authors: M. N. Hanina, M. Hairul Shahril, I. Ismatul Nurul Asyikin, A. K. Abdul Jalil, M. R. Salina, M. R. Maryam, M. Rosfarizan

Abstract:

The extracellular proteins secreted by bacteria may be increased in stressful surroundings, such as in the presence of antibiotics. It appears that many antibiotics, when used at low concentrations, have in common the ability to activate or repress gene transcription, which is distinct from their inhibitory effect. There have been comparatively few studies on the potential of antibiotics as a specific chemical signal that can trigger a variety of biological functions. Therefore, this study was carried out to determine the effect of Streptomycin Sulfate in regulating extracellular proteins secreted by Bacillus subtilis ATCC21332. Results of Microdilution assay showed that the Minimum Inhibition Concentration (MIC) of Streptomycin Sulfate on B. subtilis ATCC21332 was 2.5 mg/ml. The bacteria cells were then exposed to Streptomycin Sulfate at concentration of 0.01 MIC before being further incubated for 48h to 72 h. The extracellular proteins secreted were then isolated and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Proteins profile revealed that three additional bands with approximate sizes of 30 kDa, 22 kDa and 23 kDa were appeared for the treated bacteria with Streptomycin Sulfate. Thus, B. subtilis ATCC21332 in stressful condition with the presence of Streptomycin Sulfate at low concentration could induce the extracellular proteins secretion.

Keywords: Bacillus subtilis ATCC21332, streptomycin sulfate, extracellular proteins, antibiotics

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Authors: Nicole Scott, Emily Dwyer, Cara Patrissy, Samantha Bonventre, Lina Begdache

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Across North America, the use and abuse of Attention Deficit Hyperactivity Disorder (ADHD) medication, cannabis, nicotine, and other psychoactive substances across college campuses have become an increasingly prevalent problem. Students frequently use these substances to aid their studying or deal with their mental health issues. However, it is still unknown what psychoactive substances are likely to be abused when college students illicitly use ADHD medication. In addition, it is not clear which psychoactive substance is associated with mental distress. Thus, the purpose of this study is to fill these gaps by assessing the use of different psychoactive substances when illicit ADHD medication is used; and how this association relates to mental stress. A total of 702 undergraduate students from different college campuses in the U.S. completed an anonymous survey distributed online. Data were self-reported on demographics, the use of ADHD medications, cannabis, nicotine, other psychoactive drugs, and mental distress, and feelings and opinions on the use of illicit study drugs were all included in the survey. Mental distress was assessed using the Kessler Psychological Distress 6 Scale. Data were analyzed in SPSS, Version 25.0, using Pearson’s Correlation Coefficient. Our results show that use of ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent), there were both statistically significant positive and negative correlations to specific psychoactive substances and their corresponding frequencies. Along the same lines, ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent) had statistically significant positive and negative correlations to specific mental distress experiences. As these findings are combined, a vicious loop can initiate a cycle where individuals who abuse psychoactive substances may or may not be inclined to use other psychoactive substances. This may later inhibit brain functions in those main areas of the brain stem, amygdala, and prefrontal cortex where this vicious cycle may or may not impact their mental distress. Addressing the impact of study drug abuse and its potential to be associated with further substance abuse may provide an educational framework and support proactive approaches to promote awareness among college students.

Keywords: stimulant, depressant, nicotine, ADHD medication, psychoactive substances, mental health, illicit, ecstasy, adrenochrome

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