Search results for: competitive binding assay

Authors: Avinash Vellore Sunder, Shikha Shah, Pramod P. Wangikar

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The enzymatic conversion of nitriles to carboxylic acids by nitrilases has gained significance in the green synthesis of several pharmaceutical precursors and fine chemicals. While nitrilases have been characterized from different sources, the industrial application requires the identification of nitrilases that possess higher substrate tolerance, wider specificity and better thermostability, along with the development of an efficient bioprocess for producing large amounts of nitrilase. To produce large amounts of nitrilase, we developed a fed-batch fermentation process on defined media for the high cell density cultivation of E. coli cells expressing the well-studied nitrilase from Alcaligenes fecalis. A DO-stat feeding approach was employed combined with an optimized post-induction strategy to achieve nitrilase titer of 2.5*105 U/l and 78 g/l dry cell weight. We also identified 16 novel nitrilase sequences from genome mining and analysis of substrate binding residues. The nitrilases were expressed in E. coli and their biocatalytic potential was evaluated on a panel of 22 industrially relevant nitrile substrates using high-throughput screening and HPLC analysis. Nine nitrilases were identified to exhibit high activity on structurally diverse nitriles including aliphatic and aromatic dinitriles, heterocyclic, -hydroxy and -keto nitriles. With fed-batch biotransformation, whole-cell Zobelia galactanivorans nitrilase achieved yields of 2.4 M nicotinic acid and 1.8 M isonicotinic acid from 3-cyanopyridine and 4-cyanopyridine respectively within 5 h, while Cupravidus necator nitrilase enantioselectively converted 740 mM mandelonitrile to (R)–mandelic acid. The nitrilase from Achromobacter insolitus could hydrolyze 542 mM iminodiacetonitrile in 1 h. The availability of highly active nitrilases along with bioprocesses for enzyme production expands the toolbox for industrial biocatalysis.

Keywords: biocatalysis, isonicotinic acid, iminodiacetic acid, mandelic acid, nitrilase

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Authors: Syed Atif Hassan, Luv Mehta, Syed Asif Hassan

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Hit song science is a field of investigation wherein machine learning techniques are applied to music tracks in order to extract such features from audio signals which can capture information that could explain the popularity of respective tracks. Record companies invest huge amounts of money into recruiting fresh talents and churning out new music each year. Gaining insight into the basis of why a song becomes popular will result in tremendous benefits for the music industry. This paper aims to extract basic musical and more advanced, acoustic features from songs while also taking into account external factors that play a role in making a particular song popular. We use a dataset derived from popular Spotify playlists divided by genre. We use ten genres (blues, classical, country, disco, hip-hop, jazz, metal, pop, reggae, rock), chosen on the basis of clear to ambiguous delineation in the typical sound of their genres. We feed these features into three different classifiers, namely, SVM with RBF kernel, a deep neural network, and a recurring neural network, to build separate predictive models and choosing the best performing model at the end. Predicting song popularity is particularly important for the music industry as it would allow record companies to produce better content for the masses resulting in a more competitive market.

Keywords: classifier, machine learning, music tracks, popularity, prediction

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Authors: Klio Monokrousou, Maria Giannopoulou

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Urban areas, as they have been developed and operate today, are areas of accumulation of a significant amount of people and a large number of activities that generate desires and reasons for traveling. The territorial expansion of the cities as well as the need to preserve the importance of the central city areas lead to the continuous increase of transportation needs which in the limited urban space results in creating serious traffic and operational problems. The modern perception of urban planning is directed towards more holistic approaches and integrated policies that make it economically competitive, socially just and more environmentally friendly. Over the last 25 years, the goal of sustainable transport development has been central to the agenda of any plan or policy for the city. The modern planning of urban space takes into account the economic and social aspects of the city and the importance of the environment to sustainable urban development. In this context, the European Union promotes direct or indirect related interventions according to the cohesion and environmental policies; many countries even had the chance to actually test them. This paper is part of a wider research still in progress and it explores the methods and processes that have been developed towards this direction and presents a review and systematic presentation of this work. The ultimate purpose of this research is to effectively use this review to create a decision making methodological framework which can be the basis of a useful operational tool for sustainable urban planning.

Keywords: methods, sustainable urban development, urban mobility, methodological framework

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Authors: Siriporn Okonogi, Pimpak Phumat, Sakornrat Khongkhunthian

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Piper betle has been extensively reported for various pharmacological effects including antimicrobial activity. 4-Allylpyrocatechol (AC) is a principle active compound found in P. betle. However, AC has a problem of solubility in water. The aims of the present study were to prepare AC loaded polymeric micelles for enhancing its water solubility and to evaluate its anti-biofilm activity against oral phathogenic bacteria. AC was loaded in polymeric micelles (PM) of Pluronic F127 by using thin film hydration method to obtain AC loaded PM (PMAC). The results revealed that AC in the form of PMAC possessed high water solubility. PMAC particles were characterized using a transmission electron microscope and photon correlation spectroscopy. Determination of entrapment efficiency (EE) and loading capacity (LC) of PMAC was done by using high-performance liquid chromatography. The highest EE (86.33 ± 14.27 %) and LC (19.25 ± 3.18 %) of PMAC were found when the weight ratio of polymer to AC was 4 to 1. At this ratio, the particles showed spherical in shape with the size of 38.83 ± 1.36 nm and polydispersity index of 0.28 ± 0.10. Zeta potential of the particles is negative with the value of 16.43 ± 0.55 mV. Crystal violet assay and confocal microscopy were applied to evaluate the effects of PMAC on Streptococcus mutans biofilms using chlorhexidine (CHX) as a positive control. PMAC contained 1.5 mg/mL AC could potentially inhibit (102.01 ± 9.18%) and significantly eradicate (85.05 ± 2.03 %) these biofilms (p < 0.05). Comparison with CHX, PMAC showed slightly similar biofilm inhibition but significantly stronger biofilm eradication (p < 0.05) than CHX. It is concluded that PMAC can enhance water solubility and anti-biofilm activity of AC.

Keywords: pluronic, polymeric micelles, solubility, 4-allylpyrocathecol, Streptococcus mutans, anti-biofilm

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Authors: Asma Ansari, Afsheen Aman, Shah Ali Ul Qader

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In the past few years, numerous concerns have been raised against increased bacterial resistance towards effective drugs and become a debated issue all over the world. With the emergence of drug resistant pathogens, the interaction of natural antimicrobial compounds and antibacterial nanoparticles has emerged as a potential candidate for combating infectious diseases. Microbial diversity in the biome provides an opportunity to screen new species which are capable of producing large number of antimicrobial compounds. Among these antimicrobial compounds, bacteriocins are highly specific and efficient antagonists. A combination of bacteriocin along with nanoparticles could prove to be more potent due to broadened antibacterial spectrum with possibly lower doses. In the current study, silver nanoparticles were synthesized through biological reduction using various isolated bacterial, fungal and yeast strains. Spectroscopy and scanning electron microscopy (SEM) was performed for the confirmation of nanoparticles. Bacteriocin was characterized and purified to homogeneity through gel permeation chromatography. The estimated molecular weight of bacteriocin was 10 kDa. Amino acid analysis and N-terminal sequencing revealed the novelty of the protein. Then antibacterial potential of silver nanoparticles and broad inhibitory spectrum bacteriocin was determined through agar well diffusion assay. These synthesized bacteriocin-Nanoparticles exhibit a good potential for clinical applications as compared to bacteriocin alone. This combination of bacteriocin with nanoparticles will be used as a new sort of biocide in the field of nano-proteomics. The advancement of nanoparticles-mediated drug delivery system will open a new age for rapid eradication of pathogens from biological systems.

Keywords: BAC-IB17, multidrug resistance, purification, silver nanoparticles

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Authors: Alaa E. El-sisi, Sherin Zakaria

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Rebamipide is an antiulcer drug with unique properties such as anti-inflammatory action. It induces endogenous prostaglandin e2 (PGE2). PGE2 is considered as a potent physiological suppressor of liver fibrosis. Aim of study: This study investigated the effect of rebamipide on hepatic fibrosis. Material and Method: Hepatic fibrosis was induced by intraperitoneal injections (IP) injection of CCl4 (0.45 mL/kg) in corn oil 1:5 twice a week for 4 weeks. Rats were divided into four groups as follow: Group 1 treated with CCL4 only, group 2 and 3 treated with CCL4 and rebamipide 60 mg/kg/day (group2) or 100 mg/kg/day (group3), and the fourth group was considered as control group and treated with vehicles. ALT, AST, and Bilirubin were assayed in serum. Antioxidant markers such as malondialdhyde (MDA) and superoxide dismutase (SOD) and fibrotic markers such as hyaluronic acid (HA) and procollagen-III (procol-III) were evaluated in liver tissues. IL-10 as well as PGE2 were also assayed in liver tissues. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen precipitation in liver tissues was visualized using masson trichrom stain. Results: Rebamipide inhibit CCL4 induced increase in ALT and AST significantly (p < 0.05). Rebamipide exerted an antioxidant effect as it inhibits CCL4 induced increased MDA level and decreased SOD activity. Fibrotic markers assay revealed that repamipide (60 or 100 mg/kg/day) decreased the level of procol-III and HA compared to CCl4 (p < 0.05). Oral administration of Rebamipide was associated with a significant increase (p < 0.05) of PGE2 and IL-10. Rebamipide especially at the dose of (100 mg/kg/day) restores liver histology structure and abolish collagen precipitation in liver tissues. Conclusion: Rebamipide retards hepatic fibrosis induced by CCL4 may be through the induction of PGE2 level.

Keywords: fibrotic markers, hepatic fibrosis, PGE2, rebamipide

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Authors: Amir Saber Gharamaleki, Beitollah Alipour, Zeinab Faghfoori, Ahmad YariKhosroushahi

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Colorectal cancer (CRC) is one of the most prevalent cancers and intestinal microbial community plays an important role in colorectal tumorigenesis. Probiotics have recently been assessed as effective anti-proliferative agents and thus this study was performed to examine whether CRC undergo apoptosis by treating with isolated Iranian native dairy yeast, Kluyveromyces marxianus YAS, secretion metabolites. The cytotoxicity assessments on cells (HT-29, Caco-2) were accomplished through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as qualitative DAPI (4',6-diamidino-2-phenylindole staining) and quantitative (flow cytometry assessments) evaluations of apoptosis. To evaluate the main mechanism of apoptosis, Real time PCR method was applied. Kluyveromyces marxianus YAS secretions (IC50) showed significant cytotoxicity against HT-29 and Caco-2 cancer cell lines (66.57 % and 66.34 % apoptosis) similar to 5-Fluorouracil (5-FU) while apoptosis only was developed in 27.57 % of KDR normal cells. The prophylactic effects of Kluyveromyces marxianus (PTCC 5195), as a reference yeast, was not similar to Kluyveromyces marxianus YAS indicating strain dependency of bioactivities on CRC disease prevention. Based on real time PCR results, the main cytotoxicity is related to apoptosis phenomenon and the core related mechanism is depended on the overexpression of BAX, CASP 9, CASP 8 and CASP 3 inducing apoptosis genes. However, several investigations should be conducted to precisely determine the effective compounds to be used as anticancer therapeutics in the future.

Keywords: anticancer, anti-proliferative, apoptosis, cytotoxicity, yeast

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Authors: Salise Oktay, Nilgün Kizilcan, Başak Bengü

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At present, formaldehyde based adhesives such as urea formaldehyde (UF), melamine formaldehyde (MF), melamine – urea formaldehyde (MUF), etc. are mostly used in wood based panel industry because of their high reactivity, chemical versatility, and economic competitiveness. However, formaldehyde based wood adhesives are produced from non- renewable resources. Hence, there has been a growing interest in the development of environment friendly, economically competitive, bio-based wood adhesives in order to meet wood based panel industry requirements. In this study, as formaldehyde free adhesive, Mimosa tannin, starch, sugar based wood adhesivewas synthesized. Citric acid and tartaric acid were used as hardener for the resin system. Solid content, viscosity, and gel time analyzes of the prepared adhesive were performed in order to evaluate the adhesive processability. FTIR characterization technique was used to elucidate the chemical structures of the cured adhesivesamples. In order to evaluate the performance of the prepared bio-based resin formulation, particleboards were produced in a laboratory scale, and mechanical, physical properties of the boards were investigated. Besides, the formaldehyde contents of the boards were determined by using the perforator method. The obtained results revealed that the developed bio-based wood adhesive formulation can be a good potential candidate to use wood based panel industry with some developments.

Keywords: bio-based wood adhesives, mimosa tannin, corn starch, sugar, polycarboxyclic acid

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Authors: Tahani Amutairi, Paul May, Neil Allan

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Many properties of semiconductor materials (mechanical, electronic, magnetic, and optical) can be significantly modified by introducing a point defect. Diamond offers extraordinary properties as a semiconductor, and doping seems to be a viable method of solving the problem associated with the fabrication of diamond-based electronic devices in order to exploit those properties. The dopants are believed to play a significant role in reducing the energy barrier to conduction and controlling the mobility of the carriers and the resistivity of the film. Although it has been proven that the n-type diamond semiconductor can be obtained with phosphorus doping, the resulting ionisation energy and mobility are still inadequate for practical application. Theoretical studies have revealed that this is partly because the effects of the many phosphorus atoms incorporated in the diamond lattice are compensated by acceptor states. Using spin-polarised hybrid density functional theory and a supercell approach, we explored the effects of bonding one N atom to a P in adjacent substitutional sites in diamond. A range of hybrid functional, including HSE06, B3LYP, PBE0, PBEsol0, and PBE0-13, were used to calculate the formation, binding, and ionisation energies, in order to explore the solubility and stability of the point defect. The equilibrium geometry and the magnetic and electronic structures were analysed and presented in detail. The defect introduces a unique reconstruction in a diamond where one of the C atoms coordinated with the N atom involved in the elongated C-N bond and creates a new bond with the P atom. The simulated infrared spectra of phosphorus-nitrogen defects were investigated with different supercell sizes and found to contain two sharp peaks at the edges of the spectrum, one at a high frequency 1,379 cm⁻¹ and the second appearing at the end range, 234 cm⁻¹, as obtained with the largest supercell (216).

Keywords: DFT, HSE06, B3LYP, PBE0, PBEsol0, PBE0-13

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Authors: Amita Jain, Shantanu Prakash, Suruchi Shukla

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Introduction: Acute encephalitis syndrome (AES) is a complex multi etiology syndrome posing a great public health problem in the northern part of India. Japanese encephalitis (JE) virus is an established etiology of AES in this region. Recently, Scrub typhus (ST) is being recognized as an emerging aetiology of AES in JE endemic belt. This study was conducted to establish the direct evidence of Central nervous system invasion by Orientia tsutsugamushi leading to AES. Methodology: A total of 849 cases with clinical diagnosis of AES were enrolled from six districts (Deoria and its adjoining area) of the traditional north Indian Japanese encephalitis (JE) belt. Serum and Cerebrospinal fluid samples were collected and tested for major agent causing acute encephalitis. AES cases either positive for anti-ST IgM antibodies or negative for all tested etiologies were investigated for ST-DNA by real-time PCR. Results: Of these 505 cases, 250 patients were laboratory confirmed for O. tsutsugamushi infection either by anti-ST IgM antibodies positivity (n=206) on serum sample or by ST-DNA detection by real-time PCR assay on CSF sample (n=2) or by both (n=42).Total 29 isolate could be sequenced for 56KDa gene. Conclusion: All the strains were found to cluster with Gilliam strains. The majority of the isolates showed a 97–99% sequence similarity with Thailand and Cambodian strains. Gilliam strain of O.tsusugamushi is an emerging as one of the major aetiologies leading to AES in northern part of India.

Keywords: acute encephalitis syndrome, O. tsutsugamushi, Gilliam strain, North India, cerebrospinal fluid

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Authors: Noha Hamie Haidar

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The purpose of this case study was to explore faculty attitudes toward online learning in a Lebanese Higher Education Institution (HEI). The research problem addressed the disinterest among faculty at the Arts, Sciences, and Technology University of Lebanon (AUL) in enhancing learning using online technology. The research questions for the study examined the attitudes of the faculty toward applying online learning and the extent of the faculty readiness to adopt this technological change. A qualitative case study design was used that employed multiple sources of information including semi-structured interviews and existing literature. The target population was AUL faculty including full-time instructors and administration (n=25). Data analysis was guided by the lens of Kanter’s theoretical approach, which focused on faculty’s awareness, desire, knowledge, ability, and reinforcement model (ADKAR) for adopting change. Key findings indicated negative impressions concerning online learning such as authority (ministry of education, culture, and rules); and change (increased enrollment and different teaching styles). Yet, within AUL’s academic environment, the opportunity for the adoption of online learning was identified; faculty showed positive elements, such as the competitive advantage to first enter the Lebanese Market, and higher student enrollment. These results may encourage AUL’s faculty to adopt online learning and to achieve a positive social change by expanding the ability of students in HEIs to compete globally.

Keywords: faculty, higher education, technology, online learning

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Authors: Ji Won Kim, Moo Yeol Lee, Keon Wook Kang

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GV-1001, 16 amino acid fragment of human telomerase reverse transcriptase catalytic subunit (hTERT), has been developed as an injectable cancer vaccine for many types of solid tumors showing high-level of telomerase activity. In the present study, we evaluated the anti-cancer effect of GV-1001 on androgen-receptor-positive prostate cancer. Two signaling pathways, Gs-adenylate cyclase-cAMP and Gq-IP3-Ca2+ pathways play a central role in GnRH receptor (GnRHR)-mediated activities. We found that leuprolide acetate (LA) mainly acted on Gq-mediated Ca2+ signaling, while GV-1001 preferentially acted on cAMP signaling; and both the effects were counteracted by cetrorelix, a GnRHR antagonist. We further tested whether GV-1001 affects tumor growth of human prostate cancer cells in vivo. Prostate tumor xenografts were established using LNCap, androgen receptor-positive prostate cancer cells, and the nude mice bearing tumors were subcutaneously injected with GV-1001 (0.01, 0.1, 1, 10 microg/kg/day) and LA (0.01 microg/kg/day) for 2 weeks. GV-1001 (1 and 10 microg/kg/day) significantly inhibited tumor growth of LNCap xenografts. Interestingly, mRNA expression of MMP2 and MMP9 was significantly suppressed by GV-1001 injection, but not by LA administration. Boyden chamber assay revealed that GV-1001 potently inhibited cell migration of LNCap. Our finding suggests that GV-1001 as a novel GnRHR ligand, has anti-proliferative and anti-migratory effects on androgen receptor-positive prostate cancer cells.

Keywords: GV-1001, GnRH, hTERT, prostate cancer

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Authors: Mona T. Kashef, Omneya M. Helmy

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Multidrug resistant (MDR) bacteria have become a significant public health threat. The prevalence rates, of Gram negative MDR bacteria, are in continuous increase. However, few data are available about these resistant strains. Since, third generation cephalosporins are one of the most commonly used antimicrobials, we set out to investigate the prevalence, different mechanisms and clonal relatedness of multidrug resistance among third generation resistant Gram negative clinical isolates. A total of 114 Gram negative clinical isolates, previously characterized as being resistant to at least one of 3rd generation cephalosporins, were included in this study. Each isolate was tested, using Kirby Bauer disk diffusion method, against its assigned categories of antimicrobials. The role of efflux pump in resistance development was tested by the efflux pump inhibitor-based microplate assay using chloropromazine as an inhibitor. Detecting different aminoglycosides, β-lactams and quinolones resistance genes was done using polymerase chain reaction. The genetic diversity of MDR isolates was investigated using Random Amplification of Polymorphic DNA technique. MDR phenotype was detected in 101 isolates (89%). Efflux pump mediated resistance was detected in 49/101 isolates. Aminoglycosides resistance genes; armA and aac(6)-Ib were detected in one and 53 isolates, respectively. The aac(6)-Ib-cr allele, that also confers resistance to floroquinolones, was detected in 28/53 isolates. β-lactam resistance genes; blaTEM, blaSHV, blaCTX-M group 1 and group 9 were detected in 52, 29, 61 and 35 isolates, respectively. Quinolone resistance genes; qnrA, qnrB and qnrS were detectable in 2, 14, 8 isolates respectively, while qepA was not detectable at all. High diversity was observed among tested MDR isolates. MDR is common among 3rd generation cephalosporins resistant Gram negative bacteria, in Egypt. In most cases, resistance was caused by different mechanisms. Therefore, new treatment strategies should be implemented.

Keywords: gram negative, multidrug resistance, RAPD typing, resistance genes

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Authors: R. Posia, J. Mistry, K. Kamani

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The health screening of laboratory rodents is essential for ensuring animal health and the validity of biomedical research data. Routine health monitoring is necessary to verify the effectiveness of biosecurity and the specific pathogen free (SPF) status of the colony. The present screening was performed in barrier maintained rat (Rattus norvegicus) colony. Rats were maintained under a controlled environment and strict biosecurity in the facility. The screening was performed on quarterly bases from randomly selected animals from breeding and or maintenance colonies. Selected animals were subject to blood collection under isoflurane anaesthesia. Serum was separated from the collected blood and stored samples at -60 ± 10 °C until further use. A total of 88 samples were collected quarterly bases from animals in a year. In the serological test, enzyme-linked immunosorbent assay (ELISA) was used for screening of serum samples against sialodacryoadenitis virus (SDAV), Sendai virus (SV), and Kilham’s rat virus (KRV). ELISA kits were procured from XpressBio, USA. Test serum samples were run along with positive control, negative control serum in 96 well ELISA plates as per the procedure recommended by the vendor. Test ELISA plate reading was taken in the microplate reader. This screening observed that none of the samples was observed positive for the sialodacryoadenitis virus (SDAV), Sendai virus (SV), and Kilham’s rat virus (KRV), indicating that effectiveness of biosecurity practices followed in the rodent colony. The result of serological screening helps us to declare that our rodent colony is specifically pathogen free for these pathogens.

Keywords: biosecurity, ELISA, specific pathogen free, serological screening, serum

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Authors: Andres Calderon

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In order to avoid detection and punishment, cartels have recruited the help of third parties to organize, execute and disguise the anticompetitive practices cartel members have agreed upon. These third parties may take the form of consultancy firms, guilds or professional advisors that do not perform an economic activity in the market where the collusion takes place. This paper takes a look into how national competition authorities and national legislators have dealt with the emergence of the cartels’ facilitators in Latin America. Following the practice of other jurisdictions such as United States (Toys R' Us, Apple), European Union (AC Treuhand), United Kingdom (Replica Kits, Hasbro) and Spain (Urban, Snap-On), some countries (e.g. Argentina, Chile) in Latin America have started to conduct investigations and find antitrust liability in cartels’ facilitators for helping others to violate their national competition laws. Some countries (e.g. Peru and Colombia) have also amended their legislation to amplify the subjective scope of application in order to include cartels’ facilitators. The Latin American case is one of special relevance because public officials are often prone to promote or indulge agreements between competitors in sectors of political interest. A broad definition of cartels’ facilitator, consequently, could lead to the prosecution of punishment of public officials that may hinder the competitive process.

Keywords: anticompetitive practices, cartel, collusion, competition, facilitator, hub and spoke

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Authors: K. K. Kaidarova, Ye. K. Aibuldinov, Zh. B. Iskakova, G. Zh. Alzhanova, S. Zh. Zayrova

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Currently, the existing road infrastructure of Kazakhstan needs the reconstruction of existing highways and the construction of new roads. The solution to this problem can be achieved by replacing traditional building materials with industrial waste, which in their chemical and mineralogical composition are close to natural raw materials and can partially or completely replace some natural binding materials in road construction. In this regard, the purpose of this study is to develop building materials based on the red sludge of the Pavlodar aluminum plant, blast furnace slag of the Karaganda Metallurgical Plant, lime production waste of the Pavlodar Aluminum Plant as a binder for natural loam. Changes in physical and mechanical properties were studied for uniaxial compression strength, linear expansion coefficient, water resistance, and frost resistance of the samples. Nine mixtures were formed with different percentages of these wastes 1-20:25:4; 2-20:25:6; 3-20:25:8; 4-30:30:4; 5-30:30:6; 6-30:30:8; 7-40:35:4; 8-40:35:6; 9-40:35:8 and the mixture identifier were labeled based on the waste content and composition number. The results of strength measurement during uniaxial compression of the samples showed an almost constant increase in strength and amounted to 0.67–3.56 MPa after three days and 3.33–7.38 MPa after 90 days. This increase in compressive strength is a consequence of the addition of lime and becomes more pronounced over time. The water resistance of the developed materials after 90 days was 7.12 MPa, and the frost resistance for the same period was 7.35 MPa. The maximum values of strength determination were shown by a sample of the composition 9-40:35:8. The study of the mineral composition showed that there was no contamination with heavy metals or dangerous substances. It was determined that road materials made of red sludge, blast furnace slag, lime production waste, and natural loam mixture could be used due to their strength indicators and environmental characteristics.

Keywords: production waste, uniaxial compression, water resistance of materials, frost resistance of samples

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Authors: Bernard L. Middleton, Susan P. Cosgrove

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There is an immediate need for alternative anti-herpetic treatment options effective for both primary infections and reoccurring reactivations of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Alternatives currently approved for the purposes of clinical administration includes antivirals and a reduced set of nucleoside analogues. The present article tests a treatment based on a systemic understanding of how the herpes virus affects cell inhibition and breakdown and targets different phases of the viral cycle, including the entry stage, reproductive cross mutation, and cell-to-cell infection. The treatment consisted of five immunotherapeutic core compounds (5CC), which were hypothesized to be capable of neutralizing human monoclonal antibodies. The tested 5CC were noted as being functional in the application of eliminating the DNA synthesis of herpes viral interferon (IFN) - induced cellular antiviral response. They were here found to neutralize antiviral reproduction by blocking cell-to-cell infection. The activity of the 5CC was tested on RC-37 in vitro using an assay plaque reduction and in vivo against HSV-1 and HSV-2. The 50% inhibitory concentration (IC50) of 5CC was 0.0009% for HSV-1 plaque formation and 0.0008% for HSV-2 plaque formation. Further tests were performed to evaluate the susceptibility of HSV-1 and HSV-2 to anti-herpetic drugs in Vero cells after virus entry. There were high-level markers of the 5CC virucidal activity in the viral suspension of HSV-1 and HSV-2. These concentrations of the 5CC are nontoxic and reduced plaque formation by 98.2% for HSV-1 and 93.0% for HSV-2. Virus HSV-1 and HSV-2 titers were reduced significantly by 5CC to the point of being negative, ranging 0.01–0.09 in 72%. The results concluded the 5CC as being an effective treatment option for the herpes simplex virus.

Keywords: synergy pharmaceuticals, herpes treatment, herpes cure, synergy pharmaceuticals treatment

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Authors: Qiang Wang, Hongyang Yu

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Multi-human 3D pose estimation is a challenging task in computer vision, which aims to recover the 3D joint locations of multiple people from multi-view images. In contrast to traditional methods, which typically only use color (RGB) images as input, our approach utilizes both color and depth (D) information contained in RGB-D images. We also employ a transformer-based model as the backbone of our approach, which is able to capture long-range dependencies and has been shown to perform well on various sequence modeling tasks. Our method is trained and tested on the Carnegie Mellon University (CMU) Panoptic dataset, which contains a diverse set of indoor and outdoor scenes with multiple people in varying poses and clothing. We evaluate the performance of our model on the standard 3D pose estimation metrics of mean per-joint position error (MPJPE). Our results show that the transformer-based approach outperforms traditional methods and achieves competitive results on the CMU Panoptic dataset. We also perform an ablation study to understand the impact of different design choices on the overall performance of the model. In summary, our work demonstrates the effectiveness of using a transformer-based approach with RGB-D images for multi-human 3D pose estimation and has potential applications in real-world scenarios such as human-computer interaction, robotics, and augmented reality.

Keywords: multi-human 3D pose estimation, RGB-D images, transformer, 3D joint locations

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Authors: Chloe Fauchon

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In Europe, the right to a fair trial is enshrined in the European Convention on Human Rights, signed in 1950, in its famous Article 6, and, in the field of the European Union, in Article 47 of the Charter of Fundamental Rights, binding since 2009. The right to a fair trial is, therefore, a fundamental right protected by all the relevant treaties. The right to a fair trial is an "umbrella right" which encompasses various sub-rights and principles. Although this right applies in all the proceedings, it gets a special relevance in criminal matters and, particularly, regarding the defendant. In criminal proceedings, the parties are not equal: the accusation is represented by a State-organ, with specific prerogatives, and the defense does not benefit from these specific powers and is often inexperienced in criminal law. Equality of arms, and consequently the right to a fair trial, needs some specific mechanisms to be effective in criminal proceedings. For instance, the defendant benefits from some procedural rights, such as the right to a lawyer, the right to be informed of the charges against them, the right to confront witnesses, and so on. These rights aim to give the defendant the tools to dispute the accusation. The role of the defense is, therefore, very important in criminal matters to avoid unjustified convictions. This specificity of criminal matters justifies that the focus will be put on them during this study. Then this paper will also focus on French and Spanish legal orders. Indeed, if the European Court and Convention on Human Rights are the most famous instruments to protect the right to a fair trial, this right is also guaranteed at a constitutional level in European national legal orders in Europe. However, this enshrinement differs from one country to the other: for instance, in Spain, the right to a fair trial is protected explicitly by the 1978 constitutional text, whereas, in France, it is more of a case-law construction. Nevertheless, this difference between both legal orders does not imply huge variations in the substantive aspect of the right to a fair trial. This can be specifically explained by the submission of both States to the European Convention on Human Rights. This work aims to show that, although the French and Spanish legal orders differ in the way they protect the right to a fair trial, this right eventually has the same substantive meaning in both legal orders.

Keywords: right to a fair trial, constitutional law, French law, Spanish law, European Court of Human Rights

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Authors: Sandy Van Vuuren, Lerato Kose, Annah Moteetee

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Lesotho, a country surrounded by South Africa has one of the highest rates of sexually transmitted infections (STI’s) in the world. In fact, the country ranks third highest with respect to infections related to the human immunodeficiency virus (HIV). Despite the high prevalence of STI’s, treatment has been a challenge due to limited accessibility to health facilities. An estimated 77% of the population lives in rural areas and more than 60% of the country is mountainous. Therefore, many villages remain accessible only by foot or horse-back. Thus, the Basotho (indigenous people from Lesotho) have a rich cultural heritage of plant use. The aim of this study was to determine what plant species are used for the treatment of STI’s and which of these have in vitro efficacy against pathogens such as Candida albicans, Gardnerella vaginalis, Oligella ureolytica, and Neisseria gonorrhoeae. A total of 34 medicinal plants were reported by traditional practitioners for the treatment of STI’s. Sixty extracts, both aqueous and organic (mixture of methanol and dichloromethane), from 24 of the recorded plant species were assessed for antimicrobial activity using the minimum inhibition concentration (MIC) micro-titre plate dilution assay. Neisseria gonorrhoeae (ATCC 19424) was found to be the most susceptible among the test pathogens, with the majority of the extracts (21) displaying noteworthy activity (MIC values ≤ 1 mg/ml). Helichrysum caespititium was found to be the most antimicrobially active species (MIC value of 0.01 mg/ml). The results of this study support, to some extent, the traditional medicinal uses of the evaluated plants for the treatment of STI’s, particularly infections related to gonorrhoea.

Keywords: Africa, Candida albicans, Gardnerella vaginalis, Neisseria gonorrhoeae, Oligella urealytica

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Authors: Sina Mahdavi, Mahdi Asghari Ozma

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Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human Varicella-zoster virus (VZV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on VZV retrovirus infection in MS disease progression. For this study, the keywords "Multiple sclerosis", " Human Varicella-zoster virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles were chosen, studied, and analyzed. Analysis of the amino acid sequences of HNRNPA1 with VZV proteins has shown a 62% amino acid sequence similarity between VZV gE and the PrLD/M9 epitope region (TNPO1 binding domain) of mutant HNRNPA1. A heterogeneous nuclear ribonucleoprotein (hnRNP), which is produced by HNRNPA1, is involved in the processing and transfer of mRNA and pre-mRNA. Mutant HNRNPA1 mimics gE of VZV as an antigen that leads to autoantibody production. Mutant HnRNPA1 translocates to the cytoplasm, after aggregation is presented by MHC class I, followed by CD8 + cells. Of these, antibodies and immune cells against the gE epitopes of VZV remain due to the memory immune response, causing neurodegeneration and the development of MS in genetically predisposed individuals. VZV expression during the course of MS is present in genetically predisposed individuals with HNRNPA1 mutation, suggesting a link between VZV and MS, and that this virus may play a role in the development of MS by inducing an inflammatory state. Therefore, measures to modulate VZV expression may be effective in reducing inflammatory processes in demyelinated areas of MS patients in genetically predisposed individuals.

Keywords: multiple sclerosis, varicella-zoster virus, central nervous system, autoimmunity

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Authors: Reza Alikhani

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This research focuses on the establishment of horizontal cooperation among companies to enhance their operational efficiency and competitiveness. The study proposes an approach to horizontal collaboration, called coalition configuration, which involves partnering companies sharing distribution centers in a network design problem. The paper investigates which coalition should be formed in each distribution center to minimize the total cost of the network. Moreover, potential uncertainties, such as operational and disruption risks, are considered during the collaborative design phase. To address this problem, a two-stage robust optimization model for collaborative distribution network design under surging demand and facility disruptions is presented, along with a column-and-constraint generation algorithm to obtain exact solutions tailored to the proposed formulation. Extensive numerical experiments are conducted to analyze solutions obtained by the model in various scenarios, including decisions ranging from fully centralized to fully decentralized settings, collaborative versus non-collaborative approaches, and different amounts of uncertainty budgets. The results show that the coalition formation mechanism proposes some solutions that are competitive with the savings of the grand coalition. The research also highlights that collaboration increases network flexibility and resilience while reducing costs associated with demand and capacity uncertainties.

Keywords: logistics, warehouse sharing, robust facility location, collaboration for resilience

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Authors: Veepaul Kaur Mann Balwinder Singh

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The COVID-19 had an intense impact on several countries across the world. National governments have imposed widespread restrictions to prevent the growth of this pandemic. The new health competitive scenario induced by the COVID-19 crisis raised many issues on how business activities should be reorganized due to the difficulties of physical interactions with distributors, suppliers and customers. The pandemic has particularly affected the whole selling process because of the relevant issues that emerged in managing physical sale channels and interactions with one another, both in the Business-to-Consumer and in the Business-to-Business markets. Recent research about the appropriate actions and strategies that could help firms overcome the crisis has highlighted the key role of digital expertise that may ensure connections and, thus, help business activities run smoothly. This could be true, especially with the occurrence of strong limitations on physical interactions during the COVID-19 pandemic. The catastrophe changes life publically and economically. People are living alone for following the social distancing norms. In that set-up, Digital Marketing is playing an important role in civilization. Anyone can buy any item, pay bills, transfer money and compare items through Digital Marketing without physical interactions. After COVID-19, people will be more aware of health safety and trust. So, through Digital Marketing, organizations can approach customers and provide good service environments. In such a situation, the online network becomes the most important encouraging for online customers to get in contact with the firm and carry out online selling and purchasing activities around the world.

Keywords: COVID-19, business, digital marketing, online customer

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Authors: Guneet Inder Jit Kaur, Kuldeep Singh, Sunil G. Purohit

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Being a collective phrase for Martial arts that originated from China, Wushu is a form of self-defense and an international (Olympic) sport. Having emerged as a competitive sport, the competitions are generally in two disciplines in Wushu, namely ‘taolu,’ which refers to the forms, and ‘sanda’, which refers to the sparring. Indeed, the competition at the elite level is challenging more mentally than physically. Being masters of their games, excellence at that level is immensely defined by the mental strength characterized by perseverance and passion (grit) along with the psychological wellbeing. Thus, research attempting to understand this relationship is important. The present study was aimed to investigate the relationship between grit and psychological wellbeing among elite Wushu players. The sample of the present study comprised of 35 elite wushu players from India. Out of the 35 players, 16 were females (45.7%), and 19 were males (54.3%), and all had represented at the National and International level. 14 players were from the event of Taolu, and 21 players were from the event of Sanda. The questionnaires used were the short grit scale (Duckworth & Quinn, 2009) and the flourishing scale for psychological wellbeing (Diener et. al., 2009). The statistics included Descriptive (Mean, Standard deviation) and Inferential analysis (correlation). The results highlighted the relationship between the two variables. The insights gained from this study indeed seem immensely helpful in adding to the research of the psychological profile of Elite wushu players and has implications for psychological interventions and mental training for the players.

Keywords: wushu, elite athletes, grit, psychological wellbeing, excellence

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Authors: Sadegh Lotfieblisofla, Arash Khodabakhshi

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Tissue plasminogen activator (tPA) as a serine protease plays an important role in the fibrinolytic system and the dissolution of fibrin clots in human body. The production of this drug in plants such as tobacco could reduce its production costs. In this study, expression of tPA gene and protein targeting to different plant cell compartments, using various signal peptides has been investigated. For high level of expression, Kozak sequence was used after CaMV35S in the beginning of the gene. In order to design the final construction, Extensin, KDEL (amino acid sequence including Lys-Asp-Glu-Leu) and SP (γ-zein signal peptide coding sequence) were used as leader signals to conduct this protein into apoplast, endoplasmic reticulum and cytosol spaces, respectively. Cloned human tPA gene under the CaMV (Cauliflower mosaic virus) 35S promoter and NOS (Nopaline Synthase) terminator into pBI121 plasmid was transferred into tobacco explants by Agrobacterium tumefaciens strain LBA₄₄₀₄. The presence and copy number of genes in transgenic tobacco was proved by Southern blotting. Enzymatic activity of the rt-PA protein in transgenic plants compared to non-transgenic plants was confirmed by Zymography assay. The presence and amount of rt-PA recombinant protein in plants was estimated by ELISA analysis on crude protein extract of transgenic tobacco using a specific antibody. The yield of recombinant tPA in transgenic tobacco for SP, KDEL, Extensin signals were counted 0.50, 0.68, 0.69 microgram per milligram of total soluble proteins.

Keywords: tPA, recombinant, transgenic, tobacco

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Authors: Luciana P. Mazur, Tatiana A. Pozdniakova, Rui A. R. Boaventura, Vitor J. P. Vilar

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The electroplating industry requires a lot of process water, which generates a large volume of wastewater loaded with heavy metals. Two different wastewaters were collected in a company’s wastewater treatment plant, one after the use of zinc in the metal plating process and the other after the use of chromium. The main characteristics of the Zn(II) and Cr(VI) wastewaters are: pH = 6.7/5.9; chemical oxygen demand = 55/<5 mg/L; sodium, potassium, magnesium and calcium ions concentrations of 326/28, 4/28, 11/7 and 46/37 mg/L, respectively; zinc(II) = 11 mg/L and Cr(VI) = 39 mg/L. Batch studies showed that L. hyperborea can be established as a natural cation exchanger for heavy metals uptake mainly due to the presence of negatively charged functional groups in the surface of the biomass. Beyond that, L. hyperborea can be used as a natural electron donor for hexavalent chromium reduction to trivalent chromium at acidic medium through the oxidation of the biomass, and Cr(III) can be further bound to the negatively charged functional groups. The uptake capacity of Cr(III) by the oxidized biomass after Cr(VI) reduction was higher than by the algae in its original form. This can be attributed to the oxidation of the biomass during Cr(VI) reduction, turning other active sites available for Cr(III) binding. The brown macroalgae Laminaria hyperborea was packed in a fixed-bed column in order to evaluate the feasibility of the system for the continuous treatment of the two galvanization wastewaters. The column, with an internal diameter of 4.8 cm, was packed with 59 g of algae up to a bed height of 27 cm. The operation strategy adopted for the treatment of the two wastewaters consisted in: i) treatment of the Zn(II) wastewater in the first sorption cycle; ii) desorption of pre-loaded Zn(II) using an 1.0 M HCl solution; iii) treatment of the Cr(VI) wastewater, taking advantage of the acidic conditions of the column after the desorption cycle, for the reduction of the Cr(VI) to Cr(III), in the presence of the electrons resulting from the biomass oxidation. This cycle ends when all the oxidizing groups are used.

Keywords: biosorption, brown marine macroalgae, zinc, chromium

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Authors: Jie Gao

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The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

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Authors: Amir Halabianfar, Jamshid Razmjoo

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In order to evaluate the competitive effects of Lambsqua on the germination and early growth of two wheat (Triticum aestivum L.) varieties, an experiment was conducted in laboratory conditions in researches of agronomy, College of agriculture, Isfahan University of Technology in 2015. A laboratory experiment was conducted on a factorial arrangement in a randomized complete design with four replications. Testing factors include two wheat cultivars (Flat and Atila -4) and three level of Lambsqua (Chenopodium album) extract (30, 60 and 90 percent) plus control with no extract. Twenty-five seeds of each wheat varieties were placed in petri dish, then the root extract of lambsqua, which was prepared previously at three levels, was poured on the seeds in each petri dish. The result showed that allelopathic effect of Lambsquarter on germination, root, and shoot dry weight of two varieties was highly significant. Among varieties, the Atila–4 showed minimum germination at 60% while the Flat showed minimum germination at 90% concentration. In case of root dry weight, Atila–4 was more suppressed as compared to Flat at 60% concentration but at 90% concentration, the both wheat varieties were reduced non-significantly. Shoot dry weight of Flat were decreased non-significantly concentrations except Atila -4 that was more reduced at 60 % than 90% concentration.

Keywords: allelopathy, Chenopodium album, extract, germination, wheat, early growth

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Authors: Mennani Maha, Attak El Houssain

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Under the massive effect of the Covid-19 health crisis, marked by a loss of competitiveness, a slowdown in growth and an accumulation of the repercussions of socio-economic inequalities, a considerable effort must be combined, in Morocco, to put into perspective macro-political, macro-economic and social opportunities. The development of a new economic and social approach is essential in order to respond to the authenticity of the new development model that will be used by the country. The appropriation of strategies of solidarity and social cohesion constitutes a participatory, competitive and inclusive approach to support the functionalities of the economic, social and political system. Therefore, the search for alternative financial resources has become a necessity to achieve the objectives of sustainable socio-economic growth on the one hand; and to promote, on the other hands, the dynamics, of large scale, social investments. The zakat remains a site of the Islamic economy dedicated to stimulating the bases of a collective adhesion of the population on the economic, as well as on the social level, thanks to a fair and equitable distribution of the zakat funds. However, Morocco is one of the few Muslim countries that has not yet had an institution for collecting and distributing this Islamic duty, which makes it difficult to measure the socio-economic impact of zakat. This theoretical document essentially ensures the development of the crucial utility of institutionalizing zakat in order to reinforce the objectives of social solidarity in Morocco in line with the process of conceptualizing a new development model.

Keywords: zakat, socio-economic development, solidarity, social investment

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Authors: Xin Li, Yan-Rong Guo, Jin-Fang Lin, Yi Feng, Håkan Billig, Ruijin Shao

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Background: Young women with polycystic ovary syndrome (PCOS) have a high risk of developing endometrial carcinoma. There is a need for the development of new medical therapies that can reduce the need for surgical intervention so as to preserve the fertility of these patients. The aim of the study was to describe and discuss cases of PCOS and insulin resistance (IR) women with early endometrial carcinoma while being co-treated with Diane-35 and metformin. Methods: Five PCOS-IR women who were scheduled for diagnosis and therapy for early endometrial carcinoma were recruited. The hospital records and endometrial pathology reports were reviewed. All patients were co-treated with Diane-35 and metformin for 6 months to reverse the endometrial carcinoma and preserve their fertility. Before, during, and after treatment, endometrial biopsies and blood samples were obtained and oral glucose tolerance tests were performed. Endometrial pathology was evaluated. Body weight (BW), body mass index (BMI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), insulin area under curve (IAUC), and homeostasis model assessment of insulin resistance (HOMA-IR) were determined. Results: Clinical stage 1a, low grade endometrial carcinoma was confirmed before treatment. After 6 months of co-treatment, all patients showed normal epithelia. No evidence of atypical hyperplasia or endometrial carcinoma was found. Co-treatment resulted in significant decreases in BW, BMI, TT, FAI, IAUC, and HOMA-IR in parallel with a significant increase in SHBG. There were no differences in the FSH and LH levels after co-treatment. Conclusions: Combined treatment with Diane-35 and metformin has the potential to revert the endometrial carcinoma into normal endometrial cells in PCOS-IR women. The cellular and molecular mechanisms behind this effect merit further investigation.

Keywords: PCOS, progesterone resistance, insulin resistance, steroid hormone receptors, endometrial carcinoma

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