Search results for: small molecule inhibitor

Authors: Cassandra Springate, Alexandra Furber, Jack E. Hines

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Objectives: To create an evidence map of the cost-utility studies available with non-small cell lung cancer patients, and identify the geographical settings and interventions used. Methods: Using the Disease, Study Type, and Model Type filters in heoro.com we identified all cost-utility studies published between 1960 and 2017 with patients with non-small cell lung cancer. These papers were then indexed according to pre-specified categories. Results: Heoro.com identified 89 independent publications, published between 1995 and 2017. Of the 89 papers, 74 were published since 2010, 28 were from the USA, and 35 were from Europe, 16 of which were from the UK. Other publications were from China and Japan (13), Canada (9), Australia and New Zealand (4), and other countries (8). Fifty-nine studies included a chemotherapy intervention, of which 23 included erlotinib or gefitinib, 21 included pemetrexed or docetaxel, others included nivolumab (3), pembrolizumab (2), crizotinib (2), denosumab (2), necitumumab (1), and bevacizumab (1). Also, 19 studies modeled screening, staging, or surveillance strategies. Conclusions: The cost-utility studies found for NSCLC most commonly looked at the effectiveness of different chemotherapy treatments, with some also evaluating the addition of screening strategies. Most were also conducted with patient data from the USA and Europe.

Keywords: cancer, cost-utility, economic model, non-small cell lung cancer

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Authors: Renata Gerhardt, Detlev Belder

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Raman spectroscopy has attracted much attention as a structurally descriptive and label-free detection method. It is particularly suited for chemical analysis given as it is non-destructive and molecules can be identified via the fingerprint region of the spectra. In this work possibilities are investigated how to integrate Raman spectroscopy as a detection method for chip-based chromatography, making use of a droplet interface. A demanding task in lab-on-a-chip applications is the specific and sensitive detection of low concentrated analytes in small volumes. Fluorescence detection is frequently utilized but restricted to fluorescent molecules. Furthermore, no structural information is provided. Another often applied technique is mass spectrometry which enables the identification of molecules based on their mass to charge ratio. Additionally, the obtained fragmentation pattern gives insight into the chemical structure. However, it is only applicable as an end-of-the-line detection because analytes are destroyed during measurements. In contrast to mass spectrometry, Raman spectroscopy can be applied on-chip and substances can be processed further downstream after detection. A major drawback of Raman spectroscopy is the inherent weakness of the Raman signal, which is due to the small cross-sections associated with the scattering process. Enhancement techniques, such as surface enhanced Raman spectroscopy (SERS), are employed to overcome the poor sensitivity even allowing detection on a single molecule level. In SERS measurements, Raman signal intensity is improved by several orders of magnitude if the analyte is in close proximity to nanostructured metal surfaces or nanoparticles. The main gain of lab-on-a-chip technology is the building block-like ability to seamlessly integrate different functionalities, such as synthesis, separation, derivatization and detection on a single device. We intend to utilize this powerful toolbox to realize Raman detection in chip-based chromatography. By interfacing on-chip separations with a droplet generator, the separated analytes are encapsulated into numerous discrete containers. These droplets can then be injected with a silver nanoparticle solution and investigated via Raman spectroscopy. Droplet microfluidics is a sub-discipline of microfluidics which instead of a continuous flow operates with the segmented flow. Segmented flow is created by merging two immiscible phases (usually an aqueous phase and oil) thus forming small discrete volumes of one phase in the carrier phase. The study surveys different chip designs to realize coupling of chip-based chromatography with droplet microfluidics. With regards to maintaining a sufficient flow rate for chromatographic separation and ensuring stable eluent flow over the column different flow rates of eluent and oil phase are tested. Furthermore, the detection of analytes in droplets with surface enhanced Raman spectroscopy is examined. The compartmentalization of separated compounds preserves the analytical resolution since the continuous phase restricts dispersion between the droplets. The droplets are ideal vessels for the insertion of silver colloids thus making use of the surface enhancement effect and improving the sensitivity of the detection. The long-term goal of this work is the first realization of coupling chip based chromatography with droplets microfluidics to employ surface enhanced Raman spectroscopy as means of detection.

Keywords: chip-based separation, chip LC, droplets, Raman spectroscopy, SERS

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Authors: Todor Nickolov Stoyanov

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These factors appear as a reason for difficulties in financing from programs for rural development of the European Union. Credit conditions for commercial banks are difficult to implement, and its interest rate is too high. One of the possibilities for short-term loans at preferential conditions for the small and medium-sized agricultural and forest owners is credit cooperative. After the changes, occurred in the country after 1990, the need to restore credit cooperatives raised. The purpose for the creation of credit cooperatives is to assist private agricultural and forest owners to take care for them, to assist in the expansion and strengthening of their farms, to increase the quality of life and to improve the local economy. It was found that: in Bulgaria there is a legal obstacle for credit cooperatives to expand their business in the deposit and lending sphere; private forest and agricultural owners need small loans to solve a small problem for a certain season; providing such loans is not attractive for banks, but it is extremely necessary for owners of small forests and lands; if a special law on credit cooperatives is adopted, as required by the Cooperatives Act, it will allow more local people to be members of such credit structures and receive the necessary loans. In conclusion, proposals to create conditions for the development of credit cooperatives in the country are made and positive results expected from the creation of credit cooperatives, are summarized.

Keywords: cooperatives, credit cooperatives, forestry, forest owners

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Authors: Mark A. Spooner

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The growth of technological advances in the digital communications industry has dictated the way forensic examination laboratories receive, analyze, and report on digital evidence. This study looks at the trends in a medium sized digital forensics lab that examines small communications devices (i.e., cellular telephones, tablets, thumb drives, etc.) over the past five years. As law enforcement and homeland security organizations budgets shrink, many agencies are being asked to perform more examinations with less resources available. Using multi-level statistical analysis using five years of examination data, this research shows the increasing technological demand trend. The research then extrapolates the current data into the model created and finds a continued exponential growth curve of said demands is well within the parameters defined earlier on in the research.

Keywords: digital forensics, forensic examination, small device, trends

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Authors: Lidija R. Jevrić, Sanja O. Podunavac-Kuzmanović, Strahinja Z. Kovačević

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Quantitative structure-retention relationship (QSRR) analysis was used to predict the chromatographic behavior of s-triazine derivatives by using theoretical descriptors computed from the chemical structure. Fundamental basis of the reported investigation is to relate molecular topological descriptors with chromatographic behavior of s-triazine derivatives obtained by reversed-phase (RP) thin layer chromatography (TLC) on silica gel impregnated with paraffin oil and applied ethanol-water (φ = 0.5-0.8; v/v). Retention parameter (RM0) of 14 investigated s-triazine derivatives was used as dependent variable while simple connectivity index different orders were used as independent variables. The best QSRR model for predicting RM0 value was obtained with simple third order connectivity index (3χ) in the second-degree polynomial equation. Numerical values of the correlation coefficient (r=0.915), Fisher's value (F=28.34) and root mean square error (RMSE = 0.36) indicate that model is statistically significant. In order to test the predictive power of the QSRR model leave-one-out cross-validation technique has been applied. The parameters of the internal cross-validation analysis (r2CV=0.79, r2adj=0.81, PRESS=1.89) reflect the high predictive ability of the generated model and it confirms that can be used to predict RM0 value. Multivariate classification technique, hierarchical cluster analysis (HCA), has been applied in order to group molecules according to their molecular connectivity indices. HCA is a descriptive statistical method and it is the most frequently used for important area of data processing such is classification. The HCA performed on simple molecular connectivity indices obtained from the 2D structure of investigated s-triazine compounds resulted in two main clusters in which compounds molecules were grouped according to the number of atoms in the molecule. This is in agreement with the fact that these descriptors were calculated on the basis of the number of atoms in the molecule of the investigated s-triazine derivatives.

Keywords: s-triazines, QSRR, chemometrics, chromatography, molecular descriptors

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Authors: Jiawen Wang, Qijun Chen

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The performance of most machine-learning methods for image inpainting depends on the quantity and quality of the training samples. However, it is very expensive or even impossible to obtain a great number of training samples in many scenarios. In this paper, an image inpainting model based on a generative adversary network (GAN) is constructed for the cases when the number of training samples is small. Firstly, a feature extraction network (F-net) is incorporated into the GAN network to utilize the available information of the inpainting image. The weighted sum of the extracted feature and the random noise acts as the input to the generative network (G-net). The proposed network can be trained well even when the sample size is very small. Secondly, in the phase of the completion for each damaged image, a genetic algorithm is designed to search an optimized noise input for G-net; based on this optimized input, the parameters of the G-net and F-net are further learned (Once the completion for a certain damaged image ends, the parameters restore to its original values obtained in the training phase) to generate an image patch that not only can fill the missing part of the damaged image smoothly but also has visual semantics.

Keywords: image inpainting, generative adversary nets, genetic algorithm, small-sample size

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Authors: Gulnaz Erkomaishvili

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Introduction: The paper assesses the impact of the COVID-19 pandemic on the activities of small and medium-sized enterprises in Georgia, identifies their problems, and analyzes the state economic policy measures. During the pandemic, entrepreneurs named the imposition of restrictions, access to financial resources, shortage of qualified personnel, high tax rates, unhealthy competition in the market, etc. as the main challenges. The Georgian government has had to take special measures to mitigate the crisis impact caused by the pandemic. For example - in 2020, they mobilized more than 1,6 billion Gel for various eventsto support entrepreneurs. Small and medium-sized entrepreneurship development strategy is presented based on the research; Corresponding conclusions are made, and recommendations are developed. Objectives: The object of research is small and medium-sized enterprises and economic-political decisions aimed at their promotion.Methodology: This paper uses general and specific methods, in particular, analysis, synthesis, induction, deduction, scientific abstraction, comparative and statistical methods, as well as experts’ evaluation. In-depth interviews with experts were conducted to determine quantitative and qualitative indicators; Publications of the National Statistics Office of Georgia are used to determine the regularity between analytical and statistical estimations. Also, theoretical and applied research of international organizations and scientist-economists are used. Contributions: The COVID-19pandemic has had a significant impact on small and medium-sized enterprises. For them, Lockdown is a major challenge. Total sales volume decreased. At the same time, the innovative capabilities of enterprises and the volume of sales in remote channels have increased. As for the assessment of state support measures by small and medium-sizedentrepreneurs, despite the existence of support programs, a large number of entrepreneurs still do not evaluate the measures taken by the state positively. Among the desirable measures to be taken by the state, which would improve the activities of small and medium-sized entrepreneurs, who negatively or largely negatively assessed the activity of the state, named: tax incentives/exemption from certain taxes at the initial stage; Need for periodic trainings/organization of digital technologies, marketing training courses to improve the qualification of employees; Logic and adequacy of criteria when awarding grants and funding; Facilitating the finding of investors; Less bureaucracy, etc.

Keywords: small and medium enterprises, small and medium entrepreneurship, economic policy for small and medium entrepreneurship development, government regulations in Georgia, COVID-19 pandemic

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Authors: Shanakr Bhattarai, V. S. Tiwari, Barak Akabayov

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The plummeting number of infections and death is due to the development of drug-resistant bacteria. In addition, the number of approved antibiotic drugs by the Food and Drug Administration (FDA) is insufficient. Therefore, developing new drugs and finding novel targets for central metabolic pathways in bacteria is urgently needed. One of the promising targets is DNA replication machinery which consists of many essential proteins and enzymes. DnaG primase is an essential enzyme and a central part of the DNA replication machinery. DnaG primase synthesizes short RNA primers that initiate the Okazaki fragments by the lagging strand DNA polymerase. Therefore, it is reasonable to assume that inhibition of primase activity will stall DNA replication and prevent bacterial proliferation. We did the expression and purification of eight different bacterial DnaGs (Mycobacterium tuberculosis(Mtb), Bacillus anthracis (Ba), Mycobacterium smegmatis (Msmeg), Francisella tularencis (Ft), Vibrio cholerae (Vc) and Yersinia pestis (Yp), Staphylococcus aureus(Saureus), Escherichia coli(Ecoli)) followed by the radioactive activity assay. After obtaining the pure and active protein DnaG, we synthesized the inhibitors for them. The inhibitors were divided into five different groups, each containing five molecules, and the cocktail inhibition assay was performed against each DnaGs. The groups of molecules inhibiting the DnaGs were further tested with individual molecules belonging to inhibiting groups. Each molecule showing inhibition was titrated against the corresponding DnaGs to find IC50. We got a molecule(VS167) that acted as broad inhibitors, inhibiting all eight DnaGs. Molecules VS180 and VS186 inhibited seven DnaGs (except Saureus). Similarly, two molecules(VS 173, VS176) inhibited five DnaGs (Mtb, Ba, Ft, Yp, Ecoli). VS261 inhibited four DnaGs (Mtb, Ba, Ft, Vc). MS50 inhibited Ba and Vc DnaGs. And some of the inhibitors inhibited only one DnaGs. Thus we found the broad and specific inhibitors for different bacterial DnaGs, and their Structure-activity analysis(SAR) was done. Further, We tried to explain the similarities among the enzyme DnaGs from different bacteria based on their inhibition pattern.

Keywords: DNA replication, DnaG, okazaki fragments, antibiotic drugs

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Authors: Nicolae Constantin, Ştefan Sorohan

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The small and medium wind turbines are running in quite different conditions as compared to the big ones. Consequently, they need also a different approach concerning the structural health monitoring (SHM) issues. There are four main differences between the above mentioned categories: (i) significantly smaller dimensions, (ii) considerably higher rotation speed, (iii) generally small distance between the turbine and the energy consumer and (iv) monitoring assumed in many situations by the owner. In such conditions, nondestructive inspections (NDI) have to be made as much as possible with affordable, yet effective techniques, requiring portable and accessible equipment. Additionally, the turbines and accessories should be easy to mount, dispose and repair. As the materials used for such unit can be metals, composites and combined, the technologies should be adapted accordingly. An example in which the two materials co-exist is the situation in which the damaged metallic skin of a blade is repaired with a composite patch. The paper presents the inspection of the bonding state of the patch, using portable ultrasonic equipment, able to put in place the Lamb wave method, which proves efficient in global and local inspections as well. The equipment is relatively easy to handle and can be borrowed from specialized laboratories or used by a community of small wind turbine users, upon the case. This evaluation is the first in a row, aimed to evaluate efficiency of NDI performed with rather accessible, less sophisticated equipment and related inspection techniques, having field inspection capabilities. The main goal is to extend such inspection procedures to other components of the wind power unit, such as the support tower, water storage tanks, etc.

Keywords: structural health monitoring, small wind turbines, non-destructive inspection, field inspection capabilities

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Authors: El Hadji Mamadou Sonko, Ndiogou Sankhare, Maïmouna Lo, Jean Birane Gning, Cheikh Diop

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In Senegal, access to water, hygiene, and sanitation in small island towns is a particular problem, which is still poorly understood by the public authorities and development aid actors. The main objective of this study carried out in the Municipality of Foundiougne is to contribute to the knowledge of the problems related to the supply of drinking water, access to sanitation, and hygiene in small island towns in Senegal. The methodology adopted consisted of a literature review and quantitative surveys of a sample of 100 households in the Municipality. Semi-structured interviews using interview guides and informal interviews were also conducted with mechanical and manual emptiers, municipal authorities, public toilet managers, and neighbourhood leaders. Direct observation with photography was also used. The results show that, with regard to access to drinking water, 35% of households have unimproved water services, 46% have a limited level of service, and 19% have a basic level of service. Regarding sanitation, 77% of households are considered to have access to basic sanitation services, compared to 23% with limited sanitation services. However, these figures hide the dysfunctions of the sanitation system. Indeed, manual emptying is practiced exclusively by 4% of households, while 17% of households combine it with mechanical emptying. In addition, domestic wastewater is mainly evacuated outside the sanitation facilities, and all the sludge extracted from the pits is discharged directly into the environment without treatment. As a matter of fact, the surveys showed that 52% of households do not have access to a basic level of hygiene-related to handwashing when leaving the toilet. These results show that there is real work to be done at the level of small urban centres if we want to achieve MDG 6.

Keywords: Foundiougne, Senegal, small island, small town, water-sanitation, hygiene

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Authors: Pooja Kumari, Anandkumar Tengli

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Aurora kinase enzyme, a protein on overexpression, leads to metastasis and is extremely important for women’s health in terms of prevention or treatment. While creating a targeted technique, the aim of the work is to design purine molecules that inhibit in aurora kinase enzyme and helps to suppress breast cancer. Purine molecules attached to an amino acid in DNA block protein synthesis or halt the replication and metastasis caused by the aurora kinase enzyme. Various protein related to the overexpression of aurora protein was docked with purine molecule using Biovia Drug Discovery, the perpetual software. Various parameters like X-ray crystallographic structure, presence of ligand, Ramachandran plot, resolution, etc., were taken into consideration for selecting the target protein. A higher negative binding scored molecule has been taken for simulation studies. According to the available research and computational analyses, purine compounds may be powerful enough to demonstrate a greater affinity for the aurora target. Despite being clinically effective now, purines were originally meant to fight breast cancer by inhibiting the aurora kinase enzyme. In in-silico studies, it is observed that purine compounds have a moderate to high potency compared to other molecules, and our research into the literature revealed that purine molecules have a lower risk of side effects. The research involves the design, synthesis, and identification of active purine molecules against breast cancer. Purines are structurally similar to the normal metabolites of adenine and guanine; hence interfere/compete with protein synthesis and suppress the abnormal proliferation of cells/tissues. As a result, purine target metastasis cells and stop the growth of kinase; purine derivatives bind with DNA and aurora protein which may stop the growth of protein or inhibits replication and stop metastasis of overexpressed aurora kinase enzyme.

Keywords: aurora kinases, in silico studies, medicinal chemistry, combination therapies, chronic cancer, clinical translation

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Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

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Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

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Authors: Arpit Kumar Shrivastava, Subrat Kumar, Rajani Kanta Mohapatra, Priyadarshi Soumyaranjan Sahu

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Computational approaches to predict structure, function and other biological characteristics of proteins are becoming more common in comparison to the traditional methods in drug discovery. Cryptosporidiosis is a major zoonotic diarrheal disease particularly in children, which is caused primarily by Cryptosporidium hominis and Cryptosporidium parvum. Currently, there are no vaccines for cryptosporidiosis and recommended drugs are not effective. With the availability of complete genome sequence of C. hominis, new targets have been recognized for the development of effective and better drugs and/or vaccines. We identified a unique hypothetical epitopic protein in C. hominis genome through BLASTP analysis. A 3D model of the hypothetical protein was generated using I-Tasser server through threading methodology. The quality of the model was validated through Ramachandran plot by PROCHECK server. The functional annotation of the hypothetical protein through DALI server revealed structural similarity with human Transportin 3. Phylogenetic analysis for this hypothetical protein also showed C. hominis hypothetical protein (CUV04613) was the closely related to human transportin 3 protein. The 3D protein model is further subjected to virtual screening study with inhibitors from the Zinc Database by using Dock Blaster software. Docking study reported N-(3-chlorobenzyl) ethane-1,2-diamine as the best inhibitor in terms of docking score. Docking analysis elucidated that Leu 525, Ile 526, Glu 528, Glu 529 are critical residues for ligand–receptor interactions. The molecular dynamic simulation was done to access the reliability of the binding pose of inhibitor and protein complex using GROMACS software at 10ns time point. Trajectories were analyzed at each 2.5 ns time interval, among which, H-bond with LEU-525 and GLY- 530 are significantly present in MD trajectories. Furthermore, antigenic determinants of the protein were determined with the help of DNA Star software. Our study findings showed a great potential in order to provide insights in the development of new drug(s) or vaccine(s) for control as well as prevention of cryptosporidiosis among humans and animals.

Keywords: cryptosporidium hominis, hypothetical protein, molecular docking, molecular dynamics simulation

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Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

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Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

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Authors: S. Ben-Shabat, T. Turgeman, O. Leubinski, N. Roth-Bejerano, V. Kagan-Zur, Y. Sitrit

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The ectomycorrhizal (ECM) desert truffle Terfezia boudieri produces edible fruit bodies and forms symbiosis with its host plant Helianthemum sessiliflorum (Cistaceae) in the Negev desert of Israel. The symbiosis is vital for both partners' survival under desert conditions. Under desert habitat conditions, ECMs must form symbiosis before entering the dry season. To secure a successful encounter, in the course of evolution, both partners have responded by evolving special signals exchange that facilitates recognition. Members of the Cistaceae family serve as host plants for many important truffles. Conceivably, during evolution a common molecule present in Cistaceae plants was recruited to facilitate successful encounter with ectomycorrhizas. Arbuscular vesicular fungi (AM) are promiscuous in host preferences, in contrast, ECM fungi show specificity to host plants. Accordingly, we hypothesize that H. sessiliflorum secretes a chemotrophic-signaling, which is common to plants hosting ECM fungi belonging to the Pezizales. However, thus far no signaling molecules have been identified in ECM fungi. We developed a bioassay for chemotrophic activity. Fractionation of root exudates revealed a substance with chemotrophic activity and molecular mass of 534. Following the above concept, screening the transcriptome of Terfezia, grown under chemoattraction, discovered genes showing high homology to G proteins-coupled receptors of plant pathogens involved in positive chemotaxis and chemotaxis suppression. This study aimed to identify the active molecule using analytical methods (LC-MS, NMR etc.). This should contribute to our understanding of how ECM fungi communicate with their hosts in the rhizosphere. In line with the ability of Terfezia to form also endomycorrhizal symbiosis like AM fungi, analysis of the mechanisms may likewise be applicable to AM fungi. Developing methods to manipulate fungal growth by the chemoattractant can open new ways to improve inoculation of plants.

Keywords: chemotrophic signal, Helianthemum sessiliflorum, Terfezia boudieri, ECM

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Authors: Meet Patel, Darshan Patel, Nilay Shah

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Excess growth of wind-based renewable energy sources is required to identify the optimal location and damping capacity of doubly fed induction-generator-based (DFIG) wind farms while it penetrates into the transmission network. In this analysis, various ratings of DFIG wind farms are penetrated into the Single Machine Infinite Bus (SMIB ) at a different distance of the transmission line. On the basis of detailed examinations, a prime position is evaluated to maximize the stability of overall systems. A damping controller is designed at an optimum location to mitigate the small oscillations. The proposed model was validated using eigenvalue analysis, calculation of the participation factor, and time-domain simulation.

Keywords: DFIG, small signal stability, eigenvalues, time domain simulation

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Authors: Balazs Kulcsar

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Professional energy organizations perform analyses mainly on the global and national levels about the expected development of the share of renewables in electric power generation, heating, and cooling, as well as the transport sectors. There are just a few publications, research institutions, non-profit organizations, and national initiatives with a focus on studies in the individual towns, settlements. Issues concerning the self-supply of energy on the settlement level have not become too wide-spread. The goal of our energy geographic studies is to determine the share of local renewable energy sources in the settlement-based electricity supply across Hungary. The Hungarian energy supply system defines four categories based on the installed capacities of electric power generating units. From these categories, the theoretical annual electricity production of small-sized household power plants (SSHPP) featuring installed capacities under 50 kW and small power plants with under 0.5 MW capacities have been taken into consideration. In the above-mentioned power plant categories, the Hungarian Electricity Act has allowed the establishment of power plants primarily for the utilization of renewable energy sources since 2008. Though with certain restrictions, these small power plants utilizing renewable energies have the closest links to individual settlements and can be regarded as the achievements of the host settlements in the shift of energy use. Based on the 2017 data, we have ranked settlements to reflect the level of self-sufficiency in electricity production from renewable energy sources. The results show that the supply of all the energy demanded by settlements from local renewables is within reach now in small settlements, e.g., in the form of the small power plant categories discussed in the study, and is not at all impossible even in small towns and cities. In Hungary, 30 settlements produce more renewable electricity than their own annual electricity consumption. If these overproductive settlements export their excess electricity towards neighboring settlements, then full electricity supply can be realized on further 29 settlements from renewable sources by local small power plants. These results provide an opportunity for governmental planning of the realization of energy shift (legislative background, support system, environmental education), as well as framing developmental forecasts and scenarios until 2030.

Keywords: energy geography, Hungary, local small power plants, renewable energy sources, self-sufficiency settlements

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Authors: H. Trabelsi, A. Chehma, I. Benseddik

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Animals can play an important role in the seed dispersal cycle through the active or passive uptake of seeds and the subsequent external (epizoochory) or internal transport (endozoochory) of seeds. In Algeria, small ruminants and camels are generally conducted in extensive livestock exploiting the Saharan and steppe rangelands. To get an idea on the ecological potential role of these animals in the spontaneous plants proliferation, we propose to make a study of seeds dispersal and germination possibilities by camel faeces compared to those of small ruminants. Manual faeces decortication of the two animals categories has allowed to inventory 72 seed which 71% are in good condition, while 29% of the seeds that are encountered are partially altered and could not be identified. The species that have been identified, from small ruminants dung are weeds of cultures, while those identified from camel dung are spontaneous plants of Saharan rangeland. Concerning germination in the laboratory, only 3 species seeds were germinated from camel feces, whose germination rate varies from 25% to 100%. Contrary to Sheep-Goat feces, a single species germinated with 71%. The three months seed germination in greenhouse allowed to identify 10 species belonging to 4 botanical families (5 species from small ruminants dung and 3 species from Camel dung). In general, the results show the positive effect played by two animals categories for plants seed dispersal with the camel particularity for spontaneous plants due to its capacity to cover long distances in different rangeland types.

Keywords: Algeria, camel, endozoochory, seeds, sheep-goat, rangeland

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Authors: Noppatee Sabpayakom, Somporn Sirisumrannukul

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Due to incentive policies to promote renewable energy and energy efficiency, high penetration levels of very small power producers (VSPP) located in distribution networks have imposed technical barriers and established new requirements for protection and control of the networks. Although VSPPs have economic and environmental benefit, they may introduce negative effects and cause several challenges on the issue of protection and control system. This paper presents comprehensive studies of possible impacts on control and protection systems based on real distribution systems located in a metropolitan area. A number of scenarios were examined primarily focusing on state of islanding, and un-disconnected VSPP during faults. It is shown that without proper measures to address the issues, the system would be unable to maintain its integrity of electricity power supply for disturbance incidents.

Keywords: control and protection systems, distributed generation, renewable energy, very small power producers

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Authors: Zhao Xinlei

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In general, interstate relations are diverse and include economic, political, military, and diplomatic. Therefore, by analyzing the development of the relationship between Malaysia and China, we can better verify how the Hirschman effect works between small countries and great powers. This paper mainly adopts qualitative research methods and uses Malaysia's 2020-2022 political crisis as a specific case to verify the practice of the Hirschman effect between small and large countries. In particular, the interest groups in small countries that are closely related to trade with extraordinary abilities, as the primary beneficiaries in the development of trade between the two countries, although they may use their resources to a certain extent to influence the decisions of small countries towards great powers, they do not fundamentally determine the small countries' response to large countries. In this process, the relative power asymmetry between states plays a dominant role, as small states lack trust and suspicion in political diplomacy towards large states based on the perception of threat arising from the relative power asymmetry. When developing bilateral relations with large countries, small states seek practical cooperation to promote economic and trade development but become more cautious in their political ties to avoid being caught in power struggles between large states or being controlled by them. The case of Malaysia-China relations also illustrates that despite the ongoing political crisis in Malaysia, which saw the country go through the transition from (Perikatan Nasional) PN to (Barisan Nasional) BN, different governments have maintained a pragmatic and proactive economic policy towards China to reduce suspicion and mistrust between the two countries in political and diplomatic affairs, thereby enhancing cooperation and interactions between the two countries. At the same time, the Malaysian government is developing multi-dimensional foreign relations and actively participating in multilateral, regional organizations and platforms, such as those organized by the United States, to maintain a relative balance in the influence of the US and China on Malaysia.

Keywords: Hirschman effect, interest groups, Malaysia, China, bilateral relations

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Authors: Yaw Opoku-Damoah, Run Zhang, Hang Thu Ta, Zhi Ping Xu

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Gas therapy is still at an early stage of research and development. Even though most gasotransmitters have proven their therapeutic potential, their handling, delivery, and controlled release have been extremely challenging. This research work employs a versatile nanosystem that is capable of delivering a gasotransmitter in the form of a photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The therapeutic action was mediated by upconversion nanoparticles (UCNPs) designed to transfer bio-friendly low energy near-infrared (NIR) light to ultraviolet (UV) light capable of triggering carbon monoxide (CO) from a water-soluble amphiphilic manganese carbonyl complex CORM incorporated into a carefully designed lipid drug delivery system. Herein, gaseous CO that plays a role as a gasotransmitter with cytotoxic and homeostatic properties was investigated to instigate cellular apoptosis. After successfully synthesizing the drug delivery system, the ability of the system to encapsulate and mediate the sustained release of CO after light excitation was demonstrated. CO fluorescence probe (COFP) was successfully employed to determine the in vitro drug release profile upon NIR light irradiation. The uptake of nanoparticles enhanced by folates and its receptor interaction was also studied for cellular uptake purposes. The anticancer potential of the final lipid nanoparticle Lipid/UCNPs/CORM/FA (LUCF) was also determined by cell viability assay. Intracellular CO release and a subsequent therapeutic action involving ROS production, mitochondrial damage, and CO production was also evaluated. In all, this current project aims to use in vitro studies to determine the potency and efficiency of a NIR-mediated CORM prodrug delivery system.

Keywords: carbon monoxide-releasing molecule, upconversion nanoparticles, site-specific delivery, amphiphilic manganese carbonyl complex, prodrug delivery system.

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Authors: M. Stelmachowski, M. Wojtczak

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The aim of the work was to assess the environmental impact of the selected small and medium-sized companies supplying heat and electricity to the cities with a population of about 50,000 inhabitants. Evaluation and comparison of the impact on the environment have been carried out for the three plants producing heat and two CHP plants with particular attention to emissions into the atmosphere and the impact of introducing a system of trading carbon emissions of these companies.

Keywords: CO2 emission, district heating, heat and power plant, impact on environment

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Authors: Swati Mishra

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In recent years, there has been an explosion in Gold NanoParticle (GNP) research, with a rapid increase in publications in diverse fields, including imaging, bioengineering, and molecular biology. GNPs exhibit unique physicochemical properties, including surface plasmon resonance (SPR) and bind amine and thiol groups, allowing surface modification and use in biomedical applications. Nanoparticle functionalization is the subject of intense research at present, with rapid progress being made towards developing biocompatible, multi-functional particles. In the present study, the photochemical method has been done to functionalize various-shaped GNPs like nanostars by the molecules like ninhydrin. Ninhydrin is bactericidal, virucidal, fungicidal, antigen-antibody reactive, and used in fingerprint technology in forensics. The GNPs functionalized with ninhydrin efficiently will bind to the amino acids on the target protein, which is of eminent importance during the pandemic, especially where long-term treatments of COVID- 19 bring many side effects of the drugs. The photochemical method is adopted as it provides low thermal load, selective reactivity, selective activation, and controlled radiation in time, space, and energy. The GNPs exhibit their characteristic spectrum, but a distinctly blue or redshift in the peak will be observed after UV irradiation, ensuring efficient ninhydrin binding. Now, the bound ninhydrin in the GNP carrier, upon chemically reacting with any amino acid, will lead to the formation of Rhumann purple. A common method of GNP production includes citrate reduction of Au [III] derivatives such as aurochloric acid (HAuCl4) in water to Au [0] through a one-step synthesis of size-tunable GNPs. The following reagents are prepared to validate the approach. Reagent A solution 1 is0.0175 grams ninhydrin in 5 ml Millipore water Reagent B 30 µl of HAuCl₄.3H₂O in 3 ml of solution 1 Reagent C 1 µl of gold nanostars in 3 ml of solution 1 Reagent D 6 µl of cetrimonium bromide (CTAB) in 3 ml of solution1 ReagentE 1 µl of gold nanostars in 3 ml of ethanol ReagentF 30 µl of HAuCl₄.₃H₂O in 3 ml of ethanol ReagentG 30 µl of HAuCl₄.₃H₂O in 3 ml of solution 2 ReagentH solution 2 is0.0087 grams ninhydrin in 5 ml Millipore water ReagentI 30 µl of HAuCl₄.₃H₂O in 3 ml of water The reagents were irradiated at 254 nm for 15 minutes, followed by their UV Visible spectroscopy. The wavelength was selected based on the one reported for excitation of a similar molecule Pthalimide. It was observed that the solution B and G deviate around 600 nm, while C peaks distinctively at 567.25 nm and 983.9 nm. Though it is tough to say about the chemical reaction happening, butATR-FTIR of reagents will ensure that ninhydrin is not forming Rhumann purple in the absence of amino acids. Therefore, these experiments, we achieved the functionalization of gold nanostars with ninhydrin corroborated by the deviation in the spectrum obtained in a mixture of GNPs and ninhydrin irradiated with UV light. It prepares them as a carrier molecule totake up amino acids for targeted delivery or germicidal action.

Keywords: gold nanostars, ninhydrin, photochemical method, UV visible specgtroscopy

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Authors: Eetedal Alanjem, Majedah Alnajem

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The importance of innovation in entrepreneurship can be seen in the invention of new ways to produce products or improved solutions. A service industry can expand with new or improved types of services to fulfill the ever changing needs of their clients. Manufacturers can come up with new products from raw materials and by-products. Innovation is vital for the durability of any business. Innovation usually begins with a need. Small businesses are generally directly involved in their communities and they know exactly what the communities need and strive to come up with solutions to fulfill those needs. They seize the opportunity to innovate to ease communal problems and make lives more comfortable. And then, these solutions keep getting better, easier and more useful as entrepreneurs and their small businesses come up with improved formulas and solutions. Keeping abreast with current trends and demands is an important factor for entrepreneurs to fuel their creativity and innovation. Manufacturers are constantly innovating to produce more without sacrificing quality. Small businesses should make innovation as a fundamental part of their organisational development since innovation creates business success. Entrepreneurs must not see just one solution to a need. They should come up with ideas for multiple solutions. It is imperative for small businesses to encourage growth of innovation among their employees. Competition is another factor that elevates the importance of innovation in entrepreneurship. It motivates entrepreneurs to come up with better, improved products and services than their competitors for a higher share of the market. In this paper will go in-depth for each factor and will discuss some of cases studies to know how innovation it’s important for entrepreneurs by facts & lessons?

Keywords: innovation, entrepreneurship, creativity, organisational development

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Authors: Piacentini Diego, Della Rovere Federica, Fattorini Laura, Lanni Francesca, Cittadini Martina, Altamura Maria Maddalena, Falasca Giuseppina

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Plants have evolved sophisticated mechanisms to cope with environmental cues. Changes in intracellular content and distribution of phytohormones, such as the auxin indole-3-acetic acid (IAA), have been involved in morphogenic adaptation to environmental stresses. In addition to phytohormones, plants can rely on a plethora of small signal molecules able to promptly sense and transduce the stress signals, resulting in morpho/physiological responses thanks also to their capacity to modulate the levels/distribution/reception of most hormones. Among these signaling molecules, nitrogen monoxide (nitric oxide – NO) is a critical component in several plant acclimation strategies to both biotic and abiotic stresses. Depending on its levels, NO increases plant adaptation by enhancing the enzymatic or non-enzymatic antioxidant systems or by acting as a direct scavenger of reactive oxygen/nitrogen (ROS/RNS) species produced during the stress. In addition, exogenous applications of NO-specific donor compounds showed the involvement of the signal molecule in auxin metabolism, transport, and signaling, under both physiological and stress conditions. However, the complex mechanisms underlying NO action in interacting with phytohormones, such as auxins, during metal stress responses are still poorly understood and need to be better investigated. Emphasis must be placed on the response of the root system since it is the first plant organ system to be exposed to metal soil pollution. The monocot Oryza sativa L. (rice) has been chosen given its importance as a stable food for some 4 billion people worldwide. In addition, increasing evidence has shown that rice is often grown in contaminated paddy soils with high levels of heavy metal cadmium (Cd) and metalloid arsenic (As). The facility through which these metals are taken up by rice roots and transported to the aerial organs up to the edible caryopses makes rice one of the most relevant sources of these pollutants for humans. This study aimed to evaluate if NO has a mitigatory activity in the roots of rice seedlings against Cd or As toxicity and to understand if this activity requires interactions with auxin. Our results show that exogenous treatments with the NO-donor SNP alleviate the stress induced by Cd, but not by As, in in-vitro-grown rice seedlings through increased intracellular root NO levels. The damages induced by the pollutants include root growth inhibition, root histological alterations and ROS (H2O2, O2●ˉ), and RNS (ONOOˉ) production. Also, SNP treatments mitigate both the root increase in root IAA levels and the IAA alteration in distribution monitored by the OsDR5::GUS system due to the toxic metal exposure. Notably, the SNP-induced mitigation of the IAA homeostasis altered by the pollutants does not involve changes in the expression of OsYUCCA1 and ASA2 IAA-biosynthetic genes. Taken together, the results highlight a mitigating role of NO in the rice root system, which is pollutant-specific, and involves the interaction of the signal molecule with both IAA and brassinosteroids at different (i.e., transport, levels, distribution) and multiple levels (i.e., transcriptional/post-translational levels). The research is supported by Progetti Ateneo Sapienza University of Rome, grant number: RG120172B773D1FF

Keywords: arsenic, auxin, cadmium, nitric oxide, rice, root system

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Authors: Özlen Altun, Zeliha Yoruç

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In the present study, the reactions involving 4-Bromo-2,6-bis-hydroxymethyl-phenol (BBHMP) and nikotinamide (NA) in the presence Pd (II) ion were investigated. Optimum conditions for the reactions were established as pH 7 and λ = 450 nm. According to absorbance measurements, the mole ratio of BBHMP : NA : Pd2+ was found as 1 : 2 : 2. As a result of physico-chemical, spectrophotometric and thermal analysis results, the reactions of BBHMP and NA with Pd (II) is complexation reactions and one molecule BBHMP and two molecules of NA react with two molecules of metal (II) ion.

Keywords: 4-Bromo-2, 6-bis-hydroxymethyl-phenol, nicotinamide, Pd(II), spectral analysis, synthesis

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Authors: Wondmnew Derebe Yohannis

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Farming irrigation plays a crucial role in rural development strategies, impacting both annual household income and livelihood. This research aims to evaluate the factors influencing irrigation participation and assess the impact of small-scale irrigation on rural households' annual income. The study collected data from 287 farmers in the Dahana district of northern Ethiopia. The research investigates the driving forces behind farmers' decisions to adopt small-scale irrigation and its effect on annual income gain. The findings reveal that several factors positively influence the probability of adoption, including access to credit, cultivated land size, livestock holding, extension contact, and the education level of the household head. Conversely, the distance to local markets and water schemes negatively affects the likelihood of adoption. To understand the differences in annual income between farm households that adopted irrigation and those that did not, a simultaneous equations model with endogenous switching regression is estimated. This accounts for the heterogeneity in the adoption decision and unobservable characteristics of farmers and their farms. The analysis compares the expected income gain under actual and counterfactual scenarios, considering whether the farm household adopted irrigation or not. The study reveals that the group of farm households that adopted irrigation has distinct characteristics compared to those that did not adopt it. Furthermore, the research demonstrates that the adoption of irrigation practices leads to an increase in annual income. Interestingly, the impact of small-scale irrigation on annual income is greater for the farm households that actually adopted irrigation compared to those in the counterfactual scenario where they did not adopt. Based on the findings, the researcher concludes that small-scale irrigation is a practical solution for meeting household financial needs in the study area. It is recommended that investments in small-scale irrigation continue to further improve the livelihoods of rural farming communities by enhancing annual income gains.

Keywords: small-scale irrigation, income, rural farm households, endogenous switching regression, user, non-user

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Authors: Mdluli Fezile, Schmidt Stefan, Thamaga-Chitja Joyce

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In view of the frequently reported foodborne disease outbreaks caused by contaminated fresh produce, consumers have a preference for foods that meet requisite hygiene standards to reduce the risk of foodborne illnesses. Producing good quality fresh produce then becomes critical in improving market access and food security, especially for small-scale farmers. Questions of hygiene and subsequent microbiological quality in the rural small-scale farming sector of South Africa are even more crucial, given the policy drive to develop small-scale farming as a measure for reinforcement of household food security and reduction of poverty. Farming practices and methods, throughout the fresh produce value chain, influence the quality of the final product, which in turn determines its success in the market. This study’s aim was to therefore determine the extent to which training on organic farming methods, including modules such as Importance of Production Hygiene, influenced the hygienic farming practices employed by eTholeni small-scale organic farmers in uMbumbulu, KwaZulu-Natal- South Africa. Questionnaires were administered to 73 uncertified organic farmers and analysis showed that a total of 33 farmers were trained and supplied the local Agri-Hub while 40 had not received training. The questionnaire probed respondents’ attitudes, knowledge of hygiene and composting practices. Data analysis included descriptive statistics such as the Chi-square test and a logistic regression model. Descriptive analysis indicated that a majority of the farmers (60%) were female, most of which (73%) were above the age of 40. The logistic regression indicated that factors such as farmer training and prior experience in the farming sector had a significant influence on hygiene practices both at 5% significance levels. These results emphasize the importance of training, education and farming experience in implementing good hygiene practices in small-scale farming. It is therefore recommended that South African policies should advocate for small-scale farmer training, not only for subsistence purposes, but also with an aim of supplying produce markets with high fresh produce.

Keywords: small-scale farmers, leafy salad vegetables, organic produce, food safety, hygienic practices, food security

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Authors: Małgorzata Smolarek

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One of the barriers to the development of small and medium-sized enterprises (SME) are difficulties connected with management of human resources. The first part of article defines the specifics of staff management in small and medium enterprises. The practical part presents results of own studies in the area of diagnosis of the state of the human resources management in small and medium-sized enterprises in Poland. It takes into account its impact on the functioning of SME in a variable environment. This part presents findings of empirical studies, which enabled verification of the hypotheses and formulation of conclusions. The findings presented in this paper were obtained during the implementation of the project entitled 'Tendencies and challenges in strategic managing SME in Silesian Voivodeship.' The aim of the studies was to diagnose the state of strategic management and human resources management taking into account its impact on the functioning of small and medium enterprises operating in Silesian Voivodeship in Poland and to indicate improvement areas of the model under diagnosis. One of the specific objectives of the studies was to diagnose the state of the process of strategic management of human resources and to identify fundamental problems. In this area, the main hypothesis was formulated: The enterprises analysed do not have comprehensive strategies for management of human resources. The survey was conducted by questionnaire. Main Research Results: Human resource management in SMEs is characterized by simplicity of procedures, and the lack of sophisticated tools and its specificity depends on the size of the company. The process of human resources management in SME has to be adjusted to the structure of an organisation, result from its objectives, so that an organisation can fully implement its strategic plans and achieve success and competitive advantage on the market. A guarantee of success is an accurately developed policy of human resources management based on earlier analyses of the existing procedures and possessed human resources.

Keywords: human resources management, human resources policy, personnel strategy, small and medium enterprises

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Authors: Barsha Saha, Shouvik Chakravarty, Sukanta Ray, Kshaunish Das, Nidhan K. Biswas, Srikanta Goswami

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Pancreatic Ductal Adenocarcinoma is a well-recognised cause of cancer death with a five-year survival rate of about 9%, and its incidence in India has been found to be increased manifold in recent years. Due to delayed detection, this highly metastatic disease has a poor prognosis. Several molecular alterations happen during the progression of the disease from pre-cancerous conditions, and many such alterations could be investigated for their biomarker potential. MicroRNAs have been shown to be prognostic for PDAC patients in a variety of studies. We hereby used NGS technologies to evaluate the role of small RNA changes during pancreatic cancer development from chronic pancreatitis. Plasma samples were collected from pancreatic cancer patients (n=16), chronic pancreatitis patients (n=8), and also from normal individuals (n=16). Pancreatic tumour tissue (n=5) and adjacent normal tissue samples (n=5) were also collected. Sequencing of small RNAs was carried out after small RNAs were isolated from plasma samples and tissue samples. We find that certain microRNAs are highly deregulated in pancreatic cancer patients in comparison to normal samples. A combinatorial analysis of plasma and tissue microRNAs and subsequent exploration of their targets and altered molecular pathways could not only identify potential biomarkers for disease diagnosis but also help to understand the underlying mechanism.

Keywords: small RNA sequencing, pancreatic cancer, biomarkers, tissue sample

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