Search results for: drug target

Authors: Sonal Gupta, Rakhi Bansal, Javed Ali, Reema Gabrani, Shweta Dang

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Nanoemulsions (NEs) and microemulsions (MEs) have been an attractive tool for encapsulation of both hydrophilic and lipophillic actives. Both these systems are composed of oil phase, surfactant, co-surfactant and aqueous phase. Depending upon the application and intended use, both oil-in-water and water-in-oil emulsions can be designed. NEs are fabricated using high energy methods employing less percentage of surfactant as compared to MEs which are self assembled drug delivery systems. Owing to the nanometric size of the droplets these systems have been widely used to enhance solubility and bioavailability of natural as well as synthetic molecules. The aim of the present study is to assess the effect of % age of surfactants on cell viability of Vero cells (African Green Monkeys’ Kidney epithelial cells) via MTT assay. Green tea catechin (Polyphenon 60) loaded ME employing low energy vortexing and NE employing high energy ultrasonication were prepared using same excipients (labrasol as oil, cremophor EL as surfactant and glycerol as co-surfactant) however, the % age of oil and surfactant needed to prepare the ME was higher as compared to NE. These formulations along with their excipients (oilME=13.3%, SmixME=26.67%; oilNE=10%, SmixNE=13.52%) were added to Vero cells for 24 hrs. The tetrazolium dye, 3-(4,5-dimethylthia/ol-2-yl)-2,5-diphi-iiyltclrazolium bromide (MTT), is reduced by live cells and this reaction is used as the end point to evaluate the cytoxicity level of a test formulation. Results of MTT assay indicated that oil at different percentages exhibited almost equal cell viability (oilME ≅ oilNE) while surfactant mixture had a significant difference in the cell viability values (SmixME < SmixNE). Polyphenon 60 loaded ME and its PlaceboME showed higher toxicity as compared to Polyphenon 60 loaded NE and its PlaceboNE that can be attributed to the higher concentration of surfactants present in MEs. Another probable reason for high % cell viability of Polyphenon 60 loaded NE might be due to the effective release of Polyphenon 60 from NE formulation that helps in the sustenance of Vero cells.

Keywords: cell viability, microemulsion, MTT, nanoemulsion, surfactants, ultrasonication

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Authors: Muhammad Faheem Khakhi, Jian Yu Wang, Salman Muhammad, Muhammad Faisal Shabir

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Population growth and Chinese two-child policy will boost pharmaceutical market, and it will continue to maintain the growth for a period of time in the future, the traditional pharmacy dispensary has been unable to meet the growing medical needs of the peoples. Under the strong support of the national policy, the automatic transformation of traditional pharmacies is the inclination of the Times, the new type of intelligent pharmacy system will continue to promote the development of the pharmaceutical industry. Under this background, based on PLC control, the paper proposed an intelligent storage and automatic drug delivery system; complete design of the lower computer's control system and the host computer's software system has been present. The system can be applied to dispensing work for Chinese herbal medicinal and Western medicines. Firstly, the essential of intelligent control system for pharmacy is discussed. After the analysis of the requirements, the overall scheme of the system design is presented. Secondly, introduces the software and hardware design of the lower computer's control system, including the selection of PLC and the selection of motion control system, the problem of the human-computer interaction module and the communication between PC and PLC solves, the program design and development of the PLC control system is completed. The design of the upper computer software management system is described in detail. By analyzing of E-R diagram, built the establish data, the communication protocol between systems is customize, C++ Builder is adopted to realize interface module, supply module, main control module, etc. The paper also gives the implementations of the multi-threaded system and communication method. Lastly, each module of the lower computer control system is tested. Then, after building a test environment, the function test of the upper computer software management system is completed. On this basis, the entire control system accepts the overall test.

Keywords: automatic pharmacy, PLC, control system, management system, communication

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Authors: Seyed Mostafa Jafari Raad, Hassan Hassanzadeh

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Injection of impurities along with CO₂ into saline aquifers provides an exceptional prospect for low-cost carbon capture and storage technologies and can potentially accelerate large-scale implementation of geological storage of CO₂. We have conducted linear stability analyses and numerical simulations to investigate the effects of permitted impurities in CO₂ streams on the onset of natural convection and dynamics of subsequent convective mixing. We have shown that the rate of dissolution of an impure CO₂ stream with H₂S highly depends on the operating conditions such as temperature, pressure, and composition of impurity. Contrary to findings of previous studies, our results show that an impurity such as H₂S can potentially reduce the onset time of natural convection and can accelerate the subsequent convective mixing. However, at the later times, the rate of convective dissolution is adversely affected by the impurities. Therefore, the injection of an impure CO₂ stream can be engineered to improve the rate of dissolution of CO₂, which leads to higher storage security and efficiency. Accordingly, we have identified the most favorable CO₂ stream compositions based on the geophysical properties of target aquifers. Information related to the onset of natural convection such as the scaling relations and the most favorable operating conditions for CO₂ storage developed in this study are important in proper design, site screening, characterization and safety of geological storage. This information can be used to either identify future geological candidates for acid gas disposal or reviewing the current operating conditions of licensed injection sites.

Keywords: CO₂ storage, solubility trapping, convective dissolution, storage efficiency

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Authors: Selim Kara, Ertan Arda, Fahrettin Dolastir, Önder Pekcan

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Biomaterials and thin film coatings play a fundamental role in medical, food and pharmaceutical industries. Carrageenan is a linear sulfated polysaccharide extracted from algae and seaweeds. To date, such biomaterials have been used in many smart drug delivery systems due to their biocompatibility and antimicrobial activity properties. Poly (N-isopropylacrylamide) (PNIPAm) gels and copolymers have also been used in medical applications. PNIPAm shows lower critical solution temperature (LCST) property at about 32-34 °C which is very close to the human body temperature. Below and above the LCST point, PNIPAm gels exhibit distinct phase transitions between swollen and collapsed states. A special class of gels are microgels which can react to environmental changes significantly faster than microgels due to their small sizes. Quartz crystal microbalance (QCM) measurement technique is one of the attractive techniques which has been used for monitoring the thin-film formation process. A sensitive QCM system was designed as to detect 0.1 Hz difference in resonance frequency and 10-7 change in energy dissipation values, which are the measures of the deposited mass and the film rigidity, respectively. PNIPAm microgels with the diameter around few hundred nanometers in water were produced via precipitation polymerization process. 5 MHz quartz crystals with functionalized gold surfaces were used for the deposition of the carrageenan molecules and microgels in the solutions which were slowly pumped through a flow cell. Interactions between charged carrageenan and microgel particles were monitored during the formation of the film layers, and the Sauerbrey masses of the deposited films were calculated. The critical phase transition temperatures around the LCST were detected during the heating and cooling cycles. It was shown that it is possible to monitor the interactions between PNIPAm microgels and biopolymer molecules, and it is also possible to specify the critical phase transition temperatures by using a QCM system.

Keywords: carrageenan, phase transitions, PNIPAm microgels, quartz crystal microbalance (QCM)

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Authors: Harish Rajak, Kamlesh Raghuwanshi

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Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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Authors: J. D. Villanueva, N. Peyraube, I. Allan, G. D. Salvosa, M. Reid, C. Harman, K. D. Salvosa, J. M. V. Castro, M. V. O. Espaldon, J. B. Sevilla-Nastor, P. Le Coustumer

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The main objectives of this research are to (1) assess the occurrence of the pharmaceutical compounds and (2) present the environmental challenges posed by the existence of these pharmaceutical compounds in the surface water. These pharmaceuticals were measured in Napindan Lake, Philippines. This lake is not only a major tributary of the Pasig River (an estuary) and Laguna Lake (freshwater). It also joins these two important surface waters of the National Capital Region. Pharmaceutical compounds such as Atenolol, Carbamazepine, and two other over the counter medicines: Cetirizine, and Ibuprofen were measured in Napindan Lake. Atenolol is a beta blocker that helps in lowering hypertensions. Carbamazepine is an anticonvulsant used as treatment for epilepsy and neuropathic pain. Cetirizine is an antihistamine that can relieve allergies. Ibuprofen is a non-steroidal anti-inflammatory drug normally used to relieve pains. Three different climatological conditions with corresponding hydro physico chemical characteristics were considered. First, was during a dry season with a simultaneous dredging. Second was during a transition period from dry to wet season. Finally, the third was during a continuous wet event. Based from the results of the study, most of these pharmaceuticals can be found in Napindan Lake. This is a proof that these pharmaceutical compounds are being released to a natural surface water. Even though climatological conditions were different, concentrations of these pharmaceuticals can still be detected. This implies that there is an incessant supply of these pharmaceutical compounds in Napindan Lake. Chronic exposure to these compounds even at low concentrations can lead to possible environmental and health risks. Given this information and since consistent occurrence of these compounds can be expected, the main challenge, at present, is on how to control the sources of these pharmaceutical compounds. Primarily, there is a need to manage the disposal of the pharmaceutical compounds. Yet, the main question is how to? This study would like to present the challenges and institutional roles in helping manage the pharmaceutical disposals in a developing country like the Philippines.

Keywords: atenolol, carbamazepine, cetirizine, ibuprofen, institutional roles, Napindan lake, pharmaceutical compound disposal management, surface water, urban lake

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Authors: H. Hajimolahoseini, J. Hashemi, D. Redfearn

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Background: Catheter ablation is an effective therapy for symptomatic atrial fibrillation (AF). The intracardiac electrocardiogram (IEGM) collected during this procedure contains precious information that has not been explored to its full capacity. Novel processing techniques allow looking at these recordings from different perspectives which can lead to improved therapeutic approaches. In our previous study, we showed that variation in amplitude measured through Shannon Entropy could be used as an AF recurrence risk stratification factor in patients who received Ibutilide before the electrograms were recorded. The aim of this study is to further investigate the effect of Ibutilide on characteristics of the recorded signals from the left atrium (LA) of a patient with persistent AF before and after administration of the drug. Methods: The IEGMs collected from different intra-atrial sites of 12 patients were studied and compared before and after Ibutilide administration. First, the before and after Ibutilide IEGMs that were recorded within a Euclidian distance of 3 mm in LA were selected as pairs for comparison. For every selected pair of IEGMs, the Probability Distribution Function (PDF) of the amplitude in time domain and magnitude in frequency domain was estimated using the regression analysis. The PDF represents the relative likelihood of a variable falling within a specific range of values. Results: Our observations showed that in time domain, the PDF of amplitudes was fitted to a Gaussian distribution while in frequency domain, it was fitted to a Rayleigh distribution. Our observations also revealed that after Ibutilide administration, the IEGMs would have significantly narrower short-tailed PDFs both in time and frequency domains. Conclusion: This study shows that the PDFs of the IEGMs before and after administration of Ibutilide represents significantly different properties, both in time and frequency domains. Hence, by fitting the PDF of IEGMs in time domain to a Gaussian distribution or in frequency domain to a Rayleigh distribution, the effect of Ibutilide can easily be tracked using the statistics of their PDF (e.g., standard deviation) while this is difficult through the waveform of IEGMs itself.

Keywords: atrial fibrillation, catheter ablation, probability distribution function, time-frequency characteristics

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Authors: Y. S. Zhou, C. R. Li, L. L. Tang, C. X. Gao, D. J. Wang, Y. Y. Guo

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Triangular trihedral corner reflector (CR) has been widely used as point target for synthetic aperture radar (SAR) calibration and image quality assessment. The additional “tip” of the triangular plate does not contribute to the reflector’s theoretical RCS and if it interacts with a perfectly reflecting ground plane, it will yield an increase of RCS at the radar bore-sight and decrease the accuracy of SAR calibration and image quality assessment. Regarding this problem, two types of CRs were manufactured. One was the hexagonal trihedral CR. It is a self-illuminating CR with relatively small plate edge length, while large edge length usually introduces unexpected edge diffraction error. The other was the triangular trihedral CR with extended bottom plate which considers the effect of ‘tip’ into the total RCS. In order to assess the performance of the two types of new CRs, flight campaign over the National Calibration and Validation Site for High Resolution Remote Sensors was carried out. Six hexagonal trihedral CRs and two bottom-extended trihedral CRs, as well as several traditional triangular trihedral CRs, were deployed. KOMPSAT-5 X-band SAR image was acquired for the performance analysis of the hexagonal trihedral CRs. C-band airborne SAR images were acquired for the performance analysis of the bottom-extended trihedral CRs. The analysis results showed that the impulse response function of both the hexagonal trihedral CRs and bottom-extended trihedral CRs were much closer to the ideal sinc-function than the traditional triangular trihedral CRs. The flight campaign results validated the advantages of new types of CRs and they might be useful in the future SAR calibration mission.

Keywords: synthetic aperture radar, calibration, corner reflector, KOMPSAT-5

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Authors: Julian Wise

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Newcrest Mining is one of the world’s top five gold and rare earth mining organizations by production, reserves and market capitalization in the world. This paper elaborates on the data acquisition processes employed by Newcrest in collaboration with Fortune 500 listed organization, Insight Enterprises, to standardize machine learning solutions which process data from over a hundred thousand distributed Internet of Things (IoT) devices located at mine sites globally. Through the utilization of software architecture cloud technologies and edge computing, the technological developments enable for standardized processes of machine learning applications to influence the strategic optimization of mineral processing. Target objectives of the machine learning optimizations include time savings on mineral processing, production efficiencies, risk identification, and increased production throughput. The data acquired and utilized for predictive modelling is processed through edge computing by resources collectively stored within a data lake. Being involved in the digital transformation has necessitated the standardization software architecture to manage the machine learning models submitted by vendors, to ensure effective automation and continuous improvements to the mineral process models. Operating at scale, the system processes hundreds of gigabytes of data per day from distributed mine sites across the globe, for the purposes of increased improved worker safety, and production efficiency through big data applications.

Keywords: mineral technology, big data, machine learning operations, data lake

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Authors: Philipp Zopf, Franz Haas

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Manufacturing of very hard and refractory materials like ceramics, glass or carbide poses particular challenges on tools and machines. The company Sauer GmbH developed especially for this application area ultrasonic tool holders working in a frequency range from 15 to 60 kHz and superimpose the common tool movement in the vertical axis. This technique causes a structural weakening in the contact area and facilitates the machining. The possibility of the force reduction for these special materials especially in drilling of carbide with diamond tools up to 30 percent made the authors try to expand the application range of this method. To make the results evaluable, the authors decide to start with existing processes in which the positive influence of the ultrasonic assistance is proven to understand the mechanism. The comparison of a grinding process the Institute use to machine materials mentioned in the beginning and steel could not be more different. In the first case, the authors use tools with geometrically undefined edges. In the second case, the edges are geometrically defined. To get valid results of the tests, the authors decide to investigate two manufacturing methods, drilling and milling. The main target of the investigation is to reduce the cutting force measured with a force measurement platform underneath the workpiece. Concerning to the direction of the ultrasonic assistance, the authors expect lower cutting forces and longer endurance of the tool in the drilling process. To verify the frequencies and the amplitudes an FFT-analysis is performed. It shows the increasing damping depending on the infeed rate of the tool. The reducing of amplitude of the cutting force comes along.

Keywords: drilling, machining, milling, ultrasonic

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Authors: Simona Pileviciene

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On 24th January 2014, Lithuania notified two primary cases of African swine fever (ASF) in wild boars. The animals were tested positive for ASF virus (ASFV) genome by real-time PCR at the National Reference Laboratory for ASF in Lithuania (NRL), results were confirmed by the European Union Reference Laboratory for African swine fever (CISA-INIA). Intensive wild and domestic animal monitoring program was started. During the period of 2014-2017 ASF was confirmed in two large commercial pig holding with the highest biosecurity. Pigs were killed and destroyed. Since 2014 ASF outbreak territory from east and south has expanded to the middle of Lithuania. Diagnosis by PCR is one of the highly recommended diagnostic methods by World Organization for Animal Health (OIE) for diagnosis of ASF. The aim of the present study was to compare singleplex real-time PCR assays to a duplex assay allowing the identification of ASF and internal control in a single PCR tube and to compare primers, that target the p72 gene (ASF 250 bp and ASF 75 bp) effectivity. Multiplex real-time PCR assays prove to be less time consuming and cost-efficient and therefore have a high potential to be applied in the routine analysis. It is important to have effective and fast method that allows virus detection at the beginning of disease for wild boar population and in outbreaks for domestic pigs. For experiments, we used reference samples (INIA, Spain), and positive samples from infected animals in Lithuania. Results show 100% sensitivity and specificity.

Keywords: African swine fewer, real-time PCR, wild boar, domestic pig

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Authors: Ahmad Ali Shahid, M Shakil Shaukat

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Agriculture is the backbone of economy of Pakistan and Cotton is the major agricultural export and supreme source of raw fiber for our textile industry. To combat against the developing resistance in the target insects and combating these challenges wholesomely, a novel combination of pyramided/stacked genes was conceptualized and later realized, through the means of biotechnology i.e., transformation of three genes namely, Cry1Ac, Cry2A, and EPSP synthase (glyphosate tolerant) genes in the locally cultivated cotton variety. The progenies of the transformed plants were successfully raised and screened under the tunnel conditions for two generations and the present study focused on the screening of plants which were confirmed for containing all of these three genes and their expressions. Initially, the screening was done through glyphosate spray assay and the plants which were healthy and showed no damage on leaves were selected after 07 days of spray. In the laboratory, the DNA of these plants were isolated and subjected to amplification of the three genes. Thus, seventeen out of twenty were confirmed positive for Cry1Ac gene and ten out of twenty were positive for Cry2A gene and all twenty were positive for presence of EPSP synthase gene. Then, the ten plant samples which were confirmed with presence of all three genes were subjected to expression analysis of these proteins through ELISA. The results showed that eight out of ten plants were actively expressing the three transgenes. Real-time PCR was also done to quantify the expression levels of the EPSP synthase gene. Finally, eight plants were confirmed for the presence and active expression of all three genes in T3 generation of the triple gene transformed cotton. These plants may be subjected to T4 generation to develop a new stable variety in due course of time.

Keywords: agriculture, cotton, transformation, cry genes, ELISA, PCR

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Authors: Harold Mauricio Díaz-Vargas, Cristian Alfonso Jimenez-Castaño, David Augusto Cárdenas-Peña, Guillermo Alberto Ortiz-Gómez, Alvaro Angel Orozco-Gutierrez

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Precise identification of the nerves is a crucial task performed by anesthesiologists for an effective Peripheral Nerve Blocking (PNB). Now, anesthesiologists use ultrasound imaging equipment to guide the PNB and detect nervous structures. However, visual identification of the nerves from ultrasound images is difficult, even for trained specialists, due to artifacts and low contrast. The recent advances in deep learning make neural networks a potential tool for accurate nerve segmentation systems, so addressing the above issues from raw data. The most widely spread U-Net network yields pixel-by-pixel segmentation by encoding the input image and decoding the attained feature vector into a semantic image. This work proposes a conditioning approach and encoder pre-training to enhance the nerve segmentation of traditional U-Nets. Conditioning is achieved by the one-hot encoding of the kind of target nerve a the network input, while the pre-training considers five well-known deep networks for image classification. The proposed approach is tested in a collection of 619 US images, where the best C-UNet architecture yields an 81% Dice coefficient, outperforming the 74% of the best traditional U-Net. Results prove that pre-trained models with the conditional approach outperform their equivalent baseline by supporting learning new features and enriching the discriminant capability of the tested networks.

Keywords: nerve segmentation, U-Net, deep learning, ultrasound imaging, peripheral nerve blocking

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Authors: Hannah S. Elizabeth, D. Gnanasekaran, M. R. Manju Gowda, Antony George

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Phytoremediation a new technology of remediating the contaminated soil, water and air using plants and serves as a green technology with environmental friendly approach. The main aim of this technique is cleansing and detoxifying of organic compounds, organo-phosphorous pesticides, heavy metals like arsenic, iron, cadmium, gold, radioactive elements which cause teratogenic and life threatening diseases to mankind and animal kingdom when consume the food crops, vegetables, fruits, cerals, and millets obtained from the contaminated soil. Also, directly they may damage the genetic materials thereby alters the biosynthetic pathways of secondary metabolites and other phytoconstituents which may have different pharmacological activities which lead to lost their efficacy and potency as well. It would reflect in mutagenicity, drug resistance and affect other antagonistic properties of normal metabolism. Is the technology for real clean-up of contaminated soils and the contaminants which are potentially toxic. It reduces the risks produced by a contaminated soil by decreasing contaminants using plants as a source. The advantages are cost-effectiveness and less ecosystem disruption. Plants may also help to stabilize contaminants by accumulating and precipitating toxic trace elements in the roots. Organic pollutants can potentially be chemically degraded and ultimately mineralized into harmless biological compounds. Hence, the use of plants to revitalize contaminated sites is gaining more attention and preferred for its cost-effective when compared to other chemical methods. The introduction of harmful substances into the environment has been shown to have many adverse effects on human health, agricultural productivity, and natural ecosystems. Because the costs of growing a crop are minimal compared to those of soil removal and replacement, the use of plants to remediate hazardous soils is seen as having great promise.

Keywords: cost effective, eco-friendly, phytoremediation, secondary metabolites

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Authors: Rajandeep Kaur, Rajeev Gupta

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Background: Chronic myeloid leukemia (CML) is the most common leukaemia in India. The annual incidence of chronic myeloid leukemia in India was originally reported to be 0.8 to 2.2 per 1,00,000 population. CML is a clonal disorder that is usually easily diagnosed because the leukemic cells of more than 95% of patients have a distinctive cytogenetic abnormality, the Philadelphia chromosome (Ph1). The approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity, has significantly reduced the mortality rate associated with chronic myeloid leukemia (CML) and revolutionized treatment. Material and Methods: 80 diagnosed cases of CML were taken. Investigations were done. Bone marrow and molecular studies were also done and with EUTOS, patients were stratified into low and high-risk groups and then treatment with Imatinib was given to all patients and the molecular response was evaluated at 6 months and 12 months follow up with BCR-ABL by RT-PCR quantitative assay. Results: In the study population, out of 80 patients in the study population, 40 were females and 40 were males, with M: F is 1:1. Out of total 80 patients’ maximum patients (54) were in 31-60 years age group. Our study showed a most common symptom of presentation is abdominal discomfort followed by fever. Out of the total 80 patients, 25 (31.3%) patients had high EUTOS scores and 55 (68.8%) patients had low EUTOS scores. On 6 months follow up 36.3% of patients had Complete Molecular Response, 16.3% of patients had Major Molecular Response and 47.5% of patients had No Molecular Response but on 12 months follow up 71.3% of patients had Complete Molecular Response, 16.25% of patients had Major Molecular Response and 12.5% patients had No Molecular Response. Conclusion: In this study, we found a significant correlation between EUTOS score and Molecular response at 6 months and 12 months follow up after Imatinib therapy.

Keywords: chronic myeloid leukemia, European treatment and outcome study score, hematological response, molecular response, tyrosine kinase inhibitor

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Authors: B. M. Pardeshi

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Introduction: Minerals and trace elements are chemical elements required by our bodies for numerous biological and physiological processes that are necessary for the maintenance of health. Medicinal plants are highly beneficial for the maintenance of good health and prevention of diseases. They are known as potential sources of minerals and vitamins. 30 to 40% of today’s conventional drugs used in the medicinal and curative properties of various plants are employed in herbal supplement botanicals, nutraceuticals and drug. Aim: The authors explored the mineral element content of some herbs, because mineral elements may have significant role in the development and treatment of gastrointestinal diseases, and a close connection between the presence or absence of mineral elements and inflammatory mediators was noted. Methods: Present study deals with the elemental analysis of medicinal plants by Instrumental Neutron activation Analysis and Atomic Absorption Spectroscopy. Medicinal herbals prescribed for skin diseases were purchased from markets and were analyzed by Instrumental Neutron Activation Analysis (INAA) using 252Cf Californium spontaneous fission neutron source (flux* 109 n s-1) and the induced activities were counted by γ-ray spectrometry and Atomic Absorption Spectroscopy (AAS) techniques (Perkin Elmer 3100 Model) available at Department of Chemistry University of Pune, India, was used for the measurement of major, minor and trace elements. Results: 15 elements viz. Al, K, Cl, Na, Mn by INAA and Cu, Co, Pb Ni, Cr, Ca, Fe, Zn, Hg and Cd by AAS were analyzed from different medicinal plants from India. A critical examination of the data shows that the elements Ca , K, Cl, Al, and Fe are found to be present at major levels in most of the samples while the other elements Na, Mn, Cu, Co, Pb, Ni, Cr, Ca, Zn, Hg and Cd are present in minor or trace levels. Conclusion: The beneficial therapeutic effect of the studied herbs may be related to their mineral element content. The elemental concentration in different medicinal plants is discussed.

Keywords: instrumental neutron activation analysis, atomic absorption spectroscopy, medicinal plants, trace elemental analysis, mineral contents

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Authors: Abdelsalam Gomaa, Mahjabeen Ramzan, Tooba Ali Akbar, Huma Nadeem

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The use of tobacco and the health risks linked to it are well known in this day and age due to the presence of easily available information through the internet. The media is a powerful platform that is used by many anti-smoking awareness campaigns to reach their target audience; yet, it has been found that adolescents are taking up smoking every passing day. Half of this smoking population of youngsters resides in Asia alone, which includes Qatar, the focus country of this study. As smoking happens to be one of the largest avoidable causes of serious diseases like cancers and heart problems, children are taking up smoking at an alarming rate everywhere including Qatar. Importance of the health of the citizens of Qatar is one of the pillars of the Qatar vision 2030, which is to ensure a healthy population, both physically and mentally. Since the youth makes up a significant percentage of the population and in order to achieve the health objectives of the Qatar vision 2030, it is essential to ensure the health and well-being of this part of the population of the country as they are the future of Qatar. Children, especially boys who tend to be more aggressive by nature, are highly likely to develop behavioral and health issues due to smoking at an early age. Research conducted around the world has also emphasized on this association between the smokers developing a bad behaviour as well as poor social communication skills. However, due to lack of research into this association, very little is known about the extent to which smoking impacts the children’s academics, health and behaviour. Moreover, a study of this nature has not yet been conducted in Qatar previously as most of the studies focus on adult smokers and ways to minimize the number of smoking habits in universities and workplaces. This study solely focuses on identifying a relationship between smoking and its impacts on the adolescents by conducting a research on different schools across Qatar.

Keywords: adolescents, modelling techniques, Qatar, smoking

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Authors: Arezoo Fallahi, Siamak Derakhshan, Parvaneh Taymoori, Babak Nematshahrbabaki

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Background: Osteoporosis, the most common metabolic bone disease, is an important health care issue. Not only the cost of disease is high but also is one of the causes of disability and mortality and effect on quality of life. Although self-care is effective on disease, s control and treatment but still effective factors on self-care of patient, s viewpoint have not been survey. The aim of this study was to explore effective factors on self-care in women with osteoporosis. Materials and methods: This study was done by conventional content analysis approach in year 2014. Through purposeful sampling 15 women referred to bone mass densitometry centers participated in this study. Inclusion criteria were: Women older than 50 years old with osteoporosis, final diagnosis of osteoporosis for over six –month period, T-score index below -2.5 (lower back or hip), drug use by patients with a physician’s prescription, ability in speaking and attending to participate in the study. Data was collected by face to face and group semi-structure deep interviews and analyzed via content analysis method. To support of rigor of data, criteria credibility, confirmability and transferability were used. Results: during data analysis five categories developed: “hope and disability in the face of illness”, “mutual roles of physician”, “role of family” and “administrative centers and organizations”. To perform self-care behaviors, the participations of this study emphasized on pay attention to their own healthy, regarding patients' rights by physician, pay attention to women's health by men, and the role of media especially radio and television. Conclusion: the finding of the study showed that women’s responsibility with osteoporosis for their health is not a factor but it is multifactorial. Increasing life expectancy in patients, attention to patients needs by physician, increasing health promotion programs in the media and enhancing role of family may provide conditions and infrastructure to empowerment women in doing self-care behavior.

Keywords: women, osteoporosis, self-care, content analysis

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Authors: Micheale Yifter Weldemichael, Hailay Mehari Gebremedhn, Teklehaimanot Hailesslasie

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The advancement of target-specific genome editing tools, including clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein9 (Cas9), mega-nucleases, base editing (BE), prime editing (PE), transcription activator-like endonucleases (TALENs), and zinc-finger nucleases (ZFNs), have paved the way for a modern era of gene editing. CRISPR/Cas9, as a versatile, simple, cost-effective and robust system for genome editing, has dominated the genome manipulation field over the last few years. The application of CRISPR/Cas9 in sorghum improvement is particularly vital in the context of ecological, environmental and agricultural challenges, as well as global climate change. In this context, gene editing using CRISPR/Cas9 can improve nutritional value, yield, resistance to pests and disease and tolerance to different abiotic stress. Moreover, CRISPR/Cas9 can potentially perform complex editing to reshape already available elite varieties and new genetic variations. However, existing research is targeted at improving even further the effectiveness of the CRISPR/Cas9 genome editing techniques to fruitfully edit endogenous sorghum genes. These findings suggest that genome editing is a feasible and successful venture in sorghum. Newer improvements and developments of CRISPR/Cas9 techniques have further qualified researchers to modify extra genes in sorghum with improved efficiency. The fruitful application and development of CRISPR techniques for genome editing in sorghum will not only help in gene discovery, creating new, improved traits in sorghum regulating gene expression sorghum functional genomics, but also in making site-specific integration events.

Keywords: CRISPR/Cas9, genome editing, quality, sorghum, stress, yield

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Authors: I. Hua Chu, Hsiang-Chi Yu, Hsuan Su

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Purpose: To examine the associations between self-determined motivation and physical activity in patients with coronary heart disease (CHD) in a longitudinal study. Methods: Patients with CHD were recruited for this study. Their motivations for exercise were measured by the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2). Physical activity was assessed using the 7-day physical activity recall questionnaire. Duration and energy expenditure of moderate to vigorous physical activity (MVPA) were used in data analysis. All outcome measures were assessed at baseline and 12 months follow up. Data were analyzed using Pearson correlation analysis and regression analysis. Results: The results of the 45 participants (mean age 60.24 yr; 90.2% male) revealed that there were significant negative correlations between amotivation at baseline and duration (r=-.295, p=.049) and energy expenditure (r=-.300, p=.045) of MVPA at 12 months. In contrast, there were significant positive correlations between calculated relative autonomy index (RAI) at baseline and duration (r=.377, p=.011) and energy expenditure (r=.382, p=.010) of MVPA at 12 months. There was no significant correlation between other subscales of the BREQ-2 and duration or energy expenditure of MVPA. Regression analyses revealed that RAI was a significant predictor of duration (p=.011) and energy expenditure (p=.010) of MVPA at 12 months follow-up. Conclusions: These results suggest that the relative degree of self-determined motivation could predict long-term MVPA behaviors in CHD patients. Physical activity interventions are recommended to target enhancing one’s identified and intrinsic motivation to increase the likelihood of physical activity participation in this population.

Keywords: self-determined motivation, physical activity, coronary heart disease, relative autonomy index (RAI)

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Authors: Massimo Tadi, M. Hadi Mohammad Zadeh, Ozge Ogut

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Although how cities’ forms are structured is studied, more efforts are needed on systemic comprehensions and evaluations of the urban morphology through quantitative metrics that are able to describe the performance of a city in relation to its formal properties. More research is required in this direction in order to better describe the urban form characteristics and their impact on the environmental performance of cities and to increase their sustainability stewardship. With the aim of developing a better understanding of the built environment’s systemic structure, the intention of this paper is to present a holistic methodology for studying the behavior of the built environment and investigate the methods for measuring the effect of urban structure to the environmental performance. This goal will be pursued through an inquiry into the morphological components of the urban systems and the complex relationships between them. Particularly, this paper focuses on proximity, referring to the proximity of different land-uses, is a concept with which Integrated Modification Methodology (IMM) explains how land-use allocation might affect the choice of mobility in neighborhoods, and especially, encourage or discourage non-motived mobility. This paper uses proximity to demonstrate that the structure attributes can quantifiably relate to the performing behavior in the city. The target is to devise a mathematical pattern from the structural elements and correlate it directly with urban performance indicators concerned with environmental sustainability. The paper presents some results of this rigorous investigation of urban proximity and its correlation with performance indicators in four different areas in the city of Milan, each of them characterized by different morphological features.

Keywords: built environment, ecology, sustainable indicators, sustainability, urban morphology

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Authors: Yeaji Seok, Myung Kyung Lee

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Background: Even if patients survive after a stroke, stroke patients may experience disability in mobility, sensation, cognition, and speech and language. Stroke patients require rehabilitation for functional recovery and daily life for a considerable time. During rehabilitation, the role of caregivers is important. However, the stroke patients’ quality of life may deteriorate due to family caregivers’ non-preparedness and increased role burden. Purpose: To investigate the prediction of caregivers' preparedness and role burden on stroke patients’ quality of life. Methods: The target population was stroke patients who were hospitalized for rehabilitation and their family care providers. A total of 153 patient-family caregiver dyads were recruited from June to August 2021. Data were collected from self-reported questionnaires and analyzed using descriptive statistics, t-tests, chi-squared test, one-way analysis of variance, Pearson’s correlation coefficients, and multiple regression with SPSS statistics 28 programs. Results: Family caregivers’ preparedness affected stroke patients’ mobility (β = .20, p < 0.05) and character (β = -.084, p < 0.05) and production activities (β = -.197, p < 0.05) in quality of life. The role burden of family caregivers affected language skills (β = .310, p<0.05), visual functions (β=-.357, p < 0.05), thinking skills (β = 0.443, p = 0.05), mood conditions (β = 0.565, p < 0.001), family roles (β = -0.361, p < 0.001), and social roles (β = -0.304, p < 0.001), while the caregivers’ burden of performing self-protection negatively affected patients’ social roles (β = .180, p=.048). In addition, caregivers’ role burden of personal life sacrifice affected patients’ mobility (β = .311, p < 0.05), self-care (β =.232, p < 0.05) and energy (β = .239, p < 0.05). Conclusion: This study indicated that family caregivers' preparedness and role burden affected stroke patients’ quality of life. The results of this study suggested that intervention to improve family caregivers’ preparedness and to reduce role burden should be required for quality of life in stroke patients.

Keywords: quality of life, preparedness, role burden, caregivers, stroke

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Authors: Kuan Yin Hsiao, Shyh Ming Kuo, Yi Jhen Wu, Chin Wen Chuang, Chuen-Fu Lin, Wei-qing Yang, Han Hsiang Huang

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Anti-tumor effects of natural products, like compounds from marine sponges and soft corals, have been investigated for decades. Polymeric nanoparticles prepared from biodegradable and biocompatible molecules, such as Hyaluronan (HA), Chitosan (CHI) and gelatin have been widely studied. Encapsulation of anti-cancer therapies by the biopolymeric nanoparticles in drug delivery system is potentially capable of improving the therapeutic effects and attenuating their toxicity. In the current study, the anti-bladder cancer effects of heteronemin extracted from the sponge Hippospongia sp. with or without HA and CHI nanoparticle encapsulation were assessed and evaluated in vitro. Results showed that IC50 (half maximal inhibitory concentration) of heteronemin toward T24 human bladder cancer cell viability is approximately 0.18 µg/mL. Both plain and HA nanoparticles-encapsulated heteronemin at 0.2 and 0.4 µg/mL significantly reduced T24 cell viability (P<0.001) while HA nanoparticles-encapsulated heteronemin showed weaker viability-inhibitory effects on L929 fibroblasts compared with plain heteronemin at the identical concentrations. HA and CHI nanoparticles-encapsulated heteronemin exhibited significantly stronger inhibitory effects against migration of T24 human bladder cancer cell than those exerted by plain heteronemin at the same concentrations (P<0.001). The flow cytometric results showed that 0.2 µg/mL HA and CHI nanoparticles-encapsulated heteronemin induced higher early apoptosis rate than that induced by plain heteronemin at the same concentration. These results show that HA and CHI nanoparticle encapsulation is able to elevate anti-migratory and apoptosis-inducing effects exerted by heteronemin against bladder cancer cells in vitro. The in vivo anti-bladder cancer effects of the compound with or without HA/CHI nanoparticle encapsulation will be further investigated and examined using murine tumor models. The data obtained from this study will extensively evaluate of the anti-bladder cancer effects of heteronemin as well as HA/CHI-encapsulated heteronemin and pave a way to develop potential bladder cancer treatment.

Keywords: heteronemin, nanoparticles, hyaluronan, chitosan, bladder cancer

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Authors: Keerthie Dissanayake, Chandrika Jayasinghe, Priyani Wanigasekara, Jayampathy Dissanayake, Ajith Sominanda

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The routine use of Disease Activity Score-28 (DAS28) to assess the disease activity in rheumatoid arthritis (RA) is limited due to its dependency on laboratory investigations and the complex calculations involved. In contrast, the clinical disease activity index (CDAI) is simple to calculate, which makes the "treat to target" strategy for the management of RA more practical. We aimed to assess the validity of CDAI compared to DAS28 in RA patients in Sri Lanka. A total of 103 newly diagnosed RA patients were recruited, and their disease activity was calculated using DAS 28 and CDAI during the first visit to the clinic (0 months) and re-assessed at 4 and 9 months of the follow-up visits. The validity of the CDAI, compared to DAS 28, was evaluated. Patients had a female preponderance (6:1) and a short symptom duration (mean = 6.33 months). The construct validity of CDAI, as assessed by Cronbach's α test, was 0.868. Convergent validity was assessed by correlation and Kappa statistics. Strong positive correlations were observed between CDAI and DAS 28 at the baseline (0 months), 4, and 9 months of evaluation (Spearman's r = 0.9357, 0.9354, 0.9106, respectively). Moderate-good inter-rater agreements between the DAS-28 and CDAI were observed (Weighted kappa of 0.660, 0.519, and 0.741 at 0, 4, and 9 months respectively). Discriminant validity, as assessed by ROC curves at 0, 4th, and 9th months of the evaluation, showed the area under the curve (AUC) of 0.958, 0.985, and 0.914, respectively. The suggested cut-off points for different CDAI disease activity categories according to ROC curves were ≤ 2 (Remission), >2 to ≤ 5 (low), >5 to ≤ 18 (moderate), > 18 (high). These findings indicate that the CDAI has good concordance with DAS 28 in assessing the disease activity in RA patients in this study sample.

Keywords: rheumatoid arthritis, CDAI, disease activity, Sri Lanka, validation

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Authors: Pibool Waijittragum

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The purpose of this research is to analyze the marketing strategies of Thai Halal products which related to the way of life for Thai Muslims. The expected benefit is the marketing strategy for brand building process for Halal products in Thailand. 4 elements of marketing strategies which necessary for the brand identity creation is the research framework: Consists of Attributes, Benefits, Values and Personality. The research methodology was applied using qualitative and quantitative; 19 marketing experts with dynamic roles in Thai consumer products were interviewed. In addition, a field survey of 122 Thai Muslims selected from 175 Muslim communities in Bangkok was studied. Data analysis will be according to 5 categories of Thai Halal product: 1) Meat 2) Vegetable and Fruits 3) Instant foods and Garnishing ingredient 4) Beverages, desserts and snacks 5) Hygienic daily products; such as soap, shampoo and body lotion. The results will explain some suitable representation in the marketing strategies of Thai Halal products as are: 1) Benefit; the characteristics of the product with its benefit. Consumers will purchase this product with the reason of; it is beneficial nutrients product, there are no toxic or chemical residues. Fresh and clean materials 2) Attribute; the exterior images that attract to consumer. Consumers will purchase this product with the reason of; there is a standard proof mark, food and drug secure proof mark and Halal products mark. Packaging and its materials should be draw attention. Use an attractive graphic. Use outstanding images of product, material or ingredients. 3) Value; the value of products that affect to consumers perception; it is healthy products. Accumulate quality of life. It is a product of expertise, manufacturing of research result. Consumers are important. It’s sincere, honest and reliable to all. 4) Personality; reflection of consumers thought. The personality feedback to them after they were consumes this product; they are health care persons. They are the rational person, moral person, justice person and thoughtful person like a progressive thinking.

Keywords: marketing strategies, product identity, branding, Thai Halal products

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Authors: Chairun Wiedyaningsih, Sri Suryawati, Yati Soenarto, Muhammad Hakimi

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Background: Many drugs used in paediatrics are not commercially available in suitable dosage forms. Therefore, the drugs often prescribed in extemporaneous compounding dosage form. Compounding can pose health risks include poor quality and unsafe products. Studies of compounding dosage form have primarily focused on prescription profiles, reasons of prescribing never be explored. Objectives: The study was conducted to identify factors influencing physicians’ decision to prescribe extemporaneous compounding dosage form for paediatric outpatients. Setting: Daerah Istimewa Yogyakarta (DIY) province, Indonesia. Method: Qualitative semi-structured interviews were conducted with 15 general physicians and 7 paediatricians to identify the reason of prescribing extemporaneous compounding dosage form. The interviews were transcribed and analysed using thematic analysis. Results: Factors underlying prescribing of compounding could be categorized to therapy, healthcare system, patient and past experience. The primary reasons of therapy factors were limited availability of drug compositions, dosages or formulas specific for children. Beliefs in efficacy of the compounding forms were higher when the drugs used primarily to overcome complex cases. Physicians did not concern about compounding form containing several active substances because manufactured syrups may also contain several active substances. Although medicines were available in manufactured syrups, limited institutional budget was healthcare system factor of compounding prescribing. The prescribing factors related to patients include easy to use, efficient and lower price. The prescribing factors related to past experience were physicians’ beliefs to the progress of patient's health status. Conclusions: Compounding was prescribed based on therapy-related factors, healthcare system factors, patient factors and past experience.

Keywords: compounding dosage form, interview, physician, prescription

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Authors: Reuben Kinyuru Njuguna, Martin Mabuya Njuguna

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Digital platforms, such as The Internet, and the advent of digital marketing strategies, have led to many changes in the marketing of goods and services. These have resulted in improved service quality, enhanced customer relations, productivity gains, marketing transaction cost reductions, improved customer service and flexibility in fulfilling customers’ changing needs and lifestyles. Consequently, the purpose of this study was to determine the effect of digital marketing practices on the financial performance of mobile network operators in the telecommunications industry in Kenya. The objectives of the study were to establish how digital customer relationship management strategies on performance of mobile network operators in Kenya. The study used an explanatory cross-sectional survey research design, while the target population was made up of from the 4 major mobile network operators in Kenya, namely Safaricom Limited, Airtel Networks Kenya Limited, Finserve Africa Limited and Telkom Kenya Limited. Sampling strategy was stratified sampling with a sample size of 97 respondents. Digital customer relationship strategies were seen to influence firm performance, through enhancing convenience, building trust, encouraging growth in market share through creating sustainable relationships, building commitment with customers, enhancing customer retention and customer satisfaction. Digital customer relationship management were seen to maximize gross profits by increasing customer satisfaction, loyalty and retention. The study recommended upscaling the use of digital customer relationship management strategies to further enhance firm performance, given their great potential in this regard.

Keywords: customer relationship management, customer service delivery, performance, customer satisfaction

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Authors: M. Kowalski, M. Brodowski, K. Dziabowska, E. Czaczyk, W. Bialobrzeska, N. Malinowska, S. Zoledowska, R. Bogdanowicz, D. Nidzworski

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Boron-doped-carbon nanowall (BCNW) electrodes are recently in much interest among scientists. BCNWs are good candidates for biosensor purposes as they possess interesting electrochemical characteristics like a wide potential range and the low difference between redox peaks. Moreover, from technical parameters, they are mechanically resistant and very tough. The production process of the microwave plasma-enhanced chemical vapor deposition (MPECVD) allows boron to build into the structure of the diamond being formed. The effect is the formation of flat, long structures with sharp ends. The potential of these electrodes was checked in the biosensing field. The procedure of simple carbon electrodes modification by antibodies was adopted to BCNW for specific antigen recognition. Surface protein D deriving from H. influenzae pathogenic bacteria was chosen as a target analyte. The electrode was first modified with the aminobenzoic acid diazonium salt by electrografting (electrochemical reduction), next anti-protein D antibodies were linked via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) chemistry, and free sites were blocked by BSA. Cyclic voltammetry measurements confirmed the proper electrode modification. Electrochemical impedance spectroscopy records indicated protein detection. The sensor was proven to detect protein D in femtograms. This work was supported by the National Centre for Research and Development (NCBR) TECHMATSTRATEG 1/347324/12/NCBR/ 2017.

Keywords: anti-protein D antibodies, boron-doped carbon nanowall, impedance spectroscopy, Haemophilus influenzae.

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Authors: M. G. Cattaneo

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The non-effectiveness of certain codified human rights is particularly apparent with reference to the lack of access to essential drugs in developing countries, which represents a breach of the human right to receive adequate health assistance. This paper underlines the conflict and the legal contradictions between human rights, namely health rights, international Intellectual Property Rights, in particular patent law, as well as international trade law. The paper discusses the crucial links between R&D costs for innovation, patents and new medical drugs, with the goal of reformulating the hierarchies of priorities and of interests at stake in the international intellectual property (IP) law system. Different from what happens today, International patent law should be a legal instrument apt at rebalancing an axiological asymmetry between the (conflicting) needs at stake The core argument in the paper is the proposal of an alternative pathway, namely a feasible proposal for a patent law reform. IP laws tend to balance the benefits deriving from innovation with the costs of the provided monopoly, but since developing countries and industrialized countries are in completely different political and economic situations, it is necessary to (re)modulate such exchange according to the different needs. Based on this critical analysis, the paper puts forward a proposal, called Trading Time for Space (TTS), whereby a longer time for patent exclusive life in western countries (Time) is offered to the patent holder company, in exchange for the latter selling the medical drug at cost price in developing countries (Space). Accordingly, pharmaceutical companies should sell drugs in developing countries at the cost price, or alternatively grant a free license for the sale in such countries, without any royalties or fees. However, such social service shall be duly compensated. Therefore, the consideration for such a service shall be an extension of the temporal duration of the patent’s exclusive in the country of origin that will compensate the reduced profits caused by the supply at the price cost in developing countries.

Keywords: global health, global justice, patent law reform, access to drugs

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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