Search results for: Drug targets

Authors: Dhananjay C. Joshi, Jung-Hsin Lin

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Protein-protein interactions (PPI) play a crucial role in many biological processes such as cell signalling, transcription, translation, replication, signal transduction, and drug targeting, etc. Structural information about protein-protein interaction is essential for understanding the molecular mechanisms of these processes. Structures of protein-protein complexes are still difficult to obtain by biophysical methods such as NMR and X-ray crystallography, and therefore protein-protein docking computation is considered an important approach for understanding protein-protein interactions. However, reliable prediction of the protein-protein complexes is still under way. In the past decades, several grid-based docking algorithms based on the Katchalski-Katzir scoring scheme were developed, e.g., FTDock, ZDOCK, HADDOCK, RosettaDock, HEX, etc. However, the success rate of protein-protein docking prediction is still far from ideal. In this work, we first propose a more practical measure for evaluating the success of protein-protein docking predictions,the rate of first success (RFS), which is similar to the concept of mean first passage time (MFPT). Accordingly, we have assessed the ZDOCK bound and unbound benchmarks 2.0 and 3.0. We also createda new benchmark set for protein-protein docking predictions, in which the complexes have experimentally determined binding affinity data. We performed free energy calculation based on the solution of non-linear Poisson-Boltzmann equation (nlPBE) to improve the binding mode prediction. We used the well-studied thebarnase-barstarsystem to validate the parameters for free energy calculations. Besides,thenlPBE-based free energy calculations were conducted for the badly predicted cases by ZDOCK and ZRANK. We found that direct molecular mechanics energetics cannot be used to discriminate the native binding pose from the decoys.Our results indicate that nlPBE-based calculations appeared to be one of the promising approaches for improving the success rate of binding pose predictions.

Keywords: protein-protein docking, protein-protein interaction, molecular mechanics energetics, Poisson-Boltzmann calculations

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Authors: Saurabh Sharma, Yong Sun, Bruce Vernham

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Accurate prediction of NOx emission is a continuous challenge in the field of diesel engine-out emission modeling. Performing experiments for each conditions and scenario cost significant amount of money and man hours, therefore model-based development strategy has been implemented in order to solve that issue. NOx formation is highly dependent on the burn gas temperature and the O₂ concentration inside the cylinder. The current empirical models are developed by calibrating the parameters representing the engine operating conditions with respect to the measured NOx. This makes the prediction of purely empirical models limited to the region where it has been calibrated. An alternative solution to that is presented in this paper, which focus on the utilization of in-cylinder combustion parameters to form a predictive semi-empirical NOx model. The result of this work is shown by developing a fast and predictive NOx model by using the physical parameters and empirical correlation. The model is developed based on the steady state data collected at entire operating region of the engine and the predictive combustion model, which is developed in Gamma Technology (GT)-Power by using Direct Injected (DI)-Pulse combustion object. In this approach, temperature in both burned and unburnt zone is considered during the combustion period i.e. from Intake Valve Closing (IVC) to Exhaust Valve Opening (EVO). Also, the oxygen concentration consumed in burnt zone and trapped fuel mass is also considered while developing the reported model.  Several statistical methods are used to construct the model, including individual machine learning methods and ensemble machine learning methods. A detailed validation of the model on multiple diesel engines is reported in this work. Substantial numbers of cases are tested for different engine configurations over a large span of speed and load points. Different sweeps of operating conditions such as Exhaust Gas Recirculation (EGR), injection timing and Variable Valve Timing (VVT) are also considered for the validation. Model shows a very good predictability and robustness at both sea level and altitude condition with different ambient conditions. The various advantages such as high accuracy and robustness at different operating conditions, low computational time and lower number of data points requires for the calibration establishes the platform where the model-based approach can be used for the engine calibration and development process. Moreover, the focus of this work is towards establishing a framework for the future model development for other various targets such as soot, Combustion Noise Level (CNL), NO₂/NOx ratio etc.

Keywords: Diesel engine, machine learning, NOx emission, semi-empirical.

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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: Wisam H. Benamer, Ehab A. Elfallah, Mohamed A. Elshaari, Farag A. Elshaari

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A challenge for laboratories is to provide bacterial identification and antibiotic sensitivity results within a short time. Hence, advancement in the required technology is desirable to improve timing, accuracy and quality. Even with the current advances in methods used for both phenotypic and genotypic identification of bacteria the need is there to develop method(s) that enhance the outcome of bacteriology laboratories in accuracy and time. The hypothesis introduced here is based on the assumption that the chromosome of any bacteria contains unique sequences that can be used for its identification and typing. The outcome of a pilot study designed to test this hypothesis is reported in this manuscript. Methods: The complete chromosome sequences of several bacterial species were downloaded to use as search targets for unique sequences. Visual basic and SQL server (2014) were used to generate a complete set of 18-base long primers, a process started with reverse translation of randomly chosen 6 amino acids to limit the number of the generated primers. In addition, the software used to scan the downloaded chromosomes using the generated primers for similarities was designed, and the resulting hits were classified according to the number of similar chromosomal sequences, i.e., unique or otherwise. Results: All primers that had identical/similar sequences in the selected genome sequence(s) were classified according to the number of hits in the chromosomes search. Those that were identical to a single site on a single bacterial chromosome were referred to as unique. On the other hand, most generated primers sequences were identical to multiple sites on a single or multiple chromosomes. Following scanning, the generated primers were classified based on ability to differentiate between medically important bacterial and the initial results looks promising. Conclusion: A simple strategy that started by generating primers was introduced; the primers were used to screen bacterial genomes for match. Primer(s) that were uniquely identical to specific DNA sequence on a specific bacterial chromosome were selected. The identified unique sequence can be used in different molecular diagnostic techniques, possibly to identify bacteria. In addition, a single primer that can identify multiple sites in a single chromosome can be exploited for region or genome identification. Although genomes sequences draft of isolates of organism DNA enable high throughput primer design using alignment strategy, and this enhances diagnostic performance in comparison to traditional molecular assays. In this method the generated primers can be used to identify an organism before the draft sequence is completed. In addition, the generated primers can be used to build a bank for easy access of the primers that can be used to identify bacteria.

Keywords: Bacteria chromosome, bacterial identification, sequence, primer generation.

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Authors: Rupinder Bakshi, Geeta Walia, Anita Gupta

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Urinary Tract Infections are considered as one of the most common bacterial infections with an estimated annual global incidence of 150 million. Antimicrobial drug resistance is one of the major threats due to wide spread usage of uncontrolled antibiotics. In this study, a total number of 9149 urine samples were collected from R.H Patiala and processed in the Department of Microbiology G. M. C Patiala (January 2013 to December 2013). Urine samples were inoculated on MacConkey’s and blood agar plates and incubated at 370C for 24 hrs. The organisms were identified by colony characters, Gram’s staining, and biochemical reactions. Antimicrobial susceptibility of the isolates was determined against various antimicrobial agents (Hi – Media Mumbai India) by Kirby Bauer DISK diffusion method on Muller Hinton agar plates. Maximum patients were in the age group of 21-30 yrs followed by 31-40 yrs. Males (34%) are less prone to urinary tract infections than females (66%). Culture was positive in 25% of the samples. Escherichia coli was the most common isolate 60.3% followed by Klebsiella pneumoniae 13.5%, Proteus spp. 9% and Staphylococcus aureus 7.6%. Most of the urinary isolates were sensitive to, carbepenems, Aztreonam, Amikacin, and Piperacillin + Tazobactum. All the isolates showed a good sensitivity towards Nitrofurantoin (82%). ESBL production was found to be 70.6% in Escherichia coli and 29.4% in Klebsiella pneumonia. Susceptibility of ESBL producers to Imipenem, Nitrofurantoin and Amikacin were found to be 100%, 76%, and 75% respectively. Uropathogens are increasingly showing resistance to many antibiotics making empiric management of outpatient UTIs challenging. Ampicillin, Cotrimoxazole and Ciprofloxacin should not be used in empiric treatment. Nitrofurantoin could be used in lower urinary tract infection. Knowledge of uropathogens and their antimicrobial susceptibility pattern in a geographical region will help in appropriate and judicious antibiotic usage in a health care setup.

Keywords: Urinary Tract Infection, UTI, antibiotic susceptibility pattern, ESBL.

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Authors: Anna Pick Kiong Ling, Jia May Chin, Rhun Yian Koh, Ying Pei Wong

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Background: Uncontrolled inflammation may cause serious inflammatory diseases if left untreated. Non-steroidal anti-inflammatory drug (NSAIDs) is commonly used to inhibit pro-inflammatory enzymes, thus, reduce inflammation. However, long term administration of NSAIDs leads to various complications. Medicinal plants are getting more attention as it is believed to be more compatible with human body. One of them is a flavonoid-containing medicinal plants, Strobilanthes crispus which has been traditionally claimed to possess anti-inflammatory and antioxidant activities. Nevertheless, its anti-inflammatory activities are yet to be scientifically documented. Objectives: This study aimed to examine the anti-inflammatory activity of S. crispus by investigating its effects on intracellular oxidative stress and prostaglandin E₂ (PGE₂) levels. Materials and Methods: In this study, the Maximum Non-toxic Dose (MNTD) of methanol extract of both leaves and stems of S. crispus was first determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenytetrazolium Bromide (MTT) assay. The effects of S. crispus extracts at MNTD and half MNTD (½MNTD) on intracellular ROS as well as PGE₂ levels in 1.0 µg/mL LPS-stimulated RAW 264.7 macrophages were then be measured using DCFH-DA and a competitive enzyme immunoassay kit, respectively. Results: The MNTD of leaf extract was determined as 700µg/mL while for stem was as low as 1.4µg/mL. When LPS-stimulated RAW 264.7 macrophages were subjected to the MNTD of S. crispus leaf extract, both intracellular ROS and PGE₂ levels were significantly reduced. In contrast, stem extract at both MNTD and ½MNTD did not significantly reduce the PGE₂ level, but significantly increased the intracellular ROS level. Conclusion: The methanol leaf extract of S. crispus may possess anti-inflammatory properties as it is able to significantly reduce the intracellular ROS and PGE₂ levels of LPS-stimulated cells. Nevertheless, further studies such as investigating the interleukin, nitric oxide and cytokine tumor necrosis factor-α (TNFα) levels has to be conducted to further confirm the anti-inflammatory properties of S. crispus.

Keywords: Anti-inflammatory, natural products, prostaglandin E2, reactive oxygen species.

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Authors: S. Vijayakumar, M. Sasikala, T. S. Mohammed Saleem, Gurusharan, K. Gauthaman

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The main objective of our study is to collect data about the profile of the asthmatic patients in Assam and thereby have a comprehensive knowledge of the factors influencing the asthmatic patients of the state and their medication pattern. We developed a search strategy to find any publication about the community based survey asthma related and used. These to search the MEDLINE (1996 to current literature) CINAHL DOAJ pubmed databases using the key phrases, Asthma, Respiratory disorders, Drug therapy of Asthma, database decision support system and asthma. The appropriate literature was printed out from the online source and library (Journal) source. The study was conducted through a set of structured and non-structured questionnaires targeted on the asthmatic patients belonging to the rural and urban areas of Assam, during the month of Dec 2006 to July 2007, 138 cases were studied in Gauwathi Medical College & Hospital located in Bhangagarh, Assam in India. The demographic characteristics a factor in 138 patients with asthma with allergic rhinitis (cases) gives the detail profile of asthmatic patient-s distribution of Assam as classified on the basis of age and sex. It is evident from the study that male populations (66%) are more prone to asthma as compared to the females (34%).Another striking features that emerged from this survey is the maximum prevalence of asthma in the age group of 20- 30 years followed by infants belonging to the age group of 7 (0.05%) 0-10years among both male and female populations of Assam. The high incidence of asthma in the age group of 20-30 years may probably be due to the allergy arising out of sudden exposure to dust and pollen which the children face while playing and going to the school. The rural females in the age group of 30-40 years are more prone to asthma than urban females in the same age group may be due to sex differentiation among the tribal population of the state. Pharmacists should educate the asthmatics how to use inhalers considering growing menace of asthma in the state. Safer drugs should be produced in the form of aerosol so that easy administration by the asthmatic patients and physicians of the state is possible for curing asthma. The health centers should be more equipped with the medicines to cure asthma in the state like Assam.

Keywords: Asthma, Respiratory disease, Smoker.

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Authors: Abdullah Faqihi, John Hedley

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Biosensors play a significant role in the healthcare sectors, scientific and technological progress. Developing electrodes that are easy to manufacture and deliver better electrochemical performance is advantageous for diagnostics and biosensing. They can be implemented extensively in various analytical tasks such as drug discovery, food safety, medical diagnostics, process controls, security and defence, in addition to environmental monitoring. Development of biosensors aims to create high-performance electrochemical electrodes for diagnostics and biosensing. A biosensor is a device that inspects the biological and chemical reactions generated by the biological sample. A biosensor carries out biological detection via a linked transducer and transmits the biological response into an electrical signal; stability, selectivity, and sensitivity are the dynamic and static characteristics that affect and dictate the quality and performance of biosensors. In this research, a developed experimental study for laser scribing technique for graphene oxide inside a vacuum chamber for processing of graphene oxide is presented. The processing of graphene oxide (GO) was achieved using the laser scribing technique. The effect of the laser scribing on the reduction of GO was investigated under two conditions: atmosphere and vacuum. GO solvent was coated onto a LightScribe DVD. The laser scribing technique was applied to reduce GO layers to generate rGO. The micro-details for the morphological structures of rGO and GO were visualised using scanning electron microscopy (SEM) and Raman spectroscopy so that they could be examined. The first electrode was a traditional graphene-based electrode model, made under normal atmospheric conditions, whereas the second model was a developed graphene electrode fabricated under a vacuum state using a vacuum chamber. The purpose was to control the vacuum conditions, such as the air pressure and the temperature during the fabrication process. The parameters to be assessed include the layer thickness and the continuous environment. Results presented show high accuracy and repeatability achieving low cost productivity.

Keywords: Laser scribing, LightScribe DVD, graphene oxide, scanning electron microscopy.

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

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

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

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Authors: Rajan Rajabalaya, Li-Qun Tor, Sheba David

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Transdermal delivery of ondansetron hydrochloride (OdHCl) can prevent the problems encountered with oral ondansetron. In previously conducted studies, effect of amount of polyvinyl pyrrolidone, permeation enhancer and casting solvent on the physicochemical properties on OdHCl were investigated. It is feasible to develop ondansetron transdermal patch by using ethyl cellulose and polyvinyl pyrrolidone with dibutyl pthalate as plasticizer, however, the desired flux is not achieved. The primary aim of this study is to use dimethyl succinate (DMS) and propylene glycol that are not incorporated in previous studies to determine their effect on the physicochemical properties of an OdHCl transdermal patch using ethyl cellulose and polyvinyl pyrrolidone. This study also investigates the effect of permeation enhancer (eugenol and phosphatidylcholine) on the release of OdHCl. The results showed that propylene glycol is a more suitable plasticizer compared to DMS in the fabrication of OdHCl transdermal patch using ethyl cellulose and polyvinyl pyrrolidone as polymers. Propylene glycol containing patch has optimum drug content, thickness, moisture content and water absorption, tensile strength, and a better release profile than DMS. Eugenol and phosphatidylcholine can increase release of OdHCl from the patches. From the physicochemical result and permeation profile, a combination of 350mg of ethyl cellulose, 150mg polyvinyl pyrrolidone, 3% of total polymer weight of eugenol, and 40% of total polymer weight of propylene glycol is the most suitable formulation to develop an OdHCl patch. OdHCl release did not increase with increasing the percentage of plasticiser. DMS 4, PG 4, DMS 9, PG 9, DMS 14, and PG 14 gave better release profiles where using 300mg: 0mg, 300mg: 100mg, and 350mg: 150mg of EC: PVP. Thus, 40% of PG or DMS appeared to be the optimum amount of plasticiser when the above combination where EC: PVP was used. It was concluded from the study that a patch formulation containing 350mg EC, 150mg PVP, 40% PG and 3% eugenol is the best transdermal matrix patch compositions for the uniform and continuous release/permeation of OdHCl over an extended period. This patch design can be used for further pharmacokinetic and pharmacodynamic studies in suitable animal models.

Keywords: Ondansetron hydrochloride, dimethyl succinate, eugenol.

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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: R. Tamborrino, F. Rinaudo

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Digital technologies offer possibilities to effectively convert historical archives into instruments of knowledge able to provide a guide for the interpretation of historical phenomena. Digital conversion and management of those documents allow the possibility to add other sources in a unique and coherent model that permits the intersection of different data able to open new interpretations and understandings. Urban history uses, among other sources, the inventories that register human activities in a specific space (e.g. cadastres, censuses, etc.). The geographic localisation of that information inside cartographic supports allows for the comprehension and visualisation of specific relationships between different historical realities registering both the urban space and the peoples living there. These links that merge the different nature of data and documentation through a new organisation of the information can suggest a new interpretation of other related events. In all these kinds of analysis, the use of GIS platforms today represents the most appropriate answer. The design of the related databases is the key to realise the ad-hoc instrument to facilitate the analysis and the intersection of data of different origins. Moreover, GIS has become the digital platform where it is possible to add other kinds of data visualisation. This research deals with the industrial development of Turin at the beginning of the 20th century. A census of factories realized just prior to WWI provides the opportunity to test the potentialities of GIS platforms for the analysis of urban landscape modifications during the first industrial development of the town. The inventory includes data about location, activities, and people. GIS is shaped in a creative way linking different sources and digital systems aiming to create a new type of platform conceived as an interface integrating different kinds of data visualisation. The data processing allows linking this information to an urban space, and also visualising the growth of the city at that time. The sources, related to the urban landscape development in that period, are of a different nature. The emerging necessity to build, enlarge, modify and join different buildings to boost the industrial activities, according to their fast development, is recorded by different official permissions delivered by the municipality and now stored in the Historical Archive of the Municipality of Turin. Those documents, which are reports and drawings, contain numerous data on the buildings themselves, including the block where the plot is located, the district, and the people involved such as the owner, the investor, and the engineer or architect designing the industrial building. All these collected data offer the possibility to firstly re-build the process of change of the urban landscape by using GIS and 3D modelling technologies thanks to the access to the drawings (2D plans, sections and elevations) that show the previous and the planned situation. Furthermore, they access information for different queries of the linked dataset that could be useful for different research and targets such as economics, biographical, architectural, or demographical. By superimposing a layer of the present city, the past meets to the present-industrial heritage, and people meet urban history.

Keywords: Digital urban history, census, digitalisation, GIS, modelling, digital humanities.

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Authors: Samar Saadeldin Abdelmotalab Omer, Ikram Mohamed Eltayeb Elsiddig, Amna Beshir Medani Ahmed, Saad Mohamed Hussein Ayoub

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Many herbal medicinal products are considered potential anti-hypercholesterolemic agents with encouraging safety profiles, however only a limited amount of clinical research exists to support their efficacy. The present study was designed to compare the antihypercholesterolemic and antioxidant activities of the crude ethanolic extracts of Citrus reticulata fruit peel, Zingiber officinale rhizome and Sesamum indicum seeds. Forty-five rats were used throughout the experiment which are extended for four weeks. These were divided into nine groups, five rats per each group as follows; group 1 was the normal control group (rats only fed standard normal rat diet), group 2 was the hypercholesterolemic control group (rats fed only hypercholesterolemic diet which contained 1% cholesterol plus 10% saturated animal fat added to the normal rat diet), groups 3 and 4 were fed hypercholesterolemic diet in addition to Citrus reticulata ethanolic extract at doses of (250mg/kg (group 3) and 500mg/kg (group 4)) administered daily via oral route, groups 5 and 6 were given hypercholesterolemic diet in addition to Zingiber officinale ethanolic extract at doses of (250mg/kg (group 5) and 500mg/kg (group 6)) daily through oral route, groups 7 and 8 fed on hypercholesterolemic diet in addition to Sesamum indicum ethanolic extract at doses of (250mg/kg (group 7) and 500mg/kg (group 8)) daily orally; and group 9 rats were given hypercholesterolemic diet in addition to atorvastatin (0.18mg/kg) daily via oral route as a standard reference antihypercholesterolemic drug. Blood samples from all groups were drawn from the retro-orbital venous plexus four weeks following treatment after overnight fasting and the lipid profile (total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and triglyceride levels) were measured and the risk ratio (TC/HDL-C) was assessed. The antioxidant activity of the three plants extracts was determined using DPPH free-radical antioxidant assay. Results of in vivo and in vitro antihypercholesterolemic and antioxidant assay respectively, revealed that the three extracts possess comparable antioxidant and antihypercholesterolemic activities.

Keywords: Antihypercholesterolemic effects, Antioxidant activity, HDL, LDL, TC, TGs, Citrus reticulata, Sesamum indicum, Zingiber officinale.

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Authors: Payam Mousavi, Andrew L. Stewart, Huiwen You, Aryeh F. G. Fayerman

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We present a decision-support tool to assist an operator in the detection and tracking of a suspect vehicle traveling to an unknown target destination. Multiple data sources, such as traffic cameras, traffic information, weather, etc., are integrated and processed in real-time to infer a suspect’s intended destination chosen from a list of pre-determined high-value targets. Previously, we presented our work in the detection and tracking of vehicles using traffic and airborne cameras. Here, we focus on the fusion and processing of that information to predict a suspect’s behavior. The network of cameras is represented by a directional graph, where the edges correspond to direct road connections between the nodes and the edge weights are proportional to the average time it takes to travel from one node to another. For our experiments, we construct our graph based on the greater Los Angeles subset of the Caltrans’s “Performance Measurement System” (PeMS) dataset. We propose a Bayesian approach where a posterior probability for each target is continuously updated based on detections of the suspect in the live video feeds. Additionally, we introduce the concept of ‘soft interventions’, inspired by the field of Causal Inference. Soft interventions are herein defined as interventions that do not immediately interfere with the suspect’s movements; rather, a soft intervention may induce the suspect into making a new decision, ultimately making their intent more transparent. For example, a soft intervention could be temporarily closing a road a few blocks from the suspect’s current location, which may require the suspect to change their current course. The objective of these interventions is to gain the maximum amount of information about the suspect’s intent in the shortest possible time. Our system currently operates in a human-on-the-loop mode where at each step, a set of recommendations are presented to the operator to aid in decision-making. In principle, the system could operate autonomously, only prompting the operator for critical decisions, allowing the system to significantly scale up to larger areas and multiple suspects. Once the intended target is identified with sufficient confidence, the vehicle is reported to the authorities to take further action. Other recommendations include a selection of road closures, i.e., soft interventions, or to continue monitoring. We evaluate the performance of the proposed system using simulated scenarios where the suspect, starting at random locations, takes a noisy shortest path to their intended target. In all scenarios, the suspect’s intended target is unknown to our system. The decision thresholds are selected to maximize the chances of determining the suspect’s intended target in the minimum amount of time and with the smallest number of interventions. We conclude by discussing the limitations of our current approach to motivate a machine learning approach, based on reinforcement learning in order to relax some of the current limiting assumptions.

Keywords: Autonomous surveillance, Bayesian reasoning, decision-support, interventions, patterns-of-life, predictive analytics, predictive insights.

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is a clinical state associated with low-grade inflammation. It is also a major risk factor for insulin resistance (IR). In its advanced stages, metabolic syndrome (MetS), a much more complicated disease which may lead to life-threatening problems, may develop. Obesity-mediated IR seems to correlate with the inflammation. Human studies performed particularly on pediatric population are scarce. The aim of this study is to detect possible associations between inflammation and IR in terms of some related ratios. 549 children were grouped according to their age- and sex-based body mass index (BMI) percentile tables of WHO. MetS components were determined. Informed consent and approval from the Ethics Committee for Clinical Investigations were obtained. The principles of the Declaration of Helsinki were followed. The exclusion criteria were infection, inflammation, chronic diseases and those under drug treatment. Anthropometric measurements were obtained. Complete blood cell, fasting blood glucose, insulin, and C-reactive protein (CRP) analyses were performed. Homeostasis model assessment of insulin resistance (HOMA-IR), systemic immune inflammation (SII) index, tense index, alanine aminotransferase to aspartate aminotransferase ratio (ALT/AST), neutrophils to lymphocyte (NLR), platelet to lymphocyte, and lymphocyte to monocyte ratios were calculated. Data were evaluated by statistical analyses. The degree for statistical significance was 0.05. Statistically significant differences were found among the BMI values of the groups (p < 0.001). Strong correlations were detected between the BMI and waist circumference (WC) values in all groups. Tense index values were also correlated with both BMI and WC values in all groups except overweight (OW) children. SII index values of children with normal BMI were significantly different from the values obtained in OW, obese, morbid obese and MetS groups. Among all the other lymphocyte ratios, NLR exhibited a similar profile. Both HOMA-IR and ALT/AST values displayed an increasing profile from N towards MetS3 group. BMI and WC values were correlated with HOMA-IR and ALT/AST. Both in morbid obese and MetS groups, significant correlations between CRP versus SII index as well as HOMA-IR versus ALT/AST were found. ALT/AST and HOMA-IR values were correlated with NLR in morbid obese group and with SII index in MetS group, (p < 0.05), respectively. In conclusion, these findings showed that some parameters may exhibit informative differences between the early and late stages of obesity. Important associations among HOMA-IR, ALT/AST, NLR and SII index have come to light in the morbid obese and MetS groups. This study introduced the SII index and NLR as important inflammatory markers for the discrimination of normal and obese children. Interesting links were observed between inflammation and IR in morbid obese children and those with MetS, both being late stages of obesity.

Keywords: Children, inflammation, insulin resistance, metabolic syndrome, obesity.

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Authors: K. Beheshti Maal, R. Shafiee

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According to FDA (Food and Drug Administration of the United States), vinegar is definedas a sour liquid containing at least 4 grams acetic acid in 100 cubic centimeter (4% solution of acetic acid) of solution that is produced from sugary materials by alcoholic fermentation. In the base of microbial starters, vinegars could be contained of more than 50 types of volatile and aromatic substances that responsible for their sweet taste and smelling. Recently the vinegar industry has a great proportion in agriculture, food and microbial biotechnology. The acetic acid bacteria are from the family Acetobacteraceae. Regarding to the latest version of Bergy-s Mannual of Systematic Bacteriology that has categorized bacteria in the base of their 16s RNA differences, the most important acetic acid genera are included Acetobacter (genus I), Gluconacetobacter (genus VIII) and Gluconobacter (genus IX). The genus Acetobacter that is primarily used in vinegar manufacturing plants is a gram negative, obligate aerobe coccus or rod shaped bacterium with the size 0.6 - 0.8 X 1.0 - 4.0 μm, nonmotile or motile with peritrichous flagella and catalase positive – oxidase negative biochemically. Some strains are overoxidizer that could convert acetic acid to carbon dioxide and water.In this research one Acetobacter native strain with high acetic acid productivity was isolated from Iranian white – red cherry. We used two specific culture media include Carr medium [yeast extract, 3%; ethanol, 2% (v/v); bromocresol green, 0.002%; agar, 2% and distilled water, 1000 ml], Frateur medium [yeast extract, 10 g/l; CaCO3, 20 g/l; ethanol, 20 g/l; agar, 20 g/l and distilled water, 1000 ml] and an industrial culture medium. In addition to high acetic acid production and high growth rate, this strain had a good tolerance against ethanol concentration that was examined using modified Carr media with 5%, 7% and 9% ethanol concentrations. While the industrial strains of acetic acid bacteria grow in the thermal range of 28 – 30 °C, this strain was adapted for growth in 34 – 36 °C after 96 hours incubation period. These dramatic characteristics suggest a potential biotechnological strain in production of cherry vinegar with a sweet smell and different nutritional properties in comparison to recent vinegar types. The lack of growth after 24, 48 and 72 hours incubation at 34 – 36 °C and the growth after 96 hours indicates a good and fast thermal flexibility of this strain as a significant characteristic of biotechnological and industrial strains.

Keywords: Acetobacte, acetic acid bacteria, white – red cherry, food and agriculture biotechnology, industrial fermentation, vinegar

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Authors: R. U. Hamzah, H. L. Muhammad, A. Sayyadi, M. B Busari, R. Garba, M. B. Umar, A. N Abubakar

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Lead (Pb) and Cadmium (Cd) are toxic, non-essential transition metals that pose many health risks for both humans and animals. They are environmental toxicants which contribute to testicular damage resulting to infertility problem among male populace worldwide. Chelating agents used for lead and cadmium toxicity are not readily available, toxic, expensive and unable to mop up most of the toxic metals accumulated in various organs. In this study, the effect of crude extract (CE), ethyl acetate fraction (EF) and acetone fraction (AF) of Pterocarpus mildbraedii leaf extract was assessed on cadmium-lead chloride induced testicular damaged in male albino Wistar rats. CE of the leaf was obtained by extracting in absolute methanol which was further subjected to solvent partitioning via vacuum liquid chromatographic (VLC) techniques using ethyl acetate, acetone and 70% methanol. A preliminary phytochemical screening and in vitro antioxidants guided activities on the CE and fractions were determined using standard methods. EF, AF and CE which exhibited significant in vitro activity were subjected to an in vivo study using Wistar rats. In vivo antioxidant markers, male reproductive hormones, testicular enzymes and DNA damage markers were analyzed on the rats’ testes supernatant. AF had the highest quantities of phenols (319.00 mg/g), flavonoids (8.87 mg/g) and tannins (8.87 mg/g) while methanol and EFs were richer in saponins (135.32 µg/g) and alkaloids (38.34 µg/g) respectively. A dose dependent 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP) and lipid peroxidation were observed in all the extract with high antioxidants power in CE and AF. Administration of lead-cadmium chloride solution significantly (p > 0.05) decreases the testicular superoxide dismutase (SOD) activity to 6.82 unit/mg protein, Catalase (CAT) activity to 8.07 of H2O2 consumed/unit/mg protein and Glutathione (GSH) concentration to 31.30 ug/mg protein. There was a concomitant increase in the level of Malondialdehyde (MDA) to a value of 23.70 mmol/mg protein. In addition, lead-cadmium chloride solution significantly (p > 0.05) increases the testicular marker enzymes (Alkaline phosphatase (119.57 u/L), lactate dehydrogenase (357.05 u/L), Acid phosphatase (98.65 u/L)) and DNA damage markers (conjugated dienes (93.39 nmol/mg protein), carbonyl protein (35.39 nmol/mg protein), DNA fragmentation percentage (32.12%)) with lowered testicular hormones (Testosterone (3.1 ng/mL), Follicle stimulating (0.35 IU/mL) and Luteinizing hormones (0.15 IU/mL)) of the animals in negative control group when compared with other treated groups. Treatment with Pterocarpus mildbraedii leaf extract reverts the observed changes with the best activities found in the CE and AFs in a dose dependent manner. Pterocarpus mildbraedii leaf extract ameliorated the lead/cadmium induced testicular damage in male albino rats. The restoration of the aforementioned parameters by some of the extract dosages were comparable to the standard drug with higher activities in the crude and AF. Therefore, Pterocarpus mildbraedii leaf extract can be explored further for the management of lead/cadmium induced toxicity.

Keywords: Cadmium, lead, Pterocarpus mildbraedii, testicular damage.

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Authors: Sotirios Raptis

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Health and Social care (HSc) services planning and scheduling are facing unprecedented challenges, due to the pandemic pressure and also suffer from unplanned spending that is negatively impacted by the global financial crisis. Data-driven approaches can help to improve policies, plan and design services provision schedules using algorithms that assist healthcare managers to face unexpected demands using fewer resources. The paper discusses services packing using statistical significance tests and machine learning (ML) to evaluate demands similarity and coupling. This is achieved by predicting the range of the demand (class) using ML methods such as Classification and Regression Trees (CART), Random Forests (RF), and Logistic Regression (LGR). The significance tests Chi-Squared and Student’s test are used on data over a 39 years span for which data exist for services delivered in Scotland. The demands are associated using probabilities and are parts of statistical hypotheses. These hypotheses, as their NULL part, assume that the target demand is statistically dependent on other services’ demands. This linking is checked using the data. In addition, ML methods are used to linearly predict the above target demands from the statistically found associations and extend the linear dependence of the target’s demand to independent demands forming, thus, groups of services. Statistical tests confirmed ML coupling and made the prediction statistically meaningful and proved that a target service can be matched reliably to other services while ML showed that such marked relationships can also be linear ones. Zero padding was used for missing years records and illustrated better such relationships both for limited years and for the entire span offering long-term data visualizations while limited years periods explained how well patients numbers can be related in short periods of time or that they can change over time as opposed to behaviours across more years. The prediction performance of the associations were measured using metrics such as Receiver Operating Characteristic (ROC), Area Under Curve (AUC) and Accuracy (ACC) as well as the statistical tests Chi-Squared and Student. Co-plots and comparison tables for the RF, CART, and LGR methods as well as the p-value from tests and Information Exchange (IE/MIE) measures are provided showing the relative performance of ML methods and of the statistical tests as well as the behaviour using different learning ratios. The impact of k-neighbours classification (k-NN), Cross-Correlation (CC) and C-Means (CM) first groupings was also studied over limited years and for the entire span. It was found that CART was generally behind RF and LGR but in some interesting cases, LGR reached an AUC = 0 falling below CART, while the ACC was as high as 0.912 showing that ML methods can be confused by zero-padding or by data’s irregularities or by the outliers. On average, 3 linear predictors were sufficient, LGR was found competing well RF and CART followed with the same performance at higher learning ratios. Services were packed only when a significance level (p-value) of their association coefficient was more than 0.05. Social factors relationships were observed between home care services and treatment of old people, low birth weights, alcoholism, drug abuse, and emergency admissions. The work found  that different HSc services can be well packed as plans of limited duration, across various services sectors, learning configurations, as confirmed by using statistical hypotheses.

Keywords: Class, cohorts, data frames, grouping, prediction, probabilities, services.

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