Search results for: mass drug administration

Authors: J. Skibinski, P. Caban, T. Wejrzanowski, K. J. Kurzydlowski

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In the present study, numerical simulations of heat and mass transfer during gallium nitride growth process in Metal Organic Vapor Phase Epitaxy reactor AIX-200/4RF-S is addressed. Existing knowledge about phenomena occurring in the MOVPE process allows to produce high quality nitride based semiconductors. However, process parameters of MOVPE reactors can vary in certain ranges. Main goal of this study is optimization of the process and improvement of the quality of obtained crystal. In order to investigate this subject a series of computer simulations have been performed. Numerical simulations of heat and mass transfer in GaN epitaxial growth process have been performed to determine growth rate for various mass flow rates and pressures of reagents. According to the fact that it’s impossible to determine experimentally the exact distribution of heat and mass transfer inside the reactor during the process, modeling is the only solution to understand the process precisely. Main heat transfer mechanisms during MOVPE process are convection and radiation. Correlation of modeling results with the experiment allows to determine optimal process parameters for obtaining crystals of highest quality.

Keywords: Finite Volume Method, semiconductors, epitaxial growth, metalorganic vapor phase epitaxy, gallium nitride

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Authors: Elham Zarenezhad, Ali Zarenezhad, Mehdi Mardkhoshnood

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We described the synthesis and biological study of O-oxime ethers having a-amino acid residues as new analogs of IPS-339. In this synthesis, the reaction of fluorene O-oxime with epichlorohydrin or epibromohydrin afforded the corresponding O-oxime ether adducts. The N-alkylation of valine amino acid with O-oxime ether adducts led to the synthesis of new analogs of IPS-339. The cardiovascular properties of the compound have been studied. In this regard, six clinically healthy same sex mongrel dogs were examined. The dogs were randomly divided into 3 groups of two members. 1 groups received 2 mg kg-1 body weight of compound (2-(3-(9H-fluoren-9-ylideneaminooxy)-2- hydroxypropylamino)-3-methylbutanoic acid) intravenously, whereas group 2 and 3 received only DMSO–water (distil.) and propranolol (Inderal) (2 mg kg-1), respectively. The electrocardiograph (ECG) was recorded with lead II. The recording was run successively by 5 min time interval on each dog before, simultaneously, and after compound infusion. Data after administration were taken from normal sinus beats that were closely related to the arrhythmias whenever they occurred. In general, no detectable arrhythmia was observed in all ECG records regardless of increasing the heart rate that likely caused by stress origin from invasive procedure just after infusion. Compound diminished the heart rate during study especially at 20th minute compared to propranolol as a reference drug. Compound (2-(3-(9H-fluoren-9-ylideneaminooxy)-2- hydroxypropylamino)-3-methylbutanoic acid) was the most effective compound with remarkable ability in declining of the heart rate.

Keywords: electrocardiograph (ECG), cardiovascular, IPS-339, dogs

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Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

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Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

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Authors: Arlinda Memetaj

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Building up of a well-functioning administrative justice system is one of the key prerequisites for ensuring the existence of an accountable and efficient public administration in Kosovo as well. To this aim, the country has already established an almost comprehensive legislative and institutional frameworks. The latter derives from (among others) the Kosovo`s Stabilisation and Association Agreement with the EU of 2016. A series of efforts are being presently still undertaken by all relevant domestic and international stakeholders being active in both the Kosovo`s public administration reform and the country` s system of a local self-government. Both systems are thus under a constant state of reform. Despite the aforesaid, there is still a series of shortcomings in the country in above context. There is a lot of backlog of administrative cases in the Prishtina Administrative court; there is a public lack in judiciary; the public administration is organized in a fragmented way; the administrative laws are still not properly implemented at local level; the municipalities` legislative and executive branches are not sufficiently transparent for the ordinary citizens ... Against the above short background, the full paper firstly outlines the legislative and institutional framework of the Kosovo's systems of an administrative justice and local self-government (on the basis of the fact that public administration and local government are not separate fields). It then illustrates the key specific shortcomings in those fields, as seen from the perspective of the citizens' right to good administration. It finally claims that the current status quo situation in the country may be resolved (among others) by granting Kosovo a status of full member state of the Council of Europe or at least granting it with a temporary status of a contracting party of (among others) the European Human Rights Convention. The later would enable all Kosovo citizens (regardless their ethnic or other origin whose human rights are violated by the Kosovo`s relative administrative authorities including the administrative courts) to bring their case/s before the respective well-known European Strasbourg-based Human Rights Court. This would consequently put the State under permanent and full monitoring process, with a view to obliging the country to properly implement the European Court`s decisions (as adopted by this court in those cases). This would be a benefit first of all for the very Kosovo`s ordinary citizens regardless their ethnic or other background. It would provide for a particular positive input in the ongoing efforts being undertaken by Kosovo and Serbia states within the EU-facilitated Dialogue, with a view to building up of an integral administrative justice system at central and local level in the whole Kosovo` s territory. The main method used in this paper is the descriptive, analytical and comparative one.

Keywords: administrative courts, administrative justice, administrative procedure, benefit, European Human Rights Court, human rights, monitoring, reform.

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Authors: Kareem Adedokun

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Official secrecy is one of the colonial vestiges which upholds non – disclosure of essential information for public consumption. Information, though an indispensable tool in tax administration, is not to be divulged by any person in an official duty of the revenue agency. As a matter o fact, the Federal Inland Revenue Service (Establishment) Act, 2007 emphasizes secrecy and confidentiality in dealing with tax payer’s document, information, returns and assessment in a manner reminiscent of protecting tax payer’s privacy in all situations. It is so serious that any violation attracts criminal sanction. However, Nigeria, being a democratic and egalitarian state recently enacted Freedom of Information Act which heralded in openness in governance and takes away the confidentialities associated with official secrets Laws. Official secrecy no doubts contradicts the philosophy of freedom of information but maintaining a proper balance between protected rights of tax payers and public interest which revenue agency upholds is an uphill task. Adopting the Doctrinal method, therefore, the author of this paper probes into the real nature of the relationship between taxpayers and Revenue Agencies. It also interfaces official secrecy with the doctrine of Freedom of Information and consequently queries the retention of non – disclosure clause under Federal Inland Revenue Service (Establishment) Act (FIRSEA) 2007. The paper finds among others that non – disclosure provision in tax statutes particularly as provided for in FIRSEA is not absolute; so also is the constitutional rights and freedom of information and unless the non – disclosure clause finds justification under any recognized exemption provided under the Freedom of Information Act, its retention is antithesis to democratic ethos and beliefs as it may hinder public interest and public order.

Keywords: confidentiality, information, official secrecy, tax administration

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Authors: Malahat Rezaee, Mahiran Basri, Raja Noor Zaliha Raja Abdul Rahman, Abu Bakar Salleh

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Sodium diclofenac is one of the most commonly used drugs of nonsteroidal anti-inflammatory drugs (NSAIDs). It is especially effective in the controlling the severe conditions of inflammation and pain, musculoskeletal disorders, arthritis, and dysmenorrhea. Formulation as nanoemulsions is one of the nanoscience approaches that have been progressively considered in pharmaceutical science for transdermal delivery of drug. Nanoemulsions are a type of emulsion with particle sizes ranging from 20 nm to 200 nm. An emulsion is formed by the dispersion of one liquid, usually the oil phase in another immiscible liquid, water phase that is stabilized using surfactant. Palm kernel oil esters (PKOEs), in comparison to other oils; contain higher amounts of shorter chain esters, which suitable to be applied in micro and nanoemulsion systems as a carrier for actives, with excellent wetting behavior without the oily feeling. This research was aimed to study the effect of O/S ratio on stability and rheological behavior of sodium diclofenac loaded and unloaded palm kernel oil esters nanoemulsion systems. The effect of different O/S ratio of 0.25, 0.50, 0.75, 1.00 and 1.25 on stability of the drug-loaded and unloaded nanoemulsion formulations was evaluated by centrifugation, freeze-thaw cycle and storage stability tests. Lecithin and cremophor EL were used as surfactant. The stability of the prepared nanoemulsion formulations was assessed based on the change in zeta potential and droplet size as a function of time. Instability mechanisms including coalescence and Ostwald ripening for the nanoemulsion system were discussed. In comparison between drug-loaded and unloaded nanoemulsion formulations, drug-loaded formulations represented smaller particle size and higher stability. In addition, the O/S ratio of 0.5 was found to be the best ratio of oil and surfactant for production of a nanoemulsion with the highest stability. The effect of O/S ratio on rheological properties of drug-loaded and unloaded nanoemulsion systems was studied by plotting the flow curves of shear stress (τ) and viscosity (η) as a function of shear rate (γ). The data were fitted to the Power Law model. The results showed that all nanoemulsion formulations exhibited non-Newtonian flow behaviour by displaying shear thinning behaviour. Viscosity and yield stress were also evaluated. The nanoemulsion formulation with the O/S ratio of 0.5 represented higher viscosity and K values. In addition, the sodium diclofenac loaded formulations had more viscosity and higher yield stress than drug-unloaded formulations.

Keywords: nanoemulsions, palm kernel oil esters, sodium diclofenac, rheoligy, stability

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Authors: Shuafeng Yuan, Bojian Zheng

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The RNA-dependent RNA polymerase of influenza a virus comprises conserved and independently folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitor assay with the DNA gel-based endonuclease inhibitor assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted ANA-0 bound the endonuclease cavity of PAN by interacting with the metal-binding and catalytic residues. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.

Keywords: anti-influenza, novel compound, inhibition of endonuclease, PA

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Authors: Maarten J. Van der Burgt

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A universe containing matter and antimatter can only exist when matter and antimatter repel each other. Such a system, where like attracts like and like repels unlike, will always expand. Calculations made for such a symmetric universe demonstrate that the expansion is consistent with Hubble’s law, the observed increase in the expansion velocity with time, the initial high acceleration and the foam structure of the universe. Conversely, these observations can be considered as proof for a symmetrical universe and for antimatter possessing a negative gravitational mass. A second proof can be found by reinterpreting the behavior of relativistic moving charged particles. Attributing their behavior to a charge defect of √(1-v2/c2) instead of to a mass defect of 1/√(1-v2/c2) makes it plausible that gravitation is an electromagnetic force, as already suggested by Feynman. This would automatically imply that antimatter has a negative gravitational mass. These proofs underpin the untenability of the Weak Equivalence Principle which states that in a gravitational field all structure less point-like particles follow the same path.

Keywords: celestial mechanics, cosmology, gravitation astrophysics, origin of structure, miscellaneous (matter and antimatter)

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Authors: Mohammed A. Gharawi, Majed M. Khoja

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This paper is a report on the findings of a study conducted at the Institute of Public Administration (IPA) in Saudi Arabia. The paper applied both qualitative and quantitative research methods to assess the levels of basic computer applications’ skills among students enrolled in the preparatory programs of the institution. qualitative data have been collected from semi-structured interviews with the instructors who have previously been assigned to teach Introduction to information technology courses. Quantitative data were collected by executing a self-report questionnaire and a written statistical test. 380 enrolled students responded to the questionnaire and 142 accomplished the statistical test. The results indicate the lack of necessary skills to deal with computer applications among most of the students who are enrolled in the IPA’s preparatory programs.

Keywords: assessment, computer applications, computer literacy, Institute of Public Administration, Saudi Arabia

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Authors: Seungho Shin, Keunwoo Choi, Ali Akbar, Sukkee Um

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In this study, the nanoscale transport properties and catalyst utilization of vertically aligned carbon nanotube (VACNT) catalyst layers are computationally predicted by the three-dimensional lattice Boltzmann simulation based on the quasi-random nanostructural model in pursuance of fuel cell catalyst performance improvement. A series of catalyst layers are randomly generated with statistical significance at the 95% confidence level to reflect the heterogeneity of the catalyst layer nanostructures. The nanoscale gas transport phenomena inside the catalyst layers are simulated by the D3Q19 (i.e., three-dimensional, 19 velocities) lattice Boltzmann method, and the corresponding mass transport characteristics are mathematically modeled in terms of structural properties. Considering the nanoscale reactant transport phenomena, a transport-based effective catalyst utilization factor is defined and statistically analyzed to determine the structure-transport influence on catalyst utilization. The tortuosity of the reactant mass transport path of VACNT catalyst layers is directly calculated from the streaklines. Subsequently, the corresponding effective mass diffusion coefficient is statistically predicted by applying the pre-estimated tortuosity factors to the Knudsen diffusion coefficient in the VACNT catalyst layers. The statistical estimation results clearly indicate that the morphological structures of VACNT catalyst layers reduce the tortuosity of reactant mass transport path when compared to conventional catalyst layer and significantly improve consequential effective mass diffusion coefficient of VACNT catalyst layer. Furthermore, catalyst utilization of the VACNT catalyst layer is substantially improved by enhanced mass diffusion and electric current paths despite the relatively poor interconnections of the ion transport paths.

Keywords: Lattice Boltzmann method, nano transport phenomena, polymer electrolyte fuel cells, vertically aligned carbon nanotube

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Authors: Jerickson Abbie Flores, Jana Fragante, Jan Paolo Dipasupil, Jan Jorge Francisco

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Malnutrition is one of the rapidly growing health problems affecting the world at present. Children affected are not only at risk for significant health problems, but are also faced with psychological and social consequences, including low self-esteem. School-age children are specifically vulnerable to develop poor self-esteem especially when their peers find them physically unattractive. Thus, malnutrition, whether obesity or undernourishment, contributes a significant role to a developing child’s health and behavior. This research aims to determine if there is a significant difference on the level of self-esteem among Filipino children ages 9-12 years old with abnormal body mass index (BMI) and those children with desirable BMI. Using a cross-sectional study design, the correlation between body mass index (BMI) and self-esteem was observed among children ages 9-12 years old. Participants took the Hare self esteem questionnaire, which is specifically designed to measure self-esteem in school age children. The lowest possible score is 15 and the highest possible score is 45. A total of 1140 students with ages 9-12 years old from Cembo Elementary School (public school) participated in the study. Among the participants, 239 out of the 1140 have desirable body mass index, 878 are underweight, and 23 are overweight. Using the test questionnaire, the computed mean scores were 36.599, 36.045 and 36.583 for normal, underweight and overweight categories respectively. Using Pearson’s Correlation Test and Spearman’s Correlation Coefficient Test, the study showed positive correlation (p value of 0.047 and 0.004 respectively) between BMI and Self-esteem scores which indicates that the higher the BMI, the higher the self-esteem of the participants.

Keywords: body mass index, malnutrition, school-age children, self-esteem

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Authors: A. V. Shrirao, N. I. Kochar, A. V. Chandewar

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The flower extract of Butea monosperma herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of Butea monosperma flowers on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intraperitonial (i.p.) injection of Triton WR 1339 (400 mg/kg) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of Butea monosperma flowers (Et-BM) (250 and 500 mg/kg/day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analyzed at three different time intervals for lipid profile and antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, Atorvastatin (10 mg/kg). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-BM treatment or standard drug Atorvastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-BM treated rats. Pronounced changes were observed at 500 mg/kg of Et-BM for 2 weeks and it was comparable to the standard drug Atorvastatin. The current study provides strong evidence that Et-BM has a remarkable beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.

Keywords: antioxidant, butea monopserma, hyperlipidemia, triton WR 1339

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Authors: Geetakshi Arora, Danish Malhotra

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Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

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Authors: Nihar Ranjan, Derrick Watkins, Dev P. Arya

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Current methods in the study of antibiotic activity of ribosome targeted antibiotics are dependent on cell based bacterial inhibition assays or various forms of ribosomal binding assays. These assays are typically independent of each other and little direct correlation between the ribosomal binding and bacterial inhibition is established with the complementary assay. We have developed novel high-throughput capable assays for ribosome targeted drug discovery. One such assay examines the compounds ability to bind to a model ribosomal RNA A-site. We have also coupled this assay to other functional orthogonal assays. Such analysis can provide valuable understanding of the relationships between two complementary drug screening methods and could be used as standard analysis to correlate the affinity of a compound for its target and the effect the compound has on a cell.

Keywords: bacterial resistance, aminoglycosides, screening, drugs

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Authors: Daniel O. Wasonga, Jouko Kleemola, Laura Alakukku, Pirjo Makela

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Cassava (Manihot esculenta Crantz) is a major food crop for millions of people in the tropics. Growth and yield of cassava in the arid-tropics are seriously constrained by intermittent water deficit and low soil K content. Therefore, experiments were conducted to investigate the effects of interaction between water deficit and K fertigation on growth and yield response of biofortified cassava at early growth phase. Yellow cassava cultivar was grown under controlled glasshouse conditions in 5-L pots containing 1.7 kg of pre-fertilized potting mix. Plants were watered daily for 30 days after planting. Treatments were three watering levels (30%, severe water deficit; 60%, mild water deficit; 100%, well-watered), on which K (0.01, 1, 4, 16 and 32 mM) was split. Plants were harvested at 90 days after planting. Leaf area was smallest in plants grown with 30% watering and 0.01 mM K, and largest in plants grown with 100% watering and 32 mM K. Leaf, root, and total dry mass decreased in water-stressed plants. However, dry mass was markedly higher when plants were grown with 16 mM K under all watering levels in comparison to other K concentrations. The highest leaf, root and total dry mass were in plants with 100% watering and 16 mM K. In conclusion, K improved the growth of plants under water deficit and thus, K application on soils with low moisture and low K may improve the productivity of cassava.

Keywords: dry mass, interaction, leaf area, Manihot esculenta

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Authors: Opeyemi Awau Adepoju

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The task of nation-building for Nigeria, like other developing nations, has continued to be riddled with audacious challenges that kept threatening to consume the state itself. Among the destabilizing factors that are sometimes mutually reinforcing are poverty and insecurity. Nigeria has been bedeviled with poverty since the onset of the 1980s when the country metamorphosed from an agricultural to an oil-based economy coupled with unbridled political corruption and wasteful management of resources by successive governments. The crippling poverty started manifesting in the scourge of criminalities and a general state of insecurity. Poverty gradually becomes the breeder of insecurity and threats to human life in Nigeria. Interestingly, successive governments tended to recognize the destructive tendencies of poverty and took several interventionist initiatives towards abating or slowing down the spate of poverty so as to reverse the trend of insecurity, but none of those initiatives can be adjudged good or enduring legacies. The emergence of the Buhari administration in 2015 provided a new opportunity to tackle poverty and, in turn, insecurity that had permeated every aspect of national life before that year’s presidential elections. Expectedly, the government took ambitious steps through its innovative ideas of intervention through its National Social Intervention Programmes (NSIP). Therefore, this paper is an assessment of the Buhari administration’s initiatives in poverty eradication in Nigeria as one of its strategies to fight insecurity, and the paper adopted a qualitative approach. The theoretical arguments put up by this paper are with respect to the connection between poverty and insecurity sourced from the theory of Relative Deprivation. The paper found that the Buhari administration has done better than any government since 1999 in inventing a social intervention program and that the poverty of the people has been addressed to a notable extent. However, the problem of politicization of intervention programs has continued to be the practice under the administration, and if this is not abated, the post-Buhari era may as well be like the eras before it. The paper recommends legislation that can make poverty ameliorating programs permanent, at least for some years to come, so as to avoid the usual policy summersault at every instance of political transition, which has limited the sustainability of public policies and indeed hindered nation-building efforts in Nigeria.

Keywords: insecurity, poverty alleviation, public policies, social intervention

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Authors: Grace C. Kuroki, Yixin Hu, Bailey Surtees, Rebecca Krimins, Nicholas J. Durr, Dara L. Kraitchman

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The purpose of this study was to perform a Phase I veterinary clinical trial with a low-cost, carbon-dioxide-based, passive thaw cryoablation device as proof-of-principle for application in pets and translation to third-world treatment of breast cancer. This study was approved by the institutional animal care and use committee. Client-owned dogs with subcutaneous masses, primarily lipomas or mammary cancers, were recruited for the study. Inclusion was based on clinical history, lesion location, preanesthetic blood work, and fine needle aspirate or biopsy confirmation of mass. Informed consent was obtained from the owners for dogs that met inclusion criteria. Ultrasound assessment of mass extent was performed immediately prior to mass cryoablation. Dogs were placed under general anesthesia and sterilely prepared. A stab incision was created to insert a custom 4.19 OD x 55.9 mm length cryoablation probe (Kubanda Cryotherapy) into the mass. Originally designed for treating breast cancer in low resource settings, this device has demonstrated potential in effectively necrosing subcutaneous masses. A dose escalation study of increasing freeze-thaw cycles (5/4/5, 7/5/7, and 10/7/10 min) was performed to assess the size of the iceball/necrotic extent of cryoablation. Each dog was allowed to recover for ~1-2 weeks before surgical removal of the mass. A single mass was treated in seven dogs (2 mammary masses, a sarcoma, 4 lipomas, and 1 adnexal mass) with most masses exceeding 2 cm in any dimension. Mass involution was most evident in the malignant mammary and adnexal mass. Lipomas showed minimal shrinkage prior to surgical removal, but an area of necrosis was evident along the cryoablation probe path. Gross assessment indicated a clear margin of cryoablation along the cryoprobe independent of tumor type. Detailed histopathology is pending, but complete involution of large lipomas appeared to be unlikely with a 10/7/10 protocol. The low-cost, carbon dioxide-based cryotherapy device permits a minimally invasive technique that may be useful for veterinary applications but is also informative of the unlikely resolution of benign adipose breast masses that may be encountered in third world countries.

Keywords: cryoablation, cryotherapy, interventional oncology, veterinary technology

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Authors: Che Hsiu Chen, Su Yun Chen, Hon Wen Cheng

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Greater core stability may benefit sports performance by providing a foundation for greater force production in the upper and lower extremities. Core stability exercises on instability device (such as the TRX suspension systems) were found to be able to induce higher core muscle activity than performing on a stable surface. However, high intensity interval TRX suspension exercises training on sport performances remain unclear. The purpose of this study was to examine whether high intensity TRX suspension training could improve sport performance. Twenty-four healthy university female students (age 19.0 years, height 157.9 cm, body mass 51.3 kg, fat mass 25.2 %) were voluntarily participated in this study. After a familiarization session, each participant underwent five suspension exercises (e.g., hip abduction in plank alternative, hamstring curl, 45-degree row, lunge and oblique crunch). Each type of exercise was performed for 30 seconds, followed by 30 seconds break, two times per week for eight weeks while each exercise session was increased by 10 seconds every week. The results showed that the fat mass (about 12.92%) decreased significantly, sit and reach test (9%), 1 minute sit-up test (17.5%), standing broad jump (4.8%), physical fitness index (10.3%) increased significantly after 8-week high intensity TRX suspension training. Hence, eight weeks of high intensity interval TRX suspension exercises training can improve hamstring flexibility, trunk endurance, jump ability, aerobic fitness and fat mass percentage decreased substantially.

Keywords: core endurance, jump, flexibility, cardiovascular fitness

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Authors: Matej Buzgo, Erico Himawan, Ksenija JašIna, Aiva Simaite

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Electrospinning is a versatile and efficient technology for producing nanofibers for biomedical applications. One of the most common polymers used for the preparation of nanofibers for regenerative medicine and drug delivery applications is polycaprolactone (PCL). PCL is a biocompatible and bioabsorbable material that can be used to stimulate the regeneration of various tissues. It is also a common material used for the development of drug delivery systems by blending the polymer with small active molecules. However, for many drug delivery applications, e.g. cancer immunotherapy, PCL biodegradation rate that may exceed 9 months is too long, and faster nanofiber dissolution is needed. In this paper, we investigate the dissolution and small molecule release rates of PCL blends with two hydrophilic polymers: polyethylene oxide (PEO) or polyvinylpyrrolidone (PVP). We show that adding hydrophilic polymer to the PCL reduces the water contact angle, increases the dissolution rate, and strengthens the interactions between the hydrophilic drug and polymer matrix that further sustain its release. Finally using this method, we were also able to increase the nanofiber degradation rate when PCL-PEO and PCL-PVP were used as a shell in the electrospun core-shell nanofibers and spread up the release of active proteins from their core. Electrospinning can be used for the preparation of the core-shell nanofibers, where active ingredients are encapsulated in the core and their release rate is regulated by the shell. However, such fibers are usually prepared by coaxial electrospinning that is an extremely low-throughput technique. An alternative is emulsion electrospinning that could be upscaled using needleless blades. In this work, we investigate the possibility of using emulsion electrospinning for encapsulation and sustained release of the growth factors for the development of the organotypic skin models. The core-shell nanofibers were prepared using the optimized formulation and the release rate of proteins from the fibers was investigated for 2 weeks – typical cell culture conditions.

Keywords: electrospinning, polycaprolactone (PCL), polyethylene oxide (PEO), polyvinylpyrrolidone (PVP)

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Authors: R. M. Noah, N. M. Nasir, M. R. Jais, M. S. S. Wahab, M. H. Abdullah, A. S. S. Raj

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Infectious diseases are getting more difficult to treat due to the resistant strains of bacteria. Current generations of antibiotics are most likely ineffective against multi-drug resistant strains bacteria. Thus, there is an urgent need in search of natural antibiotics in particular from medicinal plants. One of the common medicinal plants, Melaleuca cajuputi, has been reported to possess antibacterial properties. The study was conducted to evaluate and justify the presence of antibacterial activity of Melaleuca cajuputi essential oil (EO) against the multi-drug resistant bacteria. Clinical isolates obtained from the teaching hospital were re-assessed to confirm the exact identity of the bacteria to be tested, namely methicillin-resistant staphylococcus aureus (MRSA), carbapenem-resistant enterobacteriaceae (CRE), and extended-spectrum beta-lactamases producer (ESBLs). A well diffusion method was done to observe the inhibition zones of the essential oil against the bacteria. Minimum inhibitory concentration (MIC) was determined using the microdilution method in 96-well flat microplate. The absorbance was measured using a microplate reader. Minimum bactericidal concentration (MBC) was performed using the agar medium method. The zones of inhibition produced by the EO against MRSA, CRE, and ESBL were comparable to that of generic antibiotics used, gentamicin and augmentin. The MIC and MBC results highlighted the antimicrobial efficacy of the EO. The outcome of this study indicated that the EO of Melaleuca cajuputi had antibacterial activity on the multi-drug resistant bacteria. This finding was eventually substantiated by electron microscopy work.

Keywords: melaleuca cajuputi, antibacterial, resistant bacteria, essential oil

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Authors: Smruti Mahapatra, Dipankar Biswas, Richard Um, Michael Meggyesy, Riccardo Serra, Noah Gorelick, Steven Marra, Amir Manbachi, Mark G. Luciano

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Intracranial pressure (ICP) is profoundly regulated by the effects of cardiac pulsation and the volume of the incoming blood. Furthermore, these effects on ICP are incremented by the presence of a rigid skull that does not allow for changes in total volume during the cardiac cycle. These factors play a pivotal role in cerebrospinal fluid (CSF) dynamics and distribution, with consequences that are not well understood to this date and that may have a deep effect on the Central Nervous System (CNS) functioning. We designed this study with two specific aims: (a) To study how pulsatility influences local CSF flow, and (b) To study how modulating intracranial pressure affects drug distribution throughout the SAS globally. In order to achieve these aims, we built an elaborate in-vitro model of the SAS closely mimicking the dimensions and flow rates of physiological systems. To modulate intracranial pressure, we used an intracranially implanted, cardiac-gated, volume-oscillating balloon (CADENCE device). Commercially available dye was used to visualize changes in CSF flow. We first implemented two control cases, seeing how the tracer behaves in the presence of pulsations from the brain phantom and the balloon individually. After establishing the controls, we tested 2 cases, having the brain and the balloon pulsate together in sync and out of sync. We then analyzed the distribution area using image processing software. The in-sync case produced a significant increase, 5x times, in the tracer distribution area relative to the out-of-sync case. Assuming that the tracer fluid would mimic blood flow movement, a drug introduced in the SAS with such a system in place would enhance drug distribution and increase the bioavailability of therapeutic drugs to a wider spectrum of brain tissue.

Keywords: blood-brain barrier, cardiac-gated, cerebrospinal fluid, drug delivery, neurosurgery

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Authors: Rihab Gamaoun, Cynthia El Hage, Laura Ruiz, Erin Prosk, Antonio Vigano

Abstract:

Introduction: Santé Cannabis (SC), a Canadian medical cannabis-specialized group of clinics based in Montreal and in the province of Québec, has served more than 5000 patients seeking cannabis-based treatment prescription for medical indications over the past five years. Within a research frame, data on the use of medical cannabis products from all the above patients were prospectively collected, leading to a large real-world database on the use of medical cannabis. The aim of this study was to gather information on the profiles of both patients and prescribed medical cannabis products at SC clinics and to assess the safety of medical cannabis among Canadian patients. Methods: Using a retrospective analysis of the database, records of 2585 patients who were prescribed medical cannabis products for therapeutic purposes between 01-November 2017 and 04-September 2019 were included. Patients’ demographics, primary diagnosis, route of administration, and chemovars recorded at the initial visits were investigated. Results: At baseline: 9% of SC patients were female, with a mean age of 57 (SD= 15.8, range= [18-96]); Cannabis products were prescribed mainly for patients with a diagnosis of chronic pain (65.9% of patients), cancer (9.4%), neurological disorders (6.5%), mood disorders (5.8 %) and inflammatory diseases (4.1%). Route of administration and chemovars of prescribed cannabis products were the following: 96% of patients received cannabis oil (51% CBD rich, 42.5% CBD:THC); 32.1% dried cannabis (21.3% CBD:THC, 7.4% THC rich, 3.4 CBD rich), and 2.1% oral spray cannabis (1.1% CBD:THC, 0.8% CBD rich, 0.2% THC rich). Most patients were prescribed simultaneously, a combination of products with different administration routes and chemovars. Safety analysis is undergoing. Conclusion: Our results provided initial information on the profile of medical cannabis products prescribed in a Canadian population and the experienced adverse events over the past three years. The Santé Cannabis database represents a unique opportunity for comparing clinical practices in prescribing and titrating cannabis-based medications across different centers. Ultimately real-world data, including information about safety and effectiveness, will help to create standardized and validated guidelines for choosing dose, route of administration, and chemovars types for the cannabis-based medication in different diseases and indications.

Keywords: medical cannabis, real-world data, safety, pharmacovigilance

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Authors: Peter Yamoah, Frasia Oosthuizen

Abstract:

Introduction: Reporting of Adverse Events Following Immunization continues to be a challenge. Pharmacovigilance centers throughout the world are mandated by the WHO to submit AEFI reports from various countries to a large pool of adverse drug reaction electronic database called Vigibase. Despite the relevant information of AEFI in Vigibase, it is unavailable to the general public. However, the WHO has an alternative website called VigiAccess which is an open access website serving as a repository of reported adverse drug reactions and AEFIs. The aim of the study was to ascertain the reporting pattern of a number of commonly used vaccines in VigiAccess. Methods: VigiAccess was thoroughly searched on the 5th of February 2018 for AEFI reports of measles vaccine, oral polio vaccine (OPV), yellow fever vaccine, pneumococcal vaccine, rotavirus vaccine, meningococcal vaccine, tetanus vaccine and tuberculosis (BCG) vaccine. These were reports from all pharmacovigilance centers in the world from the time they joined the WHO drug monitoring program. Results: After a thorough search in VigiAccess, there were 9,062 measles vaccine AEFIs, 185,829 OPV AEFIs, 24,577 yellow fever vaccine AEFIs, 317,208 pneumococcal vaccine AEFIs, 73,513 rotavirus vaccine AEFIs, 145,447 meningococcal vaccine AEFIs, 22,781 tetanus vaccine AEFIs and 35,556 BCG vaccine AEFIs. Conclusion: The study revealed that out of the eight vaccines studied, pneumococcal vaccines are associated with the highest number of AEFIs whilst measles vaccines were associated with the least AEFIs.

Keywords: vaccines, adverse reactions, VigiAccess, adverse event reporting

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Authors: Menan M. Elsayed, Hussein A. Heshmat

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The aim of the study is to determine the effect of 100 mg/d Pregnenolone on biological variables after plyometric training for volleyball players. Methods: 15 male volleyball players participated in this study. Serum levels of testosterone, creatine phosphokinase (CPK), lactate, and glucose were measured before and post-exercise. Results: Testosterone was not altered, while creatine phosphokinase (CPK), lactate, and glucose levels significantly decreased. It is recommended to use Pregnenolone administration to decreased muscle damage and delayed fatigue for volleyball players after plyometric training. In conclusion, this study demonstrated that oral Pregnenolone administration of 100 mg/d might decrease muscle damage and delayed fatigue which may affect positively the volleyball players after a plyometric training bout.

Keywords: biological variables, plyometric exercise program, pregnenolone, volleyball player

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Authors: J. O. Ezekwesili-Ofili, L. I. Okorafor, S. C. Nsofor

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Diabetes mellitus is a carbohydrate metabolism disorder due to an absolute or relative deficiency of insulin secretion, action or both. Many known hypoglycaemic drugs are known to produce serious side effects. However, the search for safer and more effective agents has shifted to plant products, including foods and spices. One of such is the rhizome of Curcuma longa or turmeric, which is a spice with high medicinal value. A drawback in the use of C. longa is the poor bioavailability of curcumin, the active ingredient. It has been reported that piperine, an alkaloid present in peppers increases the bioavailability of curcumin. This work therefore investigated the hypoglycaemic and antioxidant effects of ethanolic extract of C. longa rhizomes, alone and with two pepper adjuvants in alloxan-induced diabetic rats. A total of 48 rats were divided into 6 groups of 8 rats each. Groups A–E were induced with diabetes using 150mg/kg body weight of alloxan monohydrate, while group F was normoglycaemic: Group A: Diabetic; fed with 400 mg/g body weight of turmeric extract; group B: Diabetic, fed with 400 mg/kg b. w. and 200mg/kg b. w of ethanolic extract of seeds of Piper guinensee; group C: Diabetic, fed with 400 mg/kg b. w. and 200 mg /kg b. w. of ethanolic extract of seeds of Capsicum annum var cameroun, group D: Diabetic, treated with standard drug, glibenclamide (0.3mg/kg body weight), group E: Diabetic; no treatment i.e. Positive control and group F: non diabetic, no treatment i.e. Negative control. Blood glucose levels were monitored for 14 days using a glucometer. The levels of the antioxidant enzymes; glutathione peroxidase, catalase and superoxide dismutase were also assayed in serum. The ethanolic extracts of C. longa rhizomes at the dose given (400 mg/kg b. w) significantly reduced the blood glucose levels of the diabetic rats (p<0.05) comparable to the standard drug. Co administration of extract of the peppers did not significantly increase the efficiency of the extract, although C. annum var cameroun showed greater effect, though not significantly. The antioxidant effect of the extract was significant in diabetic rats. The use of piperine-containing peppers enhanced the antioxidant effect. Phytochemical analyses of the ethanolic extract of C. longa showed the presence of alkaloids, flavonoids, steroids, saponins, tannins, glycosides, and terpenoids. These results suggest that the ethanolic extract of C. longa had antidiabetic with antioxidant effects and could thus be of benefit in the treatment and management of diabetes as well as ameliorate pro-oxidant effects that may lead to diabetic complications. However, while the addition of piperine did not affect the antidiabetic effect of C. longa, the antioxidant effect was greatly enhanced.

Keywords: antioxidant, Curcuma longa rhizome, hypoglycaemic, pepper adjuvants, piperine

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Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

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Authors: Vigen Barkhudaryan

Abstract:

The influence of external effects (γ-, UV–radiations, high temperature) in presence of air oxygen on structural transformations of low-density polyethylene (LDPE) have been investigated dependent on the polymers’ thickness, the intensity and the dose of external actions. The methods of viscosimetry, light scattering, turbidimetry and gelation measuring were used for this purpose. The comparison of influence of external effects on LDPE shows, that the destruction and cross-linking processes of macromolecules proceed simultaneously with all kinds of external effects. A remarkable growth of average molecular mass of LDPE along with the irradiation doses and heat treatment exposure growth was established. It was linear for the mass average molecular mass and at the initial doses is mainly the result of the increase of the macromolecular branching. As a result, the macromolecular hydrodynamic volumes have been changed, and therefore the dependence of viscosity average molecular mass on the doses was going through the minimum at initial doses. A significant change of molecular mass, sizes and shape of macromolecules of LDPE occurs under the influence of external effects. The influence is limited only by diffusion of oxygen during -irradiation and heat treatment. At UV–irradiation the influence is limited both by diffusion of oxygen and penetration of radiation. Consequently, the molecular transformations are deeper and evident in case of -irradiation, as soon as the polymer is transformed in a whole volume. It was also established, that the mechanism of molecular transformations in polymers from the surface layer distinctly differs from those of the sample deeper layer. A comparison of the results of these investigations allows us to conclude, that the mechanisms of influence of investigated external effects on polyethylene are similar.

Keywords: cross-linking, destruction, high temperature, LDPE, γ-radiations, UV-radiations

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Authors: Frazer G. Thompson

Abstract:

The 1990s in America ended with a mass-school-shooting (at least four killed by gunfire excluding the perpetrator(s)) at Columbine High School in Littleton, Colorado. Post-event, many demanded that government and civilian experts develop a ‘profile’ of the potential school shooter in order to identify and preempt likely future acts of violence. This grounded theory research study seeks to explore the validity of the original hypotheses proposed by the Federal Bureau of Investigation (FBI) in 2000, as it relates to the commonality of disclosure by perpetrators of mass-school-shootings, by evaluating fourteen mass-school-shooting events between 2000 and 2019 at locations around the United States. Methods: The strategy of inquiry seeks to investigate case files, public records, witness accounts, and available psychological profiles of the shooter. The research methodology is inclusive of one-on-one interviews with members of the FBI’s Critical Incident Response Group seeking perspective on commonalities between individuals; specifically, disclosure of intent pre-event. Results: The research determined that school shooters do not ‘unfailingly’ notify others of their plans. However, in nine of the fourteen mass-school-shooting events analyzed, the perpetrator did inform the third party of their intent pre-event in some form of written, oral, or electronic communication. In the remaining five instances, the so-called ‘red-flag’ indicators of the potential for an event to occur were profound, and unto themselves, might be interpreted as notification to others of an imminent deadly threat. Conclusion: Data indicates that conclusions drawn in the FBI’s threat assessment perspective published in 2000 are relevant and current. There is evidence that despite potential ‘red-flag’ indicators which may or may not include a variety of other characteristics, perpetrators of mass-school-shooting events are likely to share their intentions with others through some form of direct or indirect communication. More significantly, implications of this research might suggest that society is often informed of potential danger pre-event but lacks any equitable means by which to disseminate, prevent, intervene, or otherwise act in a meaningful way considering said revelation.

Keywords: columbine, FBI profiling, guns, mass shooting, mental health, school violence

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Authors: Ravi Kumar, Santhosh Kumar Dubba

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This paper presents an experimental study of a diabatic flow of R-600a through a concentric configured capillary tube suction line heat exchanger. The details of experimental facility for testing the diabatic capillary tube with different inlet sub-cooling degree and pressure are discussed. The effect of coil diameter, capillary length, capillary tube diameter, sub-cooling degree and inlet pressure on mass flow rate are presented. The degree of sub-cooling at the inlet of capillary tube is varied from 3-20°C. The refrigerant mass flow rate is scattered up with rising of pressure. A semi-empirical correlation to predict the mass flow rate of R-600a flowing through a diabatic capillary tube is proposed for sub-cooled inlet conditions. The proposed correlation predicts measured data with an error band of ±20 percent.

Keywords: diabatic, capillary tube, concentric, R-600a

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Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

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