Search results for: drug target

Authors: Elif Tugce Aksun Tumerkan, Chris Lowe, Hannah Krupa

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Fluorescent proteins are self-sufficient in forming chromophores with a visible wavelength from 3 amino acids sequence within their own polypeptide structure. This chromophore – a molecule that absorbs a photon of light and exhibits an energy transition equal to the energy of the absorbed photon. Fluorescent proteins (FPs) consisted of a chain of 238 amino acid residues and composed of 11 beta strands shaped in a cylinder surrounding an alpha helix structure. A better understanding of the system of the chromospheres and the increasing advance in protein engineering in recent years, the properties of FPs offers the potential for new applications. They have used sensors and probes in molecular biology and cell-based research that giving a chance to observe these FPs tagged cell localization, structural variation and movement. For clarifying functional uses of fluorescent proteins, electrophoretic properties of these proteins are one of the most important parameters. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analysis is used for determining electrophoretic properties commonly. While there are many techniques are used for determining the functionality of protein-based research, SDS-PAGE analysis can only provide a molecular level assessment of the proteolytic fragments. Before SDS-PAGE analysis, fluorescent proteins need to successfully purified. Due to directly purification of the target, FPs is difficult from the animal, gene expression is commonly used which must be done by transformation with the plasmid. Furthermore, used gel within electrophoresis and staining agents properties have a key role. In this review, the different factors that have the impact on the electrophoretic properties of fluorescent proteins explored. Fluorescent protein separation and purification are the essential steps before electrophoresis that should be done very carefully. For protein purification, gene expression process and following steps have a significant function. For successful gene expression, the properties of selected bacteria for expression, used plasmid are essential. Each bacteria has own characteristics which are very sensitive to gene expression, also used procedure is the important factor for fluorescent protein expression. Another important factors are gel formula and used staining agents. Gel formula has an effect on the specific proteins mobilization and staining with correct agents is a key step for visualization of electrophoretic bands of protein. Visuality of proteins can be changed depending on staining reagents. Apparently, this review has emphasized that gene expression and purification have a stronger effect than electrophoresis protocol and staining agents.

Keywords: cell biology, gene expression, staining agents, SDS-page

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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Authors: Okunola Oluseye Ademola

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The study investigated various socio-cultural factors influencing adherence to antiretroviral drugs among people living with HIV in a University Teaching Hospital in South-western Nigeria. The objectives are to examine the perception of people living with HIV/AIDS (PLWHA) of antiretroviral therapy (ART) in Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, investigate the influence of socio-cultural factors on adherence of PLWHA to treatment regimen in the study area and assess the prevalence of adherence to ART among PLWHA in the study area. It was a cross-sectional where both qualitative and quantitative research methods were adopted. The participants were HIV diagnosed patients attending clinic at the Obafemi Awolowo University Teaching Hospitals Complex in Ile-Ife between the ages of 18 and 60 years. Also three healthcare delivery personnel working in the clinic were interviewed. Out of the 3007 patients receiving treatment, using Fischer’s formula of sampling technique, 336 patients living with HIV/AIDS were selected for the study. These participants had been on antiretroviral drugs for more than six months prior to the study and were selected using simple random sampling technique. Two focus group discussion sessions comprising of 10 male and 10 female living with HIV and currently on ART were conducted. These groups were purposively selected based on their being on ART for more than one year. Also in-depth interviews were conducted among three purposively selected healthcare givers (an experienced nurse, a doctor and a pharmacist) who are working in this clinic. All the participants were interviewed at the clinic on the various clinic days. Data were collected using a structured questionnaire, an interview guide and tape-recorder. The quantitative data were analysed using descriptive and inferential statistics. Content analysis was employed to analyse responses from IDI and FGD sessions. The findings from the study revealed a very positive perception to ART among PLWHA which was about 86.3% while the level of adherence to ART was 89.0% among the respondents. There was a very strong relationship between social and family supports and the degree of adherence to ART in the PLWHA. Nutrition, polygamy, difficulty in financing transportation fare to the clinic, unemployment, drug hawkers, religion, excuse duty from work and waking up very early were highlighted as socio-cultural barriers to adherence to ART. Fear of death, strong family support, religion belief, not seeking alternative treatment, absence of rituals and perceived improved health status were identified as very strong facilitators to adherence. The study concluded that to achieve a very optimal outcome in the management of HIV among PLWHA, various social and cultural contexts should be taken into consideration as this study was able to ascertain the influence of various socio-cultural factors militating and facilitating adherence to ART.

Keywords: ART, HIV, PLWHA, socio-cultural

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Authors: Emiliano Matta

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Passive resonant vibration absorbers are among the most widely used dynamic control systems in civil engineering. They typically consist in a single-degree-of-freedom mechanical appendage of the main structure, tuned to one structural target mode through frequency and damping optimization. One classical scheme is the pendulum absorber, whose mass is constrained to move along a curved trajectory and is damped by viscous dashpots. Even though the principle is well known, the search for improved arrangements is still under way. In recent years this investigation inspired a type of bidirectional pendulum absorber (BPA), consisting of a mass constrained to move along an optimal three-dimensional (3D) concave surface. For such a BPA, the surface principal curvatures are designed to ensure a bidirectional tuning of the absorber to both principal modes of the main structure, while damping is produced either by horizontal viscous dashpots or by vertical friction dashpots, connecting the BPA to the main structure. In this paper, a variant of BPA is proposed, where damping originates from the variable tangential friction force which develops between the pendulum mass and the 3D surface as a result of a spatially-varying friction coefficient pattern. Namely, a friction coefficient is proposed that varies along the pendulum surface in proportion to the modulus of the 3D surface gradient. With such an assumption, the dissipative model of the absorber can be proven to be nonlinear homogeneous in the small displacement domain. The resulting homogeneous BPA (HBPA) has a fundamental advantage over conventional friction-type absorbers, because its equivalent damping ratio results independent on the amplitude of oscillations, and therefore its optimal performance does not depend on the excitation level. On the other hand, the HBPA is more compact than viscously damped BPAs because it does not need the installation of dampers. This paper presents the analytical model of the HBPA and an optimal methodology for its design. Numerical simulations of single- and multi-story building structures under wind and earthquake loads are presented to compare the HBPA with classical viscously damped BPAs. It is shown that the HBPA is a promising alternative to existing BPA types and that homogeneous tangential friction is an effective means to realize systems provided with amplitude-independent damping.

Keywords: amplitude-independent damping, homogeneous friction, pendulum nonlinear dynamics, structural control, vibration resonant absorbers

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Authors: Alireza Akbari, Gelareh Babaee Khou

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Ground Penetrating Radar (GPR) is an important nondestructive remote sensing tool that has been used in both military and civilian fields. Recently, GPR imaging has attracted lots of attention in detection of subsurface shallow small targets such as landmines and unexploded ordnance and also imaging behind the wall for security applications. For the monostatic arrangement in the space-time GPR image, a single point target appears as a hyperbolic curve because of the different trip times of the EM wave when the radar moves along a synthetic aperture and collects reflectivity of the subsurface targets. With this hyperbolic curve, the resolution along the synthetic aperture direction shows undesired low resolution features owing to the tails of hyperbola. However, highly accurate information about the size, electromagnetic (EM) reflectivity, and depth of the buried objects is essential in most GPR applications. Therefore hyperbolic curve behavior in the space-time GPR image is often willing to be transformed to a focused pattern showing the object's true location and size together with its EM scattering. The common goal in a typical GPR image is to display the information of the spatial location and the reflectivity of an underground object. Therefore, the main challenge of GPR imaging technique is to devise an image reconstruction algorithm that provides high resolution and good suppression of strong artifacts and noise. In this paper, at first, the standard back-projection (BP) algorithm that was adapted to GPR imaging applications used for the image reconstruction. The standard BP algorithm was limited with against strong noise and a lot of artifacts, which have adverse effects on the following work like detection targets. Thus, an improved BP is based on cross-correlation between the receiving signals proposed for decreasing noises and suppression artifacts. To improve the quality of the results of proposed BP imaging algorithm, a weight factor was designed for each point in region imaging. Compared to a standard BP algorithm scheme, the improved algorithm produces images of higher quality and resolution. This proposed improved BP algorithm was applied on the simulation and the real GPR data and the results showed that the proposed improved BP imaging algorithm has a superior suppression artifacts and produces images with high quality and resolution. In order to quantitatively describe the imaging results on the effect of artifact suppression, focusing parameter was evaluated.

Keywords: algorithm, back-projection, GPR, remote sensing

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Authors: Eric Granholm, Christophe Delay, Jason Holden, Peter Link

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Negative symptoms are an important unmet treatment needed for schizophrenia. We conducted an open trial of a novel blended intervention called mobile-assisted cognitive behavior therapy for negative symptoms (mCBTn). mCBTn is a weekly group therapy intervention combining in-person and smartphone-based CBT (CBT2go app) to improve experiential negative symptoms in people with schizophrenia. Both the therapy group and CBT2go app included recovery goal setting, thought challenging, scheduling of pleasurable activities and social interactions, and pleasure savoring interventions to modify defeatist attitudes, a target mechanism associated with negative symptoms, and improve experiential negative symptoms. We tested whether participants with schizophrenia or schizoaffective disorder (N=31) who met prospective criteria for persistent negative symptoms showed improvement in experiential negative symptoms. Retention was excellent (87% at 18 weeks) and severity of defeatist attitudes and motivation and pleasure negative symptoms declined significantly in mCBTn with large effect sizes. We also tested whether pupillary responses, a measure of cognitive effort, predicted improvement in negative symptoms mCBTn. Pupillary responses were recorded at baseline using a Tobii pupillometer during the digit span task with 3-, 6- and 9-digit spans. Mixed models showed that greater dilation during the task at baseline significantly predicted a greater reduction in experiential negative symptoms. Pupillary responses may provide a much-needed prognostic biomarker of which patients are most likely to benefit from CBT. Greater pupil dilation during a cognitive task predicted greater improvement in experiential negative symptoms. Pupil dilation has been linked to motivation and engagement of executive control, so these factors may contribute to benefits in interventions that train cognitive skills to manage negative thoughts and emotions. The findings suggest mCBTn is a feasible and effective treatment for experiential negative symptoms and justify a larger randomized controlled clinical trial. The findings also provide support for the defeatist attitude model of experiential negative symptoms and suggest that mobile-assisted interventions like mCBTn can strengthen and shorten intensive psychosocial interventions for schizophrenia.

Keywords: cognitive-behavioral therapy, mobile interventions, negative symptoms, pupillometry schizophrenia

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Authors: Yunjia Yang, Peng Li, Gordon Xu, Timothy Mahony, Bing Zhang, Neena Mitter, Karishma Mody

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Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls and the parasite has developed resistance to nearly all control chemicals used in the past. It is therefore critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi and insects. However, the environmental instability of dsRNA is a major bottleneck for successful RNAi. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for the controlled release of dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. To investigate the potential of BenPol technology for dsRNA delivery, four different BenPol carriers were tested for their dsRNA loading capabilities, and three of them were found to be capable of affording dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in sheep serum. Based on stability results, dsRNA from potential targeted genes was loaded onto BenPol carriers and tested in larvae feeding assays, three genes resulting in knockdowns. Meanwhile, a primary blowfly embryo cell line (BFEC) derived from L. cuprina embryos was successfully established, aim for an effective insect cell model for testing RNAi efficacy for preliminary assessments and screening. The results of this study establish that the dsRNA is stable when loaded on BenPol particles, unlike naked dsRNA rapidly degraded in sheep serum. The stable nanoparticle delivery system offered by BenPol technology can protect and increase the inherent stability of dsRNA molecules at higher temperatures in a complex biological fluid like serum, providing promise for its future use in enhancing animal protection.

Keywords: flystrike, RNA interference, bentonite polymer technology, Lucillia cuprina

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Authors: Ammar Asma, Bouafia Nabiha, Ben Cheikh Asma, Ezzi Olfa, Mahjoub Mohamed, Sma Nesrine, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

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Background: Ventilator-associated pneumonia (VAP) is currently recognized as one of the most relevant causes of morbidity and mortality among intensive care unit (ICU) patients worldwide. Identifying modifiable risk factors for VAP could be helpful for future controlled interventional studies aiming at improving prevention of VAP. The purposes of this study were to determine the incidence and risk factors for VAP in in a Tunisian medical ICU. Materials / Methods: A retrospective case-control study design based on the prospective database collected over a 14-month period from September 15th, 2015 through November 15th, 2016 in an 8-bed medical ICU. Patients under ventilation for over 48 h were included. The number of cases was estimated by Epi-info Software with the power of statistical test equal to 90 %. Each case patient was successfully matched to two controls according to the length of mechanical ventilation (MV) before VAP for cases and the total length of MV in controls. VAP in the ICU was defined according to American Thoracic Society; Infectious Diseases Society of America guidelines. Early onset or late-onset VAP were defined whether the infectious process occurred within or after 96 h of ICU admission. Patients’ risk factors, causes of admission, comorbidities and respiratory specimens collected were reviewed. Univariate and multivariate analyses were performed to determine variables associated with VAP with a p-value < 0.05. Results: During the period study, a total of 169 patients under mechanical ventilation were considered, 34 patients (20.11%) developed at least one episode of VAP in the ICU. The incidence rate for VAP was 14.88/1000 ventilation days. Among these cases, 9 (26.5 %) were early-onset VAP and 25 (73.5 %) were late-onset VAP. It was a certain diagnosis in 66.7% of cases. Tracheal aspiration was positive in 80% of cases. Multi-drug resistant Acinerobacter baumanii was the most common species detected in cases; 67.64% (n=23). The rate of mortality out of cases was 88.23% (n= 30). In univariate analysis, the patients with VAP were statistically more likely to suffer from cardiovascular diseases (p=0.035) and prolonged duration of sedation (p=0.009) and tracheostomy (p=0.001), they also had a higher number of re-intubation (p=0.017) and a longer total time of intubation (p=0.012). Multivariate analysis showed that cardiovascular diseases (OR= 4.44; 95% IC= [1.3 - 14]; p=0.016), tracheostomy (OR= 4.2; 95% IC= [1.16 -15.12]; p= 0.028) and prolonged duration of sedation (OR=1.21; 95% IC= [1.07, 1.36]; p=0.002) were independent risk factors for the development of VAP. Conclusion: VAP constitutes a therapeutic challenge in an ICU setting, therefore; strategies that effectively prevent VAP are needed. An infection control-training program intended to all professional heath care in this unit insisting on bundles and elaboration of procedures are planned to reduce effectively incidence rate of VAP.

Keywords: case control study, intensive care unit, risk factors, ventilator associated pneumonia

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Authors: Malkit Singh

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This paper presents an in-depth analysis of the problem of migration from Punjab to the West while analyzing the history and patterns of generations of migration of Punjabis to the West. A special emphasis is given to link the present socio-economic and political crisis with the historical pattern of Punjabis’ migration to the West from colonial India to Independent Bharat, along with the stories of the success and failures of Western aspirants’ youth from Punjab. The roots of the migration from Punjab to the West have been traced from the invasion of the British in Punjab, resulting in the socio-economic and political dismantling of the Punjabi society, which resulted in the migration of the Punjabis to the other colonies of the British Empire. The grim position at home despite of all the efforts and hard work by the majority of the Punjabis, particularly from the farmer community and the shining lifestyle of some families of the village or vicinity who have some relatives in the West have encouraged the large number of Punjabis to change their fortune by working in West. However, the Visa and Work Permit regime has closed the doors of the West for those who are unskilled, semi-skilled and not qualified for the visa and work permit norms, but their inspiration to change their fortune by working abroad at any cost has resulted into the development of big business fraud of immigration agent and firms in Punjab that resulted into the loss of the thousands lives, imprisonment in the foreign and selling of the properties of the Punjabis. The greed for the greener pastures in the West and, the plight of the deserted wives of NRIs and the illegal routes adopted by the Punjabi youth due to the non-availability of visas and work permits are dealt in a comprehensive method. The rise and fall of Punjab as a land of the breadbasket of Bharat and the marginalization of the farmers with middle and small holdings due to the capital-intensive techniques are linked with the forced migration of the Punjabis. The failure of the government to address and respond to the rampant corruption, agriculture failure and the resulting problems of law and order before and after the troubled period of militancy in Punjab and the resulting migration to the West are comprehensively covered. The new trend of the Student Visa and Study abroad, particularly in Canada, Australia, and New Zealand, despite of the availability of quality education at very low cost in India. The early success of some students in getting study visas from Australia, Canada, New Zealand etc. and getting permanent immigration to these countries have encouraged the majority of Punjabi youth to leave their motherland for better opportunities in the prosperous lands, that is, again, failed as these countries are flooded with the Punjabi students. Moreover, the total failure of the political leadership of Punjab to address the basic needs of society, like law and order and stop the drug menace issues in the post-militancy Punjab is also done to understand the problem.

Keywords: Punjab, migration, West, agriculture

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Authors: Mansir Abubakar, Hazlina Hamdan, Norwati Mustapha, Teh Noranis Mohd Aris

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In order to build a matching pattern for each class correspondences of ontology, it is required to specify a set of attribute correspondences across two corresponding classes by clustering. Clustering reduces the size of potential attribute correspondences considered in the matching activity, which will significantly reduce the computation workload; otherwise, all attributes of a class should be compared with all attributes of the corresponding class. Most existing ontology matching approaches lack scalable attributes discovery methods, such as cluster-based attribute searching. This problem makes ontology matching activity computationally expensive. It is therefore vital in ontology matching to design a scalable element or attribute correspondence discovery method that would reduce the size of potential elements correspondences during mapping thereby reduce the computational workload in a matching process as a whole. The objective of this work is 1) to design a clustering method for discovering similar attributes correspondences and relationships between ontologies, 2) to discover element correspondences by classifying elements of each class based on element’s value features using K-medoids clustering technique. Discovering attribute correspondence is highly required for comparing instances when matching two ontologies. During the matching process, any two instances across two different data sets should be compared to their attribute values, so that they can be regarded to be the same or not. Intuitively, any two instances that come from classes across which there is a class correspondence are likely to be identical to each other. Besides, any two instances that hold more similar attribute values are more likely to be matched than the ones with less similar attribute values. Most of the time, similar attribute values exist in the two instances across which there is an attribute correspondence. This work will present how to classify attributes of each class with K-medoids clustering, then, clustered groups to be mapped by their statistical value features. We will also show how to map attributes of a clustered group to attributes of the mapped clustered group, generating a set of potential attribute correspondences that would be applied to generate a matching pattern. The K-medoids clustering phase would largely reduce the number of attribute pairs that are not corresponding for comparing instances as only the coverage probability of attributes pairs that reaches 100% and attributes above the specified threshold can be considered as potential attributes for a matching. Using clustering will reduce the size of potential elements correspondences to be considered during mapping activity, which will in turn reduce the computational workload significantly. Otherwise, all element of the class in source ontology have to be compared with all elements of the corresponding classes in target ontology. K-medoids can ably cluster attributes of each class, so that a proportion of attribute pairs that are not corresponding would not be considered when constructing the matching pattern.

Keywords: attribute correspondence, clustering, computational workload, k-medoids clustering, ontology matching

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Authors: Yunha Ryu, Kyoungsik Kim

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Raman spectroscopy is one of the most powerful techniques for chemical detection, but the low sensitivity originated from the extremely small cross-section of the Raman scattering limits the practical use of Raman spectroscopy. To overcome this problem, Surface Enhanced Raman Scattering (SERS) has been intensively studied for several decades. Because the SERS effect is mainly induced from strong electromagnetic near-field enhancement as a result of localized surface plasmon resonance of metallic nanostructures, it is important to design the plasmonic structures with high density of electromagnetic hot spots for SERS substrate. One of the useful fabrication methods is using porous nanomaterial as a template for metallic structure. Internal pores on a scale of tens of nanometers can be strong EM hotspots by confining the incident light. Also, porous structures can capture more target molecules than non-porous structures in a same detection spot thanks to the large surface area. Herein we report the facile fabrication method of porous SERS substrate by integrating solvent-assisted nanoimprint lithography and selective etching of block copolymer. We obtained nanostructures with high porosity via simple selective etching of the one microdomain of the diblock copolymer. Furthermore, we imprinted of the nanocone patterns into the spin-coated flat block copolymer film to make three-dimensional SERS substrate for the high density of SERS hot spots as well as large surface area. We used solvent-assisted nanoimprint lithography (SAIL) to reduce the fabrication time and cost for patterning BCP film by taking advantage of a solvent which dissolves both polystyrenre and poly(methyl methacrylate) domain of the block copolymer, and thus block copolymer film was molded under the low temperature and atmospheric pressure in a short time. After Ag deposition, we measured Raman intensity of dye molecules adsorbed on the fabricated structure. Compared to the Raman signals of Ag coated solid nanocone, porous nanocone showed 10 times higher Raman intensity at 1510 cm(-1) band. In conclusion, we fabricated porous metallic nanocone arrays with high density electromagnetic hotspots by templating nanoimprinted diblock copolymer with selective etching and demonstrated its capability as an effective SERS substrate.

Keywords: block copolymer, porous nanostructure, solvent-assisted nanoimprint, surface-enhanced Raman spectroscopy

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Authors: Eashan Hatti

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In software development, programmers often must make a choice between high-level programming and high-performance programs. High-level programming encourages the use of complex, pervasive abstractions. However, the use of these abstractions degrades performance-high performance demands that programs be low-level. In a compiler, the optimizer attempts to let the user have both. The optimizer takes high-level, abstract code as an input and produces low-level, performant code as an output. However, there is a problem with having the optimizer be a built-in part of the compiler. Domain-specific abstractions implemented as libraries are common in high-level languages. As a language’s library ecosystem grows, so does the number of abstractions that programmers will use. If these abstractions are to be performant, the optimizer must be extended with new optimizations to target them, or these abstractions must rely on existing general-purpose optimizations. The latter is often not as effective as needed. The former presents too significant of an effort for the compiler developers, as they are the only ones who can extend the language with new optimizations. Thus, the language becomes more high-level, yet the optimizer – and, in turn, program performance – falls behind. Programmers are again confronted with a choice between high-level programming and high-performance programs. To investigate a potential solution to this problem, we developed Peridot, a prototype programming language. Peridot’s main contribution is that it enables library developers to easily extend the language with new optimizations themselves. This allows the optimization workload to be taken off the compiler developers’ hands and given to a much larger set of people who can specialize in each problem domain. Because of this, optimizations can be much more effective while also being much more numerous. To enable this, Peridot supports metaprogramming designed for implementing program transformations. The language is split into two fragments or “levels”, one for metaprogramming, the other for high-level general-purpose programming. The metaprogramming level supports logic programming. Peridot’s key idea is that optimizations are simply implemented as metaprograms. The meta level supports several specific features which make it particularly suited to implementing optimizers. For instance, metaprograms can automatically deduce equalities between the programs they are optimizing via unification, deal with variable binding declaratively via higher-order abstract syntax, and avoid the phase-ordering problem via non-determinism. We have found that this design centered around logic programming makes optimizers concise and easy to write compared to their equivalents in functional or imperative languages. Overall, implementing Peridot has shown that its design is a viable solution to the problem of writing code which is both high-level and performant.

Keywords: optimization, metaprogramming, logic programming, abstraction

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Authors: Getahun Lemma

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Introduction Guinea Worm Disease (GWD), also known as dracunculiasisis, is one of the oldest diseases in the history of mankind. Dracunculiasis is caused by a parasitic nematode, Dracunculus medinensis. Infection is acquired by drinking contaminated water with copepods containing infective Guinea Worm (GW) larvae). Almost one year after the infection, the worm usually emerges out through the skin on a lower, causing severe pain and disabilities. Although there is no effective drug or vaccine against the disease, the chain of transmission can be effectively prevented with simple and cost effective public health measures. Death due to dracunculiasis is very rare. However, it results in a wide range of physical, social and economic sequels. The disease is usually common in the rural, remote places of Sub-Saharan African countries among the marginalized societies. Currently, GWD is one of the neglected tropical diseases, which is on the verge of eradication. The global Guinea Worm Eradication Program (GWEP) was started in 1980. Since then, the program has achieved a tremendous success in reducing the global burden and number of GW case from 3.5 million to only 28 human cases at the end of 2018. However, it has recently been shown that not only humans can become infected, with a total of 1,105 animal infections have been reported at the end of 2018. Therefore, the objective of this study was to identify the existing challenges in the last mile of the GWEP in order To inform Policy makers and stakeholders on potential measures to finally achieve eradication. Method Systematic literature review on articles published from January 1, 2000 until May 30, 2019. Papers listed in Cochrane Library, Google Scholar, ProQuest PubMed and Web of Science databases were searched and reviewed. Results Twenty-five articles met inclusion criteria of the study and were selected for analysis. Hence, relevant data were extracted, grouped and descriptively analyzed. Results showed the main challenges complicating the last mile of global GWEP: 1. Unusual mode of transmission; 2. Rising animal Guinea Worm infection; 3. Suboptimal surveillance; 4. Insecurity; 5. Inaccessibility; 6. Inadequate safe water points; 7. Migration; 8. Poor case containment measures, 9. Ecological changes; and 10. New geographic foci of the disease. Conclusion This systematic review identified that most of the current challenges in the GWEP have been present since the start of the campaign. However, the recent change in epidemiological patterns and nature of GWD in the last remaining endemic countries illustrates a new twist in the global GWEP. Considering the complex nature of the current challenges, there seems to be a need for a more coordinated and multidisciplinary approach of GWD prevention and control measures in the last mile of the campaign. These new strategies would help to make history by eradicating dracunculiasis as the first ever parasitic disease.

Keywords: dracunculiasis, eradication program, guinea worm, last mile

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Authors: Ruslin, R. E. Kartasasmita, M. S. Wibowo, S. Ibrahim

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An aphrodisiac is a substance contained in food or drug that can arouse sexual instinct and increase pleasure while working, these substances derived from plants, animals, and minerals. When consuming substances that have aphrodisiac activity and duration can improve the sexual instinct. The natural aphrodisiac effect can be obtained through plants, animals, and minerals. Leonurine compound has aphrodisiac activity, these compounds can be isolated from plants of Leonurus Sp, Sundanese people is known as deundereman, this plant is empirical has aphrodisiac activity and based on the isolation of active compounds from plants known to contain compounds leonurine, so that the compound is expected to have activity aphrodisiac. Leonurine compound can be isolated from plants or synthesized chemically with material dasa siringat acid. Leonurine compound can be obtained commercial and derivatives of these compounds can be synthesized in an effort to increase its activity. This study aims to obtain derivatives leonurine better aphrodisiac activity compared with the parent compound, modified the structure of the compounds in the form leonurin guanidino butyl ester group with butyl amin and bromoetanol. ArgusLab program version 4.0.1 is used to determine the binding energy, hydrogen bonds and amino acids involved in the interaction of the compound PDE5 receptor. The in vivo test leonurine compounds and derivatives as an aphrodisiac ingredients and hormone testosterone levels using 27 male rats Wistar strain and 9 female mice of the same species, ages ranged from 12 weeks rats weighing + 200 g / tail. The test animal is divided into 9 groups according to the type of compounds and the dose given. Each treatment group was orally administered 2 ml per day for 5 days. On the sixth day was observed male rat sexual behavior and taking blood from the heart to measure testosterone levels using ELISA technique. Statistical analysis was performed in this study is the ANOVA test Least Square Differences (LSD) using the program Statistical Product and Service Solutions (SPSS). Aphrodisiac efficacy of the leonurine compound and its derivatives have proven in silico and in vivo test, the in silico testing leonurine derivatives have smaller binding energy derivatives leonurine so that activity better than leonurine compounds. Testing in vivo using rats of wistar strain that better leonurine derivative of this compound shows leonurine that in silico studies in parallel with in vivo tests. Modification of the structure in the form of guanidine butyl ester group with butyl amin and bromoethanol increase compared leonurine compound for aphrodisiac activity, testosterone derivatives of compounds leonurine experienced a significant improvement especial is 1RD compounds especially at doses of 100 and 150 mg/bb. The results showed that the compound leonurine and its compounds contain aphrodisiac activity and increase the amount of testosterone in the blood. The compound test used in this study acts as a steroid precursor resulting in increased testosterone.

Keywords: aphrodisiac dysfunction erectile leonurine 1-RD 2-RD, dysfunction, erectile leonurine, 1-RD 2-RD

Procedia PDF Downloads 279

Authors: Sharib Ahmed, Mansoor Rafi, Kamran Ali Awan, Faraz Khaskhali, Amir Maqbool, Altaf Hashmi

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Medical linear accelerators (LINAC’s) used in radiotherapy treatments produce undesired neutrons when they are operated at energies above 8 MeV, both in electron and photon configuration. Neutrons are produced by high-energy photons and electrons through electronuclear (e, n) a photonuclear giant dipole resonance (GDR) reactions. These reactions occurs when incoming photon or electron incident through the various materials of target, flattening filter, collimators, and other shielding components in LINAC’s structure. These neutrons may reach directly to the patient, or they may interact with the surrounding materials until they become thermalized. A work has been set up to study the effect of different parameter on the production of neutron around the room by photonuclear reactions induced by photons above ~8 MeV. One of the commercial available neutron detector (Ludlum Model 42-31H Neutron Detector) is used for the detection of thermal and fast neutrons (0.025 eV to approximately 12 MeV) inside and outside of the treatment room. Measurements were performed for different field sizes at 100 cm source to surface distance (SSD) of detector, at different distances from the isocenter and at the place of primary and secondary walls. Other measurements were performed at door and treatment console for the potential radiation safety concerns of the therapists who must walk in and out of the room for the treatments. Exposures have taken place from Elekta Synergy® linear accelerators for two different energies (10 MV and 18 MV) for a given 200 MU’s and dose rate of 600 MU per minute. Results indicates that neutron doses at 100 cm SSD depend on accelerator characteristics means jaw settings as jaws are made of high atomic number material so provides significant interaction of photons to produce neutrons, while doses at the place of larger distance from isocenter are strongly influenced by the treatment room geometry and backscattering from the walls cause a greater doses as compare to dose at 100 cm distance from isocenter. In the treatment room the ambient dose equivalent due to photons produced during decay of activation nuclei varies from 4.22 mSv.h−1 to 13.2 mSv.h−1 (at isocenter),6.21 mSv.h−1 to 29.2 mSv.h−1 (primary wall) and 8.73 mSv.h−1 to 37.2 mSv.h−1 (secondary wall) for 10 and 18 MV respectively. The ambient dose equivalent for neutrons at door is 5 μSv.h−1 to 2 μSv.h−1 while at treatment console room it is 2 μSv.h−1 to 0 μSv.h−1 for 10 and 18 MV respectively which shows that a 2 m thick and 5m longer concrete maze provides sufficient shielding for neutron at door as well as at treatment console for 10 and 18 MV photons.

Keywords: equivalent doses, neutron contamination, neutron detector, photon energy

Procedia PDF Downloads 449

Authors: Tomasz Łęga, Marta Sosnowska, Mirosława Panasiuk, Lilit Hovhannisyan, Beata Gromadzka, Marcin Olszewski, Sabina Zoledowska, Dawid Nidzworski

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Toxic heavy metal ion contamination of industrial wastewater has recently become a significant environmental concern in many regions of the world. Although the majority of heavy metals are naturally occurring elements found on the earth's surface, anthropogenic activities such as mining and smelting, industrial production, and agricultural use of metals and metal-containing compounds are responsible for the majority of environmental contamination and human exposure. The permissible limits (ppm) for heavy metals in food, water and soil are frequently exceeded and considered hazardous to humans, other organisms, and the environment as a whole. Human exposure to highly nickel-polluted environments causes a variety of pathologic effects. In 2008, nickel received the shameful name of “Allergen of the Year” (GILLETTE 2008). According to the dermatologist, the frequency of nickel allergy is still growing, and it can’t be explained only by fashionable piercing and nickel devices used in medicine (like coronary stents and endoprostheses). Effective remediation methods for removing heavy metal ions from soil and water are becoming increasingly important. Among others, methods such as chemical precipitation, micro- and nanofiltration, membrane separation, conventional coagulation, electrodialysis, ion exchange, reverse and forward osmosis, photocatalysis and polymer or carbon nanocomposite absorbents have all been investigated so far. The importance of environmentally sustainable industrial production processes and the conservation of dwindling natural resources has highlighted the need for affordable, innovative biosorptive materials capable of recovering specific chemical elements from dilute aqueous solutions. The use of combinatorial phage display techniques for selecting and recognizing material-binding peptides with a selective affinity for any target, particularly inorganic materials, has gained considerable interest in the development of advanced bio- or nano-materials. However, due to the limitations of phage display libraries and the biopanning process, the accuracy of molecular recognition for inorganic materials remains a challenge. This study presents the isolation, identification and characterisation of metal binding phage clones that preferentially recover nickel.

Keywords: Heavy metal recovery, cleaning water, phage display, nickel

Procedia PDF Downloads 99

Authors: B. Petrović, M. Petrović, L. Rutonjski, I. Djan, V. Ivanović

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Objective: Cardiac pacemakers are very sensitive to radiotherapy treatment from two sources: electromagnetic influence from the medical linear accelerator producing ionizing radiation- influencing electronics within the pacemaker, and the absorption of dose to the device. On the other hand, patients with cardiac pacemakers at the place of a tumor are rather rare, and single clinic hardly has experience with the management of such patients. The widely accepted international guidelines for management of radiation oncology patients recommend that these patients should be closely monitored and examined before, during and after radiotherapy treatment by cardiologist, and their device and condition followed up. The number of patients having both cancer and pacemaker, is growing every year, as both cancer incidence, as well as cardiac diseases incidence, are inevitably growing figures. Materials and methods: Female patient, age 69, was diagnozed with valvular cardiomyopathy and got implanted a pacemaker in 2005 and prosthetic mitral valve in 1993 (cancer was diagnosed in 2012). She was stable cardiologically and came to radiation therapy department with the diagnosis of right breast cancer, with the tumor in upper lateral quadrant of the right breast. Since she had all lymph nodes positive (28 in total), she had to have irradiated the supraclavicular region, as well as the breast with the tumor bed. She previously received chemotherapy, approved by the cardiologist. The patient was estimated to be with the high risk as device was within the field of irradiation, and the patient had high dependence on her pacemaker. The radiation therapy plan was conducted as 3D conformal therapy. The delineated target was breast with supraclavicular region, where the pacemaker was actually placed, with the addition of a pacemaker as organ at risk, to estimate the dose to the device and its components as recommended, and the breast. The targets received both 50 Gy in 25 fractions (where 20% of a pacemaker received 50 Gy, and 60% of a device received 40 Gy). The electrode to the heart received between 1 Gy and 50 Gy. Verification of dose planned and delivered was performed. Results: Evaluation of the patient status according to the guidelines and especially evaluation of all associated risks to the patient during treatment was done. Patient was irradiated by prescribed dose and followed up for the whole year, with no symptoms of failure of the pacemaker device during, or after treatment in follow up period. The functionality of a device was estimated to be unchanged, according to the parameters (electrode impedance and battery energy). Conclusion: Patient was closely monitored according to published guidelines during irradiation and afterwards. Pacemaker irradiated with the full dose did not show any signs of failure despite recommendations data, but in correlation with other published data.

Keywords: cardiac pacemaker, breast cancer, radiotherapy treatment planning, complications of treatment

Procedia PDF Downloads 438

Authors: Gianluca Castelnuovo, Giada Pietrabissa, Gian Mauro Manzoni, Margherita Novelli, Emanuele Maria Giusti, Roberto Cattivelli, Enrico Molinari

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Diabesity could be defined as a new global epidemic of obesity and being overweight with many complications and chronic conditions. Such conditions include not only type 2 diabetes, but also cardiovascular diseases, hypertension, dyslipidemia, hypercholesterolemia, cancer, and various psychosocial and psychopathological disorders. The financial direct and indirect burden (considering also the clinical resources involved and the loss of productivity) is a real challenge in many Western health-care systems. Recently the Lancet journal defined diabetes as a 21st-century challenge. In order to promote patient compliance in diabesity treatment reducing costs, evidence-based interventions to improve weight-loss, maintain a healthy weight, and reduce related comorbidities combine different treatment approaches: dietetic, nutritional, physical, behavioral, psychological, and, in some situations, pharmacological and surgical. Moreover, new technologies can provide useful solutions in this multidisciplinary approach, above all in maintaining long-term compliance and adherence in order to ensure clinical efficacy. Psychological therapies with diet and exercise plans could better help patients in achieving weight loss outcomes, both inside hospitals and clinical centers and during out-patient follow-up sessions. In the management of chronic diseases clinical psychology play a key role due to the need of working on psychological conditions of patients, their families and their caregivers. mHealth approach could overcome limitations linked with the traditional, restricted and highly expensive in-patient treatment of many chronic pathologies: one of the best up-to-date application is the management of obesity with type 2 diabetes, where mHealth solutions can provide remote opportunities for enhancing weight reduction and reducing complications from clinical, organizational and economic perspectives. A stepped care mHealth-based approach is an interesting perspective in chronic care management of obesity with type 2 diabetes. One promising future direction could be treating obesity, considered as a chronic multifactorial disease, using a stepped-care approach: -mhealth or traditional based lifestyle psychoeducational and nutritional approach. -health professionals-driven multidisciplinary protocols tailored for each patient. -inpatient approach with the inclusion of drug therapies and other multidisciplinary treatments. -bariatric surgery with psychological and medical follow-up In the chronic care management of globesity mhealth solutions cannot substitute traditional approaches, but they can supplement some steps in clinical psychology and medicine both for obesity prevention and for weight loss management.

Keywords: clinical health psychology, mhealth, obesity, type 2 diabetes, stepped care, chronic care management

Procedia PDF Downloads 344

Authors: Shahid Noor, Kazim Najjad, Muhammad Nasir, Irshad Bhutto, Abdul Samad Memon, Khurram Anwar, Tehseen Riaz, Mian Muhammad Hanif, Nauman A. Mallik, Saeed Ahmed, Israr Ahmed, Ali Yasir

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Background: Musculoskeletal pain is the most common complaint presented to the health practitioner. It is well known that untreated or under-treated pain can have a significant negative impact on an individual’s quality of life (QoL). Objectives: This study was conducted across 10 sites in six (6) major cities of Pakistan to evaluate the tolerability, safety, and the clinical response of Nuberol Forte® (Paracetamol 650 mg + Orphenadrine 50 mg) to musculoskeletal pain in routine Pakistani practice and its impact on improving the patient’s QoL. Design & Methods: This NFORT-EFFECT observational, prospective multicenter study was conducted in compliance with Good Clinical Practice guidelines and local regulatory requirements. The study sponsor was "The Searle Company Limited, Pakistan. To maintain the GCP compliances, the sponsor assigned the CRO for the site and data management. Ethical approval was obtained from an independent ethics committee. The IEC reviewed the progress of the study. Written informed consent was obtained from the study participants, and their confidentiality was maintained throughout the study. A total of 399 patients with known prescreened musculoskeletal conditions and pain who attended the study sites were recruited, as per the inclusion/exclusion criteria (clinicaltrials.gov ID# NCT04765787). The recruited patients were then prescribed Paracetamol (650 mg) and Orphenadrine (50 mg) combination (Nuberol Forte®) for 7 to 14 days as per the investigator's discretion based on the pain intensity. After the initial screening (visit 1), a follow-up visit was conducted after 1-2 weeks of the treatment (visit 2). Study Endpoints: The primary objective was to assess the pain management response of Nuberol Forte treatment and the overall safety of the drug. The Visual Analogue Scale (VAS) scale was used to measure pain severity. Secondary to pain, the patients' health-related quality of life (HRQoL) was also assessed using the Muscle, Joint Measure (MJM) scale. The safety was monitored on the first dose by the patients. These assessments were done on each study visit. Results: Out of 399 enrolled patients, 49.4% were males, and 50.6% were females with a mean age of 47.24 ± 14.20 years. Most patients were presented with Knee Osteoarthritis (OA), i.e., 148(38%), followed by backache 70(18.2%). A significant reduction in the mean pain score was observed after the treatment with the combination of Paracetamol and Orphenadrine (p<0.05). Furthermore, an overall improvement in the patient’s QoL was also observed. During the study, only ten patients reported mild adverse events (AEs). Conclusion: The combination of Paracetamol and Orphenadrine (Nuberol Forte®) exhibited effective pain management among patients with musculoskeletal conditions and also improved their QoL.

Keywords: musculoskeletal pain, orphenadrine/paracetamol combination, pain management, quality of life, Pakistani population

Procedia PDF Downloads 169

Authors: Lahari Ramya Pa, Sudhakar Ib, Madhu Vc, Madhusudhan Reddy Gd, Srinivasa Rao E.

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Selection of suitable armor materials for defense applications is very crucial with respect to increasing mobility of the systems as well as maintaining safety. Therefore, determining the material with the lowest possible areal density that resists the predefined threat successfully is required in armor design studies. A number of light metal and alloys are come in to forefront especially to substitute the armour grade steels. AA5083 aluminium alloy which fit in to the military standards imposed by USA army is foremost nonferrous alloy to consider for possible replacement of steel to increase the mobility of armour vehicles and enhance fuel economy. Growing need of AA5083 aluminium alloy paves a way to develop supplement aluminium alloys maintaining the military standards. It has been witnessed that AA 2xxx aluminium alloy, AA6xxx aluminium alloy and AA7xxx aluminium alloy are the potential material to supplement AA5083 aluminium alloy. Among those cited aluminium series alloys AA7xxx aluminium alloy (heat treatable) possesses high strength and can compete with armour grade steels. Earlier investigations revealed that layering of AA7xxx aluminium alloy can prevent spalling of rear portion of armour during ballistic impacts. Hence, present investigation deals with fabrication of hard layer (made of boron carbide) i.e. layer on AA 7075 aluminium alloy using friction stir processing with an intention of blunting the projectile in the initial impact and backing tough portion(AA7xxx aluminium alloy) to dissipate residual kinetic energy. An analytical approach has been adopted to unfold the ballistic performance of projectile. Penetration of projectile inside the armour has been resolved by considering by strain energy model analysis. Perforation shearing areas i.e. interface of projectile and armour is taken in to account for evaluation of penetration inside the armour. Fabricated surface composites (targets) were tested as per the military standard (JIS.0108.01) in a ballistic testing tunnel at Defence Metallurgical Research Laboratory (DMRL), Hyderabad in standardized testing conditions. Analytical results were well validated with experimental obtained one.

Keywords: AA7075 aluminium alloy, friction stir processing, boron carbide, ballistic performance, target

Procedia PDF Downloads 330

Authors: Chenxiao Yang, Li Li

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In this decade, the sportswear market rapidly expanded while numerous sports brands are conducting fierce competitions to hold their market shares and trying to act as a leader in professional competition sports areas to set the trends. Thus, various advancing sports equipment is being deeply explored to improving athletes’ performance in fierce competitions. Although there is plenty protective equipment such as cuff, running legging, etc., on the market, there is still blank in the field of sportswear during prerace warm-up this important time gap, especially for those competitions host in cold environment. Because there is always time gaps between warm-up and race due to event logistics or unexpected weather factors. Athletes will be exposed to chilly condition for an unpredictable long period of time. As a consequence, the effects of warm-up will be negated, and the competition performance will be degraded. However, reviewing the current market, there is none effective sports equipment provided to help athletes against this harsh environment or the rare existing products are so blocky or heavy to restrict the actions. An ideal thermal-protective sportswear should be light, flexible, comfort and aesthetic at the same time. Therefore, this design research adopted the textile circular knitting methodology to integrate soft silver-coated conductive yarns (ab. SCCYs), elastic nylon yarn and polyester yarn to develop the proposed electrical, thermal sportswear, with the strengths aforementioned. Meanwhile, the relationship between heating performance, stretch load, and energy consumption were investigated. Further, a simulation model was established to ensure providing sufficient warm and flexibility at lower energy cost and with an optimized production, parameter determined. The proposed circular knitting technology and simulation model can be directly applied to instruct prototype developments to cater different target consumers’ needs and ensure prototypes’’ safety. On the other hand, high R&D investment and time consumption can be saved. Further, two prototypes: a kneecap and an elbow guard, were developed to facilitate the transformation of research technology into an industrial application and to give a hint on the blur future blueprint.

Keywords: cold environment, silver-coated conductive yarn, electrical thermal textile, stretchable

Procedia PDF Downloads 269

Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

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Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

Procedia PDF Downloads 432

Authors: Mustafa Sengul, Enes Sahin, Sertac Arslan

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Pumpjets are one of the marine propulsion systems frequently used in underwater vehicles nowadays. The reasons for frequent use of pumpjet as a propulsion system are that it has higher relative efficiency at high speeds, better cavitation, and acoustic performance than its rivals. Pumpjets are composed of rotor, stator, and duct, and there are two different types of pumpjet configurations depending on the desired hydrodynamic characteristic, which are with accelerating and decelerating duct. Pumpjet with an accelerating channel is used at cargo ships where it works at low speeds and high loading conditions. The working principle of this type of pumpjet is to maximize the thrust by reducing the pressure of the fluid through the channel and throwing the fluid out from the channel with high momentum. On the other hand, for decelerating ducted pumpjets, the main consideration is to prevent the occurrence of the cavitation phenomenon by increasing the pressure of the fluid about the rotor region. By postponing the cavitation, acoustic noise naturally falls down, so decelerating ducted systems are used at noise-sensitive vehicle systems where acoustic performance is vital. Therefore, duct design becomes a crucial step during pumpjet design. This study, it is aimed to optimize the duct geometry of a decelerating ducted pumpjet for a highly speed underwater vehicle by using proper optimization tools. The target output of this optimization process is to obtain a duct design that maximizes fluid pressure around the rotor region to prevent from cavitation and minimizes drag force. There are two main optimization techniques that could be utilized for this process which are parameter-based optimization and gradient-based optimization. While parameter-based algorithm offers more major changes in interested geometry, which makes user to get close desired geometry, gradient-based algorithm deals with minor local changes in geometry. In parameter-based optimization, the geometry should be parameterized first. Then, by defining upper and lower limits for these parameters, design space is created. Finally, by proper optimization code and analysis, optimum geometry is obtained from this design space. For this duct optimization study, a commercial codedparameter-based optimization algorithm is used. To parameterize the geometry, duct is represented with b-spline curves and control points. These control points have x and y coordinates limits. By regarding these limits, design space is generated.

Keywords: pumpjet, decelerating duct design, optimization, underwater vehicles, cavitation, drag minimization

Procedia PDF Downloads 209

Authors: Francesco Pantano, Marta Fogolari, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Marco Russano, Fabrizio Citarella, Bruno Vincenzi, Silvia Angeletti, Giuseppe Tonini

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Background: Although immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of non–small cell lung cancer (NSCLC), these drugs fail to elicit durable responses in the majority of NSCLC patients. The gut microbiota, able to regulate immune responsiveness, is emerging as a promising, modifiable target to improve ICIs response rates. Since the oral microbiome has been demonstrated to be the primary source of bacterial microbiota in the lungs, we investigated its composition as a potential predictive biomarker to identify and select patients who could benefit from immunotherapy. Methods: Thirty-five patients with stage IV squamous and non-squamous cell NSCLC eligible for an anti-PD-1/PD-L1 as monotherapy were enrolled. Saliva samples were collected from patients prior to the start of treatment, bacterial DNA was extracted using the QIAamp® DNA Microbiome Kit (QIAGEN) and the 16S rRNA gene was sequenced on a MiSeq sequencing instrument (Illumina). Results: NSCLC patients were dichotomized as “Responders” (partial or complete response) and “Non-Responders” (progressive disease), after 12 weeks of treatment, based on RECIST criteria. A prevalence of the phylum Candidatus Saccharibacteria was found in the 10 responders compared to non-responders (abundance 5% vs 1% respectively; p-value = 1.46 x 10-7; False Discovery Rate (FDR) = 1.02 x 10-6). Moreover, a higher prevalence of Saccharibacteria Genera Incertae Sedis genus (belonging to the Candidatus Saccharibacteria phylum) was observed in "responders" (p-value = 6.01 x 10-7 and FDR = 2.46 x 10-5). Finally, the patients who benefit from immunotherapy showed a significant abundance of TM7 Phylum Sp Oral Clone FR058 strain, member of Saccharibacteria Genera Incertae Sedis genus (p-value = 6.13 x 10-7 and FDR=7.66 x 10-5). Conclusions: These preliminary results showed a significant association between oral microbiota and ICIs response in NSCLC patients. In particular, the higher prevalence of Candidatus Saccharibacteria phylum and TM7 Phylum Sp Oral Clone FR058 strain in responders suggests their potential immunomodulatory role. The study is still ongoing and updated data will be presented at the congress.

Keywords: oral microbiota, immune checkpoint inhibitors, non-small cell lung cancer, predictive biomarker

Procedia PDF Downloads 97

Authors: Mingjiang Dai, Qian Shi, Fang Hu, Songsheng Lin, Huijun Hou, Chunbei Wei

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A diamond-like carbon (DLC) is considered as a promising protective film since its high hardness and excellent tribological properties. However, DLC films are very sensitive to the environmental condition, its friction coefficient could dramatic change in high humidity, therefore, limited their further application in aerospace, the watch industry, and micro/nano-electromechanical systems. Therefore, most studies focus on the low friction coefficient of DLC films at a high humid environment. However, this is out of satisfied in practical application. An important thing was ignored is that the DLC coated components are usually used in the diversed environment, which means its friction coefficient may evidently change in different humid condition. As a result, the invalidation of DLC coated components or even sometimes disaster occurred. For example, DLC coated minisize gears were used in the watch industry, and the customer may frequently transform their locations with different weather and humidity even in one day. If friction coefficient is not stable in dry and high moisture conditions, the watch will be inaccurate. Thus, it is necessary to investigate the stable tribological behavior of DLC films in various environments. In this study, a-C:H:Si films were deposited by multi-function magnetron sputtering system, containing one ion source device and a pair of SiC dual mid-frequent targets and two direct current Ti/C targets. Hydrogenated carbon layers were manufactured by sputtering the graphite target in argon and methane gasses. The silicon was doped in DLC coatings by sputtering silicon carbide targets and the doping content were adjusted by mid-frequent sputtering current. The microstructure of the film was characterized by Raman spectrometry, X-ray photoelectron spectroscopy, and transmission electron microscopy while its friction behavior under different humidity conditions was studied using a ball-on-disc tribometer. The a-C:H films with Si content from 0 to 17at.% were obtained and the influence of Si content on the structure and tribological properties under the relative humidity of 50% and 85% were investigated. Results show that the a-C:H:Si film has typical diamond-like characteristics, in which Si mainly existed in the form of Si, SiC, and SiO2. As expected, the friction coefficient of a-C:H films can be effectively changed after Si doping, from 0.302 to 0.176 in RH 50%. The further test shows that the friction coefficient value of a-C:H:Si film in RH 85% is first increase and then decrease as a function of Si content. We found that the a-C:H:Si films with a Si content of 3.75 at.% show a stable friction coefficient of 0.13 in different humidity environment. It is suggestion that the sp3/sp2 ratio of a-C:H films with 3.75 at.% Si was higher than others, which tend to form the silica-gel-like sacrificial layers during friction tests. Therefore, the films deliver stable low friction coefficient under controlled RH value of 50 and 85%.

Keywords: diamond-like carbon, Si doping, moisture environment, table low friction coefficient

Procedia PDF Downloads 365

Authors: Syed Benazir Firdaus, Debosree Ghosh, Aindrila Chattyopadhyay, Kuladip Jana, Debasish Bandyopadhyay

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Gastro-toxic effect of piroxicam, a classical non-steroidal anti-inflammatory drug (NSAID), has restricted its use in arthritis and similar diseases. The present study aims to find if a combination of melatonin and Murraya koenigii leaf extract therapy can protect against piroxicam induced ulcerative damage in rats. For this study, rats were divided into four groups namely control group where rats were orally administered distilled water, only combination treated group, piroxicam treated group and combination pre-administered piroxicam treated group. Each group of rats consisted of six animals. Melatonin at a dose of 20mg/kg body weight and antioxidant rich Murraya koenigii leaf extract at a dose of 50 mg /kg body weight were successively administered at 30 minutes interval one hour before oral administration of piroxicam at a dose of 30 mg/kg body weight to Wistar rats in the combination pre-administered piroxicam treated group. The rats of the animal group which was only combination treated were administered both the drugs respectively without piroxicam treatment whereas the piroxicam treated animal group was administered only piroxicam at 30mg/kg body weight without any pre-treatment with the combination. Macroscopic examination along with histo-pathological study of gastric tissue using haemotoxylin-eosin staining and alcian blue dye staining showed protection of the gastric mucosa in the combination pre-administered piroxicam treated group. Determination of adherent mucus content biochemically and collagen content through Image J analysis of picro-sirius stained sections of rat gastric tissue also revealed protective effects of the combination in piroxicam mediated toxicity. Gelatinolytic activity of piroxicam was significantly reduced by pre-administration of the drugs which was well exhibited by the gelatin zymography study of the rat gastric tissue. Mean ulcer index determined from macroscopic study of rat stomach reduced to a minimum (0±0.00; Mean ± Standard error of mean and number of animals in the group=6) indicating the absence of ulcer spots on pre-treatment of rats with the combination. Gastro-friendly prostaglandin (PGE2) which otherwise gets depleted on piroxicam treatment was also well protected when the combination was pre-administered in the rats prior to piroxicam treatment. The requirement of the individual drugs in low doses in this combinatorial therapeutic approach will possibly minimize the cost of therapy as well as it will eliminate the possibility of any pro-oxidant side effects on the use of high doses of antioxidants. Beneficial activity of this combination therapy in the rat model raises the possibility that similar protective actions might be also observed if it is adopted by patients consuming NSAIDs like piroxicam. However, the introduction of any such therapeutic approach is subject to future studies in human.

Keywords: gastro-protective action, melatonin, Murraya koenigii leaf extract, piroxicam

Procedia PDF Downloads 308

Authors: Priscila A. Bernardes, Marcos E. Buzanskas, Luciana C. A. Regitano, Ricardo V. Ventura, Danisio P. Munari

Abstract:

Genotype imputation has been used to reduce genomic selections costs. In order to increase haplotype detection accuracy in methods that considers the linkage disequilibrium, another approach could be used, such as combined genotype data from different panels. Therefore, this study aimed to evaluate the linkage disequilibrium and haplotype blocks in two high-density panels before and after the imputation to a combined panel in Nelore beef cattle. A total of 814 animals were genotyped with the Illumina BovineHD BeadChip (IHD), wherein 93 animals (23 bulls and 70 progenies) were also genotyped with the Affymetrix Axion Genome-Wide BOS 1 Array Plate (AHD). After the quality control, 809 IHD animals (509,107 SNPs) and 93 AHD (427,875 SNPs) remained for analyses. The combined genotype panel (CP) was constructed by merging both panels after quality control, resulting in 880,336 SNPs. Imputation analysis was conducted using software FImpute v.2.2b. The reference (CP) and target (IHD) populations consisted of 23 bulls and 786 animals, respectively. The linkage disequilibrium and haplotype blocks studies were carried out for IHD, AHD, and imputed CP. Two linkage disequilibrium measures were considered; the correlation coefficient between alleles from two loci (r²) and the |D’|. Both measures were calculated using the software PLINK. The haplotypes' blocks were estimated using the software Haploview. The r² measurement presented different decay when compared to |D’|, wherein AHD and IHD had almost the same decay. For r², even with possible overestimation by the sample size for AHD (93 animals), the IHD presented higher values when compared to AHD for shorter distances, but with the increase of distance, both panels presented similar values. The r² measurement is influenced by the minor allele frequency of the pair of SNPs, which can cause the observed difference comparing the r² decay and |D’| decay. As a sum of the combinations between Illumina and Affymetrix panels, the CP presented a decay equivalent to a mean of these combinations. The estimated haplotype blocks detected for IHD, AHD, and CP were 84,529, 63,967, and 140,336, respectively. The IHD were composed by haplotype blocks with mean of 137.70 ± 219.05kb, the AHD with mean of 102.10kb ± 155.47, and the CP with mean of 107.10kb ± 169.14. The majority of the haplotype blocks of these three panels were composed by less than 10 SNPs, with only 3,882 (IHD), 193 (AHD) and 8,462 (CP) haplotype blocks composed by 10 SNPs or more. There was an increase in the number of chromosomes covered with long haplotypes when CP was used as well as an increase in haplotype coverage for short chromosomes (23-29), which can contribute for studies that explore haplotype blocks. In general, using CP could be an alternative to increase density and number of haplotype blocks, increasing the probability to obtain a marker close to a quantitative trait loci of interest.

Keywords: Bos taurus indicus, decay, genotype imputation, single nucleotide polymorphism

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Authors: Hannah Bigelow, Marcus D. Gottlieb, Michelle Ogrodnik, Jeffrey, D. Graham, Barbara Fenesi

Abstract:

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders affecting approximately 6% of children worldwide. ADHD is characterized by a combination of persistent deficits including impaired inhibitory control, working memory and task-switching. Many children with ADHD also have comorbid mental health issues such as anxiety and depression. There are several treatment options to manage ADHD impairments, including drug and behavioural management therapy, but they all have drawbacks, such as worsening mood disturbances or being inaccessible to certain demographics. Both physical exercise and mindfulness meditation serve as alternative options to potentially help mitigate ADHD symptoms. Although there is extensive support for the benefits of long-term physical exercise or mindfulness meditation programs, there is insufficient research investigating how acute bouts (i.e., single, short bouts) can help children with ADHD. Thus, the current study aimed to understand how single, short bouts of exercise and mindfulness meditation impacts executive functioning and psycho-emotional well-being in children with ADHD, as well as to directly compare the efficacy of these two interventions. The study used a a pre- post-test, within-subjects design to assess the effects of a 10-minute bout of moderate intensity exercise versus a 10-minute bout of mindfulness meditation (versus 10 minutes of a reading control) on the executive functioning and psycho-emotional well-being of 16 children and youth with ADHD aged 10-14 (male=11; White=80%). Participants completed all three interventions: 10 minutes of exercise, 10 minutes of mindfulness meditation, and 10 minutes of reading (control). Executive functioning (inhibitory control, working memory, task-switching) and psycho-emotional well-being (mood, self-efficacy) were assessed before and after each intervention. Mindfulness meditation promoted executive functioning, while exercise enhanced positive mood and self-efficacy. Critically, this work demonstrates that a single, short bout of mindfulness meditation session can promote inhibitory control among children with ADHD. This is especially important for children with ADHD as inhibitory control deficits are among the most pervasive challenges that they face. Furthermore, the current study provides preliminary evidence for the benefit of acute exercise for promoting positive mood and general self-efficacy for children and youth with ADHD. These results may increase the accessibility of acute exercise for children with ADHD, providing guardians and teachers a feasible option to incorporate just 10 minutes of exercise to assist children emotionally. In summary, this research supports the use of acute exercise and mindfulness meditation on varying aspects of executive functioning and psycho-emotional well-being in children and youth with ADHD. This work offers important insight into how behavioural interventions could be personalized according to a child’s needs.

Keywords: attention-deficit hyperactivity disorder (ADHD), acute exercise, mindfulness meditation, executive functioning, psycho-emotional well-being

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Authors: Ampe Mohottige Sachinthi Sandaruwani Amarasiri, Anoja Priyadarshani Attanayake, Kamani Ayoma Perera Wijewardana Jayatilaka, Lakmini Kumari Boralugoda Mudduwa

Abstract:

The search for alternative pharmacological therapies based on natural extracts for renal failure has become an urgent need, due to paucity of effective pharmacotherapy. The current study was undertaken to evaluate the acute nephroprotective effect of aqueous leaf extract of Plectranthus amboinicus (Roxb.) (Family: Lamiaceae), a medicinal plant used in traditional Ayurvedic medicine for the management of renal diseases in Sri Lanka. The study was performed in adriamycin (ADR) induced nephrotoxic in Wistar rats. Wistar rats were randomly divided into four groups each with six rats. A single dose of ADR (20 mg/kg body wt., ip) was used for the induction of nephrotoxicity in all groups of rats except group one. The treatments were started 24 hours after induction of nephrotoxicity and continued for three days. Group one and two served as healthy and nephrotoxic control rats and were administered equivalent volumes of normal saline (0.9% NaCl) orally. Group three and four nephrotoxic rats were administered the lyophilized powder of the aqueous extract of P. amboinicus (400 mg/ kg body wt.; equivalent human therapeutic dose) and the standard drug, fosinopril sodium (0.09 mg/ kg body wt.) respectively. Urine and blood samples were collected from rats in each group at the end of the period of intervention for the estimation of selected renal parameters. H and E stained sections of the kidney tissues were examined for histopathological changes. Rats treated with the plant extract showed significant improvement in biochemical parameters and histopathological changes compared to ADR induced nephrotoxic group. The elevation of serum concentrations of creatinine and β2-microglobulin were decreased by 38%, and 66% in plant extract treated nephrotoxic rats respectively (p < 0.05). In addition, serum concentrations of total protein and albumin were significantly increased by 25% and 14% in rats treated with P. amboinicus respectively (p < 0.05). The results of β2 –microglobulin and serum total protein demonstrated a significant reduction in the elevated values in rats administered with the plant extract (400 mg/kg) compared to that of fosinopril (0.09 mg/kg). Urinary protein loss in 24hr urine samples was significantly decreased in rats treated with both fosinopril (86%) and P. ambonicus (56%) at the end of the intervention (p < 0.01). Accordingly, an attenuation of morphological destruction was observed in the H and E stained sections of the kidney with the treatments of plant extract and fosinopril. The results of the present study revealed that the aqueous leaf extract of P. amboinicus possesses significant nephroprotective activity at the equivalent therapeutic dose of 400 mg/ kg against adriamycin induced acute nephrotoxicity.

Keywords: biochemical assessment, histopathological assessment, nephroprotective activity, Plectranthus amboinicus

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Authors: Mohkammad Nur Cahyadi, Hepi Hapsari Handayani, Agus Budi Raharjo, Ronny Mardianto, Daud Wahyu Imani, Arizal Bawazir, Luki Adi Triawan

Abstract:

PDAM (local water company) determines customer charges by considering the customer's building or house. Charges determination significantly affects PDAM income and customer costs because the PDAM applies a subsidy policy for customers classified as small households. Periodic updates are needed so that pricing is in line with the target. A thorough customer survey in Surabaya is needed to update customer building data. However, the survey that has been carried out so far has been by deploying officers to conduct one-by-one surveys for each PDAM customer. Surveys with this method require a lot of effort and cost. For this reason, this research offers a technology called moblie mapping, a mapping method that is more efficient in terms of time and cost. The use of this tool is also quite simple, where the device will be installed in the car so that it can record the surrounding buildings while the car is running. Mobile mapping technology generally uses lidar sensors equipped with GNSS, but this technology requires high costs. In overcoming this problem, this research develops low-cost mobile mapping technology using a webcam camera sensor added to the GNSS and IMU sensors. The camera used has specifications of 3MP with a resolution of 720 and a diagonal field of view of 78⁰. The principle of this invention is to integrate four camera sensors, a GNSS webcam, and GPS to acquire photo data, which is equipped with location data (latitude, longitude) and IMU (roll, pitch, yaw). This device is also equipped with a tripod and a vacuum cleaner to attach to the car's roof so it doesn't fall off while running. The output data from this technology will be analyzed with artificial intelligence to reduce similar data (Cosine Similarity) and then classify building types. Data reduction is used to eliminate similar data and maintain the image that displays the complete house so that it can be processed for later classification of buildings. The AI method used is transfer learning by utilizing a trained model named VGG-16. From the analysis of similarity data, it was found that the data reduction reached 50%. Then georeferencing is done using the Google Maps API to get address information according to the coordinates in the data. After that, geographic join is done to link survey data with customer data already owned by PDAM Surya Sembada Surabaya.

Keywords: mobile mapping, GNSS, IMU, similarity, classification

Procedia PDF Downloads 84