Search results for: wheatstone bridge load cell
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 7000

Search results for: wheatstone bridge load cell

700 Histological Study on the Effect of Bone Marrow Transplantation Combined with Curcumin on Pancreatic Regeneration in Streptozotocin Induced Diabetic Rats

Authors: Manal M. Shehata, Kawther M. Abdel-Hamid, Nashwa A. Mohamed, Marwa H. Bakr, Maged S. Mahmoud, Hala M. Elbadre

Abstract:

Introduction: The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Therapeutic utility of bone marrow transplantation in diabetes is an attractive approach. However, the oxidative stress generated by hyperglycemia may hinder β-cell regeneration. Curcumin, is a dietary spice with antioxidant activity. Aim of work: The present study was undertaken to investigate the therapeutic potential of curcumin, bone marrow transplantation, and their combined effects in the reversal of experimental diabetes. Material and Methods: Fifty adult male healthy albino rats were included in the present study.They were divided into two groups: Group І: (control group) included 10 rats. Group П: (diabetic group): included 40 rats. Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ). Group II will be further subdivided into four groups (10 rats for each): Group II-a (diabetic control). Group II-b: rats were received single intraperitoneal injection of bone marrow suspension (un-fractionated bone marrow cells) prepared from rats of the same family. Group II-c: rats were treated with curcumin orally by gastric intubation for 6 weeks. Group II-d: rats were received a combination of single bone marrow transplantation and curcumin for 6 weeks. After 6 weeks, blood glucose, insulin levels were measured and the pancreas from all rats were processed for Histological, Immunohistochemical and morphometric examination. Results: Diabetic group, showed progressive histological changes in the pancreatic islets. Treatment with either curcumin or bone marrow transplantation improved the structure of the islets and reversed streptozotocin-induced hyperglycemia and hypoinsulinemia. Combination of curcumin and bone marrow transplantation elicited more profound alleviation of streptozotocin-induced changes including islet regeneration and insulin secretion. Conclusion: The use of natural antioxidants combined with bone marrow transplantation to induce pancreatic regeneration is a promising strategy in the management of diabetes.

Keywords: diabtes, panceatic islets, bone marrow transplantation, curcumin

Procedia PDF Downloads 392
699 Study of the Design and Simulation Work for an Artificial Heart

Authors: Mohammed Eltayeb Salih Elamin

Abstract:

This study discusses the concept of the artificial heart using engineering concepts, of the fluid mechanics and the characteristics of the non-Newtonian fluid. For the purpose to serve heart patients and improve aspects of their lives and since the Statistics review according to world health organization (WHO) says that heart disease and blood vessels are the first cause of death in the world. Statistics shows that 30% of the death cases in the world by the heart disease, so simply we can consider it as the number one leading cause of death in the entire world is heart failure. And since the heart implantation become a very difficult and not always available, the idea of the artificial heart become very essential. So it’s important that we participate in the developing this idea by searching and finding the weakness point in the earlier designs and hoping for improving it for the best of humanity. In this study a pump was designed in order to pump blood to the human body and taking into account all the factors that allows it to replace the human heart, in order to work at the same characteristics and the efficiency of the human heart. The pump was designed on the idea of the diaphragm pump. Three models of blood obtained from the blood real characteristics and all of these models were simulated in order to study the effect of the pumping work on the fluid. After that, we study the properties of this pump by using Ansys15 software to simulate blood flow inside the pump and the amount of stress that it will go under. The 3D geometries modeling was done using SOLID WORKS and the geometries then imported to Ansys design modeler which is used during the pre-processing procedure. The solver used throughout the study is Ansys FLUENT. This is a tool used to analysis the fluid flow troubles and the general well-known term used for this branch of science is known as Computational Fluid Dynamics (CFD). Basically, Design Modeler used during the pre-processing procedure which is a crucial step before the start of the fluid flow problem. Some of the key operations are the geometry creations which specify the domain of the fluid flow problem. Next is mesh generation which means discretization of the domain to solve governing equations at each cell and later, specify the boundary zones to apply boundary conditions for the problem. Finally, the pre–processed work will be saved at the Ansys workbench for future work continuation.

Keywords: Artificial heart, computational fluid dynamic heart chamber, design, pump

Procedia PDF Downloads 463
698 Drug Delivery Nanoparticles of Amino Acid Based Biodegradable Polymers

Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

Abstract:

Nanosized environmentally responsive materials are of special interest for various applications, including targeted drug to a considerable potential for treatment of many human diseases. The important technological advantages of nanoparticles (NPs) usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic (water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. As the next step of this research an evaluation of biocompatibility and bioavailability of the synthesized NPs has been performed, using two stable human cell culture lines – HeLa and A549. This part of study is still in progress now.

Keywords: amino acids, biodegradable polymers, nanoparticles (NPs), non-toxic building blocks

Procedia PDF Downloads 438
697 Deformation Characteristics of Fire Damaged and Rehabilitated Normal Strength Concrete Beams

Authors: Yeo Kyeong Lee, Hae Won Min, Ji Yeon Kang, Hee Sun Kim, Yeong Soo Shin

Abstract:

Fire incidents have been steadily increased over the last year according to national emergency management agency of South Korea. Even though most of the fire incidents with property damage have been occurred in building, rehabilitation has not been properly done with consideration of structure safety. Therefore, this study aims at evaluating rehabilitation effects on fire damaged normal strength concrete beams through experiments and finite element analyses. For the experiments, reinforced concrete beams were fabricated having designed concrete strength of 21 MPa. Two different cover thicknesses were used as 40 mm and 50 mm. After cured, the fabricated beams were heated for 1hour or 2hours according to ISO-834 standard time-temperature curve. Rehabilitation was done by removing the damaged part of cover thickness and filling polymeric mortar into the removed part. Both fire damaged beams and rehabilitated beams were tested with four point loading system to observe structural behaviors and the rehabilitation effect. To verify the experiment, finite element (FE) models for structural analysis were generated using commercial software ABAQUS 6.10-3. For the rehabilitated beam models, integrated temperature-structural analyses were performed in advance to obtain geometries of the fire damaged beams. In addition to the fire damaged beam models, rehabilitated part was added with material properties of polymeric mortar. Three dimensional continuum brick elements were used for both temperature and structural analyses. The same loading and boundary conditions as experiments were implemented to the rehabilitated beam models and non-linear geometrical analyses were performed. Test results showed that maximum loads of the rehabilitated beams were 8~10% higher than those of the non-rehabilitated beams and even 1~6 % higher than those of the non-fire damaged beam. Stiffness of the rehabilitated beams were also larger than that of non-rehabilitated beams but smaller than that of the non-fire damaged beams. In addition, predicted structural behaviors from the analyses also showed good rehabilitation effect and the predicted load-deflection curves were similar to the experimental results. From this study, both experiments and analytical results demonstrated good rehabilitation effect on the fire damaged normal strength concrete beams. For the further, the proposed analytical method can be used to predict structural behaviors of rehabilitated and fire damaged concrete beams accurately without suffering from time and cost consuming experimental process.

Keywords: fire, normal strength concrete, rehabilitation, reinforced concrete beam

Procedia PDF Downloads 509
696 Comparing Quality of Care in Family Planning Services in Primary Public and Private Health Care Facilities in Ethiopia

Authors: Gizachew Assefa Tessema, Mohammad Afzal Mahmood, Judith Streak Gomersall, Caroline O. Laurence

Abstract:

Introduction: Improving access to quality family planning services is the key to improving health of women and children. However, there is currently little evidence on the quality and scope of family planning services provided by private facilities, and this compares to the services provided in public facilities in Ethiopia. This is important, particularly in determining whether the government should further expand the roles of the private sector in the delivery of family planning facility. Methods: This study used the 2014 Ethiopian Services Provision Assessment Plus (ESPA+) survey dataset for comparing the structural aspects of quality of care in family planning services. The present analysis used a weighted sample of 1093 primary health care facilities (955 public and 138 private). This study employed logistic regression analysis to compare key structural variables between public and private facilities. While taking the structural variables as an outcome for comparison, the facility type (public vs private) were used as the key exposure of interest. Results: When comparing availability of basic amenities (infrastructure), public facilities were less likely to have functional cell phones (AOR=0.12; 95% CI: 0.07-0.21), and water supply (AOR=0.29; 95% CI: 0.15-0.58) than private facilities. However, public facilities were more likely to have staff available 24 hours in the facility (AOR=0.12; 95% CI: 0.07-0.21), providers having family planning related training in the past 24 months (AOR=4.4; 95% CI: 2.51, 7.64) and possessing guidelines/protocols (AOR= 3.1 95% CI: 1.87, 5.24) than private facilities. Moreover, comparing the availability of equipment, public facilities had higher odds of having pelvic model for IUD demonstration (AOR=2.60; 95% CI: 1.35, 5.01) and penile model for condom demonstration (AOR=2.51; 95% CI: 1.32, 4.78) than private facilities. Conclusion: The present study suggests that Ethiopian government needs to provide emphasis towards the private sector in terms of providing family planning guidelines and training on family planning services for their staff. It is also worthwhile for the public health facilities to allocate funding for improving the availability of basic amenities. Implications for policy and/ or practice: This study calls policy makers to design appropriate strategies in providing opportunities for training a health care providers working in private health facility.

Keywords: quality of care, family planning, public-private, Ethiopia

Procedia PDF Downloads 359
695 An Experimental Determination of the Limiting Factors Governing the Operation of High-Hydrogen Blends in Domestic Appliances Designed to Burn Natural Gas

Authors: Haiqin Zhou, Robin Irons

Abstract:

The introduction of hydrogen into local networks may, in many cases, require the initial operation of those systems on natural gas/hydrogen blends, either because of a lack of sufficient hydrogen to allow a 100% conversion or because existing infrastructure imposes limitations on the % hydrogen that can be burned before the end-use technologies are replaced. In many systems, the largest number of end-use technologies are small-scale but numerous appliances used for domestic and industrial heating and cooking. In such a scenario, it is important to understand exactly how much hydrogen can be introduced into these appliances before their performance becomes unacceptable and what imposes that limitation. This study seeks to explore a range of significantly higher hydrogen blends and a broad range of factors that might limit operability or environmental acceptability. We will present tests from a burner designed for space heating and optimized for natural gas as an increasing % of hydrogen blends (increasing from 25%) were burned and explore the range of parameters that might govern the acceptability of operation. These include gaseous emissions (particularly NOx and unburned carbon), temperature, flame length, stability and general operational acceptability. Results will show emissions, Temperature, and flame length as a function of thermal load and percentage of hydrogen in the blend. The relevant application and regulation will ultimately determine the acceptability of these values, so it is important to understand the full operational envelope of the burners in question through the sort of extensive parametric testing we have carried out. The present dataset should represent a useful data source for designers interested in exploring appliance operability. In addition to this, we present data on two factors that may be absolutes in determining allowable hydrogen percentages. The first of these is flame blowback. Our results show that, for our system, the threshold between acceptable and unacceptable performance lies between 60 and 65% mol% hydrogen. Another factor that may limit operation, and which would be important in domestic applications, is the acoustic performance of these burners. We will describe a range of operational conditions in which hydrogen blend burners produce a loud and invasive ‘screech’. It will be important for equipment designers and users to find ways to avoid this or mitigate it if performance is to be deemed acceptable.

Keywords: blends, operational, domestic appliances, future system operation.

Procedia PDF Downloads 35
694 Simulation: A Tool for Stabilization of Welding Processes in Lean Production Concepts

Authors: Ola Jon Mork, Lars Andre Giske, Emil Bjørlykhaug

Abstract:

Stabilization of critical processes in order to have the right quality of the products, more efficient production and smoother flow is a key issue in lean production. This paper presents how simulation of key welding processes can stabilize complicated welding processes in small scale production, and how simulation can impact the entire production concept seen from the perspective of lean production. First, a field study was made to learn the production processes in the factory, and subsequently the field study was transformed into a value stream map to get insight into each operation, the quality issues, operation times, lead times and flow of materials. Valuable practical knowledge of how the welding operations were done by operators, appropriate tools and jigs, and type of robots that could be used, was collected. All available information was then implemented into a simulation environment for further elaboration and development. Three researchers, the management of the company and skilled operators at the work floor where working on the project over a period of eight months, and a detailed description of the process was made by the researchers. The simulation showed that simulation could solve a number of technical challenges, the robot program can be tuned in off line mode, and the design and testing of the robot cell could be made in the simulator. Further on the design of the product could be optimized for robot welding and the jigs could be designed and tested in simulation environment. This means that a key issue of lean production can be solved; the welding operation will work with almost 100% performance when it is put into real production. Stabilizing of one key process is critical to gain control of the entire value chain, then a Takt Time can be established and the focus can be directed towards the next process in the production which should be stabilized. Results show that industrial parameters like welding time, welding cost and welding quality can be defined on the simulation stage. Further on, this gives valuable information for calculation of the factories business performance, like manufacturing volume and manufacturing efficiency. Industrial impact from simulation is more efficient implementation of lean manufacturing, since the welding process can be stabilized. More research should be done to gain more knowledge about simulation as a tool for implementation of lean, especially where there complex processes.

Keywords: simulation, lean, stabilization, welding process

Procedia PDF Downloads 324
693 Structural Performance of Mechanically Connected Stone Panels under Cyclic Loading: Application to Aesthetic and Environmental Building Skin Design

Authors: Michel Soto Chalhoub

Abstract:

Building designers in the Mediterranean region and other parts of the world utilize natural stone panels on the exterior façades as skin cover. This type of finishing is not only intended for aesthetic reasons but also environmental. The stone, since the earliest ages of civilization, has been used in construction and to-date some of the most appealing buildings owe their beauty to stone finishing. The stone also provides warmth in winter and freshness in summer as it moderates heat transfer and absorbs radiation. However, as structural codes became increasingly stringent about the dynamic performance of buildings, it became essential to study the performance of stone panels under cyclic loading – a condition that arises under the building is subjected to wind or earthquakes. The present paper studies the performance of stone panels using mechanical connectors when subjected to load reversal. In this paper, we present a theoretical model that addresses modes of failure in the steel connectors, by yield, and modes of failure in the stone, by fracture. Then we provide an experimental set-up and test results for rectangular stone panels of varying thickness. When the building is subjected to an earthquake, its rectangular panels within the structural system are subjected to shear deformations, which in turn impart stress into the stone cover. Rectangular stone panels, which typically range from 40cmx80cm to 60cmx120cm, need to be designed to withstand transverse loading from the direct application of lateral loads, and to withstand simultaneously in-plane loading (membrane stress) caused by inter-story drift and overall building lateral deflection. Results show correlation between the theoretical model which we derive from solid mechanics fundamentals and the experimental results, and lead to practical design recommendations. We find that for panel thickness below a certain threshold, it is more advantageous to utilize structural adhesive materials to connect stone panels to the main structural system of the building. For larger panel thicknesses, it is recommended to utilize mechanical connectors with special detailing to ensure a minimum level of ductility and energy dissipation.

Keywords: solid mechanics, cyclic loading, mechanical connectors, natural stone, seismic, wind, building skin

Procedia PDF Downloads 258
692 Mongolian Water Quality Problem and Health of Free-Grazing Sheep

Authors: Yu Yoshihara, Chika Tada, Moe Takada, Nyam-Osor Purevdorj, Khorolmaa Chimedtseren, Yutaka Nakai

Abstract:

Water pollution from animal waste and its influence on grazing animals is a current concern regarding Mongolian grazing lands. We allocated 32 free-grazing lambs to four groups and provided each with water from a different source (upper stream, lower stream, well, and pond) for 49 days. We recorded the amount of water consumed by the lambs, as well as their body weight, behavior, white blood cell count, acute phase (haptoglobin) protein level, and fecal condition. We measured the chemical and biological qualities of the four types of water, and we detected enteropathogenic and enterohemorrhagic Escherichia coli in fecal samples by using a genetic approach. Pond water contained high levels of nitrogen and minerals, and well water contained high levels of bacteria. The odor concentration index decreased in order from pond water to upper stream, lower stream, and well. On day 15 of the experiment, the following parameters were the highest in lambs drinking water from the following sources: water intake (pond or lower stream), body weight gain (pond), WBC count (lower stream), haptoglobin concentration (well), and enteropathogenic E. coli infection rate (lower stream). Lambs that drank well water spent more time lying down and less time grazing than the others, and lambs that drank pond water spent more time standing and less time lying down. Lambs given upper or lower stream water exhibited more severe diarrhea on day 15 of the experiment than before the experiment. Mongolian sheep seemed to adapt to chemically contaminated water: their productivity benefited the most from pond water, likely owing to its rich mineral content. Lambs that drank lower stream water showed increases in enteropathogenic E. coli infection, clinical diarrhea, and WBC count. Lambs that drank well water, which was bacteriologically contaminated, had increased serum acute phase protein levels and poor physical condition; they were thus at increased risk of negative health and production effects.

Keywords: DNA, Escherichia coli, fecal sample, lower stream, well water

Procedia PDF Downloads 477
691 Effect of Cutting Tools and Working Conditions on the Machinability of Ti-6Al-4V Using Vegetable Oil-Based Cutting Fluids

Authors: S. Gariani, I. Shyha

Abstract:

Cutting titanium alloys are usually accompanied with low productivity, poor surface quality, short tool life and high machining costs. This is due to the excessive generation of heat at the cutting zone and difficulties in heat dissipation due to relatively low heat conductivity of this metal. The cooling applications in machining processes are crucial as many operations cannot be performed efficiently without cooling. Improving machinability, increasing productivity, enhancing surface integrity and part accuracy are the main advantages of cutting fluids. Conventional fluids such as mineral oil-based, synthetic and semi-synthetic are the most common cutting fluids in the machining industry. Although, these cutting fluids are beneficial in the industries, they pose a great threat to human health and ecosystem. Vegetable oils (VOs) are being investigated as a potential source of environmentally favourable lubricants, due to a combination of biodegradability, good lubricous properties, low toxicity, high flash points, low volatility, high viscosity indices and thermal stability. Fatty acids of vegetable oils are known to provide thick, strong, and durable lubricant films. These strong lubricating films give the vegetable oil base stock a greater capability to absorb pressure and high load carrying capacity. This paper details preliminary experimental results when turning Ti-6Al-4V. The impact of various VO-based cutting fluids, cutting tool materials, working conditions was investigated. The full factorial experimental design was employed involving 24 tests to evaluate the influence of process variables on average surface roughness (Ra), tool wear and chip formation. In general, Ra varied between 0.5 and 1.56 µm and Vasco1000 cutting fluid presented comparable performance with other fluids in terms of surface roughness while uncoated coarse grain WC carbide tool achieved lower flank wear at all cutting speeds. On the other hand, all tools tips were subjected to uniform flank wear during whole cutting trails. Additionally, formed chip thickness ranged between 0.1 and 0.14 mm with a noticeable decrease in chip size when higher cutting speed was used.

Keywords: cutting fluids, turning, Ti-6Al-4V, vegetable oils, working conditions

Procedia PDF Downloads 281
690 Performance of HVOF Sprayed Ni-20CR and Cr3C2-NiCr Coatings on Fe-Based Superalloy in an Actual Industrial Environment of a Coal Fired Boiler

Authors: Tejinder Singh Sidhu

Abstract:

Hot corrosion has been recognized as a severe problem in steam-powered electricity generation plants and industrial waste incinerators as it consumes the material at an unpredictably rapid rate. Consequently, the load-carrying ability of the components reduces quickly, eventually leading to catastrophic failure. The inability to either totally prevent hot corrosion or at least detect it at an early stage has resulted in several accidents, leading to loss of life and/or destruction of infrastructures. A number of countermeasures are currently in use or under investigation to combat hot corrosion, such as using inhibitors, controlling the process parameters, designing a suitable industrial alloy, and depositing protective coatings. However, the protection system to be selected for a particular application must be practical, reliable, and economically viable. Due to the continuously rising cost of the materials as well as increased material requirements, the coating techniques have been given much more importance in recent times. Coatings can add value to products up to 10 times the cost of the coating. Among the different coating techniques, thermal spraying has grown into a well-accepted industrial technology for applying overlay coatings onto the surfaces of engineering components to allow them to function under extreme conditions of wear, erosion-corrosion, high-temperature oxidation, and hot corrosion. In this study, the hot corrosion performances of Ni-20Cr and Cr₃C₂-NiCr coatings developed by High Velocity Oxy-Fuel (HVOF) process have been studied. The coatings were developed on a Fe-based superalloy, and experiments were performed in an actual industrial environment of a coal-fired boiler. The cyclic study was carried out around the platen superheater zone where the temperature was around 1000°C. The study was conducted for 10 cycles, and one cycle was consisting of 100 hours of heating followed by 1 hour of cooling at ambient temperature. Both the coatings deposited on Fe-based superalloy imparted better hot corrosion resistance than the uncoated one. The Ni-20Cr coated superalloy performed better than the Cr₃C₂-NiCr coated in the actual working conditions of the coal fired boiler. It is found that the formation of chromium oxide at the boundaries of Ni-rich splats of the coating blocks the inward permeation of oxygen and other corrosive species to the substrate.

Keywords: hot corrosion, coating, HVOF, oxidation

Procedia PDF Downloads 89
689 The Importance of Oral Mucosal Biopsy Selection Site in Areas of Field Change: A Case Report

Authors: Timmis W., Simms M., Thomas C.

Abstract:

This case discusses the management of two floors of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk and second primary cancer development.

Keywords: alcohol dependence, biopsy, oral carcinoma, tobacco

Procedia PDF Downloads 118
688 Insulin-Producing Cells from Adult Human Bone Marrow Mesenchymal Stem Cells Control Chemically-Induced Diabetes in Dogs

Authors: Maha Azzam, Mahmoud Gabr, Mahmoud Zakaria, Ayman Refaie, Amani Ismail, Sherry Khater, Sylvia Ashamallah, Mohamed Ghoniem

Abstract:

Evidence was provided that human bone marrow-derived mesenhymal stem cells (HBM-MSCs) could be differentiated to form insulin-producing cells (IPCs). Transplantation of these cells was able to cure chemically-induced diabetes in nude mice. The efficacy of these cells to control diabetes in large animals was carried out to evaluate the sufficient number of cells needed/Kg body weight and to determine the functional longevity in vivo. Materials/Methods: Ten male mongrel dogs weighing 15-20 Kg were used in this study. Diabetes was chemically-induced in 7 dogs by a mixture of alloxan and streptozotocin. Three non-diabetic served as normal controls. Differentiated HBM-MSCs (5 million/Kg) were encapsulated in theracyte capsules and transplanted beneath the rectus sheath. Each dog received 2 capsules. One dog died 4 days postoperative from inhalation pneumonia. The remaining 6 dogs were followed up for 6-18 months. Results: Four dogs became normoglycemic within 6-8 weeks with normal glucose tolerance curves providing evidence that the transplanted cells were glucose-sensitive and insulin-responsive. In the remaining 2 dogs, fasting blood glucose was reduced but did not reach euglycemic levels. The sera of all transplanted dogs contained human insulin and c-peptide but negligible levels of canine insulin. When the HBM-MSCs loaded capsules were removed, rapid return of diabetic state was noted. The harvested capsules were examined by immunofluorescence. IPCs were seen and co-expression of with c-peptide was confirmed. Furthermore, all the pancreatic endocrine genes were expressed by the transplanted cells. Conclusions: This study provided evidence that theracyte capsules could protect the xenogenic HBM-MSCs from the host immune response. This is an important issue when clinical stem cell therapy is considered for definitive treatment for T1DM.

Keywords: diabetes, mesenchymal stem cells, dogs, Insulin-producing cells

Procedia PDF Downloads 209
687 Determination of the Structural Parameters of Calcium Phosphate for Biomedical Use

Authors: María Magdalena Méndez-González, Miguel García Rocha, Carlos Manuel Yermo De la Cruz

Abstract:

Calcium phosphate (Ca5(PO4)3(X)) is widely used in orthopedic applications and is widely used as powder and granules. However, their presence in bone is in the form of nanometric needles 60 nm in length with a non-stoichiometric phase of apatite contains CO3-2, Na+, OH-, F-, and other ions in a matrix of collagen fibers. The crystal size, morphology control and interaction with cells are essential for the development of nanotechnology. The structural results of calcium phosphate, synthesized by chemical precipitation with crystal size of 22.85 nm are presented in this paper. The calcium phosphate powders were analyzed by X-ray diffraction, energy dispersive spectroscopy (EDS), infrared spectroscopy and FT-IR transmission electron microscopy. Network parameters, atomic positions, the indexing of the planes and the calculation of FWHM (full width at half maximum) were obtained. The crystal size was also calculated using the Scherer equation d (hkl) = cλ/βcosѲ. Where c is a constant related to the shape of the crystal, the wavelength of the radiation used for a copper anode is 1.54060Å, Ѳ is the Bragg diffraction angle, and β is the width average peak height of greater intensity. Diffraction pattern corresponding to the calcium phosphate called hydroxyapatite phase of a hexagonal crystal system was obtained. It belongs to the space group P63m with lattice parameters a = 9.4394 Å and c = 6.8861 Å. The most intense peak is obtained 2Ѳ = 31.55 (FWHM = 0.4798), with a preferred orientation in 121. The intensity difference between the experimental data and the calculated values is attributable to the temperature at which the sintering was performed. The intensity of the highest peak is at angle 2Ѳ = 32.11. The structure of calcium phosphate obtained was a hexagonal configuration. The intensity changes in the peaks of the diffraction pattern, in the lattice parameters at the corners, indicating the possible presence of a dopant. That each calcium atom is surrounded by a tetrahedron of oxygen and hydrogen was observed by infrared spectra. The unit cell pattern corresponds to hydroxyapatite and transmission electron microscopic crystal morphology corresponding to the hexagonal phase with a preferential growth along the c-plane was obtained.

Keywords: structure, nanoparticles, calcium phosphate, metallurgical and materials engineering

Procedia PDF Downloads 509
686 Engineering Topology of Construction Ecology in Urban Environments: Suez Canal Economic Zone

Authors: Moustafa Osman Mohammed

Abstract:

Integration sustainability outcomes give attention to construction ecology in the design review of urban environments to comply with Earth’s System that is composed of integral parts of the (i.e., physical, chemical and biological components). Naturally, exchange patterns of industrial ecology have consistent and periodic cycles to preserve energy flows and materials in Earth’s System. When engineering topology is affecting internal and external processes in system networks, it postulated the valence of the first-level spatial outcome (i.e., project compatibility success). These instrumentalities are dependent on relating the second-level outcome (i.e., participant security satisfaction). Construction ecology approach feedback energy from resources flows between biotic and abiotic in the entire Earth’s ecosystems. These spatial outcomes are providing an innovation, as entails a wide range of interactions to state, regulate and feedback “topology” to flow as “interdisciplinary equilibrium” of ecosystems. The interrelation dynamics of ecosystems are performing a process in a certain location within an appropriate time for characterizing their unique structure in “equilibrium patterns”, such as biosphere and collecting a composite structure of many distributed feedback flows. These interdisciplinary systems regulate their dynamics within complex structures. These dynamic mechanisms of the ecosystem regulate physical and chemical properties to enable a gradual and prolonged incremental pattern to develop a stable structure. The engineering topology of construction ecology for integration sustainability outcomes offers an interesting tool for ecologists and engineers in the simulation paradigm as an initial form of development structure within compatible computer software. This approach argues from ecology, resource savings, static load design, financial other pragmatic reasons, while an artistic/architectural perspective, these are not decisive. The paper described an attempt to unify analytic and analogical spatial modeling in developing urban environments as a relational setting, using optimization software and applied as an example of integrated industrial ecology where the construction process is based on a topology optimization approach.

Keywords: construction ecology, industrial ecology, urban topology, environmental planning

Procedia PDF Downloads 137
685 Citrullinated Myelin Basic Protein Mediated Inflammation in Astrocytes

Authors: Lali Shanshiashvili, Marika Chikviladze, Nino Mamulashvili, Maia Sepashvili, Nana Narmania, David Mikeladze

Abstract:

Purpose: During demyelinating inflammatory diseases and after the damage of the myelin sheet, myelin-derived proteins, including myelin basic protein (MBP), are secreted into the extracellular space. MBP shows extensive post-translational modifications, including the deimination of arginine residues. Deiminated MBP is structurally less ordered, susceptible to proteolytic attack, and more immunogenic than the unmodified one. It is hypothesized that MBP could change the inflammatory response in astrocytes. Methods: MBP was isolated and purified from bovine brain white matter. Primary astrocyte cultures were prepared from whole brains of 2-day-old Wistar rats. For evaluation of glutamate uptake/release in astrocytes following treatment of cells with MBP charge isomers, Glutamate Assay Kit was used. The expression of EAAT-2 (excitatory amino acid transporters), peroxisome proliferator-activated receptor gamma (PPAR- γ), inhibitor of nuclear factor kappa B (IkB), and high mobility group protein B1 (HMGB1) in astrocytes were assayed by Western Blot analysis. Results: This study investigated the action of deiminated isomer (C8) on the cultured primary astrocytes and compared its effects with the effects of unmodified C1 isomers. The study found that C8 and C1 MBP differently act on the uptake and release of glutamate in astrocytes: nonmodified C1 MBP increases the uptake of glutamate and does not change the release, whereas C8 decreases the release of glutamate but does not alter the uptake. Nevertheless, both isomers increased the expression of PPAR-γ and EAAT2 in the same intensity. However, immunostaining and Western Blots of cell lysates showed a decrease of IkB and increased expression of HMGB1 after the treatment of astrocytes by C8. Moreover, in the presence of C8, astrocytes release more nitric oxide than unmodified C1 isomers. Conclusion: These data suggest that the deiminated isomer of MBP evokes an inflammatory response and enhances the ability of astrocytes to release proinflammatory mediators through activation of NF-kB after the breakdown of myelin sheets. Acknowledgment: This research was supported by the SRNSF Georgia RF17_534 grant.

Keywords: myelin basic protein, glutamate, deimination, astrocytes, inflammation

Procedia PDF Downloads 209
684 Drug Design Modelling and Molecular Virtual Simulation of an Optimized BSA-Based Nanoparticle Formulation Loaded with Di-Berberine Sulfate Acid Salt

Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed

Abstract:

Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.

Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX

Procedia PDF Downloads 176
683 Treating Complex Pain and Addictions with Bioelectrode Therapy: An Acupuncture Point Stimulus Method for Relieving Human Suffering

Authors: Les Moncrieff

Abstract:

In a world awash with potent opioids flaming an international crisis, the need to explore safe alternatives has never been more urgent. Bio-electrode Therapy is a novel adjunctive treatment method for relieving acute opioid withdrawal symptoms and many types of complex acute and chronic pain (often the underlying cause of opioid dependence). By combining the science of developmental bioelectricity with Traditional Chinese Medicine’s theory of meridians, rapid relief from pain is routinely being achieved in the clinical setting. Human body functions are dependent on electrical factors, and acupuncture points on the body are known to have higher electrical conductivity than surrounding skin tissue. When tiny gold- and silver-plated electrodes are secured to the skin at specific acupuncture points using established Chinese Medicine principles and protocols, an enhanced microcurrent and electrical field are created between the electrodes, influencing the entire meridian and connecting meridians. No external power source or electrical devices are required. Endogenous DC electric fields are an essential fundamental component for development, regeneration, and wound healing. Disruptions in the normal ion-charge in the meridians and circulation of blood will manifest as pain and development of disease. With the application of these simple electrodes (gold acting as cathode and silver as anode) according to protocols, the resulting microcurrent is directed along the selected meridians to target injured or diseased organs and tissues. When injured or diseased cells have been stimulated by the microcurrent and electrical fields, the permeability of the cell membrane is affected, resulting in an immediate relief of pain, a rapid balancing of positive and negative ions (sodium, potassium, etc.) in the cells, the restoration of intracellular fluid levels, replenishment of electrolyte levels, pH balance, removal of toxins, and a re-establishment of homeostasis.

Keywords: bioelectricity, electrodes, electrical fields, acupuncture meridians, complex pain, opioid withdrawal management

Procedia PDF Downloads 85
682 Addressing Educational Injustice through Collective Teacher Professional Development

Authors: Wenfan Yan, Yumei Han

Abstract:

Objectives: Educational inequality persists between China's ethnic minority regions and the mainland. The key to rectifying this disparity lies in enhancing the quality of educators. This paper delves into the Chinese government's innovative policy, "Group Educators Supporting Tibet" (GEST), designed to bridge the shortage of high-quality teachers in Tibet, a representative underprivileged ethnic minority area. GEST aims to foster collective action by networking provincial expert educators with Tibetan counterparts and collaborating between supporting provincial educational entities and Tibetan education entities. Theoretical Framework: The unequal distribution of social capital contributes significantly to the educational gap between ethnic minority areas and other regions in China. Within the framework of social network theory, motivated GEST educators take action to foster resources and relationships. This study captures grassroots perspectives to outline how social networking contributes to the policy objective of enhancing Tibetan teachers' quality and eradicating educational injustice. Methodology: A sequential mixed-methods approach was adopted to scrutinize policy impacts from the vantage point of social networking. Quantitative research involved surveys for GEST and Tibetan teachers, exploring demographics, perceptions of policy significance, motivations, actions, and networking habits. Qualitative research included focus group interviews with GEST educators, local teachers, and students from program schools. The findings were meticulously analyzed to provide comprehensive insights into stakeholders' experiences and the impacts of the GEST policy. Key Findings: The policy empowers individuals to impact Tibetan education significantly. Motivated GEST educators with prior educational support experiences contribute to its success. Supported by a collective -school, city, province, and government- the new social structure fosters higher efficiency. GEST's approach surpasses conventional methods. The individual, backed by educators, realizes the potential of transformative class design. Collective activities -pedagogy research, teaching, mentoring, training, and partnerships- equip Tibetan teachers, enhancing educational quality and equity. This collaborative effort establishes a robust foundation for the policy's success, emphasizing the collective impact on Tibetan education. Contributions: This study contributes to international policy studies focused on educational equity through collective teacher action. Using a mixed-methods approach and guided by social networking theory, it accentuates stakeholders' perspectives, elucidating the genuine impacts of the GEST policy. The study underscores the advancement of social networking, the reinforcement of local teacher quality, and the transformative potential of cultivating a more equitable and adept teaching workforce in Tibet. Limitations of the Study and Suggestions for Future Research Directions: While the study emphasizes the positive impacts of motivated GEST educators, there might be aspects or challenges not fully explored. A more comprehensive understanding of potential drawbacks or obstacles would provide a more balanced view. For future studies, investigating the long-term impact of the GEST policy on educational quality could provide insights into the sustainability of the improvements observed. Also, understanding the perspectives of Tibetan teachers who may not have directly benefited from GEST could reveal potential disparities in policy implementation.

Keywords: teacher development, social networking, teacher quality, mixed research method

Procedia PDF Downloads 68
681 Prognosis of Patients with COVID-19 and Hematologic Malignancies

Authors: Elizabeth Behrens, Anne Timmermann, Alexander Yerkan, Joshua Thomas, Deborah Katz, Agne Paner, Melissa Larson, Shivi Jain, Seo-Hyun Kim, Celalettin Ustun, Ankur Varma, Parameswaran Venugopal, Jamile Shammo

Abstract:

Coronavirus Disease-2019 (COVID-19) causes persistent concern for poor outcomes in vulnerable populations. Patients with hematologic malignancies (HM) have been found to have higher COVID-19 case fatality rates compared to those without malignancy. While cytopenias are common in patients with HM, especially in those undergoing chemotherapy treatment, hemoglobin (Hgb) and platelet count have not yet been studied, to our best knowledge, as potential prognostic indicators for patients with HM and COVID-19. The goal of this study is to identify factors that may increase the risk of mortality in patients with HM and COVID-19. In this single-center, retrospective, observational study, 65 patients with HM and laboratory confirmed COVID-19 were identified between March 2020 and January 2021. Information on demographics, laboratory data the day of COVID-19 diagnosis, and prognosis was extracted from the electronic medical record (EMR), chart reviewed, and analyzed using the statistical software SAS version 9.4. Chi-square testing was used for categorical variable analyses. Risk factors associated with mortality were established by logistic regression models. Non-Hodgkin lymphoma (37%), chronic lymphocytic leukemia (20%), and plasma cell dyscrasia (15%) were the most common HM. Higher Hgb level upon COVID-19 diagnosis was related to decreased mortality, odd ratio=0.704 (95% confidence interval [CI]: 0.511-0.969; P = .0263). Platelet count the day of COVID-19 diagnosis was lower in patients who ultimately died (mean 127 ± 72K/uL, n=10) compared to patients who survived (mean 197 ±92K/uL, n=55) (P=.0258). Female sex was related to decreased mortality, odd ratio=0.143 (95% confidence interval [CI]: 0.026-0.785; P = .0353). There was no mortality difference between the patients who were on treatment for HM the day of COVID-19 diagnosis compared to those who were not (P=1.000). Lower Hgb and male sex are independent risk factors associated with increased mortality of HM patients with COVID-19. Clinicians should be especially attentive to patients with HM and COVID-19 who present with cytopenias. Larger multi-center studies are urgently needed to further investigate the impact of anemia, thrombocytopenia, and demographics on outcomes of patients with hematologic malignancies diagnosed with COVID-19.

Keywords: anemia, COVID-19, hematologic malignancy, prognosis

Procedia PDF Downloads 153
680 The Impact of Electrospinning Parameters on Surface Morphology and Chemistry of PHBV Fibers

Authors: Lukasz Kaniuk, Mateusz M. Marzec, Andrzej Bernasik, Urszula Stachewicz

Abstract:

Electrospinning is one of the commonly used methods to produce micro- or nano-fibers. The properties of electrospun fibers allow them to be used to produce tissue scaffolds, biodegradable bandages, or purification membranes. The morphology of the obtained fibers depends on the composition of the polymer solution as well as the processing parameters. Interesting properties such as high fiber porosity can be achieved by changing humidity during electrospinning. Moreover, by changing voltage polarity in electrospinning, we are able to alternate functional groups at the surface of fibers. In this study, electrospun fibers were made of natural, thermoplastic polyester – PHBV (poly(3-hydroxybutyric acid-co-3-hydrovaleric acid). The fibrous mats were obtained using both positive and negative voltage polarities, and their surface was characterized using X-ray photoelectron spectroscopy (XPS, Ulvac-Phi, Chigasaki, Japan). Furthermore, the effect of the humidity on surface morphology was investigated using scanning electron microscopy (SEM, Merlin Gemini II, Zeiss, Germany). Electrospun PHBV fibers produced with positive and negative voltage polarity had similar morphology and the average fiber diameter, 2.47 ± 0.21 µm and 2.44 ± 0.15 µm, respectively. The change of the voltage polarity had a significant impact on the reorientation of the carbonyl groups what consequently changed the surface potential of the electrospun PHBV fibers. The increase of humidity during electrospinning causes porosity in the surface structure of the fibers. In conclusion, we showed within our studies that the process parameters such as humidity and voltage polarity have a great influence on fiber morphology and chemistry, changing their functionality. Surface properties of polymer fiber have a significant impact on cell integration and attachment, which is very important in tissue engineering. The possibility of changing surface porosity allows the use of fibers in various tissue engineering and drug delivery systems. Acknowledgment: This study was conducted within 'Nanofiber-based sponges for atopic skin treatment' project., carried out within the First TEAM programme of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund, project no POIR.04.04.00-00- 4571/18-00.

Keywords: cells integration, electrospun fiber, PHBV, surface characterization

Procedia PDF Downloads 122
679 BSYJ Promoting Homing and Differentiation of Mesenchymal Stem Cells at the Retina of Age-Related Macular Degeneration Model Mice Induced by Sodium Iodate

Authors: Lina Liang, Kai Xu, Jing Zhang

Abstract:

Purpose: Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement is discussed as a potential therapy for AMD. Besides intravitreal injection and subretinal injection, intravenous administration has been explored as an alternative route. This study is to observe the effect of BSYJ, a traditional Chinese medicine on the homing and differentiation of mesenchymal stem cells transplanted via tail vein injection in an age-related macular degeneration mouse model. Methods: Four-week-old C57BL/6J mice were injected with 40 mg/kg NaIO₃ to induce age-related macular degeneration model. At the second day after NaIO₃ injection, 1×10⁷ GFP labeled bone marrow-derived mesenchymal stem cells (GFP-MSCs) were transplanted via tali vein injection into the experimental mice. Then the mice were randomly divided into two groups, gavaged with either BSYJ solution (BSYJ group, n=12) or distilled water (DW group, n=12). 12 age-matched healthy C57BL/6J mice were fed regularly as normal control. At day 7, day 14, and day 28 after treatment, retina flat mounting was used to detect the homing of mesenchymal stem cells at the retina. Double-labeling immunofluorescence was used to determine the differentiation of mesenchymal stem cells. Results: At 7, 14, 28 days after treatment, the numbers of GFP-MSCs detected by retina flatmount were 10.2 ± 2.5, 14.5 ± 3.4 and 18.7 ± 5.8, respectively in the distilled water group, while 15.7 ± 3.8, 32.3 ± 3.5 and 77.3 ± 6.4 in BSYJ group, the differences between the two groups were significant (p < 0.05). At 28 days after treatment, it was shown by double staining immunofluorescence that there were more GFP positive cells in the retina of BSYJ group than that of the DW group, but none of the cells expressed RPE specific genes such as RPE65 and CRALBP, or photoreceptor genes such as recoverin and rhodopsin either in BSYJ group or DW group. However, GFAP positive cells were found among the cells labeled with GFP, and the double labeling cells were much more in the BSYJ group than the distilled water group. Conclusion: BSYJ could promote homing of mesenchymal stem cells at the retina of age-related macular degeneration model mice induced by NaIO₃, and the differentiation towards to glial cells. Acknowledgement: National Natural Foundation of China (No: 81473736, 81674033,81973912).

Keywords: BSYJ, differentiation, homing, mesenchymal stem cells

Procedia PDF Downloads 151
678 An Analytical Approach for the Fracture Characterization in Concrete under Fatigue Loading

Authors: Bineet Kumar

Abstract:

Many civil engineering infrastructures frequently encounter repetitive loading during their service life. Due to the inherent complexity observed in concrete, like quasi-brittle materials, understanding the fatigue behavior in concrete still posesa challenge. Moreover, the fracture process zone characteristics ahead of the crack tip have been observed to be different in fatigue loading than in the monotonic cases. Therefore, it is crucial to comprehend the energy dissipation associated with the fracture process zone (FPZ) due to repetitive loading. It is well known that stiffness degradation due to cyclic loadingprovides a better understanding of the fracture behavior of concrete. Under repetitive load cycles, concrete members exhibit a two-stage stiffness degradation process. Experimentally it has been observed that the stiffness decreases initially with an increase in crack length and subsequently increases. In this work, an attempt has been made to propose an analytical expression to predict energy dissipation and later the stiffness degradation as a function of crack length. Three-point bend specimens have been considered in the present work to derive the formulations. In this approach, the expression for the resultant stress distribution below the neutral axis has been derived by correlating the bending stress with the cohesive stresses developed ahead of the crack tip due to the existence of the fracture process zone. This resultant stress expression is utilized to estimate the dissipated energydue to crack propagation as a function of crack length. Further, the formulation for the stiffness degradation has been developed by relating the dissipated energy with the work done. It can be used to predict the critical crack length and fatigue life. An attempt has been made to understand the influence of stress amplitude on the damage pattern by using the information on the rate of stiffness degradation. It has been demonstrated that with the increase in the stress amplitude, the damage/FPZ proceeds more in the direction of crack propagation compared to the damage in the direction parallel to the span of the beam, which causes a lesser rate of stiffness degradation for the incremental crack length. Further, the effect of loading frequency has been investigated in terms of stiffness degradation. Under low-frequency loading cases, the damage/FPZ has been found to spread more in the direction parallel to the span, in turn reducing the critical crack length and fatigue life. In such a case, a higher rate of stiffness degradation has been observed in comparison to the high-frequency loading case.

Keywords: fatigue life, fatigue, fracture, concrete

Procedia PDF Downloads 101
677 Improved Intracellular Protein Degradation System for Rapid Screening and Quantitative Study of Essential Fungal Proteins in Biopharmaceutical Development

Authors: Patarasuda Chaisupa, R. Clay Wright

Abstract:

The selection of appropriate biomolecular targets is a crucial aspect of biopharmaceutical development. The Auxin-Inducible Degron Degradation (AID) technology has demonstrated remarkable potential in efficiently and rapidly degrading target proteins, thereby enabling the identification and acquisition of drug targets. The AID system also offers a viable method to deplete specific proteins, particularly in cases where the degradation pathway has not been exploited or when the adaptation of proteins, including the cell environment, occurs to compensate for the mutation or gene knockout. In this study, we have engineered an improved AID system tailored to deplete proteins of interest. This AID construct combines the auxin-responsive E3 ubiquitin ligase binding domain, AFB2, and the substrate degron, IAA17, fused to the target genes. Essential genes of fungi with the lowest percent amino acid similarity to human and plant orthologs, according to the Basic Local Alignment Search Tool (BLAST), were cloned into the AID construct in S. cerevisiae (AID-tagged strains) using a modular yeast cloning toolkit for multipart assembly and direct genetic modification. Each E3 ubiquitin ligase and IAA17 degron was fused to a fluorescence protein, allowing for real-time monitoring of protein levels in response to different auxin doses via cytometry. Our AID system exhibited high sensitivity, with an EC50 value of 0.040 µM (SE = 0.016) for AFB2, enabling the specific promotion of IAA17::target protein degradation. Furthermore, we demonstrate how this improved AID system enhances quantitative functional studies of various proteins in fungi. The advancements made in auxin-inducible protein degradation in this study offer a powerful approach to investigating critical target protein viability in fungi, screening protein targets for drugs, and regulating intracellular protein abundance, thus revolutionizing the study of protein function underlying a diverse range of biological processes.

Keywords: synthetic biology, bioengineering, molecular biology, biotechnology

Procedia PDF Downloads 100
676 Identification and Characterization of Polysaccharide Biosynthesis Protein (CAPD) of Enterococcus faecium

Authors: Liaqat Ali, Hubert E. Blum, Türkân Sakinc

Abstract:

Enterococcus faecium is an emerging multidrug-resistant nosocomial pathogen increased dramatically worldwide and causing bacteremia, endocarditis, urinary tract and surgical site infections in immunocomprised patients. The capsular polysaccharides that contribute to pathogenesis through evasion of the host innate immune system are also involved in hindering leukocyte killing of enterococci. The gene cluster (enterococcal polysaccharide antigen) of E. faecalis encoding homologues of many genes involved in polysaccharide biosynthesis. We identified two putative loci with 22 kb and 19 kb which contained 11 genes encoding for glycosyltransferases (GTFs); this was confirmed by using genome comparison of already sequenced strains that has no homology to known capsule genes and the epa-locus. The polysaccharide-conjugate vaccines have rapidly emerged as a suitable strategy to combat different pathogenic bacteria, therefore, we investigated a polysaccharide biosynthesis CapD protein in E. faecium contains 336 amino acids and had putative function for N-linked glycosylation. The deletion/knock-out capD mutant was constructed and complemented by homologues recombination method and confirmed by using PCR and sequencing. For further characterization and functional analysis, in-vitro cell culture and in-vivo a mouse infection models were used. Our ΔcapD mutant shows a strong hydrophobicity and all strains exhibited biofilm production. Subsequently, the opsonic activity was tested in an opsonophagocytic assay which shows increased in mutant compared complemented and wild type strains but more than two fold decreased in colonization and adherence was seen on surface of uroepithelial cells. However, a significant higher bacterial colonialization was observed in capD mutant during animal bacteremia infection. Unlike other polysaccharides biosynthesis proteins, CapD does not seems to be a major virulence factor in enterococci but further experiments and attention is needed to clarify its function, exact mechanism and involvement in pathogenesis of enteroccocal nosocomial infections eventually to develop a vaccine/ or targeted therapy.

Keywords: E. faecium, pathogenesis, polysaccharides, biofilm formation

Procedia PDF Downloads 337
675 Experimental Study of Moisture Effect on the Mechanical Behavior of Flax Fiber Reinforcement

Authors: Marwa Abida, Florian Gehring, Jamel Mars, Alexandre Vivet, Fakhreddine Dammak, Mohamed Haddar

Abstract:

The demand for bio-based materials in semi-structural and structural applications is constantly growing to conform to new environmental policies. Among them, Plant Fiber Reinforced Composites (PFRC) are attractive for the scientific community as well as the industrial world. Due to their relatively low densities and low environmental impact, vegetal fibers appear to be suitable as reinforcing materials for polymers. However, the major issue of plant fibers and PFRC in general is their hydrophilic behavior (high affinity to water molecules). Indeed, when absorbed, water causes fiber swelling and a loss of mechanical properties. Thus, the environmental loadings (moisture, temperature, UV) can strongly affect their mechanical properties and therefore play a critical role in the service life of PFRC. In order to analyze the influence of conditioning at relative humidity on the behavior of flax fiber reinforced composites, a preliminary study on flax fabrics has been conducted. The conditioning of the fabrics in different humid atmospheres made it possible to study the influence of the water content on the hygro-mechanical behavior of flax reinforcement through mechanical tensile tests. This work shows that increasing the relative humidity of the atmosphere induces an increase of the water content in the samples. It also brings up the significant influence of water content on the stiffness and elongation at break of the fabric, while no significant change of the breaking load is detected. Non-linear decrease of flax fabric rigidity and increase of its elongation at maximal force with the increase of water content are observed. It is concluded that water molecules act as a softening agent on flax fabrics. Two kinds of typical tensile curves are identified. Most of the tensile curves of samples show one unique linear region where the behavior appears to be linear prior to the first yarn failure. For some samples in which water content is between 2.7 % and 3.7 % (regardless the conditioning atmosphere), the emergence of a two-linear region behavior is pointed out. This phenomenon could be explained by local heterogeneities of water content which could induce premature local plasticity in some regions of the flax fabric sample behavior.

Keywords: hygro-mechanical behavior, hygroscopy, flax fabric, relative humidity, mechanical properties

Procedia PDF Downloads 192
674 Transformation of ectA Gene From Halomonas elongata in Tomato Plant

Authors: Narayan Moger, Divya B., Preethi Jambagi, Krishnaveni C. K., Apsana M. R., B. R. Patil, Basvaraj Bagewadi

Abstract:

Salinity is one of the major threats to world food security. Considering the requirement for salt tolerant crop plants in the present study was undertaken to clone and transferred the salt tolerant ectA gene from marine ecosystem into agriculture crop system to impart salinity tolerance. Ectoine is the compatible solute which accumulates in the cell membrane, is known to be involved in salt tolerance activity in most of the Halophiles. The present situation is insisting to development of salt tolerant transgenic lines to combat abiotic stress. In this background, the investigation was conducted to develop transgenic tomato lines by cloning and transferring of ectA gene is an ectoine derivative capable of enzymatic action for the production of acetyl-diaminobutyric acid. The gene ectA is involved in maintaining the osmotic balance of plants. The PCR amplified ectA gene (579bp) was cloned into T/A cloning vector (pTZ57R/T). The construct pDBJ26 containing ectA gene was sequenced by using gene specific forward and reverse primers. Sequence was analyzed using BLAST algorithm to check similarity of ectA gene with other isolates. Highest homology of 99.66 per cent was found with ectA gene sequences of isolates Halomonas elongata with the available sequence information in NCBI database. The ectA gene was further sub cloned into pRI101-AN plant expression vector and transferred into E. coli DH5α for its maintenance. Further pDNM27 was mobilized into A. tumefaciens LBA4404 through tri-parental mating system. The recombinant Agrobacterium containing pDNM27 was transferred into tomato plants through In planta plant transformation method. Out of 300 seedlings, co-cultivated only twenty-seven plants were able to well establish under the greenhouse condition. Among twenty-seven transformants only twelve plants showed amplification with gene specific primers. Further work must be extended to evaluate the transformants at T1 and T2 generations for ectoine accumulation, salinity tolerance, plant growth and development and yield.

Keywords: salinity, computable solutes, ectA, transgenic, in planta transformation

Procedia PDF Downloads 84
673 Novel Routes to the Synthesis and Functionalization of Metallic and Semiconductor Thin Film and Nanoparticles

Authors: Hanan. Al Chaghouri, Mohammad Azad Malik, P. John Thomas, Paul O’Brien

Abstract:

The process of assembling metal nanoparticles at the interface of two liquids has received a great deal of attention over the past few years due to a wide range of important applications and their unusual properties as compared to bulk materials. We present a low cost, simple and cheap synthesis of metal nanoparticles, core/shell structures and semiconductors followed by assembly of these particles between immiscible liquids. The aim of this talk is divided to three parts: Firstly, to describe the achievement of a closed loop recycling for producing cadmium sulfide as powders and/or nanostructured thin films for solar cells or other optoelectronic devices applications by using a different chain length of commercially available secondary amines of dithiocarbamato complexes. The approach can be extended to other metal sulfides such as those of Zn, Pb, Cu, or Fe and many transition metals and oxides. Secondly, to synthesis significantly cheaper magnetic particles suited for the mass market. Ni/NiO nanoparticles with ferromagnetic properties at room temperature were among the smallest and strongest magnets (5 nm) were made in solution. The applications of this work can be to produce viable storage devices and the other possibility is to disperse these nanocrystals in solution and use it to make ferrofluids which have a number of mature applications. The third part is about preparing and assembling of submicron silver, cobalt and nickel particles by using polyol methods and liquid/liquid interface, respectively. Coinage metals like gold, copper and silver are suitable for plasmonic thin film solar cells because of their low resistivity and strong interactions with visible light waves. Silver is the best choice for solar cell application since it has low absorption losses and high radiative efficiency compared to gold and copper. Assembled cobalt and nickel as films are promising for spintronic, magnetic and magneto-electronic and biomedics.

Keywords: metal nanoparticles, core/shell structures and semiconductors, ferromagnetic properties, closed loop recycling, liquid/liquid interface

Procedia PDF Downloads 464
672 Maresin Like 1 Treatment: Curbing the Pathogenesis of Behavioral Dysfunction and Neurodegeneration in Alzheimer's Disease Mouse Model

Authors: Yan Lu, Song Hong, Janakiraman Udaiyappan, Aarti Nagayach, Quoc-Viet A. Duong, Masao Morita, Shun Saito, Yuichi Kobayashi, Yuhai, Zhao, Hongying Peng, Nicholas B. Pham, Walter J Lukiw, Christopher A. Vuong, Nicolas G. Bazan

Abstract:

Aims: Neurodegeneration and behavior dysfunction occurs in patients with Alzheimer's Disease (AD), and as the disease progresses many patients develop cognitive impairment. 5XFAD mouse model of AD is widely used to study AD pathogenesis and treatment. This study aimed to investigate the effect of maresin like 1 (MaR-L1) treatment in AD pathology using 5XFAD mice. Methods: We tested 12-month-old male 5XFAD mice and wild type control mice treated with MaR-L1 in a battery of behavioral tasks. We performed open field test, beam walking test, clasping test, inverted grid test, acetone test, marble burring test, elevated plus maze test, cross maze test and novel object recognition test. We also studied neuronal loss, amyloid β burden, and inflammation in the brains of 5XFAD mice using immunohistology and Western blotting. Results: MaR-L1 treatment to the 5XFAD mice showed improved cognitive function of 5XFAD mice. MaR-L1 showed decreased anxiety behavior in open field test and marble burring test, increased muscular strength in the beam walking test, clasping test and inverted grid test. Cognitive function was improved in MaR-L1 treated 5XFAD mice in the novel object recognition test. MaR-L1 prevented neuronal loss and aberrant inflammation. Conclusion: Our finding suggests that behavioral abnormalities were normalized by the administration of MaR-L1 and the neuroprotective role of MaR-L1 in the AD. It also indicates that MaR-L1 treatment is able to prevent and or ameliorate neuronal loss and aberrant inflammation. Further experiments to validate the results are warranted using other AD models in the future.

Keywords: Alzheimer's disease, motor and cognitive behavior, 5XFAD mice, Maresin Like 1, microglial cell, astrocyte, neurodegeneration, inflammation, resolution of inflammation

Procedia PDF Downloads 183
671 Integrating Dynamic Brain Connectivity and Transcriptomic Imaging in Major Depressive Disorder

Authors: Qingjin Liu, Jinpeng Niu, Kangjia Chen, Jiao Li, Huafu Chen, Wei Liao

Abstract:

Functional connectomics is essential in cognitive science and neuropsychiatry, offering insights into the brain's complex network structures and dynamic interactions. Although neuroimaging has uncovered functional connectivity issues in Major Depressive Disorder (MDD) patients, the dynamic shifts in connectome topology and their link to gene expression are yet to be fully understood. To explore the differences in dynamic connectome topology between MDD patients and healthy individuals, we conducted an extensive analysis of resting-state functional magnetic resonance imaging (fMRI) data from 434 participants (226 MDD patients and 208 controls). We used multilayer network models to evaluate brain module dynamics and examined the association between whole-brain gene expression and dynamic module variability in MDD using publicly available transcriptomic data. Our findings revealed that compared to healthy individuals, MDD patients showed lower global mean values and higher standard deviations, indicating unstable patterns and increased regional differentiation. Notably, MDD patients exhibited more frequent module switching, primarily within the executive control network (ECN), particularly in the left dorsolateral prefrontal cortex and right fronto-insular regions, whereas the default mode network (DMN), including the superior frontal gyrus, temporal lobe, and right medial prefrontal cortex, displayed lower variability. These brain dynamics predicted the severity of depressive symptoms. Analyzing human brain gene expression data, we found that the spatial distribution of MDD-related gene expression correlated with dynamic module differences. Cell type-specific gene analyses identified oligodendrocytes (OPCs) as major contributors to the transcriptional relationships underlying module variability in MDD. To the best of our knowledge, this is the first comprehensive description of altered brain module dynamics in MDD patients linked to depressive symptom severity and changes in whole-brain gene expression profiles.

Keywords: major depressive disorder, module dynamics, magnetic resonance imaging, transcriptomic

Procedia PDF Downloads 34