Search results for: genetic circuit

Authors: Ramesh P., Aby Joseph

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Micro Inverters provide Module Embedded Solution for harvesting energy from small-scale solar photovoltaic (PV) panels. In addition to higher modularity & reliability (25 years of life), the MicroInverter has inherent advantages such as avoidance of long DC cables, eliminates module mismatch losses, minimizes partial shading effect, improves safety and flexibility in installations etc. Due to the above-stated benefits, the renewable energy technology with Solar Photovoltaic (PV) Micro Inverter becomes more widespread in Village Nano Grid application ensuring grid independence for rural communities and areas without access to electricity. While the primary objective of this paper is to discuss the problems related to rural electrification, this concept can also be extended to urban installation with grid connectivity. This work presents a comprehensive analysis of the power circuit design, control methodologies and prototyping of 300Wₚ Single Phase PV Micro Inverter. This paper investigates two different topologies for PV Micro Inverters, based on the first hand on Single Stage Flyback/ Forward PV Micro-Inverter configuration and the other hand on the Double stage configuration including DC-DC converter, H bridge DC-AC Inverter. This work covers Power Decoupling techniques to reduce the input filter capacitor size to buffer double line (100 Hz) ripple energy and eliminates the use of electrolytic capacitors. The propagation of the double line oscillation reflected back to PV module will affect the Maximum Power Point Tracking (MPPT) performance. Also, the grid current will be distorted. To mitigate this issue, an independent MPPT control algorithm is developed in this work to reject the propagation of this double line ripple oscillation to PV side to improve the MPPT performance and grid side to improve current quality. Here, the power hardware topology accepts wide input voltage variation and consists of suitably rated MOSFET switches, Galvanically Isolated gate drivers, high-frequency magnetics and Film capacitors with a long lifespan. The digital controller hardware platform inbuilt with the external peripheral interface is developed using floating point microcontroller TMS320F2806x from Texas Instruments. The firmware governing the operation of the PV Micro Inverter is written in C language and was developed using code composer studio Integrated Development Environment (IDE). In this work, the prototype hardware for the Single Phase Photovoltaic Micro Inverter with Double stage configuration was developed and the comparative analysis between the above mentioned configurations with experimental results will be presented.

Keywords: double line oscillation, micro inverter, MPPT, nano grid, power decoupling

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Authors: Savitha Janakiraman, Shivakumar M. C

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Anidulafungin, an advanced class of antifungal agent used for the treatment of chronic fungal infections, is derived from Echinocandin B nucleus, an intermediate metabolite of Echinocandin B produced by Aspergillus nidulans. The enzyme acylase derived from the fermentation broth of Actinoplanes utahensis (NRRL 12052) plays a key role in the bioconversion of echinocandin B to echinocandin B nucleus. The membrane-bound nature of acylase and low levels of expression contributes to the rate-limiting process of enzymatic deacylation, hence low yields of ECB nucleus and anidulafungin. In the present study, this is addressed through novel genetic engineering approaches of overexpression and heterologous expression studies, immobilization of whole cells of Actinoplanes utahensis (NRRL 12052) and Co-cultivation studies. Overexpression of the acylase gene in Actinoplanes utahensis (NRRL 12052) was done by increasing the gene copy number to increase the echinocandin B nucleus production. Echinocandin B acylase gene, under the control of a PermE* promoter, was cloned in pSET152 vector and introduced into Actinoplanes utahensis (NRRL12052) by a ɸC31-directed site-specific recombination method. The resultant recombinant strain (C2-18) showed a 3-fold increase in acylase expression, which was confirmed by HPLC analysis. Pichia pastoris is one of the most effective and versatile host systems for the production of heterologous proteins. The ECB acylase gene was cloned into pPIC9K vector with AOX1 promoter and was transformed into Pichia pastoris (GS115). The acylase expression was confirmed by protein expression and bioconversion studies. The heterologous expression of acylase in Pichia pastoris, is a milestone in the development of antifungals. Actively growing cells of Actinoplanes utahensis (NRRL 12052) were immobilized and tested for bioconversion ability which showed >90% conversion in each cycle. The stability of immobilized cell beads retained the deacylation ability up to 60 days and reusability was confirmed up to 4 cycles. The significant findings from the study have revealed that immobilization of whole cells of Actinoplanes utahensis (NRRL 12052) could be an alternative option for bioconversion of echinocandin B to echinocandin B nucleus, which has not been reported to date. The concept of co-cultivation of Aspergillus nidulans and Actinoplanes utahensis strains for the production of the echinocandin B nucleus was also carried out in order to produce echinocandin B nucleus. The process completely reduced the ECB purification step and, therefore, could be recommended as an ingenious method to improve the yield of the ECB nucleus.

Keywords: acylase, anidulafungin, antifungals, Aspergillus nidulans

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Authors: Valencia Fernandes, Dharmendra Kumar Khatri, Shashi Bala Singh

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Background and Aim: Epigenetics are the inaudible signatures of several pathological processes in the brain. This study understands the influence of DNA methylation, a major epigenetic modification, in the prefrontal cortex and hippocampus of the diabetic brain and its notable effect on the cellular chaperones and synaptic proteins. Method: Chronic high fat diet and STZ-induced diabetic mice were studied for cognitive dysfunction, and global DNA methylation, as well as DNA methyltransferase (DNMT) activity, were assessed. Further, the cellular chaperones and synaptic proteins were examined using DNMT inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC)-via intracerebroventricular injection. Moreover, % methylation of these synaptic proteins were also studied so as to correlate its epigenetic involvement. Computationally, its interaction with the DNMT enzyme were also studied using bioinformatic tools. Histological studies for morphological alterations and neuronal degeneration were also studied. Neurogenesis, a characteristic marker for new learning and memory formation, was also assessed via the BrdU staining. Finally, the most important behavioral studies, including the Morris water maze, Y maze, passive avoidance, and Novel object recognition test, were performed to study its cognitive functions. Results: Altered global DNA methylation and increased levels of DNMTs within the nucleus were confirmed in the cortex and hippocampus of the diseased mice, suggesting hypermethylation at a genetic level. Treatment with AzadC, a global DNA demethylating agent, ameliorated the protein and gene expression of the cellular chaperones and synaptic fidelity. Furthermore, the methylation analysis profile showed hypermethylation of the hsf1 protein, a master regulator for chaperones and thus, confirmed the epigenetic involvement in the diseased brain. Morphological improvements and decreased neurodegeneration, along with enhanced neurogenesis in the treatment group, suggest that epigenetic modulations do participate in learning and memory. This is supported by the improved behavioral test battery seen in the treatment group. Conclusion: DNA methylation could possibly accord in dysregulating the memory-associated proteins at chronic stages in type 2 diabetes. This could suggest a substantial contribution to the underlying pathophysiology of several metabolic syndromes like insulin resistance, obesity and also participate in transitioning this damage centrally, such as cognitive dysfunction.

Keywords: epigenetics, cognition, chaperones, DNA methylation

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Authors: Ife Elegbeleye, Nnditshedzeni Eric, Regina Maphanga, Femi Elegbeleye, Femi Agunbiade

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The global potential of other renewable energy sources such as wind, hydroelectric, bio-mass, and geothermal is estimated to be approximately 13 %, with hydroelectricity constituting a larger percentage. Sunlight provides by far the largest of all carbon-neutral energy sources. More energy from the sunlight strikes the Earth in one hour (4.3 × 1020 J) than all the energy consumed on the planet in a year (4.1 × 1020 J), hence, solar energy remains the most abundant clean, renewable energy resources for mankind. Photovoltaic (PV) devices such as silicon solar cells, dye sensitized solar cells are utilized for harnessing solar energy. Polyene-diphenylaniline organic molecules are important sets of molecules that has stirred many research interest as photosensitizers in TiO₂ semiconductor-based dye sensitized solar cells (DSSCs). The advantages of organic dye molecule over metal-based complexes are higher extinction coefficient, moderate cost, good environmental compatibility, and electrochemical properties. The polyene-diphenylaniline organic dyes with basic configuration of donor-π-acceptor are affordable, easy to synthesize and possess chemical structures that can easily be modified to optimize their photocatalytic and spectral properties. The enormous interest in polyene-diphenylaniline dyes as photosensitizers is due to their fascinating spectral properties which include visible light to near infra-red-light absorption. In this work, density functional theory approach via GPAW software, Avogadro and ASE were employed to study the effect of methoxy functionalized group on the spectral properties of polyene-diphenylaniline dyes and their photons absorbing characteristics in the visible region to near infrared region of the solar spectrum. Our results showed that the two-phenyl based complexes D5 and D7 exhibits maximum absorption peaks at 750 nm and 850 nm, while D9 and D11 with methoxy group shows maximum absorption peak at 800 nm and 900 nm respectively. The highest absorption wavelength is notable for D9 and D11 containing additional polyene and methoxy groups. Also, D9 and D11 chromophores with the methoxy group shows lower energy gap of 0.98 and 0.85 respectively than the corresponding D5 and D7 dyes complexes with energy gap of 1.32 and 1.08. The analysis of their electron injection kinetics ∆Ginject into the band gap of TiO₂ shows that D9 and D11 with the methoxy group has higher electron injection kinetics of -2.070 and -2.030 than the corresponding polyene-diphenylaniline complexes without the addition of polyene group with ∆Ginject values of -2.820 and -2.130 respectively. Our findings suggest that the addition of functionalized group as an extension of the organic complexes results in higher light harvesting efficiencies and bathochromic shift of the absorption spectra to higher wavelength which suggest higher current densities and open circuit voltage in DSSCs. The study suggests that the photocatalytic properties of organic chromophores/complexes with donor-π-acceptor configuration can be enhanced by the addition of functionalized groups.

Keywords: renewable energy resource, solar energy, dye sensitized solar cells, polyene-diphenylaniline organic chromophores

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Authors: J. H. Bang, H. J. Baek, K. I. Kim, B. J. Lee, H. J. Jung, H. J. Jang, S. K. Jung

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Asthma is a chronic inflammatory lung disease characterized by airway hyper responsiveness (AHR), airway obstruction and airway wall remodeling responsible for significant morbidity and mortality worldwide. Genetic and environment factors may result in asthma, but there are no the exact causes of asthma. Chungpye-tang (CPT) has been prescribed as a representative aerosol agent for patients with dyspnea, cough and phlegm in the respiratory clinic at Kyung Hee Korean Medicine Hospital. This Korean herbal medicines have the effect of dispelling external pathogen and dampness pattern. CPT is composed of 4 species of herbal medicines. The 4 species of herbal medicines are Ephedrae herba, Pogostemonis(Agatachis) herba, Caryophylli flos and Zingiberis rhizoma crudus. CPT suppresses neutrophil infiltration and the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Moreover, the anti-inflammatory effects of CPT on a mouse model of Chronic Obstructive Pulmonary Disease (COPD) was proved. Activation of the NF-κB has been proven that it plays an important role in inflammation via inducing transcription of pro-inflammatory genes. Over-expression of NF-κB has been believed be related to many inflammatory diseases such as arthritis, gastritis, asthma and COPD. So we firstly hypothesize whether CPT has an anti-inflammatory effect on asthmatic human airway epithelial tissue via inhibiting NF-κB pathway. In this study, CPT was extracted with distilled water for 3 hours at 100°C. After process of filtration and evaporation, it was freeze dried. And asthmatic human lung tissues were provided by MatTek Corp. We investigated the precise mechanism of the anti-inflammatory effect of CPT by western blotting analysis. We observed whether the decoction extracts could reduce NF-κB activation, COX-2 protein expression and NF-κB-mediated pro-inflammatory cytokines such as TNF-α, eotaxin, IL-4, IL-9 and IL-13 in asthmatic human lung tissue. As results of this study, there was a trend toward decreased NF-κB expression in asthmatic human airway epithelial tissue. We found that the inhibition effects of CPT on COX-2 expression was not determined. IL-9 and IL-13 secretion was significantly reduced in the asthmatic human lung tissue treated with CPT. Overall, our results indicate that CPT has an anti-inflammatory effect through blocking the signaling pathway of NF-κB, thereby CPT may be a potential remedial agent for allergic asthma.

Keywords: Chungpye-tang, allergic asthma, asthmatic human airway epithelial tissue, nuclear factor kappa B (NF-κB) pathway, COX-2

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Authors: Franco Van De Velde, Debora Esposito, Maria E. Pirovani, Mary A. Lila

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The physiology of various inflammatory diseases is a complex process mediated by inflammatory and immune cells such as macrophages and monocytes. Chronic inflammation, as observed in many cardiovascular and autoimmune disorders, occurs when the low-grade inflammatory response fails to resolve with time. Because of the complexity of the chronic inflammatory disease, major efforts have focused on identifying novel anti-inflammatory agents and dietary regimes that prevent the pro-inflammatory process at the early stage of gene expression of key pro-inflammatory mediators and cytokines. The ability of the extracts of three blackberry cultivars (‘Jumbo’, ‘Black Satin’ and ‘Dirksen’), and one strawberry cultivar (‘Camarosa’) to inhibit four well-known genetic biomarkers of inflammation: inducible nitric oxide synthase (iNOS), cyclooxynase-2 (Cox-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an in vitro lipopolysaccharide-stimulated murine RAW 264.7 macrophage model were investigated. Moreover, the effect of latter extracts on the intracellular reactive oxygen species (ROS) and nitric oxide (NO) production was assessed. Assay was conducted with 50 µg/mL crude extract concentration, an amount that is easily achievable in the gastrointestinal tract after berries consumption. The mRNA expression levels of Cox-2 and IL-6 were reduced consistently (more than 30%) by extracts of ‘Jumbo’ and ‘Black Satin’ blackberries. Strawberry extracts showed high reduction in mRNA expression levels of IL-6 (more than 65%) and exhibited moderate reduction in mRNA expression of Cox-2 (more than 35%). The latter behavior mirrors the intracellular ROS production of the LPS stimulated RAW 264.7 macrophages after the treatment with blackberry ‘Black Satin’ and ‘Jumbo’, and strawberry ‘Camarosa’ extracts, suggesting that phytochemicals from these fruits may play a role in the health maintenance by reducing oxidative stress. On the other hand, effective inhibition in the gene expression of IL-1β and iNOS was not observed by any of blackberry and strawberry extracts. However, suppression in the NO production in the activated macrophages among 5–25% was observed by ‘Jumbo’ and ‘Black Satin’ blackberry extracts and ‘Camarosa’ strawberry extracts, suggesting a higher NO suppression property by phytochemicals of these fruits. All these results suggest the potential beneficial effects of studied berries as functional foods with antioxidant and anti-inflammatory roles. Moreover, the underlying role of phytochemicals from these fruits in the protection of inflammatory process will deserve to be further explored.

Keywords: cyclooxygenase-2, functional foods, interleukin-6, reactive oxygen species

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Authors: George Zhou, Yunchan Chen, Candace Chien

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Kidney replacement therapy is the current standard of care for end-stage renal diseases. In-center or home hemodialysis remains an integral component of the therapeutic regimen. Arteriovenous fistulas (AVF) make up the vascular circuit through which blood is filtered and returned. Naturally, AVF patency determines whether adequate clearance and filtration can be achieved and directly influences clinical outcomes. Our aim was to build a deep learning model for automated AVF stenosis screening based on the sound of blood flow through the AVF. A total of 311 patients with AVF were enrolled in this study. Blood flow sounds were collected using a digital stethoscope. For each patient, blood flow sounds were collected at 6 different locations along the patient’s AVF. The 6 locations are artery, anastomosis, distal vein, middle vein, proximal vein, and venous arch. A total of 1866 sounds were collected. The blood flow sounds are labeled as “patent” (normal) or “stenotic” (abnormal). The labels are validated from concurrent ultrasound. Our dataset included 1527 “patent” and 339 “stenotic” sounds. We show that blood flow sounds vary significantly along the AVF. For example, the blood flow sound is loudest at the anastomosis site and softest at the cephalic arch. Contextualizing the sound with location metadata significantly improves classification performance. How to encode and incorporate categorical metadata is an active area of research1. Herein, we study ordinal (i.e., integer) encoding schemes. The numerical representation is concatenated to the flattened feature vector. We train a vision transformer (ViT) on spectrogram image representations of the sound and demonstrate that using scalar multiples of our integer encodings improves classification performance. Models are evaluated using a 10-fold cross-validation procedure. The baseline performance of our ViT without any location metadata achieves an AuROC and AuPRC of 0.68 ± 0.05 and 0.28 ± 0.09, respectively. Using the following encodings of Artery:0; Arch: 1; Proximal: 2; Middle: 3; Distal 4: Anastomosis: 5, the ViT achieves an AuROC and AuPRC of 0.69 ± 0.06 and 0.30 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 10; Proximal: 20; Middle: 30; Distal 40: Anastomosis: 50, the ViT achieves an AuROC and AuPRC of 0.74 ± 0.06 and 0.38 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 100; Proximal: 200; Middle: 300; Distal 400: Anastomosis: 500, the ViT achieves an AuROC and AuPRC of 0.78 ± 0.06 and 0.43 ± 0.11. respectively. Interestingly, we see that using increasing scalar multiples of our integer encoding scheme (i.e., encoding “venous arch” as 1,10,100) results in progressively improved performance. In theory, the integer values do not matter since we are optimizing the same loss function; the model can learn to increase or decrease the weights associated with location encodings and converge on the same solution. However, in the setting of limited data and computation resources, increasing the importance at initialization either leads to faster convergence or helps the model escape a local minimum.

Keywords: arteriovenous fistula, blood flow sounds, metadata encoding, deep learning

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Authors: Sebastian Hiergeist

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It is a common view that Unmanned Aerial Vehicles (UAV) tend to migrate into the civil airspace. This trend is challenging UAV manufacturer in plenty ways, as there come up a lot of new requirements and functional aspects. On the higher application levels, this might be collision detection and avoidance and similar features, whereas all these functions only act as input for the flight control components of the aircraft. The flight control computer (FCC) is the central component when it comes up to ensure a continuous safe flight and landing. As these systems are flight critical, they have to be built up redundantly to be able to provide a Fail-Operational behavior. Recent architectural approaches of FCCs used in UAV systems are often based on very simple microprocessors in combination with proprietary Application-Specific Integrated Circuit (ASIC) or Field Programmable Gate Array (FPGA) extensions implementing the whole redundancy functionality. In the future, such simple microprocessors may not be available anymore as they are more and more replaced by higher sophisticated System on Chip (SoC). As the avionic industry cannot provide enough market power to significantly influence the development of new semiconductor products, the use of solutions from foreign markets is almost inevitable. Products stemming from the industrial market developed according to IEC 61508, or automotive SoCs, according to ISO 26262, can be seen as candidates as they have been developed for similar environments. Current available SoC from the industrial or automotive sector provides quite a broad selection of interfaces like, i.e., Ethernet, SPI or FlexRay, that might come into account for the implementation of a redundancy network. In this context, possible network architectures shall be investigated which could be established by using the interfaces stated above. Of importance here is the avoidance of any single point of failures, as well as a proper segregation in distinct fault containment regions. The performed analysis is supported by the use of guidelines, published by the aviation authorities (FAA and EASA), on the reliability of data networks. The main focus clearly lies on the reachable level of safety, but also other aspects like performance and determinism play an important role and are considered in the research. Due to the further increase in design complexity of recent and future SoCs, also the risk of design errors, which might lead to common mode faults, increases. Thus in the context of this work also the aspect of dissimilarity will be considered to limit the effect of design errors. To achieve this, the work is limited to broadly available interfaces available in products from the most common silicon manufacturer. The resulting work shall support the design of future UAV FCCs by giving a guideline on building up a redundancy network between SoCs, solely using on board interfaces. Therefore the author will provide a detailed usability analysis on available interfaces provided by recent SoC solutions, suggestions on possible redundancy architectures based on these interfaces and an assessment of the most relevant characteristics of the suggested network architectures, like e.g. safety or performance.

Keywords: redundancy, System-on-Chip, UAV, flight control computer (FCC)

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Authors: Atitallah Sofien, Bouyahia Olfa, Romdhani Meriam, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Spondylothoracic dysostosis, also known as Jarcho-Levin syndrome, is defined by a shortened neck and thorax, a protruding abdomen, inguinal and umbilical hernias, atypical spinal structure and rib fusion, leading to restricted chest movement or difficulty in breathing, along with urinary tract abnormalities and, potentially severe scoliosis. Aim: This is the case of a patient diagnosed with Jarcho-Levin syndrome, aiming to detail the range of abnormalities observed in this syndrome, the observed complications, and the therapeutic approaches employed. Results: A three-month-old male infant, born of a consanguineous marriage, delivered at full term by cesarean section, was admitted to the pediatric department for severe acute bronchiolitis. In his prenatal history, morphological ultrasound revealed macrosomia, a shortened spine, irregular vertebrae with thickened skin, normal fetal cardiac ultrasound, and the absence of the right kidney. His perinatal history included respiratory distress, requiring ventilatory support for five days. Upon physical examination, he had stunted growth, scoliosis, a short neck and trunk, longer upper limbs compared to lower limbs, varus equinus in the right foot, a neural tube defect, a low hairline, and low-set ears. Spondylothoracic dysostosis was suspected, leading to further investigations, including a normal transfontaneous ultrasound, a spinal cord ultrasound revealing a lipomyelocele-type closed dysraphism with a low-attached cord, an abdominal ultrasound indicating a single left kidney, and a cardiac ultrasound identifying Kommerell syndrome. Due to a lack of resources, genetic testing could not be performed, and the diagnosis was based on clinical criteria. Conclusion: Jarcho-Levin syndrome can result in a mortality rate of about 50%, primarily due to respiratory complications associated with thoracic insufficiency syndrome. Other complications, like heart and neural tube defects, can also lead to premature mortality. Therefore, early diagnosis and comprehensive treatment involving various specialists are essential.

Keywords: Jarcho-Levin syndrome, congenital disorder, scoliosis, spondylothoracic dysostosis, neural tube defect

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Authors: Cecilia Moreira, Rita Paiva, Daniela Macedo, Leonor Ribeiro, Isabel Fernandes, Luis Costa

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Background: Head and neck paragangliomas are a rare group of tumors with a large spectrum of clinical manifestations. The approach to evaluate and treat these lesions has evolved over the last years. Surgery was the standard for the approach of these patients, but nowadays new techniques of imaging and radiation therapy changed that paradigm. Despite advances in treating, the growth potential and clinical outcome of individual cases remain largely unpredictable. Objectives: Characterization of our institutional experience with clinical management of these tumors. Methods: This was a cross-sectional study of patients followed in our institution between 01 January and 31 December 2017 with paragangliomas of the head and neck and cranial base. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic workup, treatment modality, tumor control and recurrence, complications of treatment and hereditary status were collected and summarized. Results: A total of four female patients were followed between 01 January and 31 December 2017 in our institution. The mean age of our cohort was 53 (± 16.1) years. The primary locations were at the level of the tympanic jug (n=2, 50%) and carotid body (n=2, 50%), and only one of the tumors of the carotid body presented pulmonary metastasis at the time of diagnosis. None of the lesions were catecholamine-secreting. Two patients underwent genetic testing, with no mutations identified. The initial clinical presentation was variable highlighting the decrease of visual acuity and headache as symptoms present in all patients. In one of the cases, loss of all teeth of the lower jaw was the presenting symptomatology. Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were employed as treatment approaches according to anatomical location and resectability of lesions. As post-therapeutic sequels the persistence of tinnitus and disabling pain stands out, presenting one of the patients neuralgia of the glossopharyngeal. Currently, all patients are under regular surveillance with a median follow up of 10 months. Conclusion: Ultimately, clinical management of these tumors remains challenging owing to heterogeneity in clinical presentation, the existence of multiple treatment alternatives, and potential to cause serious detriment to critical functions and consequently interference with the quality of life of the patients.

Keywords: clinical outcomes, head and neck, management, paragangliomas

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Authors: Oibar Martinez, Clara Oliver, Jose Miguel Miranda

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In this paper, we discuss the standard improvements which can be made to reduce the earth resistance in difficult terrains for optimum lightning protection, what are the practical limitations, and how the modeling can be refined for accurate diagnostics and ground resistance minimization. Ground resistance minimization can be made via three different approaches: burying vertical electrodes connected in parallel, burying horizontal conductive plates or meshes, or modifying the own terrain, either by changing the entire terrain material in a large volume or by adding earth-enhancing compounds. The use of vertical electrodes connected in parallel pose several practical limitations. In order to prevent loss of effectiveness, it is necessary to keep a minimum distance between each electrode, which is typically around five times larger than the electrode length. Otherwise, the overlapping of the local equipotential lines around each electrode reduces the efficiency of the configuration. The addition of parallel electrodes reduces the resistance and facilitates the measurement, but the basic parallel resistor formula of circuit theory will always underestimate the final resistance. Numerical simulation of equipotential lines around the electrodes overcomes this limitation. The resistance of a single electrode will always be proportional to the soil resistivity. The electrodes are usually installed with a backfilling material of high conductivity, which increases the effective diameter. However, the improvement is marginal, since the electrode diameter counts in the estimation of the ground resistance via a logarithmic function. Substances that are used for efficient chemical treatment must be environmentally friendly and must feature stability, high hygroscopicity, low corrosivity, and high electrical conductivity. A number of earth enhancement materials are commercially available. Many are comprised of carbon-based materials or clays like bentonite. These materials can also be used as backfilling materials to reduce the resistance of an electrode. Chemical treatment of soil has environmental issues. Some products contain copper sulfate or other copper-based compounds, which may not be environmentally friendly. Carbon-based compounds are relatively inexpensive and they do have very low resistivities, but they also feature corrosion issues. Typically, the carbon can corrode and destroy a copper electrode in around five years. These compounds also have potential environmental concerns. Some earthing enhancement materials contain cement, which, after installation acquire properties that are very close to concrete. This prevents the earthing enhancement material from leaching into the soil. After analyzing different configurations, we conclude that a buried conductive ring with vertical electrodes connected periodically should be the optimum baseline solution for the grounding of a large size structure installed on a large resistivity terrain. In order to show this, a practical example is explained here where we simulate the ground resistance of a conductive ring buried in a terrain with a resistivity in the range of 1 kOhm·m.

Keywords: grounding improvements, large scale scientific instrument, lightning risk assessment, lightning standards

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Authors: A. M. Tarola, R. Preti, A. M. Girelli, P. Campana

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Safeguarding, studying and enhancing biodiversity play an important and indispensable role in re-launching agriculture. The ancient local varieties are therefore a precious resource for genetic and health improvement. In order to protect biodiversity through the recovery and valorization of autochthonous varieties, in this study we analyzed 12 samples of four ancient apple cultivars representative of Friuli Venezia Giulia, selected by local farmers who work on a project for the recovery of ancient apple cultivars. The aim of this study is to evaluate the polyphenolic profile and the antioxidant capacity that characterize the organoleptic and functional qualities of this fruit species, besides having beneficial properties for health. In particular, for each variety, the following compounds were analyzed, both in the skins and in the pulp: gallic acid, catechin, chlorogenic acid, epicatechin, caffeic acid, coumaric acid, ferulic acid, rutin, phlorizin, phloretin and quercetin to highlight any differences in the edible parts of the apple. The analysis of individual phenolic compounds was performed by High Performance Liquid Chromatography (HPLC) coupled with a diode array UV detector (DAD), the antioxidant capacity was estimated using an in vitro essay based on a Free Radical Scavenging Method and the total phenolic compounds was determined using the Folin-Ciocalteau method. From the results, it is evident that the catechins are the most present polyphenols, reaching a value of 140-200 μg/g in the pulp and of 400-500 μg/g in the skin, with the prevalence of epicatechin. Catechins and phlorizin, a dihydrohalcone typical of apples, are always contained in larger quantities in the peel. Total phenolic compounds content was positively correlated with antioxidant activity in apple pulp (r² = 0,850) and peel (r² = 0,820). Comparing the results, differences between the varieties analyzed and between the edible parts (pulp and peel) of the apple were highlighted. In particular, apple peel is richer in polyphenolic compounds than pulp and flavonols are exclusively present in the peel. In conclusion, polyphenols, being antioxidant substances, have confirmed the benefits of fruit in the diet, especially as a prevention and treatment for degenerative diseases. They demonstrated to be also a good marker for the characterization of different apple cultivars. The importance of protecting biodiversity in agriculture was also highlighted through the exploitation of native products and ancient varieties of apples now forgotten.

Keywords: apple, biodiversity, polyphenols, antioxidant activity, HPLC-DAD, characterization

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Authors: Justin Fu, Thomas Mazzuchi, Shahram Sarkani

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A key factor in technological immaturity in defense weapons acquisition is lack of understanding critical integrations at the subsystem and component level. To address this shortfall, recent research in integration readiness level (IRL) combines with technology readiness level (TRL) to form a system readiness level (SRL). SRL can be enriched with more robust quantitative methods to provide the program manager a useful tool prior to committing to major weapons acquisition programs. This research harnesses previous mathematical models based on graph theory, Petri nets, and tropical algebra and proposes a modification of the desirable SRL mathematical properties such that a tightly integrated (multitude of interfaces) subsystem can display a lower SRL than an inherently less coupled subsystem. The synthesis of these methods informs an improved decision tool for the program manager to commit to expensive technology development. This research ties the separately developed manufacturing readiness level (MRL) into the network representation of the system and addresses shortfalls in previous frameworks, including the lack of integration weighting and the over-importance of a single extremely immature component. Tropical algebra (based on the minimum of a set of TRLs or IRLs) allows one low IRL or TRL value to diminish the SRL of the entire system, which may not be reflective of actuality if that component is not critical or tightly coupled. Integration connections can be weighted according to importance and readiness levels are modified to be a cardinal scale (based on an analytic hierarchy process). Integration arcs’ importance are dependent on the connected nodes and the additional integrations arcs connected to those nodes. Lack of integration is not represented by zero, but by a perfect integration maturity value. Naturally, the importance (or weight) of such an arc would be zero. To further explore the impact of grouping subsystems, a multi-objective genetic algorithm is then used to find various clusters or communities that can be optimized for the most representative subsystem SRL. This novel calculation is then benchmarked through simulation and using past defense acquisition program data, focusing on the newly introduced Middle Tier of Acquisition (rapidly field prototypes). The model remains a relatively simple, accessible tool, but at higher fidelity and validated with past data for the program manager to decide major defense acquisition program milestones.

Keywords: readiness, maturity, system, integration

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Authors: Lei Zhou, Chao Li, Ruiqi Ren, Dan Li, Yali Wang, Daxin Ni, Zijian Feng, Qun Li

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Background: Since the first human infection with avian influenza A(H7N9) case was reported in China on 31 March 2013, five epidemics have been observed in China through February 2013 and September 2017. Though the overall mortality rate of H7N9 has remained as high as around 40% throughout the five epidemics, the specific mortality rate in Mainland China varied by provinces. We conducted a descriptive analysis of mortality rates of H7N9 cases to explore the various severity features of the disease and then to provide clues of further analyses of potential factors associated with the severity of the disease. Methods: The data for analysis originated from the National Notifiable Infectious Disease Report and Surveillance System (NNIDRSS). The surveillance system and identification procedure for H7N9 infection have not changed in China since 2013. The definition of a confirmed H7N9 case is as same as previous reports. Mortality rates of H7N9 cases are described and compared by time and location of reporting, age and sex, and genetic features of H7N9 virus strains. Results: The overall mortality rate, the male and female specific overall rates of H7N9 is 39.6% (608/1533), 40.3% (432/1072) and 38.2% (176/461), respectively. There was no significant difference between the mortality rates of male and female. The age-specific mortality rates are significantly varied by age groups (χ²=38.16, p < 0.001). The mortality of H7N9 cases in the age group between 20 and 60 (33.17%) and age group of over 60 (51.16%) is much higher than that in the age group of under 20 (5.00%). Considering the time of reporting, the mortality rates of cases which were reported in the first (40.57%) and fourth (42.51%) quarters of each year are significantly higher than the mortality of cases which were reported in the second (36.02%) and third (27.27%) quarters (χ²=75.18, p < 0.001). The geographic specific mortality rates vary too. The mortality rates of H7N9 cases reported from the Northeast China (66.67%) and Westeast China (56.52%) are significantly higher than that of H7N9 cases reported from the remained area of mainland China. The mortality rate of H7N9 cases reported from the Central China is the lowest (34.38%). The mortality rates of H7N9 cases reported from rural (37.76%) and urban (38.96%) areas are similar. The mortality rate of H7N9 cases infected with the highly pathogenic avian influenza A(H7N9) virus (48.15%) is higher than the rate of H7N9 cases infected with the low pathogenic avian influenza A(H7N9) virus (37.57%), but the difference is not statistically significant. Preliminary analyses showed that age and some clinical complications such as respiratory failure, heart failure, and septic shock could be potential risk factors associated with the death of H7N9 cases. Conclusions: The mortality rates of H7N9 cases varied by age, sex, time of reporting and geographical location in mainland China. Further in-depth analyses and field investigations of the factors associated with the severity of H7N9 cases need to be considered.

Keywords: H7N9 virus, Avian Influenza, mortality, China

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Authors: Ratneev Kaur, Tajinder Kaur, Anupam Kaur

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Introduction: Polycystic Ovary Syndrome (PCOS) is a heterogenous disorder of endocrine system among women of reproductive age. PCOS is characterized by hyperandrogenism, anovulation, polycystic ovaries, hirsutism, obesity, and hyperinsulinemia. Several pathways are implicated in its etiology including the metabolic pathway of steroid hormone synthesis regulatory pathways. PCOS is an androgen excess disorder, genes operating in steroidogenesis may alter pathogenesis of PCOS. The cytochrome P450scc is a cholesterol side chain cleavage enzyme coded by CYP11A1 gene and catalyzes conversion of cholesterol to pregnenolone, the initial and rate-limiting step in steroid hormone synthesis. It is postulated that polymorphisms in this gene may play an important role in the regulation of CYP11A1 expression and leading to increased or decreased androgen production. The present study will be the first study from north India to best of our knowledge, to analyse the association of CYP11A1 (rs11632698) polymorphism in women suffering from PCOS. Methodology: The present study was approved by ethical committee of Guru Nanak Dev University in consistent with declaration of Helsinki. A total of 300 samples (150 PCOS cases and 150 controls) were recruited from Hartej hospital, for the present study. Venous blood sample (3ml) was withdrawn from women diagnosed with PCOS by doctor, according to Rotterdam 2003 criteria and from healthy age matched controls only after informed consent and detailed filled proforma. For molecular genetics analysis, blood was stored in EDTA vials. After DNA isolation by organic method, PCR-RFLP approach was used for genotyping and association analysis of rs11632698 polymorphism. Statistical analysis was done to check for significance of selected polymorphism with PCOS. Results: In 150 PCOS cases, the frequency of AA, AG and GG genotype was found to be 48%, 35%, and 13% compared to 62%, 27% and 8% in 150 controls. The major allele (A) and minor allele (G) frequency was 68% and 32% in cases and 78% and 22% in controls. Minor allele frequency was higher in cases as compared to controls, as well as the distribution of genotype was observed to be statistically significant (ᵡ²=6.525, p=0.038). Odds ratio in dominant, co-dominant and recessive models observed was 1.81 (p=0.013), 1.54 (p=0.012) and 1.77 (p=0.132) respectively. Conclusion: The present study showed statistically significant association of rs11632698 with PCOS (p=0.038) in North Indian women.

Keywords: polycystic ovary syndrome, CYP11A1, rs11632698, hyperandrogenism

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Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Hyeon-Seung Kim, Sang-Mi Park, Sun-Ju Han, Leen-Seok Kang

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As BIM (Building Information Modeling) application continually expands, the visual simulation techniques used for facility design and construction process information are becoming increasingly advanced and diverse. For building structures, BIM application is design - oriented to utilize 3D objects for conflict management, whereas for civil engineering structures, the usability of nD object - oriented construction stage simulation is important in construction management. Simulations of 5D and 6D objects, for which cost and resources are linked along with process simulation in 4D objects, are commonly used, but they do not provide a decision - making function for process management problems that occur on site because they mostly focus on the visual representation of current status for process information. In this study, an nD CAD system is constructed that facilitates an optimized schedule simulation that minimizes process conflict, a construction duration reduction simulation according to execution progress status, optimized process plan simulation according to project cost change by year, and optimized resource simulation for field resource mobilization capability. Through this system, the usability of conventional simple simulation objects is expanded to the usability of active simulation objects with which decision - making is possible. Furthermore, to close the gap between field process situations and planned 4D process objects, a technique is developed to facilitate a comparative simulation through the coordinated synchronization of an actual video object acquired by an on - site web camera and VR concept 4D object. This synchronization and simulation technique can also be applied to smartphone video objects captured in the field in order to increase the usability of the 4D object. Because yearly project costs change frequently for civil engineering construction, an annual process plan should be recomposed appropriately according to project cost decreases/increases compared with the plan. In the 5D CAD system provided in this study, an active 5D object utilization concept is introduced to perform a simulation in an optimized process planning state by finding a process optimized for the changed project cost without changing the construction duration through a technique such as genetic algorithm. Furthermore, in resource management, an active 6D object utilization function is introduced that can analyze and simulate an optimized process plan within a possible scope of moving resources by considering those resources that can be moved under a given field condition, instead of using a simple resource change simulation by schedule. The introduction of an active BIM function is expected to increase the field utilization of conventional nD objects.

Keywords: 4D, 5D, 6D, active BIM

Procedia PDF Downloads 256

Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

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Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

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Authors: Haohua Zong, Marios Kotsonis

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Plasma synthetic jet actuator (PSJA) is a new concept of zero net mass flow actuator which utilizes pulsed arc/spark discharge to rapidly pressurize gas in a small cavity under constant-volume conditions. The unique combination of high exit jet velocity (>400 m/s) and high actuation frequency (>5 kHz) provides a promising solution for high-speed high-Reynolds-number flow control. This paper focuses on the performance of PSJA in repetitive working mode which is more relevant to future flow control applications. A two-electrodes PSJA (cavity volume: 424 mm3, orifice diameter: 2 mm) together with a capacitive discharge circuit (discharge energy: 50 mJ-110 mJ) is designed to enable repetitive operation. Time-Resolved Particle Imaging Velocimetry (TR-PIV) system working at 10 kHz is exploited to investigate the influence of discharge frequency on performance of PSJA. In total, seven cases are tested, covering a wide range of discharge frequencies (20 Hz-560 Hz). The pertinent flow features (shock wave, vortex ring and jet) remain the same for single shot mode and repetitive working mode. Shock wave is issued prior to jet eruption. Two distinct vortex rings are formed in one cycle. The first one is produced by the starting jet whereas the second one is related with the shock wave reflection in cavity. A sudden pressure rise is induced at the throat inlet by the reflection of primary shock wave, promoting the shedding of second vortex ring. In one cycle, jet exit velocity first increases sharply, then decreases almost linearly. Afterwards, an alternate occurrence of multiple jet stages and refresh stages is observed. By monitoring the dynamic evolution of exit velocity in one cycle, some integral performance parameters of PSJA can be deduced. As frequency increases, the jet intensity in steady phase decreases monotonically. In the investigated frequency range, jet duration time drops from 250 µs to 210 µs and peak jet velocity decreases from 53 m/s to approximately 39 m/s. The jet impulse and the expelled gas mass (0.69 µN∙s and 0.027 mg at 20 Hz) decline by 48% and 40%, respectively. However, the electro-mechanical efficiency of PSJA defined by the ratio of jet mechanical energy to capacitor energy doesn’t show significant difference (o(0.01%)). Fourier transformation of the temporal exit velocity signal indicates two dominant frequencies. One corresponds to the discharge frequency, while the other accounts for the alternation frequency of jet stage and refresh stage in one cycle. The alternation period (300 µs approximately) is independent of discharge frequency, and possibly determined intrinsically by the actuator geometry. A simple analytical model is established to interpret the alternation of jet stage and refresh stage. Results show that the dynamic response of exit velocity to a small-scale disturbance (jump in cavity pressure) can be treated as a second-order under-damping system. Oscillation frequency of the exit velocity, namely alternation frequency, is positively proportional to exit area, but inversely proportional to cavity volume and throat length. Theoretical value of alternation period (305 µs) agrees well with the experimental value.

Keywords: plasma, synthetic jet, actuator, frequency effect

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Authors: Salma A. Mahmoud

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Epigenetic, or alteration in gene expression influenced by extragenetic factors, has emerged as one of the most promising areas that will address some of the gaps in our current knowledge in understanding patterns of human variation. In the last decade, the research investigating epigenetic mechanisms in many fields has flourished and witnessed significant progress. It paved the way for a new era of integrated research especially between anthropology/archeology and life sciences. Skeletal remains are considered the most significant source of information for studying human variations across history, and by utilizing these valuable remains, we can interpret the past events, cultures and populations. In addition to archeological, historical and anthropological importance, studying bones has great implications in other fields such as medicine and science. Bones also can hold within them the secrets of the future as they can act as predictive tools for health, society characteristics and dietary requirements. Bones in their basic forms are composed of cells (osteocytes) that are affected by both genetic and environmental factors, which can only explain a small part of their variability. The primary objective of this project is to examine the epigenetic landscape/signature within bones of archeological remains as a novel marker that could reveal new ways to conceptualize chronological events, gender differences, social status and ecological variations. We attempted here to address discrepancies in common variants such as methylome as well as novel epigenetic regulators such as chromatin remodelers, which to our best knowledge have not yet been investigated by anthropologists/ paleoepigenetists using plethora of techniques (biological, computational, and statistical). Moreover, extracting epigenetic information from bones will highlight the importance of osseous material as a vector to study human beings in several contexts (social, cultural and environmental), and strengthen their essential role as model systems that can be used to investigate and construct various cultural, political and economic events. We also address all steps required to plan and conduct an epigenetic analysis from bone materials (modern and ancient) as well as discussing the key challenges facing researchers aiming to investigate this field. In conclusion, this project will serve as a primer for bioarcheologists/anthropologists and human biologists interested in incorporating epigenetic data into their research programs. Understanding the roles of epigenetic mechanisms in bone structure and function will be very helpful for a better comprehension of their biology and highlighting their essentiality as interdisciplinary vectors and a key material in archeological research.

Keywords: epigenetics, archeology, bones, chromatin, methylome

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Authors: Sneha Shankar, Orlando Buendia, Will Evans

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Alpha-1 antitrypsin deficiency (AATD) is a rare, genetic, and multisystemic condition. Underdiagnosis is common, leading to chronic pulmonary and hepatic complications, increased resource utilization, and additional costs to the healthcare system. Currently, there is limited evidence of the direct medical costs of AATD diagnosis in the UK. This study explores the economic impact of AATD patients during the 3 years before diagnosis and to identify the major cost drivers using primary and secondary care electronic health record (EHR) data. The 3 years before diagnosis time period was chosen based on the ability of our tool to identify patients earlier. The AATD algorithm was created using published disease criteria and applied to 148 known AATD patients’ EHR found in a primary care database of 936,148 patients (413,674 Biobank and 501,188 in a single primary care locality). Among 148 patients, 9 patients were flagged earlier by the tool and, on average, could save 3 (1-6) years per patient. We analysed 101 of the 148 AATD patients’ primary care journey and 20 patients’ Hospital Episode Statistics (HES) data, all of whom had at least 3 years of clinical history in their records before diagnosis. The codes related to laboratory tests, clinical visits, referrals, hospitalization days, day case, and inpatient admissions attributable to AATD were examined in this 3-year period before diagnosis. The average cost per patient was calculated, and the direct medical costs were modelled based on the mean prevalence of 100 AATD patients in a 500,000 population. A deterministic sensitivity analysis (DSA) of 20% was performed to determine the major cost drivers. Cost data was obtained from the NHS National tariff 2020/21, National Schedule of NHS Costs 2018/19, PSSRU 2018/19, and private care tariff. The total direct medical cost of one hundred AATD patients three years before diagnosis in primary and secondary care in the UK was £3,556,489, with an average direct cost per patient of £35,565. A vast majority of this total direct cost (95%) was associated with inpatient admissions (£3,378,229). The DSA determined that the costs associated with tier-2 laboratory tests and inpatient admissions were the greatest contributors to direct costs in primary and secondary care, respectively. This retrospective study shows the role of EHRs in calculating direct medical costs and the potential benefit of new technologies for the early identification of patients with AATD to reduce the economic burden in primary and secondary care in the UK.

Keywords: alpha-1 antitrypsin deficiency, costs, digital health, early diagnosis

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Authors: Danna Jia, Bin Li

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Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

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Authors: Srinivas Bathini, Duraichelvan Raju, Simona Badilescu, Muthukumaran Packirisamy

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A bio-sensing method, based on the plasmonic property of gold nano-islands, has been developed for detection of exosomes in a clinical setting. The position of the gold plasmon band in the UV-Visible spectrum depends on the size and shape of gold nanoparticles as well as on the surrounding environment. By adsorbing various chemical entities, or binding them, the gold plasmon band will shift toward longer wavelengths and the shift is proportional to the concentration. Exosomes transport cargoes of molecules and genetic materials to proximal and distal cells. Presently, the standard method for their isolation and quantification from body fluids is by ultracentrifugation, not a practical method to be implemented in a clinical setting. Thus, a versatile and cutting-edge platform is required to selectively detect and isolate exosomes for further analysis at clinical level. The new sensing protocol, instead of antibodies, makes use of a specially synthesized polypeptide (Vn96), to capture and quantify the exosomes from different media, by binding the heat shock proteins from exosomes. The protocol has been established and optimized by using a glass substrate, in order to facilitate the next stage, namely the transfer of the protocol to a microfluidic environment. After each step of the protocol, the UV-Vis spectrum was recorded and the position of gold Localized Surface Plasmon Resonance (LSPR) band was measured. The sensing process was modelled, taking into account the characteristics of the nano-island structure, prepared by thermal convection and annealing. The optimal molar ratios of the most important chemical entities, involved in the detection of exosomes were calculated as well. Indeed, it was found that the results of the sensing process depend on the two major steps: the molar ratios of streptavidin to biotin-PEG-Vn96 and, the final step, the capture of exosomes by the biotin-PEG-Vn96 complex. The microfluidic device designed for sensing of exosomes consists of a glass substrate, sealed by a PDMS layer that contains the channel and a collecting chamber. In the device, the solutions of linker, cross-linker, etc., are pumped over the gold nano-islands and an Ocean Optics spectrometer is used to measure the position of the Au plasmon band at each step of the sensing. The experiments have shown that the shift of the Au LSPR band is proportional to the concentration of exosomes and, thereby, exosomes can be accurately quantified. An important advantage of the method is the ability to discriminate between exosomes having different origins.

Keywords: exosomes, gold nano-islands, microfluidics, plasmonic biosensing

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Authors: J. Jessa

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Background: Autism is a pervasive developmental disorder, the incidence of which has significantly increased in recent years. Children with autism have impairments in social skills, communication, and imagination. Children with autism has more common than healthy children feeding problems: food selectivity, problems with gastrointestinal tract: diarrhea, constipations, abdominal pain, reflux and others. Many parents of autistic children report that after implementation of gluten-, casein- and sugar free diet those symptoms disappear and even cognitive functions become better. Some children begin to understand speech and to communicate with parents, regain eye contact, become more calm, sleep better and has better concentration. Probably at the root of this phenomenon lies elimination from the diet peptides construction of which is similar to opiates. Enhanced permeability of gut causes absorption of not fully digested opioid-like peptides from food, like gluten and casein and probably others (proteins from soy and corn) which impact on brain of autistic children. Aim of the study: The aim of the study is to assess the safety of gluten-free diet in children with autism, aged 2,5-7. Methods: Participants of the study (n=70) – children aged 2,5-7 with autism are divided into 3 groups. The first group (research group) are patients whose parents want to implement a gluten-free diet. The second group are patients who have been recommended to eliminate from the diet artificial substances, such as preservatives, artificial colors and flavors, and others (control group 1). The third group (control group 2) are children whose parents did not agree for implementation of the diet. Caregivers of children on the diet are educated about the specifics of the diet and how to avoid malnutrition. At the start of the study we exclude celiac disease. Before the implementation of the diet we performe a blood test for patients (morphology, ferritin, total cholesterol, dry peripheral blood drops to detect some genetic metabolic diseases), plasma aminogram) and urine tests (excretion of ions: Mg, Na, Ca, the profile of organic acids in urine), which assess nutritional status as well as the psychological test assessing the degree of the child's psychological functioning (PEP-R). All of these tests will be repeated after one year from the implementation of the diet. Results: To the present moment we examined 42 children with autism. 12 of children are on gluten- free diet. Our preliminary results are promising. Parents of 9 of them report that, there is a big improvement in child behavior, concentration, less aggression incidents, better eye contact and better verbal skills. Conclusion: Our preliminary results suggest that dietary intervention may positively affect developmental outcome for some children diagnosed with ASD.

Keywords: gluten free diet, autism spectrum disorder, autism, blood test

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Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

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Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

Procedia PDF Downloads 140

Authors: Sonia Tamanna, Akramul Hassan, Mohammad Shakil Mahmood, Farzana Ansari, Gowhar Rashid, Mir Fahim Faisal, M. Zakir Hossain Howlader

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Background: Preeclampsia (PE), a pregnancy-specific hypertensive disorder, significantly impacts maternal and fetal health. It is particularly prevalent in underdeveloped countries and is linked to preterm delivery and fetal growth. The renin-angiotensin system (RAS) plays a crucial role in ensuring a successful pregnancy outcome, with Angiotensin-Converting Enzyme 2 (ACE2) being a key component. ACE2 converts ANG II to Ang-(1-7), offering protection against ANG II-induced stress and inflammation while regulating blood pressure and osmotic balance during pregnancy. The reduced maternal plasma angiotensin-converting enzyme 2 (ACE2) seen in preeclampsia might contribute to its pathogenesis. However, there has been a dearth of comprehensive research into the association between ACE2 gene polymorphism and preeclampsia. In the South Asian population, hypertension is strongly linked to two SNPs: rs2285666 and rs879922. This genotype was therefore considered, and the possible association of maternal and fetal ACE2 gene polymorphism with preeclampsia within the Bangladeshi population was evaluated. Method: DNA was extracted from peripheral white blood cells (WBCs) using the organic method, and SNP genotyping was done via PCR-RFLP. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using logistic regression to determine relative risk. Result: A comprehensive case-control study was conducted on 51 PE patients and their infants, along with 56 control subjects and their infants. Maternal single nuvleotide polymorphisms (SNP) (rs2285666) analysis revealed a strong association between the TT genotype and preeclampsia, with a four-fold increased risk in mothers (P=0.024, OR=4.00, 95% CI=1.36-11.37) compared to their ancestral genotype CC. However, the CT genotype (rs2285666) showed no significant difference (P=0.46, OR=1.54, 95% CI=0.57-4.14). Notably, no significant correlation was found in infants, regardless of their gender. For rs879922, no significant association was observed in both mothers and infants. This pioneering study suggests that mothers carrying the ACE2 gene variant rs2285666 (TT allele) may be at higher risk for preeclampsia, potentially influencing hypertension characteristics, whereas rs879922 does not appear to be associated with developing preeclampsia. Conclusion: This study sheds light on the role of ACE2 gene polymorphism, particularly the rs2285666 TT allele, in maternal susceptibility to preeclampsia. However, rs879922 does not appear to be linked to the risk of PE. This research contributes to our understanding of the genetic underpinnings of preeclampsia, offering insights into potential avenues for prevention and management.

Keywords: ACE2, PCR-RFLP, preeclampsia, single nuvleotide polymorphisms (SNPs)

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Authors: Sven Tackenberg, Sönke Duckwitz, Andreas Petz, Christopher M. Schlick

Abstract:

This paper introduces an extension to the well-established Resource-Constrained Project Scheduling Problem (RCPSP) to apply it to complex maintenance problems. The problem is to assign technicians to a team which has to process several tasks with multi-level skill requirements during a work shift. Here, several alternative activities for a task allow both, the temporal shift of activities or the reallocation of technicians and tools. As a result, switches from one valid work process variant to another can be considered and may be selected by the developed evolutionary algorithm based on the present skill level of technicians or the available tools. An additional complication of the observed scheduling problem is that the locations of the construction sites are only temporarily accessible during a day. Due to intensive rail traffic, the available time slots for maintenance and repair works are extremely short and are often distributed throughout the day. To identify efficient working periods, a first concept of a Bayesian network is introduced and is integrated into the extended RCPSP with pre-emptive and non-pre-emptive tasks. Thereby, the Bayesian network is used to calculate the probability of a maintenance task to be processed during a specific period of the shift. Focusing on the domain of maintenance of the railway infrastructure in metropolitan areas as the most unproductive implementation process at construction site, the paper illustrates how the extended RCPSP can be applied for maintenance planning support. A multi-criteria evolutionary algorithm with a problem representation is introduced which is capable of revising technician-task allocations, whereas the duration of the task may be stochastic. The approach uses a novel activity list representation to ensure easily describable and modifiable elements which can be converted into detailed shift schedules. Thereby, the main objective is to develop a shift plan which maximizes the utilization of each technician due to a minimization of the waiting times caused by rail traffic. The results of the already implemented core algorithm illustrate a fast convergence towards an optimal team composition for a shift, an efficient sequence of tasks and a high probability of the subsequent implementation due to the stochastic durations of the tasks. In the paper, the algorithm for the extended RCPSP is analyzed in experimental evaluation using real-world example problems with various size, resource complexity, tightness and so forth.

Keywords: maintenance management, scheduling, resource constrained project scheduling problem, genetic algorithms

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Authors: Habtamu Abera Goshu, Ping Yan

Abstract:

Copy number variation (CNV) is a significant marker of the genetic and phenotypic diversity among individuals that accounts for complex quantitative traits of phenotype and diseases via modulating gene dosage, position effects, alteration of downstream pathways, modification of chromosome structure, and position within the nucleus and disrupting coding regions in the genome. Associating copy number variations (CNVs) with growth and gene expression are a powerful approach for identifying genomic characteristics that contribute to phenotypic and genotypic variation. A previous study using next-generation sequencing illustrated that the choline kinase beta (CHKB), Krüpple-like factor 6 (KLF6), glypican 1(GPC1), and cholinergic receptor muscarinic 3 (CHRM3) genes reside within copy number variable regions (CNVRs) of yak populations that overlap with quantitative trait loci (QTLs) of meat quality and growth. As a result, this research aimed to determine the association of CNVs of the KLF6, CHKB, GPC1, and CHRM3 genes with growth traits in the Datong yak breed. The association between the CNV types of the KLF6, CHKB, GPC1, and CHRM3 genes and the growth traits in the Datong yak breed was determined by one-way analysis of variance (ANOVA) using SPSS software. The CNV types were classified as a loss (a copy number of 0 or 1), gain (a copy number >2), and normal (a copy number of 2) relative to the reference gene, BTF3 in the 387 individuals of Datong yak. These results indicated that the normal CNV types of the CHKB and GPC1 genes were significantly (P<0.05) associated with high body length, height and weight, and chest girth in six-month-old and five-year-old Datong yaks. On the other hand, the loss CNV types of the KLF6 gene is significantly (P<0.05) associated with body weight and length and chest girth at six-month-old and five-year-old Datong yaks. In the contrary, the gain CNV type of the CHRM3 gene is highly (P<0.05) associated with body weight, length, height, and chest girth in six-month-old and five-year-old. This work provides the first observation of the biological role of CNVs of the CHKB, KLF6, GPC1, and CHRM3 genes in the Datong yak breed and might, therefore, provide a novel opportunity to utilize data on CNVs in designing molecular markers for the selection of animal breeding programs for larger populations of various yak breeds. Therefore, we hypothesized that this study provided inclusive information on the application of CNVs of the CHKB, KLF6, GPC1, and CHRM3 genes in growth traits in Datong yaks and its possible function in bovine species.

Keywords: Copy number variation, growth traits, yak, genes

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Authors: Christelle E. Chua, Alicia L. Ho

Abstract:

The development of a panel of differential gene expression signatures has been of interest in the field of biomarker discovery for radiation exposure. In the absence of the availability of exposed human subjects, lymphocyte cell lines have often been used as a surrogate to human whole blood, when performing ex vivo irradiation studies. The extent of variation between different lymphocyte cell lines is currently unclear, especially with regard to the expression of extracellular miRNA. This study compares the expression profile of extracellular miRNA isolated from different lymphocyte cell lines. It also compares the profile of miRNA obtained when different exosome isolation kits are used. Lymphocyte cell lines were created using lymphocytes isolated from healthy adult males of similar racial descent (Chinese American and Chinese Singaporean) and immortalised with Epstein-Barr virus. The cell lines were cultured in exosome-free cell culture media for 72h and the cell culture supernatant was removed for exosome isolation. Two exosome isolation kits were used. Total exosome isolation reagent (TEIR, ThermoFisher) is a polyethylene glycol (PEG)-based exosome precipitation kit, while ExoSpin (ES, Cell Guidance Systems) is a PEG-based exosome precipitation kit that includes an additional size exclusion chromatography step. miRNA from the isolated exosomes were isolated using miRNEASY minikit (Qiagen) and analysed using nCounter miRNA assay (Nanostring). Principal component analysis (PCA) results suggested that the overall extracellular miRNA expression profile differed between the lymphocyte cell line originating from the Chinese American donor and the cell line originating from the Chinese Singaporean donor. As the gender, age and racial origins of both donors are similar, this may suggest that there are other genetic or epigenetic differences that account for the variation in extracellular miRNA gene expression in lymphocyte cell lines. However, statistical analysis showed that only 3 miRNA genes had a fold difference > 2 at p < 0.05, suggesting that the differences may not be of that great a significance as to impact overall conclusions drawn from different cell lines. Subsequent analysis using cell lines from other donors will give further insight into the reproducibility of results when difference cell lines are used. PCA results also suggested that the method of exosome isolation impacted the expression profile. 107 miRNA had a fold difference > 2 at p < 0.05. This suggests that the inclusion of an additional size exclusion chromatography step altered the subset of the extracellular vesicles that were isolated. In conclusion, these results suggest that extracellular miRNA can be isolated and analysed from exosomes derived from lymphocyte cell lines. However, care must be taken in the choice of cell line and method of exosome isolation used.

Keywords: biomarker, extracellular miRNA, isolation methods, lymphocyte cell line

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Authors: Mirosław Krzemieniewski, Marcin Zieliński, Marcin Dębowski

Abstract:

Electrokinetic disintegration is one of the high-voltage electric methods. The design of systems is exceptionally simple. Biomass flows through a system of pipes with alongside mounted electrodes that generate an electric field. Discharges in the electric field deform cell walls and lead to their successive perforation, thereby making their contents easily available to bacteria. The spark-over occurs between electrode surface and pipe jacket which is the second pole and closes the circuit. The value of voltage ranges from 10 to 100kV. Electrodes are supplied by normal “power grid” monophase electric current (230V, 50Hz). Next, the electric current changes into direct current of 24V in modules serving for particular electrodes, and this current directly feeds the electrodes. The installation is completely safe because the value of generated current does not exceed 250mA and because conductors are grounded. Therefore, there is no risk of electric shock posed to the personnel, even in the case of failure or incorrect connection. Low values of the electric current mean small energy consumption by the electrode which is extremely low – only 35W per electrode – compared to other methods of disintegration. Pipes with electrodes with diameter of DN150 are made of acid-proof steel and connected from both sides with 90º elbows ended with flanges. The available S and U types of pipes enable very convenient fitting with system construction in the existing installations and rooms or facilitate space management in new applications. The system of pipes for electrokinetic disintegration may be installed horizontally, vertically, askew, on special stands or also directly on the wall of a room. The number of pipes and electrodes is determined by operating conditions as well as the quantity of substrate, type of biomass, content of dry matter, method of disintegration (single or circulatory), mounting site etc. The most effective method involves pre-treatment of substrate that may be pumped through the disintegration system on the way to the fermentation tank or recirculated in a buffered intermediate tank (substrate mixing tank). Biomass structure destruction in the process of electrokinetic disintegration causes shortening of substrate retention time in the tank and acceleration of biogas production. A significant intensification of the fermentation process was observed in the systems operating in the technical scale, with the greatest increase in biogas production reaching 18%. The secondary, but highly significant for the energetic balance, effect is a tangible decrease of energy input by agitators in tanks. It is due to reduced viscosity of the biomass after disintegration, and may result in energy savings reaching even 20-30% of the earlier noted consumption. Other observed phenomena include reduction in the layer of surface scum, reduced sewage capability for foaming and successive decrease in the quantity of bottom sludge banks. Considering the above, the system for electrokinetic disintegration seems a very interesting and valuable solutions meeting the offer of specialist equipment for the processing of plant biomass, including Virginia fanpetals, before the process of methane fermentation.

Keywords: electrokinetic disintegration, biomass, biogas production, fermentation, Virginia fanpetals

Procedia PDF Downloads 350