Search results for: kidney functions and chronic renal failure

Authors: Mohammad Aladwan

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Alzheimer’s disease (AD) is a widespread dementing illness with a complex and poorly understood etiology. An important role in improving our understanding of the AD process is the modeling of disease-associated changes in tau protein phosphorylation, a protein known to mediate events essential to the onset and progression of AD. A main feature of AD is the abnormal phosphorylation of tau protein and the presence of neurofibrillary tangles. In order to evaluate the respective roles of the microtubule-binding region (MTBR) and alternatively spliced exons in the N-terminal projection domains in AD, we have constructed SHSY-5Y cell lines that stably overexpress four different species of tau protein (4R2N, 4R0N, N(E-2), N(E+2)). Since the toxicity and spreading of tau lesions in AD depends on the interactions of tau with other proteins, we have performed a proteomic analysis of exosome-fraction interactomes for cell lysates and media samples that were isolated from SHSY-5Y cell lines. Functional analysis of tau interactomes based on gene ontology (GO) terms was performed using the String 10.5 database program. The highest number of exosomes proteomes and tau associated proteins were found with 4R2N isoform (2771 and 159) in cell lysate and they have a high strength of connectivity (78%) between proteins, while N(E-2) isoform in the media proteomes has the highest number of proteins and tau associated protein (1829 and 205). Moreover, known AD markers were significantly enriched in secreted interactomes relative to lysate interactomes in the SHSY-5Y cells of tau isoforms lacking exons 2 and 3 in the N-terminal. The lack of exon 2 (E-2) from tau protein can be mediated by tau secretion and spreading to different cells. Enriched functions in the secreted E-2 interactome include signaling and developmental pathways that have been linked to a) tau misprocessing and lesion development and b) tau secretion and which, therefore, could play novel roles in AD pathogenesis.

Keywords: Alzheimer's disease, dementia, tau protein, neurodegenration disease

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Authors: Raphaelle Guillou, Matthieu Le Saux, Jean-Christophe Brachet, Thomas Guilbert, Elodie Rouesne, Denis Menut, Caroline Toffolon-Masclet, Dominique Thiaudiere

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In some hypothetical accidental situations, such as during a Loss Of Coolant Accident (LOCA) in pressurized water reactors, fuel cladding tubes made of zirconium alloys can be exposed for a few minutes to steam at High Temperature (HT up to 1200°C) before being cooled and then quenched in water. Under LOCA-like conditions, the cladding undergoes a number of metallurgical changes (phase transformations, oxygen diffusion and growth of an oxide layer...) and is consequently submitted to internal stresses whose state evolves during the transient. These stresses can have an effect on the oxide structure and the oxidation kinetics of the material. They evolve during cooling, owing to differences between the thermal expansion coefficients of the various phases and phase transformations of the metal and the oxide. These stresses may result in the failure of the cladding during quenching, once the material is embrittled by oxidation. In order to progress in the evaluation of these internal stresses, X-ray diffraction experiments were performed in-situ under synchrotron radiation during HT oxidation and subsequent cooling on Zircaloy-4 sheet samples. First, structural evolutions, such as phase transformations, have been studied as a function of temperature for both the oxide layer and the metallic substrate. Then, internal stresses generated within the material oxidized at temperatures between 700 and 900°C have been evaluated thanks to the 2θ diffraction peak position shift measured during the in-situ experiments. Electron backscatter diffraction (EBSD) analysis was performed on the samples after cooling in order to characterize their crystallographic texture. Furthermore, macroscopic strains induced by oxidation in the conditions investigated during the in-situ X-ray diffraction experiments were measured in-situ in a dilatometer.

Keywords: APRP, stains measurements, synchrotron diffraction, zirconium allows

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Authors: Emmanuel Ikechuckwu Onwubuya, Afees Adebayo Oladejo

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Background: The use of medicinal plants in the treatment of chronic diseases especially myocardial infarction, is gaining wide acceptance globally. Andrographis paniculata (Acanthaceae) is a medicinal plant commonly known as the king of bitters in Nigeria and has been acclaimed for several therapeutic activities. Materials and methods: This study investigated the cardio-protective effect of the leaf extract of A. paniculata in isoproterenol-induced myocardial infarction. Fresh green leaves of A paniculata were harvested from the Faculty of Agriculture farmland, Nnamdi Azikiwe University, Awka, Nigeria. Identification and authentication of the plant were carried out at the Department of Botany, Nnamdi Azikiwe University and a voucher specimen was deposited at the herbarium. The plant material was then shredded, air-dried under shade and pulverized. The fine powders obtained were weighed and extraction was done via a solvent combination of water and ethanol (3:7) for 72 hr via maceration. The filtrate gotten was evaporated to dryness to obtain the ethanol extract, which was used for further bioassay study. The bioactive constituents of the plant extract were quantitatively analyzed by Gas chromatography-mass spectrometry (GC-MS). The animals were administered the extract of A. paniculata orally for seven days at a divided dose of 100 mg/kg, 200 mg/kg and 400 mg/kg body weights. On the eighth day, myocardial infarction was induced through subcutaneous administration of isoproterenol at a dose of 150 mg/kg/day diluted in 2 ml of saline on two consecutive days. Subsequently, the blood pressures were monitored and blood was collected for bioassay studies. Results: The results of the study showed that the leaf extract of A. paniculata was rich in Dodecanoic acid (8.261%), 4-Dibenzofuranamine (6.03%), Cyclotrisiloxane (4.679 %). The findings also showed a significant decrease (p>0.05) in the Mean arterial blood pressure, heart rate, aspartate transaminase, alanine transaminase, creatinine kinase and lactate dehydrogenase activities of the treatment group compared with the untreated control group while the antioxidant (superoxide dismutase, catalase and glutathione) activities were significantly increased in the treatment group, compared with the untreated control group. Conclusion: The findings of this work have shown that the leaf of A. paniculata was rich in bioactive compounds, which could be synthesized to produce plant-based products to fight cardiovascular diseases, especially myocardial infarction.

Keywords: cardiovascular disease, myocardial infarction, medicinal plant, andrographis paniculata, isoproterenol

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Authors: Behrooz Daneshmand

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Software Defined Networking (SDN) is designed to meet the future needs of 5G mobile networks. The SDN architecture offers a new solution that involves separating the control plane from the data plane, which is usually paired together. Network functions traditionally performed on specific hardware can now be abstracted and virtualized on any device, and a centralized software-based administration approach is based on a central controller, facilitating the development of modern applications and services. These plan standards clear the way for a more adaptable, speedier, and more energetic network beneath computer program control compared with a conventional network. We accept SDN gives modern inquire about openings to security, and it can significantly affect network security research in numerous diverse ways. Subsequently, the SDN architecture engages systems to effectively screen activity and analyze threats to facilitate security approach modification and security benefit insertion. The segregation of the data planes and control and, be that as it may, opens security challenges, such as man-in-the-middle attacks (MIMA), denial of service (DoS) attacks, and immersion attacks. In this paper, we analyze security threats to each layer of SDN - application layer - southbound interfaces/northbound interfaces - controller layer and data layer. From a security point of see, the components that make up the SDN architecture have a few vulnerabilities, which may be abused by aggressors to perform noxious activities and hence influence the network and its administrations. Software-defined network assaults are shockingly a reality these days. In a nutshell, this paper highlights architectural weaknesses and develops attack vectors at each layer, which leads to conclusions about further progress in identifying the consequences of attacks and proposing mitigation strategies.

Keywords: software-defined networking, security, SDN, 5G/IMT-2020

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Authors: Hussain Sajid, Jung-Hun Shin, Kum-Won Cho

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Image super-resolution is the most common computer vision problem with many important applications. Generative adversarial networks (GANs) have promoted remarkable advances in single-image super-resolution (SR) by recovering photo-realistic images. However, high memory requirements of GAN-based SR (mainly generators) lead to performance degradation and increased energy consumption, making it difficult to implement it onto resource-constricted devices. To relieve such a problem, In this paper, we introduce an optimized and highly efficient architecture for SR-GAN (generator) model by utilizing model compression techniques such as Knowledge Distillation and pruning, which work together to reduce the storage requirement of the model also increase in their performance. Our method begins with distilling the knowledge from a large pre-trained model to a lightweight model using different loss functions. Then, iterative weight pruning is applied to the distilled model to remove less significant weights based on their magnitude, resulting in a sparser network. Knowledge Distillation reduces the model size by 40%; pruning then reduces it further by 18%. To accelerate the learning process, we employ the Horovod framework for distributed training on a cluster of 2 nodes, each with 8 GPUs, resulting in improved training performance and faster convergence. Experimental results on various benchmarks demonstrate that the proposed compressed model significantly outperforms state-of-the-art methods in terms of peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), and image quality for x4 super-resolution tasks.

Keywords: single-image super-resolution, generative adversarial networks, knowledge distillation, pruning

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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Authors: Fernanda M. Assef, Maria Teresinha A. Steiner

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The aim of this paper is to compare and discuss better classifier algorithm options for credit risk assessment by applying different Machine Learning techniques. Using records from a Brazilian financial institution, this study uses a database of 5,432 companies that are clients of the bank, where 2,600 clients are classified as non-defaulters, 1,551 are classified as defaulters and 1,281 are temporarily defaulters, meaning that the clients are overdue on their payments for up 180 days. For each case, a total of 15 attributes was considered for a one-against-all assessment using four different techniques: Artificial Neural Networks Multilayer Perceptron (ANN-MLP), Artificial Neural Networks Radial Basis Functions (ANN-RBF), Logistic Regression (LR) and finally Support Vector Machines (SVM). For each method, different parameters were analyzed in order to obtain different results when the best of each technique was compared. Initially the data were coded in thermometer code (numerical attributes) or dummy coding (for nominal attributes). The methods were then evaluated for each parameter and the best result of each technique was compared in terms of accuracy, false positives, false negatives, true positives and true negatives. This comparison showed that the best method, in terms of accuracy, was ANN-RBF (79.20% for non-defaulter classification, 97.74% for defaulters and 75.37% for the temporarily defaulter classification). However, the best accuracy does not always represent the best technique. For instance, on the classification of temporarily defaulters, this technique, in terms of false positives, was surpassed by SVM, which had the lowest rate (0.07%) of false positive classifications. All these intrinsic details are discussed considering the results found, and an overview of what was presented is shown in the conclusion of this study.

Keywords: artificial neural networks (ANNs), classifier algorithms, credit risk assessment, logistic regression, machine Learning, support vector machines

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Authors: Xia Luo, Cheng Zeng

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Under the promotion of the Central Committee of the Communist Party of China and the State Council in 2017, Xiong'an New Area is the third crucial new area in China established after Shenzhen and Shanghai. Its constructions' significance lies in mitigating Beijing's non-capital functions and exploring a new mode of optimizing development in densely populated and economically intensive areas. For this purpose, developing underground logistics can assume the role of goods distribution in the capital, relieve the road transport pressure in Beijing-Tianjin-Hebei Urban Agglomeration, adjust and optimize the urban layout and spatial structure of it. Firstly, the construction planning of Xiong'an New Area and underground logistics development are summarized, especially the development status abroad, the development trend, and bottlenecks of underground logistics in China. This paper explores the technicality, feasibility, and necessity of four modes of transportation. There are pneumatic capsule pipeline (PCP) technology, the CargoCap technology, cable hauled mule, and automatic guided vehicle (AGV). The above technical parameters and characteristics are introduced to relevant experts or scholars. Through establishing an indicator system, carrying out a questionnaire survey with the Delphi method, the final suggestion is obtained: China should develop logistics vehicles similar to CargoCap, adopting rail mode and driverless mode. Based on China's temporal and spatial logistics demand and the geographical pattern of Xiong'an New Area, the construction scale, technical parameters, node location, and other vital parameters of underground logistics are planned. In this way, we hope to speed up the new area's construction and the logistics industry's innovation.

Keywords: the Xiong'an new area, underground logistics, contrastive analysis, CargoCap, logistics planning

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Authors: Linda Muswaka

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The Constitution of the Republic of South Africa, 1996 ranks the Constitution as the Supreme law of the Republic. Law or conduct, inconsistent with the provisions of the Constitution is invalid to the extent of the inconsistency. The Constitution binds all persons and legislative, executive and judicial organs of the State at all levels of government. The Constitution embodies a Bill of Rights and expressly allows for judicial review. The introduction of a chapter of rights requires the judiciary to examine the decisions of the legislature and the executive. In a situation where these conflicts with the Bill of Rights, the judiciary have the constitutional power to overrule such decisions. In exercising its adjudicatory and interpretative powers, the judiciary sometimes arrives at unpopular decisions and accusations of judicial overreach are made. A problem, therefore, emerges on the issue of the separation of powers and judicial review. This paper proposes to, through the South African perspective, investigate the application of the doctrine of separation of powers and judicial review. In this regard, the qualitative method of research will be employed. The reason is that it is best suited to this type of study which entails a critical analysis of legal issues. The following findings are made: (i) a complete separation of powers is not possible. This is because some overlapping of the functions of the three branches of state are unavoidable; (ii) the powers vested in the judiciary does not make it more powerful than the executive and the legislature; (iii) interference by the judiciary in matters concerning other branches is not automatically, judicial overreach; and (iv) if both the executive and legislative organs of government adhere to their constitutional obligations there would be a decrease in the need for judicial interference through court adjudication. The researcher concludes by submitting that the judiciary should not derogate from their constitutionally mandated function of judicial review. The rationale being that that if the values contained in the Constitution are not scrupulously observed and their precepts not carried out conscientiously, the result will be a constitutional crisis of great magnitude.

Keywords: constitution, judicial review, judicial overreach, separation of powers

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Authors: Lucas Bublitz, Michael Herdrich

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By achieving the first commercialization approval in San Francisco the Autonomous Driving (AD) industry proves the technology maturity of the SAE L4 AD systems and the corresponding software and hardware stack. This milestone reflects the upcoming phase in the industry, where the focus is now about scaling and supervising larger autonomous vehicle (AV) fleets in different operation areas. This requires an operation framework, which organizes and assigns responsibilities to the relevant AV technology and operation stakeholders from the AV system provider, the Remote Intervention Operator, the MaaS provider and regulatory & approval authority. This holistic operation framework consists of technological, processual, and organizational activities to ensure safe operation for fully automated vehicles. Regarding the supervision of large autonomous vehicle fleets, a major focus is on the continuous field monitoring. The field monitoring approach must reflect the safety and security criticality of incidents in the field during driving operation. This includes an automatic containment approach, with the overall goal to avoid safety critical incidents and reduce downtime by a malfunction of the AD software stack. An End-to-end (E2E) field monitoring approach detects critical faults in the field, uses a knowledge-based approach for evaluating the safety criticality and supports the automatic containment of these E/E faults. Applying such an approach will ensure the scalability of AV fleets, which is determined by the handling of incidents in the field and the continuous regulatory compliance of the technology after enhancing the Operational Design Domain (ODD) or the function scope by Functions on Demand (FoD) over the entire digital product lifecycle.

Keywords: field monitoring, incident management, multicompliance management for AI in AD, root cause analysis, database approach

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Authors: Y. Kunitani, Y. Nakashima, S. Yamauchi, Y. Ishigami, K. Naito, K. Numata, M. Mizobe, Y. Homma, J. Takahashi, T. Inoue, T. Shiga, H. Funakoshi

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Background: Japanese Spotted Fever (JSF) is one of the Rickettsial infections, caused by Rickettsia japonica, which is transmitted by ticks. JSF is seen in limited area, such as Japan and South Korea. Its clinical triad is rash, eschar and fever. It often shows leukocytopenia, thrombopenia, elevated transaminase and high C-reactive protein (CRP). Sometimes it can be life-threatening due to disseminated intravascular coagulation or multiple organ failure. Study Aim: The aim of this study is to describe the features of JSF, as this unique infection is rapidly growing in Japan. Methods: This is a case series of JSF from 2009 to 2016, in Mie Prefectural Hospital in Japan. We collected JSF cases, which were diagnosed by polymerase chain reaction (PCR) of the skin or blood serum, or the elevation of the antibody titer of paired blood samples. Results: There were 43 JSF patients (19 male, 24 female) with a median age of 71 years [IQR:65-80]. The median body temperature was 38.1°C[IQR: 37.5-39.0]. 95% had a rash, 67% had eschar and 50% had fever. The median WBC count was 6,700 [IQR: 5,750-8,200] and leukocytopenia was observed in only 7%. The median platelet count was 14x104 [IQR10x104-17x104], thrombopenia was observed in 65%. The median aspartate transaminase (AST) was 53 IU/L [IQR: 41-93]; the median alanine aminotransferase (ALT) was 34 IU/L [IQR: 24-54]; the median CRP was 10.4 mg/dL [IQR:7.2-13.9]; the median lactate dehydrogenase (LDH) was 352IU/L [IQR:282-451]. CRP and LDH were elevated in almost all of the patients. Median length of stay in hospital was 8 days [IQR: 6-11]. All patients were treated with tetracycline and quinolone on the day of the presentation. There was no fatality from JSF. Conclusion: The patients with JSF classically presents with eschar, rash and fever. However, in this study, the half of the patients were afebrile. Although JSF is not a common infectious disease worldwide, if the patient had previously visited Japan or South Korea and presented with rash and eschar with or without fever, we should consider JSF as a potential diagnosis.

Keywords: infectious disease, Japanese spotted fever, Rickettsial disease, Rickettsia japonica

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Authors: Yafit Gabay

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Attention deficit hyperactivity disorder (ADHD) has been associated with both suboptimal functioning in the striatum and prefrontal cortex. Such abnormalities may impede the acquisition of perceptual categories, which are important for fundamental abilities such as object recognition and speech perception. Indeed, prior research has supported this possibility, demonstrating that children with ADHD have similar visual category learning performance as their neurotypical peers but use suboptimal learning strategies. However, much less is known about category learning processes in the auditory domain or among adults with ADHD in which prefrontal functions are more mature compared to children. Here, we investigated auditory and visual perceptual category learning in adults with ADHD and neurotypical individuals. Specifically, we examined learning of rule-based categories – presumed to be optimally learned by a frontal cortex-mediated hypothesis testing – and information-integration categories – hypothesized to be optimally learned by a striatally-mediated reinforcement learning system. Consistent with striatal and prefrontal cortical impairments observed in ADHD, our results show that across sensory modalities, both rule-based and information-integration category learning is impaired in adults with ADHD. Computational modeling analyses revealed that individuals with ADHD were slower to shift to optimal strategies than neurotypicals, regardless of category type or modality. Taken together, these results suggest that both explicit, frontally mediated and implicit, striatally mediated category learning are impaired in ADHD. These results suggest impairments across multiple learning systems in young adults with ADHD that extend across sensory modalities and likely arise from domain-general mechanisms.

Keywords: ADHD, category learning, modality, computational modeling

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Authors: Suleh Yusufu Godi, Ado Makama Adamu

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Marketing involves all the legal, physical, and economic services which are necessary in moving products from producer to consumers. The more efficient the marketing functions are performed the better the marketing system for the farmers, marketing agents, and the society at large. Rice marketing ensures the flow of product from producers to consumers in the form, time and place of need. Therefore, this study examined profitability of milled rice marketing in Gombe metropolis, Gombe State. Data were collected using structured questionnaires from ninety randomly selected rice marketers in Gombe metropolis. The data were analyzed using descriptive statistics, farm budget technique and regression analysis. The study revealed the total rice marketing cost incurred by rice marketers to be N6, 610,214.70. This gave an average of N73, 446.83 per marketer and N37.30 per Kilogram of rice. The Gross Income for rice marketers in Gombe metropolis was N15, 064,600.00. This value gave an average of N167, 384.44 per rice marketer or N85.00 per kilogram of rice. The study also revealed net income for all rice marketers to be N8, 454,385.30. This gave an average of N93, 937.61 per rice marketer or N47.70 per Kilogram of rice. The study further revealed a marketing margin, marketing efficiency and return per naira invested on rice marketing to be 39.30%, 150.16% and N0.56, respectively. The result of regression analysis shows that age, sex and cost of transportation are positive and significantly affect marketing margin of rice marketers in Gombe Metropolis. However, the main constraints to rice marketing in Gombe metropolis include inadequate electricity, capital, high transportation cost, instability of prices and low patronage among others. The study recommends provision of adequate electrical power supply in the State especially the State capital and also encouraging rice marketers in Gombe metropolis to form cooperative societies so as to have easy access to credit facilities especially from the formal sources.

Keywords: rice marketers, milled rice, cost and return, marketing margin, efficiency, profitability

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Authors: Scott A. Ochsner, Christopher M. Watkins, Apollo McOwiti, David L. Steffen Lauren B. Becnel, Neil J. McKenna

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Understanding signaling by nuclear receptors (NRs) requires an appreciation of their cognate ligand- and tissue-specific transcriptomes. While target gene regulation data are abundant in this field, they reside in hundreds of discrete publications in formats refractory to routine query and analysis and, accordingly, their full value to the NR signaling community has not been realized. One of the mandates of the Nuclear Receptor Signaling Atlas (NURSA) is to facilitate access of the community to existing public datasets. Pursuant to this mandate we are developing a freely-accessible community web resource, Transcriptomine, to bring together the sum total of available expression array and RNA-Seq data points generated by the field in a single location. Transcriptomine currently contains over 25,000,000 gene fold change datapoints from over 1200 contrasts relevant to over 100 NRs, ligands and coregulators in over 200 tissues and cell lines. Transcriptomine is designed to accommodate a spectrum of end users ranging from the bench researcher to those with advanced bioinformatic training. Visualization tools allow users to build custom charts to compare and contrast patterns of gene regulation across different tissues and in response to different ligands. Our resource affords an entirely new paradigm for leveraging gene expression data in the NR signaling field, empowering users to query gene fold changes across diverse regulatory molecules, tissues and cell lines, target genes, biological functions and disease associations, and that would otherwise be prohibitive in terms of time and effort. Transcriptomine will be regularly updated with gene lists from future genome-wide expression array and expression-sequencing datasets in the NR signaling field.

Keywords: target gene database, informatics, gene expression, transcriptomics

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Authors: Erika De Finis, Paola Gattinoni, Laura Scesi

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Massive rock avalanches formed some of the largest landslide deposits on Earth and they represent one of the major geohazards in high-relief mountains. This paper interprets a very large sedimentary fan (the Sernio fan, Valtellina, Northern Italy), located 20 Km SW from Val Pola Rock avalanche (1987), as the deposit of a partial collapse of a Deep Seated Gravitational Slope Deformation (DSGSD), afterwards eroded and buried by debris flows. The proposed emplacement sequence has been reconstructed based on geomorphological, structural and mechanical evidences. The Sernio fan is actually considered anomalous with reference to the very high ratio between the fan area (about 4.5km2) and the basin area (about 3km2). The morphology of the fan area is characterised by steep slopes (dip about 20%) and the fan apex is extended for 1.8 km inside the small catchment basin. This sedimentary fan was originated by a landslide that interested a part of a large deep-seated gravitational slope deformation, involving a wide area of about 55 km². The main controlling factor is tectonic and it is related to the proximity to regional fault systems and the consequent occurrence of fault weak rocks (GSI locally lower than 10 with compressive stress lower than 20MPa). Moreover, the fan deposit shows sedimentary evidences of recent debris flow events. The best current explanation of the Sernio fan involves an initial failure of some hundreds of Mm3. The run-out was quite limited because of the morphology of Valtellina’s valley floor, and the deposit filled the main valley forming a landslide dam, as confirmed by the lacustrine deposits detected upstream the fan. Nowadays the debris flow events represent the main hazard in the study area.

Keywords: anomalous sedimentary fans, deep seated gravitational slope deformation, Italy, rock avalanche

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Authors: I. Boroňová, J. Bernasovská, J. Kmec, E. Petrejčíková

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Dilated cardiomyopathy (DCM) is a primary myocardial disease, it is characterized by progressive systolic dysfunction due to cardiac chamber dilatation and inefficient myocardial contractility with estimated prevalence of 37 in 100 000 people. It is the most frequent cause of heart failure and cardiac transplantation in young adults. About one-third of all patients have a suspected familial disease indicating a genetic basis of DCM. Many candidate gene studies in humans have tested the association of single nucleotide polymorphisms (SNPs) in various genes coding for proteins with a known cardiovascular function. In our study we present the results of ZBTB17 gene rs10927875 polymorphism genotyping in relation to dilated cardiomyopathy in Slovak population. The study included 78 individuals, 39 patients with DCM and 39 healthy control persons. The mean age of patients with DCM was 50.7±11.5 years; the mean age of individuals in control group was 51.3±9.8 years. Risk factors detected at baseline in each group included age, sex, body mass index, smoking status, diabetes and blood pressure. Genomic DNA was extracted from leukocytes by a standard methodology and screened for rs10927875 polymorphism in intron of ZBTB17 gene using Real-time PCR method (Step One Applied Biosystems). The distribution of investigated genotypes for rs10927875 polymorphism in the group of patients with DCM was as follows: CC (89.74%), CT (10.26%), TT (0%), and the distribution in the control group: CC (92.31%), CT (5.13%), and TT (2.56%). Using the chi-square (χ2) test we compared genotype and allele frequencies between patients and controls. There was no difference in genotype or allele frequencies in ZBTB17 gene rs10927875 polymorphism between patients and control group (χ2=3.028, p=0.220; χ2=0.264, p=0.608). Our results represent an initial study, it can be considered as preliminary and first of its kind in Slovak population. Further studies of ZBTB17 gene polymorphisms of more numerous files and additional functional investigations are needed to fully understand the role of genetic associations.

Keywords: dilated cardiomyopathy, SNP polymorphism, ZBTB17 gene, bioscience

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Authors: Richard Wolfel, Amy Richmond

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Urban resilience and vulnerability are critical concepts in the modern city due to the increased sociocultural, political, economic, demographic, and environmental stressors that influence current urban dynamics. Urban scholars need help explaining urban resilience and vulnerability. First, cities are dominated by people, which is challenging to model, both from an explanatory and a predictive perspective. Second, urban regions are highly recursive in nature, meaning they not only influence human action, but the structures of cities are constantly changing due to human actions. As a result, explanatory frameworks must continuously evolve as humans influence and are influenced by the urban environment in which they operate. Finally, modern cities have populations, sociocultural characteristics, economic flows, and environmental impacts on order of magnitude well beyond the cities of the past. As a result, the frameworks that seek to explain the various functions of a city that influence urban resilience and vulnerability must address the complex adaptive nature of cities and the interaction of many distinct factors that influence resilience and vulnerability in the city. This project develops a taxonomy and framework for organizing and explaining urban vulnerability. The framework is built on a well-established political development model that includes six critical classes of urban dynamics: political presence, political legitimacy, political participation, identity, production, and allocation. In addition, the framework explores how environmental security and technology influence and are influenced by the six elements of political development. The framework aims to identify key tipping points in society that act as influential agents of urban vulnerability in a region. This will help analysts and scholars predict and explain the influence of both physical and human geographical stressors in a dense urban area.

Keywords: urban resilience, vulnerability, sociocultural stressors, political stressors

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Authors: Talal Asif, Maya Kosinska, Lucas Georger, Krish Sardesai, Muhammad Shah Miran

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This article presents a case review and literature review focused on the challenges of managing subaortic membranes (SAM) in young adult patients with mild aortic regurgitation (AR) or aortic stenosis (AS). The study aims to discuss the diagnosis of SAM, imaging studies used for assessment, management strategies in young patients, the risk of valvular damage, and the controversy surrounding prophylactic resection in mild AR. The management of SAM in adults poses challenges due to limited treatment options and potential complications, necessitating further investigation into the progression of AS and AR in asymptomatic SAM patients. The case presentation describes a 40-year-old male with muscular dystrophy who presented with symptoms and was diagnosed with SAM. Various imaging techniques, including CT chest, transthoracic echocardiogram (TTE), and transesophageal echocardiogram (TEE), were used to confirm the presence and severity of SAM. Based on the patient's clinical profile and the absence of surgical indications, medical therapy was initiated, and regular outpatient follow-up was recommended to monitor disease progression. The discussion highlights the challenges in diagnosing SAM, the importance of imaging studies, and the potential complications associated with SAM in young patients. The article also explores the management options for SAM, emphasizing surgical resection as the definitive treatment while acknowledging the limited success rates of alternative approaches. Close monitoring and prompt intervention for complications are crucial in the management of SAM. The concluding statement emphasizes the need for further research to explore alternative treatments for SAM in young patients.

Keywords: subaortic membrane, management, case report, literature review, aortic regurgitation, aortic stenosis, left ventricular outflow obstruction, guidelines, heart failure

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Authors: Lara Bruno, Ilaria Tipà, Franco Delogu

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Simultaneous interpreting (SI) is a demanding language task which includes the contemporary activation of different cognitive processes. This complex activity requires interpreters not only to be proficient in their working languages; but also to have a great ability in focusing attention and controlling anxiety during their performance. Effects of Qigong meditation techniques have a positive impact on several cognitive functions, including attention and anxiety control. This study aims at exploring the influence of Qigong meditation on the quality of simultaneous interpreting. 20 interpreting students, divided into two groups, were trained for 8 days in Qigong meditation practice. Before and after training, a brief simultaneous interpreting task was performed. Language combinations of group A and group B were respectively English-Italian and Chinese-Italian. Students’ performances were recorded and rated by independent evaluators. Assessments were based on 12 different parameters, divided into 4 macro-categories: content, form, delivery and anxiety control. To determine if there was any significant variation between the pre-training and post-training SI performance, ANOVA analyses were conducted on the ratings provided by the independent evaluators. Main results indicate a significant improvement of the interpreting performance after the meditation training intervention for both groups. However, group A registered a higher improvement compared to Group B. Nonetheless, positive effects of meditation have been found in all the observed macro-categories. Meditation was not only beneficial for speech delivery and anxiety control but also for cognitive and attention abilities. From a cognitive and pedagogical point of view, present results open new paths of research on the practice of meditation as a tool to improve SI performances.

Keywords: cognitive science, interpreting studies, Qigong meditation, simultaneous interpreting, training

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Authors: Shadreck Muchaku, Grey Magaiza, Jerit Dube

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The high insolvency rate of female-led emerging enterprises in the Southern African mountain region reflects the various vulnerabilities that exist. Although this is the case, there is a limited understanding of how these vulnerabilities influence entrepreneurship failure. This paper focuses on female entrepreneurs because of their role in economic development. Emerging female entrepreneurs in this region often operate in uncertain environments, which makes it difficult for them to thrive. The form and nature of entrepreneurial opportunities rural women of the Afro Montane region engage in are largely unsustainable as a lot of women struggle with confidence, and they need help with understanding their skills. However, there is still a gap in the existing literature on women entrepreneurship resilience and vulnerability reduction in the Afromontane. Furthermore, a major problem is the lack of empirical studies on this matter and limited studies indicating a general profile of emerging female entrepreneurs in this region. This systematic literature review attempts to fill in the gap of knowledge on entrepreneurship resilience and vulnerability reduction of emerging female entrepreneurs in the Afromontane regions and other similar precarious environments. In this review, we focus much on highlighting the nexus between entrepreneurship resilience and vulnerability reduction of emerging female entrepreneurs in academic literature through a chronological dispersal of publications in developing countries. This review adopts an ATLAS ti.22 software-based thematic analysis to analyze results obtained from reviewed academic journal articles. As research on entrepreneurship resilience and vulnerability reduction is still developing in the Sothern African mountain region, the results of this review will contribute to the body of literature and provide recommendations and a foundation for future research. This systematic review paper provides valuable insights and methodological approaches to scholarship in a nascent area of emerging female entrepreneurs in the Afromontane.

Keywords: entrepreneurship resiliency, vulnerability reduction, female entrepreneurs, mountain regions

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Authors: Valeria T. Dilcheva, Svetlozara L. Petkova, Ivelin Vladov

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Trichinellosis is a food-borne parasitic disease caused by nematodes of the genus Trichinella which are zoonotic parasites with cosmopolitan distribution and major socio-economic importance. Human infection is acquired through consumption of undercooked meat from domestic or wild animal. Penetration of Trichinella larvae into striated skeletal muscle cells results in ultrastructural and metabolic changes. Migration of larvae causes the typical symptoms and signs of the disease. The severity of the symptoms depends on the number of ingested Trichinella larvae and the immune response of the host. Eosinophilia is present, with few exceptions, in most cases of human trichinellosis, inasmuch as it is the earliest and most important host response. Even in human asymptomatic cases, increases in eosinophilia of up to 15% have been observed. Eosinophilia appears at an early stage of infection between the second and fifth weeks of infection. By 2005 it was considered that only two species of Trichinella genus were found in the country. After routine trichinelloscopy procedure disseminated single muscle larvae in samples of wild boars and badger were PCR-identified as T. pseudospiralis. The study aimed to observed hematological changes occurring during experimentally induced infection with Trichinella spiralis, T. britovi and T. pseudospiralis in mice. We performed hematological blood profile, tracking 15 blood indicators. In statistical analysis made by Two-way ANOVA, there were significant differences of HGB, MCHC, PLT, Lymph%, Gran% in all three types of trichinellosis compared to control animals. Capsule-forming T. spiralis showed statistically significant differences in HGB, MCHC, Lymph% and PLT compared to the other two species. Non capsule-forming T. pseudospiralis showed statistically significant differences in Lymph%, Gran% relative to the control and in Gran% relative to T. spiralis. It appears rather substantial the process of capsule formation for prolonged immune response and retention of high content of percentage of lymphocytes(Lymph%) and low of granulocyte(Gran%) in T. pseudospiralis, which is contrary to studies for T. spiralis and eosinophilia. Studies and analyzes of some specific blood profile parameters can provide additional data in favor of early diagnosis and adequate treatment as well as provide a better understanding of acute and chronic trichinosis.

Keywords: hematological test, T. britovi, T. spiralis, T. pseudospiralis

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Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

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Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.

Keywords: Doxorubicin, auto dock, in silco, in vitro

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Authors: Nosratollah Hedayatpour, Hamid Reza Taheri, Mehrdad Fathi

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Introduction: Quadriceps femoris muscle is frequently involved in various movements e.g., jumping, landing) during sport and/or daily activities. During ballistic movement when individuals are faced with unexpected knee perturbation, fast twitch muscle fibers contribute to force production to stabilize knee joint. Fast twitch muscle fiber is more susceptible to fatigue and therefor may reduce the ability of the quadriceps muscle to stabilize knee joint during fast perturbation. Aim: The aim of this study was to investigate the effect of fatigue on postural response of the knee extensor muscles to fast and slow perturbations. Methods: Fatigue was induced to the quadriceps muscle using a KinCom Isokinetic Dynamometer (Chattanooga, TN). Bipolar surface electromyography (EMG) signals were simultaneously recorded from quadriceps components (vastus medialis, rectus femoris, and vastus lateralis) during pre- and post-fatigue postural perturbation performed at two different velocities of 120 ms and 250 mes. Results: One-way ANOVA showed that maximal voluntary knee extension force and time to task failure, and associated EMG activities were significantly reduced after fatiguing knee exercise (P< 0.05). Two-ways ANOVA also showed that ARV of EMG during backward direction was significantly larger than forward direction (P< 0.05), and during fast-perturbation it was significantly higher than slow-perturbation (P< 0.05). Moreover, ARV of EMG was significantly reduced during post fatigue perturbation, with the largest reduction identified for fast-perturbation compared with slow perturbation (P< 0.05). Conclusion: A larger reduction in muscle activity of the quadriceps muscle was observed during post fatigue fast-perturbation to stabilize knee joint, most likely due to preferential recruitment of fast twitch muscle fiber which are more susceptible to fatigue. This may partly explain that why knee injuries is common after fast ballistic movement.

Keywords: electromyography, fast-slow perturbations, fatigue, quadriceps femoris muscle

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Authors: Wael Salah Shendy, Moataz Mohamed EL Semary, Hosam Salah Murad, Adham A. Mohamed

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Background: Cervicogenic headache is a major problem in many people suffering from upper cervical dysfunction with a great conflict in its physical therapy management. Objectives: To determine the effect of C1-C2 Mulligan SNAGs mobilizations on cervicogenic headache and associated dizziness symptoms. Methods: Forty-eight patients with cervicogenic headache included in the study; from the outpatient clinic of Faculty of Physical Therapy, Cairo University, and New Cairo outpatient clinics, were randomly assigned into three equal groups; group A ( Headache SNAG), group B (C1-C2 SNAG rotation) and group C (combined). Their mean age was (29.37 ± 2.6), (29.31 ± 2.54) and (29.68 ± 2.65). Neck Disability Index used to examine neck pain intensity and CEH symptoms. 6 Items Headache Impact test '6-HIT' scale used to examine headache severity and its adverse effects on social life and functions. Flexion-Rotation Test 'FRT' also used to assess rotation ROM at the level of C1-C2 by 'CROM' device. Dizziness Handicap Inventory 'DHI' scale was used to evaluate dizziness symptoms. Evaluation is done pre and post treatment, and comparison between groups was quantified. Correlations between the examined parameters were also measured. Headache SNAG and C1-C2 Rotation SNAGs were done separately in group (A- B) and combined in group C as a treatment intervention. Results: Group C has Significant improvement in whole parameters compared to group A and B, positive correlation was found between NDI and 6-HIT scores compared to negative correlation between NDI and DHI scores. Conclusion: SNAGs mobilizations used in the study were effective in reducing cervicogenic headache and dizziness symptoms in all groups with a noticeable improvement in the combined group.

Keywords: cervicogenic headache, cervical headache snag, cervical snag half rotation, cervical dizziness

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Authors: E. Chakwizira, D. J. Moot, M. Andrews, E. Teixeira

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Partitioning of macro-nutrients in wheat (Triticum aestivum L.) plant organs have not been extensively studied, particularly for modern genotypes grown under contrasting N supply. Nutrient accumulation and partitioning of phosphorus, potassium, calcium, magnesium and sulphur (P, K, Ca, Mg and S) were determined for six wheat genotypes [12S2-2021, 12S3-3019, 13S3-2026, Discovery, Duchess and Reliance] grown with (200 kg/ha) or without (0 kg/ha) nitrogen (N), in a fully irrigated field experiment in 2017-18 season at Lincoln, New Zealand. Data were collected at three growth stages (GS): tillering (GS21), anthesis (GS60) and grain maturity (GS92). Grain yield varied with both N and genotype; from 6-7.5 t/ha for the 0 kg N/ha crops and 8.1-9.3 t/ha for the 200 kg N/ha treatments. Plant nutrient uptake at maturity responded to both N supply and genotype for all nutrients, except S which did not differ among the genotypes. For example, total P uptake averaged 13.5 (12.4-14.3) kg/ha for the 0 kg N/ha treatments and 17.8 (15.1-19.7) kg/ha when 200 kg N/ha was applied. Similarly, K uptake increased from an average of 23 (21.6-25.3) for the 0 kg N/ha treatments to 34.3 (32.4-40.8) kg/ha when 200 kg N/ha was applied. Similar trends were observed for Ca and Mg. The S content only responded to N supply but not to genotype, increasing from 7.9 kg/ha for the 0 kg N treatments to 12.8 kg/ha when 200 kg N was applied. Relative nutrient content at anthesis compared with those at maturity were 30% for P, 100% for both K and Ca and 34% of Mg. Sulphur content at anthesis decreased 29% with N supply and was highest for genotypes 12S2-2021 compared with the other five genotype. At grain maturity, the ratio of nutrients in grain to total plant nutrient, defined as the nutrient harvest index (NHI) varied with both N supply and genotype. Averaged across treatments, the NHI was 0.96 for P, 0.53 for K, 0.58 for Ca, 0.90 for Mg and 0.85 for S. These results suggest that Ca and K should be provided earlier in the season as there is limited or no uptake after anthesis. These results also show that Ca and K are important for structural functions, while P, Mg and S are remobilised to the grains and become important for quality.

Keywords: anthesis, genotype, nutrient harvests index, NHI, Triticum aestivum L.

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Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

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Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

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Authors: Vipul M. Patel, Hemantkumar B. Mehta

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Technological innovations in electronic world demand novel, compact, simple in design, less costly and effective heat transfer devices. Closed Loop Pulsating Heat Pipe (CLPHP) is a passive phase change heat transfer device and has potential to transfer heat quickly and efficiently from source to sink. Thermal performance of a CLPHP is governed by various parameters such as number of U-turns, orientations, input heat, working fluids and filling ratio. The present paper is an attempt to predict the thermal performance of a CLPHP using Artificial Neural Network (ANN). Filling ratio and heat input are considered as input parameters while thermal resistance is set as target parameter. Types of neural networks considered in the present paper are radial basis, generalized regression, linear layer, cascade forward back propagation, feed forward back propagation; feed forward distributed time delay, layer recurrent and Elman back propagation. Linear, logistic sigmoid, tangent sigmoid and Radial Basis Gaussian Function are used as transfer functions. Prediction accuracy is measured based on the experimental data reported by the researchers in open literature as a function of Mean Absolute Relative Deviation (MARD). The prediction of a generalized regression ANN model with spread constant of 4.8 is found in agreement with the experimental data for MARD in the range of ±1.81%.

Keywords: ANN models, CLPHP, filling ratio, generalized regression, spread constant

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Authors: Junwen Chen, Celina Feleppa, Tingyue Sun, Satoko Sasagawa, Michael Smithson

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School refusal behaviours refer to behaviours to avoid school attendance, chronic lateness in arriving at school, or regular early dismissal. Poor attendance in schools is highly correlated with anxiety, depression, suicide attempts, delinquency, violence, and substance use and abuse. Poor attendance is also a strong indicator of lower achievement in school, as well as problematic social-emotional development. Long-term consequences of school refusal behaviours include fewer opportunities for higher education, employment, and social difficulties, and high risks of later psychiatric illness. Given its negative impacts on youth educational outcomes and well-being, a thorough understanding of factors that are involved in the development of this phenomenon is warranted for developing effective management approaches. This study investigated parental and adolescent factors that may contribute to school refusal behaviours by specifically focusing on the role of parental and adolescents’ anxiety and depression, emotion dysregulation, and parental rearing style. Findings are expected to inform the identification of both parental and adolescents’ factors that may contribute to school refusal behaviours. This knowledge will enable novel and effective approaches that incorporate these factors to managing school refusal behaviours in adolescents, which in turn improve their school and daily functioning. Results are important for an integrative understanding of school refusal behaviours. Furthermore, findings will also provide information for policymakers to weigh the benefits of interventions targeting school refusal behaviours in adolescents. One-hundred-and-six adolescents aged 12-18 years (mean age = 14.79 years old, SD = 1.78, males = 44) and their parents (mean age = 47.49 years old, SD = 5.61, males = 27) completed an online questionnaire measuring both parental and adolescents’ anxiety, depression, emotion dysregulation, parental rearing styles, and adolescents’ school refusal behaviours. Adolescents with school refusal behaviours reported greater anxiety and depression, with their parents showing greater emotion dysregulation. Parental emotion dysregulation and adolescents’ anxiety and depression predicted school refusal behaviours independently. To date, only limited studies have investigated the interplay between parental and youth factors in relation to youth school refusal behaviours. Although parental emotion dysregulation has been investigated in relation to youth emotion dysregulation, little is known about its role in the context of school refusal. This study is one of the very few that investigated both parental and adolescent factors in relation to school refusal behaviours in adolescents. The findings support the theoretical models that emphasise the role of youth and parental psychopathology in school refusal behaviours. Future management of school refusal behaviours should target adolescents’ anxiety and depression while incorporating training for parental emotion regulation skills.

Keywords: adolescents, school refusal behaviors, parental factors, anxiety and depression, emotion dysregulation

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Authors: Akshay Patil

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Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.

Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal

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Authors: Laith K. Abbas, Xiaoting Rui, Pier Marzocca

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Aerospace systems, generally speaking, are inherently nonlinear. These nonlinearities may modify the behavior of the system. However, nonlinearities in an aeroelastic system can be divided into structural and aerodynamic. Structural nonlinearities can be subdivided into distributed and concentrated ones. Distributed nonlinearities are spread over the whole structure representing the characteristic of materials and large motions. Concentrated nonlinearities act locally, representing loose of attachments, worn hinges of control surfaces, and the presence of external stores. The concentrated nonlinearities can be approximated by one of the classical structural nonlinearities, namely, cubic, free-play and hysteresis, or by a combination of these, for example, a free-play and a cubic one. Compressibility, aerodynamic heating, separated flows and turbulence effects are important aspects that result in nonlinear aerodynamic behavior. An issue related to the low-speed flutter and its catastrophic/benign character represented by Limit Cycle Oscillation (LCO) of all-movable fin, as well to their control is addressed in the present work. To the approach of this issue: (1) Quasi-Steady (QS) Theory and Computational Fluid Dynamics (CFD) of subsonic flow are implemented, (2) Flutter motion equations of a two-dimensional typical section with cubic nonlinear stiffness in the pitching direction and free play gap are established, (3) Uncoupled bending/torsion frequencies of the selected fin are computed using recently developed Transfer Matrix Method of Multibody System Dynamics (MSTMM), and (4) Time simulations are carried out to study the bifurcation behavior of the aeroelastic system. The main objective of this study is to investigate how the LCO and chaotic behavior are influenced by the coupled aeroelastic nonlinearities and intend to implement a control capability enabling one to control both the flutter boundary and its character. By this way, it may expand the operational envelop of the aerospace vehicle without failure.

Keywords: aeroelasticity, CFD, MSTMM, flutter, freeplay, fin

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