Search results for: inborn errors of metabolism (IEM)

Authors: D. W. M. S. Samarathunga, Isuru Dharmarathne

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In aphasia, various levels of symbolic language processing (semantics) are affected. It is shown that Persons with Aphasia (PWA) often experience more problems comprehending some categories of words than others. The study aimed to determine lexical semantic deficits seen in Auditory Comprehension (AC) and to describe lexical-semantic deficits across six selected word categories. Thirteen (n =13) persons diagnosed with post-stroke aphasia (PSA) were recruited to perform an AC task. Foods, objects, clothes, vehicles, body parts and animals were selected as the six categories. As the test stimuli, black and white line drawings were adapted from a picture set developed for semantic studies by Snodgrass and Vanderwart. A pilot study was conducted with five (n=5) healthy nonbrain damaged Sinhala speaking adults to decide familiarity and applicability of the test material. In the main study, participants were scored based on the accuracy and number of errors shown. The results indicate similar trends of lexical semantic deficits identified in the literature confirming ‘animals’ to be the easiest category to comprehend. Mann-Whitney U test was performed to determine the association between the selected variables and the participants’ performance on AC task. No statistical significance was found between the errors and the type of aphasia reflecting similar patterns described in aphasia literature in other languages. The current study indicates the presence of selectivity of lexical semantic deficits in AC and a hierarchy was developed based on the complexity of the categories to comprehend by Sinhala speaking PWA, which might be clinically beneficial when improving language skills of Sinhala speaking persons with post-stroke aphasia. However, further studies on aphasia should be conducted with larger samples for a longer period to study deficits in Sinhala and other Sri Lankan languages (Tamil and Malay).

Keywords: aphasia, auditory comprehension, selective lexical-semantic deficits, semantic categories

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Authors: Z. Abdessemed, N. Messaâdia, M. Houhamdi

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The PAH (Polycyclic Aromatic Hydrocarbons) represent a persistent source of pollution for oil field soils. Their degradation, essentially dominated by the aerobic bacterial and fungal flora, exhibits certain aspects for remediation of these soils microbial oxygenases have, as their substrates, a large range of PAH. The variety and the performance of these enzymes allow the initiation of the biodegradation of any PAH through many different metabolic pathways. These pathways are very important for the recycling of the PAH in the biosphere, where substances supposed indigestible by living organisms are rapidly transformed into simples compounds, directly assimilated by the intermediate metabolism of other microorganisms.

Keywords: polycyclic aromatic hydrocarbons, microbial oxygenases, biodegradation, metabolic pathways

Procedia PDF Downloads 259

Authors: Massimo Miccoli, Luca Marangoni, Alberto Aniello Scaringi, Alessandro Marceddu, Alessandro Amicone

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The susceptibility of deep neural networks (DNNs) to adversarial manipulations is a recognized challenge within the computer vision domain. Adversarial examples, crafted by adding subtle yet malicious alterations to benign images, exploit this vulnerability. Various defense strategies have been proposed to safeguard DNNs against such attacks, stemming from diverse research hypotheses. Building upon prior work, our approach involves the utilization of autoencoder models. Autoencoders, a type of neural network, are trained to learn representations of training data and reconstruct inputs from these representations, typically minimizing reconstruction errors like mean squared error (MSE). Our autoencoder was trained on a dataset of benign examples; learning features specific to them. Consequently, when presented with significantly perturbed adversarial examples, the autoencoder exhibited high reconstruction errors. The architecture of the autoencoder was tailored to the dimensions of the images under evaluation. We considered various image sizes, constructing models differently for 256x256 and 512x512 images. Moreover, the choice of the computer vision model is crucial, as most adversarial attacks are designed with specific AI structures in mind. To mitigate this, we proposed a method to replace image-specific dimensions with a structure independent of both dimensions and neural network models, thereby enhancing robustness. Our multi-modal autoencoder reconstructs the spectral representation of images across the red-green-blue (RGB) color channels. To validate our approach, we conducted experiments using diverse datasets and subjected them to adversarial attacks using models such as ResNet50 and ViT_L_16 from the torch vision library. The autoencoder extracted features used in a classification model, resulting in an MSE (RGB) of 0.014, a classification accuracy of 97.33%, and a precision of 99%.

Keywords: adversarial attacks, malicious images detector, binary classifier, multimodal transformer autoencoder

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Authors: Alan Luo, Hunter N. B. Moseley

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Many macromolecular structure entries in the Protein Data Bank (PDB) have a range of regional (localized) quality issues, be it derived from x-ray crystallography, Nuclear Magnetic Resonance (NMR) spectroscopy, or other experimental approaches. However, most PDB entries are judged by global quality metrics like R-factor, R-free, and resolution for x-ray crystallography or backbone phi-psi distribution statistics and average restraint violations for NMR. Regional quality is often ignored when PDB entries are re-used for a variety of structurally based analyses. The binding of ligands, especially ligands involved in energy metabolism, is of particular interest in many structurally focused protein studies. Using a regional quality metric that provides chemically interpretable information from electron density maps, a significant number of outliers in regional structural quality was detected across x-ray crystallographic PDB entries for proteins bound to biochemically critical ligands. In this study, a series of analyses was performed to evaluate both specific and general potential factors that could promote these outliers. In particular, these potential factors were the minimum distance to a metal ion, the minimum distance to a crystal contact, and the isotropic atomic b-factor. To evaluate these potential factors, Fisher’s exact tests were performed, using regional quality criteria of outlier (top 1%, 2.5%, 5%, or 10%) versus non-outlier compared to a potential factor metric above versus below a certain outlier cutoff. The results revealed a consistent general effect from region-specific normalized b-factors but no specific effect from metal ion contact distances and only a very weak effect from crystal contact distance as compared to the b-factor results. These findings indicate that no single specific potential factor explains a majority of the outlier ligand-bound regions, implying that human error is likely as important as these other factors. Thus, all factors, including human error, should be considered when regions of low structural quality are detected. Also, the downstream re-use of protein structures for studying ligand-bound conformations should screen the regional quality of the binding sites. Doing so prevents misinterpretation due to the presence of structural uncertainty or flaws in regions of interest.

Keywords: biomacromolecular structure, coenzyme, electron density discrepancy analysis, x-ray crystallography

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Authors: Anna-Lisa Osvalder, Jonas Borell

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There are several reasons behind the use, non-use, or inadequate use of personal protective equipment (PPE) in the construction industry. Comfort and accurate size support proper use, while discomfort, misfit, and difficulties to understand how the PPEs should be handled inhibit correct usage. The need for several protective equipments simultaneously might also create problems. The purpose of this study was to analyse the correct usage, comfort, and fit of different types of PPEs used for construction work. Correct usage was analysed as guessability, i.e., human perceptions of how to don, adjust, use, and doff the equipment, and if used as intended. The PPEs tested individually or in combinations were a helmet, ear protectors, goggles, respiratory masks, gloves, protective cloths, and safety harnesses. First, an analytical evaluation was performed with ECW (enhanced cognitive walkthrough) and PUEA (predictive use error analysis) to search for usability problems and use errors during handling and use. Then usability tests were conducted to evaluate guessability, comfort, and fit with 10 test subjects of different heights and body constitutions. The tests included observations during donning, five different outdoor work tasks, and doffing. The think-aloud method, short interviews, and subjective estimations were performed. The analytical evaluation showed that some usability problems and use errors arise during donning and doffing, but with minor severity, mostly causing discomfort. A few use errors and usability problems arose for the safety harness, especially for novices, where some could lead to a high risk of severe incidents. The usability tests showed that discomfort arose for all test subjects when using a combination of PPEs, increasing over time. For instance, goggles, together with the face mask, caused pressure, chafing at the nose, and heat rash on the face. This combination also limited sight of vision. The helmet, in combination with the goggles and ear protectors, did not fit well and caused uncomfortable pressure at the temples. No major problems were found with the individual fit of the PPEs. The ear protectors, goggles, and face masks could be adjusted for different head sizes. The guessability for how to don and wear the combination of PPE was moderate, but it took some time to adjust them for a good fit. The guessability was poor for the safety harness; few clues in the design showed how it should be donned, adjusted, or worn on the skeletal bones. Discomfort occurred when the straps were tightened too much. All straps could not be adjusted for somebody's constitutions leading to non-optimal safety. To conclude, if several types of PPEs are used together, discomfort leading to pain is likely to occur over time, which can lead to misuse, non-use, or reduced performance. If people who are not regular users should wear a safety harness correctly, the design needs to be improved for easier interpretation, correct position of the straps, and increased possibilities for individual adjustments. The results from this study can be a base for re-design ideas for PPE, especially when they should be used in combinations.

Keywords: construction work, PPE, personal protective equipment, misuse, guessability, usability

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Authors: Bolatbek Rysbaiuly, Aliya S. Azhibekova

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Problems concerning the interpretation of the well testing results belong to the class of inverse problems of subsurface hydromechanics. The distinctive feature of such problems is that additional information is depending on the capabilities of oilfield experiments. Another factor that should not be overlooked is the existence of errors in the test data. To determine reservoir properties, some inverse problems for parabolic equations were investigated. An approach to solving the inverse problems based on the method of regularization is proposed.

Keywords: iterative approach, inverse problem, parabolic equation, reservoir properties

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Authors: Feng-Ming Fan, Xiu-Hui Wen, Po-Feng Chen, Yi-Ching Tu

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Because of inborn natural conditions and man-made sabotage, the water resources insufficient phenomenon in Taiwan is a very important issue needed to face immediately. The regulations and law of water resources protection and recycling are gradually completed now but still lack of specific water recycling effectiveness checking method. The research focused on the industrial parks that already had been certificated with EIA to establish a professional checking system, carry through and forge ahead to contribute one’s bit in water resources sustainable usage. Taiwan Government Policies of Environmental Impact Assessment established in 1994, some development projects were requested to set certain water recycling ratio for water resources effective usage. The water covers and contains everything because all-inclusive companies enter and be stationed. For control the execution status of industrial park water and waste water recycling ratio about EIA commitment effectively, we invited experts and scholars in this filed to discuss with related organs to formulate the policy and audit plan. Besides, call a meeting to set public version water equilibrium diagrams and recycles parameter. We selected nine industrial parks that were requested set certain water recycling ratio in EIA examination stage and then according to the water usage quantity, we audited 340 factories in these industrial parks with spot and documents examination and got fruitful results – the average water usage of unit area per year of all these examined industrial parks is 31,000 tons/hectare/year, the value is just half of Taiwan industries average. It is obvious that the industrial parks with EIA commitment can decrease the water resources consumption effectively. Taiwan government policies of Environmental Impact Assessment took follow though tracking function into consideration at the beginning. The results of this research verify the importance of the implementing with water recycling to save water resources in EIA commitment. Inducing development units to follow EIA commitment to get the balance between environmental protection and economic development is one of the important EIA value.

Keywords: Taiwan government policies of environmental impact assessment, water recycling ratio of EIA commitment, water resources sustainable usage, water recycling

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Authors: Yung C. Lin, Kung D. Wu, Wei C. Shih, Jui P. Hung

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High speed and high precision machining have become the most important technology in manufacturing industry. The surface roughness of high precision components is regarded as the important characteristics of the product quality. However, machining chatter could damage the machined surface and restricts the process efficiency. Therefore, selection of the appropriate cutting conditions is of importance to prevent the occurrence of chatter. In addition, vibration of the spindle tool also affects the surface quality, which implies the surface precision can be controlled by monitoring the vibration of the spindle tool. Based on this concept, this study was aimed to investigate the influence of the machining conditions on the surface roughness and the vibration of the spindle tool. To this end, a series of machining tests were conducted on aluminum alloy. In tests, the vibration of the spindle tool was measured by using the acceleration sensors. The surface roughness of the machined parts was examined using white light interferometer. The response surface methodology (RSM) was employed to establish the mathematical models for predicting surface finish and tool vibration, respectively. The correlation between the surface roughness and spindle tool vibration was also analyzed by ANOVA analysis. According to the machining tests, machined surface with or without chattering was marked on the lobes diagram as the verification of the machining conditions. Using multivariable regression analysis, the mathematical models for predicting the surface roughness and tool vibrations were developed based on the machining parameters, cutting depth (a), feed rate (f) and spindle speed (s). The predicted roughness is shown to agree well with the measured roughness, an average percentage of errors of 10%. The average percentage of errors of the tool vibrations between the measurements and the predictions of mathematical model is about 7.39%. In addition, the tool vibration under various machining conditions has been found to have a positive influence on the surface roughness (r=0.78). As a conclusion from current results, the mathematical models were successfully developed for the predictions of the surface roughness and vibration level of the spindle tool under different cutting condition, which can help to select appropriate cutting parameters and to monitor the machining conditions to achieve high surface quality in milling operation.

Keywords: machining parameters, machining stability, regression analysis, surface roughness

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Authors: Raja Umer Sajjad, Chang Hee Lee

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Stormwater runoff is the leading contributor to pollution of receiving waters. In response, an efficient stormwater monitoring program is required to quantify and eventually reduce stormwater pollution. The overall goals of stormwater monitoring programs primarily include the identification of high-risk dischargers and the development of total maximum daily loads (TMDLs). The challenge in developing better monitoring program is to reduce the variability in flux estimates due to sampling errors; however, the success of monitoring program mainly depends on the accuracy of the estimates. Apart from sampling errors, manpower and budgetary constraints also influence the quality of the estimates. This study attempted to develop optimum stormwater monitoring design considering both cost and the quality of the estimated pollutants flux. Three years stormwater monitoring data (2012 – 2014) from a mix land use located within Geumhak watershed South Korea was evaluated. The regional climate is humid and precipitation is usually well distributed through the year. The investigation of a large number of water quality parameters is time-consuming and resource intensive. In order to identify a suite of easy-to-measure parameters to act as a surrogate, Principal Component Analysis (PCA) was applied. Means, standard deviations, coefficient of variation (CV) and other simple statistics were performed using multivariate statistical analysis software SPSS 22.0. The implication of sampling time on monitoring results, number of samples required during the storm event and impact of seasonal first flush were also identified. Based on the observations derived from the PCA biplot and the correlation matrix, total suspended solids (TSS) was identified as a potential surrogate for turbidity, total phosphorus and for heavy metals like lead, chromium, and copper whereas, Chemical Oxygen Demand (COD) was identified as surrogate for organic matter. The CV among different monitored water quality parameters were found higher (ranged from 3.8 to 15.5). It suggests that use of grab sampling design to estimate the mass emission rates in the study area can lead to errors due to large variability. TSS discharge load calculation error was found only 2 % with two different sample size approaches; i.e. 17 samples per storm event and equally distributed 6 samples per storm event. Both seasonal first flush and event first flush phenomena for most water quality parameters were observed in the study area. Samples taken at the initial stage of storm event generally overestimate the mass emissions; however, it was found that collecting a grab sample after initial hour of storm event more closely approximates the mean concentration of the event. It was concluded that site and regional climate specific interventions can be made to optimize the stormwater monitoring program in order to make it more effective and economical.

Keywords: first flush, pollutant load, stormwater monitoring, surrogate parameters

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Authors: Bashair Al Riyami

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Background: Acylation stimulating protein (ASP) is a small basic protein that was isolated based on its function as a potent lipogenic factor. The role of ASP in lipid metabolism has been described in numerous studies. Several association studies suggest that ASP may play a prominent role in female fat metabolism and distribution. Progesterone is established as a female lipogenic hormone, however the mechanisms by which progesterone exert its effects are not fully understood. AIM: Since ASP is an established potent lipogenic factor with a known mechanism of action, in this study we aim to investigate acute effects of different hormone treatments on ASP levels in vivo after a fat load. Methods: This is a longitudinal study including 24 female wister rats that were randomly divided into 4 groups including controls (n=6). The rats were ovariectomized, and fourteen days later the fasting rats were injected subcutaneously with a single dose of different hormone treatments (progesterone, estrogen and testosterone). An hour later, olive was administered by oral gavage, and plasma blood samples were collected at several time points after oil administration for ASP and triglyceride measurements. Area under the curve (TG-AUC) was calculated to represent TG clearance Results: RM-ANCOVA and post-analysis showed that only the progesterone treated group had a significant postprandial ASP increase at two hours compared to basal levels and to the controls (439.8± 62.4 vs 253.45± 59.03 ug/ml), P= 0.04. Interestingly, increased postprandial ASP levels coordinated negatively with corresponding TG levels and TG-AUC across the postprandial period most apparent in the progesterone and testosterone treated groups that behaved in an opposite manner. ASP levels were 3-fold higher in the progesterone compared to the testosterone treated group, whereas TG-AUC was significantly lower in the progesterone treated group compared to the testosterone treated group. Conclusion: These findings suggest that progesterone treatment enhances ASP production and TG clearance in a simultaneous manner. The strong association of postprandial ASP levels and TG clearance in the progesterone treated group support the notion of a stimulatory role for progesterone on ASP mediated TG clearance. This is the first functional study to demonstrate a cause-effect relationship between hormone treatment and ASP levels in vivo. These findings are promising and may contribute to further understanding the mechanism of progesterone function as a female lipogenic hormone through enhancing ASP production and plasma levels.

Keywords: ASP, lipids, sex hormones, wister rats

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Authors: Ei Ei Hlaing, Narissara Lailerd, Sittiruk Roytrakul, Pichapat Piamrojanaphat

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Type 2 diabetes is one of the most common metabolic diseases all over the world. The pathogenesis of type 2 diabetes is not the only dysfunction of pancreatic beta cells but also insulin resistance in muscle, liver and adipose tissue. High levels of circulating free fatty acids, an increased lipid content of muscle cells, impaired insulin-mediated glucose uptake and diminished mitochondrial functioning are pathophysiological hallmarks of diabetic skeletal muscles. Purple rice (Oryza sativa L. indica) has been shown to have antidiabetic effects. However, the underlying mechanism(s) of antidiabetic activity of purple rice is still unraveled. In this research, to explore in-depth cellular mechanism(s), proteomic profile of purple rice supplemented type 2 diabetic rats’ skeletal muscle were analyzed contract with non-supplemented rats. Diabetic rats were induced high-fat diet combined with streptozotocin injection. By using one- dimensional gel electrophoresis (1-DE) and LC-MS/MS quantitative proteomic method, we analyzed proteomic profiles in skeletal muscle of normal rats, normal rats with purple rice supplementation, type 2 diabetic rats, and type 2 diabetic rats with purple rice supplementation. Total 2676 polypeptide expressions were identified. Among them, 24 peptides were only expressed in type 2 diabetic rats, and 24 peptides were unique peptides in type 2 diabetic rats with purple rice supplementation. Acetyl CoA carboxylase 1 (ACACA) found as unique protein in type 2 diabetic rats which is the major enzyme in lipid synthesis and metabolism. Interestingly, DNA damage response protein, heterogeneous nuclear ribonucleoprotein K [Mus musculus] (Hnrnpk), was upregulated in type 2 diabetic rats’ skeletal muscle. Meanwhile, unique proteins of type 2 diabetic rats with purple rice supplementation (bone morphogenetic 7 protein preproprotein, BMP7; and forkhead box protein NX4, Foxn4) involved with muscle cells growth through the regulation of TGF-β/Smad signaling network. Moreover, BMP7 may effect on insulin signaling through the downstream signaling of protein kinase B (Akt) which acts in protein synthesis, glucose uptake, and glycogen synthesis. In conclusion, our study supports that type 2 diabetes impairs muscular lipid metabolism. In addition, purple rice might recover the muscle cells growth and insulin signaling.

Keywords: proteomics, purple rice bran, skeletal muscle, type 2 diabetic rats

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Authors: Christine Y. Yeh, Brian D. Piening, Sarah M. Totten, Kimberly Kukurba, Wenyu Zhou, Kevin P. F. Contrepois, Gucci J. Gu, Sharon Pitteri, Michael Snyder

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Three million deaths worldwide are attributed to obesity. However, the biomolecular mechanisms that describe the link between adiposity and subsequent disease states are poorly understood. Insulin resistance characterizes approximately half of obese individuals and is a major cause of obesity-mediated diseases such as Type II diabetes, hypertension and other cardiovascular diseases. This study makes use of longitudinal quantitative and high-throughput multi-omics (genomics, epigenomics, transcriptomics, glycoproteomics etc.) methodologies on blood samples to develop multigenic and multi-analyte signatures associated with weight gain and insulin resistance. Participants of this study underwent a 30-day period of weight gain via excessive caloric intake followed by a 60-day period of restricted dieting and return to baseline weight. Blood samples were taken at three different time points per patient: baseline, peak-weight and post weight loss. Patients were characterized as either insulin resistant (IR) or insulin sensitive (IS) before having their samples processed via longitudinal multi-omic technologies. This comparative study revealed a wealth of biomolecular changes associated with weight gain after using methods in machine learning, clustering, network analysis etc. Pathways of interest included those involved in lipid remodeling, acute inflammatory response and glucose metabolism. Some of these biomolecules returned to baseline levels as the patient returned to normal weight whilst some remained elevated. IR patients exhibited key differences in inflammatory response regulation in comparison to IS patients at all time points. These signatures suggest differential metabolism and inflammatory pathways between IR and IS patients. Biomolecular differences associated with weight gain and insulin resistance were identified on various levels: in gene expression, epigenetic change, transcriptional regulation and glycosylation. This study was not only able to contribute to new biology that could be of use in preventing or predicting obesity-mediated diseases, but also matured novel biomedical informatics technologies to produce and process data on many comprehensive omics levels.

Keywords: insulin resistance, multi-omics, next generation sequencing, proteogenomics, type ii diabetes

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Authors: Mustafa Metin Donma, Orkide Donma

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Obesity is a disease with an ever-increasing prevalence throughout the world. The metabolic network associated with obesity is very complicated. In metabolic syndrome (MetS), it becomes even more difficult to understand. Within this context, hormones, cytokines, and many others participate in this complex matrix. The collaboration among all of these parameters is a matter of great wonder. Cortisol, as a stress hormone, is closely associated with obesity. Thyroid hormones are involved in the regulation of energy as well as glucose metabolism with all of its associates. Fetuin A is known for years; however, the involvement of this parameter in obesity discussions is rather new. Recently, it has been defined as one of the new generation markers of obesity. In this study, the aim was to introduce complex interactions among all to be able to make clear comparisons, at least for a part of this complicated matter. Morbid obese (MO) children participated in the study. Two groups with 46 MO children and 43 with MetS were constituted. All children included in the study were above 99th age- and sex-adjusted body mass index (BMI) percentiles according to World Health Organization criteria. Forty-three morbid obese children in the second group had also MetS components. Informed consent forms were filled by the parents of the participants. The institutional ethics committee has given approval for the study protocol. Data as well as the findings of the study were evaluated from a statistical point of view. Two groups were matched for their age and gender compositions. Significantly higher body mass index (BMI), waist circumference, thyrotropin, and insulin values were observed in the MetS group. Triiodothyronine concentrations did not differ between the groups. Elevated levels for thyroxin, cortisol, and fetuin-A were detected in the MetS group compared to the first group (p > 0.05). In MO MetS- group, cortisol was correlated with thyroxin and fetuin-A (p < 0.05). In the MO MetS+ group, none of these correlations were present. Instead, a correlation between cortisol and thyrotropin was found (p < 0.05). In conclusion, findings have shown that cortisol was the key player in severely obese children. The association of this hormone with the participants of thyroid hormone metabolism was quite important. The lack of association with fetuin A in the morbid obese MetS+ group has suggested the possible interference of MetS components in the behavior of this new generation obesity marker. The most remarkable finding of the study was the unique correlation between cortisol and thyrotropin in the morbid obese MetS+ group, suggesting that thyrotropin may serve as a target along with cortisol in the morbid obese MetS+ group. This association may deserve specific attention during the development of remedies against MetS in the pediatric population.

Keywords: children, cortisol, fetuin A, morbid obesity, thyrotropin

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Authors: Aidin Foroutan, David S. Wishart, Leluo L. Guan, Carolyn Fitzsimmons

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Maximizing efficiency and growth potential of beef cattle requires not only genetic selection (i.e. residual feed intake (RFI)) but also adequate nutrition throughout all stages of growth and development. Nutrient restriction during gestation has been shown to negatively affect post-natal growth and development as well as fertility of the offspring. This, when combined with RFI may affect progeny traits. This study aims to investigate the impact of selection for divergent genetic potential for RFI and maternal nutrition during early- to mid-gestation, on bull calf traits such as fertility and muscle development using multiple ‘omics’ approaches. Comparisons were made between High-diet vs. Low-diet and between High-RFI vs. Low-RFI animals. An epigenetics experiment on semen samples identified 891 biomarkers associated with growth and development. A gene expression study on Longissimus thoracis muscle, semimembranosus muscle, liver, and testis identified 4 genes associated with muscle development and immunity of which Myocyte enhancer factor 2A [MEF2A; induces myogenesis and control muscle differentiation] was the only differentially expressed gene identified in all four tissues. An initial metabolomics experiment on serum samples using nuclear magnetic resonance (NMR) identified 4 metabolite biomarkers related to energy and protein metabolism. Once all the biomarkers are identified, bioinformatics approaches will be used to create a database covering all the ‘omics’ data collected from this project. This database will be broadened by adding other information obtained from relevant literature reviews. Association analyses with these data sets will be performed to reveal key biological pathways affected by RFI and maternal nutrition. Through these association studies between the genome and metabolome, it is expected that candidate biomarker genes and metabolites for feed efficiency, fertility, and/or muscle development are identified. If these gene/metabolite biomarkers are validated in a larger animal population, they could potentially be used in breeding programs to select superior animals. It is also expected that this work will lead to the development of an online tool that could be used to predict future traits of interest in an animal given its measurable ‘omics’ traits.

Keywords: biomarker, maternal nutrition, omics, residual feed intake

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Authors: Bojana Ž. Bajić, Siniša N. Dodić, Vladimir S. Puškaš, Jelena M. Dodić

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Increasing industrialization as a response to the demands of the consumer society greatly exploits resources and generates large amounts of waste effluents in addition to the desired product. This means it is a priority to implement technologies with the maximum utilization of raw materials and energy, minimum generation of waste effluents and/or their recycling (secondary use). Considering the process conditions and the nature of the raw materials used by the vegetable oil industry, its wastewaters can be used as substrates for the biotechnological production which requires large amounts of water. This way the waste effluents of one branch of industry become raw materials for another branch which produces a new product while reducing wastewater pollution and thereby reducing negative environmental impacts. Vegetable oil production generates wastewaters during the process of rinsing oils and fats which contain mainly fatty acid pollutants. The vegetable oil industry generates large amounts of waste effluents, especially in the processes of degumming, deacidification, deodorization and neutralization. Wastewaters from the vegetable oil industry are generated during the whole year in significant amounts, based on the capacity of the vegetable oil production. There are no known alternative applications for these wastewaters as raw materials for the production of marketable products. Since the literature has no data on the potential negative impact of fatty acids on the metabolism of the bacterium Xanthomonas campestris, these wastewaters were considered as potential raw materials for the biotechnological production of xanthan. In this research, vegetable oil industry wastewaters were used as the basis for the cultivation media for xanthan production with Xanthomonas campestris ATCC 13951. Examining the process of biosynthesis of xanthan on vegetable oil industry wastewaters as the basis for the cultivation media was performed to obtain insight into the possibility of its use in the aforementioned biotechnological process. Additionally, it was important to experimentally determine the absence of substances that have an inhibitory effect on the metabolism of the production microorganism. Xanthan content, rheological parameters of the cultivation media, carbon conversion into xanthan and conversions of the most significant nutrients for biosynthesis (carbon, nitrogen and phosphorus sources) were determined as indicators of the success of biosynthesis. The obtained results show that biotechnological production of the biopolymer xanthan by bacterium Xanthomonas campestris on vegetable oil industry wastewaters based cultivation media simultaneously provides preservation of the environment and economic benefits which is a sustainable solution to the problem of wastewater treatment.

Keywords: biotechnology, sustainable bioprocess, vegetable oil industry wastewaters, Xanthomonas campestris

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Authors: Xin Wang, Munkbayar Munkhjargal, Kumiko Miyajima, Takahiro Arakawa, Kohji Mitsubayashi

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The measurement of gaseous ethanol plays an important role of evaluation of alcohol metabolic capacity in clinical and forensic analysis. A 2-dimensional visualization system for gaseous ethanol was constructed and tested in visualization of breath and transdermal alcohol. We demonstrated breath ethanol measurement using developed high-sensitive visualization system. The concentration of breath ethanol calculated with the imaging signal was significantly different between the volunteer subjects of ALDH2 (+) and (-).

Keywords: breath ethanol, ethnaol imaging, biochemical luminescence, alcohol metabolism

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Authors: Tammeen Siraj, Wenxing Zhou, Terry Huang, Mohammad Al-Amin

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The high resolution inline inspection (ILI) tool is used extensively in the pipeline industry to identify, locate, and measure metal-loss corrosion anomalies on buried oil and gas steel pipelines. Corrosion anomalies may occur singly (i.e. individual anomalies) or as clusters (i.e. a colony of corrosion anomalies). Although the ILI technology has advanced immensely, there are measurement errors associated with the sizes of corrosion anomalies reported by ILI tools due limitations of the tools and associated sizing algorithms, and detection threshold of the tools (i.e. the minimum detectable feature dimension). Quantifying the measurement error in the ILI data is crucial for corrosion management and developing maintenance strategies that satisfy the safety and economic constraints. Studies on the measurement error associated with the length of the corrosion anomalies (in the longitudinal direction of the pipeline) has been scarcely reported in the literature and will be investigated in the present study. Limitations in the ILI tool and clustering process can sometimes cause clustering error, which is defined as the error introduced during the clustering process by including or excluding a single or group of anomalies in or from a cluster. Clustering error has been found to be one of the biggest contributory factors for relatively high uncertainties associated with ILI reported anomaly length. As such, this study focuses on developing a consistent and comprehensive framework to quantify the measurement errors in the ILI-reported anomaly length by comparing the ILI data and corresponding field measurements for individual and clustered corrosion anomalies. The analysis carried out in this study is based on the ILI and field measurement data for a set of anomalies collected from two segments of a buried natural gas pipeline currently in service in Alberta, Canada. Data analyses showed that the measurement error associated with the ILI-reported length of the anomalies without clustering error, denoted as Type I anomalies is markedly less than that for anomalies with clustering error, denoted as Type II anomalies. A methodology employing data mining techniques is further proposed to classify the Type I and Type II anomalies based on the ILI-reported corrosion anomaly information.

Keywords: clustered corrosion anomaly, corrosion anomaly assessment, corrosion anomaly length, individual corrosion anomaly, metal-loss corrosion, oil and gas steel pipeline

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Authors: Begum Rokeya, Rahelee Zinnat, Fatema Jebunnesa, Israt Ara Hossain, A. Rahman

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Background and Aims: Arsenic in drinking water is a global environmental health problem, and the exposure may increase dyslipidemia and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of lipid metabolism, atherosclerosis formation, arsenic exposure and impact in pregnancy is still unclear. Recent epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and Dyslipidemia. However, the exact mechanism of this arsenic-mediated increase in atherosclerosis risk factors remains enigmatic. We explore the association of the effect of arsenic on serum lipid profile in pregnant subjects. Methods: A total 200 pregnant mother screened in this study from arsenic exposed area. Our study group included 100 exposed subjects were cases and 100 Non exposed healthy pregnant were controls requited by a cross-sectional study. Clinical and anthropometric measurements were done by standard techniques. Lipidemic status was assessed by enzymatic endpoint method. Urinary As was measured by inductively coupled plasma-mass spectrometry and adjusted with specific gravity and Arsenic exposure was assessed by the level of urinary arsenic level > 100 μg/L was categorized as arsenic exposed and < 100 μg/L were categorized as non-exposed. Multivariate logistic regression and Student’s t - test was used for statistical analysis. Results: Systolic and diastolic blood pressure both were significantly higher in the Arsenic exposed pregnant subjects compared to the Non-exposed group (p<0.001). Arsenic exposed subjects had 2 times higher chance of developing hypertensive pregnancy (Odds Ratio 2.2). In parallel to the findings in Ar exposed subjects showed significantly higher proportion of triglyceride and total cholesterol and low density of lipo protein when compare to non- arsenic exposed pregnant subjects. Significant correlation of urinary arsenic level was also found with SBP, DBP, TG, T chol and serum LDL-Cholesterol. On multivariate logistic regression showed urinary arsenic had a positive association with DBP, SBP, Triglyceride and LDL-c. Conclusion: In conclusion, arsenic exposure may induce dyslipidemia like atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element.

Keywords: Arsenic Exposure, Dyslipidemia, Gestational Diabetes Mellitus, Serum lipid profile

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Authors: Nurdan Olguncelik Kaplan, Aysen Akay

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Nowadays soil pollution has become a global problem. External added polluters to the soil are destroying and changing the structure of the soil and the problems are becoming more complex and in this sense the correction of these problems is going to be harder and more costly. Cadmium has got a fast mobility in the soil and plant system because of that cadmium can interfere very easily to the human and animal food chain and in the same time this can be very dangerous. The cadmium which is absorbed and stored by the plants is causing to many metabolic changes of the plants like; protein synthesis, nitrogen and carbohydrate metabolism, enzyme (nitrate reductase) activation, photo and chlorophyll synthesis. The biological function of cadmium is not known over the plants and it is not a necessary element. The plant is generally taking in small amounts the cadmium and this element is competing with the zinc. Cadmium is causing root damages. Buckwheat (Fagopyrum esculentum) is an important nutraceutical because of its high content of flavonoids, minerals and vitamins, and their nutritionally balanced amino-acid composition. Buckwheat has relatively high biomass productivity, is adapted to many areas of the world, and can flourish in sterile fields; therefore buckwheat plants are widely used for the phytoremediation process.The aim of this study were to evaluate the phytoremediation capacity of the high-yielding plant Buckwheat (Fagopyrum esculentum) in soils contaminated with Cd and Zn. The soils were applied to differrent doses cd(0-12.5-25-50-100 mg Cd kg−1 soil in the form of 3CdSO4.8H2O ) and Zn (0-10-30 mg Zn kg−1 soil in the form of ZnSO4.7H2O) and incubated about 60 days. Later buckwheat seeds were sown and grown for three mounth under greenhouse conditions. The test plants were irrigated by using pure water after the planting process. Buckwheat seeds (Gunes and Aktas species) were taken from Bahri Dagdas International Agricultural Research. After harvest, Cd and Zn concentrations of plant biomass and grain, yield and translocation factors (TFs) for Cd and Cd were determined. Cadmium accumulation in biomass and grain significantly increased in dose-dependent manner. Long term field trials are required to further investigate the potential of buckwheat to reclaimed the soil. But this could be undertaken in conjunction with actual remediation schemes. However, the differences in element accumulation among the genotypes were affected more by the properties of genotypes than by the soil properties. Gunes genotype accumulated higher lead than Aktas genotypes.

Keywords: buckwheat, cadmium, phytoremediation, zinc

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Authors: Michal Pravenec, Miroslava Simakova, Jan Silhavy

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Brown adipose tissue (BAT) plays an important role in lipid and glucose metabolism in rodents and possibly also in humans. Recently, using systems genetics approach in the BAT from BXH/HXB recombinant inbred strains, derived from the SHR (spontaneously hypertensive rat) and BN (Brown Norway) progenitors, we identified Cd36 (fatty acid translocase) as the hub gene of co-expression module associated with BAT relative weight and function. An important aspect of BAT biology is to better understand the mechanisms regulating the uptake and utilization of fatty acids and glucose. Accordingly, BAT function in the SHR that harbors mutant nonfunctional Cd36 variant (hereafter referred to as SHR-Cd36⁻/⁻) was compared with SHR transgenic line expressing wild type Cd36 under control of a universal promoter (hereafter referred to as SHR-Cd36⁺/⁺). BAT was incubated in media containing insulin and 14C-U-glucose alone or 14C-U-glucose together with palmitate. Incorporation of glucose into BAT lipids was significantly higher in SHR-Cd36⁺/⁺ versus SHR-Cd36⁻/⁻ rats when incubation media contained glucose alone (SHR-Cd36⁻/⁻ 591 ± 75 vs. SHR-Cd36⁺/⁺ 1036 ± 135 nmol/gl./2h; P < 0.005). Adding palmitate into incubation media had no effect in SHR-Cd36⁻/⁻ rats but significantly reduced glucose incorporation into BAT lipids in SHR-Cd36⁺/⁺ (SHR-Cd36⁻/⁻ 543 ± 55 vs. SHR-Cd36⁺/⁺ 766 ± 75 nmol/gl./2h; P < 0.05 denotes significant Cd36 x palmitate interaction determined by two-way ANOVA). This Cd36-dependent reduced glucose uptake in SHR-Cd36⁺/⁺ BAT was likely secondary to increased palmitate incorporation and utilization due to the presence of wild type Cd36 fatty acid translocase in transgenic rats. This possibility is supported by increased incorporation of 14C-U-palmitate into BAT lipids in the presence of both palmitate and glucose in incubation media (palmitate alone: SHR-Cd36⁻/⁻ 870 ± 21 vs. SHR-Cd36⁺/⁺ 899 ± 42; glucose+palmitate: SHR-Cd36⁻/⁻ 899 ± 47 vs. SHR-Cd36⁺/⁺ 1460 ± 111 nmol/palm./2h; P < 0.05 denotes significant Cd36 x glucose interaction determined by two-way ANOVA). It is possible that addition of glucose into the incubation media increased palmitate incorporation into BAT lipids in SHR-Cd36⁺/⁺ rats because of glucose availability for glycerol phosphate production and increased triglyceride synthesis. These changes in glucose and palmitate incorporation into BAT lipids were associated with significant differential expression of Irs1, Irs2, Slc2a4 and Foxo1 genes involved in insulin signaling and glucose metabolism only in SHR-Cd36⁺/⁺ rats which suggests Cd36-dependent effects on insulin action. In conclusion, these results provide compelling evidence that Cd36 plays an important role in BAT insulin signaling and energy substrate utilization.

Keywords: brown adipose tissue, Cd36, energy substrate utilization, insulin signaling, spontaneously hypertensive rat

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Authors: Alina Muradyan, Lina Babayan, Arsen Nanyan, Gohar Galstyan, Vigen Khachatryan

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We present a photometric method for identifying stars, galaxies and quasars in multi-color surveys, which uses a library of ∼> 65000 color templates for comparison with observed objects. The method aims for extracting the information content of object colors in a statistically correct way, and performs a classification as well as a redshift estimation for galaxies and quasars in a unified approach based on the same probability density functions. For the redshift estimation, we employ an advanced version of the Minimum Error Variance estimator which determines the redshift error from the redshift dependent probability density function itself. The method was originally developed for the Calar Alto Deep Imaging Survey (CADIS), but is now used in a wide variety of survey projects. We checked its performance by spectroscopy of CADIS objects, where the method provides high reliability (6 errors among 151 objects with R < 24), especially for the quasar selection, and redshifts accurate within σz ≈ 0.03 for galaxies and σz ≈ 0.1 for quasars. For an optimization of future survey efforts, a few model surveys are compared, which are designed to use the same total amount of telescope time but different sets of broad-band and medium-band filters. Their performance is investigated by Monte-Carlo simulations as well as by analytic evaluation in terms of classification and redshift estimation. If photon noise were the only error source, broad-band surveys and medium-band surveys should perform equally well, as long as they provide the same spectral coverage. In practice, medium-band surveys show superior performance due to their higher tolerance for calibration errors and cosmic variance. Finally, we discuss the relevance of color calibration and derive important conclusions for the issues of library design and choice of filters. The calibration accuracy poses strong constraints on an accurate classification, which are most critical for surveys with few, broad and deeply exposed filters, but less severe for surveys with many, narrow and less deep filters.

Keywords: VO, ArVO, DFBS, FITS, image processing, data analysis

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Authors: Tareg Belali, Mosleh Abomughaid, Muhanad Alhujaily

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HNF4a is one of the steroid hormone receptor family of transcription factors with roles in the development of the liver and the regulation of several critical metabolic pathways, such as glycolysis, drug metabolism, and apolipoproteins and blood coagulation. The transcriptional potency of HNF4a is well known due to its involvement in diabetes and other metabolic diseases. However, recently HNF4a has been discovered to be closely associated with several haematological disorders, mainly because of genetic mutations, drugs, and hepatic disorders. We review HNF4a structure and function and its role in haematological disorders. We discuss possible good therapies that are based on targeting HNF4a.

Keywords: hepatocyte nuclear factor 4 alpha, HNF4a nuclear receptor, steroid hormone receptor family of transcription factors, hematological disorders

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Authors: Apurva Gupta, Surendra Singh

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Spirulina spp., as a promising source of many commercially valuable products, is grown photo autotrophically in open ponds and raceways on a large scale. However, the economic exploitation in an open system seems to have been limited because of lack of multiple stress-tolerant strains. The present study aims to isolate a stable stress tolerant mutant of Spirulina platensis with improved growth rate and enhanced potential to produce its commercially valuable bioactive compounds. N-methyl-n'-nitro-n-nitrosoguanidine (NTG) at 250 μg/mL (concentration permitted 1% survival) was employed for chemical mutagenesis to generate random mutants and screened against NaCl. In a preliminary experiment, wild type S. platensis was treated with NaCl concentrations from 0.5-1.5 M to calculate its LC₅₀. Mutagenized colonies were then screened for tolerance at 0.8 M NaCl (LC₅₀), and the surviving colonies were designated as NaCl tolerant mutants of S. platensis. The mutant cells exhibited 1.5 times improved growth against NaCl stress as compared to the wild type strain in control conditions. This might be due to the ability of the mutant cells to protect its metabolic machinery against inhibitory effects of salt stress. Salt stress is known to adversely affect the rate of photosynthesis in cyanobacteria by causing degradation of the pigments. Interestingly, the mutant cells were able to protect its photosynthetic machinery and exhibited 4.23 and 1.72 times enhanced accumulation of Chl a and phycobiliproteins, respectively, which resulted in enhanced rate of photosynthesis (2.43 times) and respiration (1.38 times) against salt stress. Phycocyanin production in mutant cells was observed to enhance by 1.63 fold. Nitrogen metabolism plays a vital role in conferring halotolerance to cyanobacterial cells by influx of nitrate and efflux of Na+ ions from the cell. The NaCl tolerant mutant cells took up 2.29 times more nitrate as compared to the wild type and efficiently reduce it. Nitrate reductase and nitrite reductase activity in the mutant cells also improved by 2.45 and 2.31 times, respectively against salt stress. From these preliminary results, it could be deduced that enhanced nitrogen uptake and its efficient reduction might be a reason for adaptive and halotolerant behavior of the S. platensis mutant cells. Also, the NaCl tolerant mutant of S. platensis with significant improved growth and phycocyanin accumulation compared to the wild type can be commercially promising.

Keywords: chemical mutagenesis, NaCl tolerant mutant, nitrogen metabolism, photosynthetic machinery, phycocyanin

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Authors: Leonid Zhukov, Dmytro Petrenko

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Optical thermometry has no alternative in many cases of industrial most effective continuous temperature control. Classical optical thermometry technologies can be used on available for pyrometers controlled objects with stable radiation characteristics and transmissivity of the intermediate medium. Without using temperature corrections, it is possible in the case of a “black” body for energy pyrometry and the cases of “black” and “grey” bodies for spectral ratio pyrometry or with using corrections – for any colored bodies. Consequently, with increasing the number of operating waves, optical thermometry possibilities to reduce methodical errors significantly expand. That is why, in recent 25-30 years, research works have been reoriented on more perfect spectral (multicolor) thermometry technologies. There are two physical material substances, i.e., substance (controlled object) and electromagnetic field (thermal radiation), to be operated in optical thermometry. Heat is transferred by radiation; therefore, radiation has the energy, entropy, and temperature. Optical thermometry was originating simultaneously with the developing of thermal radiation theory when the concept and the term "radiation temperature" was not used, and therefore concepts and terms "conditional temperatures" or "pseudo temperature" of controlled objects were introduced. They do not correspond to the physical sense and definitions of temperature in thermodynamics, molecular-kinetic theory, and statistical physics. Launched by the scientific thermometric society, discussion about the possibilities of temperature measurements of objects, including colored bodies, using the temperatures of their radiation is not finished. Are the information about controlled objects transferred by their radiation enough for temperature measurements? The positive and negative answers on this fundamental question divided experts into two opposite camps. Recent achievements of spectral thermometry develop events in her favour and don’t leave any hope for skeptics. This article presents the results of investigations and developments in the field of spectral thermometry carried out by the authors in the Department of Thermometry and Physics-Chemical Investigations. The authors have many-year’s of experience in the field of modern optical thermometry technologies. Innovative technologies of optical continuous temperature control have been developed: symmetric-wave, two-color compensative, and based on obtained nonlinearity equation of spectral emissivity distribution linear, two-range, and parabolic. Тhe technologies are based on direct measurements of physically substantiated and proposed by Prof. L. Zhukov, radiation temperatures with the next calculation of the controlled object temperature using this radiation temperatures and corresponding mathematical models. Тhe technologies significantly increase metrological characteristics of continuous contactless and light-guide temperature control in energy, metallurgical, ceramic, glassy, and other productions. For example, under the same conditions, the methodical errors of proposed technologies are less than the errors of known spectral and classical technologies in 2 and 3-13 times, respectively. Innovative technologies provide quality products obtaining at the lowest possible resource-including energy costs. More than 600 publications have been published on the completed developments, including more than 100 domestic patents, as well as 34 patents in Australia, Bulgaria, Germany, France, Canada, the USA, Sweden, and Japan. The developments have been implemented in the enterprises of USA, as well as Western Europe and Asia, including Germany and Japan.

Keywords: emissivity, radiation temperature, object temperature, spectral thermometry

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Authors: Alicia C. Sanchez

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This paper investigates the implementation of RAFU functions (radical functions) in robotics and automation. Specifically, the main goal is to show how these functions may be useful in lane-keeping control and the lateral control of autonomous machines, vehicles, robots or the like. From the knowledge of several points of a certain route, the RAFU functions are used to achieve the lateral control purpose and maintain the lane-keeping errors within the fixed limits. The stability that these functions provide, their ease of approaching any continuous trajectory and the control of the possible error made on the approximation may be useful in practice.

Keywords: automatic navigation control, lateral control, lane-keeping control, RAFU approximation

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Authors: S. Thomet, S. De-Paoli, F. Ghaffari, J. M. Daveau, P. Roche, O. Romain

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In this paper, we present a hardware module dedicated to understanding the fail reason of a System on Chip (SoC) exposed to a particle beam. Impact of Single-Event Effects (SEE) on processor-based SoCs is a concern that has increased in the past decade, particularly for terrestrial applications with automotive safety increasing requirements, as well as consumer and industrial domains. The SEE created by the impact of a particle on an SoC may have consequences that can end to instability or crashes. Specific hardening techniques for hardware and software have been developed to make such systems more reliable. SoC is then qualified using cosmic ray Accelerated Soft-Error Rate (ASER) to ensure the Soft-Error Rate (SER) remains in mission profiles. Understanding where errors are occurring is another challenge because of the complexity of operations performed in an SoC. Common techniques to monitor an SoC running under a beam are based on non-intrusive debug, consisting of recording the program counter and doing some consistency checking on the fly. To detect and understand SEE, we have developed a module embedded within the SoC that provide support for recording probes, hardware watchpoints, and a memory mapped register bank dedicated to software usage. To identify CPU failure modes and the most important resources to probe, we have carried out a fault injection campaign on the RTL model of the SoC. Probes are placed on generic CPU registers and bus accesses. They highlight the propagation of errors and allow identifying the failure modes. Typical resulting errors are bit-flips in resources creating bad addresses, illegal instructions, longer than expected loops, or incorrect bus accesses. Although our module is processor agnostic, it has been interfaced to a RISC-V by probing some of the processor registers. Probes are then recorded in a ring buffer. Associated hardware watchpoints are allowing to do some control, such as start or stop event recording or halt the processor. Finally, the module is also providing a bank of registers where the firmware running on the SoC can log information. Typical usage is for operating system context switch recording. The module is connected to a dedicated debug bus and is interfaced to a remote controller via a debugger link. Thus, a remote controller can interact with the monitoring module without any intrusiveness on the SoC. Moreover, in case of CPU unresponsiveness, or system-bus stall, the recorded information can still be recovered, providing the fail reason. A preliminary version of the module has been integrated into a test chip currently being manufactured at ST in 28-nm FDSOI technology. The module has been triplicated to provide reliable information on the SoC behavior. As the primary application domain is automotive and safety, the efficiency of the module will be evaluated by exposing the test chip under a fast-neutron beam by the end of the year. In the meantime, it will be tested with alpha particles and electromagnetic fault injection (EMFI). We will report in the paper on fault-injection results as well as irradiation results.

Keywords: fault injection, SoC fail reason, SoC soft error rate, terrestrial application

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Authors: Felipe Villegas-Velasquez, Harold Pantoja-Villota, Sergio Holguin-Cardona, Alejandro Osorio-Botero, Brayan Candamil-Arango

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Colombian electricity comes mainly from hydric resources, affected by environmental variations such as the El Niño phenomenon. That is why incorporating other types of resources is necessary to provide electricity constantly. This research seeks to fill the wind speed and global solar irradiance dataset for two years with the highest amount of information. A further result is the characterization of the data by region that led to infer which errors occurred and offered the incomplete dataset.

Keywords: energy, wind speed, global solar irradiance, Colombia, imputation

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Authors: Hsiang-Ru Lin

Abstract:

Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Jaehoon Ha, Byungmo Kang, Kilho Hong, Jungsoo Park

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Electro-optical (EO) stabilized platforms have been widely used for surveillance and reconnaissance on various types of vehicles, from surface ships to unmanned air vehicles (UAVs). EO stabilized platforms usually consist of an assembly of structure, bearings, and motors called gimbals in which a gyroscope is installed. EO elements such as a CCD camera and IR camera, are mounted to a gimbal, which has a range of motion in elevation and azimuth and can designate and track a target. In addition, a laser range finder (LRF) can be added to the gimbal in order to acquire the precise slant range from the platform to the target. Recently, a versatile functionality of target localization is needed in order to cooperate with the weapon systems that are mounted on the same platform. The target information, such as its location or velocity, needed to be more accurate. The accuracy of the target information depends on diverse component errors and alignment errors of each component. Specially, the type of moving platform can affect the accuracy of the target information. In the case of flying platforms, or UAVs, the target location error can be increased with altitude so it is important to measure altitude as precisely as possible. In the case of surface ships, target location error can be increased with obliqueness of the elevation angle of the gimbal since the altitude of the EO stabilized platform is supposed to be relatively low. The farther the slant ranges from the surface ship to the target, the more extreme the obliqueness of the elevation angle. This can hamper the precise acquisition of the target information. So far, there have been many studies on EO stabilized platforms of flying vehicles. However, few researchers have focused on ship-borne EO stabilized platforms of the surface ship. In this paper, we deal with a target localization method when an EO stabilized platform is located on the mast of a surface ship. Especially, we need to overcome the limitation caused by the obliqueness of the elevation angle of the gimbal. We introduce a well-known approach for target localization using Unscented Kalman Filter (UKF) and present the problem definition showing the above-mentioned limitation. Finally, we want to show the effectiveness of the approach that will be demonstrated through computer simulations.

Keywords: target localization, ship-borne electro-optical stabilized platform, unscented kalman filter

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Authors: Milijana N. Miljkovic, Viktorija M. Dragojevic-Simic, Nemanja K. Rancic, Vesna M. Jacevic, Snezana B. Djordjevic, Momir M. Mikov, Aleksandra M. Kovacevic

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Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent.

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

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