Search results for: protein profile

Authors: M. Kamimukai, M. Bhattarai, B. B. Rana, K. Maeda, H. B. Kc, T. Kawano, M. Murai

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Most of the aged people older than 70 have difficulty in chewing and swallowing more or less. According to magnitude of this difficulty, gruel, “nanhan” (semi-soft rice) and ordinary cooked rice are served in general, particularly in sanatoriums and homes for old people in Japan. Nanhan is the name of a cooked rice used in Japan, having softness intermediate between gruel and ordinary cooked rice, which is boiled with intermediate amount of water between those of the latter two kinds of cooked rice. In the present study, nanhan was made in the rate of 240g of water to 100g of milled rice with an electric rice cooker. Murai developed a high amylose-content and high-yielding elite line ‘Murai 79’. Sensory eating-quality test was performed for nanhan and ordinary cooked rice of Murai 79 and the standard variety ‘Hinohikari’ which is a high eating-quality variety representative in southern Japan. Panelists (6 to 14 persons) scored each cooked rice in six items viz. taste, stickiness, hardness, flavor, external appearance and overall evaluation. Grading (-3 ~ +3) in each trait was performed, regarding the value of the standard variety Hinohikari as 0. Paddy rice produced in a farmer’s field in 2013 and 2014 and in an experimental field of Kochi University in 2015 and 2016 were used for the sensory test. According to results of the sensory eating-quality test for nanhan, Murai 79 is higher in overall evaluation than Hinohikari in the four years. The former was less sticky than the latter in the four years, but the former was statistically significantly harder than the latter throughout the four years. In external appearance, the former was significantly higher than the latter in the four years. In the taste, the former was significantly higher than the latter in 2014, but significant difference was not noticed between them in the other three years. There were no significant differences throughout the four years in flavor. Regarding amylose content, Murai 79 is higher by 3.7 and 5.7% than Hinohikari in 2015 and 2016, respectively. As for protein content, Murai 79 was higher than Hinohikari in 2015, but the former was lower than the latter in 2016. Consequently, the nanhan of Murai 79 was harder and less sticky, keeping the shape of grains as compared with that of Hinohikari, which may be due to its higher amylose content. Hence, the nanhan of Murai 79 may be recognized as grains more easily in a human mouth, which could make easier the continuous performance of mastication and deglutition particularly in aged persons. Regarding ordinary cooked rice, Murai 79 was similar to or higher in both overall evaluation and external appearance as compared with Hinohikari, despite its higher hardness and lower stickiness. Additionally, Murai 79 had brown-rice yield of 1.55 times as compared with Hinohikari, suggesting that it would enable to supply inexpensive rice for making nanhan with high quality particularly for aged people in Japan.

Keywords: high-amylose content, high-yielding rice line, nanhan, nursing care food, sensory eating quality test

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Authors: Valentin Père, Mathieu Milhé, Fabien Baillon, Jean-Louis Dirion

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Microgrids offer potential solutions to meet the need for local grid stability and increase isolated networks autonomy with the integration of intermittent renewable energy production and storage facilities. In such a context, sizing production and storage for a given network is a complex task, highly depending on input data such as power load profile and renewable resource availability. This work aims at developing an operating cost computation methodology for different microgrid designs based on the use of deep reinforcement learning (RL) algorithms to tackle the optimal operation problem in stochastic environments. RL is a data-based sequential decision control method based on Markov decision processes that enable the consideration of random variables for control at a chosen time scale. Agents trained via RL constitute a promising class of Energy Management Systems (EMS) for the operation of microgrids with energy storage. Microgrid sizing (or design) is generally performed by minimizing investment costs and operational costs arising from the EMS behavior. The latter might include economic aspects (power purchase, facilities aging), social aspects (load curtailment), and ecological aspects (carbon emissions). Sizing variables are related to major constraints on the optimal operation of the network by the EMS. In this work, an islanded mode microgrid is considered. Renewable generation is done with photovoltaic panels; an electrochemical battery ensures short-term electricity storage. The controllable unit is a hydrogen tank that is used as a long-term storage unit. The proposed approach focus on the transfer of agent learning for the near-optimal operating cost approximation with deep RL for each microgrid size. Like most data-based algorithms, the training step in RL leads to important computer time. The objective of this work is thus to study the potential of Batch-Constrained Q-learning (BCQ) for the optimal sizing of microgrids and especially to reduce the computation time of operating cost estimation in several microgrid configurations. BCQ is an off-line RL algorithm that is known to be data efficient and can learn better policies than on-line RL algorithms on the same buffer. The general idea is to use the learned policy of agents trained in similar environments to constitute a buffer. The latter is used to train BCQ, and thus the agent learning can be performed without update during interaction sampling. A comparison between online RL and the presented method is performed based on the score by environment and on the computation time.

Keywords: batch-constrained reinforcement learning, control, design, optimal

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

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Authors: O. A. Adeyemi, M. O. Idris, W. A. Oke, O. T. Olorode, S. O. Alayande, A. E. Adeoye

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The purpose of this paper is to investigate the process of capability building at subsidiary level and the challenges to such process. The relevance of external factors for capability development, have not been explicitly addressed in empirical studies. Though, internal factors, acting as enablers, have been more extensively studied. With reference to external factors, subsidiaries are actively influenced by specific characteristics of the host country, implying a need to become fully immersed in local culture and practices. Specifically, in MNCs, there has been a widespread trend in management practice to increase subsidiary autonomy,  with subsidiary managers being encouraged to act entrepreneurially, and to take advantage of host country specificity. As such, it could be proposed that: P1: The degree at which subsidiary management is connected to the host country, will positively influence the capability development process. Dynamic capabilities reside to a large measure with the subsidiary management team, but are impacted by the organizational processes, systems and structures that the MNC headquarter has designed to manage its business. At the subsidiary level, the weight of the subsidiary in the network, its initiative-taking and its profile building increase the supportive attention of the HQs and are relevant to the success of the process of capability building. Therefore, our second proposition is that: P2: Subsidiary role and HQ support are relevant elements in capability development at the subsidiary level. Design/Methodology/Approach: This present study will adopt the multiple case studies approach. That is because a case study research is relevant when addressing issues without known empirical evidences or with little developed prior theory. The key definitions and literature sources directly connected with operations of western subsidiaries in emerging markets, such as China, are well established. A qualitative approach, i.e., case studies of three western subsidiaries, will be adopted. The companies have similar products, they have operations in China, and both of them are mature in their internationalization process. Interviews with key informants, annual reports, press releases, media materials, presentation material to customers and stakeholders, and other company documents will be used as data sources. Findings: Western Subsidiaries in Emerging Market operate in a way substantially different from those in the West. What are the conditions initiating the outsourcing of operations? The paper will discuss and present two relevant propositions guiding that process. Practical Implications: MNCs headquarter should be aware of the potential for capability development at the subsidiary level. This increased awareness could induce consideration in headquarter about the possible ways of encouraging such known capability development and how to leverage these capabilities for better MNC headquarter and/or subsidiary performance. Originality/Value: The paper is expected to contribute on the theme: drivers of subsidiary performance with focus on emerging market. In particular, it will show how some external conditions could promote a capability-building process within subsidiaries.

Keywords: case studies, dynamic capability, emerging market, subsidiary

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Authors: Sandra Smieszek, Jonathan Haines

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Introduction: Numerous research efforts have focused on searching for ‘longevity genes’. However, attempting to decipher the genetic component of the longevous phenotype have resulted in limited success and the mechanisms governing longevity remain to be explained. We conducted a genome-wide homozygosity analysis (GWHA) of the founder population of the Amish community in central Ohio. While genome-wide association studies using unrelated individuals have revealed many interesting longevity associated variants, these variants are typically of small effect and cannot explain the observed patterns of heritability for this complex trait. The Amish provide a large cohort of extended kinships allowing for in depth analysis via family-based approach excellent population due to its. Heritability of longevity increases with age with significant genetic contribution being seen in individuals living beyond 60 years of age. In our present analysis we show that the heritability of longevity is estimated to be increasing with age particularly on the paternal side. Methods: The present analysis integrated both phenotypic and genotypic data and led to the discovery of a series of variants, distinct for stratified populations across ages and distinct for paternal and maternal cohorts. Specifically 5437 subjects were analyzed and a subset of 893 successfully genotyped individuals was used to assess CHIP heritability. We have conducted the homozygosity analysis to examine if homozygosity is associated with increased risk of living beyond 90. We analyzed AMISH cohort genotyped for 614,957 SNPs. Results: We delineated 10 significant regions of homozygosity (ROH) specific for the age group of interest (>90). Of particular interest was ROH on chromosome 13, P < 0.0001. The lead SNPs rs7318486 and rs9645914 point to COL4A2 and our lead SNP. COL25A1 encodes one of the six subunits of type IV collagen, the C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. The second region of interest points to IRS2. Furthermore we built a classifier using the obtained SNPs from the significant ROH region with 0.945 AUC giving ability to discriminate between those living beyond to 90 years of age and beyond. Conclusion: In conclusion our results suggest that a history of longevity does indeed contribute to increasing the odds of individual longevity. Preliminary results are consistent with conjecture that heritability of longevity is substantial when we start looking at oldest fifth and smaller percentiles of survival specifically in males. We will validate all the candidate variants in independent cohorts of centenarians, to test whether they are robustly associated with human longevity. The identified regions of interest via ROH analysis could be of profound importance for the understanding of genetic underpinnings of longevity.

Keywords: regions of homozygosity, longevity, SNP, Amish

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Authors: Yu-Hsien Lin, Yu-Ru Lin, Yung-Chun Wu

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This work demonstrates the ultra-thin poly-Si (polycrystalline Silicon) nanowire junctionless thin film transistors (NWs JL-TFT) with nickel silicide contact. For nickel silicide film, this work designs to use two-step annealing to form ultra-thin, uniform and low sheet resistance (Rs) Ni silicide film. The NWs JL-TFT with nickel silicide contact exhibits the good electrical properties, including high driving current (>10⁷ Å), subthreshold slope (186 mV/dec.), and low parasitic resistance. In addition, this work also compares the electrical characteristics of NWs JL-TFT with nickel silicide and non-silicide contact. Nickel silicide techniques are widely used for high-performance devices as the device scaling due to the source/drain sheet resistance issue. Therefore, the self-aligned silicide (salicide) technique is presented to reduce the series resistance of the device. Nickel silicide has several advantages including low-temperature process, low silicon consumption, no bridging failure property, smaller mechanical stress, and smaller contact resistance. The junctionless thin-film transistor (JL-TFT) is fabricated simply by heavily doping the channel and source/drain (S/D) regions simultaneously. Owing to the special doping profile, JL-TFT has some advantages such as lower thermal the budget which can integrate with high-k/metal-gate easier than conventional MOSFETs (Metal Oxide Semiconductor Field-Effect Transistors), longer effective channel length than conventional MOSFETs, and avoidance of complicated source/drain engineering. To solve JL-TFT has turn-off problem, JL-TFT needs ultra-thin body (UTB) structure to reach fully depleted channel region in off-state. On the other hand, the drive current (Iᴅ) is declined as transistor features are scaled. Therefore, this work demonstrates ultra thin poly-Si nanowire junctionless thin film transistors with nickel silicide contact. This work investigates the low-temperature formation of nickel silicide layer by physical-chemical deposition (PVD) of a 15nm Ni layer on the poly-Si substrate. Notably, this work designs to use two-step annealing to form ultrathin, uniform and low sheet resistance (Rs) Ni silicide film. The first step was promoted Ni diffusion through a thin interfacial amorphous layer. Then, the unreacted metal was lifted off after the first step. The second step was annealing for lower sheet resistance and firmly merged the phase.The ultra-thin poly-Si nanowire junctionless thin film transistors NWs JL-TFT with nickel silicide contact is demonstrated, which reveals high driving current (>10⁷ Å), subthreshold slope (186 mV/dec.), and low parasitic resistance. In silicide film analysis, the second step of annealing was applied to form lower sheet resistance and firmly merge the phase silicide film. In short, the NWs JL-TFT with nickel silicide contact has exhibited a competitive short-channel behavior and improved drive current.

Keywords: poly-Si, nanowire, junctionless, thin-film transistors, nickel silicide

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Authors: Daniela Manila Bianchi, Samantha Lupi, Elisa Barcucci, Sandra Fragassi, Clara Tramuta, Lucia Decastelli

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Introduction: The undeclared allergens detection in food products plays a fundamental role in the safety of the allergic consumer. The protection of allergic consumers is guaranteed, in Europe, by Regulation (EU) No 1169/2011 of the European Parliament, which governs the consumer's right to information and identifies 14 food allergens to be mandatorily indicated on food labels: among these, an egg is included. An egg can be present as an ingredient or as contamination in raw and cooked products. The main allergen egg proteins are ovomucoid, ovalbumin, lysozyme, and ovotransferrin. This study presents the results of a survey conducted in Northern Italy aimed at detecting the presence of undeclared egg proteins in food matrices in the latest ten years (2011-2021). Method: In the period January 2011 - October 2021, a total of 1205 different types of food matrices (ready-to-eat, meats, and meat products, bakery and pastry products, baby foods, food supplements, pasta, fish and fish products, preparations for soups and broths) were delivered to Food Control Laboratory of Istituto Zooprofilattico Sperimentale of Piemonte Liguria and Valle d’Aosta to be analyzed as official samples in the frame of Regional Monitoring Plan of Food Safety or in the contest of food poisoning. The laboratory is ISO 17025 accredited, and since 2019, it has represented the National Reference Centre for the detection in foods of substances causing food allergies or intolerances (CreNaRiA). All samples were stored in the laboratory according to food business operator instructions and analyzed within the expiry date for the detection of undeclared egg proteins. Analyses were performed with RIDASCREEN®FAST Ei/Egg (R-Biopharm ® Italia srl) kit: the method was internally validated and accredited with a Limit of Detection (LOD) equal to 2 ppm (mg/Kg). It is a sandwich enzyme immunoassay for the quantitative analysis of whole egg powder in foods. Results: The results obtained through this study showed that egg proteins were found in 2% (n. 28) of food matrices, including meats and meat products (n. 16), fish and fish products (n. 4), bakery and pastry products (n. 4), pasta (n. 2), preparations for soups and broths (n.1) and ready-to-eat (n. 1). In particular, in 2011 egg proteins were detected in 5% of samples, in 2012 in 4%, in 2013, 2016 and 2018 in 2%, in 2014, 2015 and 2019 in 3%. No egg protein traces were detected in 2017, 2020, and 2021. Discussion: Food allergies occur in the Western World in 2% of adults and up to 8% of children. Allergy to eggs is one of the most common food allergies in the pediatrics context. The percentage of positivity obtained from this study is, however, low. The trend over the ten years has been slightly variable, with comparable data.

Keywords: allergens, food, egg proteins, immunoassay

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Authors: Fei Wang, Jie Meng, Qingxiang Meng

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China is rich in straw and by-product resources, whose utilization has always been a hot topic. The objective of this study was to investigate the effect of feeding soybean straw and wine distiller’s grain as a replacement for corn stover on performance of beef cattle. Sixty Simmental×local crossbred bulls averaging 12 months old and 335.7 ± 39.1 kg of body weight (BW) were randomly assigned into four groups (15 animals per group) and allocated to a diet with 40% maize stover (MSD), a diet with 40% wrapping package maize silage (PMSD), a diet with 12% soybean straw plus 28% maize stover (SSD) and a diet with 12% wine distiller’s grain plus 28% maize stover (WDD). Bulls were fed ad libitum an TMR consisting of 36.0% maize, 12.5% of DDGS, 5.0% of cottonseed meal, 4.0% of soybean meal and 40.0% of by-product as described above. Treatment period lasted for 22 weeks, consisting of 1 week of dietary adaptation. The results showed that dry matter intake (DMI) was significantly higher (P < 0.01) for PMSD group than MSD and SSD groups during 0-7 week and 8-14week, and PMSD and WDD groups had higher (P < 0.05) DMI values than MSD and SSD groups during the whole period. Average daily gain (ADG) values were 1.56, 1.72, 1.68 and 1.58 kg for MSD, PMSD, SSD and WDD groups respectively, although the differences were not significant (P > 0.05). The value of blood sugar concentration was significantly higher (P < 0.01) for MSD group than WDD group, and the blood urea nitrogen concentration of SSD group was lower (P < 0.05) than MSD and WDD groups. No significant difference (P > 0.05) of serum total cholesterol, triglycerides or total protein content was observed among the different groups. Ten bulls with similar body weight were selected at the end of feeding trial and slaughtered for measurement of slaughtering performance, carcass quality and meat chemical composition. SSD group had significantly lower (P < 0.05) shear force value and cooking loss than MSD and PMSD groups. The pH values of MSD and SSD groups were lower (P < 0.05) than PMSD and WDD groups. WDD group had a higher fat color brightness (L*) value than PMSD and SSD groups. There were no significant differences in dressing percentage, meat percentage, top grade meat weight, ribeye area, marbling score, meat color and meat chemical compositions among different dietary treatments. Based on these results, the packed maize stover silage showed a potential of improving the average daily gain and feed intake of beef cattle. Soybean straw had a significant effect on improving the tenderness and reducing cooking loss of beef. In general, soybean straw and packed maize stover silage would be beneficial to nitrogen deposition and showed a potential to substitute maize stover in beef cattle diets.

Keywords: beef cattle, by-products, carcass quality, growth performance

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Authors: Danny Barash

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Riboswitches are RNA genetic control elements that were originally discovered in bacteria and provide a unique mechanism of gene regulation. They work without the participation of proteins and are believed to represent ancient regulatory systems in the evolutionary timescale. One of the biggest challenges in riboswitch research is that many are found in prokaryotes but only a small percentage of known riboswitches have been found in certain eukaryotic organisms. The few examples of eukaryotic riboswitches were identified using sequence-based bioinformatics search methods that include some slight structural considerations. These pattern-matching methods were the first ones to be applied for the purpose of riboswitch detection and they can also be programmed very efficiently using a data structure called affix arrays, making them suitable for genome-wide searches of riboswitch patterns. However, they are limited by their ability to detect harder to find riboswitches that deviate from the known patterns. Several methods have been developed since then to tackle this problem. The most commonly used by practitioners is Infernal that relies on Hidden Markov Models (HMMs) and Covariance Models (CMs). Profile Hidden Markov Models were also carried out in the pHMM Riboswitch Scanner web application, independently from Infernal. Other computational approaches that have been developed include RMDetect by the use of 3D structural modules and RNAbor that utilizes Boltzmann probability of structural neighbors. We have tried to incorporate more sophisticated secondary structure considerations based on RNA folding prediction using several strategies. The first idea was to utilize window-based methods in conjunction with folding predictions by energy minimization. The moving window approach is heavily geared towards secondary structure consideration relative to sequence that is treated as a constraint. However, the method cannot be used genome-wide due to its high cost because each folding prediction by energy minimization in the moving window is computationally expensive, enabling to scan only at the vicinity of genes of interest. The second idea was to remedy the inefficiency of the previous approach by constructing a pipeline that consists of inverse RNA folding considering RNA secondary structure, followed by a BLAST search that is sequence-based and highly efficient. This approach, which relies on inverse RNA folding in general and our own in-house fragment-based inverse RNA folding program called RNAfbinv in particular, shows capability to find attractive candidates that are missed by Infernal and other standard methods being used for riboswitch detection. We demonstrate attractive candidates found by both the moving-window approach and the inverse RNA folding approach performed together with BLAST. We conclude that structure-based methods like the two strategies outlined above hold considerable promise in detecting riboswitches and other conserved RNAs of functional importance in a variety of organisms.

Keywords: riboswitches, RNA folding prediction, RNA structure, structure-based methods

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Authors: Roberta Martino, Viviana Ventre

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Intertemporal choices are choices under conditions of uncertainty in which the consequences are distributed over time. The Discounted Utility Model is the essential reference for describing the individual in the context of intertemporal choice. The model is based on the idea that the individual selects the alternative with the highest utility, which is calculated by multiplying the cardinal utility of the outcome, as if the reception were instantaneous, by the discount function that determines a decrease in the utility value according to how the actual reception of the outcome is far away from the moment the choice is made. Initially, the discount function was assumed to have an exponential trend, whose decrease over time is constant, in line with a profile of a rational investor described by classical economics. Instead, empirical evidence called for the formulation of alternative, hyperbolic models that better represented the actual actions of the investor. Attitudes that do not comply with the principles of classical rationality are termed anomalous, i.e., difficult to rationalize and describe through normative models. The development of behavioral finance, which describes investor behavior through cognitive psychology, has shown that deviations from rationality are due to the limited rationality condition of human beings. What this means is that when a choice is made in a very difficult and information-rich environment, the brain does a compromise job between the cognitive effort required and the selection of an alternative. Moreover, the evaluation and selection phase of the alternative, the collection and processing of information, are dynamics conditioned by systematic distortions of the decision-making process that are the behavioral biases involving the individual's emotional and cognitive system. In this paper we present an original decomposition of the discount function to investigate the psychological principles of hyperbolic discounting. It is possible to decompose the curve into two components: the first component is responsible for the smaller decrease in the outcome as time increases and is related to the individual's impatience; the second component relates to the change in the direction of the tangent vector to the curve and indicates how much the individual perceives the indeterminacy of the future indicating his or her aversion to uncertainty. This decomposition allows interesting conclusions to be drawn with respect to the concept of impatience and the emotional drives involved in decision-making. The contribution that neuroscience can make to decision theory and inter-temporal choice theory is vast as it would allow the description of the decision-making process as the relationship between the individual's emotional and cognitive factors. Neurofinance is a discipline that uses a multidisciplinary approach to investigate how the brain influences decision-making. Indeed, considering that the decision-making process is linked to the activity of the prefrontal cortex and amygdala, neurofinance can help determine the extent to which abnormal attitudes respect the principles of rationality.

Keywords: impatience, intertemporal choice, neurofinance, rationality, uncertainty

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Authors: A. S. Ibrahim Mamane, S. Giljean, M.-J. Pac, G. L’Hostis

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Fiber reinforced composite laminates are particularly subject to residual stresses due to their heterogeneity and the complex chemical, mechanical and thermal mechanisms that occur during their processing. Residual stresses are now well known to cause damage accumulation, shape instability, and behavior disturbance in composite parts. Many works exist in the literature on techniques for minimizing residual stresses in thermosetting and thermoplastic composites mainly. To study in-depth the influence of processing mechanisms on the formation of residual stresses and to minimize them by establishing a reliable correlation, it is essential to be able to measure very precisely the profile of residual stresses in the composite. Residual stresses are important data to consider when sizing composite parts and predicting their behavior. The incremental hole drilling is very effective in measuring the gradient of residual stresses in composite laminates. This method is semi-destructive and consists of drilling incrementally a hole through the thickness of the material and measuring relaxation strains around the hole for each increment using three strain gauges. These strains are then converted into residual stresses using a matrix of coefficients. These coefficients, called calibration coefficients, depending on the diameter of the hole and the dimensions of the gauges used. The reliability of the incremental hole drilling depends on the accuracy with which the calibration coefficients are determined. These coefficients are calculated using a finite element model. The samples’ features and the experimental conditions must be considered in the simulation. Any mismatch can lead to inadequate calibration coefficients, thus introducing errors on residual stresses. Several calibration coefficient correction methods exist for isotropic material, but there is a lack of information on this subject concerning composite laminates. In this work, a Python program was developed to automatically generate the adequate finite element model. This model allowed us to perform a parametric study to assess the influence of experimental errors on the calibration coefficients. The results highlighted the sensitivity of the calibration coefficients to the considered errors and gave an order of magnitude of the precisions required on the experimental device to have reliable measurements. On the basis of these results, improvements were proposed on the experimental device. Furthermore, a numerical method was proposed to correct the calibration coefficients for different types of materials, including thick composite parts for which the analytical approach is too complex. This method consists of taking into account the experimental errors in the simulation. Accurate measurement of the experimental errors (such as eccentricity of the hole, angular deviation of the gauges from their theoretical position, or errors on increment depth) is therefore necessary. The aim is to determine more precisely the residual stresses and to expand the validity domain of the incremental hole drilling technique.

Keywords: fiber reinforced composites, finite element simulation, incremental hole drilling method, numerical correction of the calibration coefficients, residual stresses

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Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim

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Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.

Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion

Procedia PDF Downloads 429

Authors: Shiamaa Eltantawy, Gihan Sobhy, Alif Alaam

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Wilson disease, or hepatolenticular degeneration, is an autosomal recessive disease that results in excess copper buildup in the body. It primarily affects the liver and basal ganglia of the brain, but it can affect other organ systems. Musculoskeletal abnormalities, including premature osteoarthritis, skeletal deformity, and pathological bone fractures, can occasionally be found in WD patients with a hepatic or neurologic type. The aim was to assess the prevalence of osteoporosis and osteopenia in Wilson’s disease patients. This case-control study was conducted on ninety children recruited from the inpatient ward and outpatient clinic of the Paediatric Hepatology, Gastroenterology, and Nutrition department of the National Liver Institute at Menofia University, aged from 1 to 18 years. Males were 49, and females were 41. Children were divided into three groups: (Group I) consisted of thirty patients with WD; (Group II) consisted of thirty patients with chronic liver disease other than WD; (Group III) consisted of thirty age- and sex-matched healthy The exclusion criteria were patients with hyperparathyroidism, hyperthyroidism, renal failure, Cushing's syndrome, and patients on certain drugs such as chemotherapy, anticonvulsants, or steroids. All patients were subjected to the following: 1- Full history-taking and clinical examination. 2-Laboratory investigations: (FBC,ALT,AST,serum albumin, total protein, total serum bilirubin,direct bilirubin,alkaline phosphatase, prothrombin time, serum critine,parathyroid hormone, serum calcium, serum phosphrus). 3-Bone mineral density (BMD, gm/cm2) values were measured by dual-energy X-ray absorptiometry (DEXA). The results revealed that there was a highly statistically significant difference between the three groups regarding the DEXA scan, and there was no statistically significant difference between groups I and II, but the WD group had the lowest bone mineral density. The WD group had a large number of cases of osteopenia and osteoporosis, but there was no statistically significant difference with the group II mean, while a high statistically significant difference was found when compared to group III. In the WD group, there were 20 patients with osteopenia, 4 patients with osteoporosis, and 6 patients who were normal. The percentages were 66.7%, 13.3%, and 20%, respectively. Therefore, the largest number of cases in the WD group had osteopenia. There was no statistically significant difference found between WD patients on different treatment regimens regarding DEXA scan results (Z-Score). There was no statistically significant difference found between patients in the WD group (normal, osteopenic, or osteoporotic) regarding phosphorus (mg/dL), but there was a highly statistically significant difference found between them regarding ionised Ca (mmol/L). Therefore, there was a decrease in bone mineral density when the Ca level was decreased. In summary, Wilson disease is associated with bone demineralization. The largest number of cases in the WD group in our study had osteopenia (66.7%). Different treatment regimens (zinc monotherapy, Artamin, and zinc) as well as different laboratory parameters have no effect on bone mineralization in WD cases. Decreased ionised Ca is associated with low BMD in WD patients. Children with WD should be investigated for BMD.

Keywords: wilson disease, Bone mineral density, liver disease, osteoporosis

Procedia PDF Downloads 34

Authors: Pomila Sharma

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Rajasthan is among regions with greatest climate sensitivity and lowest adaptive capabilities. In many parts of the Rajasthan surface water which can be highly turbid and contaminated with fecal coliform bacteria is used for drinking purposes. The majority rely almost exclusively upon traditional sources of highly turbid and untreated pathogenic surface water for their domestic water needs. In many parts of rural areas of Rajasthan, it is still difficult to obtain clean water, especially remote habitations with no groundwater due to quality issues or depletion and limited feasibility to connect with surface water schemes due to low density of population in these areas to justify large infrastructure investment. The most viable sources are rain water harvesting, community managed open wells, private wells, ponds and small-scale irrigation reservoirs have often been the main traditional sources of rural drinking water. Turbidity is conventionally removed by treating the water with expensive chemicals. This study has to investigate the use of crushed seeds from the tree Moringa oleifera (drumstick) as a natural alternative to conventional coagulant chemicals. The use of Moringa oleifera seed powder can produce potable water of higher quality than the original source. Moringa oleifera a native species of northern India, the tree is now grown extensively throughout the tropics and found in many countries of Africa, Asia & South America. The seeds of tree contains significant quantities of low molecular weight, water soluble proteins which carries the positive charge when the crushed seeds are added to water. This protein binds in raw water with negatively charged turbid water with bacteria, clay, algae, etc. Under proper mixing, these particles make flocks, which may be left to settle by gravity or be removed by filtration. Using Moringa oleifera as a replacement coagulation in such surface sources of arid and semi-arid areas can meet the need for water purification in remote places of Rajasthan state of India. The present study accesses to find out laboratory based investigation of the effect of seeds of Moringa tree on its coagulation effectiveness (purification) using turbid water samples of surface source of the Rajasthan state. In this study, moringa seed powder showed that filtering with seed powder may diminish water pollution and bacterial counts. Results showed Moringa oleifera seeds coagulate 90-95% of turbidity and color efficiently leading to an aesthetically clear supernatant & reduced about 85-90% of bacterial load reduction in samples.

Keywords: bacterial load, coagulant, turbidity, water purification

Procedia PDF Downloads 118

Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

Procedia PDF Downloads 102

Authors: Evgeniya Orlova, Dmitriy Feoktistov, Geniy Kuznetsov

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Spreading of a droplet over a solid substrate is a key phenomenon observed in the following engineering applications: thin film coating, oil extraction, inkjet printing, and spray cooling of heated surfaces. Droplet cooling systems are known to be more effective than film or rivulet cooling systems. It is caused by the greater evaporation surface area of droplets compared with the film of the same mass and wetting surface. And the greater surface area of droplets is connected with the curvature of the interface. Location of the droplets on the cooling surface influences on the heat transfer conditions. The close distance between the droplets provides intensive heat removal, but there is a possibility of their coalescence in the liquid film. The long distance leads to overheating of the local areas of the cooling surface and the occurrence of thermal stresses. To control the location of droplets is possible by changing the roughness, structure and chemical composition of the surface. Thus, control of spreading can be implemented. The most important characteristic of spreading of droplets on solid surfaces is a dynamic contact angle, which is a function of the contact line speed or capillary number. However, there is currently no universal equation, which would describe the relationship between these parameters. This paper presents the results of the experimental studies of water droplet spreading on metal substrates with different surface roughness. The effect of the droplet growth rate and the surface roughness on spreading characteristics was studied at low capillary numbers. The shadow method using high speed video cameras recording up to 10,000 frames per seconds was implemented. A droplet profile was analyzed by Axisymmetric Drop Shape Analyses techniques. According to change of the dynamic contact angle and the contact line speed three sequential spreading stages were observed: rapid increase in the dynamic contact angle; monotonous decrease in the contact angle and the contact line speed; and form of the equilibrium contact angle at constant contact line. At low droplet growth rate, the dynamic contact angle of the droplet spreading on the surfaces with the maximum roughness is found to increase throughout the spreading time. It is due to the fact that the friction force on such surfaces is significantly greater than the inertia force; and the contact line is pinned on microasperities of a relief. At high droplet growth rate the contact angle decreases during the second stage even on the surfaces with the maximum roughness, as in this case, the liquid does not fill the microcavities, and the droplet moves over the “air cushion”, i.e. the interface is a liquid/gas/solid system. Also at such growth rates pulsation of liquid flow was detected; and the droplet oscillates during the spreading. Thus, obtained results allow to conclude that it is possible to control spreading by using the surface roughness and the growth rate of droplets on surfaces as varied factors. Also, the research findings may be used for analyzing heat transfer in rivulet and drop cooling systems of high energy equipment.

Keywords: contact line speed, droplet growth rate, dynamic contact angle, shadow system, spreading

Procedia PDF Downloads 301

Authors: Antònio Inês, Davide Silva, Filipa Carvalho, Luís Filipe-Riberiro, Fernando M. Nunes, Luís Abrunhosa, Fernanda Cosme

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The presence of mycotoxins in foodstuff is a matter of concern for food safety. Mycotoxins are toxic secondary metabolites produced by certain molds, being ochratoxin A (OTA) one of the most relevant. Wines can also be contaminated with these toxicants. Several authors have demonstrated the presence of mycotoxins in wine, especially ochratoxin A. Its chemical structure is a dihydro-isocoumarin connected at the 7-carboxy group to a molecule of L-β-phenylalanine via an amide bond. As these toxicants can never be completely removed from the food chain, many countries have defined levels in food in order to attend health concerns. OTA contamination of wines might be a risk to consumer health, thus requiring treatments to achieve acceptable standards for human consumption. The maximum acceptable level of OTA in wines is 2.0 μg/kg according to the Commission regulation No. 1881/2006. Therefore, the aim of this work was to reduce OTA to safer levels using different fining agents, as well as their impact on white wine physicochemical characteristics. To evaluate their efficiency, 11 commercial fining agents (mineral, synthetic, animal and vegetable proteins) were used to get new approaches on OTA removal from white wine. Trials (including a control without addition of a fining agent) were performed in white wine artificially supplemented with OTA (10 µg/L). OTA analyses were performed after wine fining. Wine was centrifuged at 4000 rpm for 10 min and 1 mL of the supernatant was collected and added of an equal volume of acetonitrile/methanol/acetic acid (78:20:2 v/v/v). Also, the solid fractions obtained after fining, were centrifuged (4000 rpm, 15 min), the resulting supernatant discarded, and the pellet extracted with 1 mL of the above solution and 1 mL of H2O. OTA analysis was performed by HPLC with fluorescence detection. The most effective fining agent in removing OTA (80%) from white wine was a commercial formulation that contains gelatin, bentonite and activated carbon. Removals between 10-30% were obtained with potassium caseinate, yeast cell walls and pea protein. With bentonites, carboxymethylcellulose, polyvinylpolypyrrolidone and chitosan no considerable OTA removal was verified. Following, the effectiveness of seven commercial activated carbons was also evaluated and compared with the commercial formulation that contains gelatin, bentonite and activated carbon. The different activated carbons were applied at the concentration recommended by the manufacturer in order to evaluate their efficiency in reducing OTA levels. Trial and OTA analysis were performed as explained previously. The results showed that in white wine all activated carbons except one reduced 100% of OTA. The commercial formulation that contains gelatin, bentonite and activated carbon reduced only 73% of OTA concentration. These results may provide useful information for winemakers, namely for the selection of the most appropriate oenological product for OTA removal, reducing wine toxicity and simultaneously enhancing food safety and wine quality.

Keywords: wine, ota removal, food safety, fining

Procedia PDF Downloads 505

Authors: Aysen Caliskan, Hanzade Haykiri-Acma, Serdar Yaman

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Co-firing of coal and biomass blends is an effective method to reduce carbon dioxide emissions released by burning coals, thanks to the carbon-neutral nature of biomass. Besides, usage of biomass that is renewable and sustainable energy resource mitigates the dependency on fossil fuels for power generation. However, most of the biomass species has negative aspects such as low calorific value, high moisture and volatile matter contents compared to coal. Torrefaction is a promising technique in order to upgrade the fuel properties of biomass through thermal treatment. That is, this technique improves the calorific value of biomass along with serious reductions in the moisture and volatile matter contents. In this context, several woody biomass materials including Rhododendron, hybrid poplar, and ash-tree were subjected to torrefaction process in a horizontal tube furnace at 200°C under nitrogen flow. In this way, the solid residue obtained from torrefaction that is also called as 'biochar' was obtained and analyzed to monitor the variations taking place in biomass properties. On the other hand, some Turkish lignites from Elbistan, Adıyaman-Gölbaşı and Çorum-Dodurga deposits were chosen as coal samples since these lignites are of great importance in lignite-fired power stations in Turkey. These lignites were blended with the obtained biochars for which the blending ratio of biochars was kept at 10 wt% and the lignites were the dominant constituents in the fuel blends. Burning tests of the lignites, biomasses, biochars, and blends were performed using a thermogravimetric analyzer up to 900°C with a heating rate of 40°C/min under dry air atmosphere. Based on these burning tests, properties relevant to burning characteristics such as the burning reactivity and burnout yields etc. could be compared to justify the effects of torrefaction and blending. Besides, some characterization techniques including X-Ray Diffraction (XRD), Fourier Transform Infrared (FTIR) spectroscopy and Scanning Electron Microscopy (SEM) were also conducted for the untreated biomass and torrefied biomass (biochar) samples, lignites and their blends to examine the co-combustion characteristics elaborately. Results of this study revealed the fact that blending of lignite with 10 wt% biochar created synergistic behaviors during co-combustion in comparison to the individual burning of the ingredient fuels in the blends. Burnout and ignition performances of each blend were compared by taking into account the lignite and biomass structures and characteristics. The blend that has the best co-combustion profile and ignition properties was selected. Even though final burnouts of the lignites were decreased due to the addition of biomass, co-combustion process acts as a reasonable and sustainable solution due to its environmentally friendly benefits such as reductions in net carbon dioxide (CO2), SOx and hazardous organic chemicals derived from volatiles.

Keywords: burnout performance, co-combustion, thermal analysis, torrefaction pretreatment

Procedia PDF Downloads 317

Authors: Cheila Pereira, Sara C. Cunha, Miguel A. Faria, José O. Fernandes

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The increasing world population brings several concerns, one of which is food security and sustainability. To meet this challenge, aquaculture, the farming of aquatic animals and plants, including fish, mollusks, bivalves, and algae, has experienced sustained growth and development in recent years. Recent advances in this industry have focused on reducing its economic and environmental costs, for example, the substitution of protein sources in fish feed. Plant-based proteins are now a common approach, and while it is a greener alternative to animal-based proteins, there are some disadvantages, such as their putative content and intoxicants such as mycotoxins. These are naturally occurring plant contaminants, and their exposure in fish can cause health problems, stunted growth or even death, resulting in economic losses for the producers and health concerns for the consumers. Different works have demonstrated the presence of both AFB1 (aflatoxin B1) and ENNB1 (enniatin B1) in fish feed and their capacity to be absorbed and bioaccumulate in the fish organism after digestion, further reaching humans through fish ingestion. The aim of this work was to evaluate the bioaccessibility of both mycotoxins in samples of Sparus aurata muscle using a static digestion model based on the INFOGEST protocol. The samples were subjected to different cooking procedures – raw, grilled and fried – and different seasonings – none, thyme and ginger – in order to evaluate their potential reduction effect on mycotoxins bioaccessibility, followed by the evaluation of the intestinal transport of both compounds with an in vitro cell model composed of Caco-2/HT-29 co-culture monolayers, simulating the human intestinal epithelium. The bioaccessible fractions obtained in the digestion studies were used in the transport studies for a more realistic approach to bioavailability evaluation. Results demonstrated the effect of the use of different cooking procedures and seasoning on the toxin's bioavailability. Sparus aurata was chosen in this study for its large production in aquaculture and high consumption in Europe. Also, with the continued evolution of fish farming practices and more common usage of novel feed ingredients based on plants, there is a growing concern about less studied contaminants in aquaculture and their consequences for human health. In pair with greener advances in this industry, there is a convergence towards alternative research methods, such as in vitro applications. In the case of bioavailability studies, both in vitro digestion protocols and intestinal transport assessment are excellent alternatives to in vivo studies. These methods provide fast, reliable and comparable results without ethical restraints.

Keywords: AFB1, aquaculture, bioaccessibility, ENNB1, intestinal transport.

Procedia PDF Downloads 31

Authors: Victor Pena Ribeiro, Caroline Arruda, Jennyfer Andrea Aldana Mejia, Jairo Kenupp Bastos

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Leishmaniasis is a serious health problem around the world. The treatment of infected individuals with pentavalent antimonial drugs is the main therapeutic strategy. However, they present high toxicity and persistence side effects. Therefore, the discovery of new and safe natural-derived therapeutic agents against leishmaniasis is important. Propolis is a resin of viscous consistency produced by Apis mellifera bees from parts of plants. The main types of Brazilian propolis are green, red, yellow and brown. Thus, the aim of this work was to investigate the chemical composition and leishmanicidal properties of a brown propolis (BP). For this purpose, the hydroalcoholic crude extract of BP was obtained and was fractionated by liquid-liquid chromatography. The chemical profile of the extract and its fractions were obtained by HPLC-UV-DAD. The fractions were submitted to preparative HPLC chromatography for isolation of the major compounds of each fraction. They were analyzed by NMR for structural determination. The volatile compounds were obtained by hydrodistillation and identified by GC/MS. Promastigote forms of Leishmania amazonensis were cultivated in M199 medium and then 2×106 parasites.mL-1 were incubated in 96-well microtiter plates with the samples. The BP was dissolved in dimethyl sulfoxide (DMSO) and diluted into the medium, to give final concentrations of 1.56, 3.12, 6.25, 12.5, 25 and 50 µg.mL⁻¹. The plates were incubated at 25ºC for 24 h, and the lysis percentage was determined by using a Neubauer chamber. The bioassays were performed in triplicate, using a medium with 0.5% DMSO as a negative control and amphotericin B as a positive control. The leishimnicidal effect against promastigote forms was also evaluated at the same concentrations. Cytotoxicity experiments also were performed in 96-well plates against normal (CHO-k1) and tumor cell lines (AGP01 and HeLa) using XTT colorimetric method. Phenolic compounds, flavonoids, and terpenoids were identified in brown propolis. The major compounds were identified as follows: p-coumaric acid (24.6%) for a methanolic fraction, Artepelin-C (29.2%) for ethyl acetate fraction and the compounds of hexane fraction are in the process of structural elucidation. The major volatile compounds identified were β-caryophyllene (10.9%), germacrene D (9.7%), nerolidol (10.8%) and spathulenol (8.5%). The propolis did not show cytotoxicity against normal cell lines (CHO) with IC₅₀ > 100 μg.mL⁻¹, whereas the IC₅₀ < 10 μg.mL⁻¹ showed a potential against the AGP01 cell line, propolis did not demonstrate cytotoxicity against HeLa cell lines IC₅₀ > 100 μg.mL⁻¹. In the determination of the leishmanicidal activity, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations of the crude extract caused the lysis of 76% and 45% of promastigote forms of L. amazonensis, respectively. To the amastigote form, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations caused the mortality of 89% and 75% of L. amazonensis, respectively. The IC₅₀ was 2.8 μg.mL⁻¹ to amastigote form and 3.9 μg.mL⁻¹ to promastigote form, showing a promising activity against Leishmania amazonensis.

Keywords: amastigote, brown propolis, cytotoxicity, promastigote

Procedia PDF Downloads 130

Authors: Charmaine B. Distor

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Collaboration has long been recognized in different fields, but there’s been little research on operationalizing it especially on a multi-sectoral setting as per the author’s best knowledge. Also, communication is one of the factors that is usually overlooked when studying it. Specifically, this study aimed to describe the organizational profile and tasks of collaborators in the visitor management program of Make It Makiling (MIM). It also identified the factors that motivated collaborators to collaborate in MIM while determining the communication dimensions in the collaborative process. It also determined the communication channels used by collaborators in MIM while identifying the outcomes of collaboration in MIM. This study also found out if a relationship exists between collaborators’ motivations for collaboration and their perceived outcomes of collaboration, and collaborators' communication dimensions and their perceived outcomes of collaboration. Lastly, it also provided recommendations to improve the communication in MIM. Data were gathered using a self-administered survey that was patterned after Mattessich and Monsey’s (1992) collaboration experience questionnaire. Interviews and secondary sources mainly provided by the Makiling Center for Mountain Ecosystems (MCME) were also used. From the seven MIM collaborating organizations that were selected through purposive sampling, 86 respondents were chosen. Then, data were analyzed through frequency counts, percentages, measures of central tendencies, and Pearson’s and Spearman rho correlations. Collaborators’ length of collaboration ranged from seven to twenty years. Furthermore, six out of seven of the collaborators were involved in the task of 'emergency, rescue, and communication'. For the other aspect of the antecedents, the history of previous collaboration efforts ranked as the highest rated motivation for collaboration. In line with this, the top communication dimension is the governance while perceived effectiveness garnered the highest overall average among the perceived outcomes of collaboration. Results also showed that the collaborators highly rely on formal communication channels. Meetings and memos were the most commonly used communication channels throughout all tasks under the four phases of MIM. Additionally, although collaborators have a high view towards their co-collaborators, they still rely on MCME to act as their manager in coordinating with one another indirectly. Based on the correlation analysis, antecedent (motivations)-outcome relationship generally had positive relationships. However, for the process (communication dimensions)-outcome relationship, both positive and negative relationships were observed. In conclusion, this study exhibited the same trend with existing literature which also used the same framework. For the antecedent-outcome relationship, it can be deduced that MCME, as the main organizer of MIM, can focus on these variables to achieve their desired outcomes because of the positive relationships. For the process-outcome relationship, MCME should also take note that there were negative relationships where an increase in the said communication dimension may result in a decrease in the desired outcome. Recommendations for further study include a methodology that contains: complete enumeration or any parametric sampling, a researcher-administered survey, and direct observations. These might require additional funding, but all may yield to richer data.

Keywords: antecedent-outcome relationship, carrying capacity, organizational communication, process-outcome relationship

Procedia PDF Downloads 100

Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

Procedia PDF Downloads 98

Authors: Giacoma Pace

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The research seeks to evaluate whether students with impairments can achieve enhanced academic progress by actively engaging in collaborative problem-solving activities with teachers and peers, to overcome the obstacles rooted in socio-economic disparities. Furthermore, the research underscores the significance of fostering students' self-awareness regarding their learning process and encourages teachers to adopt a more interactive teaching approach. The research also posits that reducing conventional face-to-face lessons can motivate students to explore alternative learning methods, such as collaborative teamwork and peer education within the classroom. To address socio-cultural barriers it is imperative to assess their internet access and possession of technological devices, as these factors can contribute to a digital divide. The research features a case study of a Flipped Classroom Learning Unit, administered to six third-year high school classes: Scientific Lyceum, Technical School, and Vocational School, within the city of Turin, Italy. Data are about teachers and the students involved in the case study, some impaired students in each class, level of entry, students’ performance and attitude before using Flipped Classrooms, level of motivation, family’s involvement level, teachers’ attitude towards Flipped Classroom, goal obtained, the pros and cons of such activities, technology availability. The selected schools were contacted; meetings for the English teachers to gather information about their attitude and knowledge of the Flipped Classroom approach. Questionnaires to teachers and IT staff were administered. The information gathered, was used to outline the profile of the subjects involved in the study and was further compared with the second step of the study made up of a study conducted with the classes of the selected schools. The learning unit is the same, structure and content are decided together with the English colleagues of the classes involved. The pacing and content are matched in every lesson and all the classes participate in the same labs, use the same materials, homework, same assessment by summative and formative testing. Each step follows a precise scheme, in order to be as reliable as possible. The outcome of the case study will be statistically organised. The case study is accompanied by a study on the literature concerning EFL approaches and the Flipped Classroom. Document analysis method was employed, i.e. a qualitative research method in which printed and/or electronic documents containing information about the research subject are reviewed and evaluated with a systematic procedure. Articles in the Web of Science Core Collection, Education Resources Information Center (ERIC), Scopus and Science Direct databases were searched in order to determine the documents to be examined (years considered 2000-2022).

Keywords: flipped classroom, impaired, inclusivity, peer instruction

Procedia PDF Downloads 28

Authors: Navid Mosallaei, Mahmoud Reza Jaafari, Mohammad Yahya Hanafi-Bojd, Shiva Golmohammadzadeh, Bizhan Malaekeh-Nikouei

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Background: Docetaxel (DTX), a potent anticancer drug derived from the European yew tree, is effective against various human cancers by inhibiting microtubule depolymerization. Solid lipid nanoparticles (SLNs) have gained attention as drug carriers for enhancing drug effectiveness and safety. SLNs, submicron-sized lipid-based particles, can passively target tumors through the "enhanced permeability and retention" (EPR) effect, providing stability, drug protection, and controlled release while being biocompatible. Methods: The SLN formulation included biodegradable lipids (Compritol and Precirol), hydrogenated soy phosphatidylcholine (H-SPC) as a lipophilic co-surfactant, and Poloxamer 188 as a non-ionic polymeric stabilizer. Two SLN preparation techniques, probe sonication and microemulsion, were assessed. Characterization encompassed SLNs' morphology, particle size, zeta potential, matrix, and encapsulation efficacy. In-vitro cytotoxicity and cellular uptake studies were conducted using mouse colorectal (C-26) and human malignant melanoma (A-375) cell lines, comparing SLN-DTX with Taxotere®. In-vivo studies evaluated tumor inhibitory efficacy and survival in mice with colorectal (C-26) tumors, comparing SLNDTX withTaxotere®. Results: SLN-DTX demonstrated stability, with an average size of 180 nm and a low polydispersity index (PDI) of 0.2 and encapsulation efficacy of 98.0 ± 0.1%. Differential scanning calorimetry (DSC) suggested amorphous encapsulation of DTX within SLNs. In vitro studies revealed that SLN-DTX exhibited nearly equivalent cytotoxicity to Taxotere®, depending on concentration and exposure time. Cellular uptake studies demonstrated superior intracellular DTX accumulation with SLN-DTX. In a C-26 mouse model, SLN-DTX at 10 mg/kg outperformed Taxotere® at 10 and 20 mg/kg, with no significant differences in body weight changes and a remarkably high survival rate of 60%. Conclusion: This study concludes that SLN-DTX, prepared using the probe sonication, offers stability and enhanced therapeutic effects. It displayed almost same in vitro cytotoxicity to Taxotere® but showed superior cellular uptake. In a mouse model, SLN-DTX effectively inhibited tumor growth, with 10 mg/kg outperforming even 20 mg/kg of Taxotere®, without adverse body weight changes and with higher survival rates. This suggests that SLN-DTX has the potential to reduce adverse effects while maintaining or enhancing docetaxel's therapeutic profile, making it a promising drug delivery strategy suitable for industrialization.

Keywords: docetaxel, Taxotere®, solid lipid nanoparticles, enhanced permeability and retention effect, drug delivery, cancer chemotherapy, cytotoxicity, cellular uptake, tumor inhibition

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Authors: S. Wiak, L. Szymanski, Z. Kolacinski, G. Raniszewski, L. Pietrzak, Z. Staniszewska

Abstract:

The term ‘cancer’ is given to a collection of related diseases that may affect any part of the human body. It is a pathological behaviour of cells with the potential to undergo abnormal breakdown in the processes that control cell proliferation, differentiation, and death of particular cells. Although cancer is commonly considered as modern disease, there are beliefs that drastically growing number of new cases can be linked to the extensively prolonged life expectancy and enhanced techniques for cancer diagnosis. Magnetic hyperthermia therapy is a novel approach to cancer treatment, which may greatly contribute to higher efficiency of the therapy. Employing carbon nanotubes as nanocarriers for magnetic particles, it is possible to decrease toxicity and invasiveness of the treatment by surface functionalisation. Despite appearing in recent years, magnetic particle hyperthermia has already become of the highest interest in the scientific and medical environment. The reason why hyperthermia therapy brings so much hope for future treatment of cancer lays in the effect that it produces in malignant cells. Subjecting them to thermal shock results in activation of numerous degradation processes inside and outside the cell. The heating process initiates mechanisms of DNA destruction, protein denaturation and induction of cell apoptosis, which may lead to tumour shrinkage, and in some cases, it may even cause complete disappearance of cancer. The factors which have the major impact on the final efficiency of the treatment include temperatures generated inside the tissues, time of exposure to the heating process, and the character of an individual cancer cell type. The vast majority of cancer cells is characterised by lower pH, persistent hypoxia and lack of nutrients, which can be associated to abnormal microvasculature. Since in healthy tissues we cannot observe presence of these conditions, they should not be seriously affected by elevation of the temperature. The aim of this work is to investigate the influence of iron content in iron filled Carbon Nanotubes on the desired nanoparticles for cancer therapy. In the article, the development and demonstration of the method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nanocontainers. The methodology of the production carbon- ferromagnetic nanocontainers (FNCs) includes the synthesis of carbon nanotubes, chemical, and physical characterization, increasing the content of a ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. The ferromagnetic nanocontainers were synthesised in CVD and microwave plasma system. The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013.

Keywords: hyperthermia, carbon nanotubes, cancer colon cells, radio frequency field

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Authors: Bhojan Dhakal, Naba Raj Devkota, Chet Raj Upreti, Maheshwar Sapkota

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A study was conducted to find out the production potential, nutrient composition, and the variability of the most commonly available fodder trees along with the varying altitude to help optimize the dry matter requirement during winter lean period. The study was carried out from March to June, 2012 in Lho and Prok Village Development Committee of Manaslu Conservation Area (MCA), located in Gorkha district of Nepal. The other objective of the research was to learn the impact of climate change on livestock production linking it with feed availability. The study was conducted in two parts: social and biological. Accordingly, a households (HHs) survey was conducted to collect primary data from 70 HHs, focusing on the perception of respondents on impacts of climatic variability on the feeding management. The next part consisted of understanding yield potential and nutrient composition of the four most commonly available fodder trees (M. azedirach, M. alba, F. roxburghii, F. nemoralis), within two altitudes range: (1500-2000 masl and 2000-2500 masl) by using a RCB design in 2*4 factorial combination of treatments, each replicated four times. Results revealed that majority of the farmers perceived the change in climatic phenomenon more severely within the past five years. Farmers were using different adaptation technologies such as collection of forage from jungle, reducing unproductive animals, fodder trees utilization, and crop by product feeding at feed scarcity period. Ranking of the different fodder trees on the basis of indigenous knowledge and experiences revealed that F. roxburghii was the best-preferred fodder tree species (index value 0.72) in terms overall preferability whereas M. azedirach had highest growth and productivity (index value 0.77), F. roxburghii had highest adoptability (index value 0.69) and palatability (index value 0.69) as well. Similarly, fresh yield and dry matter yield of the each fodder trees was significant (P < 0.01) between the altitude and within species. Fodder trees yield analysis revealed that the highest dry matter (DM) yield (28 kg/tree) was obtained for F. roxburghii but that remained statistically similar (P > 0.05) to the other treatment. On the other hand, most of the parameters: ether extract (EE), acid detergent lignin (ADL), acid detergent fibre (ADF), cell wall digestibility (CWD), relative digestibility (RD), digestible nutrient (TDN), and Calcium (Ca) among the treatments were highly significant (P < 0.01). This indicates the scope of introducing productive and nutritive fodder trees species even at the high altitude to help reduce fodder scarcity problem during winter. The finding also revealed the scope of promoting all available local fodder trees species as crude protein content of these species were similar.

Keywords: fodder trees, yield potential, climate change, nutrient composition

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Authors: Norihiro Kato, Yuriko Takayama

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Some gram-negative bacteria enable the simultaneous activation of gene expression involved in N-acylhomoserine lactone (AHL) dependent cell-to-cell communication system. Such regulatory system for the bacterial group behavior is termed as quorum sensing (QS) because a diffusible AHL signal can accumulate around the cell during the increase of the cell density and trigger activation of the sequential QS process. By blocking the QS, the expression of diverse genes related to infection, antibiotic production, and biofilm formation is inhibited. Conditioning of QS by regulation of the DNA-receptor-AHL interaction is a potential target for enhancing host defenses against pathogenicity. We focused on engineered application of transcriptional regulator SpnR produced in opportunistic human pathogen Serratia marcescens. The SpnR can interact with AHL signals at an N-terminal domain and also with a promoter region of a QS target gene at a C-terminal domain. As the initial process of the QS activation, the SpnR forms a complex with the AHL to enhance the expression of pig cluster; the SpnR normally acts as an activator for the expression of the QS-dependent gene. In this research, we attempt to artificially control QS by changing the role of SpnR. The QS-dependent prodigiosin production is expected to inhibit by externally added SpnR in the culture broth of AS-1 strain because the AHL concentration was kept below the threshold by AHL-SpnR complex formation. Maltose-binding protein (MBP)-tagged SpnR (MBP-SpnR) was overexpressed in Escherichia coli and purified using an affinity chromatography equipped with an amylose resin column. The specific interaction between AHL and MBP-SpnR was demonstrated by quartz crystal microbalance (QCM) sensor. AHL with amino end-group was coupled with COOH-terminated self-assembled monolayer prepared on a gold electrode of 27-MHz quartz crystal sensor using water-soluble carbodiimide. After the injection of MBP-SpnR into a cup-type sensor cell filled with the buffer solution, time course of resonant frequency change (ΔFs) was determined. A decrease of ΔFs clearly showed the uptake of MBP-SpnR onto the AHL-immobilized electrode. Furthermore, no binding affinity was observed after the heat-inactivation of MBP-SpnR at 80ºC. These results suggest that MBP-SpnR possesses a specific affinity for AHL. MBP-SpnR was added to the culture medium as an AHL trap to study inhibitory effects on intracellularly accumulated prodigiosin. With approximately 2 µM MBP-SpnR, the amount of prodigiosin induced was half that of the control without any additives. In conclusion, the function of SpnR could be switched by adding it to the cell culture. Exogenously added MBP-SpnR possesses high affinity for AHL derived from cells and acts as an inhibitor of AHL-mediated QS.

Keywords: intracellular signaling, microbial biotechnology, quorum sensing, transcriptional regulator

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Authors: E. Wairimu Mwangi, Daniel Sarpong

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Background: Access to effective antiretroviral therapy in the United States has resulted in the rise in longevity in people living with HIV (PLHIV). Despite the progress, women living with HIV (WLWH) experience increasing rates of cardiometabolic disorders compared with their HIV-negative counterparts. Studies focusing on the predictors of metabolic disorders in this population have largely focused on the composite measure of metabolic syndrome (METs). This study seeks to identify the predictors of composite and individual METs factors in a nationally representative sample of WLWH. In particular, the study also examines the role of food security in predicting METs. Methods: The study comprised 1800 women, a subset of participants from the Women’s Interagency HIV Study (WIHS). The primary exposure variable, food security, was measured using the U.S. 10-item Household Food Security Survey Module. The outcome measures are the five metabolic syndrome indicators (elevated blood pressure [systolic BP > 130 mmHg and diastolic BP ≥ 85 mmHg], elevated fasting glucose [≥ 110 mg/dL], elevated fasting triglyceride [≥ 150 mg/dL], reduced HDL cholesterol [< 50 mg/dL], and waist circumference > 88 cm) and the composite measure - Metabolic Syndrome (METs) Status. Each metabolic syndrome indicator was coded one if yes and 0 otherwise. The values of the five indicators were summed, and participants with a total score of 3 or greater were classified as having metabolic syndrome. Participants classified as having metabolic syndrome were assigned a code of 1 and 0 otherwise for analysis. The covariates accounted for in this study fell into sociodemographic factors and behavioral and health characteristics. Results: The participants' mean (SD) age was 47.1 (9.1) years, with 71.4% Blacks and 10.9% Whites. About a third (33.1%) had less than a high school (HS) diploma, 60.4% were married, 32.8% were employed, and 53.7% were low-income. The prevalence of worst dietary diversity, low, moderate, and high food security were 24.1%, 26.6%, 17.0%, and 56.4%, respectively. The correlate profile of the five individual METs factors plus the composite measure of METs differ significantly, with METs based on HDL having the most correlates (Age, Education, Drinking Status, Low Income, Body Mass Index, and Health Perception). Additionally, metabolic syndrome based on waist circumference was the only metabolic factor where food security was significantly correlated (Food Security, Age, and Body Mass Index). Age was a significant predictor of all five individual METs factors plus the composite METs measure. Except for METs based on Fasting Triglycerides, body mass index (BMI) was a significant correlate of the various measures of metabolic syndrome. Conclusion: High-density Lipoprotein (HDL) cholesterol significantly correlated with most predictors. BMI was a significant predictor of all METs factors except Fasting Triglycerides. Food insecurity, the primary predictor, was only significantly associated with waist circumference.

Keywords: blood pressure, food insecurity, fasting glucose, fasting triglyceride, high-density lipoprotein, metabolic syndrome, waist circumference, women living with HIV

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Authors: Emmanuel A. David, Rebecca O. Soremekun, Roseline I. Aderemi-Williams

Abstract:

Background: The complexities involved in the management of diabetes mellitus require a multi-dimensional, multi-professional collaborative and continuous care by health care providers and a substantial self-care by the patients in order to achieve desired treatment outcomes. The effect of pharmacists’ care in the management of diabetes in resource-endowed nations is well documented in literature, but randomised-controlled assessment of the impact of pharmacist-led care among patients with diabetes in resource-limited settings like Nigeria and sub-Saharan Africa countries is scarce. Objective: To evaluate the impact of Pharmacist-led care on glycaemic control in patients with uncontrolled type 2 diabetes, using a randomised-controlled study design Methods: This study employed a prospective randomised controlled design, to assess the impact of pharmacist-led care on glycaemic control of 108 poorly controlled type 2 diabetic patients. A total of 200 clinically diagnosed type 2 diabetes patients were purposively selected using fasting blood glucose ≥ 7mmol/L and tested for long term glucose control using Glycated haemoglobin measure. One hundred and eight (108) patients with ≥ 7% Glycated haemoglobin were recruited for the study and assigned unique identification numbers. They were further randomly allocated to intervention and usual care groups using computer generated random numbers, with each group containing 54 subjects. Patients in the intervention group received pharmacist-structured intervention, including education, periodic phone calls, adherence counselling, referral and 6 months follow-up, while patients in usual care group only kept clinic appointments with their physicians. Data collected at baseline and six months included socio-demographic characteristics, fasting blood glucose, Glycated haemoglobin, blood pressure, lipid profile. With an intention to treat analysis, Mann-Whitney U test was used to compared median change from baseline in the primary outcome (Glycated haemoglobin) and secondary outcomes measure, effect size was computed and proportion of patients that reached target laboratory parameter were compared in both arms. Results: All enrolled participants (108) completed the study, 54 in each study. Mean age was 51±11.75 and majority were female (68.5%). Intervention patients had significant reduction in Glycated haemoglobin (-0.75%; P<0.001; η2 = 0.144), with greater proportion attaining target laboratory parameter after 6 months of care compared to usual care group (Glycated haemoglobin: 42.6% vs 20.8%; P=0.02). Furthermore, patients who received pharmacist-led care were about 3 times more likely to have better glucose control (AOR 2.718, 95%CI: 1.143-6.461) compared to usual care group. Conclusion: Pharmacist-led care significantly improved glucose control in patients with uncontrolled type 2 diabetes mellitus and should be integrated in the routine management of diabetes patients, especially in resource-limited settings.

Keywords: glycaemic control , pharmacist-led care, randomised-controlled trial , type 2 diabetes mellitus

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