Search results for: low molecular weight peptide

Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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Authors: Christoph Opperer

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Space syntax is a theory and method for analyzing the spatial layout of buildings and urban environments to understand how they can influence patterns of human movement, social interaction, and behavior. While direct visibility is a key factor in space syntax research, important visual information such as light, color, texture, etc., are typically not considered, even though psychological studies have shown a strong correlation to the human perceptual experience within physical space – with light and color, for example, playing a crucial role in shaping the perception of spaciousness. Furthermore, these surface properties are often the visual features that are most salient and responsible for drawing attention to certain elements within the environment. This paper explores the potential of integrating these factors into general space syntax methods and visibility-based analysis of space, particularly for architectural spatial layouts. To this end, we use a combination of geometric (isovist) and topological (visibility graph) approaches together with image-based methods, allowing a comprehensive exploration of the relationship between spatial geometry, visual aesthetics, and human experience. Custom-coded ray-tracing techniques are employed to generate spherical panorama images, encoding three-dimensional spatial data in the form of two-dimensional images. These images are then processed through computer vision algorithms to generate saliency-maps, which serve as a visual representation of areas most likely to attract human attention based on their visual properties. The maps are subsequently used to weight the vertices of isovists and the visibility graph, placing greater emphasis on areas with high saliency. Compared to traditional methods, our weighted visibility analysis introduces an additional layer of information density by assigning different weights or importance levels to various aspects within the field of view. This extends general space syntax measures to provide a more nuanced understanding of visibility patterns that better reflect the dynamics of human attention and perception. Furthermore, by drawing parallels to traditional isovist and VGA analysis, our weighted approach emphasizes a crucial distinction, which has been pointed out by Ervin and Steinitz: the difference between what is possible to see and what is likely to be seen. Therefore, this paper emphasizes the importance of including surface properties in visibility-based analysis to gain deeper insights into how people interact with their surroundings and to establish a stronger connection with human attention and perception.

Keywords: space syntax, visibility analysis, isovist, visibility graph, visual features, human perception, saliency detection, raytracing, spherical images

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Authors: Mishell E. Cabrera, Bryan G. Valencia, Anderson I. Guamán

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Human dependence on plastic products has led to global pollution, with plastic particles ranging in size from 0.001 to 5 millimeters, which are called microplastics (hereafter, MPs). The abundance of microplastics is used as an indicator of pollution. However, reports of pollution (abundance of MPs) in river sediments do not consider that the accumulation of sediments and MPs depends on the energy of the river. That is, the abundance of microplastics will be underestimated if the sediments analyzed come from places where the river flows with a lot of energy, and the abundance will be overestimated if the sediment analyzed comes from places where the river flows with less energy. This bias can generate an error greater than 300% of the MPs value reported for the same river and should increase when comparisons are made between 2 rivers with different characteristics. Sections where the river flows with higher energy allow sands to be deposited and limit the accumulation of MPs, while sections, where the same river has lower energy, allow fine sediments such as clays and silts to be deposited and should facilitate the accumulation of MPs particles. That is, the abundance of MPs in the same river is underrepresented when the sediment analyzed is sand, and the abundance of MPs is overrepresented if the sediment analyzed is silt or clay. The present investigation establishes a protocol aimed at incorporating sample granulometry to calibrate MPs quantification and eliminate over- or under-representation bias (hereafter granulometric bias). A total of 30 samples were collected by taking five samples within six work zones. The slope of the sampling points was less than 8 degrees, referred to as low slope areas, according to the Van Zuidam slope classification. During sampling, blanks were used to estimate possible contamination by MPs during sampling. Samples were dried at 60 degrees Celsius for three days. A flotation technique was employed to isolate the MPs using sodium metatungstate with a density of 2 gm/l. For organic matter digestion, 30% hydrogen peroxide and Fenton were used at a ratio of 6:1 for 24 hours. The samples were stained with rose bengal at a concentration of 200 mg/L and were subsequently dried in an oven at 60 degrees Celsius for 1 hour to be identified and photographed in a stereomicroscope with the following conditions: Eyepiece magnification: 10x, Zoom magnification (zoom knob): 4x, Objective lens magnification: 0.35x for analysis in ImageJ. A total of 630 fibers of MPs were identified, mainly red, black, blue, and transparent colors, with an overall average length of 474,310 µm and an overall median length of 368,474 µm. The particle size of the 30 samples was calculated using 100 g per sample using sieves with the following apertures: 2 mm, 1 mm, 500 µm, 250 µm, 125 µm and 0.63 µm. This sieving allowed a visual evaluation and a more precise quantification of the microplastics present. At the same time, the weight of sediment in each fraction was calculated, revealing an evident magnitude: as the presence of sediment in the < 63 µm fraction increases, a significant increase in the number of MPs particles is observed.

Keywords: microplastics, pollution, sediments, Tena River

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Authors: Wilai Masanga, Chirapha Tannanonta, Sangutid Thongsawad, Sasikarn Chamchod, Todsaporn Fuangrod

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The major factors of radiotherapy for head and neck (HN) cancers include patient’s anatomical changes and tumour shrinkage. These changes can significantly affect the planned dose distribution that causes the treatment plan deterioration. A measured transit EPID images compared to a predicted EPID images using gamma analysis has been clinically implemented to verify the dose accuracy as part of adaptive radiotherapy protocol. However, a global gamma analysis dose not sensitive to some critical organ changes as the entire treatment field is compared. The objective of this feasibility study is to evaluate the dosimetric response to patient anatomical changes during the treatment course in HN IMRT (Head and Neck Intensity-Modulated Radiation Therapy) using a novel comparison method; organ-of-interest gamma analysis. This method provides more sensitive to specific organ change detection. Random replanned 5 HN IMRT patients with causes of tumour shrinkage and patient weight loss that critically affect to the parotid size changes were selected and evaluated its transit dosimetry. A comprehensive physics-based model was used to generate a series of predicted transit EPID images for each gantry angle from original computed tomography (CT) and replan CT datasets. The patient structures; including left and right parotid, spinal cord, and planning target volume (PTV56) were projected to EPID level. The agreement between the transit images generated from original CT and replanned CT was quantified using gamma analysis with 3%, 3mm criteria. Moreover, only gamma pass-rate is calculated within each projected structure. The gamma pass-rate in right parotid and PTV56 between predicted transit of original CT and replan CT were 42.8%( ± 17.2%) and 54.7%( ± 21.5%). The gamma pass-rate for other projected organs were greater than 80%. Additionally, the results of organ-of-interest gamma analysis were compared with 3-dimensional cone-beam computed tomography (3D-CBCT) and the rational of replan by radiation oncologists. It showed that using only registration of 3D-CBCT to original CT does not provide the dosimetric impact of anatomical changes. Using transit EPID images with organ-of-interest gamma analysis can provide additional information for treatment plan suitability assessment.

Keywords: re-plan, anatomical change, transit electronic portal imaging device, EPID, head, and neck

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Authors: Teruya Goto, Hokuto Chiba, Tatsuhiro Takahashi

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Carbon fiber reinforced thermoplastic resin using short carbon fiber has been produced by melt mixing and the improvement of mechanical properties has been frequently reported up to now. One of the most frequently reported enhancement has been seen in carbon fiber / polypropylene (PP) composites by adding small amount of maleic anhydride grafted polypropylene (MA-g-PP) into PP matrix. However, the further enhancement of tensile strength and tensile modules has been expected for lightning the composite more. Our present research aims to improve the mechanical property by using a highly reactive monolayer polymer, which can react with both COOH of carbon fiber surface and maleic anhydride of MA-g-PP in the matrix, on carbon fiber for PP/CF composite. It has been known that oxazoline has much higher reactivity with COOH without catalysts, compared with amine group and alcohol OH group. However, oxazoline group has not been used for the interface. To achieve the purpose, poly-2-vinyl-2-oxazoline (Pvozo), having highly reactivity with COOH and maleic anhydride, has been originally synthesized through radical polymerization using 2-vinyl-2-oxazoline as a monomer, resulting in the Mw around 140,000. Monolayer Pvozo chemically reacted on CF was prepared in 1-methoxy-2-propanol solution of Pvozo by heating at 100oC for 3 hours. After this solution treatment, unreacted Pvozo was completely washed out by methanol, resulting the uniform formation of the monolayer Pvozo on CF. Monolayer Pvozo coated CF was melt mixed by with PP and a small amount of MA-g-PP for the preparation of the composite samples using a batch type melt mixer. With performing the tensile strength tests of the composites, the tensile strength of CF/MA-g-PP/PP showed 40% increase, compared to that of CF/PP. While, that of Pvozo coated CF/MA-g-PP/PP exhibited 80% increase, compared to that of CF/PP. To get deeper insight of the dramatic increase, the weight percentage of chemically grafted polymer based on CF was evaluated by dissolving and removing the matrix polymer by xylene using by thermos gravimetric analysis (TGA). The chemically grafted remained polymer was found to be 0.69wt% in CF/PP, 0.98wt% in CF/MA-g-PP/PP, 1.51wt% in Pvozo coated CF/MA-g-PP/PP, suggesting that monolayer Pvozo contributed to the increase of the grafted polymer amount. In addition, the very strong adhesion by Pvozo was confirmed by observing the fractured cross-sectional surface of the composite by scanning electron micrograph (SEM). As a conclusion, the effectiveness of a highly reactive monolayer Pvozo on CF for the enhancement of the mechanical properties of CF/PP composite was demonstrated, which can be interpreted by the clear evidence of the increase of the grafting polymer on CF.

Keywords: CFRTP, interface, oxazoline, polymer graft, mechanical property

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Authors: Enes Huylu, Sude Erkin, Nur A. Özdemir, Hatice K. Güney, Cemre S. Atılgan, Hüseyin Y. Altıntaş, Aysemin Top, Muammer Yılman, Özak Durmuş

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Remanufacturing (reman) applications allow manufacturers to contribute to the circular economy and help to introduce products with almost the same quality, environment-friendly, and lower cost. The objective of this study is to present that the carbon footprint of automotive spare parts used in vehicles could be reduced by reman applications based on Life Cycle Analysis which was framed with ISO 14040 principles. In that case, it was aimed to investigate reman applications for 21 parts in total. So far, research and calculations have been completed for the alternator, turbocharger, starter motor, compressor, manual transmission, auto transmission, and DPF (diesel particulate filter) parts, respectively. Since the aim of Ford Motor Company and Ford OTOSAN is to achieve net zero based on Science-Based Targets (SBT) and the Green Deal that the European Union sets out to make it climate neutral by 2050, the effects of reman applications are researched. In this case, firstly, remanufacturing articles available in the literature were searched based on the yearly high volume of spare parts sold. Paper review results related to their material composition and emissions released during incoming production and remanufacturing phases, the base part has been selected to take it as a reference. Then, the data of the selected base part from the research are used to make an approximate estimation of the carbon footprint reduction of the relevant part used in Ford OTOSAN. The estimation model is based on the weight, and material composition of the referenced paper reman activity. As a result of this study, it was seen that remanufacturing applications are feasible to apply technically and environmentally since it has significant effects on reducing the emissions released during the production phase of the vehicle components. For this reason, the research and calculations of the total number of targeted products in yearly volume have been completed to a large extent. Thus, based on the targeted parts whose research has been completed, in line with the net zero targets of Ford Motor Company and Ford OTOSAN by 2050, if remanufacturing applications are preferred instead of recent production methods, it is possible to reduce a significant amount of the associated greenhouse gas (GHG) emissions of spare parts used in vehicles. Besides, it is observed that remanufacturing helps to reduce the waste stream and causes less pollution than making products from raw materials by reusing the automotive components.

Keywords: greenhouse gas emissions, net zero targets, remanufacturing, spare parts, sustainability

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Authors: Mahsa Jalili, Essa Ehsan Khan, Signe Dille Lovmo, Augustine Akruwe, Egil Lien, Rolf Erik Olsen, Trygve Sigholt, Atle Magnus Bones

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Data from the Norwegian Directorate of Fisheries reported that >1.2 million tons of Atlantic salmon were produced in Norway aquaculture industry in 2016. Peroxisome proliferator-activated receptors (PPARs) are one of the key transcription factor families that respond to nutritional ligands. Recent studies have shown the connection between PPARs with lipid and carbohydrate metabolism in aquaculture. To our knowledge, there is no published data about the effects of krill meal, soybean meal, Bactocell ® and butyrate feedings compared to control group on PPARs gene and protein expressions in Atlantic salmon. Fish, 1year +postsmolt, average weight 250 gram were cultured for 12 weeks after acclimatization by control commercial feeding in 2 weeks after hatchery. Water oxygen rate, salinity, and temperature were monitored every second day. At the end of the trial, fish were taken from tanks randomly, and four replicates per group were collected and stored in -80 freezers until analysis. Total RNA extracted from posterior part of dorsal fin muscle tissues and Nanodrop and Bioanalyzer was used to check the quality of RNA. Gene expression of PPAR α, β and γ were determined by RT-PCR. The expression of genes of interest was measured relative to control group after normalization to three reference genes. Total protein concentration was calculated by Bradford method, and protein expression was determined with primary PPARγ antibody by western blot. All data were analyzed by ANOVA followed by Benjamini-Hochberg and Bonferroni tests. Probability values <0.05 considered significant. Bactocell® and butyrate groups showed significantly lower PPARα expression. PPARβ and γ were not significantly different among groups. PPARγ mRNA expression was approximately consistent with protein expression pattern, except than butyrate group showed lower mRNA level. The order of PPARγ expression was Bactocell® > soy meal > butyrate > krill meal > control respectively. PPARβ gene expression decreased more in soy meal > butyrate > krill meal > Bactocell® > control groups respectively. In conclusion, the increased expression of PPARγ and α is proposed to represent a reduction tendency of lipid storage in fish fed by Bactocell®, butyrate, soy and krill meal.

Keywords: aquaculture, blotting western, gene expression, krill protein extract, prebiotics, probiotics, Salmo salar

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Authors: Poojan Gharat, Haridas Pal, Sharmistha Dutta Choudhury

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Tuning photophysical properties of guest dyes through host-guest interactions involving macrocyclic hosts are the attractive research areas since past few decades, as these changes can directly be implemented in chemical sensing, molecular recognition, fluorescence imaging and dye laser applications. Excited state intramolecular proton transfer (ESIPT) is an intramolecular prototautomerization process display by some specific dyes. The process is quite amenable to tunability by the presence of different macrocyclic hosts. The present study explores the interesting effect of p-sulfonatocalix[n]arene (SCXn) and cyclodextrin (CD) hosts on the excited-state prototautomeric equilibrium of Chrysazine (CZ), a model antitumour drug. CZ exists exclusively in its normal form (N) in the ground state. However, in the excited state, the excited N* form undergoes ESIPT along with its pre-existing intramolecular hydrogen bonds, giving the excited state prototautomer (T*). Accordingly, CZ shows a single absorption band due to N form, but two emission bands due to N* and T* forms. Facile prototautomerization of CZ is considerably inhibited when the dye gets bound to SCXn hosts. However, in spite of lower binding affinity, the inhibition is more profound with SCX6 host as compared to SCX4 host. For CD-CZ system, while prototautomerization process is hindered by the presence of β-CD, it remains unaffected in the presence of γCD. Reduction in the prototautomerization process of CZ by SCXn and βCD hosts is unusual, because T* form is less dipolar in nature than the N*, hence binding of CZ within relatively hydrophobic hosts cavities should have enhanced the prototautomerization process. At the same time, considering the similar chemical nature of two CD hosts, their effect on prototautomerization process of CZ would have also been similar. The atypical effects on the prototautomerization process of CZ by the studied hosts are suggested to arise due to the partial inclusion or external binding of CZ with the hosts. As a result, there is a strong possibility of intermolecular H-bonding interaction between CZ dye and the functional groups present at the portals of SCXn and βCD hosts. Formation of these intermolecular H-bonds effectively causes the pre-existing intramolecular H-bonding network within CZ molecule to become weak, and this consequently reduces the prototautomerization process for the dye. Our results suggest that rather than the binding affinity between the dye and host, it is the orientation of CZ in the case of SCXn-CZ complexes and the binding stoichiometry in the case of CD-CZ complexes that play the predominant role in influencing the prototautomeric equilibrium of the dye CZ. In the case of SCXn-CZ complexes, the results obtained through experimental findings are well supported by quantum chemical calculations. Similarly for CD-CZ systems, binding stoichiometries obtained through geometry optimization studies on the complexes between CZ and CD hosts correlate nicely with the experimental results. Formation of βCD-CZ complexes with 1:1 stoichiometry while formation of γCD-CZ complexes with 1:1, 1:2 and 2:2 stoichiometries are revealed from geometry optimization studies and these results are in good accordance with the observed effects by the βCD and γCD hosts on the ESIPT process of CZ dye.

Keywords: intermolecular proton transfer, macrocyclic hosts, quantum chemical studies, photophysical studies

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Authors: Abdolrasoul Daneshjoo

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Introduction: Soccer is a game which draws more attention in different countries especially in Brazil. Kicking among different skills in soccer and soccer players is an excellent role for the success and preference of a team. The way of point gaining in this game is passing the ball over the goal lines which are gained by shoot skill in attack time and or during the penalty kicks.Regarding the above assumption, identifying the effective factors in instep kicking in different distances shoot with maximum force and high accuracy or pass and penalty kick, may assist the coaches and players in raising qualitative level of performing the skill. Purpose: The aim of the present study was to study of a few kinematical parameters in instep kicking from 3 and 5 meter distance among the male and female elite soccer players. Methods: 24 right dominant lower limb subjects (12 males and 12 females) among Tehran elite soccer players with average and the standard deviation (22.5 ± 1.5) & (22.08± 1.31) years, height of (179.5 ± 5.81) & (164.3 ± 4.09) cm, weight of (69.66 ± 4.09) & (53.16 ± 3.51) kg, %BMI (21.06 ± .731) & (19.67 ± .709), having playing history of (4 ± .73) & (3.08 ± .66) years respectively participated in this study. They had at least two years of continuous playing experience in Tehran soccer league.For sampling player's kick; Kinemetrix Motion analysis with three cameras with 500 Hz was used. Five reflective markers were placed laterally on the kicking leg over anatomical points (the iliac crest, major trochanter, lateral epicondyle of femur, lateral malleolus, and lateral aspect of distal head of the fifth metatarsus). Instep kick was filmed, with one step approach and 30 to 45 degrees angle from stationary ball. Three kicks were filmed, one kick selected for further analyses. Using Kinemetrix 3D motion analysis software, the position of the markers was analyzed. Descriptive statistics were used to describe the mean and standard deviation, while the analysis of variance, and independent t-test (P < 0.05) were used to compare the kinematic parameters between two genders. Results and Discussion: Among the evaluated parameters, the knee acceleration, the thigh angular velocity, the angle of knee proportionately showed significant relationship with consequence of kick. While company performance on 5m in 2 genders, significant differences were observed in internal – external displacement of toe, ankle, hip and the velocity of toe, ankle and the acceleration of toe and the angular velocity of pelvic, thigh and before time contact. Significant differences showed the internal – external displacement of toe, the ankle, the knee and the hip, the iliac crest and the velocity of toe, the ankle and acceleration of ankle and angular velocity of the pelvic and the knee.

Keywords: biomechanics, kinematics, soccer, instep kick, male, female

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Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

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Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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Authors: Khin Thandar Soe, Mark Stephen Pulham

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Ballistic building materials play a crucial role in ensuring the safety of the occupants within protective structures. Traditional options like Ordinary Portland Cement (OPC)-based walls, including reinforced concrete walls, precast concrete walls, masonry walls, and concrete blocks, are frequently employed for ballistic protection, but they have several drawbacks such as being thick, heavy, costly, and challenging to construct. On the other hand, glass and composite materials offer lightweight and easier construction alternatives, but they come with a high price tag. There has been no reported test data on magnesium-based ballistic wall panels or modular wall systems so far. This paper presents groundbreaking small arms test data related to the development of the world’s first magnesia cement ballistic wall panels and modular wall system. Non-hydraulic magnesia cement exhibits several superior properties, such as lighter weight, flexibility, acoustics, and fire performance, compared to the traditional Portland Cement. However, magnesia cement is hydrophilic and may degrade in prolonged contact with water. In this research, modified magnesia cement for water resistant and durability from UBIQ Technology is applied. The specimens are made of a modified magnesia cement formula and prepared in the Laboratory of UBIQ Technology Pty Ltd. The specimens vary in thickness, and the tests cover various small arms threats in compliance with standards AS/NZS2343 and UL752 and are performed up to the maximum threat level of Classification R2 (NATO) and UL-Level 8(NATO) by the Accredited Test Centre, BMT (Ballistic and Mechanical Testing, VIC, Australia). In addition, the results of the test conducted on the specimens subjected to the small 12mm diameter steel ball projectile impact generated by a gas gun are also presented and discussed in this paper. Gas gun tests were performed in UNSW@ADFA, Canberra, Australia. The tested results of the magnesia panels and wall systems are compared with one of concrete and other wall panels documented in the literature. The conclusion drawn is that magnesia panels and wall systems exhibit several advantages over traditional OPC-based wall systems, and they include being lighter, thinner, and easier to construct, all while providing equivalent protection against threats. This makes magnesia cement-based materials a compelling choice of application where efficiency and performance are critical to create a protective environment.

Keywords: ballistics, small arms, gas gun, projectile, impact, wall panels, modular, magnesia cement

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Authors: Radik D. Aglyamov, Alexander K. Naumov, Alexey A. Shavelev, Oleg A. Morozov, Arsenij D. Shishkin, Yury P.Brodnikovsky, Alexander A.Karabutov, Alexander A. Oraevsky, Vadim V. Semashko

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The development of medical optoacoustic tomography with the using human blood as endogenic contrast agent is constrained by the lack of reliable, easy-to-use and inexpensive sources of high-power pulsed laser radiation in the spectral region of 750-900 nm [1-2]. Currently used titanium-sapphire, alexandrite lasers or optical parametric light oscillators do not provide the required and stable output characteristics, they are structurally complex, and their cost is up to half the price of diagnostic optoacoustic systems. Here we are developing the lasers based on Cr:LiCaAlF6 crystals which are free of abovementioned disadvantages and provides intensive ten’s ns-range tunable laser radiation at specific absorption bands of oxy- (~840 nm) and -deoxyhemoglobin (~757 nm) in the blood. Cr:LiCAF (с=3 at.%) crystals were grown in Kazan Federal University by the vertical directional crystallization (Bridgman technique) in graphite crucibles in a fluorinating atmosphere at argon overpressure (P=1500 hPa) [3]. The laser elements have cylinder shape with the diameter of 8 mm and 90 mm in length. The direction of the optical axis of the crystal was normal to the cylinder generatrix, which provides the π-polarized laser action correspondent to maximal stimulated emission cross-section. The flat working surfaces of the active elements were polished and parallel to each other with an error less than 10”. No any antireflection coating was applied. The Q-switched master oscillator-power amplifiers laser system (MOPA) with the dual-Xenon flashlamp pumping scheme in diffuse-reflectivity close-coupled head were realized. A specially designed laser cavity, consisting of dielectric highly reflective reflectors with a 2 m-curvature radius, a flat output mirror, a polarizer and Q-switch sell, makes it possible to operate sequentially in a circle (50 ns - laser one pulse after another) at wavelengths of 757 and 840 nm. The programmable pumping system from Tomowave Laser LLC (Russia) provided independent to each pulses (up to 250 J at 180 μs) pumping to equalize the laser radiation intensity at these wavelengths. The MOPA laser operates at 10 Hz pulse repetition rate with the output energy up to 210 mJ. Taking into account the limitations associated with physiological movements and other characteristics of patient tissues, the duration of laser pulses and their energy allows molecular and functional high-contrast imaging to depths of 5-6 cm with a spatial resolution of at least 1 mm. Highly likely the further comprehensive design of laser allows improving the output properties and realizing better spatial resolution of medical multispectral optoacoustic tomography systems.

Keywords: medical optoacoustic, endogenic contrast agent, multiwavelength tunable pulse lasers, MOPA laser system

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Authors: Anupalli Roja Rani, Pavithra Dasari

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Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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Authors: S.Kauroo, J. Govinden Soulange, D. Marie

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Psiadia species from the Asteraceae are traditionally used in the folk medicine of Mauritius to treat cutaneous and bronchial infections. The present study aimed at validating the phytomedicinal properties of the selected species from the Asteraceae family, namely Psiadia arguta, Psiadia viscosa, Psiadia lithospermifolia, and Distephanus populifolius. Dried hexane, ethyl acetate, and methanol leaf extracts were studied for their antioxidant properties using the DPPH (1, 1-diphenyl-2-picryl-hydrazyl), FRAP (Ferric Reducing Ability of Plasma), and Deoxyribose assays. Antibacterial activity against human pathogenic bacteria namely Escherichia coli (ATCC 27853), Staphylococcus aureus (ATCC 29213), Enterococcus faecalis (ATCC 29212), Klebsiella pneumonia (ATCC27853), Pseudomonas aeruginosa (ATCC 27853), and Bacillus cereus (ATCC 11778) was measured using the broth microdilution assay. Qualitative phytochemical screening using standard methods revealed the presence of coumarins, tannins, leucoanthocyanins, and steroids in all the tested extracts. The measured phenolics level of the selected plant extracts varied from 24.0 to 231.6 mg GAE/g with the maximum level in methanol extracts in all four species. The highest flavonoids and proanthocyanidins content was noted in Psiadia arguta methanolic extracts with 65.7±1.8 mg QE/g and 5.1±0.0 mg CAT/g dry weight (DW) extract, respectively. The maximum free radical scavenging activity was measured in Psiadia arguta methanol and ethyl acetate extracts with IC50 11.3±0.2 and 11.6± 0.2 µg/mL, respectively and followed by Distephanus populifolius methanol extracts with an IC50 of 11.3± 0.8 µg/mL. The maximum ferric reducing antioxidant potential was noted in Psiadia lithospermifolia methanol extracts with a FRAP value of 18.8 ± 0.4 µmol Fe2+/L/g DW. The antioxidant capacity based on DPPH and Deoxyribose values were negatively related to total phenolics, flavonoid and proanthocyanidins content while the ferric reducing antioxidant potential were strongly correlated to total phenolics, flavonoid and proanthocyanidins content. All four species exhibited antimicrobial activity against the tested bacteria (both Gram-negative and Gram-positive). Interestingly, the hexane and ethyl acetate extracts of Psiadia viscosa and Psiadia lithospermifolia were more active than the control antibiotic Chloramphenicol. The Minimum inhibitory concentration (MIC) values for hexane and ethyl acetate extracts of Psiadia viscosa and Psiadia lithospermifolia against the tested bacteria ranged from (62.5 to 500 µg/ml). These findings validate the use of these tested Asteraceae in the traditional medicine of Mauritius and also highlight their pharmaceutical potential as prospective phytomedicines.

Keywords: antibacterial, antioxidant, DPPH, flavonoids, FRAP, Psiadia spp

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Authors: Shashi Bala, Neha A. Chugh, Subhash C. Bansal, Mohal L. Garg, Ashwani Koul

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Purpose: The present study was designed to evaluate the radioprotective efficacy of Aloe vera from whole body X-ray exposure in rodents. Materials and Methods: For this purpose, after on week’s acclimatization, male balb/c mice procured from Central Animal House, Panjab University, Chandigarh (India), were divided into four groups: Group I mice served as control. Group II mice were orally administrated Aloe vera pulp extract (50 mg/ kg body weight) on alternate days for 30 days. Group III mice were subjected to whole body X-ray irradiation to cumulative dose of 2Gy (0.258Gy twice a day for four days in the last week). Group IV animals were pretreated with Aloe vera pulp extract on alternate days as in Group II and in the last week of the study, they were exposed to X-ray as in Group III. Results: Spleen of X-ray irradiated mice showed histopathological alterations accompanied with enhanced activity of lactate dehydrogenase (LDH) in serum. Elevated levels of reactive oxygen species (ROS), lipid peroxidation (LPO), enhanced activities in Glutathione based enzymes such as Glutathione peroxidase (GSH-Px), Glutathione reductase (GR), Catalase (CAT), Superoxide dismutase (SOD) associated with depletion in reduced Glutathione (GSH) concentration were observed after X-ray exposure in blood plasma and spleen.. Pro-inflammatory cytokines like tumor necrosis factors (TNF-α) and Inteleukin-6 (IL-6) levels were also found to be enhanced in serum of irradiated mice. Irradiation-induced significant elevation in Total leucocyte counts (TLC), neutrophil counts and decline in platelet counts, associated with unaltered levels of red blood cell counts (RBC’s) and haemoglobin (Hb) in various treatment groups. Clastogenic damage and apoptosis was also found to be increase in splenic tissue of X-ray exposed mice as assessed by micronucleus and TUNEL assay. However, X-ray irradiated animals administered with Aloe vera revealed significant improvement in levels of ROS/ LPO, LDH activity, and antioxidant mechanism. Aloe vera pretreated animals exhibited less severe damage, and early recovery in micronucleated cells, hematological parameters, apoptotic cells and inflammatory markers as compared to X-ray exposed mice. Conclusion: These results indicate that the radioprotective potential of Aloe vera against X-ray induced damage. This may be due to its free radical scavenging, antioxidant, anti-apoptotic and anti-inflammatory properties.

Keywords: aloe vera, antioxidant defense system, lactate dehydrogenase (LDH), micronucleus assay, x-ray

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Authors: Xincheng Jiang, Yanyan An, Yaoyao Huang, Wei Ding, Manli Sun, Hong Li, Huaili Zheng

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The residual antibiotics in the environment will pose a threat to the environment and human health. Thus, efficient removal and rapid detection of norfloxacin (NOR) in wastewater is very important. The main sources of NOR pollution are the agricultural, pharmaceutical industry and hospital wastewater. The total consumption of NOR in China can reach 5440 tons per year. It is found that neither animals nor humans can totally absorb and metabolize NOR, resulting in the excretion of NOR into the environment. Therefore, residual NOR has been detected in water bodies. The hazards of NOR in wastewater lie in three aspects: (1) the removal capacity of the wastewater treatment plant for NOR is limited (it is reported that the average removal efficiency of NOR in the wastewater treatment plant is only 68%); (2) NOR entering the environment will lead to the emergence of drug-resistant strains; (3) NOR is toxic to many aquatic species. At present, the removal and detection technologies of NOR are applied separately, which leads to a cumbersome operation process. The development of simultaneous adsorption-flocculation removal and FTIR detection of pollutants has three advantages: (1) Adsorption-flocculation technology promotes the detection technology (the enrichment effect on the material surface improves the detection ability); (2) The integration of adsorption-flocculation technology and detection technology reduces the material cost and makes the operation easier; (3) FTIR detection technology endows the water treatment agent with the ability of molecular recognition and semi-quantitative detection for pollutants. Thus, it is of great significance to develop a smart water treatment material with high removal capacity and detection ability for pollutants. This study explored the feasibility of combining NOR removal method with the semi-quantitative detection method. A magnetic Cu-Ni-S/Ni foam was synthesized by in-situ loading Cu-Ni-S nanostructures on the surface of Ni foam. The novelty of this material is the combination of adsorption-flocculation technology and semi-quantitative detection technology. Batch experiments showed that Cu-Ni-S/Ni foam has a high removal rate of NOR (96.92%), wide pH adaptability (pH=4.0-10.0) and strong ion interference resistance (0.1-100 mmol/L). According to the Langmuir fitting model, the removal capacity can reach 417.4 mg/g at 25 °C, which is much higher than that of other water treatment agents reported in most studies. Characterization analysis indicated that the main removal mechanisms are surface complexation, cation bridging, electrostatic attraction, precipitation and flocculation. Transmission FTIR detection experiments showed that NOR on Cu-Ni-S/Ni foam has easily recognizable FTIR fingerprints; the intensity of characteristic peaks roughly reflects the concentration information to some extent. This semi-quantitative detection method has a wide linear range (5-100 mg/L) and a low limit of detection (4.6 mg/L). These results show that Cu-Ni-S/Ni foam has excellent removal performance and semi-quantitative detection ability of NOR molecules. This paper provides a new idea for designing and preparing multi-functional water treatment materials to achieve simultaneous removal and semi-quantitative detection of organic pollutants in water.

Keywords: adsorption-flocculation, antibiotics detection, Cu-Ni-S/Ni foam, norfloxacin

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Authors: Faris Mohsin Alabeedi

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Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by the presence of autoantibodies directed against the epidermis's surface proteins. There are two forms of PV, mucocutaneous and mucosal-dominant PV. Disruption of the cell junctions is a hallmark of PV due to the autoantibodies targeting the desmosomal cadherins, desmoglein-3 (Dsg3) and desmoglein-1, leading to acantholysis in the skin and mucous membrane. Although the pathogenesis of PV is known, the detailed molecular events remain not fully understood. Our recent study has shown that both the PV sera and pathogenic anti-Dsg3 antibody AK23 can induce ROS and cause oxidative stress in cultured keratinocytes. In line with our finding, other independent studies also demonstrate oxidative stress in PV. Since Nrf2 plays a crucial role in cellular anti-oxidative stress response, we hypothesize that the expression of Nrf2 may alter in PV. Thus, treatment of cells with PV sera or AK23 may cause changes in Nrf2 expression and distribution. The purpose of this study was to examine the effect of AK23 and PV sera on Nrf2 in a normal human keratinocyte cell line, such as NTERT cells. Both a time-course and dose-dependent experiments with AK23, alongside the matched isotype control IgG, were performed in keratinocyte cultures and analysed by immunofluorescence for Nrf2 and Dsg3. Additionally, the same approach was conducted with the sera from PV patients and healthy individuals that served as a control in this study. All the fluorescent images were analysed using ImageJ software. Each experiment was repeated twice. In general, variations were observed throughout this study. In the dose-response experiments, although enhanced Dsg3 expression was consistently detected in AK23 treated cells, the expression of Nrf2 showed no consistent findings between the experiments, although changes in its expression were noticeable in cells treated with AK23. In the time-course study, a trend with induction of Nrf2 over time was shown in control cells treated with mouse isotype IgG. Treatment with AK23 showed a reduction of Nrf2 in a time-dependent manner, especially at the 24-hour time point. However, the earlier time points, such as 2 hours and 6 hours with AK23 treatments, detected somewhat variations. Finally, PV sera caused a decrease of Dsg3, but on the other hand, variations were observed in Nrf2 expression in PV sera treated cells. In general, PV sera seemed to cause a reduction of Nrf2 in the majority of PV sera treated samples. In addition, more pronounced cytoplasmic expression of Nrf2 has been observed in PV sera treated cells than those treated with AK23, suggesting that polyclonal and monoclonal IgG might induce a different effect on Nrf2 expression and distribution. Further experimental studies are crucial to obtain a more coincide global view of Nrf2-mediated gene regulation. In particular, Pemphigus Voulgaris studies assessing how the Nrf2-dependent network changes from a physiological to a pathological condition can provide insight into disease mechanisms and perhaps initiate further treatment approaches.

Keywords: pemphigus vulgaris, monoclonal antibody against desmoglein-3, Nrf2 oxidative stress, keratinocyte cultures

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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Authors: Shaukat Ali Shahee, Usha Ananthakumar

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A data set exhibits class imbalance problem when one class has very few examples compared to the other class, and this is also referred to as between class imbalance. The traditional classifiers fail to classify the minority class examples correctly due to its bias towards the majority class. Apart from between-class imbalance, imbalance within classes where classes are composed of a different number of sub-clusters with these sub-clusters containing different number of examples also deteriorates the performance of the classifier. Previously, many methods have been proposed for handling imbalanced dataset problem. These methods can be classified into four categories: data preprocessing, algorithmic based, cost-based methods and ensemble of classifier. Data preprocessing techniques have shown great potential as they attempt to improve data distribution rather than the classifier. Data preprocessing technique handles class imbalance either by increasing the minority class examples or by decreasing the majority class examples. Decreasing the majority class examples lead to loss of information and also when minority class has an absolute rarity, removing the majority class examples is generally not recommended. Existing methods available for handling class imbalance do not address both between-class imbalance and within-class imbalance simultaneously. In this paper, we propose a method that handles between class imbalance and within class imbalance simultaneously for binary classification problem. Removing between class imbalance and within class imbalance simultaneously eliminates the biases of the classifier towards bigger sub-clusters by minimizing the error domination of bigger sub-clusters in total error. The proposed method uses model-based clustering to find the presence of sub-clusters or sub-concepts in the dataset. The number of examples oversampled among the sub-clusters is determined based on the complexity of sub-clusters. The method also takes into consideration the scatter of the data in the feature space and also adaptively copes up with unseen test data using Lowner-John ellipsoid for increasing the accuracy of the classifier. In this study, neural network is being used as this is one such classifier where the total error is minimized and removing the between-class imbalance and within class imbalance simultaneously help the classifier in giving equal weight to all the sub-clusters irrespective of the classes. The proposed method is validated on 9 publicly available data sets and compared with three existing oversampling techniques that rely on the spatial location of minority class examples in the euclidean feature space. The experimental results show the proposed method to be statistically significantly superior to other methods in terms of various accuracy measures. Thus the proposed method can serve as a good alternative to handle various problem domains like credit scoring, customer churn prediction, financial distress, etc., that typically involve imbalanced data sets.

Keywords: classification, imbalanced dataset, Lowner-John ellipsoid, model based clustering, oversampling

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Authors: Farzan Gity, Lida Ansari, Ian M. Povey, Roger E. Nagle, James C. Greer

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Titanium nitride (TiN) films have been widely used in variety of fields, due to its unique electrical, chemical, physical and mechanical properties, including low electrical resistivity, chemical stability, and high thermal conductivity. In microelectronic devices, thin continuous TiN films are commonly used as diffusion barrier and metal gate material. However, as the film thickness decreases below a few nanometers, electrical properties of the film alter considerably. In this study, the physical and electrical characteristics of 1.5nm to 22nm thin films deposited by Plasma-Enhanced Atomic Layer Deposition (PE-ALD) using Tetrakis(dimethylamino)titanium(IV), (TDMAT) chemistry and Ar/N2 plasma on 80nm SiO2 capped in-situ by 2nm Al2O3 are investigated. ALD technique allows uniformly-thick films at monolayer level in a highly controlled manner. The chemistry incorporates low level of oxygen into the TiN films forming titanium oxynitride (TiON). Thickness of the films is characterized by Transmission Electron Microscopy (TEM) which confirms the uniformity of the films. Surface morphology of the films is investigated by Atomic Force Microscopy (AFM) indicating sub-nanometer surface roughness. Hall measurements are performed to determine the parameters such as carrier mobility, type and concentration, as well as resistivity. The >5nm-thick films exhibit metallic behavior; however, we have observed that thin film resistivity is modulated significantly by film thickness such that there are more than 5 orders of magnitude increment in the sheet resistance at room temperature when comparing 5nm and 1.5nm films. Scattering effects at interfaces and grain boundaries could play a role in thickness-dependent resistivity in addition to quantum confinement effect that could occur at ultra-thin films: based on our measurements the carrier concentration is decreased from 1.5E22 1/cm3 to 5.5E17 1/cm3, while the mobility is increased from < 0.1 cm2/V.s to ~4 cm2/V.s for the 5nm and 1.5nm films, respectively. Also, measurements at different temperatures indicate that the resistivity is relatively constant for the 5nm film, while for the 1.5nm film more than 2 orders of magnitude reduction has been observed over the range of 220K to 400K. The activation energy of the 2.5nm and 1.5nm films is 30meV and 125meV, respectively, indicating that the TiON ultra-thin films are exhibiting semiconducting behaviour attributing this effect to a metal-semiconductor transition. By the same token, the contact is no longer Ohmic for the thinnest film (i.e., 1.5nm-thick film); hence, a modified lift-off process was developed to selectively deposit thicker films allowing us to perform electrical measurements with low contact resistance on the raised contact regions. Our atomic scale simulations based on molecular dynamic-generated amorphous TiON structures with low oxygen content confirm our experimental observations indicating highly n-type thin films.

Keywords: activation energy, ALD, metal-semiconductor transition, resistivity, titanium oxynitride, ultra-thin film

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Authors: Lennart Dimberg, Lala Joulha Ian

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Introduction: Overweight (BMI 25-30) and obesity (BMI 30+) have consistently been associated with cardiovascular (CV) risk and death since the Framingham heart study in 1948, and BMI was included in the original Framingham risk score (FRS). Background: Myocardial infarction (MI) poses a serious threat to the patient's life. In addition to BMI, several other indices of overweight have been presented and argued to replace FRS as more relevant measures of CV risk. These indices include waist circumference (WC), waist/hip ratio (WHR), sagittal abdominal diameter (SAD), and sagittal abdominal diameter to height (SADHtR). Specific research question: The research question of this study is to evaluate the interrelationship between the various body measurements, BMI, WC, WHR, SAD, and SADHtR, and which measurement is strongly associated with MI and death. Methods: In 1993, 1,000 middle-aged Caucasian, randomly selected working men of the Swedish Volvo-Renault cohort were surveyed at a nurse-led health examination with a questionnaire, EKG, laboratory tests, blood pressure, height, weight, waist, and sagittal abdominal diameter measurements. Outcome data of myocardial infarction over 28 years come from Swedeheart (the Swedish national myocardial infarction registry) and the Swedish death registry. The Aalen-Johansen and Kaplan–Meier methods were used to estimate the cumulative incidences of MI and death. Multiple logistic regression analyses were conducted to compare BMI with the other four body measurements. The risk for the various measures of obesity was calculated with outcomes of accumulated first-time myocardial infarction and death as odds ratios (OR) in quartiles. The ORs between the 4th and the 1st quartile of each measure were calculated to estimate the association between the body measurement variables and the probability of cumulative incidences of myocardial infarction (MI) over time. Double-sided P values below 0.05 will be considered statistically significant. Unadjusted odds ratios were calculated for obesity indicators, MI, and death. Adjustments for age, diabetes, SBP, and the ratio of total cholesterol/HDL-C and blue/white collar status were performed. Results: Out of 1000 people, 959 subjects had full information about the five different body measurements. Of those, 90 participants had a first MI, and 194 persons died. The study showed that there was a high and significant correlation between the five different body measurements, and they were all associated with CVD risk factors. All body measurements were significantly associated with MI, with the highest (OR=3.6) seen for SADHtR and WC. After adjustment, all but SADHtR remained significant with weaker ORs. As for all-cause mortality, WHR (OR=1.7), SAD (OR=1.9), and SADHtR (OR=1.6) were significantly associated, but not WC and BMI. However, after adjustment, only WHR and SAD were significantly associated with death, but with attenuated ORs.

Keywords: BMI, death, epidemiology, myocardial infarction, risk factor, sagittal abdominal diameter, sagittal abdominal diameter to height, waist circumference, waist-hip ratio

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Authors: Amit Sarkar, Jayanta K. Mahato, Tushar Bhattacharya, Amrita Kundu, P. C. Chakraborti

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With increasing the demand for safety and fuel efficiency of automobiles, automotive manufacturers are looking for light weight, high strength steel with excellent formability and corrosion resistance. Dual-phase steel is finding applications in automotive sectors, because of its high strength, good formability, and high corrosion resistance. During service automotive components suffer from environmental attack and thereby gradual degradation of the components occurs reducing the service life of the components. The objective of the present investigation is to assess the effect of deformation on corrosion behaviour of DP590 grade dual phase steel which is used in automotive industries. The material was received from TATA Steel Jamshedpur, India in the form of 1 mm thick sheet. Tensile properties of the steel at strain rate of 10-3 sec-1: 0.2 % Yield Stress is 382 MPa, Ultimate Tensile Strength is 629 MPa, Uniform Strain is 16.30% and Ductility is 29%. Rectangular strips of 100x10x1 mm were machined keeping the long axis of the strips parallel to rolling direction of the sheet. These strips were longitudinally deformed at a strain rate at 10-3 sec-1 to a different percentage of strain, e.g. 2.5, 5, 7.5,10 and 12.5%, and then slowly unloaded. Small specimens were extracted from the mid region of the unclamped portion of these deformed strips. These small specimens were metallographic polished, and corrosion behaviour has been studied by potentiodynamic polarization, electrochemical impedance spectra, and cyclic polarization and potentiostatic tests. Present results show that among three different environments, the 3.5 pct NaCl solution is most aggressive in case of DP 590 dual-phase steel. It is observed that with the increase in the amount of deformation, corrosion rate increases. With deformation, the stored energy increases and leads to enhanced corrosion rate. Cyclic polarization results revealed highly deformed specimen are more prone to pitting corrosion as compared to the condition when amount of deformation is less. It is also observed that stability of the passive layer decreases with the amount of deformation. With the increase of deformation, current density increases in a passive zone and passive zone is also decreased. From Electrochemical impedance spectroscopy study it is found that with increasing amount of deformation polarization resistance (Rp) decreases. EBSD results showed that average geometrically necessary dislocation density increases with increasing strain which in term increased galvanic corrosion as dislocation areas act as the less noble metal.

Keywords: dual phase 590 steel, prestrain, potentiodynamic polarization, cyclic polarization, electrochemical impedance spectra

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Authors: Madelyn N. Moawad, Hermine R. Z. Tadros, Mary G. Ghobrial, Ahmad R. Bassiouny, Kamal M. Kandeel, Athar Ata

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Seaweeds are potential renewable resources in marine environment. They provide an excellent source of bioactive substances such as dietary fibers and various functional polysaccharides that could potentially be used as ingredients for both human and animal health applications. The observations suggested that these bioactive compounds have strong antioxidant properties, which have beneficial effects on human health. The present research aimed at finding new chemical products from local marine macroalgae for natural medicinal uses and consumption for their nutritional values. Macroalgae samples were collected manually mainly from the Mediterranean Sea at shallow subtidal zone of Abu Qir Bay, Alexandria, Egypt. The chemical compositions of lyophilized materials of six selected macroalgal species; Colpomenia sinuosa, Sargassum linifolium, Padina pavonia, Pterocladiella capillacea, Laurencia pinnatifidia, and Caulerpa racemosa, were investigated for proteins using bovine serum albumin, and carbohydrates were assayed by phenol-sulfuric acid reaction. The macroalgae lipid was extracted with chloroform, methanol and phosphate buffer. Vitamins were extracted using trichloroacetic acid. Chlorophylls and total carotenoids were determined spectrophotometrically and total phenols were extracted with methanol. In addition, lipid-soluble, and water-soluble antioxidant, and anti α-glucosidase activities were measured spectrophotometrically. The antioxidant activity of hexane extracts was investigated using phosphomolybdenum reagent. The anti-α-glucosidase effect measurement was initiated by mixing α-glucosidase solution with p-nitrophenyl α-D-glucopyranoside. The results showed that the ash contents varied from 11.2 to 35.4 % on dry weight basis for P. capillacea and Laurencia pinnatifidia, respectively. The protein contents ranged from 5.63 % in brown macroalgae C. sinuosa to 8.73 % in P. pavonia. A relative wide range in carbohydrate contents was observed (20.06–46.75 %) for the test algal species. The highest lipid percentage was found in green alga C. racemosa (5.91%) followed by brown algae P. pavonia (3.57%) and C. sinuosa (2.64%). The phenolic contents varied from 1.32 mg GAE/g for C. sinuosa to 4.00 mg GAE/g in P. pavonia. The lipid-soluble compounds exhibited higher antioxidant capacity (73.18-145.95 µM/g) than that of the water-soluble ones ranging from 24.83 µM/g in C. racemosa to 74.07 µM/g in S. linifolium. The most potent anti-α-glucosidase activity was observed for P. pavonia with IC50 of 17.12 μg/ml followed by S. linifolium (IC50 = 71.75 μg/ml), C. racemosa (IC50 = 84.73 μg/ml), P. capillacea (IC50 = 92.16 μg/ml), C. sinuosa (IC50 = 112.44 μg/ml), and L. pinnatifida (IC50 = 115.11 μg/ml).

Keywords: α-glucosidase, lyophilized, macroalgae, spectrophotometrically

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Authors: Soha A Soliman, Yasser A Ahmed, Mohamed A Khalaf

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Although the enormous literature describing the histology of the stomach of different avian species during the posthatching development, the available literature on the pre-hatching development of quail stomach development is scanty. Thus, the current study was undertaken to provide a careful description of the main histological events during the embryonic development of quail stomach. To achieve this aim, daily histological specimens from the stomach of quail of 4 days post-incubation till the day 17 (few hours before hatching) were examined with light microscopy. The current study showed that the primitive gut tube of the embryonic quail appeared at the 4th day post incubation, and both parts of stomach (proventriculus and gizzard) were similar in structure and composed of endodermal epithelium of pseudostratified type surrounded by undifferentiated mesenchymal tissue. The sequences of the developmental events in the gut tube were preceded in a cranio-caudal pattern. By the 5th day, the endodermal covering of the primitive proventriculus gave rise to sac-like invaginations. The primitive gizzard was distinguished into thick-walled bodies and thin-walled sacs. In the 6th day, the prospective proventricular glandular epithelium became canalized and the muscular layer was developed in the cranial part of the proventriculus, whereas the primitive muscular coat of the gizzard was represented by a layer of condensed mesenchyme. In the 7th day, the proventricular glandular epithelial invaginations increased in depth and number, while, the muscularis mucosa and the muscular layer began to be distinguished. In the 8th day, the myoblasts differentiated into spindle shaped smooth muscle fibers. In the 10th day, branching of the proventricular glands began. The branching continued later on. The surface and the glandular epithelium were transformed into simple columnar type in the 12th day. The epithelial covering of the gizzard gave rise to tubular invaginations lined by simple cuboidal epithelium and the surface epithelium became simple columnar. Canalization of the tubular glands was recognized in the 14th day. In the 15th day, the proventricular surface epithelium invaginated in an concentric manner around a central cavity to form immature secretory units. The central cavity was lined by eosinophilic cells which form the ductal epithelia. The peripheral lamellae were lined by basophilic cells; the undifferentiated oxyntico-peptic cells. Entero-endocrine cells stained positive for silver impregnation in the proventricular glands. The mucosal folding in the gizzard appeared in the 15th day to form the plicae and the sulci. The wall of the proventriculus and gizzard in the 17th day acquired the main histological features of post-hatching birds, but neither the surface nor the ductal epithelium were differentiated to mucous producing cells. The current results shoed be considered in the molecular developmental studies.

Keywords: quail, proventriculus, gizzard, pre-hatching, histology

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Authors: Maciej Szelag

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The discovery of the carbon nanotubes (CNT), has led to a breakthrough in the material engineering. The CNT is characterized by very large surface area, very high Young's modulus (about 2 TPa), unmatched durability, high tensile strength (about 50 GPa) and bending strength. Their diameter usually oscillates in the range from 1 to 100 nm, and the length from 10 nm to 10-2 m. The relatively new approach is the CNT’s application in the concrete technology. The biggest problem in the use of the CNT to cement composites is their uneven dispersion and low adhesion to the cement paste. Putting the nanotubes alone into the cement matrix does not produce any effect because they tend to agglomerate, due to their large surface area. Most often, the CNT is used as an aqueous suspension in the presence of a surfactant that has previously been sonicated. The paper presents the results of investigations of the basic physical properties (apparent density, shrinkage) and mechanical properties (compression and tensile strength) of cement paste with the addition of the multiwall carbon nanotubes (MWCNT). The studies were carried out on four series of specimens (made of two different Portland Cement). Within each series, samples were made with three w/c ratios – 0.4, 0.5, 0.6 (water/cement). Two series were an unmodified cement matrix. In the remaining two series, the MWCNT was added in amount of 0.1% by cement’s weight. The MWCNT was used as an aqueous dispersion in the presence of a surfactant – SDS – sodium dodecyl sulfate (C₁₂H₂₅OSO₂ONa). So prepared aqueous solution was sonicated for 30 minutes. Then the MWCNT aqueous dispersion and cement were mixed using a mechanical stirrer. The parameters were tested after 28 days of maturation. Additionally, the change of these parameters was determined after samples temperature loading at 250°C for 4 hours (thermal shock). Measurement of the apparent density indicated that cement paste with the MWCNT addition was about 30% lighter than conventional cement matrix. This is due to the fact that the use of the MWCNT water dispersion in the presence of surfactant in the form of SDS resulted in the formation of air pores, which were trapped in the volume of the material. SDS as an anionic surfactant exhibits characteristics specific to blowing agents – gaseous and foaming substances. Because of the increased porosity of the cement paste with the MWCNT, they have obtained lower compressive and tensile strengths compared to the cement paste without additive. It has been observed, however, that the smallest decreases in the compressive and tensile strength after exposure to the elevated temperature achieved samples with the MWCNT. The MWCNT (well dispersed in the cement matrix) can form bridges between hydrates in a nanoscale of the material’s structure. Thus, this may result in an increase in the coherent cohesion of the cement material subjected to a thermal shock. The obtained material could be used for the production of an aerated concrete or using lightweight aggregates for the production of a lightweight concrete.

Keywords: cement paste, elevated temperature, mechanical parameters, multiwall carbon nanotubes, physical parameters, SDS

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Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

Abstract:

Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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Authors: Sumanta Daw, Gopal Chandra Saha

Abstract:

The present study was conducted to explore the basic pulmonary functions which may generally vary according to the bio-physical characteristics including age, height, body weight, and environment etc. of the sports performers. Regular and specific training exercises also change the characteristics of an athlete’s prowess and produce a positive effect on the physiological functioning, mostly upon cardio-pulmonary efficiency and thereby improving the body mechanism. The objective of the present study was to compare the differences in cardio-respiratory functions between aquatics and track and field performers. As cardio-respiratory functions are influenced by pulse rate and blood pressure (systolic and diastolic), so both of the factors were also taken into consideration. The component selected under cardio-respiratory functions for the present study were i) FEVI/FVC ratio (forced expiratory volume divided by forced vital capacity ratio, i.e. the number represents the percentage of lung capacity to exhale in one second) ii) FVC1 (this is the amount of air which can force out of lungs in one second) and iii) FVC (forced vital capacity is the greatest total amount of air forcefully breathe out after breathing in as deeply as possible). All the three selected components of the cardio-respiratory efficiency were measured by spirometry method. Pulse rate was determined manually. The radial artery which is located on the thumb side of our wrist was used to assess the pulse rate. Blood pressure was assessed by sphygmomanometer. All the data were taken in the resting condition. 36subjects were selected for the present study out of which 18were water polo players and rest were sprinters. The age group of the subjects was considered between 18 to 23 years. In this study the obtained data inform of digital score were treated statistically to get result and draw conclusions. The Mean and Standard Deviation (SD) were used as descriptive statistics and the significant difference between the two subject groups was assessed with the help of statistical ‘t’-test. It was found from the study that all the three components i.e. FEVI/FVC ratio (p-value 0.0148 < 0.01), FVC1 (p-value 0.0010 < 0.01) and FVC (p-value 0.0067 < 0.01) differ significantly as water polo players proved to be better in terms of cardio-respiratory functions than sprinters. Thus study clearly suggests that the exercise training as well as the medium of practice arena associated with water polo players has played an important role to determine better cardio respiratory efficiency than track and field athletes. The outcome of the present study revealed that the lung function in land-based activities may not provide much impact than that of in water activities.

Keywords: cardio-respiratory efficiency, spirometry, water polo players, sprinters

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Authors: D. P. Houhoula, J. Papaparaskevas, S. Konteles, A. Dargenta, A. Farka, C. Spyrou, M. Ziaka, S. Koussisis, E. Charvalos

Abstract:

Objectives: Nanotechnology is providing revolutionary opportunities for the rapid and simple diagnosis of many infectious diseases. Staphylococcus aureus, Listeria monocytogenes and Salmonella enteritis are important human pathogens. Diagnostic assays for bacterial culture and identification are time consuming and laborious. There is an urgent need to develop rapid, sensitive, and inexpensive diagnostic tests. In this study, a gold nanoprobe strategy developed and relies on the colorimetric differentiation of specific DNA sequences based approach on differential aggregation profiles in the presence or absence of specific target hybridization. Method: Gold nanoparticles (AuNPs) were purchased from Nanopartz. They were conjugated with thiolated oligonucleotides specific for the femA gene for the identification of members of Staphylococcus aureus, the mecA gene for the differentiation of Staphylococcus aureus and MRSA Staphylococcus aureus, hly gene encoding the pore-forming cytolysin listeriolysin for the identification of Listeria monocytogenes and the invA sequence for the identification of Salmonella enteritis. DNA isolation from Staphylococcus aureus Listeria monocytogenes and Salmonella enteritis cultures was performed using the commercial kit Nucleospin Tissue (Macherey Nagel). Specifically 20μl of DNA was diluted in 10mMPBS (pH5). After the denaturation of 10min, 20μl of AuNPs was added followed by the annealing step at 58oC. The presence of a complementary target prevents aggregation with the addition of acid and the solution remains pink, whereas in the opposite event it turns to purple. The color could be detected visually and it was confirmed with an absorption spectrum. Results: Specifically, 0.123 μg/μl DNA of St. aureus, L.monocytogenes and Salmonella enteritis was serially diluted from 1:10 to 1:100. Blanks containing PBS buffer instead of DNA were used. The application of the proposed method on isolated bacteria produced positive results with all the species of St. aureus and L. monocytogenes and Salmonella enteritis using the femA, mecA, hly and invA genes respectively. The minimum detection limit of the assay was defined at 0.2 ng/μL of DNA. Below of 0.2 ng/μL of bacterial DNA the solution turned purple after addition of HCl, defining the minimum detection limit of the assay. None of the blank samples was positive. The specificity was 100%. The application of the proposed method produced exactly the same results every time (n = 4) the evaluation was repeated (100% repeatability) using the femA, hly and invA genes. Using the gene mecA for the differentiation of Staphylococcus aureus and MRSA Staphylococcus aureus the method had a repeatability 50%. Conclusion: The proposed method could be used as a highly specific and sensitive screening tool for the detection and differentiation of Staphylococcus aureus Listeria monocytogenes and Salmonella enteritis. The use AuNPs for the colorimetric detection of DNA targets represents an inexpensive and easy-to-perform alternative to common molecular assays. The technology described here, may develop into a platform that could accommodate detection of many bacterial species.

Keywords: gold nanoparticles, pathogens, nanotechnology, bacteria

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Authors: Maria Luisa Barcena De Arellano, Sofya Pozdniakova, Pavelas Karkacas, Anja Kuhl, Istvan Baczko, Yury Ladilov, Vera Regitz-Zagrosek

Abstract:

Introduction: Aging is associated with deterioration of the physiological function, leading to systemic inflammation and mitochondrial dysfunction that promote the development of cardiovascular diseases. Sex differences in aging-related cardiovascular diseases have been postulated. However, their precise mechanisms remain unclear. In the current study, we aimed to investigate the sex difference in the age-related alteration in Sirt1-AMPK signaling and its relation to the mitochondrial biogenesis and inflammation. Methods: Male and female human non-disease lateral left ventricular wall tissue (young (17–40 years; n= 7 male and 7 female) and old (50–68 years; n= 9 male and 8 female)) were used. qRT-PCR, western blot and immunohistochemistry assays were performed for expression analyses of Sirt1, AMPK, pAMPK, ac-Ku70, TFAM, PGC-1α, Sirt3, SOD2 and catalase. CD68 was used as a marker for macrophages and the ratio of IL-12:IL10 (pro-inflammatory phenotype (high IL-12/low IL-10) and anti-inflammatory phenotype (low IL-12/high IL-10) was used to examine the inflammatory stage in the heart. Results: Sirt1 expression was significantly higher in young females compared to young males, whereas in aged hearts Sirt1 expression was significantly downregulated in females, but not in males. In line with the Sirt1 downregulation in aged females, acetylation of nuclear Ku70, a direct target of Sirt1, in aged female hearts was significantly elevated. The activity of AMPK was significantly decreased in aged individuals, however no sex differences in the AMPK expression or activity were found in young or old individuals. The expression of mitochondrial proteins TOM40, SOD2 and Sirt3 was significantly higher in young females compared to young males, while in aged female hearts SOD2 and TOM40 were downregulated. In addition, the expression of catalase, a key cytosolic and mitochondrial anti-oxidative enzyme was significantly higher in young females and this female sex benefit was lost in aged hearts. In addition, the number of cardiac macrophages was significantly increased in old female, but not in male hearts. Consistently, the pro-inflammatory shift in old females was further confirmed by differences in the IL12/IL10 ratio in young female cardiac tissue in a favour of the anti-inflammatory mediator IL-10 (ratio 1:4) compared to young males (ratio 1:1). The anti-inflammatory environment in the heart was lost in aged females (ratio 1:1). Conclusion: Aging leads to the significant downregulation of Sirt1 expression and elevated acetylation of Ku70 in female, but not in male hearts. Furthermore, a beneficial upregulation of mitochondrial and anti-oxidative proteins in young females is lost with aging. Moreover, the malfunctions in the expression of Sirt1 and mitochondrial proteins in aged female hearts is accompanied by a significant pro-inflammatory shift. The study provides a molecular basis for the increased incidence of cardiovascular diseases in old women.

Keywords: inflammation, mitochondrial dysfunction, aging, Sirt1-AMPK axis

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Authors: Alvarez M., Chapela M. J., Balboa E., Rubianes D., Sinde E., Fernandez de Ana C., Rodríguez-Blanco A.

Abstract:

The gut microbiota plays an important role as gut inflammation could contribute to colorectal cancer development; however, this role is still not fully understood, and tools able to prevent this progression are yet to be developed. The main objective of this study was to monitor the effects of a mushroom extracts formulation in gut microbial community composition of an Azoxymethane (AOM)/Dextran sodium sulfate (DSS) mice model of inflammation-linked carcinogenesis. For the in vivo study, 41 adult male mice of the C57BL / 6 strain were obtained. 36 of them have been induced in a state of colon carcinogenesis by a single intraperitoneal administration of AOM at a dose of 12.5 mg/kg; the control group animals received instead of the same volume of 0.9% saline. DSS is an extremely toxic polysaccharide sulfate that causes chronic inflammation of the colon mucosa, favoring the appearance of severe colitis and the production of tumors induced by AOM. Induction by AOM/DSS is an interesting platform for chemopreventive intervention studies. This time the model was used to monitor gut microbiota changes as a result of supplementation with a specific mushroom extracts formulation previously shown to have prebiotic activity. The animals have been divided into three groups: (i) Cancer + mushroom extracts formulation experimental group: to which the MicoDigest2.0 mushroom extracts formulation developed by Hifas da Terra S.L has been administered dissolved in drinking water at an estimated concentration of 100 mg / ml. (ii) Control group of animals with Cancer: to which normal water has been administered without any type of treatment. (iii) Control group of healthy animals: these are the animals that have not been induced cancer or have not received any treatment in drinking water. This treatment has been maintained for a period of 3 months, after which the animals were sacrificed to obtain tissues that were subsequently analyzed to verify the effects of the mushroom extract formulation. A microbiological analysis has been carried out to compare the microbial communities present in the intestines of the mice belonging to each of the study groups. For this, the methodology of massive sequencing by molecular analysis of the 16S gene has been used (Ion Torrent technology). Initially, DNA extraction and metagenomics libraries were prepared using the 16S Metagenomics kit, always following the manufacturer's instructions. This kit amplifies 7 of the 9 hypervariable regions of the 16S gene that will then be sequenced. Finally, the data obtained will be compared with a database that makes it possible to determine the degree of similarity of the sequences obtained with a wide range of bacterial genomes. Results obtained showed that, similarly to certain natural compounds preventing colorectal tumorigenesis, a mushroom formulation enriched the Firmicutes and Proteobacteria phyla and depleted Bacteroidetes. Therefore, it was demonstrated that the consumption of the mushroom extracts’ formulation developed could promote the recovery of the microbial balance that is disrupted in the mice model of carcinogenesis. More preclinical and clinical studies are needed to validate this promising approach.

Keywords: carcinogenesis, microbiota, mushroom extracts, inflammation

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