Search results for: isogenic lines

Authors: Fawzyah Albaldi

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Urinary tract infections (UTIs) are the most prevalent of infectious diseases and > 80% are caused by uropathogenic E. coli (UPEC). Infection occurs following adhesion to urothelial plaques on bladder epithelial cells, whose major protein constituent are the uroplakins (UPs). Two of the four uroplakins (UPIa and UPIb) are members of the tetraspanin superfamily. The UPEC adhesin FimH is known to interact directly with UPIa. Tetraspanins are a diverse family of transmembrane proteins that generally act as “molecular organizers” by binding different proteins and lipids to form tetraspanin enriched microdomains (TEMs). Previous work by our group has shown that TEMs are involved in the adhesion of many pathogenic bacteria to human cells. Adhesion can be blocked by tetraspanin-derived synthetic peptides, suggesting that tetraspanins may be valuable drug targets. In this study, we investigate the role of tetraspanins in UPEC adherence to bladder epithelial cells. Human bladder cancer cell lines (T24, 5637, RT4), commonly used as in-vitro models to investigate UPEC infection, along with primary human bladder cells, were used in this project. The aim was to establish a model for UPEC adhesion/infection with the objective of evaluating the impact of tetraspanin-derived reagents on this process. Such reagents could reduce the progression of UTI, particularly in patients with indwelling catheters. Tetraspanin expression on the bladder cells was investigated by q-PCR and flow cytometry, with CD9 and CD81 generally highly expressed. Interestingly, despite these cell lines being used by other groups to investigate FimH antagonists, uroplakin proteins (UPIa, UPIb and UPIII) were poorly expressed at the cell surface, although some were present intracellularly. Attempts were made to differentiate the cell lines, to induce cell surface expression of these UPs, but these were largely unsuccessful. Pre-treatment of bladder epithelial cells with anti-CD9 monoclonal antibody significantly decreased UPEC infection, whilst anti-CD81 had no effects. A short (15aa) synthetic peptide corresponding to the large extracellular region (EC2) of CD9 also significantly reduced UPEC adherence. Furthermore, we demonstrated specific binding of that fluorescently tagged peptide to the cells. CD9 is known to associate with a number of heparan sulphate proteoglycans (HSPGs) that have also been implicated in bacterial adhesion. Here, we demonstrated that unfractionated heparin (UFH)and heparin analogs significantly inhibited UPEC adhesion to RT4 cells, as did pre-treatment of the cells with heparinases. Pre-treatment with chondroitin sulphate (CS) and chondroitinase also significantly decreased UPEC adherence to RT4 cells. This study may shed light on a common pathogenicity mechanism involving the organisation of HSPGs by tetraspanins. In summary, although we determined that the bladder cell lines were not suitable to investigate the role of uroplakins in UPEC adhesion, we demonstrated roles for CD9 and cell surface proteoglycans in this interaction. Agents that target these may be useful in treating/preventing UTIs.

Keywords: UTIs, tspan, uroplakins, CD9

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Authors: Reza Akbari, Jalal MontazeriFashtali, PeymanMomeni Taromsari

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Pipeline systems, play an important role as a vital element in reducing or increasing the risk of earthquake damage and vulnerability. Pipelines are suitable, cheap, fast, and safe routes for transporting oil, gas, water, sewage, etc. The sepipelines must pass from a wide geographical area; hence they will structurally face different environmental and underground factors of earthquake forces’ effect. Therefore, structural engineering analysis and design for this type of lines requires the understanding of relevant parameters behavior and lack of familiarity with them can cause irreparable damages and risks to design and execution, especially in the face of earthquakes. Today, buried pipelines play an important role in human life cycle, thus, studying the vulnerability of pipeline systems is of particular importance. This study examines the behavior of buried pipelines affected by strike-slip fault. Studied fault is perpendicular to the tube axis and causes stress and deformation in the tube by sliding horizontally. In this study, the pipe-soil interaction is accurately simulated, so that one can examine the large displacements and strains, nonlinear material behavior and contact and friction conditions of soil and pipe. The results can be used for designing buried pipes and determining the amount of fault displacement that causes the failure of the buried pipes.

Keywords: pipe lines , earthquake , fault , soil-fault interaction

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Authors: Felix Jr. Garde, Eric Augustus Tingatinga

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Most analysis procedures of reinforced concrete (RC) slabs are based on elastic theory. When subjected to large forces, however, slabs deform beyond elastic range and the study of their behavior and performance require nonlinear analysis. This paper presents a numerical model to simulate nonlinear behavior of RC slabs using rigid body-spring discrete element method. The proposed slab model composed of rigid plate elements and nonlinear springs is based on the yield line theory which assumes that the nonlinear behavior of the RC slab subjected to transverse loads is contained in plastic or yield-lines. In this model, the displacement of the slab is completely described by the rigid elements and the deformation energy is concentrated in the flexural springs uniformly distributed at the potential yield lines. The spring parameters are determined from comparison of transverse displacements and stresses developed in the slab obtained using FEM and the proposed model with assumed homogeneous material. Numerical models of typical RC slabs with varying geometry, reinforcement, support conditions, and loading conditions, show reasonable agreement with available experimental data. The model was also shown to be useful in investigating dynamic behavior of slabs.

Keywords: RC slab, nonlinear behavior, yield line theory, rigid body-spring discrete element method

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Authors: Harun Gülan, Muhsin Tunay Gencoglu, Mehmet Cebeci

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The main function of the insulators used in high voltage (HV) transmission lines is to insulate the energized conductor from the pole and hence from the ground. However, when the insulators fail to perform this insulation function due to various effects, failures occur. The deterioration of the insulation results either from breakdown or surface flashover. The surface flashover is caused by the layer of pollution that forms conductivity on the surface of the insulator, such as salt, carbonaceous compounds, rain, moisture, fog, dew, industrial pollution and desert dust. The source of the majority of failures and interruptions in HV lines is surface flashover. This threatens the continuity of supply and causes significant economic losses. Pollution flashover in HV insulators is still a serious problem that has not been fully resolved. In this study, a water jet test system has been established in order to investigate the behavior of insulators under dirty conditions and to determine their flashover performance. Flashover behavior of the insulators is examined by applying impulse voltages in the test system. This study aims to investigate the insulator behaviour under high impulse voltages. For this purpose, a water jet test system was installed and experimental results were obtained over a real system and analyzed. By using the water jet test system instead of the actual insulator, the damage to the insulator as a result of the flashover that would occur under impulse voltage was prevented. The results of the test system performed an important role in determining the insulator behavior and provided predictability.

Keywords: insulator, pollution flashover, high impulse voltage, water jet model

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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: Edvard Kokanyan, Narine Babajanyan, Ninel Kokanyan, Marco Bazzan

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Lithium niobate (LN) crystals, renowned for their exceptional nonlinear optical, electro-optical, piezoelectric, and photorefractive properties, stand as foundational materials in diverse fields of study and application. While they have long been utilized in frequency converters of laser radiation, electro-optical modulators, and holographic information recording media, LN crystals doped with rare earth ions represent a compelling frontier for modern compact devices. These materials exhibit immense potential as key components in infrared lasers, optical sensors, self-cooling systems, and radiation-balanced laser setups. In this study, we present the successful synthesis of Ho-doped lithium niobate (LN:Ho) thin films on sapphire substrates employing the Sol-Gel technique. The films exhibit a strong crystallographic orientation along the perpendicular direction to the substrate surface, with X-ray diffraction analysis confirming the predominant alignment of the film's "c" axis, notably evidenced by the intense (006) reflection peak. Further characterization through Raman spectroscopy, employing a confocal Raman microscope (LabRAM HR Evolution) with exciting wavelengths of 532 nm and 785 nm, unraveled intriguing insights. Under excitation with a 785 nm laser, Raman scattering obeyed selection rules, while employing a 532 nm laser unveiled additional forbidden lines, reminiscent of behaviors observed in bulk LN:Ho crystals. These supplementary lines were attributed to luminescence induced by excitation at 532 nm. Leveraging data from anti-Stokes Raman lines facilitated the disentanglement of luminescence spectra from the investigated samples. Surface scanning affirmed the uniformity of both structure and luminescence across the thin films. Notably, despite the robust orientation of the "c" axis perpendicular to the substrate surface, Raman signals indicated a stochastic distribution of "a" and "b" axes, validating the mosaic structure of the films along the mentioned axis. This study offers valuable insights into the structural properties of Ho-doped lithium niobate thin films, with the observed luminescence behavior holding significant promise for potential applications in optoelectronic devices.

Keywords: lithium niobate, Sol-Gel, luminescence, Raman spectroscopy.

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Authors: L. I. Izhar, T. Stathaki, K. Howell

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Analyzing and interpreting of thermograms have been increasingly employed in the diagnosis and monitoring of diseases thanks to its non-invasive, non-harmful nature and low cost. In this paper, a novel system is proposed to improve diagnosis and monitoring of morphoea skin disorder based on integration with the published lines of Blaschko. In the proposed system, image registration based on global and local registration methods are found inevitable. This paper presents a modified normalized gradient cross-correlation (NGC) method to reduce large geometrical differences between two multimodal images that are represented by smooth gray edge maps is proposed for the global registration approach. This method is improved further by incorporating an iterative-based normalized cross-correlation coefficient (NCC) method. It is found that by replacing the final registration part of the NGC method where translational differences are solved in the spatial Fourier domain with the NCC method performed in the spatial domain, the performance and robustness of the NGC method can be greatly improved. It is shown in this paper that the hybrid NGC method not only outperforms phase correlation (PC) method but also improved misregistration due to translation, suffered by the modified NGC method alone for thermograms with ill-defined jawline. This also demonstrates that by using the gradients of the gray edge maps and a hybrid technique, the performance of the PC based image registration method can be greatly improved.

Keywords: Blaschko’s lines, image registration, morphoea, thermal imaging

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Authors: Leonardo Parra, Manuel Chacón-Fuentes, Andrés Quiroz

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One of the most important factors in beef and dairy production in the world as well as also in Chile, is related to the correct choice of cultivars or mixtures of forage grasses and legumes to ensure high yields and quality of grassland. However, a great problem is the persistence of the grasses as a result of the action of different hypogeous as epigean pests. The complex insect pests associated with grassland include white grubs (Hylamorpha elegans, Phytoloema herrmanni), blackworm (Dalaca pallens) and Argentine stem weevil (Listronotus bonariensis). In Chile, the principal strategy utilized for controlling this pest is chemical control, through the use of synthetic insecticides, however, underground feeding habits of larval and flight activity of adults makes this uneconomic method. Furthermore, due to problems including environmental degradation, development of resistance and chemical residues, there is a worldwide interest in the use of alternative environmentally friendly pest control methods. In this sense, in recent years there has been an increasing interest in determining the role of endophyte fungi in controlling epigean and hypogeous pest. Endophytes from ryegrass (Lolium perenne), establish a biotrophic relationship with the host, defined as mutualistic symbiosis. The plant-fungi association produces a “cocktail of alkaloids” where peramine is the main toxic substance present in endophyte of ryegrass and responsible for damage reduction of L. bonariensis. In the last decade, few studies have been developed on the effectiveness of new ryegrass cultivars carriers of endophyte in controlling insect pests. Therefore, the aim of this research is to provide knowledge concerning to evaluate the alkaloid content, such as peramine and Lolitrem B, present in new experimental lines of ryegrass and feasible to be used in grasslands of southern Chile. For this, during 2016, ryegrass plants of six experimental lines and two commercial cultivars sown at the Instituto de Investigaciones Agropecuarias Carrillanca (Vilcún, Chile) were collected and subjected to a process of chemical extraction to identify and quantify the presence of peramine and lolitrem B by the technique of liquid chromatography of high resolution (HPLC). The results indicated that the experimental lines EL-1 and EL-3 had high content of peramine (0.25 and 0.43 ppm, respectively) than with lolitrem B (0.061 and 0.19 ppm, respectively). Furthermore, the higher contents of lolitrem B were detected in the EL-4 and commercial cultivar Alto (positive control) with 0.08 and 0.17 ppm, respectively. Peramine and lolitrem B were not detected in the cultivar Jumbo (negative control). These results suggest that EL-3 would have potential as future cultivate because it has high content of peramine, alkaloid responsible for controlling insect pest. However, their current role on the complex insects attacking ryegrass grasslands should be evaluated. The information obtained in this research could be used to improve control strategies against hypogeous and epigean pests of grassland in southern Chile and also to reduce the use of synthetic pesticides.

Keywords: HPLC, Lolitrem B, peramine, pest

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Authors: Saul Emilio Rivero Mejia, Estefanya Marin Tabares, Carlos Andres Rodriguez Toro, Katherine Bolano Restrepo, Sarita Santa Cortes

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Medellin is the Colombian city with the best public transportation system in the country, which is composed of two subway lines, five metro cables, two Bus Rapid Transit lines, and a streetcar. But despite the above, the Aburra Valley, the area in which the city is located, comparatively speaking, has a lower number of urban roads per inhabitant built, compared to the national average. In addition, since there is approximately one vehicle for every three inhabitants in Medellin, the problems of congestion and environmental pollution have become more acute over the years, and it has even been necessary to implement restrictive measures to the use of private vehicles on a permanent basis. In that sense, due to the limitations of physical space, the low public investment in road infrastructure, it is necessary to opt for mobility alternatives according to the above. Within the options for the city, there is what is known as micromobility. Micromobility is understood as those small and light means of transport used to travel short distances, which use electrical energy, such as skateboards and bicycles. These transport alternatives have a high potential for use by the city's young population, but this requires an adequate infrastructure and also state regulation. Taking into account the above, this paper will analyze the current state and future of micro mobility in the city of Medellin, making a prospective analysis, supported by a PEST (political, economic, social and technological) analysis. Based on the above, it is expected to identify the growth of demand for these alternative means and its impact on the mobility of the city in the medium and short term.

Keywords: electric, micromobility, transport, sustainable

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Authors: Huazhen Lin, Ruihua Xu, Zhibin Jiang

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In this real-world case, timetabling the LRT network as a whole is rather challenging for the operator: they are supposed to create a timetable to avoid various route conflicts manually while satisfying a given interval and the number of rolling stocks, but the outcome is not satisfying. Therefore, the operator adopts a computerised timetabling tool, the Train Plan Maker (TPM), to cope with this problem. However, with various constraints in the dual-line network, it is still difficult to find an adequate pairing of turnback time, interval and rolling stocks’ number, which requires extra manual intervention. Aiming at current problems, a one-off model for timetabling is presented in this paper to simplify the procedure of timetabling. Before the timetabling procedure starts, this paper presents how the dual-line system with a ring and several branches is turned into a simpler structure. Then, a non-linear programming model is presented in two stages. In the first stage, the model sets a series of constraints aiming to calculate a proper timing for coordinating two lines by adjusting the turnback time at termini. Then, based on the result of the first stage, the model introduces a series of inequality constraints to avoid various route conflicts. With this model, an analysis is conducted to reveal the relation between the ratio of trains in different directions and the possible minimum interval, observing that the more imbalance the ratio is, the less possible to provide frequent service under such strict constraints.

Keywords: light rail transit (LRT), non-linear programming, railway timetabling, timetable coordination

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Authors: María Rosa Mucci

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Tzvetan Todorov (1971) designs a model of narrative transformation where the plot is constituted by difference and resemblance. This binary opposition is a synthesis of a central figure within narrative discourse: metaphor. Narrative operates as a metaphor since it combines different actions through similarities within a common plot. However, it sounds paradoxical that metonymy and not metaphor should be the key figure within the narrative. It is a metonymy that keeps the movement of actions within the story through syntagmatic relations. By the same token, this articulation of verbs makes it possible for the reader to engage in a dynamic interaction with the text, responding to the plot and mediating meanings with the contradictory external world. As Roland Barthes (1957) points out, there are two codes that are irreversible within the process: the codes of actions and the codes of enigmas. Virginia Woolf constructs her plots through a process of symbolism; a scene is always enduring, not only because it stands for something else but also because it connotes it. The reader is forced to elaborate the meaning at a mythological level beyond the lines. In this research, we follow a qualitative content analysis to code language through the proairetic (actions) and hermeneutic (enigmas) codes in terms of Barthes. There are two novels in particular that engage the reader in this process of construction: Mrs Dalloway (1925) and To the Lighthouse (1927). The bridge from the first to the second brings memories of childhood, allowing for the discovery of these enigmas hidden between the lines. What survives? Who survives? It is the reader's task to unravel these codes and rethink this dialogue between plot and reader to contribute to the predominance of texts and the textuality of narratives.

Keywords: metonymy, code, metaphor, myth, textuality

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Authors: Nazanin Amanat, Alison Tayler, Steve Whyard

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While chemical insecticides effectively control many insect pests, they also harm many non-target species. Double-stranded RNA (dsRNA) pesticides, in contrast, can be designed to target unique gene sequences and thus act in a species-specific manner. DsRNA insecticides do not, however, work equally well for all insects, and for some species that are considered refractory to dsRNA, a primary factor affecting efficacy is the relative ease by which dsRNA can enter a target cell’s cytoplasm. In this study, we are examining how different structured dsRNAs (linear, hairpin, and paperclip) can enter mosquito and lepidopteran cells, as they represent dsRNA-sensitive and refractory species, respectively. To determine how the dsRNAs enter the cells, we are using chemical inhibitors and RNA interference (RNAi)-mediated knockdown of key proteins associated with different endocytosis processes. Understanding how different dsRNAs enter cells will ultimately help in the design of molecules that overcome refractoriness to RNAi or develop resistance to dsRNA-based insecticides. To date, we have conducted chemical inhibitor experiments on both cell lines and have evidence that linear dsRNAs enter the cells using clathrin-mediated endocytosis, while the paperclip dsRNAs (pcRNAs) can enter both species’ cells in a clathrin-independent manner to induce RNAi. An alternative uptake mechanism for the pcRNAs has been tentatively identified, and the outcomes of our RNAi-mediated knockdown experiments, which should provide corroborative evidence of our initial findings, will be discussed.

Keywords: dsRNA, RNAi, uptake, insecticides, dipteran, lepidopteran

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Authors: A. E. Yakshin, D. Ijpes, J. M. Sturm, I. A. Makhotkin, M. D. Ackermann

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Applications like synchrotron optics, soft X-ray microscopy, X-ray astronomy, and wavelength dispersive X-ray fluorescence (WD-XRF) rely heavily on short- and ultra-short-period multilayer (ML) structures. In WD-XRF, ML serves as an analyzer crystal to disperse emission lines of light elements. The key requirement for the ML is to be highly reflective while also providing sufficient angular dispersion to resolve specific XRF lines. For these reasons, MLs with periods ranging from 1.0 to 2.5 nm are of great interest in this field. Due to the short period, the reflectance of such MLs is extremely sensitive to interface imperfections such as roughness and interdiffusion. Moreover, the thickness of the individual layers is only a few angstroms, which is close to the limit of materials to grow a continuous film. MLs with a period between 2.5 nm and 1.0 nm, combining tungsten (W) reflector with B₄C, Si, and Al spacers, were created and examined. These combinations show high theoretical reflectance in the full range from C-Kα (4.48nm) down to S-Kα (0.54nm). However, the formation of optically unfavorable compounds, intermixing, and interface roughness result in limited reflectance. A variety of techniques, including diffusion barriers, seed layers, and ion polishing for sputter-deposited MLs, were used to address these issues. Diffuse scattering measurements, photo-electron spectroscopy analysis, and X-ray reflectivity measurements showed a noticeable reduction of compound formation, intermixing, and interface roughness. This also resulted in a substantial increase in soft X-ray reflectance for W/Si, W/B4C, and W/Al MLs. In particular, the reflectivity of 1 nm period W/Si multilayers at the wavelength of 0.84 nm increased more than 3-fold – propelling forward the applicability of such multilayers for shorter wavelengths.

Keywords: interface engineering, reflectance, short period multilayer structures, x-ray optics

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Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: Deepak Kumar, Ravi Rajwanshi, Mohd. Aslam Yusuf, Nisha Kant Pandey, Preeti Singh, Mukesh Saxena, Neera Bhalla Sarin

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Global issues are leading to concerns over food security. These include climate change, urbanization, increase in population subsequently leading to greater energy and water demand. Futuristic approach for crop improvement involves gene pyramiding for agronomic traits that empower the plants to withstand multiple stresses. In an earlier study from the laboratory, the efficacy of overexpressing γ-tocopherol methyl transferase (γ-TMT) gene from the vitamin E biosynthetic pathway has been shown to result in six-fold increase of the most biologically active form, the α-tocopherol in Brassica juncea which resulted in alleviation of salt, heavy metal and osmoticum induced stress by the transgenic plants. The glyoxalase I (gly I) gene from the glyoxalase pathway has also been earlier shown by us to impart tolerance against multiple abioitc stresses by detoxification of the cytotoxic compound methylglyoxal in Brassica juncea. Recently, both the transgenes were pyramided in Brassica juncea lines through sexual crosses involving two stable Brassica juncea lines overexpressing γ-TMT and gly I genes respectively. The transgene integration was confirmed by PCR analysis and their mRNA expression was evident by RT-PCR analysis. Preliminary physiological investigations showed ~55% increased seed germination under 200 mM NaCl stress in the pyramided line and 81% higher seed germination under 200 mM mannitol stress as compared to the WT control plants. The pyramided lines also retained more chlorophyll content when the leaf discs were floated on NaCl (200, 400 and 600 mM) or mannitol (200, 400 and 600 mM) compared to the WT control plants. These plants had higher Relative Water Content and greater solute accumulation under stress compared to the parental plants having γ-TMT or the glyI gene respectively. The studies revealed the synergy of two components from different metabolic pathways in enhancing stress hardiness of the transgenic B. juncea plants. It was concluded that pyramiding of genes (γ-TMT and glyI) from diverse pathways can lead to enhanced tolerance to salt and mannitol stress (simulating drought conditions). This strategy can prove useful in enhancing the crop yields under various abiotic stresses.

Keywords: abiotic stress, brassica juncea, glyoxalase I, α-tocopherol

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Authors: Kheireddine El-Boubbou

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Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC₅₀ values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

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Authors: Amir Saber Gharamaleki, Beitollah Alipour, Zeinab Faghfoori, Ahmad YariKhosroushahi

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Colorectal cancer (CRC) is one of the most prevalent cancers and intestinal microbial community plays an important role in colorectal tumorigenesis. Probiotics have recently been assessed as effective anti-proliferative agents and thus this study was performed to examine whether CRC undergo apoptosis by treating with isolated Iranian native dairy yeast, Kluyveromyces marxianus YAS, secretion metabolites. The cytotoxicity assessments on cells (HT-29, Caco-2) were accomplished through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as qualitative DAPI (4',6-diamidino-2-phenylindole staining) and quantitative (flow cytometry assessments) evaluations of apoptosis. To evaluate the main mechanism of apoptosis, Real time PCR method was applied. Kluyveromyces marxianus YAS secretions (IC50) showed significant cytotoxicity against HT-29 and Caco-2 cancer cell lines (66.57 % and 66.34 % apoptosis) similar to 5-Fluorouracil (5-FU) while apoptosis only was developed in 27.57 % of KDR normal cells. The prophylactic effects of Kluyveromyces marxianus (PTCC 5195), as a reference yeast, was not similar to Kluyveromyces marxianus YAS indicating strain dependency of bioactivities on CRC disease prevention. Based on real time PCR results, the main cytotoxicity is related to apoptosis phenomenon and the core related mechanism is depended on the overexpression of BAX, CASP 9, CASP 8 and CASP 3 inducing apoptosis genes. However, several investigations should be conducted to precisely determine the effective compounds to be used as anticancer therapeutics in the future.

Keywords: anticancer, anti-proliferative, apoptosis, cytotoxicity, yeast

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Authors: Hugo Badia

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This research answers which is the most suitable transit network structure to serve specific demand requirements in an increasing urban dispersion process. Two main approaches of network design are found in the literature. On the one hand, a traditional answer, widespread in our cities, that develops a high number of lines to connect most of origin-destination pairs by direct trips; an approach based on the idea that users averse to transfers. On the other hand, some authors advocate an alternative design characterized by simple networks where transfer is essential to complete most of trips. To answer which of them is the best option, we use a two-step methodology. First, by means of an analytical model, three basic network structures are compared: a radial scheme, starting point for the other two structures, a direct trip-based network, and a transfer-based one, which represent the two alternative transit network designs. The model optimizes the network configuration with regard to the total cost for each structure. For a scenario of dispersion, the best alternative is the structure with the minimum cost. This dispersion degree is defined in a simple way considering that only a central area attracts all trips. If this area is small, we have a high concentrated mobility pattern; if this area is too large, the city is highly decentralized. In this first step, we can determine the area of applicability for each structure in function to that urban dispersion degree. The analytical results show that a radial structure is suitable when the demand is so centralized, however, when this demand starts to scatter, new transit lines should be implemented to avoid transfers. If the urban dispersion advances, the introduction of more lines is no longer a good alternative, in this case, the best solution is a change of structure, from direct trips to a network based on transfers. The area of applicability of each network strategy is not constant, it depends on the characteristics of demand, city and transport technology. In the second step, we translate analytical results to a real case study by the relationship between the parameters of dispersion of the model and direct measures of dispersion in a real city. Two dimensions of the urban sprawl process are considered: concentration, defined by Gini coefficient, and centralization by area based centralization index. Once it is estimated the real dispersion degree, we are able to identify in which area of applicability the city is located. In summary, from a strategic point of view, we can obtain with this methodology which is the best network design approach for a city, comparing the theoretical results with the real dispersion degree.

Keywords: analytical network design model, network structure, public transport, urban dispersion

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Authors: Suzan Ghaddar, Aline Pinon, Manuel Gallardo-villagran, Mona Diab-assaf, Bruno Therrien, Bertrand Liagre

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Colorectal cancer (CRC) is the third most common cancer and exhibits a consistently rising incidence worldwide. Despite notable advancements in CRC treatment, frequent occurrences of side effects and the development of therapy resistance persistently challenge current approaches. Eventually, innovations in focal therapies remain imperative to enhance the patient’s overall quality of life. Photodynamic therapy (PDT) emerges as a promising treatment modality, clinically used for the treatment of various cancer types. It relies on the use of photosensitive molecules called photosensitizers (PS), which are photoactivated after accumulation in cancer cells, to induce the production of reactive oxygen species (ROS) that cause cancer cell death. Among commonly used metal-based drugs in cancer therapy, ruthenium (Ru) possesses favorable attributes that demonstrate its selectivity towards cancer cells and render it suitable for anti-cancer drug design. In vitro studies using distinct arene-Ru complexes, encapsulating porphin PS, are conducted on human HCT116 and HT-29 colorectal cancer cell lines. These studies encompass the evaluation of the antiproliferative effect, ROS production, apoptosis, cell cycle progression, molecular localization, and protein expression. Preliminary results indicated that these complexes exert significant photocytotoxicity on the studied colorectal cancer cell lines, representing them as promising and potential candidates for anti- cancer agents.

Keywords: colorectal cancer, photodynamic therapy, photosensitizers, arene-ruthenium complexes, apoptosis

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Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

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Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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Authors: I. Witbooi, J. De Smidt, A. Oelofse

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Negative emotions that are common in depression are coupled with the activation of the corrugator supercilli and procerus muscles in the glabellar region of the face. This research investigated the impact of OnabotulinumtoxinA (BOTOX) in the improvement of emotional states in depressed subjects by relaxing the mentioned muscles. The aim of the study was to investigate the effectiveness of BOTOX treatment for glabellar frown lines as an adjunctive therapy for Major Depressive Disorder (MDD) and to improve the quality of life and self-esteem of the subjects. It is hypothesized that BOTOX treatment for glabellar frown lines reduces depressive symptoms significantly and therefore augment conventional antidepressant medication. Forty-five (45) subjects diagnosed with MDD were assigned to a treatment (n = 15), placebo (n = 15), and control (n = 15) group. The treatment group received BOTOX injection, while the placebo group received saline injection into the Procerus and Corrugator supercilli muscles with follow-up visits every 3 weeks (weeks 3, 6 and 12 respectively). The control group received neither BOTOX nor saline injections and were only interviewed again on the 12th week. To evaluate the effect of BOTOX treatment in the glabellar region on depressive symptoms, the Montgomery-Asberg Depression Rating (MADRS) scale and the Beck Depression Inventory (BDI) were used. The Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Rosenberg Self-Esteem Scale (RSES) were used in the assessment of self-esteem and quality of life. Participants were followed up for a 12 week period. The expected primary outcome measure is the response to treatment, and it is defined as a ≥ 50% reduction in MADRS score from baseline. Other outcome measures include a clinically significant decrease in BDI scores and the increase in quality of life and self-esteem respectively. Initial results show a clear trend towards such differences. Results showed trends towards expected differences. Patients in the Botox group had a mean MADRS score of 14.0 at 3 weeks compared to 20.3 of the placebo group. This trend was still visible at 6 weeks with the Botox and placebo group scoring an average of 10 vs. 18 respectively. The mean difference in MDRS scores from baseline to 3 weeks were 9.3 and 2.0 for the Botox and placebo group respectively. Similarly, the BDI scores were lower in the Botox group (17.25) compared to the placebo group (19.43). The two self-esteem questionnaires showed expected results at this stage with the RSES 19.1 in the Botox group compared to 18.6 in the placebo group. Similarly, the Botox patients had a higher score for the Q-LES-Q-SF of 49.2 compared to 46.1 for the placebo group. Conclusions: Initial results clearly demonstrated that the use of Botox had positive effects on both scores of depressions and that of self-esteem when compared to a placebo group.

Keywords: adjunctive therapy, depression, glabellar area, OnabotulinumtoxinA

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Authors: Letizia Maria Drammis, Maria Antonella Brandimonte

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The idea that people use space representations to think about time and number received support from several lines of research. However, how these representations develop in children and then shape space-time and space-number mappings is still a debated issue. In the present study, 40 children (20 pre-schoolers and 20 elementary-school children) performed 4 main tasks, which required the use of more concrete (non-symbolic) or more abstract (symbolic) space-time and space-number associations. In the non-symbolic conditions, children were required to order pictures of everyday-life events occurring in a specific temporal order (Temporal sequences) and of quantities varying in numerosity (Numerical sequences). In the symbolic conditions, they were asked to perform the typical time-to-position and number-to-position tasks by mapping time-related words and numbers onto lines. Results showed that children performed reliably better in the non-symbolic Time conditions than the symbolic Time conditions, independently of age, whereas only pre-schoolers performed worse in the Number-to-position task (symbolic) as compared to the Numerical sequence (non-symbolic) task. In addition, only older children mapped time-related words onto space following the typical left-right orientation, pre-schoolers’ performance being somewhat mixed. In contrast, mapping numbers onto space showed a clear left-right orientation, independently of age. Overall, these results indicate a cross-domain difference in the way younger and older children process time and number, with time-related tasks being more difficult than number-related tasks only when space-time tasks require symbolic representations.

Keywords: space-time associations, space-number associations, orientation, children

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Authors: Rakesh Kumar Meena, Tanushree Chatterjee

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Okra (Abelmoschus esculentas L. Moench) or lady’s finger is an important vegetable crop belonging to the Malvaceae family. Unfortunately, production and productivity of Okra are majorly affected by Yellow Vein mosaic virus (YVMV). The AO: 189 (resistant parent) X AO: 191(susceptible parent) used for the development of mapping population. The mapping population has 143 individuals (F₂:F₃). Population was characterized by physiological and pathological observations. Screening of 360 DNA markers was performed to survey for parental polymorphism between the contrasting parents’, i.e., AO: 189 and AO: 191. Out of 360; 84 polymorphic markers were used for genotyping of the mapping population. Total markers were distributed into four linkage groups (LG1, LG2, LG3, and LG4). LG3 covered the longest span (106.8cM) with maximum number of markers (27) while LG1 represented the smallest linkage group in terms of length (71.2cM). QTL identification using the composite interval mapping approach detected two prominent QTLs, QTL1 and QTL2 for resistance against YVMV disease. These QTLs were placed between the marker intervals of NBS-LRR72-Path02 and NBS-LRR06- NBS-LRR65 on linkage group 02 and linkage group 04 respectively. The LOD values of QTL1 and QTL2 were 5.7 and 6.8 which accounted for 19% and 27% of the total phenotypic variation, respectively. The findings of this study provide two linked markers which can be used as efficient diagnostic tools to distinguish between YVMV resistant and susceptible Okra cultivars/genotypes. Lines identified as highly resistant against YVMV infection can be used as donor lines for this trait. This will be instrumental in accelerating the trait improvement program in Okra and will substantially reduce the yield losses due to this viral disease.

Keywords: Okra, yellow vein mosaic virus, resistant, linkage map, QTLs

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Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

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Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

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Authors: Kaarour Abdelkrim, Ouardi Okkacha, Meskine Mohamed

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In this study, the υ_4 fundamental band of 12CD4 molecule has been studied by infrared spectroscopy with high resolution. Using XTDS and SPEVIEW software and the tensor formalism developed by ICB (laboratoire interdisciplinaire de Bourgogne) to several lines have been assigned and fitted with a standard deviation acceptable. This analysis allowed us to calculate several parameters of the molecule 12 CD4.

Keywords: XTDS, SPEVIEW, tetrahedral tensorial formalism, rovibrational band

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Authors: Omolola A. Tajelawi, Hari L. Garbharran

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Revenue leakages are one of the major challenges manufacturers face in production processes, as most of the input materials that should emanate as products from the lines are lost as waste. Rather than generating income from material input which is meant to end-up as products, losses are further incurred as costs in order to manage waste generated. In addition, due to the lack of a clear view of the flow of resources on the lines from input to output stage, acquiring information on the true cost of waste generated have become a challenge. This has therefore given birth to the conceptualization and implementation of waste minimization strategies by several manufacturing industries. This paper reviews the principles and applications of three environmental management accounting tools namely Activity-based Costing (ABC), Life-Cycle Assessment (LCA) and Material Flow Cost Accounting (MFCA) in the manufacturing industry and their effectiveness in curbing revenue leakages. The paper unveils the strengths and limitations of each of the tools; beaming a searchlight on the tool that could allow for optimal resource utilization, transparency in production process as well as improved cost efficiency. Findings from this review reveal that MFCA may offer superior advantages with regards to the provision of more detailed information (both in physical and monetary terms) on the flow of material inputs throughout the production process compared to the other environmental accounting tools. This paper therefore makes a case for the adoption of MFCA as a viable technique for the identification and reduction of waste in production processes, and also for effective decision making by production managers, financial advisors and other relevant stakeholders.

Keywords: MFCA, environmental management accounting, resource efficiency, waste reduction, revenue losses

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Authors: Yasir Ali, Farhatullah

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The present study was conducted to estimate the genetic variability, heritability and genetic advance in six parental lines and their 56 genotypes derived from five introgressed brassica populations on the basis of morphological and biochemical traits. The experiment was laid out in a randomized complete block design with two replications at The University of Agriculture Peshawar-Pakistan during growing season of 2015-2016. The ANOVA of all traits of F5:6 populations showed highly significant differences (P ≤ 0.01) for all morphological and biochemical traits. Among F5:6 populations, the genotype 2(526) was earlier in flowering (108.65 days), and genotype 14(485) was earlier in maturity (170 days). Tallest plants (182.5 cm), largest main raceme (91.5 cm) and maximum number of pods (80.5) on main raceme were recorded for genotype 17(34). Maximum primary branches plant-1(6.2) and longest pods (10.26 cm) were recorded for genotype 15, while genotype 16(171) had more seeds pod⁻¹ (22) and gave maximum yield plant-1 (30.22 g). The maximum 100-seed weight (0.60 g) was observed for genotype 10(506) while high protein content (22.61%) was recorded for genotype 4(99). Maximum oil content (54.08 %) and low linoleic acid (7.07 %) were produced by genotype (12(138) and low glucosinolate (59.01 µMg⁻¹) was recorded for genotype 21(113). The genotype 27(303) having high oleic acid content (51.73 %) and genotype 1(209) gave low erucic acid (35.97 %). Among the F5:6 populations moderate to high heritability observed for all morphological and biochemical traits coupled with high genetic advance. Cluster analysis grouped the 56 F5:6 populations along their parental lines into seven different groups. Each group was different from the other group on the basis of morphological and biochemical traits. Moreover all the F5:6 populations showed sufficient variability. Genotypes 10(506) and 16(171) were superior for high seed yield⁻¹, 100-seeds weight, and seed pod⁻¹ and are recommended for future breeding program.

Keywords: Brassicaceae, biochemical characterization, introgression, morphological characterization

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Authors: Soroosh Torabi, Brad Berron, Ren Xu, Christine Trinkle

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Microfluidics integrated with 3D cell culture is a powerful technology to mimic cellular environment, and can be used to study cell activities such as proliferation, migration and response to drugs. This technology has gained more attention in cancer studies over the past years, and many organ-on-a-chip systems have been developed to study cancer cell behaviors in an ex-vivo tumor microenvironment. However, there are still some barriers to adoption which include low throughput, complexity in 3D cell culture integration and limitations on non-optical analysis of cells. In this study, a user-friendly microfluidic multi-well plate was developed to mimic the in vivo tumor microenvironment. The microfluidic platform feeds multiple 3D cell culture sites at the same time which enhances the throughput of the system. The platform uses hydrophobic Cassie-Baxter surfaces created by microchannels to enable convenient loading of hydrogel/cell suspensions into the device, while providing barrier free placement of the hydrogel and cells adjacent to the fluidic path. The microchannels support convective flow and diffusion of nutrients to the cells and a removable lid is used to enable further chemical and physiological analysis on the cells. Different breast cancer cell lines were cultured in the device and then monitored to characterize nutrient delivery to the cells as well as cell invasion and proliferation. In addition, the drug response of breast cancer cell lines cultured in the device was compared to the response in xenograft models to the same drugs to analyze relevance of this platform for use in future drug-response studies.

Keywords: microfluidics, multi-well 3d cell culture, tumor microenvironment, tumor-on-a-chip

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

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

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

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Authors: Mohamad Najari, Gilbert Grondin, Marwan El-Rich

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Design trucks in standard codes are selected based on the amount of damage they cause on structures-specifically bridges- and roads to represent the real traffic loads. Some limited numbers of trucks are run on a bridge one at a time and the damage on the bridge is recorded for each truck. One design track is also run on the same bridge “n” times -“n” is the number of trucks used previously- to calculate the damage of the design truck on the same bridge. To make these damages equal a reduction factor is needed for that specific design truck in the codes. As the limited number of trucks cannot be the exact representative of real traffic through the life of the structure, these reduction factors are not accurately calculated and they should be modified accordingly. Started on July 2004, the vehicle load data were collected in six weigh in motion (WIM) sites owned by Alberta Transportation for eight consecutive years. This database includes more than 200 million trucks. Having these data gives the opportunity to compare the effect of any standard fatigue trucks weigh and the real traffic load on the fatigue life of the bridges which leads to a modification for the fatigue truck factor in the code. To calculate the damage for each truck, the truck is run on the bridge, moment history of the detail under study is recorded, stress range cycles are counted, and then damage is calculated using available S-N curves. A 2000 lines FORTRAN code has been developed to perform the analysis and calculate the damages of the trucks in the database for all eight fatigue categories according to Canadian Institute of Steel Construction (CSA S-16). Stress cycles are counted using rain flow counting method. The modification factors for design truck (CL-625) are calculated for two different bridge configurations and ten span lengths varying from 1 m to 200 m. The two considered bridge configurations are single-span bridge and four span bridge. This was found to be sufficient and representative for a simply supported span, positive moment in end spans of bridges with two or more spans, positive moment in interior spans of three or more spans, and the negative moment at an interior support of multi-span bridges. The moment history of the mid span is recorded for single-span bridge and, exterior positive moment, interior positive moment, and support negative moment are recorded for four span bridge. The influence lines are expressed by a polynomial expression obtained from a regression analysis of the influence lines obtained from SAP2000. It is found that for design truck (CL-625) fatigue truck factor is varying from 0.35 to 0.55 depending on span lengths and bridge configuration. The detail results will be presented in the upcoming papers. This code can be used for any design trucks available in standard codes.

Keywords: bridge, fatigue, fatigue design truck, rain flow analysis, FORTRAN

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