Search results for: Marcel Schneider
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 73

Search results for: Marcel Schneider

13 Cycle-Oriented Building Components and Constructions Made from Paper Materials

Authors: Rebecca Bach, Evgenia Kanli, Nihat Kiziltoprak, Linda Hildebrand, Ulrich Knaack, Jens Schneider

Abstract:

The building industry has a high demand for resources and at the same time is responsible for a significant amount of waste created worldwide. Today's building components need to contribute to the protection of natural resources without creating waste. This is defined in the product development phase and impacts the product’s degree of being cycle-oriented. Paper-based materials show advantage due to their renewable origin and their ability to incorporate different functions. Besides the ecological aspects like renewable origin and recyclability the main advantages of paper materials are its light-weight but stiff structure, the optimized production processes and good insulation values. The main deficits from building technology’s perspective are the material's vulnerability to humidity and water as well as inflammability. On material level, those problems can be solved by coatings or through material modification. On construction level intelligent setup and layering of a building component can improve and also solve these issues. The target of the present work is to provide an overview of developed building components and construction typologies mainly made from paper materials. The research is structured in four parts: (1) functions and requirements, (2) preselection of paper-based materials, (3) development of building components and (4) evaluation. As part of the research methodology at first the needs of the building sector are analyzed with the aim to define the main areas of application and consequently the requirements. Various paper materials are tested in order to identify to what extent the requirements are satisfied and determine potential optimizations or modifications, also in combination with other construction materials. By making use of the material’s potentials and solving the deficits on material and on construction level, building components and construction typologies are developed. The evaluation and the calculation of the structural mechanics and structural principals will show that different construction typologies can be derived. Profiles like paper tubes can be used at best for skeleton constructions. Massive structures on the other hand can be formed by plate-shaped elements like solid board or honeycomb. For insulation purposes corrugated cardboard or cellulose flakes have the best properties, while layered solid board can be applied to prevent inner condensation. Enhancing these properties by material combinations for instance with mineral coatings functional constructions mainly out of paper materials were developed. In summary paper materials offer a huge variety of possible applications in the building sector. By these studies a general base of knowledge about how to build with paper was developed and is to be reinforced by further research.

Keywords: construction typologies, cycle-oriented construction, innovative building material, paper materials, renewable resources

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12 Uncertainty Quantification of Crack Widths and Crack Spacing in Reinforced Concrete

Authors: Marcel Meinhardt, Manfred Keuser, Thomas Braml

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Cracking of reinforced concrete is a complex phenomenon induced by direct loads or restraints affecting reinforced concrete structures as soon as the tensile strength of the concrete is exceeded. Hence it is important to predict where cracks will be located and how they will propagate. The bond theory and the crack formulas in the actual design codes, for example, DIN EN 1992-1-1, are all based on the assumption that the reinforcement bars are embedded in homogeneous concrete without taking into account the influence of transverse reinforcement and the real stress situation. However, it can often be observed that real structures such as walls, slabs or beams show a crack spacing that is orientated to the transverse reinforcement bars or to the stirrups. In most Finite Element Analysis studies, the smeared crack approach is used for crack prediction. The disadvantage of this model is that the typical strain localization of a crack on element level can’t be seen. The crack propagation in concrete is a discontinuous process characterized by different factors such as the initial random distribution of defects or the scatter of material properties. Such behavior presupposes the elaboration of adequate models and methods of simulation because traditional mechanical approaches deal mainly with average material parameters. This paper concerned with the modelling of the initiation and the propagation of cracks in reinforced concrete structures considering the influence of transverse reinforcement and the real stress distribution in reinforced concrete (R/C) beams/plates in bending action. Therefore, a parameter study was carried out to investigate: (I) the influence of the transversal reinforcement to the stress distribution in concrete in bending mode and (II) the crack initiation in dependence of the diameter and distance of the transversal reinforcement to each other. The numerical investigations on the crack initiation and propagation were carried out with a 2D reinforced concrete structure subjected to quasi static loading and given boundary conditions. To model the uncertainty in the tensile strength of concrete in the Finite Element Analysis correlated normally and lognormally distributed random filed with different correlation lengths were generated. The paper also presents and discuss different methods to generate random fields, e.g. the Covariance Matrix Decomposition Method. For all computations, a plastic constitutive law with softening was used to model the crack initiation and the damage of the concrete in tension. It was found that the distributions of crack spacing and crack widths are highly dependent of the used random field. These distributions are validated to experimental studies on R/C panels which were carried out at the Laboratory for Structural Engineering at the University of the German Armed Forces in Munich. Also, a recommendation for parameters of the random field for realistic modelling the uncertainty of the tensile strength is given. The aim of this research was to show a method in which the localization of strains and cracks as well as the influence of transverse reinforcement on the crack initiation and propagation in Finite Element Analysis can be seen.

Keywords: crack initiation, crack modelling, crack propagation, cracks, numerical simulation, random fields, reinforced concrete, stochastic

Procedia PDF Downloads 115
11 Goal-Setting in a Peer Leader HIV Prevention Intervention to Improve Preexposure Prophylaxis Access among Black Men Who Have Sex with Men

Authors: Tim J. Walsh, Lindsay E. Young, John A. Schneider

Abstract:

Background: The disproportionate rate of HIV infection among Black men who have sex with men (BMSM) in the United States suggest the importance of Preexposure Prophylaxis (PrEP) interventions for this population. As such, there is an urgent need for innovative outreach strategies that extend beyond the traditional patient-provider relationship to reach at-risk populations. Training members of the BMSM community as peer change agents (PCAs) is one such strategy. An important piece of this training is goal-setting. Goal-setting not only encourages PCAs to define the parameters of the intervention according to their lived experience, it also helps them plan courses of action. Therefore, the aims of this mixed methods study are: (1) Characterize the goals that BMSM set at the end of their PrEP training and (2) Assess the relationship between goal types and PCA engagement. Methods: Between March 2016 and July 2016, preliminary data were collected from 68 BMSM, ages 18-33, in Chicago as part of an ongoing PrEP intervention. Once enrolled, PCAs participate in a half-day training in which they learn about PrEP, practice initiating conversations about PrEP, and identify strategies for supporting at-risk peers through the PrEP adoption process. Training culminates with a goal-setting exercise, whereby participants establish a goal related to their role as a PCA. Goals were coded for features that either emerged from the data itself or existed in extant goal-setting literature. The main outcomes were (1) number of PrEP conversations PCAs self-report during booster conversations two weeks following the intervention and (2) number of peers PCAs recruit into the study that completed the PrEP workshop. Results: PCA goals (N=68) were characterized in terms of four features: Specificity, target population, personalization, and purpose defined. To date, PCAs report a collective 52 PrEP conversations. 56, 25, and 6% of PrEP conversations occurred with friends, family, and sexual partners, respectively. PCAs with specific goals had more PrEP conversations with at-risk peers compared to those with vague goals (58% vs. 42%); PCAs with personalized goals had more PrEP conversations compared to those with de-personalized goals (60% vs. 53%); and PCAs with goals that defined a purpose had more PrEP conversations compared to those who did not define a purpose (75% vs. 52%). 100% of PCAs with goals that defined a purpose recruited peers into the study compared to 45 percent of PCAs with goals that did not define a purpose. Conclusion: Our preliminary analysis demonstrates that BMSM are motivated to set and work toward a diverse set of goals to support peers in PrEP adoption. PCAs with goals involving a clearly defined purpose had more PrEP conversations and greater peer recruitment than those with goals lacking a defined purpose. This may indicate that PCAs who define their purpose at the outset of their participation will be more engaged in the study than those who do not. Goal-setting may be considered as a component of future HIV prevention interventions to advance intervention goals and as an indicator of PCAs understanding of the intervention.

Keywords: HIV prevention, MSM, peer change agent, preexposure prophylaxis

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10 Non-Steroidal Microtubule Disrupting Analogues Induce Programmed Cell Death in Breast and Lung Cancer Cell Lines

Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

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9 Solids and Nutrient Loads Exported by Preserved and Impacted Low-Order Streams: A Comparison among Water Bodies in Different Latitudes in Brazil

Authors: Nicolas R. Finkler, Wesley A. Saltarelli, Taison A. Bortolin, Vania E. Schneider, Davi G. F. Cunha

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Estimating the relative contribution of nonpoint or point sources of pollution in low-orders streams is an important tool for the water resources management. The location of headwaters in areas with anthropogenic impacts from urbanization and agriculture is a common scenario in developing countries. This condition can lead to conflicts among different water users and compromise ecosystem services. Water pollution also contributes to exporting organic loads to downstream areas, including higher order rivers. The purpose of this research is to preliminarily assess nutrients and solids loads exported by water bodies located in watersheds with different types of land uses in São Carlos - SP (Latitude. -22.0087; Longitude. -47.8909) and Caxias do Sul - RS (Latitude. -29.1634, Longitude. -51.1796), Brazil, using regression analysis. The variables analyzed in this study were Total Kjeldahl Nitrogen (TKN), Nitrate (NO3-), Total Phosphorus (TP) and Total Suspended Solids (TSS). Data were obtained in October and December 2015 for São Carlos (SC) and in November 2012 and March 2013 for Caxias do Sul (CXS). Such periods had similar weather patterns regarding precipitation and temperature. Altogether, 11 sites were divided into two groups, some classified as more pristine (SC1, SC4, SC5, SC6 and CXS2), with predominance of native forest; and others considered as impacted (SC2, SC3, CXS1, CXS3, CXS4 and CXS5), presenting larger urban and/or agricultural areas. Previous linear regression was applied for data on flow and drainage area of each site (R² = 0.9741), suggesting that the loads to be assessed had a significant relationship with the drainage areas. Thereafter, regression analysis was conducted between the drainage areas and the total loads for the two land use groups. The R² values were 0.070, 0.830, 0.752 e 0.455 respectively for SST, TKN, NO3- and TP loads in the more preserved areas, suggesting that the loads generated by runoff are significant in these locations. However, the respective R² values for sites located in impacted areas were respectively 0.488, 0.054, 0.519 e 0.059 for SST, TKN, NO3- and P loads, indicating a less important relationship between total loads and runoff as compared to the previous scenario. This study suggests three possible conclusions that will be further explored in the full-text article, with more sampling sites and periods: a) In preserved areas, nonpoint sources of pollution are more significant in determining water quality in relation to the studied variables; b) The nutrient (TKN and P) loads in impacted areas may be associated with point sources such as domestic wastewater discharges with inadequate treatment levels; and c) The presence of NO3- in impacted areas can be associated to the runoff, particularly in agricultural areas, where the application of fertilizers is common at certain times of the year.

Keywords: land use, linear regression, point and non-point pollution sources, streams, water resources management

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8 A Novel Concept of Optical Immunosensor Based on High-Affinity Recombinant Protein Binders for Tailored Target-Specific Detection

Authors: Alena Semeradtova, Marcel Stofik, Lucie Mareckova, Petr Maly, Ondrej Stanek, Jan Maly

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Recently, novel strategies based on so-called molecular evolution were shown to be effective for the production of various peptide ligand libraries with high affinities to molecular targets of interest comparable or even better than monoclonal antibodies. The major advantage of these peptide scaffolds is mainly their prevailing low molecular weight and simple structure. This study describes a new high-affinity binding molecules based immunesensor using a simple optical system for human serum albumin (HSA) detection as a model molecule. We present a comparison of two variants of recombinant binders based on albumin binding domain of the protein G (ABD) performed on micropatterned glass chip. Binding domains may be tailored to any specific target of interest by molecular evolution. Micropatterened glass chips were prepared using UV-photolithography on chromium sputtered glasses. Glass surface was modified by (3-aminopropyl)trietoxysilane and biotin-PEG-acid using EDC/NHS chemistry. Two variants of high-affinity binding molecules were used to detect target molecule. Firstly, a variant is based on ABD domain fused with TolA chain. This molecule is in vivo biotinylated and each molecule contains one molecule of biotin and one ABD domain. Secondly, the variant is ABD domain based on streptavidin molecule and contains four gaps for biotin and four ABD domains. These high-affinity molecules were immobilized to the chip surface via biotin-streptavidin chemistry. To eliminate nonspecific binding 1% bovine serum albumin (BSA) or 6% fetal bovine serum (FBS) were used in every step. For both variants range of measured concentrations of fluorescently labelled HSA was 0 – 30 µg/ml. As a control, we performed a simultaneous assay without high-affinity binding molecules. Fluorescent signal was measured using inverse fluorescent microscope Olympus IX 70 with COOL LED pE 4000 as a light source, related filters, and camera Retiga 2000R as a detector. The fluorescent signal from non-modified areas was substracted from the signal of the fluorescent areas. Results were presented in graphs showing the dependence of measured grayscale value on the log-scale of HSA concentration. For the TolA variant the limit of detection (LOD) of the optical immunosensor proposed in this study is calculated to be 0,20 µg/ml for HSA detection in 1% BSA and 0,24 µg/ml in 6% FBS. In the case of streptavidin-based molecule, it was 0,04 µg/ml and 0,07 µg/ml respectively. The dynamical range of the immunosensor was possible to estimate just in the case of TolA variant and it was calculated to be 0,49 – 3,75 µg/ml and 0,73-1,88 µg/ml respectively. In the case of the streptavidin-based the variant we didn´t reach the surface saturation even with the 480 ug/ml concentration and the upper value of dynamical range was not estimated. Lower value was calculated to be 0,14 µg/ml and 0,17 µg/ml respectively. Based on the obtained results, it´s clear that both variants are useful for creating the bio-recognizing layer on immunosensors. For this particular system, it is obvious that the variant based on streptavidin molecule is more useful for biosensing on glass planar surfaces. Immunosensors based on this variant would exhibit better limit of detection and wide dynamical range.

Keywords: high affinity binding molecules, human serum albumin, optical immunosensor, protein G, UV-photolitography

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7 Preparation and Characterization of Anti-Acne Dermal Products Based on Erythromycin β-Cyclodextrin Lactide Complex

Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

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6 The Relationship between 21st Century Digital Skills and the Intention to Start a Digit Entrepreneurship

Authors: Kathrin F. Schneider, Luis Xavier Unda Galarza

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In our modern world, few are the areas that are not permeated by digitalization: we use digital tools for work, study, entertainment, and daily life. Since technology changes rapidly, skills must adapt to the new reality, which gives a dynamic dimension to the set of skills necessary for people's academic, professional, and personal success. The concept of 21st-century digital skills, which includes skills such as collaboration, communication, digital literacy, citizenship, problem-solving, critical thinking, interpersonal skills, creativity, and productivity, have been widely discussed in the literature. Digital transformation has opened many economic opportunities for entrepreneurs for the development of their products, financing possibilities, and product distribution. One of the biggest advantages is the reduction in cost for the entrepreneur, which has opened doors not only for the entrepreneur or the entrepreneurial team but also for corporations through intrapreneurship. The development of students' general literacy level and their digital competencies is crucial for improving the effectiveness and efficiency of the learning process, as well as for students' adaptation to the constantly changing labor market. The digital economy allows a free substantial increase in the supply share of conditional and also innovative products; this is mainly achieved through 5 ways to reduce costs according to the conventional digital economy: search costs, replication, transport, tracking, and verification. Digital entrepreneurship worldwide benefits from such achievements. There is an expansion and democratization of entrepreneurship thanks to the use of digital technologies. The digital transformation that has been taking place in recent years is more challenging for developing countries, as they have fewer resources available to carry out this transformation while offering all the necessary support in terms of cybersecurity and educating their people. The degree of digitization (use of digital technology) in a country and the levels of digital literacy of its people often depend on the economic level and situation of the country. Telefónica's Digital Life Index (TIDL) scores are strongly correlated with country wealth, reflecting the greater resources that richer countries can contribute to promoting "Digital Life". According to the Digitization Index, Ecuador is in the group of "emerging countries", while Chile, Colombia, Brazil, Argentina, and Uruguay are in the group of "countries in transition". According to Herrera Espinoza et al. (2022), there are startups or digital ventures in Ecuador, especially in certain niches, but many of the ventures do not exceed six months of creation because they arise out of necessity and not out of the opportunity. However, there is a lack of relevant research, especially empirical research, to have a clearer vision. Through a self-report questionnaire, the digital skills of students will be measured in an Ecuadorian private university, according to the skills identified as the six 21st-century skills. The results will be put to the test against the variable of the intention to start a digital venture measured using the theory of planned behavior (TPB). The main hypothesis is that high digital competence is positively correlated with the intention to start digital entrepreneurship.

Keywords: new literacies, digital transformation, 21st century skills, theory of planned behavior, digital entrepreneurship

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5 Modeling Taxane-Induced Peripheral Neuropathy Ex Vivo Using Patient-Derived Neurons

Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

Abstract:

Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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4 A Nutrient Formulation Affects Brain Myelination in Infants: An Investigative Randomized Controlled Trial

Authors: N. Schneider, M. Bruchhage, M. Hartweg, G. Mutungi, J. O Regan, S. Deoni

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Observational neuroimaging studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning and cognitive development. However, the possible effects of a nutrient formulation on myelin development in healthy term infants in an intervention study have not been investigated. Objective was, therefore, to investigate the efficacy of a nutrient formulation with higher levels of myelin-relevant nutrients as compared to a control formulation with lower levels of the same nutrients on brain myelination and cognitive development in the first 6 months of life. The study is an ongoing randomized, controlled, double-blind, two-center, parallel-group clinical trial with a nonrandomized, non-blinded arm of exclusively breastfed infants. The current findings result from a staged statistical analysis at 6 months; the recruitment and intervention period has been completed for all participants. Follow-up visits at 12, 18 and 24 months are still ongoing. N= 81 enrolled full term, neurotypical infants of both sexes were randomized into either the investigational (N= 42) or the control group (N= 39), and N= 108 children in the breast-fed arm served as a natural reference group. The effect of a blend of docosahexaenoic acid, arachidonic acid, iron, vitamin B12, folic acid as well as sphingomyelin from a uniquely proceed whey protein concentrate enriched in alpha-lactalbumin and phospholipids in an infant nutrition product matrix was investigated. The main outcomes for the staged statistical analyses at 6 months included brain myelination measures derived from MRI. Additional outcomes were brain volume, cognitive development and safety. The full analyses set at 6 months comprised N= 66 infants. Higher levels of myelin-relevant nutrients compared to lower levels resulted in significant differences in myelin structure, volume, and rate of myelination as early as 3 and 6 months of life. The cross-sectional change of means between groups for whole-brain myelin volume was 8.4% for investigational versus control formulation (3.5% versus the breastfeeding reference) group at 3 months and increased to 36.4% for investigational versus control formulation (14.1% versus breastfeeding reference) at 6 months. No statistically significant differences were detected for early cognition scores. Safety findings were largely similar across groups. This is the first pediatric nutritional neuroimaging study demonstrating the efficacy of a myelin nutrient blend on developmental myelination in well-nourished term infants. Myelination is a critical process in learning and development. The effects were demonstrated across the brain, particularly in temporal and parietal regions, known to be functionally involved in sensory, motor and language skills. These first results add to the field of nutritional neuroscience by demonstrating early life nutrition benefits for brain architecture which may be foundational for later cognitive and behavioral outcomes. ClinicalTrials.gov Identifier: NCT03111927 (Infant Nutrition and Brain Development - Full-Text View - ClinicalTrials.gov).

Keywords: brain development, infant nutrition, MRI, myelination

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3 „Real and Symbolic in Poetics of Multiplied Screens and Images“

Authors: Kristina Horvat Blazinovic

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In the context of a work of art, one can talk about the idea-concept-term-intention expressed by the artist by using various forms of repetition (external, material, visible repetition). Such repetitions of elements (images in space or moving visual and sound images in time) suggest a "covert", "latent" ("dressed") repetition – i.e., "hidden", "latent" term-intention-idea. Repeating in this way reveals a "deeper truth" that the viewer needs to decode and which is hidden "under" the technical manifestation of the multiplied images. It is not only images, sounds, and screens that are repeated - something else is repeated through them as well, even if, in some cases, the very idea of repetition is repeated. This paper examines serial images and single-channel or multi-channel artwork in the field of video/film art and video installations, which in a way implies the concept of repetition and multiplication. Moving or static images and screens (as multi-screens) are repeated in time and space. The categories of the real and the symbolic partly refer to the Lacan registers of reality, i.e., the Imaginary - Symbolic – Real trinity that represents the orders within which human subjectivity is established. Authors such as Bruce Nauman, VALIE EXPORT, Ragnar Kjartansson, Wolf Vostell, Shirin Neshat, Paul Sharits, Harun Farocki, Dalibor Martinis, Andy Warhol, Douglas Gordon, Bill Viola, Frank Gillette, and Ira Schneider, and Marina Abramovic problematize, in different ways, the concept and procedures of multiplication - repetition, but not in the sense of "copying" and "repetition" of reality or the original, but of repeated repetitions of the simulacrum. Referential works of art are often connected by the theme of the traumatic. Repetitions of images and situations are a response to the traumatic (experience) - repetition itself is a symptom of trauma. On the other hand, repeating and multiplying traumatic images results in a new traumatic effect or cancels it. Reflections on repetition as a temporal and spatial phenomenon are in line with the chapters that link philosophical considerations of space and time and experience temporality with their manifestation in works of art. The observations about time and the relation of perception and memory are according to Henry Bergson and his conception of duration (durée) as "quality of quantity." The video works intended to be displayed as a video loop, express the idea of infinite duration ("pure time," according to Bergson). The Loop wants to be always present - to fixate in time. Wholeness is unrecognizable because the intention is to make the effect infinitely cyclic. Reflections on time and space end with considerations about the occurrence and effects of time and space intervals as places and moments "between" – the points of connection and separation, of continuity and stopping - by reference to the "interval theory" of Soviet filmmaker DzigaVertov. The scale of opportunities that can be explored in interval mode is wide. Intervals represent the perception of time and space in the form of pauses, interruptions, breaks (e.g., emotional, dramatic, or rhythmic) denote emptiness or silence, distance, proximity, interstitial space, or a gap between various states.

Keywords: video installation, performance, repetition, multi-screen, real and symbolic, loop, video art, interval, video time

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2 Cellular Mechanisms Involved in the Radiosensitization of Breast- and Lung Cancer Cells by Agents Targeting Microtubule Dynamics

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

Abstract:

Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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1 Facies Analysis and Depositional Environment of the Late Carboniferous (Stephanian) Souss Basin, Morocco

Authors: Abouchouaib Belahmira, Joerg W. Schneider, Hafid Saber, Sara Akboub

Abstract:

The lithofacies analyzed herein were reported from the interbedded fluvial and lacustrine deposits of the Oued Issene and El Menizla formations. These formations are part of the sedimentary fill of the Carboniferous (Stephanian) submontaneous Souss basin. The latter is situated in the western High Atlas Mountains, south-central Morocco, about 50km east of Agadir. The Souss basin started as a single basin but was separated into sub-basins called Ida Ou Zal and Ida Ou Ziki by sinistral displacement along the west branch of the Tizi N'Test Fault during the end of the Mauritanid phase of the Variscan orogeny in Morocco, after the early Stephanian (Kasimovian) and before the late middle Permian (Capitanian). The studied succession is a monotonous finning-upward sequence of 1800 m thick. It consists of fine-grained sandstone, finely bedded siltstone and thinly laminated claystone, and black shale. Herein we provide a detailed characterization of lithofacies of the upper El Menizla and Oued Issène formations, with a focus on the prevailing overbank to flood plain fine-grained lithofacies. The studied facies are capping the Stephanian alluvial fan basal clast-supported conglomerates that are intercalated bedded coarse-grained sandstones of Ikhourba Formation in the Ou Zal subbasin and Tajgaline Formation in the Ida Ou Ziki subbasin, respectively. Within the fluvial elements, only two main facies have been observed. It comprises channel-fill and channel-bar deposits, mostly occur as lenticular –shape sand bodies or sheet-like sand greenish to gray fine-to medium (Fm), massive internally structureless, or very locally exhibits a medium to large scale trough-cross bedding medium to coarse sandstone (St), observable in relatively thicker bed. These facies are laterally extensive, with a thickness varying from a few to several meters. Finer-grained sediments such as mud can be present as drapes over bedforms. Whilst the fluvial association FA1, the overbank elements are represented by a relatively wide range of 5 facies. This exhibit mostly a cm scale horizontally bedded greenish fine- to medium sand and silt, and mm scale fossiliferous thinly laminated dark gray- black Corganic-rich clays to siltstone associated with black shale. Thus, FA2 includes flood plain fines (Fh, R) associated with the paleosols and back swamp coaly clay facies (C). The floodplain lake element comprises only laminated organic-rich dark gray facies of claystone, black shale, and graded siltstone. Bedsets are dm to several meters thick (typically < 1 m thick). They are intercalated between several m-thick fluvial sandstone, extend over a few meters, and are poorly bioturbated. The lacustrine facies described in this study have been divided into two sub-facies (Fl, B) based on field observations that indicate differing environmental conditions of formation. Thus, the thorough analysis of the lithofacies of the Souss basin units allows us to reconstruct the original environment that was interpreted as a typical fluvial-dominated braided to anastomosing wide distributary channel system and surrounding deep to shallow freshwater floodplain lakes and back swamps.

Keywords: Souss, carboniferous, facies, depositional setting

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