Search results for: Hans Magnus Gjøen

Authors: Hans Frenk, Sonya Javadi, Semih Onur Sezer

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We consider the so-called end of life inventory problem for the supplier of a product in its final phase of the service life cycle. This phase starts when the production of the items stops and continues until the warranty of the last sold item expires. At the beginning of this phase, the supplier places a final order for spare parts to serve customers coming with defective items. At any time during the final phase, the supplier may also decide to switch to an alternative and more cost-effective policy. This alternative policy may be in the form of replacing a defective item with a substitutable product or offering discounts / rebates on new generation products. In this setup, the objective is to find a final order quantity and also a switching time which will minimize the total expected discounted cost. We study this problem under a general cost structure in a continuous-time framework where arrivals of defective items are given by a non-homogeneous Poisson process. We consider four formulations which differ by the nature of the switching time. These formulations are studied in detail and properties of the objective function are derived in each case. Using these properties, we provide exact algorithms for efficient numerical implementations. Numerical examples are provided illustrating the application of these algorithms. In these examples, we also compare the costs associated with these different formulations.

Keywords: End-of-life inventory control, martingales, optimization, service parts

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Authors: Achim Kampker, Heiner Hans Heimes, Mathias Ordung, Jan-Philip Ganser

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In the past years, the automotive industry has changed significantly. Innovative mobility concepts have become more important, and electric vehicles see a chance of replacing vehicles with combustion engines in the long term. However, the coming years will be characterized by coexistence. In this context, there are two possible production scenarios: One the one hand, electric vehicles could be manufactured in bespoke assembly lines. Concerning the uncertainty regarding sales figures development, this alternative boasts a high investment risk. Therefore, an integrated assembly building upon existing structures also seems a feasible solution. This empirical study aims at validating hypotheses concerning theoretical and practical challenges of the integrated production in the final assembly. In order to take a test of approaches of the research by analyzing censored feedback of professionals, these hypotheses are validated in the framework of an expert study. For this purpose, hypotheses have been generated on the basis of a requirements analysis and a concept specification. Thereupon, a list of question has been implemented and deduced from the hypotheses to execute an online- and written-survey and interviews with professionals. The interpretation and evaluation of the findings includes an inter-component comparison for the electric drivetrain. Furthermore, key drivers for a sufficient integrated product and process design are presented.

Keywords: automotive industry, final assembly, integrated manufacturing, product and process development

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Authors: Kougioumtzis Konstantin, Rylander Pär, Karlsteen Magnus

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Ball skills as a subset of fundamental motor skills are predictors for performance in sports. Currently, most tools evaluate ball skills utilizing subjective ratings. The aim of this study was to examine the psychometric properties of a newly developed instrument to objectively measure ball handling skills (BHS-test) utilizing digital instrument. Participants were a convenience sample of 213 adolescents (age M = 17.1 years, SD =3.6; 55% females, 45% males) recruited from upper secondary schools and invited to a sports hall for the assessment. The 8-item instrument incorporated both accuracy-based ball skill tests and repetitive-performance tests with a ball. Testers counted performance manually in the four tests (one throwing and three juggling tasks). Furthermore, assessment was technologically enhanced in the other four tests utilizing a ball machine, a Kinect camera and balls with motion sensors (one balancing and three rolling tasks). 3D printing technology was used to construct equipment, while all results were administered digitally with smart phones/tablets, computers and a specially constructed application to send data to a server. The instrument was deemed reliable (α = .77) and principal component analysis was used in a random subset (53 of the participants). Furthermore, latent variable modeling was employed to confirm the structure with the remaining subset (160 of the participants). The analysis showed good factorial-related validity with one factor explaining 57.90 % of the total variance. Four loadings were larger than .80, two more exceeded .76 and the other two were .65 and .49. The one factor solution was confirmed by a first order model with one general factor and an excellent fit between model and data (χ² = 16.12, DF = 20; RMSEA = .00, CI90 .00–.05; CFI = 1.00; SRMR = .02). The loadings on the general factor ranged between .65 and .83. Our findings indicate good reliability and construct validity for the BHS-test. To develop the instrument further, more studies are needed with various age-groups, e.g. children. We suggest using the BHS-test for diagnostic or assessment purpose for talent development and sports participation interventions that focus on ball games.

Keywords: ball-handling skills, ball-handling ability, technologically-enhanced measurements, assessment

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Authors: Atul Khurana, Rajul Rastogi, Hans-Joachim Gamperl

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The pharmaceutical companies are getting more inclined towards patient support programs (PSPs) which assist patients and/or healthcare professionals (HCPs) in more desirable disease management and cost-effective treatment. The utmost objective of these programs is patient care. The PSPs may include financial assistance to patients, medicine compliance programs, access to HCPs via phone or online chat centers, etc. The PSP has a crucial role in terms of customer acquisition and retention strategies. During the conduct of these programs, Marketing Authorisation Holder (MAH) may receive information related to concerned medicinal products, which is usually reported by patients or involved HCPs. This information may include suspected adverse reaction(s) during/after administration of medicinal products. Hence, the MAH should design PSP to comply with regulatory reporting requirements and avoid non-compliance during PV inspection. The emergence of wireless health devices is lowering the burden on patients to manually incorporate safety data, and building a significant option for patients to observe major swings in reference to drug safety. Therefore, to enhance the adoption of these programs, MAH not only needs to aware patients about advantages of the program, but also recognizes the importance of time of patients and commitments made in a constructive manner. It is indispensable that strengthening the public health is considered as the topmost priority in such programs, and the MAH is compliant to Pharmacovigilance (PV) requirements along with regulatory obligations.

Keywords: drug safety, good pharmacovigilance practice, patient support program, pharmacovigilance

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Authors: Achim Kampker, Christoph Deutskens, Heiner Hans Heimes, Mathias Ordung, Felix Optehostert

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In the past years electric mobility became part of a public discussion. The trend to fully electrified vehicles instead of vehicles fueled with fossil energy has notably gained momentum. Today nearly every big car manufacturer produces and sells fully electrified vehicles, but electrified vehicles are still not as competitive as conventional powered vehicles. As the traction battery states the largest cost driver, lowering its price is a crucial objective. In addition to improvements in product and production processes a non-negligible, but widely underestimated cost driver of production can be found in logistics, since the production technology is not continuous yet and neither are the logistics systems. This paper presents an approach to evaluate cost factors on different designs of load carrier systems. Due to numerous interdependencies, the combination of costs factors for a particular scenario is not transparent. This is effecting actions for cost reduction negatively, but still cost reduction is one of the major goals for simultaneous engineering processes. Therefore a concurrent and phase appropriate cost valuation method is necessary to serve cost transparency. In this paper the four phases of this cost valuation method are defined and explained, which based upon a new approach integrating the logistics development process in to the integrated product and process development.

Keywords: research and development, technology and innovation, lithium-ion-battery production, load carrier development process, cost valuation method

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Authors: Veronika Zivicova, Petr Broz, Zdenek Fik, Alzbeta Mifkova, Jan Plzak, Zdenek Cada, Herbert Kaltner, Jana Fialova Kucerova, Hans-Joachim Gabius, Karel Smetana Jr.

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The possibility to determine genome-wide expression profiles of cells and tissues opens a new level of analysis in the quest to define dysregulation in malignancy and thus identify new tumor markers. Toward this long-term aim, we here address two issues on this level for head and neck cancer specimen: i) defining profiles in different regions, i.e. the tumor, the transition zone and normal control and ii) comparing complete data sets for seven individual patients. Special focus in the flanking immunohistochemical part is given to adhesion/growth-regulatory galectins that upregulate chemo- and cytokine expression in an NF-κB-dependent manner, to these regulators and to markers of differentiation, i.e. keratins. The detailed listing of up- and down-regulations, also available in printed form (1), not only served to unveil new candidates for testing as marker but also let the impact of the tumor in the transition zone become apparent. The extent of interindividual variation raises a strong cautionary note on assuming uniformity of regulatory events, to be noted when considering therapeutic implications. Thus, a combination of test targets (and a network analysis for galectins and their downstream effectors) is (are) advised prior to reaching conclusions on further perspectives.

Keywords: galectins, genome scale sequencing, squamous cell carcinoma, transition zone

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Authors: Johannes Bibinger, Sebastian Eibl, Hans-Joachim Gudladt

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This study considers the influence of different irradiation scenarios on the thermal degradation of carbon fiber-reinforced polymers (CFRP). Real threats are simulated, such as fires with long-lasting low heat fluxes and nuclear heat flashes with short-lasting high heat fluxes. For this purpose, coated and uncoated quasi-isotropic samples of the commercially available CFRP HexPly® 8552/IM7 are thermally irradiated from one side by a cone calorimeter and a xenon short-arc lamp with heat fluxes between 5 and 175 W/cm² at varying time intervals. The specimen temperature is recorded on the front and backside as well as at different laminate depths. The CFRP is non-destructively tested with ultrasonic testing, infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and micro-focused computed X-Ray tomography (μCT). Destructive tests are performed to evaluate the mechanical properties in terms of interlaminar shear strength (ILSS), compressive and tensile strength. The irradiation scenarios vary significantly in heat flux and exposure time. Thus, different heating rates, radiation effects, and temperature distributions occur. This leads to unequal decomposition processes, which affect the sensitivity of the strength type and damage behaviour of the specimens. However, with the use of surface coatings, thermal degradation of composite materials can be delayed.

Keywords: CFRP, one-sided thermal damage, high heat flux, heating rate, non-destructive and destructive testing

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Authors: Saskia Köbschall

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The idea of ‘being close to nature’ and the ways of achieving this proximity are socially and historically constructed, as are notions of nakedness and nudity. During the colonial period, nudity and clothedness functioned as instruments of racial domination. Nakedness became central to the colonialists’ thinking, to their binary of the ‘civilized’ and those ‘close to nature’, therefore turning the level of perceived unclothedness into a measurement of ‘civilization'. While being ‘one with nature’ continued to be a criterion of backwardness in the colonies, it emerged as a futuristic and avant-garde endeavor in the metropole: In Germany, at the height of its colonial expansion, the Life Reform Movement (Lebensreformbewegung) called for the liberation of the white body from the ‘constraints of civilization’, for its ‘return to nature’ via practices like nudism. Despite this simultaneity, the scholarship of the life reform and the nudist movement in particular does not address the colonial past of the movement or its repercussions in the present. Taking the biography of prominent life reformist Hans Paasche (1881 - 1920) as a starting point, this paper explores the work of imperial legacies in the history and present of the German nudist movement. Paasche started his career as a German colonial officer, participating in the brutal obliteration of the Maji-Maji uprising (1905/06) that claimed the lives of nearly 200.000 people. Once a passionate game hunter, he later became a known nature conservationist; once a self-proclaimed explorer of Africa, he later became one of the most prominent advocates of nudism and vegetarianism. The paper joins conceptual and historical research in order to address the German nudist movement’s colonial past and understand its repercussions in the present.

Keywords: Germany, life reform, colonialism, archives, nudity, nature

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Authors: Carl-Magnus Everitt, Bo Alfredsson

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Contact mechanics and tribology have been combined with fundamental fatigue and fracture mechanics to form the asperity mechanism which supplies an explanation for the surface-initiated rolling contact fatigue damage, called pitting or spalling. The cracks causing the pits initiates at one surface point and thereafter they slowly grow into the material before chipping of a material piece to form the pit. In the current study, the lubrication aspects on fatigue initiation are simulated by passing a single asperity through a thermal elastohydrodynamic lubricated, TEHL, contact. The physics of the lubricant was described with Reynolds equation and the lubricants pressure-viscosity relation was modeled by Roelands equation, formulated to include temperature dependence. A pressure dependent shear limit was incorporated. To capture the full phenomena of the sliding contact the temperature field was resolved through the incorporation of the energy flow. The heat was mainly generated due to shearing of the lubricant and from dry friction where metal contact occurred. The heat was then transported, and conducted, away by the solids and the lubricant. The fatigue damage caused by the asperities was evaluated through Findley’s fatigue criterion. The results show that asperities, in the size of surface roughness found in applications, may cause surface initiated fatigue damage and crack initiation. The simulations also show that the asperities broke through the lubricant in the inlet, causing metal to metal contact with high friction. When the asperities thereafter moved through the contact, the sliding provided the asperities with lubricant releasing the metal contact. The release of metal contact was possible due to the high viscosity the lubricant obtained from the high pressure. The metal contact in the inlet caused higher friction which increased the risk of fatigue damage. Since the metal contact occurred in the inlet it increased the fatigue risk more for asperities subjected to negative slip than positive slip. Therefore the fatigue evaluations showed that the asperities subjected to negative slip yielded higher fatigue stresses than the asperities subjected to positive slip of equal magnitude. This is one explanation for why pitting is more common in the dedendum than the addendum on pinion gear teeth. The simulations produced further validation for the asperity mechanism by showing that asperities cause surface initiated fatigue and crack initiation.

Keywords: fatigue, rolling, sliding, thermal elastohydrodynamic

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Authors: Gabriel K. Nzulu, Lina Rostorm, Hans Högberg, Jun Liu, per Eklund, Lars Hultman, Martin Magnuson

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Altered and gangue quartz in hydrothermal veins from the Kubi Gold deposit in Dunkwa on Offin in the central region of Ghana are investigated for possible Au associated pathfinder minerals and to provide understanding and increase the knowledge of the mineral hosting and alteration processes in quartz. X-ray diffraction, air annealing furnace, differential scanning calorimetry, energy dispersive X-ray spectroscopy, and transmission electron microscopy have been applied on different quartz types outcropping from surface and bed rocks at the Kubi Gold Mining to reveal the material properties at different temperatures. From the diffraction results of the fresh and annealed quartz samples, we find that the samples contain pathfinder and the impurity minerals FeS₂, biotite, TiO₂, and magnetite. These minerals, under oxidation process between 574-1400 °C temperatures experienced hematite alterations and a transformation from α-quartz to β-quartz and further to cristobalite as observed from the calorimetry scans for hydrothermally exposed materials. The energy dispersive spectroscopy revealed elemental species of Fe, S, Mg, K, Al, Ti, Na, Si, O, and Ca contained in the samples and these are attributed to the impurity phase minerals observed in the diffraction. The findings also suggest that during the hydrothermal flow regime, impurity minerals and metals can be trapped by voids and faults. Under favorable temperature conditions the trapped minerals can be altered to change color at different depositional stages by oxidation and reduction processes leading to hematite alteration which is a useful pathfinder in mineral exploration.

Keywords: quartz, hydrothermal, minerals, hematite, x-ray diffraction, crystal-structure, defects

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Authors: Achim Kampker, Heiner Hans Heimes, Nemanja Sarovic, Jan-Philip Ganser, Saskia Wessel, Christoph Lienemann

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The electrification of the power train is a fundamental technical transition in the automotive industry and poses a major challenge for established car companies. Providing the traction energy, requiring an ever greater amount of space within the car and having a high share of value-add the lithium-ion battery is a central component of the electric power train and a completely new component to car manufacturers at the same time. Being relatively new to the automotive industry, the current design of the product architecture and production process (including manufacturing and assembling processes) of lithium-ion battery modules do not allow for an easy and cost-efficient disassembly or product design change. Yet these two requirements will increase in importance with rising sales volumes of electric cars in the near future and need to be addressed for the electric car to be competitive with conventional power train systems. This paper focuses on the current product architecture and production process of common automotive battery modules from prismatic lithium-ion battery cells to derive impacts for a remanufacturing concept. The information necessary for this purpose were gathered by literature research, patent inquiries, industry expert interviews and first-hand experiences of the authors. On the basis of these results, the underlying causes for the design´s lack of remanufacturability and flexibility with regards to product design changes are examined. In all, this paper gives an extensive and detailed overview of the state of the art of the product architecture and production process of lithium-ion battery modules from prismatic battery cells, identifies its deficiencies and derives improvement measures.

Keywords: battery module, prismatic lithium-ion battery cell, product architecture, production process, remanufacturing, flexibility

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Authors: Ranjith Menon, Abathar Aladi, Hans-Christean Nahser, Maneesh Bhojak, Sacha Nevin, Paul Eldridge

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Background: Spontaneous subarachnoid haemorrhage (SAH) accounts for approximately 5% of all strokes. Patients with spontaneous SAH (as shown by CT or lumbar puncture) undergo investigations to identify or exclude an underlying structural cause, typically cerebral aneurysm. However in 10 - 20% of cases, no structural cause is found. This includes more than one imaging modality (intracranial MRA, CTA, 4DCTA and/or DSA) and in some spinal MRI. Objective: To determine; 1) If an underlying structural or vascular cause can be identified in non-aneurysmal SAH patients by comparing different imaging modalities at presentation and at follow-up. 2) If MRI spine in patients with non-aneurysmal SAH reveals an underlying SAH cause. 3)The functional outcome at discharge. Results: We performed a retrospective analysis of all non-traumatic SAH patients admitted to the Walton centre from January 2009 to December 2015. There were 1457 patients with non-traumatic SAH admitted to the Walton centre of whom 21.8% (n=300) patients were diagnosed with non-aneurysmal SAH. Males were 65.6% and females were 43.3%. The presenting symptoms were sudden onset headache (93.6%), the focal neurological deficit (12%), loss of consciousness (10.6%) and others (6%). About 285 patients received 2 modalities of imaging (CTA & DSA), 192 received 3 modalities of imaging (CTA, MRA & DSA) and 137 received MRI spine (51/137 whole spine). The modified Rankin Score at discharge were: mRS 0 = 292 (97.33%), mRS 1-2 = 6, mRS 6 = 1 (cardiac arrest in IHD patient) and unknown in 1. Follow-up imaging at 3 to 6 months in 190 (63.3%) patients did not identify an underlying cause. Conclusion: This retrospective analysis concludes that non-aneurysmal SAH has a good functional outcome. A single imaging modality (CTA (4DCTA) or MRA or DSA) was adequate to exclude an underlying cause of SAH and a delayed imaging failed to identify a cause. Routinely performing MRI spine in this group of patients appears not to be necessary according to this evidence.

Keywords: stroke, non-aneurysmal subarachnoid haemorrhage, neuroimaging, modified rankin score

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Authors: Caiwen Wang, Yuling Liu

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Scientific and technical discourse is non-literary, and so it is often regarded as merely informative, free of the cultural context of both the source and the target language. Thus it is supposed that translators of sci-tech texts do not need to consider cultural factors in the translation process as readers only care for the information conveyed. This paper takes a different standpoint and shows that cultural context plays an important part in scientific and technical texts and thereafter in bridging the gap between different cultural communities of readers. The paper argues that the common cultural context for members of the same cultural community, such as morals, customs, and values, also underpins the sci-tech discourse of various text types, and therefore may pose difficulties for readers of a different cultural community if this is re-presented or translated literally. The research hypothesises that depending on how it is re-presented or translated; cultural context can either encourage or discourage readers’ reading experience and subsequently their interest to read and use translation texts. Drawing upon the Reception Theory by Hans Robert Jauss, the research investigates the relationship between cultural context and scientific and technical translation from English to Chinese. Citing 55 examples of sci-tech translations from magazines, newspapers and the website of Shell, a major international oil and gas company, the research shows that the source texts for these 55 cases all have bearing on the source cultural context, and translators will need to address this in the translation process instead of doing literal translation to be merely correct. The research then interviews 15 research subjects for their views of the translations. By assessing readers’ reception and perception of translated Chinese sci-tech discourse, the research concludes that cultural context contributes to the quality of scientific and technical translation in an important way and then discusses the implications of the findings for training scientific and technical translators.

Keywords: Chinese translation, cultural context, reception theory, scientific and technical texts

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Authors: Daniella L. Pereira, Emeliana G. Imperial, Ingrid Webster, Ian Wiid, Hans Strijdom, Nireshni Chellan, Sanet H. Kotzé

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Rooibos (Aspalathus linearis) is a shrub-like bush native to the Western Cape of South Africa and commonly consumed as a herbal tea. Interest on the anti-oxidant capabilities of the tea have risen based on anecdotal evidence. Rooibos contains polyphenols that contribute to the overall antioxidant capacity of the tea. These polyphenols have been reported to attenuate the effects of oxidative stress in biological systems. The bioavailability of these compounds is compromised when exposed to light, pH fluctuations, and oxidation. It is crucial to evaluate whether the polyphenols in a typical rooibos solution remain constant over time when administered to rats in a research environment. This study aimed to determine the effects of various storage scenarios on the phenolic composition of rooibos tea commonly administered to rodents in experimental studies. A standardised aqueous solution of rooibos tea was filtered and divided into three samples namely fresh, refrigerated, and frozen. Samples were stored in air tight, light excluding bottles. Refrigerated samples were stored at 4°C for seven days. Frozen samples were stored for fourteen days at -20°C. Each sample consisted of two subgroups labeled day 1 and day 7. Teas marked day 7 of each group were kept in air tight, light protected bottles at room temperature for an additional week. All samples (n=6) were freeze-dried and underwent polyphenol characterization using liquid chromatography-mass spectrometry. The phenolic composition remained constant throughout all groups. This indicates that rooibos tea can be safely stored at the above conditions without compromising the phenolic viability of the tea typically used for research purposes.

Keywords: Aspalathus linearis, experimental studies, polyphenols, storage

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Authors: Mengwei Li

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Since the 1990s, biennials, and large-scale transnational art exhibitions, have proliferated exponentially across the globe, particularly in Asia, Africa, and Latin America. It has spurred debates regarding the inclusion of "new art cultures" and the deconstruction of the mechanism of exclusion embedded in the Western monopoly on art. Hans Belting introduced the concept of "global art" in 2013 to denounce the West's privileged canons in art by emphasising the inclusion of art practices from alleged non-Western regions. Arguably, the rise of new biennial networks developed by these locations has contributed to the asserted "inclusion of new art worlds." However, phrases such as "non-Western" and "beyond Euro-American" attached to these discussions raise the question of non- or beyond- in relation to whom. In this narrative, to become "integrated" and "equal" implies entry into the "core," a universal system in which preexisting authoritative voices define "newcomers" by what they are not. Possibly, if there is a global biennial system that symbolises a "universal language" of the contemporary art world, it is centered on the inherently dynamic yet asymmetrical interaction and negotiation between the "core" and the rest of the world's "periphery." Engaging with theories of "minor literature" developed by Deleuze and Guattari, this research proposes an epistemological framework to comprehend the global biennial discourse since the 1990s. Using this framework, this research looks at two biennial models in China: the 13th Shanghai Biennale, which was organised in the country's metropolitan art centre, and the 2nd Yinchuan Biennale, which was inaugurated in a geographically and economically marginalised city compared to domestic centres. By analysing how these two biennials from different locations in China positioned themselves and conveyed their local profiles through the universal language of the biennial, this research identifies a potential "minor" positionality within the global biennial discourse from China's perspective.

Keywords: biennials, China, contemporary, global art, minor literature

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Authors: Armand Okende, Joëlle De Weerdt, Esther Fichtler, Maaike De Ridder, Hans Beeckman

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The rainforest plays a crucial role in regulating the climate balance. The biodiversity of tropical rainforests is undeniable, but many aspects remain poorly known, which directly influences its management. Despite the efforts of sustainable forest management, human pressure in terms of exploitation and smuggling of timber forms a problem compared to exploited species whose status is considered "vulnerable" on the IUCN red list compiled by. Commercial species in Class III of the Democratic Republic of Congo are the least known in the market operating, and their biology is unknown or non-existent. Identification of wood in terms of descriptions and anatomical measurements of the wood is in great demand for various stakeholders such as scientists, customs, IUCN, etc. The objective of this study is the qualitative and quantitative description of the anatomical characteristics of commercial species in Class III of DR Congo. The site of the Luki Biosphere Reserve was chosen because of its high tree species richness. This study focuses on the wood anatomy of 14 commercial species of Class III of DR Congo. Thirty-four wooden discs were collected for these species. The following parameters were measured in the field: Diameter at breast height (DBH), total height and geographic coordinates. Microtomy, identification of vessel parameters (diameter, density and grouping) and photograph of the microscopic sections and determining age were performed in this study. The results obtained are detailed anatomical descriptions of species in Class III of the Democratic Republic of Congo.

Keywords: sustainable management of forest, rainforest, commercial species of class iii, vessel diameter, vessel density, grouping vessel

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Authors: Benedetta Isella, Aleksander Drinic, Alissa Heim, Phillip Czichowski, Lisa Lauts, Hans Leemhuis

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Introduction: Membranes for guided bone regeneration are essential to perform a barrier function between the soft and the regenerating bone tissue. Bioabsorbable membranes are desirable in this field as they do not require a secondary surgery for removal, decreasing patient surgical risk. Collagen was the first bioabsorbable alternative introduced on the market, but its degradation time may be too fast to guarantee bone regeneration, and optimisation is needed. Silk fibroin, being biocompatible, slowly bioabsorbable, and processable into different scaffold types, could be a promising alternative. Objectives: The objective is to compare the general performance of a silk fibroin membrane for guided bone regeneration to current collagen alternatives developing suitable standardized tests for the mechanical and morphological characterization. Methods: Silk fibroin and collagen-based membranes were compared from the morphological and chemical perspective, with techniques such as SEM imaging and from the mechanical point of view with techniques such as tensile and suture retention strength (SRS) tests. Results: Silk fibroin revealed a high degree of reproducibility in surface density. The SRS of silk fibroin (0.76 ± 0.04 N), although lower than collagen, was still comparable to native tissues such as the internal mammary artery (0.56 N), and the same can be extended to general mechanical behaviour in tensile tests. The SRS could be increased by an increase in thickness. Conclusion: Silk fibroin is a promising material in the field of guided bone regeneration, covering the interesting position of not being considered a product containing cells or tissues of animal origin from the regulatory perspective and having longer degradation times with respect to collagen.

Keywords: guided bone regeneration, mechanical characterization, membrane, silk fibroin

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Authors: Rishabh Hans, Saksham Sharma

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Drying of a sessile droplet imbibed with colloidal solution is a complex process in many aspects. Till now, most of the work revolves around; conditions for buckling onset, post-buckling effects, nature of change of droplet shape etc. In this work, we are determining the shape of daughter cavity (DC) formed during post-buckling onset, a less explored stage, and its relationship with experimental parameters. We have introduced solid angle as a special parameter that can quantify the shape of DC at any instant. It facilitates us to compare the shape while experimenting across different substrate types, droplet sizes and particle concentration. Furthermore, the angular location of ‘weak spot’ on the periphery of droplet, which marks the initiation of cavity growth, varies in different conditions. To solve this problem, we have evaluated the deflection angle of weak spots w.r.t. the vertical axis going through the middle of droplet. Subsequently, the solid angle subtended by DC is analyzed about that inclined axis. Finally, results of analysis allude that increasing colloidal concentration has inverse effect on the growth rate of cavity’s shape. Moreover, the cap radius of DC is observed lower for high PLR which makes the capillary pressure higher and thus tougher to expedite cavity formation relatively. This analysis can be helpful in further studies to relate the shape, deflection angle, growth rate of daughter cavity to the type of droplet crust formed in the end. Examining DC stage shall add another layer to nano-colloidal research which aims to influence many industrial applications like patterning, coatings, drug delivery, food processing etc.

Keywords: buckling of sessile droplets, daughter cavity, droplet evaporation, nanoporous shell formation, solid angle

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Authors: Elvira Lumi, Hans Jazxhi

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In the works of the writer Flutura Açka, the play with these questions is acute, and in almost each of them, the act of loneliness and isolation builds in a completely involuntary way unique and frequent conceptual spaces. Because the object of study is too broad to grasp all the works, this study lays out a rapid paradox of our access to three of the novels in the line of numerous authorial works. The novel "Woman Loneliness" (2001), also marked as the first work in prose by the author, declares in the title the paradigm of what she has decided to confess. The gender segregation proclaimed in the title will be revealed step by step in the work as conventional human segregation without gender. In this novel, the analysis of the state of "loneliness" will require a contemplation beyond man, when the role of the environment and the distance from the center of the narrative base will be extremely visible in the work. The novel "Cross of Oblivion" (2004) has another form of perception of loneliness, which, unlike the one built by the characters themselves in the novel "Woman Loneliness," is imposed and obligatory to live by the circumstances. Its characters are trapped in loneliness, as loneliness that comes from impossibility, from the past, from dependence on fate, from fear of change, and from the obligation to accept it. At the heart of the novel, the plot of the novel game is dictated by the Kanun and its rules and the loneliness of the basis of life in unbroken waves towards the periphery of the event, a periphery that has very large geography and is played in today's Europe. The novel "Where are you?" (2009) has a completely different form of constructing the concept of loneliness and isolation that comes under conditions of repression and political pressure. The loneliness in this novel takes the form of the protective element from the circumstances that actually require a social inclusion; it is personal loneliness that ensures relative mental health of the characters, up to a new trap created by the circumstances, thus building life fragmentary “healthy” in the order of a mentally ill and socially ill society.

Keywords: loneliness, existential, isolation, woman, prose

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

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

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

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Authors: Ateeqa Aslam, Hans J. Nauwynck

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Porcine hemagglutinating encephalomyelitis virus (PHEV) is a betacoronavirus that has been studied in the past as a cause of vomiting and wasting disease (VWD) in young piglets (<3 weeks). Nowadays, the virus is still circulating on most farms in Belgium, but there are no descriptions anymore of VWD. Therefore, we are interested in differences between the old and new strains. We compared the replication kinetics of the old well-studied strain VW572 (1972) and the recent isolate P412 (2020) in a susceptible continuous cell line (RPD cells) and in primary porcine respiratory epithelial cells (PoRECs). The RPD cell line was inoculated with each PHEV strain at an m.o.i. of 1 the supernatant was collected, and the cells were fixed at different time points post-inoculation. The supernatant was titrated (extracellular virus titer), and the infected cells were revealed by immunofluorescence staining and quantitated by fluorescence microscopy. We found that VW572 replicated better in the RPD cell line at earlier time points when compared to P412. Porcine respiratory epithelial cells (PoREC) were isolated, grown at air-liquid interphase in transwells and inoculated with both strains of PHEV at a virus titer of 106.6TCID50 per 200 µl either at the apical side or at the basal side of the cells. At different time points after inoculation, the transwells were fixed and stained for infected cells. VW572 preferentially infected the epithelial cells via the basolateral side of porcine nasal epithelial cells, whereas P412 preferred the apical side. These findings suggest that there has been an evolution of PHEV in its interaction with the respiratory epithelial cells. In the future, more virus strains will be enclosed and the tropism of the strains for different neuronal cell types will be examined for the change in virus neurotropism.

Keywords: porcine hemagglutinating encephalomyelitis virus (PHEV), primary porcine respiratory epithelial cells (PoRECs), virus tropism, vomiting and wasting disease (VWD)

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Authors: Yeganeh Attari, Gudmund Reidar Eiksund, Hans Peter Jostad

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In Geotechnical practice, there is no standard method recognized by the industry to account for the reduction of safety factor of a slope as an effect of soil displacement and pore pressure build-up during pile installation. Pile driving disturbs causes large strains and generates excess pore pressures in a zone that can extend many diameters from the installed pile, resulting in a decrease of the shear strength of the surrounding soil. This phenomenon may cause slope failure. Moreover, dissipation of excess pore pressure set-up may cause weakening of areas outside the volume of soil remoulded during installation. Because of complex interactions between changes in mean stress and shearing, it is challenging to predict installation induced pore pressure response. Furthermore, it is a complex task to follow the rate and path of pore pressure dissipation in order to analyze slope stability. In cohesive soils it is necessary to implement soil models that account for strain softening in the analysis. In the literature, several cases of slope failure due to pile driving activities have been reported, for instance, a landslide in Gothenburg that resulted in a slope failure destroying more than thirty houses and Rigaud landslide in Quebec which resulted in loss of life. Up to now, several methods have been suggested to predict the effect of pile driving on total and effective stress, pore pressure changes and their effect on soil strength. However, this is still not well understood or agreed upon. In Norway, general approaches applied by geotechnical engineers for this problem are based on old empirical methods with little accurate theoretical background. While the limitations of such methods are discussed, this paper attempts to capture the reduction in the factor of safety of a slope during pile driving, using coupled Finite Element analysis and cavity expansion method. This is demonstrated by analyzing a case of slope failure due to pile driving in Norway.

Keywords: cavity expansion method, excess pore pressure, pile driving, slope failure

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Authors: Arda Ozkurt, Ozlem Bozkurt

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Brain-computer interfaces (BCIs) are devices that output commands by interpreting the data collected from the brain. Electroencephalography (EEG) is a non-invasive method to measure the brain's electrical activity. Since it was invented by Hans Berger in 1929, it has led to many neurological discoveries and has become one of the essential components of non-invasive measuring methods. Despite the fact that it has a low spatial resolution -meaning it is able to detect when a group of neurons fires at the same time-, it is a non-invasive method, making it easy to use without possessing any risks. In EEG, electrodes are placed on the scalp, and the voltage difference between a minimum of two electrodes is recorded, which is then used to accomplish the intended task. The recordings of EEGs include, but are not limited to, the currents along dendrites from synapses to the soma, the action potentials along the axons connecting neurons, and the currents through the synaptic clefts connecting axons with dendrites. However, there are some sources of noise that may affect the reliability of the EEG signals as it is a non-invasive method. For instance, the noise from the EEG equipment, the leads, and the signals coming from the subject -such as the activity of the heart or muscle movements- affect the signals detected by the electrodes of the EEG. However, new techniques have been developed to differentiate between those signals and the intended ones. Furthermore, an EEG device is not enough to analyze the data from the brain to be used by the BCI implication. Because the EEG signal is very complex, to analyze it, artificial intelligence algorithms are required. These algorithms convert complex data into meaningful and useful information for neuroscientists to use the data to design BCI devices. Even though for neurological diseases which require highly precise data, invasive BCIs are needed; non-invasive BCIs - such as EEGs - are used in many cases to help disabled people's lives or even to ease people's lives by helping them with basic tasks. For example, EEG is used to detect before a seizure occurs in epilepsy patients, which can then prevent the seizure with the help of a BCI device. Overall, EEG is a commonly used non-invasive BCI technique that has helped develop BCIs and will continue to be used to detect data to ease people's lives as more BCI techniques will be developed in the future.

Keywords: BCI, EEG, non-invasive, spatial resolution

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Authors: Akram Abi, Clarissa Müller, Hans-Joachim Jördening

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Laminaribiose is a beta-1,3-glycoside which is used in the medical field for the treatment of dermatitis and also can be used as a building block for new pharmaceutics. The conventional process of laminaribiose production is the uneconomical process of hydrolysis of laminarin extracted from natural polysaccharides of plant origin. A more economical approach however is attainable by enzymatically synthesis of laminaribiose via a reverse phosphorylase reaction catalyzed by laminaribiose phosphorylase (LP) from Euglena gracilis. Different cultivation methods of Euglena gracilis and the effect on LP production have been investigated. Buffered/unbuffered heterotrophic and mixotrophic cultivations of Euglena gracilis has been carried out. Changes of biomass and LP production, glucose level and pH, cell count and shape has been monitored in the course of time. The results obtained from experiments each in three repetitions, show that in the heterotrophic cultivation of Euglena gracilis not only more biomass is produced compared to mixotrophic cultivation, but also higher specific protein concentration is achieved. Furthermore, the LP activity test showed that the protein extracted from heterotrophically cultured cells has a higher LP activity. It was also observed that the cells develop in a distinctive different shape between these two cultures and have different length to width ratios. Taking the heterotrophic culture as the more efficient cultivation method in LP production, another comparative experiment between buffered and unbuffered heterothrophic culture was carried out that showed the unbuffered culture has advantages over the other one in respect of both LP production and resulting activity. A hetrotrophic cultivation of Euglena gracilis in a 5L bioreactor with controlled operating conditions showed a distinctive improvement of all the aspects of culture compared to the shaking flask cultivations. Biomass production was improved from 5 to more than 8 g/l (dry weight) which resulted in a specific protein concentration of 45 g/l in the heterotrophic cultivation in the bioreactor. In further attempts to improve LP production, different purification methods were tested and each method was checks through an activity assay. A laminaribiose yield of 35% was achieved which was by far the highest amount amongst different methods tested.

Keywords: euglena gracilis, heterotrophic culture, laminaribiose production, mixotrophic culture

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Authors: Hans Tjio, Wee Meng Seng

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The interaction of contract and property has always been a concern in corporate and commercial law, where there are internal structures created that may not match the externally perceived image generated by the labels attached to those structures. We will focus, in particular, on the priority structures created by affirmative asset partitioning, which have increasingly come under challenge by those attempting to negotiate around them. The most prominent has been the AT1 bonds issued by Credit Suisse which were wiped out before its equity when the troubled bank was acquired by UBS. However, this should not have come as a surprise to those whose “bonds” had similarly been “redeemed” upon the occurrence of certain reference events in countries like Singapore, Hong Kong and Taiwan during their Minibond crisis linked to US sub-prime defaults. These were derivatives classified as debentures and sold as such. At the same time, we are again witnessing “liabilities” seemingly ranking higher up the balance sheet ladder, finding themselves lowered in events of default. We will examine the mechanisms holders of perpetual securities or preference shares have tried to use to protect themselves. This is happening against a backdrop that sees a rise in the strength of private credit and inter-creditor conflicts. The restructuring regime of the hybrid scheme in Singapore now, while adopting the absolute priority rule in Chapter 11 as the quid pro quo for creditor cramdown, does not apply to shareholders and so exempts them from cramdown. Complicating the picture further, shareholders are not exempted from cramdown in the Dutch scheme, but it adopts a relative priority rule. At the same time, the important UK Supreme Court decision in BTI 2014 LLC v Sequana [2022] UKSC 25 has held that directors’ duties to take account of creditor interests are activated only when a company is almost insolvent. All this has been complicated by digital assets created by businesses. Investors are quite happy to have them classified as property (like a thing) when it comes to their transferability, but then when the issuer defaults to have them seen as a claim on the business (as a choice in action), that puts them at the level of a creditor. But these hidden interests will not show themselves on an issuer’s balance sheet until it is too late to be considered and yet if accepted, may also prevent any meaningful restructuring.

Keywords: asset partitioning, creditor priority, restructuring, BTI v Sequana, digital assets

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Authors: Somayeh Pashaee

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The ever-increasing growth of the Internet and the development of information and communication technology have prompted the politicians of different countries to use virtual networks as an efficient tool for their foreign policy. The communication of governments and countries, even in the farthest places from each other, through electronic networks, has caused vast changes in the way of statecraft and governance. Importantly, in the meantime, diplomacy, which is always based on information and communication, has been affected by the new prevailing conditions and new technologies more than other areas and has faced greater changes. The emergence of virtual space and the formation of new communication tools in the field of public diplomacy has led to the redefinition of the framework of diplomacy and politics in the international arena and the appearance of a new aspect of diplomacy called digital diplomacy. Digital diplomacy is in the concept of changing relations from a face-to-face and traditional way to a non-face-to-face and new way, and its purpose is to solve foreign policy issues using virtual space. Digital diplomacy, by affecting diplomatic procedures and its change, explains the role of technology in the visualization and implementation of diplomacy in different ways. The purpose of this paper is to investigate the position of digital diplomacy in the public diplomacy of the Islamic Republic of Iran. The paper tries to answer these two questions in a descriptive-analytical way, considering the progress of communication and the role of virtual space in the service of diplomacy, what is the approach of the Islamic Republic of Iran towards digital diplomacy and the use of a new way of establishing foreign relations in public diplomacy? What capacities and damages are facing the country after the use of this type of new diplomacy? In this paper, various theoretical concepts in the field of public diplomacy and modern diplomacy, including Geoff Berridge, Charles Kegley, Hans Tuch and Ronald Peter Barston, as well as the theoretical framework of Marcus Holmes on digital diplomacy, will be used as a conceptual basis to support the analysis. As a result, in order to better achieve the political goals of the country, especially in foreign policy, the approach of the Islamic Republic of Iran to public diplomacy with a focus on digital diplomacy should be strengthened and revised. Today, only emphasizing on advancing diplomacy through traditional methods may weaken Iran's position in the public opinion level from other countries.

Keywords: digital diplomacy, public diplomacy, islamic republic of Iran, foreign policy, opportunities and challenges

Procedia PDF Downloads 113

Authors: Ghodsieh Isapour Toutizad, Aiyong Wang, Joonsoo Han, Derek Creaser, Louise Olsson, Magnus Skoglundh, Hanna HaRelind

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Nitrous oxide (N2O), which is generally formed as a byproduct of industrial chemical processes and fossil fuel combustion, has attracted considerable attention due to its destructive role in global warming and ozone layer depletion. From various developed technologies used for lean NOx reduction, the selective catalytic reduction (SCR) of NOx with ammonia is presently the most applied method. Therefore, the development of catalysts for efficient lean NOx reduction without forming N2O in the process, or only forming it to a very small extent from the exhaust gases is of crucial significance. One type of catalysts that nowadays are used for this aim are zeolite-based catalysts. It is owing to their remarkable catalytic performance under practical reaction conditions such as high thermal stability and high N2 selectivity. Among all zeolites, copper ion-exchanged zeolites, with CHA, MFI, and BEA framework structure (like SSZ-13, ZSM-5 and Beta, respectively), represent higher hydrothermal stability, high activity and N2 selectivity. This work aims at investigating the effect of the zeolite framework structure on the formation of N2O during NH3-SCR reaction conditions over three Cu-based zeolites ranging from small-pore to large-pore framework structure. In the zeolite framework, Cu exists in two cationic forms, that can catalyze the SCR reaction by activating NO to form NO+ and/or surface nitrate species. The nitrate species can thereafter react with NH3 to form another intermediate, ammonium nitrate, which seems to be one source for N2O formation at low temperatures. The results from in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) indicate that during the NO oxidation step, mainly NO+ and nitrate species are formed on the surface of the catalysts. The intensity of the absorption peak attributed to NO+ species is higher for the Cu-CHA sample compared to the other two samples, indicating a higher stability of this species in small cages. Furthermore, upon the addition of NH3, through the standard SCR reaction conditions, absorption peaks assigned to N-H stretching and bending vibrations are building up. At the same time, negative peaks are evolving in the O-H stretching region, indicating blocking/replacement of surface OH-groups by NH3 and NH4+. By removing NH3 and adding NO2 to the inlet gas composition, the peaks in the N-H stretching and bending vibration regions show a decreasing trend in intensity, with the decrease being more pronounced for increasing pore size. It can probably be owing to the higher accumulation of ammonia species in the small-pore size zeolite compared to the other two samples. Furthermore, it is worth noting that the ammonia surface species are strongly bonded to the CHA zeolite structure, which makes it more difficult to react with NO2. To conclude, the framework structure of the zeolite seems to play an important role in the formation and reactivity of surface species relevant for the SCR process. Here we intend to discuss the connection between the zeolite structure, the surface species, and the formation of N2O during ammonia-SCR.

Keywords: fast SCR, nitrous oxide, NOx, standard SCR, zeolites

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Authors: Peder O. Laugen Heggdal, Oyvind Nordvik, Jonas Brannstrom, Flemming Vassbotn, Anne Kari Aarstad, Hans Jorgen Aarstad

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Background: Hearing loss (HL) affect people of all ages and stages in life. To author's best knowledge, if patients with an HL have reduced Generic Quality of life (QoL), has yet not been answered. Aim: The aim of the present study was to investigate the relationship between HL and generic and disease-specific Health Related Quality of Life (HRQoL) in adult patients (aged 18–78 years) with an HL, seeking Hearing Aid (HA). Material and Methods: 158 adult (aged 18-78 years) patients with HL, referred for HA fitting at Haukeland University Hospital in western Norway, participated in the study. Both first-time users, as well as patients referred for HA renewals, were included. First-time users had been pre-examined by an Ear Nose and Throat specialist. The questionnaires were answered before the actual HA fitting procedure. The pure-tone average (PTA; frequencies 0.5, 1, 2 and 4 kHz) was determined for each ear. The generic European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire general part and a shortened version of the Abbreviated Profile of Hearing Aid Benefit (APHAB) were answered. In addition, EORTC HRQoL answers from a general population and patients with former head and neck cancer served as comparison. Results: In general, no lowered HRQoL scores were determined among HL patients compared to the general population. Patients with unilateral HL to some extent showed lower HRQoL than those with bilateral HL (social function and fatigue). The APHAB scores correlated significantly with the EORTC HRQoL scores. By stepwise linear regression analysis, the APHAB scores were scored secondary to PTA (best ear), cognitive and physical function. Conclusion: HRQoL scores in HL patients, in general, seems to be at the population level, but the unilateral HL patients scored to some extent lower than the bilateral HI patients. APHAB and generic QoL scores levels are associated. Both HRQoL and APHAB scores are generated more complexly than anticipated.

Keywords: quality of life, hearing loss, hearing impairment, distress, depression, anxiety, hearing aid

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Authors: Holm Zerbe, Laura Macias, Hans-Joachim Schuberth, Wolfram Petzl

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Mastitis is among the most important production diseases in cows. It accounts for large parts of antimicrobial drug use in the dairy industry worldwide. Due to the imminent normative to reduce the use of antimicrobial drugs in livestock, new ways for therapy and prophylaxis of mastitis are needed. Recently epigenetic regulation of inflammation by chromatin modifications has increasingly drawn attention. Currently, some epigenetic modifiers have already been approved for the use in humans, however little is known about their actions in the bovine system. The aim of our study was to investigate whether three selected epigenetic modifiers (Vitamin D3, SAHA and S2101) influence the initial immune response towards mastitis pathogens in bovine udder tissue in vitro. Tissue explants of the teat cistern and udder parenchyma were collected from 21 cows and were incubated for 36 hours in the absence and presence of epigenetic modifiers. Additionally, the tissue was stimulated with heat-inactivated particles of Escherichia coli and Staphylococcus aureus, which are regarded as two of the most important mastitis pathogens. After incubation, the explants were tested by RT-qPCR for transcript abundances of immune-related candidate genes. Gene expression was validated in culture supernatants by an AlphaLISA assay. Furthermore, the culture supernatants were analyzed for their chemotactic capacity through a chemotaxis assay. Statistical analysis of data was performed with the program ‘R’ version 3.2.3. Vitamin D3 had no effect on the immune response of udder tissue in vitro after stimulation with mastitis pathogens. The epigenetic modifiers SAHA and S2101 however significantly blocked the pathogen-induced upregulation of CXCL8, TNFα, S100A9 and LAP (P < 0.05). The regulation of IL10 was not affected by treatment with SAHA and S2101. Transcript abundances for CXCL8 were reflected by IL8 contents and chemotactic activity in culture supernatants. In conclusion, these data show the potential of epigenetic modifiers (SAHA and S2101) to block overshooting inflammation in the udder. Thus epigenetic modifiers may serve in future as immune modulators for the treatment and/or prophylaxis of clinical mastitis. (Funded by Deutsche Forschungsgemeinschaft PE 1495/2-1).

Keywords: mastitis, cattle, epigenetics, immunomodulation

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Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

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