Search results for: drug induced premature chromosome condensation

Authors: Turky Al-Qahtani, Roustem Miftahof

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Introduction: Under common assumptions of excitabi-lity, morphological (cellular) homogeneity, and spatial structural anomalies added as required, it has been shown that biological systems are able to display travelling wave dynamics. Being not self-sustainable, existence depends on the electrophysiological state of transmembrane ion channels and it requires an extrinsic/intrinsic periodic source. However, organs in the body are highly multicellular, heterogeneous, and their functionality is the outcome of electro-mechanical conjugation, rather than excitability only. Thus, peristalsis in the gut relies on spatiotemporal myoelectrical pattern formations between the mechanical, represented by smooth muscle cells (SM), and the control, comprised of a chain of primary sensory and motor neurones, components. Synaptically linked through the afferent and efferent pathways, they form a functional unit (FU) of the gut. Aims: These are: i) to study numerically the complex dynamics, and ii) to investigate the possibility of self-sustained myoelectrical activity in the FU. Methods: The FU recreates the following sequence of physiological events: deformation of mechanoreceptors of located in SM; generation and propagation of electrical waves of depolarisation - spikes - along the axon to the soma of the primary neurone; discharge of the primary neurone and spike propagation towards the motor neurone; burst of the motor neurone and transduction of spikes to SM, subsequently producing forces of contraction. These are governed by a system of nonlinear partial and ordinary differential equations being a modified version of the Hodgkin-Huxley model and SM fibre mechanics. In numerical experiments; the source of excitation is mechanical stretches of SM at a fixed amplitude and variable frequencies. Results: Low frequency (0.5 < v < 2 Hz) stimuli cause the propagation of spikes in the neuronal chain and, finally, the generation of active forces by SM. However, induced contractions are not sufficient to initiate travelling wave dynamics in the control system. At frequencies, 2 < v < 4 Hz, multiple low amplitude and short-lasting contractions are observed in SM after the termination of stretching. For frequencies (0.5 < v < 4 Hz), primary and sensory neurones demonstrate strong connectivity and coherent electrical activity. Significant qualitative and quantitative changes in dynamics of myoelectical patterns with a transition to a self-organised mode are recorded with the high degree of stretches at v = 4.5 Hz. Increased rates of deformation lead to the production of high amplitude signals at the mechanoreceptors with subsequent self-sustained excitation within the neuronal chain. Remarkably, the connection between neurones weakens resulting in incoherent firing. Further increase in a frequency of stimulation (v > 4.5 Hz) has a detrimental effect on the system. The mechanical and control systems become disconnected and exhibit uncoordinated electromechanical activity. Conclusion: To our knowledge, the existence of periodic activity in a multicellular, functionally heterogeneous biological system with mechano-electrical dynamics, such as the FU, has been demonstrated for the first time. These findings support the notion of possible peristalsis in the gut even in the absence of intrinsic sources - pacemaker cells. Results could be implicated in the pathogenesis of intestinal dysrythmia, a medical condition associated with motor dysfunction.

Keywords: complex dynamics, functional unit, the gut, dysrythmia

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Authors: Tugba Altin

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In an era where the impacts of climate change resonate more pronouncedly than ever, communities globally grapple with events bearing both tangible and intangible ramifications. Situating this within the evolving landscapes of Psychological and Behavioral Sciences, this research probes the profound psychological and behavioral responses evoked by such events. The Lytton Creek Fire of 2021 epitomizes these challenges. While tangible destruction is immediate and evident, the intangible repercussions—emotional distress, disintegration of cultural landscapes, and disruptions in place attachment (PA)—require meticulous exploration. PA, emblematic of the emotional and cognitive affiliations individuals nurture with their environments, emerges as a cornerstone for comprehending how environmental cataclysms influence cultural identity and bonds to land. This study, harmonizing the core tenets of an interpretive phenomenological approach with a hermeneutic framework, underscores the pivotal nature of this attachment. It delves deep into the realm of individuals' experiences post the Lytton Creek Fire, unraveling the intricate dynamics of PA amidst such calamity. The study's methodology deviates from conventional paradigms. Instead of traditional interview techniques, it employs walking audio sessions and photo elicitation methods, granting participants the agency to immerse, re-experience, and vocalize their sentiments in real-time. Such techniques shed light on spatial narratives post-trauma and capture the otherwise elusive emotional nuances, offering a visually rich representation of place-based experiences. Central to this research is the voice of the affected populace, whose lived experiences and testimonies form the nucleus of the inquiry. As they renegotiate their bonds with transformed environments, their narratives reveal the indispensable role of cultural landscapes in forging place-based identities. Such revelations accentuate the necessity of integrating both tangible and intangible trauma facets into community recovery strategies, ensuring they resonate more profoundly with affected individuals. Bridging the domains of environmental psychology and behavioral sciences, this research accentuates the intertwined nature of tangible restoration with the imperative of emotional and cultural recuperation post-environmental disasters. It advocates for adaptation initiatives that are rooted in the lived realities of the affected, emphasizing a holistic approach that recognizes the profundity of human connections to landscapes. This research advocates the interdisciplinary exchange of ideas and strategies in addressing post-disaster community recovery strategies. It not only enriches the climate change discourse by emphasizing the human facets of disasters but also reiterates the significance of an interdisciplinary approach, encompassing psychological and behavioral nuances, for fostering a comprehensive understanding of climate-induced traumas. Such a perspective is indispensable for shaping more informed, empathetic, and effective adaptation strategies.

Keywords: place attachment, community recovery, disaster response, restorative landscapes, sensory response, visual methodologies

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Authors: Ashleigh Williams

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Micro- and nanoplastics’ (MNLPs) omnipresence and ecological accumulation is evident when surveying recent environmental impact studies. For example, in 2014 it was estimated that at least 52.3 trillion plastic microparticles are floating at sea, and scientists have even found plastics present remote Arctic ice and snow (5,6). Plastics have even found their way into precipitation, with more than 1000 tons of microplastic rain precipitating onto the Western United States in 2020. Even more recent studies evaluating the chemical safety of reusable plastic bottles found that hundreds of chemicals leached into the control liquid in the bottle (ddH2O, ph = 7) during a 24-hour time period. A consequence of the increased abundance in plastic waste in the air, land, and water every year is the bioaccumulation of MNLPs in ecosystems and trophic niches of the animal food chain, which could potentially cause increased direct and indirect exposure of humans to MNLPs via inhalation, ingestion, and dermal contact. Though the detrimental, toxic effects of MNLPs have been established in marine biota, much less is known about the potentially hazardous health effects of chronic MNLP ingestion in humans. Recent data indicate that long-term exposure to MNLPs could cause possible inflammatory and dysbiotic effects. However, toxicity seems to be largely dose-, as well as size-dependent. In addition, the transcytotic uptake of MNLPs through the intestinal epithelia in humans remain relatively unknown. To this point, the goal of the current study was to investigate the mechanisms of micro- and nanoplastic uptake and transcytosis of Polystyrene (PE) in human stem-cell derived, physiologically relevant in vitro intestinal model systems, and to compare the relative effect of particle size (30 nm, 100 nm, 500 nm and 1 µm), and concentration (0 µg/mL, 250 µg/mL, 500 µg/mL, 1000 µg/mL) on polystyrene MNLP uptake, transcytosis and intestinal epithelial model integrity. Observational and quantitative data obtained from confocal microscopy, immunostaining, transepithelial electrical resistance (TEER) measurements, cryosectioning, and ELISA cytokine assays of the proinflammatory cytokines Interleukin-6 and Interleukin-8 were used to evaluate the localization and transcytosis of polystyrene MNPs and its impact on epithelial integrity in human-derived intestinal in vitro model systems. The effect of Microfold (M) cell induction on polystyrene micro- and nanoparticle (MNP) uptake, transcytosis, and potential inflammation was also assessed and compared to samples grown under standard conditions. Microfold (M) cells, link the human intestinal system to the immune system and are the primary cells in the epithelium responsible for sampling and transporting foreign matter of interest from the lumen of the gut to underlying immune cells. Given the uptake capabilities of Microfold cells to interact both specifically and nonspecific to abiotic and biotic materials, it was expected that M- cell induced in vitro samples would have increased binding, localization, and potentially transcytosis of Polystyrene MNLPs across the epithelial barrier. Experimental results of this study would not only help in the evaluation of the plastic toxicity, but would allow for more detailed modeling of gut inflammation and the intestinal immune system.

Keywords: nanoplastics, enteroids, intestinal barrier, tissue engineering, microfold (M) cells

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Authors: Gousilin Leandra Rocha Da Silva, Stéfani T. A. Dantas, Bruna F. Rossi, Erika R. Bonsaglia, Ivana G. Castilho, Terue Sadatsune, Ary Fernandes Júnior, Vera l. M. Rall

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Kidney failure causes decreased diuresis and accumulation of nitrogenous substances in the body. To increase patient survival, hemodialysis is used as a partial substitute for renal function. However, contamination of the water used in this treatment, causing bacteremia in patients, is a worldwide concern. The Burkholderia cepacia complex (Bcc), a group of bacteria with more than 20 species, is frequently isolated from hemodialysis water samples and comprises opportunistic bacteria, affecting immunosuppressed patients, due to its wide variety of virulence factors, in addition to innate resistance to several antimicrobial agents, contributing to the permanence in the hospital environment and to the pathogenesis in the host. The objective of the present work was to characterize molecularly and phenotypically Bcc isolates collected from the water and dialysate of the Hemodialysis Unit and from the blood of patients at a Public Hospital in Botucatu, São Paulo, Brazil, between 2019 and 2021. We used 33 Bcc isolates, previously obtained from blood cultures from patients with bacteremia undergoing hemodialysis treatment (2019-2021) and 24 isolates obtained from water and dialysate samples in a Hemodialysis Unit (same period). The recA gene was sequenced to identify the specific species among the Bcc group. All isolates were tested for the presence of some genes that encode virulence factors such as cblA, esmR, zmpA and zmpB. Considering the epidemiology of the outbreak, the Bcc isolates were molecularly characterized by Multi Locus Sequence Type (MLST) and by pulsed-field gel electrophoresis (PFGE). The verification and quantification of biofilm in a polystyrene microplate were performed by submitting the isolates to different incubation temperatures (20°C, average water temperature and 35°C, optimal temperature for group growth). The antibiogram was performed with disc diffusion tests on agar, using discs impregnated with cefepime (30µg), ceftazidime (30µg), ciprofloxacin (5µg), gentamicin (10µg), imipenem (10µg), amikacin 30µg), sulfametazol/trimethoprim (23.75/1.25µg) and ampicillin/sulbactam (10/10µg). The presence of ZmpB was identified in all isolates, while ZmpA was observed in 96.5% of the isolates, while none of them presented the cblA and esmR genes. The antibiogram of the 33 human isolates indicated that all were resistant to gentamicin, colistin, ampicillin/sulbactam and imipenem. 16 (48.5%) isolates were resistant to amikacin and lower rates of resistance were observed for meropenem, ceftazidime, cefepime, ciprofloxacin and piperacycline/tazobactam (6.1%). All isolates were sensitive to sulfametazol/trimethoprim, levofloxacin and tigecycline. As for the water isolates, resistance was observed only to gentamicin (34.8%) and imipenem (17.4%). According to PFGE results, all isolates obtained from humans and water belonged to the same pulsotype (1), which was identified by recA sequencing as B. cepacia¸, belonging to sequence type ST-767. By observing a single pulse type over three years, one can observe the persistence of this isolate in the pipeline, contaminating patients undergoing hemodialysis, despite the routine disinfection of water with peracetic acid. This persistence is probably due to the production of biofilm, which protects bacteria from disinfectants and, making this scenario more critical, several isolates proved to be multidrug-resistant (resistance to at least three groups of antimicrobials), turning the patient care even more difficult.

Keywords: hemodialysis, burkholderia cepacia, PFGE, MLST, multi drug resistance

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Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu

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Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.

Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma

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Authors: Rama Umesh Pandey, Jyoti Yadav

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Flooding is one of the waterborne disasters that causes extensive destruction in urban areas. Developing countries are at a higher risk of such damage and more than half of the global flooding events take place in Asian countries including India. Urban flooding is more of a human-induced disaster rather than natural. This is highly influenced by the anthropogenic factors, besides metrological and hydrological causes. Unplanned urbanization and poor management of cities enhance the impact manifold and cause huge loss of life and property in urban areas. It is an irony that urban areas have been facing water scarcity in summers and flooding during monsoon. This paper is an attempt to highlight the factors responsible for flooding in a city especially from an urban planning perspective and to suggest mitigating measures through spatial planning interventions. Analysis has been done in two stages; first is to assess the impacts of previous flooding events and second to analyze the factors responsible for flooding at macro and micro level in cities. Bhopal, a city in Central India having nearly two million population, has been selected for the study. The city has been experiencing flooding during heavy rains in monsoon. The factors responsible for urban flooding were identified through literature review as well as various case studies from different cities across the world and India. The factors thus identified were analyzed for both macro and micro level influences. For macro level, the previous flooding events that have caused huge destructions were analyzed and the most affected areas in Bhopal city were identified. Since the identified area was falling within the catchment of a drain so the catchment area was delineated for the study. The factors analyzed were: rainfall pattern to calculate the return period using Weibull’s formula; imperviousness through mapping in ArcGIS; runoff discharge by using Rational method. The catchment was divided into micro watersheds and the micro watershed having maximum impervious surfaces was selected to analyze the coverage and effect of physical infrastructure such as: storm water management; sewerage system; solid waste management practices. The area was further analyzed to assess the extent of violation of ‘building byelaws’ and ‘development control regulations’ and encroachment over the natural water streams. Through analysis, the study has revealed that the main issues have been: lack of sewerage system; inadequate storm water drains; inefficient solid waste management in the study area; violation of building byelaws through extending building structures ether on to the drain or on the road; encroachments by slum dwellers along or on to the drain reducing the width and capacity of the drain. Other factors include faulty culvert’s design resulting in back water effect. Roads are at higher level than the plinth of houses which creates submersion of their ground floors. The study recommends spatial planning interventions for mitigating urban flooding and strategies for management of excess rain water during monsoon season. Recommendations have also been made for efficient land use management to mitigate water logging in areas vulnerable to flooding.

Keywords: mitigating strategies, spatial planning interventions, urban flooding, violation of development control regulations

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Authors: Rawan Hakawati, Beatrice Smyth, David Rooney, Geoffrey McCullough

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Targets have been set in the EU to increase the share of renewable energy consumption to 20% by 2020, but developments have not occurred evenly across the member states. Northern Ireland is almost 90% dependent on imported fossil fuels. With such high energy dependency, Northern Ireland is particularly susceptible to the security of supply issues. Linked to fossil fuels are greenhouse gas emissions, and the EU plans to reduce emissions by 20% by 2020. The use of indigenously produced biomass could reduce both greenhouse gas emissions and external energy dependence. With a wide range of both crop and waste feedstock potentially available in Northern Ireland, anaerobic digestion has been put forward as a possible solution for renewable energy production, waste management, and greenhouse gas reduction. Not all feedstock, however, is the same, and an understanding of feedstock suitability is important for both plant operators and policy makers. The aim of this paper is to investigate biomass suitability for anaerobic digestion in Northern Ireland. It is also important that decisions are based on solid scientific evidence. For this reason, the methodology used is multi-criteria decision matrix analysis which takes multiple criteria into account simultaneously and ranks alternatives accordingly. The model uses the weighted sum method (which follows the Entropy Method to measure uncertainty using probability theory) to decide on weights. The Topsis method is utilized to carry out the mathematical analysis to provide the final scores. Feedstock that is currently available in Northern Ireland was classified into two categories: wastes (manure, sewage sludge and food waste) and energy crops, specifically grass silage. To select the most suitable feedstock, methane yield, feedstock availability, feedstock production cost, biogas production, calorific value, produced kilowatt-hours, dry matter content, and carbon to nitrogen ratio were assessed. The highest weight (0.249) corresponded to production cost reflecting a variation of £41 gate fee to 22£/tonne cost. The weights calculated found that grass silage was the most suitable feedstock. A sensitivity analysis was then conducted to investigate the impact of weights. The analysis used the Pugh Matrix Method which relies upon The Analytical Hierarchy Process and pairwise comparisons to determine a weighting for each criterion. The results showed that the highest weight (0.193) corresponded to biogas production indicating that grass silage and manure are the most suitable feedstock. Introducing co-digestion of two or more substrates can boost the biogas yield due to a synergistic effect induced by the feedstock to favor positive biological interactions. A further benefit of co-digesting manure is that the anaerobic digestion process also acts as a waste management strategy. From the research, it was concluded that energy from agricultural biomass is highly advantageous in Northern Ireland because it would increase the country's production of renewable energy, manage waste production, and would limit the production of greenhouse gases (current contribution from agriculture sector is 26%). Decision-making methods based on scientific evidence aid policy makers in classifying multiple criteria in a logical mathematical manner in order to reach a resolution.

Keywords: anaerobic digestion, biomass as feedstock, decision matrix, renewable energy

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Authors: Deepanwita Deka, Dhruva Kumar Jha

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Endophytes are the microbes that colonize living, internal tissues of plants without causing any immediate, overt negative effects. Endophytes are rich source of therapeutic substances like antimicrobial, anticancerous, herbicidal, insecticidal, immunomodulatory compounds. Brucea mollis, commonly known as Quinine in Assam, belonging to the family Simaroubaceae, is a shrub or small tree, recorded as endangered species in North East India by CAMP survey in 2003. It is traditionally being used as antimalarial and antimicrobial agent and has antiplasmodial, cytotoxic, anticancer, diuretic, cardiovascular effect etc. Being endangered and medicinal; this plant may host certain noble endophytes which need to be studied in depth. The aim of the present study was isolation and identification of potent endophytic fungi from Brucea mollis, an endangered medicinal plant, to protect it from extinction due to over use for medicinal purposes. Aseptically collected leaves, barks and roots samples of healthy plants were washed and cut into a total of 648 segments of about 2 cm long and 0.5 cm broad with sterile knife, comprising 216 segments each from leaves, barks and roots. These segments were surface sterilized using ethanol, mercuric chloride (HgCl2) and aqueous solution of sodium hypochlorite (NaClO). Different media viz., Czapeck-Dox-Agar (CDA, Himedia), Potato-Dextrose-Agar (PDA, Himedia), Malt Extract Agar (MEA, Himedia), Sabourad Dextrose Agar (SDA, Himedia), V8 juice agar, nutrient agar and water agar media and media amended with plant extracts were used separately for the isolation of the endophytic fungi. A total of 11 fungal species were recovered from leaf, bark and root tissues of B. mollis. The isolates were screened for antimicrobial, antioxidant and enzymatic activities using certain protocols. Cochliobolus geniculatus was identified as the most dominant species. The mycelia sterilia (creamy white) showing highest inhibitory activity against Candida albicans (MTCC 183) was induced to sporulate using modified PDA media. The isolate was identified as Geosmithia pallida. The internal transcribed spacer of rDNA was sequenced for confirmation of the taxonomic identity of the sterile mycelia (creamy white). The internal transcribed spacer r-DNA sequence was submitted to the NCBI (KU693285) for the first time from India. G. pallida and Penicillium showed highest antioxidant activity among all the isolates. The antioxidant activity of G. pallida and Penicillium didn’t show statistically significant difference (P˃0.05). G. pallida, Cochliobolus geniculatus and P. purpurogenum respectively showed highest cellulase, amylase and protease activities. Thus, endopytic fungal isolates may be used as potential natural resource of pharmaceutical importance. The endophytic fungi, Geosmithia pallida, may be used for synthesis of pharmaceutically important natural products and consequently can replace plants hitherto used for the same purpose. This study suggests that endophytes should be investigated more aggressively to better understand the endophyte biology of B. mollis.

Keywords: Antimicrobial activity, antioxidant activity, Brucea mollis, endophytic fungi, enzyme activity, Geosmithia pallida

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Authors: Mamert Mbonimpa, Ousseynou Kanteye, Élysée Tshibangu Ngabu, Rachid Amrou, Abdelkabir Maqsoud, Tikou Belem

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The management of mine wastes (waste rocks and tailings) containing sulphide minerals such as pyrite and pyrrhotite represents the main environmental challenge for the mining industry. Indeed, acid mine drainage (AMD) can be generated when these wastes are exposed to water and air. AMD is characterized by low pH and high concentrations of heavy metals, which are toxic to plants, animals, and humans. It affects the quality of the ecosystem through water and soil pollution. Different techniques involving soil materials can be used to control AMD generation, including impermeable covers (compacted clays) and oxygen barriers. The latter group includes covers with capillary barrier effects (CCBE), a multilayered cover that include the moisture retention layer playing the role of an oxygen barrier. Once AMD is produced at a mine site, it must be treated so that the final effluent at the mine site complies with regulations and can be discharged into the environment. Active neutralization with lime is one of the treatment methods used. This treatment produces sludge that is usually stored in sedimentation ponds. Other sludge management alternatives have been examined in recent years, including sludge co-disposal with tailings or waste rocks, disposal in underground mine excavations, and storage in technical landfill sites. Considering the ability of AMD neutralization sludge to maintain an alkaline to neutral pH for decades or even centuries, due to the excess alkalinity induced by residual lime within the sludge, valorization of sludge in specific applications could be an interesting management option. If done efficiently, the reuse of sludge could free up storage ponds and thus reduce the environmental impact. It should be noted that mixtures of sludge and soils could potentially constitute usable materials in CCBE for the rehabilitation of acid-generating mine sites, while sludge alone is not suitable for this purpose. The high sludge water content (up to 300%), even after sedimentation, can, however, constitute a geotechnical challenge. Adding lime to the mixtures can reduce the water content and improve the geotechnical properties. The objective of this paper is to investigate the impact of the sludge content (30, 40 and 50%) in sand-sludge mixtures (SSM) on their hydrogeotechnical properties (compaction, shrinkage behaviour, saturated hydraulic conductivity, and water retention curve). The impact of lime addition (dosages from 2% to 6%) on the moisture content, dry density after compaction and saturated hydraulic conductivity of SSM was also investigated. Results showed that sludge adding to sand significantly improves the saturated hydraulic conductivity and water retention capacity, but the shrinkage increased with sludge content. The dry density after compaction of lime-treated SSM increases with the lime dosage but remains lower than the optimal dry density of the untreated mixtures. The saturated hydraulic conductivity of lime-treated SSM after 24 hours of cure decreases by 3 orders of magnitude. Considering the hydrogeotechnical properties obtained with these mixtures, it would be possible to design CCBE whose moisture retention layer is made of SSM. Physical laboratory models confirmed the performance of such CCBE.

Keywords: mine waste, AMD neutralization sludge, sand-sludge mixture, hydrogeotechnical properties, mine site reclamation, CCBE

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Authors: Dawid Jakimiuk, Krzysztof Mitura, Leszek Szpakowski, Sławomir Pilip, Daniel Celiński

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The Emergency Medical Teams (EMS) of the Ambulance Service in Siedlce serve the population living in the Mazowieckie Voivodeship (the area of eastern Poland with approximately 550,000 inhabitants). They provide health services at the pre-hospital stage to all life-threatening patients. The analysis covered the interventions of emergency medical teams in cases of suicide attempts that occurred in the years 2015-2018. The study was retrospective. The data was obtained on the basis of digital medical records of completed call-outs. When defining the disease entity, the International Statistical Classification of Diseases and Health Problems ICD-10 prepared by WHO was used. The relationship between selected disease entities and the area of EMT intervention, the patient's sex and age, and the time of occurrence of the event were investigated. Non-urban area was defined as the area inhabited by a population below 10,000 residents. Statistical analysis was performed using Pearson's Chi ^ 2 test and presenting the percentage of cases in the study group. Of all the suicide attempts, drug abuse cases were the most frequent, including: X60 (Intentional self-poisoning by and exposure to nonopioid analgesics, antipyretics and antirheumatics); X61 (Intentional self-poisoning by and exposure to antiepileptic, sedative-hypnotic, antiparkinsonian and psychotropic drugs, not elsewhere classified); X62 (Intentional self-poisoning by and exposure to narcotics and psycholeptics [hallucinogens], not elsewhere classified); X63 (Intentional self-poisoning by and exposure to other drugs acting on the autonomic nervous system); X64 (Intentional self-poisoning by and exposure to other and unspecified drugs, medicaments and biological substance) oraz X70 (Intentional self-harm by hanging, strangulation and suffocation). In total, they accounted for 69.4% of all interventions to suicide attempts in the studied period. Statistical analysis shows significant differences (χ2 = 39.30239, p <0.0001, n = 561) between the area of EMT intervention and the type of suicide attempt. In non-urban areas, a higher percentage of X70 diagnoses was recorded (55.67%), while in urban areas, X60-X64 (72.53%). In non-urban areas, a higher proportion of patients attempting suicide was observed compared to patients living in urban areas. For X70 and X60 - X64 in total, the incidence rates in non-urban areas were 80.8% and 56%, respectively. Significant differences were found (χ2 = 119.3304, p <0.0001, n = 561) depending on the method of attempting suicide in relation to the patient's sex. The percentage of women diagnosed with X60-X64 versus X70 was 87.50%, which was the largest number of patients (n = 154) as compared to men. In the case of X70 in relation to X60-X64, the percentage of men was 62.08%, which was the largest number of patients (n = 239) as compared to women (n = 22). In the case of X70, the percentage of men compared to women was as high as 92%. Significant differences were observed (χ2 = 14.94848, p <0.01058) between the hour of EMT intervention and the type of suicide attempt. The highest percentage of X70 occurred between 04:01 - 08:00 (64.44%), while X60-X64 between 00:01 - 04:00 (70.45%). The largest number of cases of all tested suicide attempts was recorded between 16:01 - 20:00 for X70 (n = 62), X60 - X64 (n = 82), respectively. The highest percentage of patients undertaking all suicide attempts studied at work was observed in the age range of 18-30 (31.5%), while the lowest was in the age group over 60 years of age. (11%). There was no significant correlation between the day of the week or individual months of the year and the type of suicide attempt - respectively (χ2 = 6.281729, p <0.39238, n = 561) and (χ2 = 3.348913, p <0.9857, n = 561). There were also no significant differences in the incidence of suicide attempts for each year in the study period (χ2 = 3.348913, p <0.9857 n = 561). The obtained results suggest the necessity to undertake preventive measures in order to minimize the number of suicide attempts. Such activities should be directed especially at young patients living in non-urban areas.

Keywords: emergency med, emergency medical team, attempted suicide, pre-hospital

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Authors: Vaso K. Kapnopoulou, Piero Caridis

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The fatigue of ship structural details is of major concern in the maritime industry as it can generate fracture issues that may compromise structural integrity. In the present study, a fatigue analysis of the lower hopper knuckle connection of a bulk carrier was conducted using the Finite Element Method by means of ABAQUS/CAE software. The fatigue life was calculated using Miner’s Rule and the long-term distribution of stress range by the use of the two-parameter Weibull distribution. The cumulative damage ratio was estimated using the fatigue damage resulting from the stress range occurring at each load condition. For this purpose, a cargo hold model was first generated, which extends over the length of two holds (the mid-hold and half of each of the adjacent holds) and transversely over the full breadth of the hull girder. Following that, a submodel of the area of interest was extracted in order to calculate the hot spot stress of the connection and to estimate the fatigue life of the structural detail. Two hot spot locations were identified; one at the top layer of the inner bottom plate and one at the top layer of the hopper plate. The IACS Common Structural Rules (CSR) require that specific dynamic load cases for each loading condition are assessed. Following this, the dynamic load case that causes the highest stress range at each loading condition should be used in the fatigue analysis for the calculation of the cumulative fatigue damage ratio. Each load case has a different effect on ship hull response. Of main concern, when assessing the fatigue strength of the lower hopper knuckle connection, was the determination of the maximum, i.e. the critical value of the stress range, which acts in a direction normal to the weld toe line. This acts in the transverse direction, that is, perpendicularly to the ship's centerline axis. The load cases were explored both theoretically and numerically in order to establish the one that causes the highest damage to the location examined. The most severe one was identified to be the load case induced by beam sea condition where the encountered wave comes from the starboard. At the level of the cargo hold model, the model was assumed to be simply supported at its ends. A coarse mesh was generated in order to represent the overall stiffness of the structure. The elements employed were quadrilateral shell elements, each having four integration points. A linear elastic analysis was performed because linear elastic material behavior can be presumed, since only localized yielding is allowed by most design codes. At the submodel level, the displacements of the analysis of the cargo hold model to the outer region nodes of the submodel acted as boundary conditions and applied loading for the submodel. In order to calculate the hot spot stress at the hot spot locations, a very fine mesh zone was generated and used. The fatigue life of the detail was found to be 16.4 years which is lower than the design fatigue life of the structure (25 years), making this location vulnerable to fatigue fracture issues. Moreover, the loading conditions that induce the most damage to the location were found to be the various ballasting conditions.

Keywords: dynamic load cases, finite element method, high cycle fatigue, lower hopper knuckle

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Authors: Pallab Datta, Jyotirmoy Chatterjee, Santanu Dhara

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Over the past few years, phosphorous containing polymers have received widespread attention for applications such as high performance optical fibers, flame retardant materials, drug delivery and tissue engineering. Being pentavalent, phosphorous can exist in different chemical environments in these polymers which increase their versatility. In human biochemistry, phosphorous based compounds exert their functions both in soluble and insoluble form occurring as inorganic or as organophosphorous compounds. Specifically in case of biomacromolecules, phosphates are critical for functions of DNA, ATP, phosphoproteins, phospholipids, phosphoglycans and several coenzymes. Inspired by the role of phosphorous in functional biomacromolecules, design and synthesis of biomimetic materials are thus carried out by several authors to study macromolecular function or as substitutes in clinical tissue regeneration conditions. In addition, many regulatory signals of the body are controlled by phoshphorylation of key proteins present either in form of growth factors or matrix-bound scaffold proteins. This inspires works on synthesis of phospho-peptidomimetic amino acids for understanding key signaling pathways and this is extended to obtain molecules with potentially useful biological properties. Apart from above applications, phosphate groups bound to polymer backbones have also been demonstrated to improve function of osteoblast cells and augment performance of bone grafts. Despite the advantages of phosphate grafting, however, there is limited understanding on effect of degree of phosphorylation on macromolecular physicochemical and/or biological properties. Such investigations are necessary to effectively translate knowledge of macromolecular biochemistry into relevant clinical products since they directly influence processability of these polymers into suitable scaffold structures and control subsequent biological response. Amongst various techniques for fabrication of biomimetic scaffolds, nanofibrous scaffolds fabricated by electrospinning technique offer some special advantages in resembling the attributes of natural extracellular matrix. Understanding changes in physico-chemical properties of polymers as function of phosphorylation is therefore going to be crucial in development of nanofiber scaffolds based on phosphorylated polymers. The aim of the present work is to investigate the effect of phosphorous grafting on the electrospinning behavior of polymers with aim to obtain biomaterials for bone regeneration applications. For this purpose, phosphorylated derivatives of two polymers of widely different electrospinning behaviors were selected as starting materials. Poly(vinyl alcohol) is a conveniently electrospinnable polymer at different conditions and concentrations. On the other hand, electrospinning of chitosan backbone based polymers have been viewed as a critical challenge. The phosphorylated derivatives of these polymers were synthesized, characterized and electrospinning behavior of various solutions containing these derivatives was compared with electrospinning of pure poly (vinyl alcohol). In PVA, phosphorylation adversely impacted electrospinnability while in NMPC, higher phosphate content widened concentration range for nanofiber formation. Culture of MG-63 cells on electrospun nanofibers, revealed that degree of phosphate modification of a polymer significantly improves cell adhesion or osteoblast function of cultured cells. It is concluded that improvement of cell response parameters of nanofiber scaffolds can be attained as a function of controlled degree of phosphate grafting in polymeric biomaterials with implications for bone tissue engineering applications.

Keywords: bone regeneration, chitosan, electrospinning, phosphorylation

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Authors: Carolyn Hatch, Laurent Simon

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Urban mobility and the transportation industry are undergoing a transformation, shifting from an auto production-consumption model that has dominated since the early 20th century towards new forms of personal and shared multi-modality [1]. This is shaped by key forces such as climate change, which has induced a shift in production and consumption patterns and efforts to decarbonize and improve transport services through, for instance, the integration of vehicle automation, electrification and mobility sharing [2]. Advanced innovation practices and platforms for experimentation and validation of new mobility products and services that are increasingly complex and multi-stakeholder-oriented are shaping this new world of mobility. Transportation hubs – such as airports - are emblematic of these disruptive forces playing out in the mobility industry. Airports are emerging as the core of innovation ecosystems on and around contemporary mobility issues, and increasingly recognized as complex public/private nodes operating in many societal dimensions [3,4]. These include urban development, sustainability transitions, digital experimentation, customer experience, infrastructure development and data exploitation (for instance, airports generate massive and often untapped data flows, with significant potential for use, commercialization and social benefit). Yet airport innovation practices have not been well documented in the innovation literature. This paper addresses this gap by proposing a model of airport innovation that aims to equip airport stakeholders to respond to these new and complex innovation needs in practice. The methodology involves: 1 – a literature review bringing together key research and theory on airport innovation management, open innovation and innovation ecosystems in order to evaluate airport practices through an innovation lens; 2 – an international benchmarking of leading airports and their innovation practices, including such examples as Aéroports de Paris, Schipol in Amsterdam, Changi in Singapore, and others; and 3 – semi-structured interviews with airport managers on key aspects of organizational practice, facilitated through a close partnership with the Airport Council International (ACI), a major stakeholder in this research project. Preliminary results find that the most successful airports are those that have shifted to a multi-stakeholder, platform ecosystem model of innovation. The recent entrance of new actors in airports (Google, Amazon, Accor, Vinci, Airbnb and others) have forced the opening of organizational boundaries to share and exchange knowledge with a broader set of ecosystem players. This has also led to new forms of governance and intermediation by airport actors to connect complex, highly distributed knowledge, along with new kinds of inter-organizational collaboration, co-creation and collective ideation processes. Leading airports in the case study have demonstrated a unique capacity to force traditionally siloed activities to “think together”, “explore together” and “act together”, to share data, contribute expertise and pioneer new governance approaches and collaborative practices. In so doing, they have successfully integrated these many disruptive change pathways and forced their implementation and coordination towards innovative mobility outcomes, with positive societal, environmental and economic impacts. This research has implications for: 1 - innovation theory, 2 - urban and transport policy, and 3 - organizational practice - within the mobility industry and across the economy.

Keywords: airport management, ecosystem, innovation, mobility, platform, transport hubs

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Authors: Rob Schindler

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Industry-standard methods of mitigating erosion of seabed sediments rely on ‘hard engineering’ approaches which have numerous environmental shortcomings: (1) direct loss of habitat by smothering of benthic species, (2) disruption of sediment transport processes, damaging geomorphic and ecosystem functionality (3) generation of secondary erosion problems, (4) introduction of material that may propagate non-local species, and (5) provision of pathways for the spread of invasive species. Recent studies have also revealed the importance of biological cohesion, the result of naturally occurring extra-cellular polymeric substances (EPS), in stabilizing natural sediments. Mimicking the strong bonding kinetics through the deliberate addition of EPS to sediments – henceforth termed ‘biostabilisation’ - offers a means in which to mitigate against erosion induced by structures or episodic increases in hydrodynamic forcing (e.g. storms and floods) whilst avoiding, or reducing, hard engineering. Here we present unique experiments that systematically examine how biostabilisation reduces scour around a monopile in a current, a first step to realizing the potential of this new method of scouring reduction for a wide range of engineering purposes in aquatic substrates. Experiments were performed in Plymouth University’s recirculating sediment flume which includes a recessed scour pit. The model monopile was 0.048 m in diameter, D. Assuming a prototype monopile diameter of 2.0 m yields a geometric ratio of 41.67. When applied to a 10 m prototype water depth this yields a model depth, d, of 0.24 m. The sediment pit containing the monopile was filled with different biostabilised substrata prepared using a mixture of fine sand (D50 = 230 μm) and EPS (Xanthan gum). Nine sand-EPS mixtures were examined spanning EPS contents of 0.0% < b0 < 0.50%. Scour development was measured using a laser point gauge along a 530 mm centreline at 10 mm increments at regular periods over 5 h. Maximum scour depth and excavated area were determined at different time steps and plotted against time to yield equilibrium values. After 5 hours the current was stopped and a detailed scan of the final scour morphology was taken. Results show that increasing EPS content causes a progressive reduction in the equilibrium depth and lateral extent of scour, and hence excavated material. Very small amounts equating to natural communities (< 0.1% by mass) reduce scour rate, depth and extent of scour around monopiles. Furthermore, the strong linear relationships between EPS content, equilibrium scour depth, excavation area and timescales of scouring offer a simple index on which to modify existing scour prediction methods. We conclude that the biostabilisation of sediments with EPS may offer a simple, cost-effective and ecologically sensitive means of reducing scour in a range of contexts including OWFs, bridge piers, pipeline installation, and void filling in rock armour. Biostabilisation may also reduce economic costs through (1) Use of existing site sediments, or waste dredged sediments (2) Reduced fabrication of materials, (3) Lower transport costs, (4) Less dependence on specialist vessels and precise sub-sea assembly. Further, its potential environmental credentials may allow sensitive use of the seabed in marine protection zones across the globe.

Keywords: biostabilisation, EPS, marine, scour

Procedia PDF Downloads 151

Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

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Authors: Pei Yi Lin

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Objective: The objective of this study is to use machine learning methods to build an early prediction classifier model for acute delirium to improve the quality of medical care for intensive care patients. Background: Delirium is a common acute and sudden disturbance of consciousness in critically ill patients. After the occurrence, it is easy to prolong the length of hospital stay and increase medical costs and mortality. In 2021, the incidence of delirium in the intensive care unit of internal medicine was as high as 59.78%, which indirectly prolonged the average length of hospital stay by 8.28 days, and the mortality rate is about 2.22% in the past three years. Therefore, it is expected to build a delirium prediction classifier through big data analysis and machine learning methods to detect delirium early. Method: This study is a retrospective study, using the artificial intelligence big data database to extract the characteristic factors related to delirium in intensive care unit patients and let the machine learn. The study included patients aged over 20 years old who were admitted to the intensive care unit between May 1, 2022, and December 31, 2022, excluding GCS assessment <4 points, admission to ICU for less than 24 hours, and CAM-ICU evaluation. The CAMICU delirium assessment results every 8 hours within 30 days of hospitalization are regarded as an event, and the cumulative data from ICU admission to the prediction time point are extracted to predict the possibility of delirium occurring in the next 8 hours, and collect a total of 63,754 research case data, extract 12 feature selections to train the model, including age, sex, average ICU stay hours, visual and auditory abnormalities, RASS assessment score, APACHE-II Score score, number of invasive catheters indwelling, restraint and sedative and hypnotic drugs. Through feature data cleaning, processing and KNN interpolation method supplementation, a total of 54595 research case events were extracted to provide machine learning model analysis, using the research events from May 01 to November 30, 2022, as the model training data, 80% of which is the training set for model training, and 20% for the internal verification of the verification set, and then from December 01 to December 2022 The CU research event on the 31st is an external verification set data, and finally the model inference and performance evaluation are performed, and then the model has trained again by adjusting the model parameters. Results: In this study, XG Boost, Random Forest, Logistic Regression, and Decision Tree were used to analyze and compare four machine learning models. The average accuracy rate of internal verification was highest in Random Forest (AUC=0.86), and the average accuracy rate of external verification was in Random Forest and XG Boost was the highest, AUC was 0.86, and the average accuracy of cross-validation was the highest in Random Forest (ACC=0.77). Conclusion: Clinically, medical staff usually conduct CAM-ICU assessments at the bedside of critically ill patients in clinical practice, but there is a lack of machine learning classification methods to assist ICU patients in real-time assessment, resulting in the inability to provide more objective and continuous monitoring data to assist Clinical staff can more accurately identify and predict the occurrence of delirium in patients. It is hoped that the development and construction of predictive models through machine learning can predict delirium early and immediately, make clinical decisions at the best time, and cooperate with PADIS delirium care measures to provide individualized non-drug interventional care measures to maintain patient safety, and then Improve the quality of care.

Keywords: critically ill patients, machine learning methods, delirium prediction, classifier model

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Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair

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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.

Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae

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Authors: Pauline Nyssen, Ange Mouithys-Mickalad, Maryse Hoebeke

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Inflammation is a complex physiological phenomenon involving chemical and enzymatic mechanisms. Polymorphonuclear neutrophil leukocytes (PMNs) play an important role by producing reactive oxygen species (ROS) and releasing myeloperoxidase (MPO), a pro-oxidant enzyme. Released both in the phagolysosome and the extracellular medium, MPO produces during its peroxidase and halogenation cycles oxidant species, including hypochlorous acid, involved in the destruction of pathogen agents, like bacteria or viruses. Inflammatory pathologies, like rheumatoid arthritis, atherosclerosis induce an excessive stimulation of the PMNs and, therefore, an uncontrolled release of ROS and MPO in the extracellular medium, causing severe damages to the surrounding tissues and biomolecules such as proteins, lipids, and DNA. The treatment of chronic inflammatory pathologies remains a challenge. For many years, MPO has been used as a target for the development of effective treatments. Numerous studies have been focused on the design of new drugs presenting more efficient MPO inhibitory properties. However, some designed inhibitors can be toxic. An alternative consists of assessing the potential inhibitory action of clinically-known molecules, having antioxidant activity. Propofol, 2,6-diisopropyl phenol, which is used as an intravenous anesthetic agent, meets these requirements. Besides its anesthetic action employed to induce a sedative state during surgery or in intensive care units, propofol and its injectable form Diprivan indeed present antioxidant properties and act as ROS and free radical scavengers. A study has also evidenced the ability of propofol to inhibit the formation of the neutrophil extracellular traps fibers, which are important to trap pathogen microorganisms during the inflammation process. The aim of this study was to investigate the potential inhibitory action mechanism of propofol and Diprivan on MPO activity. To go into the anti-inflammatory action of propofol in-depth, two of its oxidative derivatives, 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3’,5’-tetra isopropyl-(4,4’)-diphenoquinone (PPFDQ), were studied regarding their inhibitory action. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling have evidenced the low anti-catalytic action of propofol. Stopped-flow absorption spectroscopy and direct MPO activity analysis have proved that propofol acts as a reversible MPO inhibitor by interacting as a reductive substrate in the peroxidase cycle and promoting the accumulation of redox compound II. Overall, Diprivan exhibited a weaker inhibitory action than the active molecule propofol. In contrast, PPFQ seemed to bind and obstruct the enzyme active site, preventing the trigger of the MPO oxidant cycles. PPFQ induced a better chlorination cycle inhibition at basic and neutral pH in comparison to propofol. PPFDQ did not show any MPO inhibition activity. The three interest molecules have also demonstrated their inhibition ability on an important step of the inflammation pathway, the PMNs superoxide anions production, thanks to EPR spectroscopy and chemiluminescence. In conclusion, propofol presents an interesting immunomodulatory activity by acting as a reductive substrate in the peroxidase cycle of MPO, slowing down its activity, whereas PPFQ acts more as an anti-catalytic substrate. Although PPFDQ has no impact on MPO, it can act on the inflammation process by inhibiting the superoxide anions production by PMNs.

Keywords: Diprivan, inhibitor, myeloperoxidase, propofol, spectroscopy

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Authors: Mitia Ramarosaona, Sylvie Castagnet, Damien Halm, Henri-Alexandre Cayzac, Nicolas Dufaure, Philippe Papin

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In light of the ongoing energy transition, 'Infrastructure developments' for hydrogen transportation and storage raise studies on the materials employed for hyperbaric vessels. Type IV tanks represent the most mature choice for gaseous hydrogen storage at high pressure – 70MPa. These tanks are made of a composite shell and an internal hydrogen-exposed polymer liner. High pressure conditions lead to severe mechanical loading requiring high resistance. Liner is in contact with hydrogen and undergoes compression – decompression cycles during system filling and emptying. Stresses induced by this loading, coupled with hydrogen diffusion, were found to cause microstructural changes and degradation of mechanical behaviour after decompression phase in some studies on HDPE. These phenomena are similar to those observed in elastomeric components like sealing rings, which can affect permeability and lead to their failure. They may lead to a hydrogen leak, compromising security and tightness of the tank. While these phenomena have been identified in elastomers, they remain less addressed in thermoplastics and consequences post-decompression damages on mechanical behaviour and to the best of author's knowledge was not studied either. Different additives are also included in liner formulation to improve its behaviour. This study aimed to better understand damage micro-mechanisms in PA11s exposed to hydrogen compression-decompression cycles and understand if additives influence their resistance. Samples of pure, plasticized and impact-modified PA11s are exposed to 1, 3 and 8 pressure cycles including hydrogen saturation at 70MPa followed by severe 15-second decompression. After hydrogen exposure and significantly later than full desorption, the residual mechanical behaviour is characterized through impact and monotonic tensile tests, on plain and notched samples. Several techniques of microstructure and micro-nano damage characterization are carried out to assess whether changes in macroscopic properties are driven by microstructural changes in the crystalline structure (SAXS-WAXS acquisitions and SEM micrographs). Thanks to WAXS acquisition and microscopic observation, the effects due to additives and pressure consequences can be decorrelated. Pure PA11 and PA11 with a low percentage of additives show an increase in stress level at the first yielding point after hydrogen cycles. The amplitude of the stress increase is more important in formulation with additives because of changes in PA11 matrix behavior and environment created by additives actions. Plasticizer modifies chain mobility leading to microstructure changes while other additives, more ductile than PA11, is able to cavitate inside PA11 matrix when undergoing decompression. On plasticized formulation, plasticizer migration are suspected to enhance impact of hydrogen cycling on mechanical behaviour. Compared to the literature on HDPE and elastomers, no damages like cavitation or cracking could be evidenced from SAXS experiments on every PA11 formulation tested. In perspectives, on all formulation, experimental work is underway to confirm influence of residual pressure level after decompression on post-decompression damages level, the aim is to better understand the factors affecting the mechanical behavior of thermoplastics subject to mechanical solicitation from decompression in hydrogen tank liners, not mechanical behaviour of liner in hydrogen tanks directly.

Keywords: additives, hydrogen tank liner, microstructural analysis, PA11

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Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

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Authors: Jonas Volungevicius, Kristina Amaleviciute, Rimantas Vaisvalavicius, Alvyra Slepetiene, Darijus Veteikis

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Lithuanian territory is characterized by landscape with prevailing morain hills and clayey lowlands. The largest part of it has endured agrogenization of various degrees which was the cause of changes both in the structure of landscape and soil cover, transformations of soil profile and degradation of natural background soils. These changes influence negatively geoecological potential of landscape and soil and contribute to the weakening of the sustainability of agroecosystems. Research objective: to reveal the landscape agrogenization induced alterations of catenae and their appendant soil profiles in Lithuanian morain hills and clayey lowlands. Methods: Soil cover analysis and catenae charting was conducted using landscape profiling; soil morphology detected and soil type identified following WRB 2014. Granulometric composition of soil profiles was obtained by laser diffraction method (lazer diffractometer Mastersizer 2000). pH was measured in H2O extraction using potentiometric titration; SOC was determined by the Tyurin method modified by Nikitin, measuring with spectrometer Cary 50 (VARIAN) in 590 nm wavelength using glucose standards. Results: analysis showed that the decrease of forest vegetation and the other natural landscape components following the agrogenization of the research area influenced differently but significantly the structural alterations in soil cover and vertical soil profile. The research detected that due to landscape agrogenization, the suppression of zone-specific processes and the intensification of inter-zone processes determined by agrogenic factors take place in Lithuanian agroecosystems. In forested hills historically prevailing Retisols and Histosols territorial complex is transforming into the territorial complex of Regosols, Deluvial soils and drained Histosols. Processes taking place are simplification of vertical profile structure, intensive rejuvenation of profile, disappearance of the features of zone-specific soil-forming processes (podzolization, lessivage, gley formation). Erosion and deluvial processes manifest more intensively and weakly accumulating organic material more intensively spread in a vertical soil profile. The territorial soil complex of Gleyic Luvisols and Gleysols dominating in forested clayey lowlands subjected to agrogenization is transformed into the catena of drained Luvisols and pseudo Cambisols. The best expressed are their changes in moisture regime (morphological features of gley and stagnic properties are on decline) together with alterations of pH and distribution and intensity of accumulation of organic matter in profile. A specific horizon, antraquic, uncharacteristic to natural soil formation is appearing. Important to note that due to deep ploughing and other agrotechnical measures, the natural vertical differentiation of clay particles in a soil profile is destroyed which leads not only to alterations of physical qualities of soil, but also encumbers the identification of Luvisols by creating presumptions to misidentify them as Cambisols. The latter have never developed in these ecosystems under the present climatic conditions. Acknowledgements: This work was supported by the National Science Program: The effect of long-term, different-intensity management of resources on the soils of different genesis and on other components of the agro-ecosystems [grant number SIT-9/2015] funded by the Research Council of Lithuania.

Keywords: agroecosystems, landscape agrogenization, luvisols, retisols, transformation of soil profile

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Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

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Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

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Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero

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Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.

Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up

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Authors: Nino Kupatadze, Tamar Memanishvili, Natia Ochkhikidze, David Tugushi, Zaal Kokaia, Ramaz Katsarava

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Amino acid-based Biodegradable poly(ester-amide)s (PEAs) have gained considerable interest as a promising materials for numerous biomedical applications. These polymers reveal a high biocompatibility and easily form small particles suitable for delivery various biological, as well as elastic bio-erodible films serving as matrices for constructing antibacterial coatings. In the present work we have demonstrated a potential of the PEAs for two applications: 1. cell therapy for stroke as vehicles for delivery and sustained release of growth factors, 2. bactericidal coating as prevention biofilm and applicable in infected wound management. Stroke remains the main cause of adult disability with limited treatment options. Although stem cell therapy is a promising strategy, it still requires improvement of cell survival, differentiation and tissue modulation. .Recently, microspheres (MPs) made of biodegradable polymers have gained significant attention for providing necessary support of transplanted cells. To investigate this strategy in the cell therapy of stroke, MPs loaded with transcription factors Wnt3A/BMP4 were prepared. These proteins have been shown to mediate the maturation of the cortical neurons. We have suggested that implantation of these materials could create a suitable microenvironment for implanted cells. Particles with spherical shape, porous surface, and 5-40 m in size (monitored by scanning electron microscopy) were made on the basis of the original PEA composed of adipic acid, L-phenylalanine and 1,4-butanediol. After 4 months transplantation of MPs in rodent brain, no inflammation was observed. Additionally, factors were successfully released from MPs and affected neuronal cell differentiation in in vitro. The in vivo study using loaded MPs is in progress. Another severe problem in biomedicine is prevention of surgical devices from biofilm formation. Antimicrobial polymeric coatings are most effective “shields” to protect surfaces/devices from biofilm formation. Among matrices for constructing the coatings preference should be given to bio-erodible polymers. Such types of coatings will play a role of “unstable seating” that will not allow bacteria to occupy the surface. In other words, bio-erodible coatings would be discomfort shelter for bacteria that along with releasing “killers of bacteria” should prevent the formation of biofilm. For this purpose, we selected an original biodegradable PEA composed of L-leucine, 1,6-hexanediol and sebacic acid as a bio-erodible matrix, and nanosilver (AgNPs) as a bactericidal agent (“killer of bacteria”). Such nanocomposite material is also promising in treatment of superficial wound and ulcer. The solubility of the PEA in ethanol allows to reduce AgNO3 to NPs directly in the solution, where the solvent served as a reductive agent, and the PEA served as NPs stabilizer. The photochemical reduction was selected as a basic method to form NPs. The obtained AgNPs were characterized by UV-spectroscopy, transmission electron microscope (TEM), and dynamic light scattering (DLS). According to the UV-data and TEM data the photochemical reduction resulted in spherical AgNPs with wide particle size distribution with a high contribution of the particles below 10 nm that are known as responsible for bactericidal activity of AgNPs. DLS study showed that average size of nanoparticles formed after photo-reduction in ethanol solution ranged within ca. 50 nm.

Keywords: biodegradable polymers, microparticles, nanocomposites, stem cell therapy, stroke

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Authors: Camille Perréard, Yoann Ladner, Fanny D'Orlyé, Stéphanie Descroix, Vélan Taniga, Anne Varenne, Cédric Guyon, Michael. Tatoulian, Frédéric Kanoufi, Cyrine Slim, Sophie Griveau, Fethi Bedioui

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The development of micro total analysis systems is of major interest for contaminant and biomarker analysis. As a lab-on-chip integrates all steps of an analysis procedure in a single device, analysis can be performed in an automated format with reduced time and cost, while maintaining performances comparable to those of conventional chromatographic systems. Moreover, these miniaturized systems are either compatible with field work or glovebox manipulations. This work is aimed at developing an analytical microsystem for trace and ultra trace quantitation in complex matrices. The strategy consists in the integration of a sample pretreatment step within the lab-on-chip by a confinement zone where selective ligands are immobilized for target extraction and preconcentration. Aptamers were chosen as selective ligands, because of their high affinity for all types of targets (from small ions to viruses and cells) and their ease of synthesis and functionalization. This integrated target extraction and concentration step will be followed in the microdevice by an electrokinetic separation step and an on-line detection. Polymers consisting of cyclic olefin copolymer (COC) or fluoropolymer (Dyneon THV) were selected as they are easy to mold, transparent in UV-visible and have high resistance towards solvents and extreme pH conditions. However, because of their low chemical reactivity, surface treatments are necessary. For the design of this miniaturized diagnostics, we aimed at modifying the microfluidic system at two scales : (1) on the entire surface of the microsystem to control the surface hydrophobicity (so as to avoid any sample wall adsorption) and the fluid flows during electrokinetic separation, or (2) locally so as to immobilize selective ligands (aptamers) on restricted areas for target extraction and preconcentration. We developed different novel strategies for the surface functionalization of COC and Dyneon, based on plasma, chemical and /or electrochemical approaches. In a first approach, a plasma-induced immobilization of brominated derivatives was performed on the entire surface. Further substitution of the bromine by an azide functional group led to covalent immobilization of ligands through “click” chemistry reaction between azides and terminal alkynes. COC and Dyneon materials were characterized at each step of the surface functionalization procedure by various complementary techniques to evaluate the quality and homogeneity of the functionalization (contact angle, XPS, ATR). With the objective of local (micrometric scale) aptamer immobilization, we developed an original electrochemical strategy on engraved Dyneon THV microchannel. Through local electrochemical carbonization followed by adsorption of azide-bearing diazonium moieties and covalent linkage of alkyne-bearing aptamers through click chemistry reaction, typical dimensions of immobilization zones reached the 50 µm range. Other functionalization strategies, such as sol-gel encapsulation of aptamers, are currently investigated and may also be suitable for the development of the analytical microdevice. The development of these functionalization strategies is the first crucial step in the design of the entire microdevice. These strategies allow the grafting of a large number of molecules for the development of new analytical tools in various domains like environment or healthcare.

Keywords: alkyne-azide click chemistry (CuAAC), electrochemical modification, microsystem, plasma bromination, surface functionalization, thermoplastic polymers

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Authors: Jatziri Y. Moreno-Martínez, Arturo Galván, Israel Enrique Herrera Díaz, José Ramón Gasca Tirado

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In recent years, for the elevated viaducts in Mexico City, a construction system based on precast/pre-stressed concrete elements has been used, in which the bridge girders are divided in two parts by imposing a hinged support in sections where the bending moments that are originated by the gravity loads in a continuous beam are minimal. Precast concrete girders with dapped ends are a representative sample of a behavior that has complex configurations of stresses that make them more vulnerable to cracking due to flexure–shear interaction. The design procedures for ends of the dapped girders are well established and are based primarily on experimental tests performed for different configurations of reinforcement. The critical failure modes that can govern the design have been identified, and for each of them, the methods for computing the reinforcing steel that is needed to achieve adequate safety against failure have been proposed. Nevertheless, the design recommendations do not include procedures for controlling diagonal cracking at the entrant corner under service loading. These cracks could cause water penetration and degradation because of the corrosion of the steel reinforcement. The lack of visual access to the area makes it difficult to detect this damage and take timely corrective actions. Three-dimensional non-linear numerical models based on Finite Element Method to study the cracking at the entrant corner of dapped-end beams were performed using the software package ANSYS v. 11.0. The cracking was numerically simulated by using the smeared crack approach. The concrete structure was modeled using three-dimensional solid elements SOLID65 capable of cracking in tension and crushing in compression. Drucker-Prager yield surface was used to include the plastic deformations. The longitudinal post-tension was modeled using LINK8 elements with multilinear isotropic hardening behavior using von Misses plasticity. The reinforcement was introduced with smeared approach. The numerical models were calibrated using experimental tests carried out in “Instituto de Ingeniería, Universidad Nacional Autónoma de México”. In these numerical models the characteristics of the specimens were considered: typical solution based on vertical stirrups (hangers) and on vertical and horizontal hoops with a post-tensioned steel which contributed to a 74% of the flexural resistance. The post-tension is given by four steel wires with a 5/8’’ (16 mm) diameter. Each wire was tensioned to 147 kN and induced an average compressive stress of 4.90 MPa on the concrete section of the dapped end. The loading protocol consisted on applying symmetrical loading to reach the service load (180 kN). Due to the good correlation between experimental and numerical models some additional numerical models were proposed by considering different percentages of post-tension in order to find out how much it influences in the appearance of the cracking in the reentrant corner of the dapped-end beams. It was concluded that the increasing of percentage of post-tension decreases the displacements and the cracking in the reentrant corner takes longer to appear. The authors acknowledge at “Universidad de Guanajuato, Campus Celaya-Salvatierra” and the financial support of PRODEP-SEP (UGTO-PTC-460) of the Mexican government. The first author acknowledges at “Instituto de Ingeniería, Universidad Nacional Autónoma de México”.

Keywords: concrete dapped-end beams, cracking control, finite element analysis, postension

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Authors: Sherif Keddis, Rafik Mitry, Norbert Schwesinger

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Intelligent networking of devices has rapidly been gaining importance over the past years and with recent advances in the fields of microcontrollers, integrated circuits and wireless communication, low power applications have emerged, enabling this trend even more. Connected devices provide a much larger database thus enabling highly intelligent and accurate systems. Ensuring safe drinking water is one of the fields that require constant monitoring and can benefit from an increased accuracy. Monitoring is mainly achieved either through complex measures, such as collecting samples from the points of use, or through metering systems typically distant to the points of use which deliver less accurate assessments of the quality of water. Constant metering near the points of use is complicated due to their inaccessibility; e.g. buried water pipes, locked spaces, which makes system maintenance extremely difficult and often unviable. The research presented here attempts to overcome this challenge by providing these systems with enough energy through a flow harvester inside the pipe thus eliminating the maintenance requirements in terms of battery replacements or containment of leakage resulting from wiring such systems. The proposed flow harvester exploits the piezoelectric properties of polyvinylidene difluoride (PVDF) films to convert turbulence induced oscillations into electrical energy. It is intended to be used in standard water pipes with diameters between 0.5 and 1 inch. The working principle of the harvester uses a ring shaped bluff body inside the pipe to induce pressure fluctuations. Additionally the bluff body houses electronic components such as storage, circuitry and RF-unit. Placing the piezoelectric films downstream of that bluff body causes their oscillation which generates electrical charge. The PVDF-film is placed as a multilayered wrap fixed to the pipe wall leaving the top part to oscillate freely inside the flow. The warp, which allows for a larger active, consists of two layers of 30µm thick and 12mm wide PVDF layered alternately with two centered 6µm thick and 8mm wide aluminum foil electrodes. The length of the layers depends on the number of windings and is part of the investigation. Sealing the harvester against liquid penetration is achieved by wrapping it in a ring-shaped LDPE-film and welding the open ends. The fabrication of the PVDF-wraps is done by hand. After validating the working principle using a wind tunnel, experiments have been conducted in water, placing the harvester inside a 1 inch pipe at water velocities of 0.74m/s. To find a suitable placement of the wrap inside the pipe, two forms of fixation were compared regarding their power output. Further investigations regarding the number of windings required for efficient transduction were made. Best results were achieved using a wrap with 3 windings of the active layers which delivers a constant power output of 0.53µW at a 2.3MΩ load and an effective voltage of 1.1V. Considering the extremely low power requirements of sensor applications, these initial results are promising. For further investigations and optimization, machine designs are currently being developed to automate the fabrication and decrease tolerance of the prototypes.

Keywords: maintenance-free sensors, measurements at point of use, piezoelectric flow harvesting, universal micro generator, wireless metering systems

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Authors: Keivan Davami, Michael Munther, Lloyd Hackel

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The control of properties and material behavior by implementing thermal-mechanical processes is based on mechanical deformation and annealing according to a precise schedule that will produce a unique and stable combination of grain structure, dislocation substructure, texture, and dispersion of precipitated phases. The authors recently developed a thermal-mechanical technique to stabilize the microstructure of additively manufactured nickel-based superalloys even after exposure to high temperatures. However, the mechanism(s) that controls this stability is still under investigation. Laser peening (LP), also called laser shock peening (LSP), is a shock based (50 ns duration) post-processing technique used for extending performance levels and improving service life of critical components by developing deep levels of plastic deformation, thereby generating high density of dislocations and inducing compressive residual stresses in the surface and deep subsurface of components. These compressive residual stresses are usually accompanied with an increase in hardness and enhance the material’s resistance to surface-related failures such as creep, fatigue, contact damage, and stress corrosion cracking. While the LP process enhances the life span and durability of the material, the induced compressive residual stresses relax at high temperatures (>0.5Tm, where Tm is the absolute melting temperature), limiting the applicability of the technology. At temperatures above 0.5Tm, the compressive residual stresses relax, and yield strength begins to drop dramatically. The principal reason is the increasing rate of solid-state diffusion, which affects both the dislocations and the microstructural barriers. Dislocation configurations commonly recover by mechanisms such as climbing and recombining rapidly at high temperatures. Furthermore, precipitates coarsen, and grains grow; virtually all of the available microstructural barriers become ineffective.Our results indicate that by using “cyclic” treatments with sequential LP and annealing steps, the compressive stresses survive, and the microstructure is stable after exposure to temperatures exceeding 0.5Tm for a long period of time. When the laser peening process is combined with annealing, dislocations formed as a result of LPand precipitates formed during annealing have a complex interaction that provides further stability at high temperatures. From a scientific point of view, this research lays the groundwork for studying a variety of physical, materials science, and mechanical engineering concepts. This research could lead to metals operating at higher sustained temperatures enabling improved system efficiencies. The strengthening of metals by a variety of means (alloying, work hardening, and other processes) has been of interest for a wide range of applications. However, the mechanistic understanding of the often complex processes of interactionsbetween dislocations with solute atoms and with precipitates during plastic deformation have largely remained scattered in the literature. In this research, the elucidation of the actual mechanisms involved in the novel cyclic LP/annealing processes as a scientific pursuit is investigated through parallel studies of dislocation theory and the implementation of advanced experimental tools. The results of this research help with the validation of a novel laser processing technique for high temperature applications. This will greatly expand the applications of the laser peening technology originally devised only for temperatures lower than half of the melting temperature.

Keywords: laser shock peening, mechanical properties, indentation, high temperature stability

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Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K.Lehtimäki, A. Nurmi, D. Wells

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Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle wasting disease for which there are currently no treatment that effectively prevents the muscle necrosis and progressive muscle loss. DMD is among the most common of inherited diseases affecting around 1/3500 live male births. MDX (X-linked muscular dystrophy) mice only partially encapsulate the disease in humans and display weakness in muscles, muscle damage and edema during a period deemed the “critical period” when these mice go through cycles of muscular degeneration and regeneration. Although the MDX mutant mouse model has been extensively studied as a model for DMD, to-date an extensive temporal, non-invasive imaging profile that utilizes magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (1H-MRS) has not been performed.. In addition, longitudinal imaging characterization has not coincided with attempts to exacerbate the progressive muscle damage by exercise. In this study we employed an 11.7 T small animal MRI in order to characterize the MRI and MRS profile of MDX mice longitudinally during a 12 month period during which MDX mice were subjected to exercise. Male mutant MDX mice (n=15) and male wild-type mice (n=15) were subjected to a chronic exercise regime of treadmill walking (30 min/ session) bi-weekly over the whole 12 month follow-up period. Mouse gastrocnemius and tibialis anterior muscles were profiled with baseline T2-MRI and 1H-MRS at 6 weeks of age. Imaging and spectroscopy was repeated again at 3 months, 6 months, 9 months and 12 months of age. Plasma creatine kinase (CK) level measurements were coincided with time-points for T2-MRI and 1H-MRS, but also after the “critical period” at 10 weeks of age. The results obtained from this study indicate that chronic exercise extends dystrophic phenotype of MDX mice as evidenced by T2-MRI and1H-MRS. T2-MRI revealed extent and location of the muscle damage in gastrocnemius and tibialis anterior muscles as hyperintensities (lesions and edema) in exercised MDX mice over follow-up period.. The magnitude of the muscle damage remained stable over time in exercised mice. No evident fat infiltration or cumulation to the muscle tissues was seen at any time-point in exercised MDX mice. Creatine, choline and taurine levels evaluated by 1H-MRS from the same muscles were found significantly decreased in each time-point, Extramyocellular (EMCL) and intramyocellular lipids (IMCL) did not change in exercised mice supporting the findings from anatomical T2-MRI scans for fat content. Creatine kinase levels were found to be significantly higher in exercised MDX mice during the follow-up period and importantly CK levels remained stable over the whole follow-up period. Taken together, we have described here longitudinal prophile for muscle damage and muscle metabolic changes in MDX mice subjected to chronic exercised. The extent of the muscle damage by T2-MRI was found to be stable through the follow-up period in muscles examined. In addition, metabolic profile, especially creatine, choline and taurine levels in muscles, was found to be sustained between time-points. The anatomical muscle damage evaluated by T2-MRI was supported by plasma CK levels which remained stable over the follow-up period. These findings show that non-invasive imaging and spectroscopy can be used effectively to evaluate chronic muscle pathology. These techniques can be also used to evaluate the effect of various manipulations, like here exercise, on the phenotype of the mice. Many of the findings we present here are translatable to clinical disease, such as decreased creatine, choline and taurine levels in muscles. Imaging by T2-MRI and 1H-MRS also revealed that fat content or extramyocellar and intramyocellular lipids, respectively, are not changed in MDX mice, which is in contrast to clinical manifestation of the Duchenne’s muscle dystrophy. Findings show that non-invasive imaging can be used to characterize the phenotype of a MDX model and its translatability to clinical disease, and to study events that have traditionally been not examined, like here rigorous exercise related sustained muscle damage after the “critical period”. The ability for this model to display sustained damage beyond the spontaneous “critical period“ and in turn to study drug effects on this extended phenotype will increase the value of the MDX mouse model as a tool to study therapies and treatments aimed at DMD and associated diseases.

Keywords: 1H-MRS, MRI, muscular dystrophy, mouse model

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Authors: B.L. España-Sánchez, E. Luna-Hernández, R.A. Mauricio-Sánchez, M.E. Cruz-Soto, F. Padilla-Vaca, R. Muñoz, L. Granados-López, L.R. Ovalle-Flores, J.L. Menchaca-Arredondo, G. Luna-Bárcenas

Abstract:

Treatment of burn injured has been considered an important clinical problem due to the fluid control and the presence of microorganisms during the healing process. Conventional treatment includes antiseptic techniques, topical medication and surgical removal of damaged skin, to avoid bacterial growth. In order to accelerate this process, different alternatives for tissue regeneration have been explored, including artificial skin, polymers, hydrogels and hybrid materials. Some requirements consider a nonreactive organic polymer with high biocompatibility and skin adherence, avoiding bacterial infections. Chitin-derivative biopolymer such as chitosan (CS) has been used in skin regeneration following third-degree burns. The biological interest of CS is associated with the improvement of tissue cell stimulation, biocompatibility and antibacterial properties. In particular, antimicrobial properties of CS can be significantly increased when is blended with nanostructured materials. Silver-based nanocomposites have gained attention in medicine due to their high antibacterial properties against pathogens, related to their high surface area/volume ratio at nanomolar concentrations. Silver nanocomposites can be blended or synthesized with chitin-derivative biopolymers in order to obtain a biodegradable/antimicrobial hybrid with improved physic-mechanical properties. In this study, nanocomposites based on chitosan/silver nanoparticles (CS/nAg) were synthesized by the in situ chemical reduction method, improving their antibacterial properties against pathogenic bacteria and enhancing the healing process in thermal burn injuries produced in an animal model. CS/nAg was prepared in solution by the chemical reduction method, using AgNO₃ as precursor. CS was dissolved in acetic acid and mixed with different molar concentrations of AgNO₃: 0.01, 0.025, 0.05 and 0.1 M. Solutions were stirred at 95°C during 20 hours, in order to promote the nAg formation. CS/nAg solutions were placed in Petri dishes and dried, to obtain films. Structural analyses confirm the synthesis of silver nanoparticles (nAg) by means of UV-Vis and TEM, with an average size of 7.5 nm and spherical morphology. FTIR analyses showed the complex formation by the interaction of hydroxyl and amine groups with metallic nanoparticles, and surface chemical analysis (XPS) shows low concentration of Ag⁰/Ag⁺ species. Topography surface analyses by means of AFM shown that hydrated CS form a mesh with an average diameter of 10 µm. Antibacterial activity against S. aureus and P. aeruginosa was improved in all evaluated conditions, such as nAg loading and interaction time. CS/nAg nanocomposites films did not show Ag⁰/Ag⁺ release in saline buffer and rat serum after exposition during 7 days. Healing process was significantly enhanced by the presence of CS/nAg nanocomposites, inducing the production of myofibloblasts, collagen remodelation, blood vessels neoformation and epidermis regeneration after 7 days of injury treatment, by means of histological and immunohistochemistry assays. The present work suggests that hydrated CS/nAg nanocomposites can be formed a mesh, improving the bacterial penetration and the contact with embedded nAg, producing complete growth inhibition after 1.5 hours. Furthermore, CS/nAg nanocomposites improve the cell tissue regeneration in thermal burn injuries induced in rats. Synthesis of antibacterial, non-toxic, and biocompatible nanocomposites can be an important issue in tissue engineering and health care applications.

Keywords: antibacterial, chitosan, healing process, nanocomposites, silver

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