Search results for: selective laser sintering

Authors: Giulia Fredi, Andrea Dorigato, Luca Fambri, Alessandro Pegoretti

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Thermal energy storage (TES) is the storage of heat for later use, thus filling the gap between energy request and supply. The most widely used materials for TES are the organic solid-liquid phase change materials (PCMs), such as paraffin. These materials store/release a high amount of latent heat thanks to their high specific melting enthalpy, operate in a narrow temperature range and have a tunable working temperature. However, they suffer from a low thermal conductivity and need to be confined to prevent leakage. These two issues can be tackled by confining PCMs with carbon nanotubes (CNTs). TES applications include the buildings industry, solar thermal energy collection and thermal management of electronics. In most cases, TES systems are an additional component to be added to the main structure, but if weight and volume savings are key issues, it would be advantageous to embed the TES functionality directly in the structure. Such multifunctional materials could be employed in the automotive industry, where the diffusion of lightweight structures could complicate the thermal management of the cockpit environment or of other temperature sensitive components. This work aims to produce epoxy/carbon structural laminates containing CNT-stabilized paraffin. CNTs were added to molten paraffin in a fraction of 10 wt%, as this was the minimum amount at which no leakage was detected above the melting temperature (45°C). The paraffin/CNT blend was cryogenically milled to obtain particles with an average size of 50 µm. They were added in various percentages (20, 30 and 40 wt%) to an epoxy/hardener formulation, which was used as a matrix to produce laminates through a wet layup technique, by stacking five plies of a plain carbon fiber fabric. The samples were characterized microstructurally, thermally and mechanically. Differential scanning calorimetry (DSC) tests showed that the paraffin kept its ability to melt and crystallize also in the laminates, and the melting enthalpy was almost proportional to the paraffin weight fraction. These thermal properties were retained after fifty heating/cooling cycles. Laser flash analysis showed that the thermal conductivity through the thickness increased with an increase of the PCM, due to the presence of CNTs. The ability of the developed laminates to contribute to the thermal management was also assessed by monitoring their cooling rates through a thermal camera. Three-point bending tests showed that the flexural modulus was only slightly impaired by the presence of the paraffin/CNT particles, while a more sensible decrease of the stress and strain at break and the interlaminar shear strength was detected. Optical and scanning electron microscope images revealed that these could be attributed to the preferential location of the PCM in the interlaminar region. These results demonstrated the feasibility of multifunctional structural TES composites and highlighted that the PCM size and distribution affect the mechanical properties. In this perspective, this group is working on the encapsulation of paraffin in a sol-gel derived organosilica shell. Submicron spheres have been produced, and the current activity focuses on the optimization of the synthesis parameters to increase the emulsion efficiency.

Keywords: carbon fibers, carbon nanotubes, lightweight materials, multifunctional composites, thermal energy storage

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Authors: Mingqian Zhang

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Tip-enhanced Raman spectroscopy (TERS) is a scanning probe technique for individual objects and structured surfaces investigation that provides a wealth of enhanced spectral information with nanoscale spatial resolution and high detection sensitivity. It has become a powerful and promising chemical and physical information detection method in the nanometer scale. The TERS technique uses a sharp metallic tip regulated in the near-field of a sample surface, which is illuminated with a certain incident beam meeting the excitation conditions of the wave-vector matching. The local electric field, and, consequently, the Raman scattering, from the sample in the vicinity of the tip apex are both greatly tip-enhanced owning to the excitation of localized surface plasmons and the lightning-rod effect. Typically, a TERS setup is composed of a scanning probe microscope, excitation and collection optical configurations, and a Raman spectroscope. In the illumination configuration, an objective lens or a parabolic mirror is always used as the most important component, in order to focus the incident beam on the tip apex for excitation. In this research, a novel TERS setup was built up by introducing a plasmonic lens to the excitation optics as a focusing device. A plasmonic lens with symmetry breaking semi-annular slits corrugated on gold film was designed for the purpose of generating concentrated sub-wavelength light spots with strong longitudinal electric field. Compared to conventional far-field optical components, the designed plasmonic lens not only focuses an incident beam to a sub-wavelength light spot, but also realizes a strong z-component that dominants the electric field illumination, which is ideal for the excitation of tip-enhancement. Therefore, using a PL in the illumination configuration of TERS contributes to improve the detection sensitivity by both reducing the far-field background and effectively exciting the localized electric field enhancement. The FDTD method was employed to investigate the optical near-field distribution resulting from the light-nanostructure interaction. And the optical field distribution was characterized using an scattering-type scanning near-field optical microscope to demonstrate the focusing performance of the lens. The experimental result is in agreement with the theoretically calculated one. It verifies the focusing performance of the plasmonic lens. The optical field distribution shows a bright elliptic spot in the lens center and several arc-like side-lobes on both sides. After the focusing performance was experimentally verified, the designed plasmonic lens was used as a focusing component in the excitation configuration of TERS setup to concentrate incident energy and generate a longitudinal optical field. A collimated linearly polarized laser beam, with along x-axis polarization, was incident from the bottom glass side on the plasmonic lens. The incident light focused by the plasmonic lens interacted with the silver-coated tip apex and enhanced the Raman signal of the sample locally. The scattered Raman signal was gathered by a parabolic mirror and detected with a Raman spectroscopy. Then, the plasmonic lens based setup was employed to investigate carbon nanotubes and TERS experiment was performed. Experimental results indicate that the Raman signal is considerably enhanced which proves that the novel TERS configuration is feasible and promising.

Keywords: longitudinal electric field, plasmonics, raman spectroscopy, tip-enhancement

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Authors: Helen S. Joyner (Melito), Mohammad Anvari

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Concentrated emulsions stabilized by proteins are systems of great importance in food, pharmaceutical and cosmetic products. Controlling emulsion rheology is critical for ensuring desired properties during formation, storage, and consumption of emulsion-based products. Studies on concentrated emulsions have focused on rheology of monodispersed systems. However, emulsions used for industrial applications are polydispersed in nature, and this polydispersity is regarded as an important parameter that also governs the rheology of the concentrated emulsions. Therefore, the objective of this study was to characterize rheological (small and large deformation behaviors) and microstructural properties of concentrated emulsions which were not truly monodispersed as usually encountered in food products such as margarines, mayonnaise, creams, spreads, and etc. The concentrated emulsions were prepared at different concentrations of fish gelatin (0.2, 0.4, 0.8% w/v in the whole emulsion system), oil-water ratio 80-20 (w/w), homogenization speed 10000 rpm, and 25oC. Confocal laser scanning microscopy (CLSM) was used to determine the microstructure of the emulsions. To prepare samples for CLSM analysis, FG solutions were stained by Fluorescein isothiocyanate dye. Emulsion viscosity profiles were determined using shear rate sweeps (0.01 to 100 1/s). The linear viscoelastic regions (LVRs) of the emulsions were determined using strain sweeps (0.01 to 100% strain) for each sample. Frequency sweeps were performed in the LVR (0.1% strain) from 0.6 to 100 rad/s. Large amplitude oscillatory shear (LAOS) testing was conducted by collecting raw waveform data at 0.05, 1, 10, and 100% strain at 4 different frequencies (0.5, 1, 10, and 100 rad/s). All measurements were performed in triplicate at 25oC. The CLSM results revealed that increased fish gelatin concentration resulted in more stable oil-in-water emulsions with homogeneous, finely dispersed oil droplets. Furthermore, the protein concentration had a significant effect on emulsion rheological properties. Apparent viscosity and dynamic moduli at small deformations increased with increasing fish gelatin concentration. These results were related to increased inter-droplet network connections caused by increased fish gelatin adsorption at the surface of oil droplets. Nevertheless, all samples showed shear-thinning and weak gel behaviors over shear rate and frequency sweeps, respectively. Lissajous plots, or plots of stress versus strain, and phase lag values were used to determine nonlinear behavior of the emulsions in LAOS testing. Greater distortion in the elliptical shape of the plots followed by higher phase lag values was observed at large strains and frequencies in all samples, indicating increased nonlinear behavior. Shifts from elastic-dominated to viscous dominated behavior were also observed. These shifts were attributed to damage to the sample microstructure (e.g. gel network disruption), which would lead to viscous-type behaviors such as permanent deformation and flow. Unlike the small deformation results, the LAOS behavior of the concentrated emulsions was not dependent on fish gelatin concentration. Systems with different microstructures showed similar nonlinear viscoelastic behaviors. The results of this study provided valuable information that can be used to incorporate concentrated emulsions in emulsion-based food formulations.

Keywords: concentrated emulsion, fish gelatin, microstructure, rheology

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Authors: Diego Giuseppe Romano, Gianvito Apuleo, Jiri Duda

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Mobility is one of the most important societal needs for amusement, business activities and health. Thus, transport needs are continuously increasing, with the consequent traffic congestion and pollution increase. Aeronautic effort aims at smarter infrastructures use and in introducing greener concepts. A possible solution to address the abovementioned topics is the development of Small Air Transport (SAT) system, able to guarantee operability from today underused airfields in an affordable and green way, helping meanwhile travel time reduction, too. In the framework of Horizon2020, EU (European Union) has funded the Clean Sky 2 SAT TA (Transverse Activity) initiative to address market innovations able to reduce SAT operational cost and environmental impact, ensuring good levels of operational safety. Nowadays, most of the key technologies to improve passenger comfort and to reduce community noise, DOC (Direct Operating Costs) and pilot workload for SAT have reached an intermediate level of maturity TRL (Technology Readiness Level) 3/4. Thus, the key technologies must be developed, validated and integrated on dedicated ground and flying aircraft demonstrators to reach higher TRL levels (5/6). Particularly, SAT TA focuses on the integration at aircraft level of the following technologies [1]: 1)    Low-cost composite wing box and engine nacelle using OoA (Out of Autoclave) technology, LRI (Liquid Resin Infusion) and advance automation process. 2) Innovative high lift devices, allowing aircraft operations from short airfields (< 800 m). 3) Affordable small aircraft manufacturing of metallic fuselage using FSW (Friction Stir Welding) and LMD (Laser Metal Deposition). 4)       Affordable fly-by-wire architecture for small aircraft (CS23 certification rules). 5) More electric systems replacing pneumatic and hydraulic systems (high voltage EPGDS -Electrical Power Generation and Distribution System-, hybrid de-ice system, landing gear and brakes). 6) Advanced avionics for small aircraft, reducing pilot workload. 7) Advanced cabin comfort with new interiors materials and more comfortable seats. 8) New generation of turboprop engine with reduced fuel consumption, emissions, noise and maintenance costs for 19 seats aircraft. (9) Alternative diesel engine for 9 seats commuter aircraft. To address abovementioned market innovations, two different platforms have been designed: Reference and Green aircraft. Reference aircraft is a virtual aircraft designed considering 2014 technologies with an existing engine assuring requested take-off power; Green aircraft is designed integrating the technologies addressed in Clean Sky 2. Preliminary integration of the proposed technologies shows an encouraging reduction of emissions and operational costs of small: about 20% CO₂ reduction, about 24% NO_x reduction, about 10 db (A) noise reduction at measurement point and about 25% DOC reduction. Detailed description of the performed studies, analyses and validations for each technology as well as the expected benefit at aircraft level are reported in the present paper.

Keywords: affordable, European, green, mobility, technologies development, travel time reduction

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Authors: Alexandre Faure, Yoko Mizokami, éRic Dinet

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These recent years, the potential of light in assisting visually impaired people in their indoor mobility has been demonstrated by different studies. Implementing smart lighting systems for selective visual enhancement, especially designed for low-vision people, is an approach that breaks with the existing visual aids. The appearance of the surface of an object is significantly influenced by the lighting conditions and the constituent materials of the objects. Appearance of objects may appear to be different from expectation. Therefore, lighting conditions lead to an important part of accurate material recognition. The main objective of this work was to investigate the effect of the spatial distribution of light on object identification in the context of low vision. The purpose was to determine whether and what specific lighting approaches should be preferred for visually impaired people. A psychophysical experiment was designed to study the ability of individuals to identify the smallest cube of a pair under different lighting diffusion conditions. Participants were divided into two distinct groups: a reference group of observers with normal or corrected-to-normal visual acuity and a test group, in which observers were required to wear visual impairment simulation glasses. All participants were presented with pairs of cubes in a "miniature room" and were instructed to estimate the relative size of the two cubes. The miniature room replicates real-life settings, adorned with decorations and separated from external light sources by black curtains. The correlated color temperature was set to 6000 K, and the horizontal illuminance at the object level at approximately 240 lux. The objects presented for comparison consisted of 11 white cubes and 11 black cubes of different sizes manufactured with a 3D printer. Participants were seated 60 cm away from the objects. Two different levels of light diffuseness were implemented. After receiving instructions, participants were asked to judge whether the two presented cubes were the same size or if one was smaller. They provided one of five possible answers: "Left one is smaller," "Left one is smaller but unsure," "Same size," "Right one is smaller," or "Right one is smaller but unsure.". The method of constant stimuli was used, presenting stimulus pairs in a random order to prevent learning and expectation biases. Each pair consisted of a comparison stimulus and a reference cube. A psychometric function was constructed to link stimulus value with the frequency of correct detection, aiming to determine the 50% correct detection threshold. Collected data were analyzed through graphs illustrating participants' responses to stimuli, with accuracy increasing as the size difference between cubes grew. Statistical analyses, including 2-way ANOVA tests, showed that light diffuseness had no significant impact on the difference threshold, whereas object color had a significant influence in low vision scenarios. The first results and trends derived from this pilot experiment clearly and strongly suggest that future investigations could explore extreme diffusion conditions to comprehensively assess the impact of diffusion on object identification. For example, the first findings related to light diffuseness may be attributed to the range of manipulation, emphasizing the need to explore how other lighting-related factors interact with diffuseness.

Keywords: Lighting, Low Vision, Visual Aid, Object Identification, Psychophysical Experiment

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Dace Grauda, Inta Belogrudova, Alexei Katashev, Linda Lancere, Isaak Rashal

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The goal of study was the elaboration of easy applicable flow cytometry method for detection of influence of abiotic stress factors on plants, which could be useful for detection of environmental stresses in urban areas. The lime tree Tillia vulgaris H. is a popular tree species used for urban landscaping in Europe and is one of the main species of street greenery in Riga, Latvia. Tree decline and low vitality has observed in the central part of Riga. For this reason lime trees were select as a model object for the investigation. During the period of end of June and beginning of July 12 samples from different urban environment locations as well as plant material from a greenhouse were collected. BD FACSJazz® cell sorter (BD Biosciences, USA) with flow cytometer function was used to test viability of plant cells. The method was based on changes of relative fluorescence intensity of cells in blue laser (488 nm) after influence of stress factors. SpheroTM rainbow calibration particles (3.0–3.4 μm, BD Biosciences, USA) in phosphate buffered saline (PBS) were used for calibration of flow cytometer. BD PharmingenTM PBS (BD Biosciences, USA) was used for flow cytometry assays. The mean fluorescence intensity information from the purified cell suspension samples was recorded. Preliminary, multiple gate sizes and shapes were tested to find one with the lowest CV. It was found that low CV can be obtained if only the densest part of plant cells forward scatter/side scatter profile is analysed because in this case plant cells are most similar in size and shape. The young pollen cells in one nucleus stage were found as the best for detection of influence of abiotic stress. For experiments only fresh plant material was used– the buds of Tillia vulgaris with diameter 2 mm. For the cell suspension (in vitro culture) establishment modified protocol of microspore culture was applied. The cells were suspended in the MS (Murashige and Skoog) medium. For imitation of dust of urban area SiO2 nanoparticles with concentration 0.001 g/ml were dissolved in distilled water. Into 10 ml of cell suspension 1 ml of SiO2 nanoparticles suspension was added, then cells were incubated in speed shaking regime for 1 and 3 hours. As a stress factor the irradiation of cells for 20 min by UV was used (Hamamatsu light source L9566-02A, L10852 lamp, A10014-50-0110), maximum relative intensity (100%) at 365 nm and at ~310 nm (75%). Before UV irradiation the suspension of cells were placed onto a thin layer on a filter paper disk (diameter 45 mm) in a Petri dish with solid MS media. Cells without treatment were used as a control. Experiments were performed at room temperature (23-25 °C). Using flow cytometer BS FACS Software cells plot was created to determine the densest part, which was later gated using oval-shaped gate. Gate included from 95 to 99% of all cells. To determine relative fluorescence of cells logarithmic fluorescence scale in arbitrary fluorescence units were used. 3x103 gated cells were analysed from the each sample. The significant differences were found among relative fluorescence of cells from different trees after treatment with SiO2 nanoparticles and UV irradiation in comparison with the control.

Keywords: flow cytometry, fluorescence, SiO2 nanoparticles, UV irradiation

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Authors: Catherine Bradshaw

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Educators often report difficulty managing behavior problems and other mental health concerns that students display at school. These concerns also interfere with the learning process and can create distraction for teachers and other students. As such, schools play an important role in both preventing and intervening with students who experience these types of challenges. A number of models have been proposed to serve as a framework for delivering prevention and early intervention services in schools. One such model is called Positive Behavioral Interventions and Supports (PBIS), which has been scaled-up to over 26,000 schools in the U.S. and many other countries worldwide. PBIS aims to improve a range of student outcomes through early detection of and intervention related to behavioral and mental health symptoms. PBIS blends and applies social learning, behavioral, and organizational theories to prevent disruptive behavior and enhance the school’s organizational health. PBIS focuses on creating and sustaining tier 1 (universal), tier 2 (selective), and tier 3 (individual) systems of support. Most schools using PBIS have focused on the core elements of the tier 1 supports, which includes the following critical features. The formation of a PBIS team within the school to lead implementation. Identification and training of a behavioral support ‘coach’, who serves as a on-site technical assistance provider. Many of the individuals identified to serve as a PBIS coach are also trained as a school psychologist or guidance counselor; coaches typically have prior PBIS experience and are trained to conduct functional behavioral assessments. The PBIS team also identifies a set of three to five positive behavioral expectations that are implemented for all students and by all staff school-wide (e.g., ‘be respectful, responsible, and ready to learn’); these expectations are posted in all settings across the school, including in the classroom, cafeteria, playground etc. All school staff define and teach the school-wide behavioral expectations to all students and review them regularly. Finally, PBIS schools develop or adopt a school-wide system to reward or reinforce students who demonstrate those 3-5 positive behavioral expectations. Staff and administrators create an agreed upon system for responding to behavioral violations that include definitions about what constitutes a classroom-managed vs. an office-managed discipline problem. Finally, a formal system is developed to collect, analyze, and use disciplinary data (e.g., office discipline referrals) to inform decision-making. This presentation provides a brief overview of PBIS and reports findings from a series of four U.S. based longitudinal randomized controlled trials (RCTs) documenting the impacts of PBIS on school climate, discipline problems, bullying, and academic achievement. The four RCTs include 80 elementary, 40 middle, and 58 high schools and results indicate a broad range of impacts on multiple student and school-wide outcomes. The session will highlight lessons learned regarding PBIS implementation and scale-up. We also review the ways in which PBIS can help educators and school leaders engage in data-based decision-making and share data with other decision-makers and stakeholders (e.g., students, parents, community members), with the overarching goal of increasing use of evidence-based programs in schools.

Keywords: positive behavioral interventions and supports, mental health, randomized trials, school-based prevention

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Authors: Ariesny Vera, Rodrigo Montecinos

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The rare-earth elements (REEs) or rare-earth metals (REMs), correspond to seventeen chemical elements composed by the fifteen lanthanoids, as well as scandium and yttrium. Lanthanoids corresponds to lanthanum and the f-block elements, from cerium to lutetium. Scandium and yttrium are considered rare-earth elements because they have ionic radii similar to the lighter f-block elements. These elements were called rare earths because they are simply more difficult to extract and separate individually than the most metals and, generally, they do not accumulate in minerals, they are rarely found in easily mined ores and are often unfavorably distributed in common ores/minerals. REEs show unique chemical and physical properties, in comparison to the other metals in the periodic table. Nowadays, these physicochemical properties are utilized in a wide range of synthetic, catalytic, electronic, medicinal, and military applications. Because of their applications, the global demand for rare earth metals is becoming progressively more important in the transition to a self-sustaining society and greener economy. However, due to the difficult separation between lanthanoid ions, the high cost and pollution of these processes, the scientists search the development of a method that combines selectivity and quantitative separation of lanthanoids from the leaching liquor, while being more economical and environmentally friendly processes. This motivation has favored the design and development of more efficient and environmentally friendly cation extractors with the incorporation of compounds as ionic liquids, membrane inclusion polymers (PIM) and supramolecular systems. Supramolecular chemistry focuses on the development of host-guest systems, in which a host molecule can recognize and bind a certain guest molecule or ion. Normally, the formation of a host-guest complex involves non-covalent interactions Additionally, host-guest interactions can be influenced among others effects by the structural nature of host and guests. The different macrocyclic hosts for lanthanoid species that have been studied are crown ethers, cyclodextrins, cucurbituryls, calixarenes and pillararenes.Among all the factors that can influence and affect lanthanoid (III) coordination, perhaps the most basic of them is the systematic control using macrocyclic substituents that promote a selective coordination. In this sense, macrocycles pillar[n]arenes (P[n]As) present a relatively easy functionalization and they have more π-rich cavity than other host molecules. This gives to P[n]As a negative electrostatic potential in the cavity which would be responsible for the selectivity of these compounds towards cations. Furthermore, the cavity size, the linker, and the functional groups of the polar headgroups could be modified in order to control the association of lanthanoid cations. In this sense, different P[n]As systems, specifically derivatives of the pentamer P[5]A functionalized with amide, amine, phosphate and sulfate derivatives, have been designed in terms of experimental synthesis and molecular dynamics, and the interaction between these P[5]As and some lanthanoid ions such as La³+, Eu³+ and Lu³+ has been studied by physicochemical characterization by 1H-NMR, ITC and fluorescence in the case of Eu³+ systems. The molecular dynamics study of these systems was developed in hexane as solvent, also taking into account the lanthanoid ions mentioned above, and the respective comparison studies between the different ions.

Keywords: lanthanoids, macrocycles, pillar[n]arenes, rare-earth metal extraction, supramolecular chemistry, supramolecular complexes.

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Authors: Sarah Fitzpatrick, Hossein Zare-Behtash, Konstantinos Kontis

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Traditionally, the focus of horizontal axis wind turbine (HAWT) blade aerodynamic optimisation studies has been the outer working region of the blade. However, recent works seek to better understand, and thus improve upon, the performance of the inboard blade region to enhance power production, maximise load reduction and better control the wake behaviour. This paper presents the design considerations and characterisation of a wind turbine wind tunnel model devised to further the understanding and fundamental definition of horizontal axis wind turbine root vortex shedding and interactions. Additionally, the application of passive and active flow control mechanisms – vortex generators and plasma actuators – to allow for the manipulation and mitigation of unsteady aerodynamic behaviour at the blade inboard section is investigated. A static, modular blade wind turbine model has been developed for use in the University of Glasgow’s de Havilland closed return, low-speed wind tunnel. The model components - which comprise of a half span blade, hub, nacelle and tower - are scaled using the equivalent full span radius, R, for appropriate Mach and Strouhal numbers, and to achieve a Reynolds number in the range of 1.7x105 to 5.1x105 for operational speeds up to 55m/s. The half blade is constructed to be modular and fully dielectric, allowing for the integration of flow control mechanisms with a focus on plasma actuators. Investigations of root vortex shedding and the subsequent wake characteristics using qualitative – smoke visualisation, tufts and china clay flow – and quantitative methods – including particle image velocimetry (PIV), hot wire anemometry (HWA), and laser Doppler anemometry (LDA) – were conducted over a range of blade pitch angles 0 to 15 degrees, and Reynolds numbers. This allowed for the identification of shed vortical structures from the maximum chord position, the transitional region where the blade aerofoil blends into a cylindrical joint, and the blade nacelle connection. Analysis of the trailing vorticity interactions between the wake core and freestream shows the vortex meander and diffusion is notably affected by the Reynold’s number. It is hypothesized that the shed vorticity from the blade root region directly influences and exacerbates the nacelle wake expansion in the downstream direction. As the design of inboard blade region form is, by necessity, driven by function rather than aerodynamic optimisation, a study is undertaken for the application of flow control mechanisms to manipulate the observed vortex phenomenon. The designed model allows for the effective investigation of shed vorticity and wake interactions with a focus on the accurate geometry of a root region which is representative of small to medium power commercial HAWTs. The studies undertaken allow for an enhanced understanding of the interplay of shed vortices and their subsequent effect in the near and far wake. This highlights areas of interest within the inboard blade area for the potential use of passive and active flow control devices which contrive to produce a more desirable wake quality in this region.

Keywords: vortex shedding, wake interactions, wind tunnel model, wind turbine

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Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

Procedia PDF Downloads 97

Authors: Maria Karnachoriti, Ellas Spyratou, Dimitrios Lykidis, Maria Lambropoulou, Yiannis S. Raptis, Ioannis Seimenis, Efstathios P. Efstathopoulos, Athanassios G. Kontos

Abstract:

Colorectal cancer is the third most common cancer diagnosed in Europe, according to the latest incidence data provided by the World Health Organization (WHO), and early diagnosis has proved to be the key in reducing cancer-related mortality. In cases where surgical interventions are required for cancer treatment, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. The current study focuses on the ex vivo handling of surgically excised colorectal specimens and the acquisition of their spectral fingerprints using Raman spectroscopy. Acquired data were analyzed in an effort to discriminate, in microscopic scale, between healthy and malignant margins. Raman spectroscopy is a spectroscopic technique with high detection sensitivity and spatial resolution of few micrometers. The spectral fingerprint which is produced during laser-tissue interaction is unique and characterizes the biostructure and its inflammatory or cancer state. Numerous published studies have demonstrated the potential of the technique as a tool for the discrimination between healthy and malignant tissues/cells either ex vivo or in vivo. However, the handling of the excised human specimens and the Raman measurement conditions remain challenging, unavoidably affecting measurement reliability and repeatability, as well as the technique’s overall accuracy and sensitivity. Therefore, tissue handling has to be optimized and standardized to ensure preservation of cell integrity and hydration level. Various strategies have been implemented in the past, including the use of balanced salt solutions, small humidifiers or pump-reservoir-pipette systems. In the current study, human colorectal specimens of 10X5 mm were collected from 5 patients up to now who underwent open surgery for colorectal cancer. A novel, non-toxic zinc-based fixative (Z7) was used for tissue preservation. Z7 demonstrates excellent protein preservation and protection against tissue autolysis. Micro-Raman spectra were recorded with a Renishaw Invia spectrometer from successive random 2 micrometers spots upon excitation at 785 nm to decrease fluorescent background and secure avoidance of tissue photodegradation. A temperature-controlled approach was adopted to stabilize the tissue at 2 °C, thus minimizing dehydration effects and consequent focus drift during measurement. A broad spectral range, 500-3200 cm-1,was covered with five consecutive full scans that lasted for 20 minutes in total. The average spectra were used for least square fitting analysis of the Raman modes.Subtle Raman differences were observed between normal and cancerous colorectal tissues mainly in the intensities of the 1556 cm-1 and 1628 cm-1 Raman modes which correspond to v(C=C) vibrations in porphyrins, as well as in the range of 2800-3000 cm-1 due to CH2 stretching of lipids and CH3 stretching of proteins. Raman spectra evaluation was supported by histological findings from twin specimens. This study demonstrates that Raman spectroscopy may constitute a promising tool for real-time verification of clear margins in colorectal cancer open surgery.

Keywords: colorectal cancer, Raman spectroscopy, malignant margins, spectral fingerprints

Procedia PDF Downloads 67

Authors: Adeline Meriaux, Claire Gaiani, Jennifer Burgain, Frantz Fournier, Lionel Muniglia, Jérémy Petit

Abstract:

Spray-drying process is widely used for the production of dairy powders for food and pharmaceuticals industries. It involves the atomization of a liquid feed into fine droplets, which are subsequently dried through contact with a hot air flow. The resulting powders permit transportation cost reduction and shelf life increase but can also exhibit various interesting functionalities (flowability, solubility, protein modification or acid gelation), depending on operating conditions and milk composition. Indeed, particles porosity, surface composition, lactose crystallization, protein denaturation, protein association or crust formation may change. Links between spray-drying conditions and physicochemical and functional properties of powders were investigated by a design of experiment methodology and analyzed by principal component analysis. Quadratic models were developed, and multicriteria optimization was carried out by the use of genetic algorithm. At the time of abstract submission, verification spray-drying trials are ongoing. To perform experiments, milk from dairy farm was collected, skimmed, froze and spray-dried at different air pressure (between 1 and 3 bars) and outlet temperature (between 75 and 95 °C). Dry matter, minerals content and proteins content were determined by standard method. Solubility index, absorption index and hygroscopicity were determined by method found in literature. Particle size distribution were obtained by laser diffraction granulometry. Location of the powder color in the Cielab color space and water activity were characterized by a colorimeter and an aw-value meter, respectively. Flow properties were characterized with FT4 powder rheometer; in particular compressibility and shearing test were performed. Air pressure and outlet temperature are key factors that directly impact the drying kinetics and powder characteristics during spray-drying process. It was shown that the air pressure affects the particle size distribution by impacting the size of droplet exiting the nozzle. Moreover, small particles lead to more cohesive powder and less saturated color of powders. Higher outlet temperature results in lower moisture level particles which are less sticky and can explain a spray-drying yield increase and the higher cohesiveness; it also leads to particle with low water activity because of the intense evaporation rate. However, it induces a high hygroscopicity, thus, powders tend to get wet rapidly if they are not well stored. On the other hand, high temperature provokes a decrease of native serum proteins which is positively correlated to gelation properties (gel point and firmness). Partial denaturation of serum proteins can improve functional properties of powder. The control of air pressure and outlet temperature during the spray-drying process significantly affects the physicochemical and functional properties of powder. This study permitted to better understand the links between physicochemical and functional properties of powder, to identify correlations between air pressure and outlet temperature. Therefore, mathematical models have been developed and the use of genetic algorithm will allow the optimization of powder functionalities.

Keywords: dairy powders, spray-drying, powders functionalities, design of experiment

Procedia PDF Downloads 46

Authors: Adeline Meriaux, Claire Gaiani, Jennifer Burgain, Frantz Fournier, Lionel Muniglia, Jérémy Petit

Abstract:

Spray-drying process is widely used for the production of dairy powders for food and pharmaceuticals industries. It involves the atomization of a liquid feed into fine droplets, which are subsequently dried through contact with a hot air flow. The resulting powders permit transportation cost reduction and shelf life increase but can also exhibit various interesting functionalities (flowability, solubility, protein modification or acid gelation), depending on operating conditions and milk composition. Indeed, particles porosity, surface composition, lactose crystallization, protein denaturation, protein association or crust formation may change. Links between spray-drying conditions and physicochemical and functional properties of powders were investigated by a design of experiment methodology and analyzed by principal component analysis. Quadratic models were developed, and multicriteria optimization was carried out by the use of genetic algorithm. At the time of abstract submission, verification spray-drying trials are ongoing. To perform experiments, milk from dairy farm was collected, skimmed, froze and spray-dried at different air pressure (between 1 and 3 bars) and outlet temperature (between 75 and 95 °C). Dry matter, minerals content and proteins content were determined by standard method. Solubility index, absorption index and hygroscopicity were determined by method found in literature. Particle size distribution were obtained by laser diffraction granulometry. Location of the powder color in the Cielab color space and water activity were characterized by a colorimeter and an aw-value meter, respectively. Flow properties were characterized with FT4 powder rheometer; in particular, compressibility and shearing test were performed. Air pressure and outlet temperature are key factors that directly impact the drying kinetics and powder characteristics during spray-drying process. It was shown that the air pressure affects the particle size distribution by impacting the size of droplet exiting the nozzle. Moreover, small particles lead to more cohesive powder and less saturated color of powders. Higher outlet temperature results in lower moisture level particles which are less sticky and can explain a spray-drying yield increase and the higher cohesiveness; it also leads to particle with low water activity because of the intense evaporation rate. However, it induces a high hygroscopicity, thus, powders tend to get wet rapidly if they are not well stored. On the other hand, high temperature provokes a decrease of native serum proteins, which is positively correlated to gelation properties (gel point and firmness). Partial denaturation of serum proteins can improve functional properties of powder. The control of air pressure and outlet temperature during the spray-drying process significantly affects the physicochemical and functional properties of powder. This study permitted to better understand the links between physicochemical and functional properties of powder to identify correlations between air pressure and outlet temperature. Therefore, mathematical models have been developed, and the use of genetic algorithm will allow the optimization of powder functionalities.

Keywords: dairy powders, spray-drying, powders functionalities, design of experiment

Procedia PDF Downloads 40

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

Abstract:

In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

Procedia PDF Downloads 110

Authors: Mohammadreza Kashizadeh, Mohammadamin Hashemi

Abstract:

Solymorph, a kinetic building facade designed for optimal energy capture and architectural expression, is explored in this paper. The system integrates photovoltaic panels with soft robotic actuators for precise solar tracking, resulting in enhanced electricity generation compared to static facades. Driven by the growing interest in dynamic building envelopes, the exploration of novel facade systems is necessitated. Increased energy generation and regulation of energy flow within buildings are potential benefits offered by integrating photovoltaic (PV) panels as kinetic elements. However, incorporating these technologies into mainstream architecture presents challenges due to the complexity of coordinating multiple systems. To address this, Solymorph leverages soft robotic actuators, known for their compliance, resilience, and ease of integration. Additionally, the project investigates the potential for employing Large Language Models (LLMs) to streamline the design process. The research methodology involved design development, material selection, component fabrication, and system assembly. Grasshopper (GH) was employed within the digital design environment for parametric modeling and scripting logic, and an LLM was experimented with to generate Python code for the creation of a random surface with user-defined parameters. Various techniques, including casting, 3D printing, and laser cutting, were utilized to fabricate the physical components. Finally, a modular assembly approach was adopted to facilitate installation and maintenance. A case study focusing on the application of Solymorph to an existing library building at Politecnico di Milano is presented. The facade system is divided into sub-frames to optimize solar exposure while maintaining a visually appealing aesthetic. Preliminary structural analyses were conducted using Karamba3D to assess deflection behavior and axial loads within the cable net structure. Additionally, Finite Element (FE) simulations were performed in Abaqus to evaluate the mechanical response of the soft robotic actuators under pneumatic pressure. To validate the design, a physical prototype was created using a mold adapted for a 3D printer's limitations. Casting Silicone Rubber Sil 15 was used for its flexibility and durability. The 3D-printed mold components were assembled, filled with the silicone mixture, and cured. After demolding, nodes and cables were 3D-printed and connected to form the structure, demonstrating the feasibility of the design. Solymorph demonstrates the potential of soft robotics and Artificial Intelligence (AI) for advancements in sustainable building design and construction. The project successfully integrates these technologies to create a dynamic facade system that optimizes energy generation and architectural expression. While limitations exist, Solymorph paves the way for future advancements in energy-efficient facade design. Continued research efforts will focus on cost reduction, improved system performance, and broader applicability.

Keywords: artificial intelligence, energy efficiency, kinetic photovoltaics, pneumatic control, soft robotics, sustainable building

Procedia PDF Downloads 17

Authors: Fossarello Maurizio, Mattana Giorgio, Tatti Filippo.

Abstract:

The most widely performed surgical procedure in Open-Angle Glaucoma (OAG) is trabeculectomy. Although this filtering procedure is extremely effective, surgical failure and postoperative complications are reported. Due to the its invasive nature and possible complications, trabeculectomy is usually reserved, in practice, for patients who are refractory to medical and laser therapy. Recently, a number of micro-invasive surgical techniques (MIGS: Micro-Invasive Glaucoma Surgery), have been introduced in clinical practice. They meet the criteria of micro-incisional approach, minimal tissue damage, short surgical time, reliable IOP reduction, extremely high safety profile and rapid post-operative recovery. Xen45 Gel Implant (Allergan, Dublin, Ireland) is one of the MIGS alternatives, and consists in a porcine gelatin tube designed to create an aqueous flow from the anterior chamber to the subconjunctival space, bypassing the resistance of the trabecular meshwork. In this study we report the results of this technique as a favorable option in the treatment of OAG for its benefits in term of efficacy and safety, either alone or in combination with cataract surgery. This is a retrospective, single-center study conducted in consecutive OAG patients, who underwent Xen45 Gel Stent implantation alone or in combination with phacoemulsification, from October 2018 to June 2019. The primary endpoint of the study was to evaluate the reduction of both IOP and number of antiglaucoma medications at 12 months. The secondary endpoint was to correlate filtering bleb morphology evaluated by means of anterior segment OCT with efficacy in IOP lowering and eventual further procedures requirement. Data were recorded on Microsoft Excel and study analysis was performed using Microsoft Excel and SPSS (IBM). Mean values with standard deviations were calculated for IOPs and number of antiglaucoma medications at all points. Kolmogorov-Smirnov test showed that IOP followed a normal distribution at all time, therefore the paired Student’s T test was used to compare baseline and postoperative mean IOP. Correlation between postoperative Day 1 IOP and Month 12 IOP was evaluated using Pearson coefficient. Thirty-six eyes of 36 patients were evaluated. As compared to baseline, mean IOP and the mean number of antiglaucoma medications significantly decreased from 27,33 ± 7,67 mmHg to 16,3 ± 2,89 mmHg (38,8% reduction) and from 2,64 ± 1,39 to 0,42 ± 0,8 (84% reduction), respectively, at 12 months after surgery (both p < 0,001). According to bleb morphology, eyes were divided in uniform group (n=8, 22,2%), subconjunctival separation group (n=5, 13,9%), microcystic multiform group (n=9, 25%) and multiple internal layer group (n=14, 38,9%). Comparing to baseline, there was no significative difference in IOP between the 4 groups at month 12 follow-up visit. Adverse events included bleb function decrease (n=14, 38,9%), hypotony (n=8, 22,2%) and choroidal detachment (n=2, 5,6%). All eyes presenting bleb flattening underwent needling and MMC injection. The higher percentage of patients that required secondary needling was in the uniform group (75%), with a significant difference between the groups (p=0,03). Xen45 gel stent, either alone or in combination with phacoemulsification, provided a significant lowering in both IOP and medical antiglaucoma treatment and an elevated safety profile.

Keywords: anterior segment OCT, bleb morphology, micro-invasive glaucoma surgery, open angle glaucoma, Xen45 gel implant

Procedia PDF Downloads 100

Authors: Rob Schindler

Abstract:

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 141

Authors: Wonil Nam, Xiang Ren, Inyoung Kim, Masoud Agah, Wei Zhou

Abstract:

Despite its ultrasensitive detection capability, surface-enhanced Raman spectroscopy (SERS) faces challenges as a quantitative biochemical analysis tool due to the significant dependence of local field intensity in hotspots on nanoscale geometric variations of plasmonic nanostructures. Therefore, despite enormous progress in plasmonic nanoengineering of high-performance SERS devices, it is still challenging to quantitatively correlate the measured SERS signals with the actual molecule concentrations at hotspots. A significant effort has been devoted to developing SERS calibration methods by introducing internal standards. It has been achieved by placing Raman tags at plasmonic hotspots. Raman tags undergo similar SERS enhancement at the same hotspots, and ratiometric SERS signals for analytes of interest can be generated with reduced dependence on geometrical variations. However, using Raman tags still faces challenges for real-world applications, including spatial competition between the analyte and tags in hotspots, spectral interference, laser-induced degradation/desorption due to plasmon-enhanced photochemical/photothermal effects. We show that electronic Raman scattering (ERS) signals from metallic nanostructures at hotspots can serve as the internal calibration standard to enable quantitative SERS analysis and improve biostatistical analysis. We perform SERS with Au-SiO₂ multilayered metal-insulator-metal nano laminated plasmonic nanostructures. Since the ERS signal is proportional to the volume density of electron-hole occupation in hotspots, the ERS signals exponentially increase when the wavenumber is approaching the zero value. By a long-pass filter, generally used in backscattered SERS configurations, to chop the ERS background continuum, we can observe an ERS pseudo-peak, IERS. Both ERS and SERS processes experience the |E|⁴ local enhancements during the excitation and inelastic scattering transitions. We calibrated IMRS of 10 μM Rhodamine 6G in solution by IERS. The results show that ERS calibration generates a new analytical value, ISERS/IERS, insensitive to variations from different hotspots and thus can quantitatively reflect the molecular concentration information. Given the calibration capability of ERS signals, we performed label-free SERS analysis of living biological systems using four different breast normal and cancer cell lines cultured on nano-laminated SERS devices. 2D Raman mapping over 100 μm × 100 μm, containing several cells, was conducted. The SERS spectra were subsequently analyzed by multivariate analysis using partial least square discriminant analysis. Remarkably, after ERS calibration, MCF-10A and MCF-7 cells are further separated while the two triple-negative breast cancer cells (MDA-MB-231 and HCC-1806) are more overlapped, in good agreement with the well-known cancer categorization regarding the degree of malignancy. To assess the strength of ERS calibration, we further carried out a drug efficacy study using MDA-MB-231 and different concentrations of anti-cancer drug paclitaxel (PTX). After ERS calibration, we can more clearly segregate the control/low-dosage groups (0 and 1.5 nM), the middle-dosage group (5 nM), and the group treated with half-maximal inhibitory concentration (IC50, 15 nM). Therefore, we envision that ERS calibrated SERS can find crucial opportunities in label-free molecular profiling of complicated biological systems.

Keywords: cancer cell drug efficacy, plasmonics, surface-enhanced Raman spectroscopy (SERS), SERS calibration

Procedia PDF Downloads 109

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

Procedia PDF Downloads 229

Authors: Victoria L. Chester, Usha Kuruganti

Abstract:

The forest industry is a major economic sector of Canada and also one of the most dangerous industries for workers. The use of mechanized mobile forestry harvesting machines has successfully reduced the incidence of injuries in forest workers related to manual labor. However, these machines have also created additional concerns, including a high machine operation learning curve, increased the length of the workday, repetitive strain injury, cognitive load, physical and mental fatigue, and increased postural loads due to sitting in a confined space. It is critical to obtain objective performance data for employers to develop appropriate work practices for this industry, however ergonomic field studies of this industry are lacking mainly due to the difficulties in obtaining comprehensive data while operators are cutting trees in the woods. The purpose of this study was to establish a measurement and experimental protocol to examine the effects of worker skill level and movement training speed (joystick crane speed) on harvesting performance using a forestry simulator. A custom wrist angle measurement device was developed as part of the study to monitor Euler angles during operation of the simulator. The device of the system consisted of two accelerometers, a Bluetooth module, three 3V coin cells, a microcontroller, a voltage regulator and an application software. Harvesting performance and crane data was provided by the simulator software and included tree to frame collisions, crane to tree collisions, boom tip distance, number of trees cut, etc. A pilot study of 3 operators with various skill levels was tested to identify factors that distinguish highly skilled operators from novice or intermediate operators. Dependent variables such as reaction time, math skill, past work experience, training movement speed (e.g. joystick control speeds), harvesting experience level, muscle activity, and wrist biomechanics were measured and analyzed. A 10-channel wireless surface EMG system was used to monitor the amplitude and mean frequency of 10 upper extremity muscles during pre and postperformance on the forestry harvest stimulator. The results of the pilot study showed inconsistent changes in median frequency pre-and postoperation, but there was the increase in the activity of the flexor carpi radialis, anterior deltoid and upper trapezius of both arms. The wrist sensor results indicated that wrist supination and pronation occurred more than flexion and extension with radial-ulnar rotation demonstrating the least movement. Overall, wrist angular motion increased as the crane speed increased from slow to fast. Further data collection is needed and will help industry partners determine those factors that separate skill levels of operators, identify optimal training speeds, and determine the length of training required to bring new operators to an efficient skill level effectively. In addition to effective and employment training programs, results of this work will be used for selective employee recruitment strategies to improve employee retention after training. Further, improved training procedures and knowledge of the physical and mental demands on workers will lead to highly trained and efficient personnel, reduced risk of injury, and optimal work protocols.

Keywords: EMG, forestry, human factors, wrist biomechanics

Procedia PDF Downloads 113

Authors: Dmitriy Berillo, Areej K. A. Al-Jwaid, Jonathan L. Caplin, Andrew Cundy, Irina Savina

Abstract:

Chlorophenols (CPs) are used as a precursor in the production of higher CPs and dyestuffs, and as a preservative. Contamination by CPs of the ground water is located in the range from 0.15-100mg/L. The EU has set maximum concentration limits for pesticides and their degradation products of 0.1μg/L and 0.5μg/L, respectively. People working in industries which produce textiles, leather products, domestic preservatives, and petrochemicals are most heavily exposed to CPs. The International Agency for Research on Cancers categorized CPs as potential human carcinogens. Existing multistep water purification processes for CPs such as hydrogenation, ion exchange, liquid-liquid extraction, adsorption by activated carbon, forward and inverse osmosis, electrolysis, sonochemistry, UV irradiation, and chemical oxidation are not always cost effective and can cause the formation of even more toxic or mutagenic derivatives. Bioremediation of CPs derivatives utilizing microorganisms results in 60 to 100% decontamination efficiency and the process is more environmentally-friendly compared with existing physico-chemical methods. Microorganisms immobilized onto a substrate show many advantages over free bacteria systems, such as higher biomass density, higher metabolic activity, and resistance to toxic chemicals. They also enable continuous operation, avoiding the requirement for biomass-liquid separation. The immobilized bacteria can be reused several times, which opens the opportunity for developing cost-effective processes for wastewater treatment. In this study, we develop a bioremediation system for CPs based on macroporous materials, which can be efficiently used for wastewater treatment. Conditions for the preparation of the macroporous material from specific bacterial strains (Pseudomonas mendocina and Rhodococus koreensis) were optimized. The concentration of bacterial cells was kept constant; the difference was only the type of cross-linking agents used e.g. glutaraldehyde, novel polymers, which were utilized at concentrations of 0.5 to 1.5%. SEM images and rheology analysis of the material indicated a monolithic macroporous structure. Phenol was chosen as a model system to optimize the function of the cryogel material and to estimate its enzymatic activity, since it is relatively less toxic and harmful compared to CPs. Several types of macroporous systems comprising live bacteria were prepared. The viability of the cross-linked bacteria was checked using Live/Dead BacLight kit and Laser Scanning Confocal Microscopy, which revealed the presence of viable bacteria with the novel cross-linkers, whereas the control material cross-linked with glutaraldehyde(GA), contained mostly dead cells. The bioreactors based on bacteria were used for phenol degradation in batch mode at an initial concentration of 50mg/L, pH 7.5 and a temperature of 30°C. Bacterial strains cross-linked with GA showed insignificant ability to degrade phenol and for one week only, but a combination of cross-linking agents illustrated higher stability, viability and the possibility to be reused for at least five weeks. Furthermore, conditions for CPs degradation will be optimized, and the chlorophenol degradation rates will be compared to those for phenol. This is a cutting-edge bioremediation approach, which allows the purification of waste water from sustainable compounds without a separation step to remove free planktonic bacteria. Acknowledgments: Dr. Berillo D. A. is very grateful to Individual Fellowship Marie Curie Program for funding of the research.

Keywords: bioremediation, cross-linking agents, cross-linked microbial cell, chlorophenol degradation

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Authors: Divya SY. Ang, Mark B. Tan, Nicholas EM. Yeo, Siti RB. Sudirman, Khong Yik Chew

Abstract:

Introduction: The importance of the amalgamation of technological and engineering advances with surgical principles of reconstruction cannot be overemphasized. With earlier detection of cancer, consequences of high-speed living and neglect, like traumatic injuries and infection, resulting in increasingly younger patients with bone defects. This may result in malformations and suboptimal function that is more noticeable and palpable in the younger, active demographic. Our team proposes a technique that encapsulates a mesh of multidisciplinary effort, tissue engineering and reconstructive principles. Methods/Materials: Our patient was a young competitive footballer in his early 30s who was diagnosed with submandibular adenoid cystic carcinoma with bony involvement. He was thus counselled for a right hemi mandibulectomy, the floor of mouth resection, right selective neck dissection, tracheostomy, and free fibular flap reconstruction of his mandible and required post-operative radiotherapy. Being young and in his prime sportsman years, he was unable to accept the morbidities associated with using his fibula to reconstruct his mandible despite it being the gold standard reconstructive option. The fibula is an ideal vascularized bone flap because it’s reliable and easily shaped with relatively minimal impact on functional outcomes. The fibula contributes to 30% of weightbearing and is the attachment for the lateral compartment muscles; it is stronger in footballers concerning lateral bending. When harvesting the fibula, the distal 6-8cm and up to 10% of the total length is preserved to maintain the ankle’s stability, thus, minimizing the impact on daily activities. There are studies that have noted gait variability post-operatively. Therefore, returning to a premorbid competitive level may be doubtful. To improve his functional outcomes, the decision was made to try and restore the fibula's form and function. Using the concept of Fused Deposition Modelling (FDM), our team comprising of Plastics, Otolaryngology, Orthopedics and Radiology, worked with Osteopore to design a 3D bioresorbable implant to regenerate the fibula defect (14.5cm). Bone marrow was harvested via reaming the contralateral hip prior to the wide resection. 30mls of his blood was obtained for extracting platelet rich plasma. These were packed into the Osteopore 3D-printed bone scaffold. This was then secured into the fibula defect with titanium plates and screws. The flexor hallucis longus and soleus were anchored along the construct and intraosseous membrane, done in a single setting. Results: He was reviewed closely as an outpatient over 10 months post operatively. He reported no discernable loss or difference in ankle function. He is satisfied and back in training and our team has video and photographs that substantiate his progress. Conclusion: FDM allows regeneration of long bone defects. However, we aimed to also restore his eversion and inversion that is imperative for footballers and hence reattached his previously dissected muscles along the length of the Osteopore implant. We believe that the reattachment of the muscle stabilizes not only the construct but allows optimum muscle tensioning when moving his ankle. This is a simple but effective technique in restoring complete function and form in a young patient whose minute muscle control is imperative to life.

Keywords: fused deposition modelling, functional reconstruction, lower limb bony defects, regenerative surgery, 3D printing, tissue engineering

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Authors: Ananya Barui, Provas Banerjee, Jyotirmoy Chatterjee

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Application of optical technology in medicine and biology has a long track-record. In this endeavor, OCT is able to attract both engineers and biologists to work together in the field of photonics for establishing a striking non-invasive imaging technology. In contrast to other in vivo imaging modalities like Raman imaging, confocal imaging, two-photon microscopy etc. which can perform in vivo imaging upto 100-200 micron depth due to limitation in numerical aperture or scattering, however, OCT can achieve high-resolution imaging upto few millimeters of tissue structures depending on their refractive index in different anatomical location. This tomographic system depends on interference of two light waves in an interferometer to produce a depth profile of specimen. In wound healing, frequent collection of biopsies for follow-up of repair process could be avoided by such imaging technique. Real time skin OCT (the optical biopsy) has efficacy in deeper and faster illumination of cutaneou tissue to acquire high resolution cross sectional images of their internal micro-structure. Swept Source-OCT (SS-OCT), a novel imaging technique, can generate high-speed depth profile (~ 2 mm) of wound at a sweeping rate of laser with micron level resolution and optimum coherent length of 5-6 mm. Normally multi-layered skin tissue depicts different optical properties along with variation in thickness, refractive index and composition (i.e. keratine layer, water, fat etc.) according to their anatomical location. For instance, stratum corneum, the upper-most and relatively dehydrated layer of epidermis reflects more light and produces more lucid and a sharp demarcation line with rest of the hydrated epidermal region. During wound healing or regeneration, optical properties of cutaneous tissue continuously altered with maturation of wound bed. More mature and less hydrated tissue component reflects more light and becomes visible as a brighter area in comparison to immature region which content higher amount water or fat that depicts as a darker area in OCT image. Non-healing wound possess prolonged inflammation and inhibits nascent proliferative stage. Accumulation of necrotic tissues also prevents the repair of non-healing wounds. Due to high resolution and potentiality to reflect the compositional aspects of tissues in terms of their optical properties, this tomographic method may facilitate in differentiating non-healing and acute wounds in addition to clinical observations. Non-invasive OCT offers better insight regarding specific biological status of tissue in health and pathological conditions, OCT images could be associated with histo-pathological ‘gold standard’. This correlated SS-OCT and microscopic evaluation of the wound edges can provide information regarding progressive healing and maturation of the epithelial components. In the context of searching analogy between two different imaging modalities, their relative performances in imaging of healing bed were estimated for probing an alternative approach. Present study validated utility of SS-OCT in revealing micro-anatomic structure in the healing bed with newer information. Exploring precise correspondence of OCT images features with histo-chemical findings related to epithelial integrity of the regenerated tissue could have great implication. It could establish the ‘optical biopsy’ as a potent non-invasive diagnostic tool for cutaneous pathology.

Keywords: histo-pathology, non invasive imaging, OCT, wound healing

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Authors: Adela Diepoltova, Klara Konecna, Ondrej Jandourek, Petr Nachtigal

Abstract:

A loss of control over antibiotic-resistant pathogens has become a global issue due to severe and often untreatable infections. This state is reflected in complicated treatment, health costs, and higher mortality. All these factors emphasize the urgent need for the discovery and development of new anti-infectives. One of the most common pathogens mentioned in the phenomenon of antibiotic resistance are bacteria of the genus Staphylococcus. These bacterial agents have developed several mechanisms against the effect of antibiotics. One of them is biofilm formation. In staphylococci, biofilms are associated with infections such as endocarditis, osteomyelitis, catheter-related bloodstream infections, etc. To author's best knowledge, no validated and standardized methodology evaluating candidate compound activity against staphylococcal biofilms exists. However, a variety of protocols for in vitro drug activity testing has been suggested, yet there are often fundamental differences. Based on our experience, a key methodological step that leads to credible results is to form a robust biofilm with appropriate attributes such as firm adherence to the substrate, a complex arrangement in layers, and the presence of extracellular polysaccharide matrix. At first, for the purpose of drug antibiofilm activity evaluation, the focus was put on various conditions (supplementation of cultivation media by human plasma/fetal bovine serum, shaking mode, the density of initial inoculum) that should lead to reproducible and robust in vitro staphylococcal biofilm formation in microtiter plate model. Three model staphylococcal reference strains were included in the study: Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (ATCC 43300), and Staphylococcus epidermidis (ATCC 35983). The total biofilm biomass was quantified using the Christensen method with crystal violet, and results obtained from at least three independent experiments were statistically processed. Attention was also paid to the viability of the biofilm-forming staphylococcal cells and the presence of extracellular polysaccharide matrix. The conditions that led to robust biofilm biomass formation with attributes for biofilms mentioned above were then applied by introducing an alternative method analogous to the commercially available test system, the Calgary Biofilm Device. In this test system, biofilms are formed on pegs that are incorporated into the lid of the microtiter plate. This system provides several advantages (in situ detection and quantification of biofilm microbial cells that have retained their viability after drug exposure). Based on our preliminary studies, it was found that the attention to the peg surface and substrate on which the bacterial biofilms are formed should also be paid to. Therefore, further steps leading to the optimization were introduced. The surface of pegs was coated by human plasma, fetal bovine serum, and L-polylysine. Subsequently, the willingness of bacteria to adhere and form biofilm was monitored. In conclusion, suitable conditions were revealed, leading to the formation of reproducible, robust staphylococcal biofilms in vitro for the microtiter model and the system analogous to the Calgary biofilm device, as well. The robustness and typical slime texture could be detected visually. Likewise, an analysis by confocal laser scanning microscopy revealed a complex three-dimensional arrangement of biofilm forming organisms surrounded by an extracellular polysaccharide matrix.

Keywords: anti-biofilm drug activity screening, in vitro biofilm formation, microtiter plate model, the Calgary biofilm device, staphylococcal infections, substrate modification, surface coating

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Authors: Hooshag Asadi Haroni, Maryam Veiskarami, Yongjun Lu

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The Dalli gold-rich porphyry deposit (17 Mt @ 0.5% Cu and 0.65 g/t Au) is located in the Urumieh-Dokhtar Magmatic Arc (UDMA), a small segment of the Tethyan metallogenic belt, hosting several porphyry Cu (Mo-Au) systems in Iran. This research characterizes the Dalli deposit to define exploration criteria in advanced exploration such as the drilling of possible blind porphyry centers. Geological map, trench/drill hole geochemical and ground magnetic data, and age dating and isotope trace element analyses, carried out at the John De Laeter Research Center of Curtin University, were used to characterize the Delli deposit. Mineralization at Dalli is hosted by NE-trending quartz-diorite porphyry stocks (~ 200m in diameter) intruded by a wall-rock andesite porphyry. Disseminated and stockwork Cu-Au mineralization is related to potassic alteration, comprising magnetite, late K-feldspar and biotite, and quartz-sericite-specularite overprint, surrounded by extensive barren argillic and propylitic alterations. In the peripheries of the porphyry centers, there are N-trending vuggy quartz veins, hosting epithermal Au-Ag-As-Sb mineralization. Geochemical analyses of drill core samples showed that the core of the porphyry stocks is low-grade, whereas the high-grade disseminated and stockwork mineralization (~ 1% Cu and ~ 1.2 g/t Au) occurred at the contact of the porphyry stocks and andesite porphyry. Geochemical studies of the drill hole and trench samples showed a strong correlation between Cu and Au and both show a second-order correlation with Fe and As. Magnetic survey revealed two significant magnetic anomalies, associated with intensive potassic alteration, in the reduced-to-the-pole magnetic map of the area. A relatively weaker magnetic anomaly, showing no surface porphyry expressions, is located on a lithocap, consisting of advanced argillic alteration, vuggy quartz veins, and surface expressions of epithermal geochemical signatures. The association of the lithocap and the weak magnetic anomaly could be indicative of a hidden mineralized porphyry center. Litho-geochemical analyses of the least altered Dalli intrusions and volcanic rocks indicated high Sr/Y (49-61) and Eu/Eu* (0.89-0.92), features typical of Cu porphyries. The U-Pb dating of zircons of the mineralized quartz diorite and andesite porphyry, carried out by laser ablation inductively coupled plasma mass spectrometry, yielded magmatic crystallization ages of 15.4-16.0 Ma (Middle Miocene). The zircon trace element concentrations of Dalli are characterized by high Eu/Eu* (0.3-0.8), (Ce/Nd)/Y (0.01-0.3), and 10000*(Eu/Eu*)/Y (2-15) ratios, similar to fertile porphyry suites such as the giant Sar-Cheshmeh and Qulong porphyry Cu deposits along the Tethyan belt. This suggests that the Middle Miocene Dalli intrusions are fertile and require extensive deep drillings to define their potential. Chondrite-normalized rare earth element (REE) patterns show no significant Eu anomalies, and are characterized by light-REE enrichments (La/Sm)n = 2.57–6.40). In normalized multi-element diagrams, analyzed rocks are characterized by enrichments in large ion lithophile elements (LILE) and depletions in high field strength elements (HFSE), and display typical features of subduction-related calc-alkaline magmas. The characteristics of the Dalli deposit provided several recognition criteria for detailed exploration of Cu-Au porphyry deposits and highlighted the importance of the UDMA as a potentially significant, economically important, but relatively underexplored porphyry province.

Keywords: porphyry, gold, geochronology, magnetic, exploration

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Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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