Search results for: PQ signal filtering

Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou

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Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.

Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase

Procedia PDF Downloads 308

Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

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Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

Procedia PDF Downloads 104

Authors: Vincent Schlageter, Maroua Mestiri, Florian Denzinger, Hugo Raetzo, Michel Demierre

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Precise landslide monitoring with differential global navigation satellite system (GNSS) is well known, but technical or economic reasons limit its application by geotechnical companies. This study demonstrates the reliability and the usefulness of Geomon (Infrasurvey Sàrl, Switzerland), a stand-alone and cost-effective rover network. The system permits deploying up to 15 rovers, plus one reference station for differential GNSS. A dedicated radio communication links all the modules to a base station, where an embedded computer automatically provides all the relative positions (L1 phase, open-source RTKLib software) and populates an Internet server. Each measure also contains information from an internal inclinometer, battery level, and position quality indices. Contrary to standard GNSS survey systems, which suffer from a limited number of beacons that must be placed in areas with good GSM signal, Geomon offers greater flexibility and permits a real overview of the whole landslide with good spatial resolution. Each module is powered with solar panels, ensuring autonomous long-term recordings. In this study, we have tested the system on several sites in the Swiss mountains, setting up to 7 rovers per site, for an 18 month-long survey. The aim was to assess the robustness and the accuracy of the system in different environmental conditions. In one case, we ran forced blind tests (vertical movements of a given amplitude) and compared various session parameters (duration from 10 to 90 minutes). Then the other cases were a survey of real landslides sites using fixed optimized parameters. Sub centimetric-accuracy with few outliers was obtained using the best parameters (session duration of 60 minutes, baseline 1 km or less), with the noise level on the horizontal component half that of the vertical one. The performance (percent of aborting solutions, outliers) was reduced with sessions shorter than 30 minutes. The environment also had a strong influence on the percent of aborting solutions (ambiguity search problem), due to multiple reflections or satellites obstructed by trees and mountains. The length of the baseline (distance reference-rover, single baseline processing) reduced the accuracy above 1 km but had no significant effect below this limit. In critical weather conditions, the system’s robustness was limited: snow, avalanche, and frost-covered some rovers, including the antenna and vertically oriented solar panels, leading to data interruption; and strong wind damaged a reference station. The possibility of changing the sessions’ parameters remotely was very useful. In conclusion, the rover network tested provided the foreseen sub-centimetric-accuracy while providing a dense spatial resolution landslide survey. The ease of implementation and the fully automatic long-term survey were timesaving. Performance strongly depends on surrounding conditions, but short pre-measures should allow moving a rover to a better final placement. The system offers a promising hazard mitigation technique. Improvements could include data post-processing for alerts and automatic modification of the duration and numbers of sessions based on battery level and rover displacement velocity.

Keywords: GNSS, GSM, landslide, long-term, network, solar, spatial resolution, sub-centimeter.

Procedia PDF Downloads 89

Authors: Leila Safazadeh, Brad Berron

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Self-assembled monolayers have tremendous impact in interfacial science, due to the unique opportunity they offer to tailor surface properties. Low-density self-assembled monolayers are an emerging class of monolayers where the environment-interfacing portion of the adsorbate has a greater level of conformational freedom when compared to traditional monolayer chemistries. This greater range of motion and increased spacing between surface-bound molecules offers new opportunities in tailoring adsorption phenomena in sensing systems. In particular, we expect low-density surfaces to offer a unique opportunity to intercalate surface bound ligands into the secondary structure of protiens and other macromolecules. Additionally, as many conventional sensing surfaces are built upon gold surfaces (SPR or QCM), these surfaces must be compatible with gold substrates. Here, we present the first stable method of generating low-density self assembled monolayer surfaces on gold for the analysis of their interactions with protein targets. Our approach is based on the 2:1 addition of thiol-yne chemistry to develop new classes of y-shaped adsorbates on gold, where the environment-interfacing group is spaced laterally from neighboring chemical groups. This technique involves an initial deposition of a crystalline monolayer of 1,10 decanedithiol on the gold substrate, followed by grafting of a low-packed monolayer on through a photoinitiated thiol-yne reaction in presence of light. Orthogonality of the thiol-yne chemistry (commonly referred to as a click chemistry) allows for preparation of low-density monolayers with variety of functional groups. To date, carboxyl, amine, alcohol, and alkyl terminated monolayers have been prepared using this core technology. Results from surface characterization techniques such as FTIR, contact angle goniometry and electrochemical impedance spectroscopy confirm the proposed low chain-chain interactions of the environment interfacing groups. Reductive desorption measurements suggest a higher stability for the click-LDMs compared to traditional SAMs, along with the equivalent packing density at the substrate interface, which confirms the proposed stability of the monolayer-gold interface. In addition, contact angle measurements change in the presence of an applied potential, supporting our description of a surface structure which allows the alkyl chains to freely orient themselves in response to different environments. We are studying the differences in protein adsorption phenomena between well packed and our loosely packed surfaces, and we expect this data will be ready to present at the GRC meeting. This work aims to contribute biotechnology science in the following manner: Molecularly imprinted polymers are a promising recognition mode with several advantages over natural antibodies in the recognition of small molecules. However, because of their bulk polymer structure, they are poorly suited for the rapid diffusion desired for recognition of proteins and other macromolecules. Molecularly imprinted monolayers are an emerging class of materials where the surface is imprinted, and there is not a bulk material to impede mass transfer. Further, the short distance between the binding site and the signal transduction material improves many modes of detection. My dissertation project is to develop a new chemistry for protein-imprinted self-assembled monolayers on gold, for incorporation into SPR sensors. Our unique contribution is the spatial imprinting of not only physical cues (seen in current imprinted monolayer techniques), but to also incorporate complementary chemical cues. This is accomplished through a photo-click grafting of preassembled ligands around a protein template. This conference is important for my development as a graduate student to broaden my appreciation of the sensor development beyond surface chemistry.

Keywords: low-density self-assembled monolayers, thiol-yne click reaction, molecular imprinting

Procedia PDF Downloads 196

Authors: Andrew Gennett

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Designing for fungal development means embracing the symbiotic relationship between the living system and built environment. The potential of mycelium post-colonization is explored for the fabrication of advanced pure mycelium products, going beyond the conventional methods of aggregating materials. Fruiting induction imparts desired material properties such as enhanced environmental resistance. Production approach allows for simultaneous generation of multiple products while scaling up raw materials supply suitable for architectural applications. The following work explores the integration of fungal environmental perception with computational design of built fruiting chambers. Polyporales, are classified by their porous reproductive tissues supported by a wood-like context tissue covered by a hard waterproofing coat of hydrobpobins. Persisting for years in the wild, these species represent material properties that would be highly desired in moving beyond flat sheets of arial mycelium as with leather or bacon applications. Understanding the inherent environmental perception of fungi has become the basis for working with and inducing desired hyphal differentiation. Working within the native signal interpretation of a mycelium mass during fruiting induction provides the means to apply textures and color to the final finishing coat. A delicate interplay between meeting human-centered goals while designing around natural processes of living systems represents a blend of art and science. Architecturally, physical simulations inform model design for simple modular fruiting chambers that change as fungal growth progresses, while biological life science principles describe the internal computations occurring within the fungal hyphae. First, a form filling phase of growth is controlled by growth chamber environment. Second, an initiation phase of growth forms the final exterior finishing texture. Hyphal densification induces cellular cascades, in turn producing the classical hardened cuticle, UV protective molecule production, as well, as waterproofing finish. Upon fruiting process completion, the fully colonized spent substrate holds considerable value and is not considered waste. Instead, it becomes a valuable resource in the next cycle of production scale-up. However, the acquisition of new substrate resources poses a critical question, particularly as these resources become increasingly scarce. Pursuing a regenerative design paradigm from the environmental perspective, the usage of “agricultural waste” for architectural materials would prove a continuation of the destructive practices established by the previous industrial regime. For these residues from fields and forests serve a vital ecological role protecting the soil surface in combating erosion while reducing evaporation and fostering a biologically diverse food web. Instead, urban centers have been identified as abundant sources of new substrate material. Diverting the waste from secondary locations such as food processing centers, papers mills, and recycling facilities not only reduces landfill burden but leverages the latent value of these waste steams as precious resources for mycelium cultivation. In conclusion, working with living systems through innovative built environments for fungal development, provides the needed gain of function and resilience of mycelium products. The next generation of sustainable fungal products will go beyond the current binding process, with a focus upon reducing landfill burden from urban centers. In final considerations, biophilic material builds to an ecologically regenerative recycling production cycle.

Keywords: regenerative agriculture, mycelium fabrication, growth chamber design, sustainable resource acquisition, fungal morphogenesis, soil fertility

Procedia PDF Downloads 35