Multiple Processing Steps Research Articles

Identification of Debris‐Flow Channels Using High‐Resolution Topographic Data: A Case Study in the Quebrada del Toro, NW Argentina

AbstractResolving Earth's surface at the meter scale is essential for an improved understanding of the dynamics of mass‐movement processes. In this study, we explore the applicability and potential of digital elevation models (DEMs) derived from stereophotogrammetry to detect debris‐flow channels in the Quebrada del Toro in the northwestern Argentine Andes. Our analysis relies on a high‐resolution (3 m) DEM created from SPOT‐7 tri‐stereo satellite data. We carefully validated DEM quality with ∼6,000 differential GPS points and identified optimal parameters for DEM generation in high‐relief terrain. After multiple processing steps, we achieved an accuracy of 0.051 ± 1.915 m (1σ) using n = 3,139 control points with cm precision. Previous studies have used the drainage area and slope framework to identify topographic signatures of debris flows within a catchment. We built upon this and investigated individual river‐channel segments using connected‐component (CC) analysis on meter‐scale topographic data. We define CC as segments of similar slope along the channel profile. Based on seven manually identified debris‐flow catchments, we developed a debris‐flow similarity index using component length and mean channel‐segment slope and identified channel segments that have likely been shaped by debris flows. The presented approach has the potential to resolve intra‐catchment variability of transport processes, allows to constrain the extent of debris‐flow channels more precisely than slope‐area analysis, and highlights the versatility of combined space‐ and field‐based observations for natural‐hazard assessments.

Observation of 4th-order water oxidation kinetics by time-resolved photovoltage spectroscopy

Artificial photo-driven water oxidation has been proposed over half a century through a four-charge involved multiple-step oxygen evolution process. However, the knowledge of the intrinsic activity, such as the rate-law of the water oxidation reactions, has been inadequately studied. Up to date, the highest order reported is the third one under photoelectrochemical condition. In this work, we identified the fourth-order charge decay reactions on hematite by using a time-resolved surface photovoltage probe technique. A theoretical turnover frequency (TOF) > 100nm-2·s-1 can be expected for O2 molecules when the hole density >0.1nm-2. This work demonstrates a facile and robust method to investigate the high-order reaction kinetics. More excitingly, this research built the bridge between the rate-law, rate-determining step, and energy barrier of intermediates.

A Novel Processing Model for P300 Brainwaves Detection

Event-related potential (ERP) is a distinctive pattern of brain activity that is elicited by the brain’s sensitivity and cognition whereas P300 evoked potential changes in cognitive functions. Since P300 wave is a cognitive response across multiple brain channels correlated between the measured electroencephalogram (EEG) and deviant stimulus in a specific period, it requires a suitable signal processing application for interpretation. Moreover, multiple steps of data processing under neuroscience criteria make the P300 reflection difficult to analyze by common methods. Therefore, this study proposes the processing model for brainwave applications based on P300 peak signal detection in multiple brain channels. This study applies 64 channels ERP datasets throughout bandpass filter in fast Fourier transform (FFT) with the specific ranges of signal processing while ERP averaging is applied as a feature extraction method. Furthermore, the experimental metadata is applied with the filtered P300 peak signals in channel classification via a machine learning method, the Decision Tree. The experimental results indicate the accurate mental reflection of P300 evoked potential in different brain channels with high classification accuracy relying on the contrast condition throughout the original data source averaged across the individual electrodes.

Optimisation of an Automated DNA Extraction Method for Bone and Teeth Samples and Applicability to Two Forensic Cases

Bones and teeth are highly challenging sources of DNA in forensic science and human remains identification, requiring multiple laborious processing steps. In this study, we compared an organic phenol–chloroform method to the QIAamp® DNA Investigator and PrepFiler Express BTA™ methods in order to identify the most efficient automated DNA extraction method for bones and teeth. Results from individual tooth powder replicates showed that the PrepFiler Express BTA™ method extracted the highest yields of DNA per mg of tooth powder, returning a minimum of 20/21 PowerPlex® 21 loci. Samples extracted using the organic extraction or QIAamp® DNA Investigator methods produced PowerPlex® 21 profiles displaying a ski-slope morphology. The improved DNA quality and yield from the PrepFiler Express BTA™ method was verified using aged samples, where higher DNA yields per mg of powder and more informative profiles were obtained. Furthermore, the PrepFiler Express BTA™ method subsequently provided useful DNA profiles for two forensic cases involving degraded bone samples. Overall, this study showed that the PrepFiler Express BTA™ chemistry is a reliable and robust method for DNA extraction from bone and teeth samples, and will allow larger numbers of samples to be efficiently extracted in the event of a Disaster Victim Identification event.

A simple route to prepare supramolecular block copolymers using telechelic polystyrene/polydimethylsiloxane pairs

AbstractWhile supramolecular block copolymer (BCP) self‐assembly has been widely studied over the past decades as an effective means to generate functional nanomaterials, most of these systems require multiple steps of synthesis and processing. In this report, we introduce a facile approach to form linear multiblock copolymers by directly blending telechelic homopolymer pairs, using di‐sulfonated polystyrene and commercially available, aminopropyl terminated polydimethylsiloxane. A series of model multiblock copolymers were prepared, in which proton transfers between polymer chain ends enable the formation of strong ionic associations. These ionic junctions not only significantly enhance thin film stability of polymer blends by forming higher molecular weight copolymers, but also improve the chemical incompatibility between different segments, resulting in ordered nanostructures upon self‐assembly. These include different morphologies such as lamellae and cylinders. We also demonstrate that feature size of these BCPs can be adjusted by varying the molecular weight of the homopolymers, with a smallest domain spacing of approximately 12.9 nm being obtained. Utilizing low‐cost and widely available polymers as building blocks, our simple and efficient supramolecular assembly strategy for forming multiblock copolymers may provide a promising platform for cost‐efficient nanomanufacturing of polymeric materials. © 2021 Society of Industrial Chemistry.

Metagenomic Sequencing for Identification of Xylella fastidiosa from Leaf Samples.

ABSTRACTXylella fastidiosa (Xf) is a globally distributed plant-pathogenic bacterium. The primary control strategy for Xf diseases is eradicating infected plants; therefore, timely and accurate detection is necessary to prevent crop losses and further pathogen dispersal. Conventional Xf diagnostics primarily relies on quantitative PCR (qPCR) assays. However, these methods do not consider new or emerging variants due to pathogen genetic recombination and sensitivity limitations. We developed and tested a metagenomics pipeline using in-house short-read sequencing as a complementary approach for affordable, fast, and highly accurate Xf detection. We used metagenomics to identify Xf to the strain level in single- and mixed-infected plant samples at concentrations as low as 1 pg of bacterial DNA per gram of tissue. We also tested naturally infected samples from various plant species originating from Europe and the United States. We identified Xf subspecies in samples previously considered inconclusive with real-time PCR (quantification cycle [Cq], >35). Overall, we showed the versatility of the pipeline by using different plant hosts and DNA extraction methods. Our pipeline provides taxonomic and functional information for Xf diagnostics without extensive knowledge of the disease. This pipeline demonstrates that metagenomics can be used for early detection of Xf and incorporated as a tool to inform disease management strategies.IMPORTANCE Destructive Xylella fastidiosa (Xf) outbreaks in Europe highlight this pathogen’s capacity to expand its host range and geographical distribution. The current disease diagnostic approaches are limited by a multiple-step process, biases to known sequences, and detection limits. We developed a low-cost, user-friendly metagenomic sequencing tool for Xf detection. In less than 3 days, we were able to identify Xf subspecies and strains in field-collected samples. Overall, our pipeline is a diagnostics tool that could be easily extended to other plant-pathogen interactions and implemented for emerging plant threat surveillance.

Characterization of blast furnace flue dust- an assessment for its utilization

Industrial growth of any country governs its magnitude of development. India after independence laid stress on industrial revolution. Of various industrial set up, steel industry took a leading role across the globe. Manufacturing of steel is a multiple step process. Steel industry is considered as resource intensive and pollution prone as well. In present study flue dust from Bhilai steel plant is examined to assess its potential to be reused. Considering its volume of generation and composition, it requires through characterization (physical and chemical) and detailed beneficiation study before its utilization. The study concluded that significant volume of iron and carbon can be recovered and utilized subsequently. However, the scale of utilization is dependent on the composition of flue dust.

Ultra-Small Bismuth Nanoparticle Synthesis from a Wire Precursor Via Atmospheric Pressure Plasma

Metal nanoparticles have shown interesting optical and electronic properties. At the nanoscale, metal nanoparticles exhibit a transition into a semiconductor behaviour and bandgap widening due to quantum confinement.1,2 Bismuth is a metal of great interest due to good thermoelectric properties,2 high density of states and potential for carrier multiplication. These are highly important attributes for optoelectronic applications. Commonly employed methods to synthesise bismuth nanostructures such nanotubes, nanorods, flakes and nanodots involve use of hazard chemicals, use of expensive vacuum equipment and/or multiple processing steps.3–5 Therefore, there is a need for a safe and low-cost synthesis method. In this regard, atmospheric pressure plasma processes are promising as they operate at ambient pressure and temperature eliminating the need of expensive vacuum equipment.Here we present work on the synthesis of bismuth nanoparticles (Bi-NPs) by a one-step atmospheric pressure plasma process from a bismuth wire, either for direct deposition in the form of films or directly dispersed in liquid. Various plasma reactor architectures are examined to study the possible deposition conditions. The synthesised Bi-NPs are studied for their morphological, chemical, optical and electronic properties. The mean diameter of these NPs is in the range of 2-3 nm and present a degree of surface oxidation after being exposed to the atmosphere. Particle size can be finely controlled by simply regulating input power and gas flow.Reference: El-sayed, M. A. Some Interesting Properties of Metals Confined in Time and Nanometer Space of Different Shapes. 34, 257–264 (2001).Zhou, G., Li, L. & Li, G. H. Semimetal to semiconductor transition and thermoelectric properties of bismuth nanotubes. J. Appl. Phys. 109, (2011).Wang, Y. W., Hong, H. & Kim, K. S. Size Control of Semimetal Bismuth Nanoparticles and the UV-Visible and IR Absorption Spectra. (2005) doi:10.1021/jp046423v.Mayorga-Martinez, C. C., Cadevall, M., Guix, M., Ros, J. & Merkoçi, A. Bismuth nanoparticles for phenolic compounds biosensing application. Biosens. Bioelectron. 40, 57–62 (2013).Sepulveda-Guzman, S. et al. In situ formation of bismuth nanoparticles through electron-beam irradiation in a transmission electron microscope. Nanotechnology 18, (2007).

A mass casualty incident of infectious diseases at the port of Hamburg: an analysis of organizational structures and emergency concepts

BackgroundThe project “ARMIHN” (Adaptive Resiliency Management in Port) focuses on strengthening the capability to act in a mass casualty incident (MCI) due to an outbreak of infectious diseases (MCI-ID). In addition to the current threat from the COVID-19 pandemic and associated outbreaks on cruise ships, previous MCI-ID were especially caused by pathogens such as Influenza virus or Norovirus. The first step was, to get an overview of processes and resources using the example of the Port of Hamburg, and to show the associated interaction of involved parties. This will serve as a basis for developing an operational strategy and offers the opportunity to optimize current work processes.MethodsA selective literature research using specified key words was performed and existing MCI concepts were received from local authorities. Identified structures and processes were analyzed in a multiple step process and also brought together through discussions in workshops with involved organizations and other experts. Additionally, the distances between the nearest rescue stations and selected hospitals from the Port of Hamburg were analyzed.ResultsThe current available concepts are proven, but an adaptation to an MCI-ID shows opportunities for a further cross-organizational development. The organizational structure of an MCI-ID in the Port of Hamburg was described, including a large number of involved organizations (n = 18). There are 17 involved fire and rescue stations and the port can be reached from these locations within 6 to 35 min. Based on their specialist expertise, 14 of the 31 listed clinics were selected.ConclusionThe purpose of the study was to provide an analysis of the current situation and show how involved parties would cope an MCI. A description of processes and resources at the Port of Hamburg will be used when designing a management plan for responding to an MCI-ID.

Improving the single crystal LiNi0.8Co0.1Mn0.1O2 cathode material performance by fluorine doping

With the rapid popularization of new energy vehicles, the demands for high energy density power batteries and related cathode materials are becoming increasingly urgent. Layered Li–Ni–Co–Mn–O cathode materials are attracting much attention because of their high specific capacity; however, their cycling and high voltage performance need to be further improved. Herein, single crystal structure LiNi0.8Co0.1Mn0.1O2 materials, prepared using a multiple-step calcination process, are further controllably doped with fluorine to improve the Li storage performance. Fluorine doping not only improves the crystal space but also increases the Co3+ and lattice oxygen content, therefore promoting the lithium ion diffusion and crystal structure stability of layered LiNi0.8Co0.1Mn0.1O2. With an appropriate amount of fluorine doping, the LiNi0.8Co0.1Mn0.1O2 single crystal material demonstrates a remarkable specific capacity of 202.7 mAh g−1 (0.1C) and a high capacity retention of 86.6% after 100 cycles (1.0C), higher than the control sample and promising for application in lithium-ion batteries.

A direct transfer solution for digital laser printing of CVD graphene

State-of-the-art methods for printing highly resolved pixels of two-dimensional (2D) materials on technologically important substrates typically involve multiple and time-consuming processing steps which increase device fabrication complexity and the risk of impurity contamination. This work introduces an alternative printing approach based on the laser induced forward transfer (LIFT) technique for the successful digital transfer of graphene, the 2D material par excellence. Using LIFT, CVD graphene pixels of 30 μm × 30 μm in size are transferred on SiO2/Si and flexible polymer substrates. The potential of upscaling this novel approach by reaching sizes of up to 300 μm × 300 μm for transferred graphene patches is also demonstrated. The feasibility of laser-induced transfer of graphene is corroborated with ab initio molecular dynamics simulations which elucidate atomic-scale details of the seamless detachment of the monolayer from a metallic donor surface and its subsequent attachment to a receiver substrate.

Sox9CreER-mediated deletion of β-catenin in palatal mesenchyme results in delayed palatal elevation accompanied with repressed canonical Wnt signaling and reduced actin polymerization.

Cleft palate is a good model to pushing us toward a deeper understanding of the molecular mechanisms of spatiotemporal patterns in tissues and organisms because of the multiple-step processes such as elevation and fusion. Previous studies have shown that the epithelial β-catenin is crucial for palatal fusion, however, the function of the mesenchymal β-catenin remains elusive. We investigate the role of mesenchymal β-catenin in palatal development by generating a β-catenin conditional knockout mouse (CKO) (Sox9CreER; Ctnnb1F/F ). We found that the CKO mice exhibited delayed palatal elevation, leading to cleft palate in both in vivo and ex vivo. Abnormal cell proliferation and repressed mesenchymal canonical Wnt signaling were found in the CKO palate. Interestingly, Filamentous actin (F-actin) polymerization was significantly reduced in the palatal mesenchyme of mutant embryos. Furthermore, overexpression of adenovirus-mediated transfection with Acta1 in the mutant could help to elevate the palatal shelves but could not prevent cleft palate in ex vivo. Our results suggest that conditionally knock out β-catenin in the palatal mesenchyme by Sox9CreER leading to delayed palatal elevation, which results in repressed mesenchymal canonical Wnt signaling, decreased cell proliferation, and reduced actin polymerization, finally causes cleft palate.

Multi-temporal cloud detection based on robust PCA for optical remote sensing imagery

Cloud detection is an essential pre-processing step for optical remote sensing imagery in various applications due to the huge negative effect of cloud occlusion. Multi-temporal cloud detection methods are usually more effective than single-image based methods by providing extra temporal information, which is a worthwhile supplement to spatial-spectral information for distinguishing clouds from clear-sky observations. Nevertheless, most of the existing multi-temporal cloud detection algorithms cannot estimate the cloud-free reference background accurately, especially when pixels have no or very few clear-sky observations in time series data, which limits the performance of cloud detection to a large degree. To deal with this problem, a novel multi-temporal cloud detection method based on robust principal component analysis (MCD-RPCA) is proposed for optical remote sensing imagery. Firstly, several spectral tests are performed to extract spectral features based on the physical attributes of clouds and obtain an initial rough cloud mask. Secondly, a low-rank matrix decomposition model, known as robust principal component analysis (RPCA), is constructed based on multi-temporal images to estimate the cloud-free background. By detecting the change between the cloudy image and the estimated clear-sky background image, a change cloud mask can be obtained by the extraction of temporal information. A refined cloud mask is then acquired by taking the intersection of the initial cloud mask and the change cloud mask. Lastly, multiple spatial morphological processing steps are implemented to incorporate the spatial information to further refine the cloud detection map. By fully exploiting the spectral-temporal-spatial features of clouds in optical remote sensing images, the proposed MCD-PRCA method seeks to facilitate the estimation of the clear background component and support the improved detection of cloudy pixels. The performance of MCD-RPCA was evaluated on four Landsat-8 OLI images from the Biome dataset and three popular cloud detection methods were used as benchmarks for comparisons. In general, a mean overall accuracy of 93.79% was achieved by the proposed MCD-RPCA method, outperforming the other state-of-the-art cloud detection algorithms.

Expression and prognostic significance of CBX2 in colorectal cancer: database mining for CBX family members in malignancies and vitro analyses

BackgroundThe Chromobox (CBX) domain protein family, a core component of polycomb repressive complexes 1, is involved in transcriptional repression, cell differentiation, and program development by binding to methylated histone tails. Each CBX family member plays a distinct role in various biological processes through their own specific chromatin domains, due to differences in conserved sequences of the CBX proteins. It has been demonstrated that colorectal cancer (CRC) is a multiple-step biological evolutionary process, whereas the roles of the CBX family in CRC remain largely unclear.MethodsIn the present study, the expression and prognostic significance of the CBX family in CRC were systematically analyzed through a series of online databases, including Cancer Cell Line Encyclopedia (CCLE), Oncomine, Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis (GEPIA). For in vitro verification, we performed cell cloning, flow cytometry and transwell experiments to verify the proliferation and invasion ability of CRC cells after knocking down CBX2.ResultsMost CBX proteins were found to be highly expressed in CRC, but only the elevated expression of CBX2 could be associated with poor prognosis in patients with CRC. Further examination of the role of CBX2 in CRC was performed through several in vitro experiments. CBX2 was overexpressed in CRC cell lines via the CCLE database and the results were verified by RT-qPCR. Moreover, the knockdown of CBX2 significantly suppressed CRC cell proliferation and invasion. Furthermore, the downregulation of CBX2 was found to promote CRC cell apoptosis.ConclusionsBased on these findings, CBX2 may function as an oncogene and potential prognostic biomarker. Thus, the association between the abnormal expression of CBX2 and the initiation of CRC deserves further exploration.

FAIRSCAPE: a Framework for FAIR and Reproducible Biomedical Analytics

Results of computational analyses require transparent disclosure of their supporting resources, while the analyses themselves often can be very large scale and involve multiple processing steps separated in time. Evidence for the correctness of any analysis should include not only a textual description, but also a formal record of the computations which produced the result, including accessible data and software with runtime parameters, environment, and personnel involved. This article describes FAIRSCAPE, a reusable computational framework, enabling simplified access to modern scalable cloud-based components. FAIRSCAPE fully implements the FAIR data principles and extends them to provide fully FAIR Evidence, including machine-interpretable provenance of datasets, software and computations, as metadata for all computed results. The FAIRSCAPE microservices framework creates a complete Evidence Graph for every computational result, including persistent identifiers with metadata, resolvable to the software, computations, and datasets used in the computation; and stores a URI to the root of the graph in the result’s metadata. An ontology for Evidence Graphs, EVI (https://w3id.org/EVI), supports inferential reasoning over the evidence. FAIRSCAPE can run nested or disjoint workflows and preserves provenance across them. It can run Apache Spark jobs, scripts, workflows, or user-supplied containers. All objects are assigned persistent IDs, including software. All results are annotated with FAIR metadata using the evidence graph model for access, validation, reproducibility, and re-use of archived data and software.

The impact of mediated learning on the academic writing performance of medical students in flipped and traditional classrooms: scaffolding techniques

Writing as a multiple-step process is one of the most complex and demanding skills for graduate students to master. Foreign or second language learners who are required to write for academic purposes at the university level may even find it more demanding to master. One of the ways of decreasing the burden of mastering this skill for learners is mediation, using scaffolding techniques to teach writing. Hence, having a good understanding of the impact(s) of adopting mediating or scaffolding techniques in writing classes is absolutely indispensable. To this end, the present study employed an experimental research design to investigate the impact of mediation in the flipped writing classrooms of the students of medicine. To peruse this goal, 47 medical students were selected through purposive sampling and put into control and treatment groups. Medical students in the treatment group watched teacher-made video content(s) before their writing classes. The students in this group experienced organized-interactive writing group activities in their classes. Unlike the experimental group, the students in the control group received all the instructions in the classroom and were assigned homework. The findings obtained through the ANOVA and t-test indicated that the students in the experimental group significantly outperformed their counterparts in the control group in terms of their writing. A probable conclusion could be that by requiring students to study in advance and take responsibility for their learning, flipped classroom can provide the opportunity for learners to actively construct knowledge rather than receive the information passively in the classroom. Flipped classroom can also cultivate interactive class time for teachers and enable them to invest in more fruitful academic practices, instead of asking students to spend a substantial amount of time each week doing homework independently.

Structural Factors Inducing Cracking of Brass Fittings.

Cu–Zn–Pb brasses are popular materials, from which numerous industrially and commercially used components are fabricated. These alloys are typically subjected to multiple-step processing—involving casting, extrusion, hot forming, and machining—which can introduce various defects to the final product. The present study focuses on the detailed characterization of the structure of a brass fitting—i.e., a pre-shaped medical gas valve, produced by hot die forging—and attempts to assess the factors beyond local cracking occurring during processing. The analyses involved characterization of plastic flow via optical microscopy, and investigations of the phenomena in the vicinity of the crack, for which we used scanning and transmission electron microscopy. Numerical simulation was implemented not only to characterize the plastic flow more in detail, but primarily to investigate the probability of the occurrence of cracking based on the presence of stress. Last, but not least, microhardness in specific locations of the fitting were examined. The results reveal that the cracking occurring in the location with the highest probability of the occurrence of defects was most likely induced by differences in the chemical composition; the location the crack in which developed exhibited local changes not only in chemical composition—which manifested as the presence of brittle precipitates—but also in beta phase depletion. Moreover, as a result of the presence of oxidic precipitates and the hard and brittle alpha phase, the vicinity of the crack exhibited an increase in microhardness, which contributed to local brittleness.

Single Step 2-Port Device De-Embedding Algorithm for Fixture-DUT-Fixture Network Assembly

The de-embedding of measurement fixtures is relevant for an accurate experimental characterization of radio frequency and digital electronic devices. The standard technique consists in removing the effects of the measurement fixtures by the calculation of the transfer scattering parameters (T-parameters) from the available measured (or simulated) global scattering parameters (S-parameters). The standard de-embedding is achieved by a multiple steps process, involving the S-to-T and subsequent T-to-S parameter conversion. In a typical measurement setup, two fixtures are usually placed before and after the device under test (DUT) allowing the connection of the device to the calibrated vector network analyzer coaxial ports. An alternative method is proposed in this paper: it is based on the newly developed multi-network cascading algorithm. The matrices involved in the fixture-DUT-fixture cascading gives rise to a non-linear set of equations that is in one step analytically solved in closed form, obtaining a unique solution. The method is shown to be effective and at least as accurate as the standard multi-step de-embedding one.

MiR-145 suppresses the motility of prostate cancer cells by targeting cadherin-2.

Metastasis is the main cause of poor prognosis in the advanced prostate cancer in clinic. Accumulating evidences have proposed that cell motility greatly contributes to the multiple steps of the metastatic process. MicroRNA-145 (miR-145) has been found to be downregulated in prostate cancer and serve as a putative tumor suppressor via decrease of cell growth and augmentation of cell death; however, the effects and the underlying mechanisms of miR-145 in prostate cancer cell motility have not been completely clarified. In the current study, we first demonstrated that miR-145 exerted inhibitory effects on the aggressive phenotype of the prostate cancer cells. Based on the bioinformatics analysis of the putative target genes of miR-145, we further experimentally identified a novel mechanism of miR-145 suppressing the aggressive phenotype of prostate cancer cells via directly targeting cadherin-2 (CDH2) protein translation. Re-expression of CDH2 could rescue miR-145-triggered cell migration and invasion defects. Our results suggested that miR-145 suppressed the motility of prostate cancer cells via post-transcriptional downregulation of CDH2 expression, and miR-145-CDH2 pair might serve as a potential target for intervention of prostate cancer metastasis.

The Chronotopic™ System for Pulsatile and Colonic Delivery of Active Molecules in the Era of Precision Medicine: Feasibility by 3D Printing via Fused Deposition Modeling (FDM).

The pulsatile-release Chronotopic™ system was conceived of as a drug-containing core surrounded by a coat made of swellable/soluble hydrophilic polymers, the latter being able to provide a programmable lag phase prior to drug liberation. This system was also proposed in a colon-targeting configuration, entailing a gastroresistant film to prevent early interaction of the inner coat with gastric fluids and enabling the attainment of a lag phase matching the small intestinal transit time. Over the years, various multiple-step manufacturing processes have been tested for the fabrication of the Chronotopic™ system in both its configurations. This work focused on the evaluation of 3D printing by fused deposition modeling in view of its potential towards product personalization, on demand one-step manufacturing and efficient scale down of batches. The feasibility of each part of the Chronotopic™ system was independently investigated starting from in-house made filaments, characterizing the resulting specimens for physico-technological and performance characteristics. The printing parameters identified as suitable during the set-up phase were then used to fabricate prototypes either in a single step for the pulsatile configuration or following two different fabrication approaches for the colon-targeting one.