Search

The development of a non-invasive infection-specific diagnostic probe holds the potential to vastly improve early-stage detection of infection, enabling precise therapeutic intervention and potentially reducing the incidence of antibiotic resistance. Towards this goal, a commercially available bacteria-targeting Zinc(II)-dipicolylamine (ZnDPA)-derived fluorophore, PSVue794, was assessed as a photoacoustic (PA) imaging probe (PIP). A radiolabeled version of the dye, [99mTc]Tc-PSVue794, was developed to facilitate quantitative biodistribution studies beyond optical imaging methods, which showed a target-to-non-target ratio of 10.1 ± 1.1, 12 h post-injection. The ability of the PIP to differentiate between bacterial infection, sterile inflammation, and healthy tissue in a mouse model, was then evaluated via PA imaging. The PA signal in sites of sterile inflammation (0.062 ± 0.012 a.u.) was not statistically different from that of the background (0.058 ± 0.006 a.u.). In contrast, high PA signal was detected at sites of bacterial infection (0.176 ± 0.011 a.u.) as compared to background (0.081 ± 0.04 a.u., where P ≤ 0.03). This work demonstrates the potential of utilizing established fluorophores towards PAI and utilizing PAI as a modality in the distinction of bacterial infection from sites of sterile inflammation. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells play an important role in driving tumor growth and treatment resistance, which makes them a promising therapeutic target to prevent cancer recurrence. Emerging cancer stem cell-targeted therapies would benefit from companion diagnostic imaging probes to aid in patient selection and monitoring response to therapy. To this end, zirconium-89-radiolabeled immunoPET probes that target the cancer stem cell-antigen CD133 were developed using fully human antibody and antibody scFv-Fc scaffolds. Results: ImmunoPET probes [89Zr]-DFO-RW03IgG (CA = 0.7 ± 0.1), [89Zr]-DFO-RW03IgG (CA = 3.0 ± 0.3), and [89Zr]-DFO-RW03scFv − Fc (CA = 2.9 ± 0.3) were radiolabeled with zirconium-89 (radiochemical yield 42 ± 5%, 97 ± 2%, 86 ± 12%, respectively) and each was isolated in > 97% radiochemical purity with specific activities of 120 ± 30, 270 ± 90, and 200 ± 60 MBq/mg, respectively. In vitro binding assays showed a low-nanomolar binding affinity of 0.6 to 1.1 nM (95% CI) for DFO-RW03IgG (CA = 0.7 ± 0.1), 0.3 to 1.9 nM (95% CI) for DFO-RW03IgG (CA = 3.0 ± 0.3), and 1.5 to 3.3 nM (95% CI) for DFO-RW03scFv − Fc (C/A = 0.3). Biodistribution studies found that [89Zr]-DFO-RW03scFv − Fc (CA = 2.9 ± 0.3) exhibited the highest tumor uptake (23 ± 4, 21 ± 2, and 23 ± 4%ID/g at 24, 48, and 72 h, respectively) and showed low uptake (< 6%ID/g) in all off-target organs at each timepoint (24, 48, and 72 h). Comparatively, [89Zr]-DFO-RW03IgG (CA = 0.7 ± 0.1) and [89Zr]-DFO-RW03IgG (CA = 3.0 ± 0.3) both reached maximum tumor uptake (16 ± 3%ID/g and 16 ± 2%ID/g, respectively) at 96 h p.i. and showed higher liver uptake (10.2 ± 3%ID/g and 15 ± 3%ID/g, respectively) at that timepoint. Region of interest analysis to assess PET images of mice administered [89Zr]-DFO-RW03scFv − Fc (CA = 2.9 ± 0.3) showed that this probe reached a maximum tumor uptake of 22 ± 1%ID/cc at 96 h, providing a tumor-to-liver ratio that exceeded 1:1 at 48 h p.i. Antibody-antigen mediated tumor uptake was demonstrated through biodistribution and PET imaging studies, where for each probe, co-injection of excess unlabeled RW03IgG resulted in > 60% reduced tumor uptake. Conclusions: Fully human CD133-targeted immunoPET probes [89Zr]-DFO-RW03IgG and [89Zr]-DFO-RW03scFv − Fc accumulate in CD133-expressing tumors to enable their delineation through PET imaging. Having identified [89Zr]-DFO-RW03scFv − Fc (CA = 2.9 ± 0.3) as the most attractive construct for CD133-expressing tumor delineation, the next step is to evaluate this probe using patient-derived tumor models to test its detection limit prior to clinical translation. [ABSTRACT FROM AUTHOR]

The construction supply chain is complex. This complexity causes problems and errors. In Iran, due to an anarchic atmosphere, it is very common for problems and errors to occur. The Sustainable Antifragile Fragile Lean (SAAL) supply chain was designed to deal with these conditions. One of the widely used tools in this supply chain is the use of information systems such as the control tower. But these systems may also have errors. The main purpose of Poka-yoke is to make mistakes impossible. Therefore, in this research, the main dimensions of Poka-yoke solutions are categorised based on previous research and then experts' opinions are collected with the help of a questionnaire tool. In order to prioritise the factors based on control tower systems, the best-worst method was used. The results showed factors such as proper planning of quality management programs, building information modeling and proper implementation of the productivity cycle is the most important. [ABSTRACT FROM AUTHOR]

In the Chaos/Anarchy business environment of the construction industry of Iran, the Sustainable Antifragile Agile Lean (SAAL) supply chain strategy was proposed as antifragile and value-creating approach. In this strategy, just-in-time data management and analysis are very important to make decisions. The control tower as a controlling unit based on data is the core of this supply chain. The purpose of this article is to investigate the implementation of the control tower in the supply chain of the construction industry. For this purpose, two goals should be followed. The first step is to determine the main indicators to focus on for the initial implementation of the control tower. The second step is to measure the considered indicators using the available data from before the implementation, and after the implementation to compare the performance. To achieve the first goal and to identify the categories of information these categories were divided into three main categories: upstream, midstream and downstream. According to experts’ opinion was considered the middle part of the supply chain, which is carried out on the site by an executive team. At this stage, among the available indicators, the most important indicators were considered using the best-worst method according to previous projects’ data to compare the data. The results of the implementation of a control tower approach showed that it provides the possibility of managing manufacturing operations. This system can guide the managers of the organisation to identify the best strategies and improve risk management in response to the needs, requirements, guidelines, and changing opinions of the stakeholders and external global conditions. [ABSTRACT FROM AUTHOR]

SAAL supply chain management is a comprehensive approach of combining sustainable, Antifragile, agile, and lean strategies. The aim of the current research is to evaluate the SAAL supply chain management strategies using the gap analysis approach in the construction industry. The statistical sample includes 246 of the industry's activists who were randomly selected. First, it is calculated the gap between the existing and ideal situation of each of the indicators and requirements of SAAL supply chain management strategies. Then, the weight of indicators and requirements is determined using the HF-BWM, and based on that, the weighted gap of each is calculated and analyzed. The results of the research show that based on the GWA obtained, Antifragile and Sustainable strategies are the most critical SAAL supply chain management strategies for evaluating the supply chain management performance of Iran's construction industry. [ABSTRACT FROM AUTHOR]

In the challenging environment of the construction industry and especially after the Corona pandemic crisis in Iran, supply chains (SCs) needed to adopt a new management model to continue the activity. Among the investigated approaches, the four sustainable, anti-fragile, agile and lean (SAAL) approaches were given more attention. The main objective of this paper is to draw a conceptual model for SAAL SCs with the aim of improving their operational, economic and environmental performance. For this purpose, several performance measures have been proposed. This concept is drawn based on the literature review of four supply chain management (SCM) approaches and their performance measurement system. Among the measures proposed by SAAL, which affect SC performance, are just-in-time relationships as well as supplier relationships (modular suppliers) and creating anti-fragile infrastructure. [ABSTRACT FROM AUTHOR]

Due to the changing and complex environment of the construction industry, and the critical conditions prevailing in Iran, the managers of this industry have started to identify management approaches such as Sustainable, Antifragile, Agile and Lean (SAAL) as approaches to achieve sustainable competitive advantage. In order to use them, organizations need to adapt and create new business models. A systematic approach to integrating SAAL construction supply chain principles into the Business Model Canvas (BMC) perspective of Blue Ocean Strategy will be the first step in the process of achieving this approach. This model can identify critical factors to be included in the organisation's business model due to its wide perspective and compatibility with the supply chain. In addition, it provides how and why they are related and the conditions and boundaries of these relationships. Although this research helped identify some limitations when trying to align, it also showed that the chosen model was aligned with the supply chain, and the SAAL strategy was aligned with the blue ocean. [ABSTRACT FROM AUTHOR]

The development of new 18F‐based radiopharmaceuticals constantly demands innovations in the search for new radiofluorination methods. [18F]fluoride is the simplest and most convenient chemical form of the isotope for the synthesis of 18F‐based radiopharmaceuticals. The ease of production and handling, as well as the possibility of obtaining high molar activities, makes it the preferred choice for radiofluorination. However, the use of [18F]fluoride in late‐stage radiofluorination comes with challenges, especially for the radiolabeling of electron‐rich molecules where SN2 and SNAr reactions are not suitable. New developments in fluorination chemistry have been extensively studied to overcome these difficulties. Selective electrochemical oxidation of precursors, using a controlled potential, is one method to create reactive intermediates and overcome the activation energy required for nucleophilic fluorination of electron‐rich moieties. This method has been used for years in cold fluorination of organic molecules and more recently has been adapted as an alternative to traditional radiofluorination methods. Although relatively young, this field stands out as a promising route for the synthesis of new PET probes as well as fluorinated pharmaceuticals. This review focuses on recent advances in electrochemical radiofluorination as an alternative for the late‐stage radiolabeling of organic molecules. [ABSTRACT FROM AUTHOR]

Tailoring carbon nanotube surface chemistry is essential for biomedical applications. Bisphosphonate–carbon nanotube conjugates were prepared to target regions of active bone metabolism. The conjugates were synthesized using covalent functionalization (G1) or latently reactive polymer–nanotube complexes (G2), and it was found that the noncovalent G2 method afforded higher quality colloidal dispersions. The in vitro cytotoxicity tests against C2C12 cells were carried out and the results revealed low cytotoxicity and good biocompatibility profile for both bisphosphonate–carbon nanotube conjugates. The conjugates were radiolabeled with 99mTc in high radiochemical yield (80–92%). In vitro binding studies to hydroxyapatite showed binding of 77 and 36% for G1 and G2, respectively, after 1 h incubation at room temperature. A biodistribution study of G1 and G2in vivo in a Balb/c mouse model demonstrated rapid blood clearance after 1 h and superior bone localization of G2 conjugates as compared to G1 conjugates. Photoacoustic imaging of nanotube conjugates confirmed superior in vivo bone localization of G2 as compared to G1. Together, biodistribution studies of radiolabeled complexes and photoacoustic imaging demonstrated that latently reactive polymer–nanotube complexes are a promising platform to modulate carbon nanotube surface chemistry for targeted diagnostic and drug delivery. [ABSTRACT FROM AUTHOR]

In light of the United States Food and Drug Administration (FDA) requirement of 21 CFR 212 current Good Manufacturing Practice (cGMP) for FDA-approved position emission tomography (PET) drugs, the University of California Los Angeles (UCLA) Biomedical Cyclotron (BMC) transformed from a pre-cGMP era academic cyclotron and radiochemistry facility to a current cGMP-compliant PET drug manufacturer. In this article, we share the financial and regulatory compliance aspects of the "transformation" required to develop a sustainable quality system to support the production of two PET drugs under Abbreviated New Drug Applications (ANDAs). [ABSTRACT FROM AUTHOR]

Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts2,3. However, our understanding of oxidative mitochondrial metabolism in cancer is limited because most studies have been performed in vitro in cell culture models. This highlights a need for in vivo studies to better understand how oxidative metabolism supports tumour growth. Here we measure mitochondrial membrane potential in non-small-cell lung cancer in vivo using a voltage-sensitive, positron emission tomography (PET) radiotracer known as 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP)4. By using PET imaging of 18F-BnTP, we profile mitochondrial membrane potential in autochthonous mouse models of lung cancer, and find distinct functional mitochondrial heterogeneity within subtypes of lung tumours. The use of 18F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours. A positron emission tomography imaging tracer is developed to image mitochondrial function in vivo, and application of this tracer to a mouse model of lung cancer identifies distinct functional mitochondrial heterogeneity between tumour cells. [ABSTRACT FROM AUTHOR]

A new method for rapid late‐stage fluorination using the cation pool technique is presented. Fluorination and no‐carrier‐added radiofluorination of methyl (phenylthio) acetate, methyl 2‐(methylthio) acetate, and methyl 2‐(ethylthio) acetate were performed. The carbocations formed through electrochemical oxidation were stabilized by using a divided electrochemical cell and 2,2,2‐trifluoroethanol (TFE) as the solvent at −20 °C. At the end of electrolysis, either stable‐isotope [19F]fluoride or no‐carrier‐added radioactive [18F]fluoride was added to the reaction mixture to form the fluorinated or radiofluorinated product. Radio‐labelling using cation pool: Successful electrochemical fluorination and radiofluorination using the cation pool technique is reported. This method provides a truly late‐stage fluorination reaction, maximizing radiochemical yield by minimizing decay through a rapid reaction of the previously prepared cations with [18F] fluoride. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was the automated synthesis of the mitochondrial membrane potential sensor 4-[18F]fluorobenzyl-triphenylphosphonium ([18F]FBnTP) on a commercially available synthesizer in activity yields (AY) that allow for imaging of multiple patients.Procedures: A three-pot, four-step synthesis was implemented on the ELIXYS FLEX/CHEM radiosynthesizer (Sofie Biosciences) and optimized for radiochemical yield (RCY), radiochemical purity (RCP) as well as chemical purity during several production runs (n = 24). The compound was purified by solid-phase extraction (SPE) with a Sep-Pak Plus Accell CM cartridge, thereby avoiding HPLC purification.Results: Under optimized conditions, AY of 1.4-2.2 GBq of [18F]FBnTP were obtained from 9.4 to 12.0 GBq [18F]fluoride in 90-92 min (RCY = 28.6 ± 5.1 % with n = 3). Molar activities ranged from 80 to 99 GBq/μmol at the end of synthesis. RCP of final formulations was > 99 % at the end of synthesis and > 95 % after 8 h. With starting activities of 23.2-33.0 GBq, RCY decreased to 16.1 ± 0.4 % (n = 3). The main cause of the decline in RCY when high amounts of [18F]fluoride are used is radiolytic decomposition of [18F]FBnTP during SPE purification.Conclusions: In initial attempts, the probe was synthesized with RCY < 0.6 % when starting activities up to 44.6 GBq were used. Rapid radiolysis of the intermediate 4-[18F]fluorobenzaldehyde and the final product [18F]FBnTP during purification was identified as the main cause for low yields in high-activity runs. Radiolytic decomposition was hindered by the addition of radical scavengers during synthesis, purification, and formulation, thereby improving AY and RCP. The formulated probe in injectable form was synthesized without the use of HPLC and passed all applicable quality control tests. [ABSTRACT FROM AUTHOR]

Radiopharmaceuticals labeled with short-lived positron-emitting or gamma-emitting isotopes are injected into patients just prior to performing positron emission tomography (PET) or single photon emission tomography (SPECT) scans, respectively. These imaging modalities are widely used in clinical care, as well as in the development and evaluation of new therapies in clinical research. Prior to injection, these radiopharmaceuticals (tracers) must undergo quality control (QC) testing to ensure product purity, identity, and safety for human use. Quality tests can be broadly categorized as (i) pharmaceutical tests, needed to ensure molecular identity, physiological compatibility and that no microbiological, pyrogenic, chemical, or particulate contamination is present in the final preparation; and (ii) radioactive tests, needed to ensure proper dosing and that there are no radiochemical and radionuclidic impurities that could interfere with the biodistribution or imaging. Performing the required QC tests is cumbersome and time-consuming, and requires an array of expensive analytical chemistry equipment and significant dedicated lab space. Calibrations, day of use tests, and documentation create an additional burden. Furthermore, in contrast to ordinary pharmaceuticals, each batch of short-lived radiopharmaceuticals must be manufactured and tested within a short period of time to avoid significant losses due to radioactive decay. To meet these challenges, several efforts are underway to develop integrated QC testing instruments that automatically perform and document all of the required tests. More recently, microfluidic quality control systems have been gaining increasing attention due to vastly reduced sample and reagent consumption, shorter analysis times, higher detection sensitivity, increased multiplexing, and reduced instrumentation size. In this review, we describe each of the required QC tests and conventional testing methods, followed by a discussion of efforts to directly miniaturize the test or examples in the literature that could be implemented for miniaturized QC testing. [ABSTRACT FROM AUTHOR]

New radiolabeled probes for positron-emission tomography (PET) are providing an ever-increasing ability to answer diverse research and clinical questions and to facilitate the discovery, development, and clinical use of drugs in patient care. Despite the high equipment and facility costs to produce PET probes, many radiopharmacies and radiochemistry laboratories use a dedicated radiosynthesizer to produce each probe, even if the equipment is idle much of the time, to avoid the challenges of reconfiguring the system fluidics to switch from one probe to another. To meet growing demand, more cost-efficient approaches are being developed, such as radiosynthesizers based on disposable "cassettes," that do not require reconfiguration to switch among probes. However, most cassette-based systems make sacrifices in synthesis complexity or tolerated reaction conditions, and some do not support custom programming, thereby limiting their generality. In contrast, the design of the ELIXYS FLEX/CHEM cassette-based synthesizer supports higher temperatures and pressures than other systems while also facilitating flexible synthesis development. In this paper, the syntheses of 24 known PET probes are adapted to this system to explore the possibility of using a single radiosynthesizer and hot cell for production of a diverse array of compounds with wide-ranging synthesis requirements, alongside synthesis development efforts. Most probes were produced with yields and synthesis times comparable to literature reports, and because hardware modification was unnecessary, it was convenient to frequently switch among probes based on demand. Although our facility supplies probes for preclinical imaging, the same workflow would be applicable in a clinical setting. [ABSTRACT FROM AUTHOR]

New radiochemistry techniques can yield novel PET tracers for COX-2 and address the shortcomings in in vivo stability and specificity, which have held back clinical translation of tracers to image COX-2 expression. Current techniques limit radiosynthesis to analogs of the COX-2 inhibitors with fluorine-18 added via a carbon chain, or on an aromatic position which renders the radiolabeled analog less specific towards COX-2, resulting in tracers with low in vivo stability or specificity. To solve this problem, we have developed a new high affinity, 18F-labelled COX-2 inhibitor that is radiolabeled directly on a heteroaromatic ring. This molecule exhibits favorable biodistribution and increased metabolic stability. Synthesis of this molecule cannot be achieved by traditional means; consequently, we have developed an automated electrochemical radiosynthesis platform to synthesize up to 5 mCi of radiochemically pure 18F-COX-2ib in 4 hours (2% decay-corrected radiochemical yield). In vitro studies demonstrated clear correlation between COX-2 expression and uptake of the tracer. PET imaging of healthy animals confirmed that the molecule is excreted from blood within an hour, mainly through the hepatobiliary excretion pathway. In vivo metabolism data demonstrated that > 95% of the injected radioactivity remains in the form of the parent molecule 1 hour after injection. [ABSTRACT FROM AUTHOR]

Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds--[18F]Clofarabine; 2-chloro-2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosyl-adenine ([18F]CFA) and 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG)--for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [18F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [18F]F-AraG is a better substrate for dGK than for dCK. [18F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [18F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [18F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [18F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [18F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [18F]CFA PET as a new cancer biomarker for treatment stratification and monitoring. [ABSTRACT FROM AUTHOR]

Direct nucleophilic radiosynthesis of di- tert-butyl-(4-[F]fluoro-1,2-phenylene)-dicarbonate was conducted through no-carrier-added electrochemical reactions. 10 mM of triethylamine acetic acid (EtN·3HAc) in acetonitrile was used to release [F]fluoride ion trapped in the quaternary ammonium anion exchange resin. The relationship between radiofluorination efficiency, concentration of the EtN·3HAc, and the working potential were studied with a di- tert-butyl-(4-( tert-butyl)-1,2-phenylene)-dicarbonate substrate in nonaqueous acetonitrile solution. Radiochemical yields of 6.8 ± 1.3 % with specific activity of up to 13 GBq/µmol were achieved with a precursor concentration of 50 mM after a reaction time of 57 min at 0 °C. [ABSTRACT FROM AUTHOR]

We have developed an efficient, streamlined, cost-effective approach to obtain Investigational New Drug (IND) approvals from the Food and Drug Administration (FDA) for positron emission tomography (PET) imaging probes (while the FDA uses the terminology PET drugs, we are using 'PET imaging probes,' 'PET probes,' or 'probes' as the descriptive terms). The required application and supporting data for the INDs were collected in a collaborative effort involving appropriate scientific disciplines. This path to INDs was successfully used to translate three [ F]fluoro-arabinofuranosylcytosine (FAC) analog PET probes to phase 1 clinical trials. In doing this, a mechanism has been established to fulfill the FDA regulatory requirements for translating promising PET imaging probes from preclinical research into human clinical trials in an efficient and cost-effective manner. [ABSTRACT FROM AUTHOR]

Organic chemistry applications on digital microfluidic devices often involve reagents that are volatile or sensitive and must be introduced to the chip immediately before use. We present a new technique for automated, on-demand loading of ∼1 μL droplets from large (∼1 mL), sealed, off-chip reservoirs to a digital microfluidic chip in order to address this challenge. Unlike aqueous liquids which generally are non-wetting to the hydrophobic surface and must be actively drawn into the electrowetting-on-dielectric (EWOD) chip by electrode activation, organic liquids tend to be wetting and can spontaneously flood the chip, and hence require a retracting force for controlled liquid delivery. Using a combination of compressed inert gas and gravity to exert driving and retracting forces on the liquid, the simple loading technique enables precise loading of droplets of both wetting and non-wetting liquids in a reliable manner. A key feature from a practical point of view is that all of the wetted parts are inexpensive and potentially disposable, thus avoiding cross-contamination in chemical and biochemical applications. We provide a theoretical treatment of the underlying physics, discuss the effect of geometry and liquid properties on its performance, and show repeatable reagent loading using the technique. Its versatility is demonstrated with the loading of several aqueous and non-aqueous liquids on an EWOD digital microfluidic device. [ABSTRACT FROM AUTHOR]

The response of electrodissolution dynamics of nickel in sulfuric acid electrolyte was studied and categorized using efficient signal processing techniques. Time-frequency and phase analysis revealed complex dynamical patterns in anodic currents observed in the system. These patterns which respond to three-dimensional changes in the electrolyte and surface conditions, have a multitude of spatio-temporal properties which proved sensitive to oscillatory voltage perturbations, allowing signal recognition through distinct response patterns. Experimental work included studies on identification of control parameters, characterization of subsequent temporal patterns and examination of system response to information in the form of oscillatory voltage perturbations. Various data processing and pattern recognition techniques revealed the complexity and dynamics of these distinctive responses, which illustrate the capacity of the system to store information, with varying memory lengths. These patterns can be recalled upon excitation with particular perturbation cues. [ABSTRACT FROM AUTHOR]

An Amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The Cover Feature illustrates radio‐labelling using a cation pool technique. This method provides a truly late‐stage fluorination reaction, maximizing radiochemical yield by minimizing decay through rapid reaction of the previously prepared cations with [18F] fluoride. More information can be found in the Communication by M. Balandeh et al. on page 3353 in Issue 22, 2018 (DOI: 10.1002/celc.201800973). [ABSTRACT FROM AUTHOR]