Distinctive Electric Properties of Group 14 Oxides: SiO2, SiO, and SnO2.

The oxides of group 14 have been widely used in numerous applications in glass, ceramics, optics, pharmaceuticals, and food industries and semiconductors, photovoltaics, thermoelectrics, sensors, and energy storage, namely, batteries. Herein, we simulate and experimentally determine by scanning kelvin probe (SKP) the work functions of three oxides, SiO2, SiO, and SnO2, which were found to be very similar. Electrical properties such as electronic band structure, electron localization function, and carrier mobility were also simulated for the three crystalline oxides, amorphous SiO, and surfaces. The most exciting results were obtained for SiO and seem to show Poole-Frankel emissions or trap-assisted tunneling and propagation of surface plasmon polariton (SPP) with nucleation of solitons on the surface of the Aluminum. These phenomena and proposed models may also describe other oxide-metal heterojunctions and plasmonic and metamaterials devices. The SiO2 was demonstrated to be a stable insulator interacting less with the metals composing the cell than SnO2 and much less than SiO, configuring a typical Cu/SiO2/Al cell potential well. Its surface charge carrier mobility is small, as expected for an insulator. The highest charge carrier mobility at the lowest conduction band energy is the SnO2's and the most symmetrical the SiO's with a similar number of electron holes at the conduction and valence bands, respectively. The SnO2 shows it may perform as an n-type semiconductor.

Solid-phase synthesis of imprinted nanoparticles as artificial antibodies against the C-terminus of the cannabinoid CB1 receptor: exploring a viable alternative for bioanalysis.

The production of artificial anti-CB1 antibodies in nanoparticle format is described using the solid-phase imprinting approach. Instead of whole protein imprinting, a linear C-terminus sequence of the receptor comprising 15 amino acids (458-KVTMSVSTDTSAEAL-472) has been used as template, in accordance with the epitope imprinting approach. This sequence is located intracellularly, and it is involved in coupling to Gi/o proteins, being responsible for CB1 receptor desensitisation and internalisation. Developed molecularly imprinted materials were found to be in the nanometre scale, with a particle size of 126.4 ± 10.5 nm at pH 3 (25 ºC) and spherical shape. It was also observed that the size was sensible to temperature changes being reduced to 106.3 ± 15.2 nm at 35 °C. Lower critical solution temperature of this polymer was found to be ≈ 33.4 °C. The affinity and selectivity of the artificial antibody were assessed through dot blot and Western blot experiments. For the latter, recombinant fusion proteins GST-CB1414-472 and GST-CB1414-442 were produced to work respectively as target and negative control proteins. The control protein did not carry the target epitope for being devoid of last 30 amino acids at the C-terminus. The results demonstrated that the anti-CB1 material recognised selectively the target protein, thanks to the presence of the 15-amino acid sequence selected as epitope, which revealed that binding occurred at the C-terminus of the receptor itself. The methodology presented may pave the way for the development of novel imprinted nanomaterials for other proteins included in the superfamily of the G-protein-coupled receptors (GPCR).

Probing Peptide Sequences on Their Ability to Generate Affinity Sites in Molecularly Imprinted Polymers.

An array of 4000 defined and addressable tripeptides on a polymer-coated glass slide is used to synthesize molecularly imprinted polymer (MIP) nanoparticles. This work is undertaken to systematically probe the impact of the peptide sequence on the ability to generate affinity MIPs. The polymer affinity is assessed by measuring the fluorescence of bound MIP nanoparticles at each peptide spot on the surface after washing the array to remove any low-affinity polymer. The generic composition commonly used in the preparation of MIPs against proteins seems to be equally suitable for imprinting hydrophobic and hydrophilic tripeptides. The amino acids frequently contributing to the formation of high-affinity MIPs include T, F, D, N, Y, W, and P. The amino acids that rarely contribute to the formation of high-affinity interactions with MIPs are G, V, A, L, I, and M. These observations are confirmed by computational modeling. The basic technique proposed here may be applicable in optimizing polymer compositions for the production of high-affinity MIPs or, more specifically, for the selection of appropriate amino acid sequences when peptide epitopes are used instead of whole protein imprinting.

Specific Drug Delivery to Cancer Cells with Double-Imprinted Nanoparticles against Epidermal Growth Factor Receptor.

Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, is over-expressed in many tumors, including almost half of triple-negative breast cancers. The latter belong to a very-aggressive and drug-resistant form of malignancy. Although humanized anti-EGFR antibodies can work efficiently against these cancers both as monotherapy and in combination with genotoxic drugs, instability and high production costs are some of their known drawbacks in clinical use. In addition, the development of antibodies to target membrane proteins is a very challenging task. Accordingly, the main focus of the present work is the design of supramolecular agents for the targeting of membrane proteins in cancer cells and, hence, more-specific drug delivery. These were produced using a novel double-imprinting approach based on the solid-phase method for preparation of molecularly imprinted polymer nanoparticles (nanoMIPs), which were loaded with doxorubicin and targeted toward a linear epitope of EGFR. Additionally, upon binding, doxorubicin-loaded anti-EGFR nanoMIPs elicited cytotoxicity and apoptosis only in those cells that over-expressed EGFR. Thus, this approach can provide a plausible alternative to conventional antibodies and sets up a new paradigm for the therapeutic application of this class of materials against clinically relevant targets. Furthermore, nanoMIPs can promote the development of cell imaging tools against difficult targets such as membrane proteins.

Modulation of Quorum Sensing in a Gram-Positive Pathogen by Linear Molecularly Imprinted Polymers with Anti-infective Properties.

We describe the development, characterization, and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as an anti-infective by blocking the quorum sensing (QS) mechanism and so abrogating the virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches, no cross-linker is used. This results in soluble low-molecular-weight oligomers that can act as a therapeutic agent in vitro and in vivo. The LMIP was characterized by mass spectrometry to determine its monomer composition. Fragments identified were then aligned along the peptide template by computer modeling to predict the possible monomer sequence of the LMIP. These findings provide a proof of principle that LMIPs can be used to block QS, thus setting the stage for the development of LMIPs a novel drug-discovery platform and class of materials to target Gram-positive pathogens.

Preliminary evaluation of military, commercial and novel skin decontamination products against a chemical warfare agent simulant (methyl salicylate).

Rapid decontamination is vital to alleviate adverse health effects following dermal exposure to hazardous materials. There is an abundance of materials and products which can be utilised to remove hazardous materials from the skin. In this study, a total of 15 products were evaluated, 10 of which were commercial or military products and five were novel (molecular imprinted) polymers. The efficacies of these products were evaluated against a 10 µl droplet of (14)C-methyl salicylate applied to the surface of porcine skin mounted on static diffusion cells. The current UK military decontaminant (Fuller's earth) performed well, retaining 83% of the dose over 24 h and served as a benchmark to compare with the other test products. The five most effective test products were Fuller's earth (the current UK military decontaminant), Fast-Act® and three novel polymers [based on itaconic acid, 2-trifluoromethylacrylic acid and N,N-methylenebis(acrylamide)]. Five products (medical moist-free wipes, 5% FloraFree™ solution, normal baby wipes, baby wipes for sensitive skin and Diphotérine™) enhanced the dermal absorption of (14)C-methyl salicylate. Further work is required to establish the performance of the most effective products identified in this study against chemical warfare agents.

Detection of Waterborne Viruses Using High Affinity Molecularly Imprinted Polymers.

Molecularly imprinted polymers (MIPs) are artificial receptor ligands which can recognize and specifically bind to a target molecule. They are more resistant to chemical and biological damage and inactivation than antibodies. Therefore, target specific-MIP nanoparticles are aimed to develop and implemented to biosensors for the detection of biological toxic agents such as viruses, bacteria, and fungi toxins that cause many diseases and death due to the environmental contamination. For the first time, a molecularly imprinted polymer (MIP) targeting the bacteriophage MS2 as the template was investigated using a novel solid-phase synthesis method to obtain the artificial affinity ligand for the detection and removal of waterborne viruses through optical-based sensors. A high affinity between the artificial ligand and the target was found, and a regenerative MIP-based virus detection assay was successfully developed using a new surface plasmon resonance (SPR)-biosensor which provides an alternative technology for the specific detection and removal of waterborne viruses that lead to high disease and death rates all over the world.

Introducing MINA--The Molecularly Imprinted Nanoparticle Assay.

A new ELISA- (enzyme-linked immunosorbent assay)-like assay is demonstrated in which no elements of biological origin are used for molecular recognition or signaling. Composite imprinted nanoparticles that contain a catalytic core and which are synthesized by using a solid-phase approach can simultaneously act as recognition/signaling elements, and be used with minimal modifications to standard assay protocols. This assay provides a new route towards replacement of unstable biomolecules in immunoassays.

Selective vancomycin detection using optical fibre long period gratings functionalised with molecularly imprinted polymer nanoparticles.

An optical fibre long period grating (LPG) sensor modified with molecularly imprinted polymer nanoparticles (nanoMIPs) for the specific detection of antibiotics is presented. The operation of the sensor is based on the measurement of changes in refractive index induced by the interaction of nanoMIPs deposited onto the cladding of the LPG with free vancomycin (VA). The binding of nanoMIPs to vancomycin was characterised by a binding constant of 4.3 ± 0.1 × 10(-8) M. The lowest concentration of analyte measured by the fibre sensor was 10 nM. In addition, the sensor exhibited selectivity, as much smaller responses were obtained for high concentrations (∼700 µM) of other commonly prescribed antibiotics such as amoxicillin, bleomycin and gentamicin. In addition, the response of the sensor was characterised in a complex matrix, porcine plasma, spiked with 10 µM of VA.

A molecular imprinted polymer based sensor for measuring phosphate in wastewater samples.

Phosphate detection in water samples is still completed using colorimetric standard methods, which have a number of disadvantages, to such as being time consuming, requiring filtration, a number of different reagents, frequent calibration and proper disposal of waste chemicals generated. Hence, a simple cost effective analytical method and instrumentation is highly desirable to aid the optimisation of treatment processes and assist the water industry in their efforts to comply with stringent regulations such as the EU's Water Framework Directive. A sensor based on molecular imprinted polymer (MIP) and a conductance transducer was developed for direct and label-free detection of phosphate in water. The sensor was able to measure the presence of phosphate in wastewater samples with good reproducibility, a linear range of 0.66-8 mg P L(-1) and a lower detection limit of 0.16 mg P L(-1). The sensor was further tested to measure phosphate concentrations in unfiltered field samples such as domestic wastewater treatment influent and river water and demonstrated a close correlation with reference measurements. The phosphate MIP sensor offers a way forward as either a handheld sensor for use in the field, or as a potential solution for remote, continuous monitoring of phosphate.

Correction: An impedimetric sensor based on molecularly imprinted nanoparticles for the determination of trypsin in artificial matrices - towards point-of-care diagnostics.

Correction for 'An impedimetric sensor based on molecularly imprinted nanoparticles for the determination of trypsin in artificial matrices - towards point-of-care diagnostics' by Sabrina Di Masi et al., Anal. Methods, 2024, 16, 742-750, https://doi.org/10.1039/D3AY01762A.

An impedimetric sensor based on molecularly imprinted nanoparticles for the determination of trypsin in artificial matrices - towards point-of-care diagnostics.

A high-performance impedimetric sensing platform was designed to detect proteins by employing molecularly imprinted polymeric nanoparticles (nanoMIPs) as selective receptors. This was achieved via the combination of the nanoMIPs with a self-assembled thioctic acid (SAM-TA) monolayer onto screen-printed gold electrodes, providing stable covalent attachment of the selective binder to the transducer. Taguchi design has been modelled to achieve the optimal level of sensor fabrication parameters and to maximise the immobilisation of nanoMIPs and their response (e.g. the response of imprinted polymers compared with the non-imprinted control). The developed sensor was tested towards a range of concentrations of trypsin dissolved in ammonium acetate (pH = 6) and showed promising applicability in artificial saliva, with a recovery percentage between 103 and 107%.

Direct replacement of antibodies with molecularly imprinted polymer nanoparticles in ELISA--development of a novel assay for vancomycin.

A simple and straightforward technique for coating microplate wells with molecularly imprinted polymer nanoparticles (nanoMIPs) to develop assays similar to the enzyme-linked immunosorbent assay (ELISA) is presented here for the first time. NanoMIPs were synthesized by a solid-phase approach with an immobilized vancomycin (template) and characterized using Biacore 3000, dynamic light scattering, and electron microscopy. Immobilization, blocking, and washing conditions were optimized in microplate format. The detection of vancomycin was achieved in competitive binding experiments with a horseradish peroxidase-vancomycin conjugate. The assay was capable of measuring vancomycin in buffer and in blood plasma within the range of 0.001-70 nM with a detection limit of 0.0025 nM (2.5 pM). The sensitivity of the assay was 3 orders of magnitude better than a previously described ELISA based on antibodies. In these experiments, nanoMIPs have shown high affinity and minimal interference from blood plasma components. Immobilized nanoMIPs were stored for 1 month at room temperature without any detrimental effects to their binding properties. The high affinity of nanoMIPs and the lack of a requirement for cold chain logistics make them an attractive alternative to traditional antibodies used in ELISA.

Solid-Phase Synthesis of Molecularly Imprinted Polymer Nanoparticles with a Reusable Template - "Plastic Antibodies".

Molecularly Imprinted Polymers (MIPs) are generic alternatives to antibodies in sensors, diagnostics and separations. To displace biomolecules without radical changes in infrastructure in device manufacture, MIPs should share their characteristics (solubility, size, specificity and affinity, localized binding domain) whilst maintaining the advantages of MIPs (low-cost, short development time and high stability) hence the interest in MIP nanoparticles. Herein we report a reusable solid-phase template approach (fully compatible with automation) for the synthesis of MIP nanoparticles and their precise manufacture using a prototype automated UV photochemical reactor. Batches of nanoparticles (30-400 nm) with narrow size distributions imprinted with: melamine (d = 60 nm, Kd = 6.3 × 10-8 m), vancomycin (d = 250 nm, Kd = 3.4 × 10-9 m), a peptide (d = 350 nm, Kd = 4.8 × 10-8 m) and proteins have been produced. Our instrument uses a column packed with glass beads, bearing the template. Process parameters are under computer control, requiring minimal manual intervention. For the first time we demonstrate the reliable re-use of molecular templates in the synthesis of MIPs (≥ 30 batches of nanoMIPs without loss of performance). NanoMIPs are produced template-free and the solid-phase acts both as template and affinity separation medium.

PEG-stabilized core-shell surface-imprinted nanoparticles.

Here we present a simple technique to produce target-specific molecularly imprinted polymeric nanoparticles (MIP NPs) and their surface modification in order to prevent the aggregation process that is ever-present in most nanomaterial suspensions/dispersions. Specifically, we studied the influence of surface modification of MIP NPs with polymerizable poly(ethylene glycol) on their degree of stability in water, in phosphate buffer, and in the presence of serum proteins. Grafting a polymer shell on the surface of nanoparticles decreases the surface energy, enhances the polarity, and as a result improves the dispersibility, storage, and colloidal stability as compared to those of core (unmodified) particles. Because of the unique solid-phase approach used for synthesis, the binding sites of MIP NPs are protected during grafting, and the recognition properties of nanoparticles are not affected. These results are significant for developing nanomaterials with selective molecular recognition, increased biocompatibility, and stability in solution. Materials synthesized this way have the potential to be used in a variety of technological fields, including in vivo applications such as drug delivery and imaging.

Converting to a capitation system for dialysis payment--the Portuguese experience.

Due to the challenge of operating within an economically strained healthcare budget, Portuguese health authorities convened with dialysis providers and agreed on a framework to change from a fee-for-service reimbursement modality to a capitation payment system for hemodialysis. This article reviews the components of the agreed capitation package implemented in 2008 as well as the necessary preparatory work undertaken by a for-profit 34-unit dialysis network (approx. 4,200 patients) to cope with the introduction of this system. Furthermore, trends in clinical quality indicators and in resource management are reviewed for 3 years immediately following capitation introduction. Here, improvements were observed over time for the specified clinical targets. Simultaneously, costs controllable by the physician could be reduced. As more countries convert to a capitation or bundled payment system for hemodialysis services, this article offers insight into the scope of the necessary preparatory work and the possible consequences in terms of costs and treatment quality.

Patients' Perspectives on Determinants Avoidable Hospitalizations: Development and Validation of a Questionnaire.

Ambulatory care sensitive conditions (ACSC) can be avoided through effective care in the ambulatory setting. Patients are the most qualified individuals to express the social and individual contexts of their own experience. Thus, understanding why potentially preventable hospitalizations occur is important to develop patient-centred policies or interventions that may reduce them. This study aims to develop and validate a questionnaire to capture the patients' perspective on the causes of the hospitalizations for ACSC. The development of a new questionnaire involved four phases: a literature review, face validity, pre-test, and validation. We conducted a three-step face validity verification to confirm the relevance of the identified determinants and to collect determinants not previously identified by interviewing healthcare providers, representatives of patients' associations, and patients. Determinants were identified through the literature review predominantly in the "Healthcare Access", "Disease self-management", and "Social Support" domains. The validated resulting questionnaire comprises 25 questions, distributed by two dimensions (individual/contextual) covering seven domains and 20 determinants of ACSC hospitalization. Currently, there are no validated instruments as comprehensive and easy to use as the one described in this paper. This questionnaire should provide a base for further language/context validations.

Conception, synthesis, and biological evaluation of original discodermolide analogues.

Due to its intriguing biological activity profile and potential chemotherapeutic application discodermolide (DDM) proved to be an attractive target. Therefore, notable efforts have been carried out directed toward its total synthesis and toward the production and evaluation of synthetic analogues. Recently, we achieved the total synthesis of DDM. At the present, guided by the knowledge gained during our DDM total synthesis and by the requirement of keeping the bioactive "U" shape conformation, we report the convergent preparation of five original analogues. Three types of changes were realized through modification of the terminal (Z)-diene moiety, of the methyl group at the C14-position, and the lactone region. All analogues were active in the nanomolar range and two of them turned out to be equipotent to DDM.

Role of 13C-urea breath test in experimental model of Helicobacter pylori infection in mice.

BACKGROUND: Animal models have been widely used to study Helicobacter pylori infection. Evaluation of H. pylori infection status following experimental inoculation of mice usually requires euthanasia. The (13) C-urea breath test ((13) C-UBT) is both sensitive and specific for detection of H. pylori in humans. Thus, it would be very useful to have such a test with the same accuracy for the follow-up of this infection in animal models of gastric infection. Accordingly, the purpose of this study was to develop and evaluate a (13) C-UBT method for following the course of H. pylori infection in a mouse model. MATERIAL AND METHODS: A total of 50 female C57BL/6 mice were gavaged three times with either 10(8) colony-forming units of H. pylori (n=29) or saline solution only (n=21). After 2 months of infection, mice were fasted for 14 hours and (13) C-UBT was performed using 300 µg of (13) C-urea. The mice were killed, and the stomach was removed and processed for immunohistochemistry and PCR. RESULTS: The optimal time for breath sample collection in mice was found to be 15 minutes. The (13) C-UBT cutoff was set at 3.0‰ δPDB. Using PCR as the gold standard, the sensitivity of (13) C-UBT and immunohistochemistry was 96.6 and 72.4%, respectively, while the specificity was 85.7 and 95.2%, respectively. CONCLUSIONS: (13) C-UBT was shown to be a reliable method for the detection of H. pylori infection in C57BL/6 mice and was even more accurate than immunohistochemistry. The use of (13) C-UBT in the mouse model of H. pylori infection can be very useful to detect the bacterium without the need to kill the animals in long-term time course studies.

Nonsemantic word graphs of texts spanning ∼ 4500 years, including pre-literate Amerindian oral narratives.

Non-semantic word graphs obtained from oral reports are useful to describe cognitive decline in psychiatric conditions such as Schizophrenia, as well as education-related gains in discourse structure during typical development. Here we provide non-semantic word graph attributes of texts spanning approximately 4500 years of history, and pre-literate Amerindian oral narratives. The dataset assessed comprises 707 literary texts representative of 9 different Afro-Eurasian traditions (Syro-Mesopotamian, Egyptian, Hinduist, Persian, Judeo-Christian, Greek-Roman, Medieval, Modern and Contemporary), and Amerindian narratives (N = 39) obtained from a single ethnic group from South America (Kalapalo, N = 18), or from a mixed ethnic group from South, Central and North America (non-Kalapalo, N = 21). The present article provides detailed information about each text or narrative, including measurements of four graph attributes of interest: number of nodes (lexical diversity), repeated edges (short-range recurrence), largest strongly connected component (long-range recurrence), and average shortest path (graph length).