Crystallographic Texture Evolution of a Zinc Sheet Subjected to Different Strain Paths

Metallurgical and Materials Transactions A - The use of zinc sheets has largely increased in the last years, fundamentally because of new tendencies in architecture and, at the same time, due to...     

Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia

The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients.     

A quantitative investigation of the role of information and communication technologies in the implementation of a product-service system

This paper reports evidence from a survey, aimed at testing whether and how Information and Communication Technologies (ICTs), which enable the adoption of product-service systems, can contribute to value creation. This analysis builds on previous contributions, according to which companies that are enriching their product offering through value-added services (the so-called servitisation strategy) often report lower levels of profitability, owing to the poor performance of their operating process. A wide stream of research claims that companies that invest in ICTs can enjoy valuable outcomes, since the adoption of such technologies results in processes that are more efficient and more responsive. Our hypothesis concerns the possibility of leveraging ICTs at operating process level so as to pursue a servitisation strategy. The in-field analysis presented in this paper concerns a sample of 109 companies located in Italy; data collected through the survey have been analysed using the structural equation modelling approach. The evidence presented demonstrates that ICTs can have a relevant impact on value creation because they lead to superior responsiveness of operating processes and to sound improvements in the product offering. In particular, companies that are able to embed such superior responsiveness into their product offering can further boost value creation.     

Design and Evaluation In Vitro of Controlled Release Mucoadhesive Tablets Containing Chlorhexidine

ABSTRACT

This investigation deals with the development of buccal tablets containing chlorhexidine (CHX), a bis-bis-guanide with antimicrobial and antiseptic effects in the oral cavity, and able to adhere to the buccal mucosa to give local controlled release of drug. A mucoadhesive formulation was designed to swell and form a gel adhering to the mucosa and controlling the drug release into the oral cavity.

Some batches of tablets were developed by direct compression, containing different amounts of hydroxypropylmethylcellulose (HPMC) and carbomer; changing the amount ratio of these excipients in formulations, it is possible easily modulate the mucoadhesive effect and release of drug. The in vitro tests were performed using the USP 26/NF paddle apparatus, a specifically developed apparatus, and a modified Franz diffusion cells apparatus. This last method allows a simultaneous study of drug release rate from the tablets and drug permeation through the buccal mucosa.

Similar tests have also been carried out on a commercial product, Corsodyl gel^®, in order to compare the drug release control of gel with respect to that of the mucoadhesive tablet, as a formulation for buccal delivery of CHX. While the commercial formulation does not appear to control the release, the formulation containing 15% w/w methocel behaves the best, ensuring the most rapid and complete release of the drug, together with a negligible absorption of the active agent as required for a local antiseptic action in the oral cavity.     

MT1‐Selective Melatonin Receptor Ligands: Synthesis,Pharmacological Evaluation,and Molecular Dynamics Investigation of N‐{[(3‐O‐Substituted)anilino]alkyl}amides

The design of compounds selective for the MT₁ melatonin receptor is still a challenging task owing to the limited knowledge of the structural features conferring selectivity for the MT₁ subtype, and only few selective compounds have been reported so far. N‐(Anilinoalkyl)amides are a versatile class of melatonin receptor ligands that include nonselective MT₁/MT₂ agonists and MT₂‐selective antagonists. We synthesized a new series of N‐(anilinoalkyl)amides bearing 3‐arylalkyloxy or 3‐alkyloxy substituents at the aniline ring, looking for new potent and MT₁‐selective ligands. To evaluate the effect of substituent size and shape on binding affinity and intrinsic activity, both flexible and conformationally constrained derivatives were prepared. The phenylbutyloxy substituent gave the best result, providing the partial agonist 4 a , which was endowed with high MT₁ binding affinity (pK_i=8.93) and 78‐fold selectivity for the MT₁ receptor. To investigate the molecular basis for agonist recognition, and to explain the role of the 3‐arylalkyloxy substituent, we built a homology model of the MT₁ receptor based on the β₂ adrenergic receptor crystal structure in its activated state. A binding mode for MT₁ agonists is proposed, as well as a hypothesis regarding the receptor structural features responsible for MT₁ selectivity of compounds with lipophilic arylalkyloxy substituents.     

Tokenism or Political Activism? Some Reflections on Participatory Planning

With the communicative turn in planning theory and the emergence of governance, public participation has become a central issue with respect to inclusionary discourse and the institutionalization of more democratic planning practices. A multitude of participatory planning practices have been implemented with reference to different theoretical perspectives and technical approaches ranging from the traditional to the radical model. Although the current debate about these different participatory activities has brought to the fore an increasing gap between rhetoric and the reality of various models, there are few attempts to compare them in practice. A comparison of participatory activities according to traditional/tokenist and radical models, respectively, should be of interest in the current debate on the crisis of participatory planning and barriers to the institutionalization of participatory planning. This paper discusses tokenist participation in the development planning of Hammarby Sjöstad in Stockholm, Sweden and political activism in a deprived community, Enziteto in Bari, Italy. These two different examples of planner–'community' interaction show the necessity to understand power politics that underlie the ideal of public participation in planning.     

Effects of toasting on the carbohydrate profile and antioxidant properties of chickpea (Cicer arietinum L.) flour added to durum wheat pasta

The effects of the toasting process on the carbohydrate profile and antioxidant properties of chickpea flour were studied, along with the cooking behaviour, and antioxidant and nutritional properties of pasta enriched with the chickpea flour. The toasting process increased the resistant starch, insoluble dietary fibre and antioxidant properties of the flour. Addition of chickpea flour (raw and toasted) to durum wheat semolina changed the carbohydrate profile in the uncooked and cooked enriched pasta, especially with the toasted chickpea, and worsened the overall quality of the pasta. The increase in total phenolic content and total free phenolic acid content in the uncooked pasta was due to positive effects of addition of the chickpea flours, while the increase in the bound phenolics fraction in the cooked pasta was from the durum wheat, which was crucial for its high concentrations of ferulic acid. The increase in the free fraction of the Trolox equivalent antioxidant capacity in cooked pasta was consistent with the addition of chickpea.     

Oxidation Processes in Sicilian Olive Oils Investigated by a Combination of Optical and EPR Spectroscopy

Abstract: Extra virgin olive oil (EVOO) is recognized as one of the healthiest foods for its high content of antioxidants, which forestall and slow down radical formation. Free radical‐initiated oxidation is considered one of the main causes of rancidity in fats and oils. As a consequence, reliable protocols for the investigation of oil oxidation based on selective, noninvasive, and fast methods are highly desirable. Here we report an experimental approach based on UV‐Vis absorbance, steady‐state fluorescence, and electron paramagnetic resonance (EPR) spectroscopy for studying oxidation processes induced by temperature for a period up to 35 d on Sicilian EVOO samples. We followed the decrease in β‐carotene content during incubation time and observed changes in polyphenols and tocopherols during the oxidation processes, focusing on the time scale of those changes. Using EPR spectroscopy, the free radical formation in different oil samples is reported, providing a fingerprint for both the antioxidant content and temporal features of the oxidation process at its early stage. Practical Application: We monitor β‐carotene and chlorophyll in an auto‐oxidation process. A protocol based on spectroscopic measurements is presented and can be used for the quality control process of commercial olive oil.     

Nanodiamond-mediated crystallization in fibers of PANI nanocomposites produced by template-free polymerization: Conductive and thermal properties of the fibrillar networks

The detonation nanodiamond is a novel versatile nanomaterial with tunable properties and surface chemistry. In this work, we report on a template-free method to synthesize polyaniline based nanocomposite fibers during a chemical oxidative precipitation polymerization where the cooperative interactions between nanodiamond and polyaniline nucleates trigger the final morphology of the nanocomposite. FE–SEM and TEM observations evidence the prominent growth of fibril-like structures assembled in 2-D networks of tightly woven, partially oriented fibers. Optical and Raman spectroscopy and X-ray diffraction analyses reveal that the polymer chains are in a protonated emeraldine form and organize themselves in a highly ordered 3-D spatial arrangement. Conductivity measurements performed on isolated fibers by a conductive tip of an AFM apparatus highlight that the diamond filler does not affect the conductive properties of the polyaniline matrix while increases the thermal stability of the polymer as confirmed by TGA studies.