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Wastewater treatment plants (WWTPs) are complex systems presenting stochastic, non-linear, and non-stationary behavior, which makes their operational management very challenging. In this context, data collected from distributed sources across the plant play a central role in the optimized operation and control of WWTPs. However, even when available, the use of collected data is far from trivial due to the coexistence of asynchronous measurements, data with different granularity, measurements of different quality (precision, accuracy), multimodal sources (sensors, spectra, images, hyphenated instrumentation), among other aspects related to the data life cycle. Such heterogeneity in process data characteristics hinders the application of most off-the-shelf data analytics methods. Flexible solutions able to cope with the complexity of systems and of the data they generate are therefore necessary to overcome these limitations and enable an effective analysis and operation of WWTPs. In this article, data-fusion approaches for handling multiple heterogeneous sources of process data are developed and comparatively tested. Priority is given to solutions that can flexibly be adapted to different specific operational contexts. The methodologies are tested on an industrial case study (WWTP), where the concentration of a toxin in the effluent stream is to be predicted from available heterogeneous data. Single- and multi-source modeling approaches are contemplated and a nested cross-validation method was developed to handle the time-series nature of the models. Bayesian fusion synergistically combines data from different sources considering their uncertainty, standing out among the methodologies tested as offering a good balance in terms of accuracy (RMSEP = 1.34), stability (prequential IQR = 0.034), and flexibility (to accommodate missing and new sources). [Display omitted] • WWTP data is multimodal and asynchronous, exhibiting multiscale dynamics, non-linearity, and non-stationarity. • Current single-source methods fall short in handling all these complex features. • Multi-source methods present better performance and are more flexible and scalable. • An analytical workflow was developed that uses the prequential cross-validation method. • Bayesian fusion offers the best compromise of accuracy, stability, and flexibility. [ABSTRACT FROM AUTHOR]

Highlights • A new two-stage feature selection methodology for high-dimensional regression problems is proposed. • It is called wide spectrum feature selection for regression (WiSe). • Pearson correlation, Spearman rank correlation, Symmetrical uncertainty, and all their pairwise combinations are considered in the first stage. • In the second stage, the first-pass screened features are further selected using regression-dependent approaches. • Results confirm the increased predictive accuracy of models built after filtering out irrelevant features. Abstract Developing predictive models from industrial datasets implies the consideration of many possible predictor variables (features). Using all available features for data-driven modelling is not recommended, as most of them are expected to be irrelevant and their inclusion in the model may compromise robustness and accuracy. In this work, we present, test and compare a new two-stage feature selection method called wide spectrum feature selection for regression (WiSe). In the first stage, a combination of efficient bivariate filters analyzes linear and non-linear association patterns between predictors and responses, screening out clearly noisy features. In the second stage, the reduced set of retained features is subject to further selection in the scope of the predictive methods considered, optimizing their predictive performance. Three simulated datasets and an industrial case illustrate the effectiveness and benefits of applying WiSe to support model development in a wide range of high-dimensional regression problems. [ABSTRACT FROM AUTHOR]

Two cytotoxic copper(II) complexes with N-H and N -methylated benzimidazole-derived ligands (Cu- L 1 and Cu- L 1Me ; L 1 = bis(2-methylbenzimidazolyl)(2-methylthioethyl)amine, L 1Me = bis(1-methyl-2-methylbenzimidazolyl)(2-methylthioethyl)amine) were synthesized and exposed to human erythrocytes and molecular models of its membrane. The latter were bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), classes of lipids present in the external and internal moieties of the human red cell membrane, respectively. Scanning electron microscopy (SEM) of erythrocytes incubated with solutions of both Cu(II) complexes showed that they induced morphological changes to the normal cells to echinocytes, and hemolysis at higher concentrations. Real-time observation of the dose-dependent effects of the complexes on live erythrocytes by defocusing microscopy (DM) confirmed SEM results. The formation of echinocytes implied that complex molecules inserted into the outer moiety of the red cell membrane. X-ray diffraction studies on DMPC and DMPE showed that none of these complexes interacted with DMPE and only Cu- L 1 interacted with DMPC. This difference was explained by the fact that Cu- L 1Me complex is more voluminous than Cu- L 1 because it has two additional methyl groups; on the other hand, DMPC molecule has three methyl groups in its bulky terminal amino end. Thus, by steric hindrance Cu- L 1Me molecules cannot intercalate into DMPC bilayer, which besides is present in the gel phase. These results, together with the increased antiproliferative capacity of the N -methylated complex Cu- L 1Me over that of Cu- L 1 are rationalized mainly based on its higher lipophilicity. [ABSTRACT FROM AUTHOR]

Two cytotoxic copper(II) complexes with N–H and N-methylated benzimidazole-derived ligands (Cu- L 2 and Cu- L 2Me ) were synthesized and made to interact with human erythrocytes and molecular models of their plasmatic membranes. The latter consisted in lipid bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), lipids of the types present in the outer and inner monolayers of the human erythrocyte membrane, respectively. Initial assessment of the interaction of the complexes with DMPC and DMPE consisted of X-ray diffraction studies, which showed preferential interactions with the former. Scanning electron microscopy (SEM) of erythrocytes incubated with solutions of the Cu(II) complexes evidenced deformation of the cells to stomatocytes and knizocytes by Cu- L 2 and Cu- L 2Me due to interactions with the inner and outer leaflets of the cell membranes, respectively. This was further confirmed by real-time observation of the dose-dependent effects of the complexes on live erythrocytes by defocusing microscopy (DM). The combined observations, including the increased antiproliferative activity of the N-methylated complex Cu- L 2Me over that of Cu- L 2 is rationalized based on the higher lipophilicity of the former. This property would facilitate passive diffusion of Cu- L 2Me through the cell membrane, particularly in the initial stages when the DMPC-rich outer leaflet is involved. In contrast, the benzimidazole N–H groups of Cu- L 2 may participate in hydrogen bonding with DMPE polar groups; this result is consistent with the formation of stomatocyte induced by the latter complex. [ABSTRACT FROM AUTHOR]

Mixed N,S tripodal ligands bis(2,4-dimethylphenylthioethyl)(2-methylbenzimidazolyl)amine L 1 , bis(2,4-dimethylphenylthioethyl)(1-methyl-2-methylbenzimidazolyl)amine L 2 , and bis(1-methyl-2-methylbenzimidazolyl)(2-methylthioethyl)amine L 3 were employed to prepare the corresponding copper complexes. L 1 and L 2 associate weakly with Cu 2+ , while the reaction of CuI with L 1 affords [ L 1 CuI]. This was characterized in the solid state by the chelating tridentate coordination mode of L 1 , with a free thioether, and a terminal iodide, in contrast with the commonly observed Cu–I–Cu bridges. For L 3 , Cu + and Cu 2+ complexes are accessible as [ L 3 Cu]PF 6 , and the crystallographically characterized [ L 3 CuCl]Cl. The latter has a square pyramidal coordination around the Cu 2+ ion, with the thioether as an axial ligand that remains coordinated in solution, as evidenced by UV–Vis spectroscopy. [ABSTRACT FROM AUTHOR]

Abstract: The molecular interactions of 5,6-dichloro-2-(trifluoromethyl)-1H-benzimidazole (G2), an antiprotozoa with poor aqueous solubility, with 2-hydroxypropyl-α-cyclodextrin (HPαCD), methyl-β-cyclodextrin (MβCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) were examined. The aqueous solubility enhancement by cyclodextrins (CDs) was evidenced in phase-solubility diagrams, and the stoichiometry of G2/CD systems was determined by Job''s plots. Two-dimensional NMR spectroscopic data revealed that a different mode of interaction took place between G2 and CDs in solution. With HPαCD, a non-inclusion complex was generated. In the case of MβCD, a typical host–guest system was obtained and with HPβCD a partial inclusion complex through the narrow side of the macrocycle was formed. ESI-mass spectrometric data confirmed the stoichiometry and mode of interaction of these systems in solution. Solid-state characterization (scanning calorimetry and powder X-ray diffraction) supported the inclusion complex formation. The leishmanicidal activity, trypanocidal activity and non-toxic profile of G2/MβCD showed the advantages of using this inclusion complex to promote the biological assays extension of G2. [Copyright &y& Elsevier]

Abstract: Reaction of p-tert-butylcalix[8]arene 1 with 2,6-bis(chloromethyl)pyridine results in the regioselective introduction of the nitrogen-containing heterocycle to the 1 and 5 phenolic positions. The deprotonated form of the 1,5-bridged compound 2 acts as a dianionic ligand toward Cs+. The dicesium complex [2·Cs2O(H2O)], which has water molecules as additional ligands for the cesium cations, was characterized by X-ray crystallography. [Copyright &y& Elsevier]

Abstract: Octakis(dimethylsiloxy)-octa-p-tert-butylcalix[8]arene was prepared from the parent p-tert-butylcalix[8]arene and 1,1,3,3-tetramethyldisilazane. Desilylation of the siloxy-calix[8]arene with tetrabutylammonium fluoride hydrate under different conditions afforded di- and tetraanionic derivatives. Determination of the solid state structure of the dianion revealed the formation of an inclusion compound with one tetrabutylammonium cation inside the macrocyclic cavity. [Copyright &y& Elsevier]

: PurposeTo report a new treatment for acquired periodic alternating nystagmus in which medical therapy with baclofen was not tolerated.: DesignInterventional case report and literature review.: InterventionSimultaneous adjustable bilateral retroequatorial horizontal rectus muscle recessions.: Main outcome measuresOcular alignment and ocular motility recordings.: ResultsA 30-year-old man had blurred vision after an emergency left temporal craniotomy for gunshot wounds. Ophthalmologic examination revealed periodic alternating nystagmus that was documented by an infrared electronystagmogram. Baclofen was started but was not tolerated. Bilateral lateral and medial retroequatorial rectus muscle recessions were performed and were successful in the treatment of this patient.: ConclusionSimultaneous bilateral retroequatorial horizontal rectus recessions may be an effective treatment for intractable acquired periodic alternating nystagmus. [Copyright &y& Elsevier]

Purpose: To describe a patient with congenital nystagmus that decreased in one eye after the development of a cavernous sinus meningioma.Design: Interventional case report.Methods: A 45-year-old man with congenital nystagmus, albinism, and high myopia presented with right upper eyelid ptosis that was corrected surgically on three occasions during a 3-year period. An episode of syncope was followed by diagnostic evaluation that disclosed a cavernous sinus meningioma. He commented that his right eye nystagmus progressively decreased. He was found to have ophthalmoplegia on the right eye due to nerve compression by the meningioma.Results: A magnetic resonance imaging scan disclosed a cavernous sinus meningioma extending into the parachiasmal and clival areas. A biopsy specimen of the lesion demonstrated a meningioma.Conclusions: Any patient with acquired ptosis should have a complete ophthalmic examination, including evaluation of extraocular motility. [ABSTRACT FROM AUTHOR]

A 19-year-old woman presented with frontal headaches, papilledema, and binocular horizontal double vision due to a left VI nerve palsy. MRV demonstrated sagittal sinus and bilateral transverse sinus thrombosis. The clinical and neuro-radiologic signs resolved after anticoagulation. [Copyright &y& Elsevier]

Study Objective: To show laparoscopic management of a symptomatic parasitic leiomyoma of paravesical and obturator fossa.Design: Edited video demonstrating a step-by-step explanation of the surgical technique of this case.Setting: University hospital.Interventions: Uterine leiomyomas are the most common benign pelvic tumors in women. They occur in approximately 25% of women of reproductive age. Parasitic leiomyomas are rare, with few cases reported in the literature [1,2]. They are classified according to their location in relation to the myometrium. Parasitic leiomyomas are in group 8 of the International Federation of Gynecology and Obstetrics classification [3]. It is not clear why they are produced; it is thought that they could derive from subserous leiomyomas that achieved a blood supply from neighboring structures outside the uterus [1,3]. They can also have iatrogenic origin in patients who have undergone previous surgery such as myomectomy with power morcellation use [4]. We present the case of a 32-year-old women, gravida 1 para 1, without previous pelvic surgery. She complained of lower back and sacrum pain and nonspecific discomfort in her inner thigh. Her physical examination showed a 6- to 7-cm solid right paravaginal tumor. Ultrasonography and nuclear magnetic resonance confirmed the presence of a 7 × 5-cm solid tumor in the right paravesical and obturator fossa. The diagnosis of a probable parasitic myoma was proposed, and a laparoscopic resection was scheduled. The video demonstrates the surgical technique with special emphasis on the anatomy of the surgical site. The patient was discharged 24 hours after surgery without complications. The final pathology confirmed uterine leiomyoma. Written informed consent was requested according to the regulations of our institution.Conclusion: A successful laparoscopic resection of a symptomatic parasitic leiomyoma of the paravesical and obturator fossa was achieved. The importance of knowledge of the pelvic anatomy for the management of this type of case is underlined. [ABSTRACT FROM AUTHOR]

• Calixarene derivative with phenanthroline moiety acts as nitrogen ligand for nickel complexes. • The chelating phenantrholine places nickel (II) ions within large calix[8]arene cavity. • Ni(II) complexes are catalyst precursors for electrochemical reduction of carbon dioxide. The electrochemical behavior and catalytic activity for the electroreduction of CO 2 of complexes of Ni(II) containing phenanthroline-based ligands, with or without a calixarene scaffold, were tested. The complexes were characterized by spectroscopic techniques, and their electrocatalytic properties determined by cyclic voltammetry. With water as proton source the complex [(1,5-(2,9-dimethyl-1,10-phenanthro)- p-tert -butylcalix[8]arene)NiCl 2 ] (1) presented a significant increase in current at E = −2.36 V (relative to Ag/AgCl reference electrode) when reduced under an atmosphere of CO 2 , indicating that an electrocatalytic process occurs. Thus, calix[8]arenes that feature a phenanthroyl moiety as bidentate N -ligands, and an intramolecular proton source in the phenolic –OH groups, afford Ni(II) electrocatalysts for the reduction of CO 2. [ABSTRACT FROM AUTHOR]

Equipment degradation is ubiquitous in the Chemical Process Industry (CPI), causing significant losses in efficiency, controllability, and plant economy, as well as an increased environmental fingerprint and additional operational safety risks. The case of fouling in heat exchangers, in particular, is well-known and pervasive but still hard to cope with, given the complexity of the underlying mechanisms and the difficulty of assessing its extension in real-time. This problem becomes even more complex in batch processes producing different products, where multiple recipes are used, bringing additional variability and new challenges to the analysis. In this work, we propose a functional data-driven approach for streamlining the analysis and monitoring of the progression of fouling taking place in heat exchangers in multiproduct batch processes. With the approach developed and presented in this paper, process analysis can be efficiently conducted by integrating historical data with engineering knowledge. Furthermore, a surrogate measure of fouling extension in heat exchangers is proposed, that can be readily implemented as an equipment health indicator (EHI) leading to a safer operation of the heat exchanger. [ABSTRACT FROM AUTHOR]

Two novel Iron (II) complexes featuring tetrapodal bis(benzimidazole)amino thio- and selenoether ligands (LS and LSe) were synthesized, characterized, and tested as electrocatalysts for the hydrogen evolution reaction. The bromide complexes [Fe( LS , LSe )Br 2 ] (1–2) are highly insoluble, but their DMSO solvates were characterized by single crystal X-ray diffraction, revealing an octahedral coordination environment that does not feature coordination of the chalcogen atoms. The corresponding triflate derivatives [Fe(LS , LSe)(MeCN) 3 ]OTf 2 (1c-2c) were employed for electrocatalytic proton reduction, with 1c exhibiting higher activity, thus suggesting that the thioether may participate as a more competent pendant ligand for proton transfer. Bis(benzimidazole)-based Iron(II) complexes are competent Hydrogenase-inspired hydrogen evolution electrocatalysts that feature potentially proton-accepting intramolecular thio- and selenoethers groups. [Display omitted] • Synthesis and characterization of benzimidazole-based Fe(II) complexes • Solid-state structures of Fe(II) complexes show non-coordinated selenoether groups. • Proton reduction evidenced by cyclic voltammetry. • Fe(I) proposed as active species in electrocatalytic hydrogen evolution. [ABSTRACT FROM AUTHOR]

We explore the use of tools from Riemannian geometry for the analysis of symmetric positive definite matrices (SPD). An SPD matrix is a versatile data representation that is commonly used in chemical engineering (e.g., covariance/correlation/Hessian matrices and images) and powerful techniques are available for its analysis (e.g., principal component analysis). A key observation that motivates this work is that SPD matrices live on a Riemannian manifold and that implementing techniques that exploit this basic property can yield significant benefits in data-centric tasks such as classification and dimensionality reduction. We demonstrate this via a couple of case studies that conduct anomaly detection in the context of process monitoring and image analysis. • Mathematical introduction to Riemannian manifolds and their geometric analysis. • Framework (and code) for the analysis of SPD matrices through Riemannian geometry. • Benefits of geometric approach to data analysis illustrated through two real world case studies. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this work is to study the molecular association that occurs between 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20), an antiparasitic compound recently found by our research group, with poor aqueous solubility. The complex stability constant and stoichiometric ratio determined by phase-solubility diagram and Job’s plot provided evidence that HPβCD enhanced water solubility of RCB20 through inclusion complex formation. Two-dimensional 1H NMR spectroscopy is used to study the molecular arrangement of inclusion complex in solution. These results are further supported using molecular modeling studies. In the solid state, the complexation is confirmed by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy. Finally, RCB20/HPβCD complex has better activity than RCB20 against the adult and muscle larvae phase of Trichinella spiralis. [ABSTRACT FROM AUTHOR]

• Hybrid modeling has been attracting the interest of the scientific community for almost 30 years. • Big data and the industry 4.0 bring opportunities for new hybrid modeling solutions. • We review hybrid modeling schemes, their training, validation and applications. • Usually mechanistic models are improved by data-driven models. • There is the need for a generic framework balancing prior and data-driven knowledge. The chemical processing industry has relied on modeling techniques for process monitoring, control, diagnosis, optimization, and design, especially since the third industrial revolution and the emergence of Process Systems Engineering. The fourth industrial revolution, connected to massive digitization, made it possible to collect and process large volumes of data triggering the development of data-driven frameworks for knowledge extraction. However, one must not leave behind the successful solutions developed over decades based on first principle mechanistic modeling approaches. At present, both industry and researchers are realizing the need for new ways to incorporate process and phenomenological knowledge in big data and machine learning frameworks, leading to more robust and intelligible artificial intelligence solutions, capable of assisting the target stakeholders in their activities and decision processes. In this article, we review hybrid modeling techniques, associated system identification methodologies and model assessment criteria. Applications in chemical and biochemical processes are also referred. [ABSTRACT FROM AUTHOR]

This paper explores dimensionality reduction (DR) approaches for visualizing high dimensional data in chemical processes. Visualization provides powerful insight and process understanding in the industrial context, and accelerates process troubleshooting. A diverse array of existing, easy-to-use DR methods are evaluated in three case studies on large-scale industrial manufacturing plants. Supervised and unsupervised cases are presented with the objective of solving typical industrial problems related to unplanned events, plant performance improvement, and quality underperformance troubleshooting. For the unsupervised case, the evaluation aims to identify approaches that provide insight beyond those of PCA (Principal Component Analysis), and also examines quality metrics of the reduced (latent) space which characterize the degree of trust in the DR. UMAP (Uniform Manifold Approximation and Projection) outperforms other techniques, bringing new insights when comparing with other methods. For the supervised case, UMAP is combined with traditional variable selection methods, such as VIP (Variable Influence on Projection) weights from PLS-DA (Partial Least Squares Discriminant Analysis), in order to improve latent space visualization by increasing separation between classes. • Dimensionality reduction techniques are applied to three industrial case studies. • UMAP has outperformed other methods that solve unsupervised problems. • Combining UMAP with feature selection techniques improves latent space visualization. [ABSTRACT FROM AUTHOR]

The synthesis of bis(N-methylbenzimidazol-2-yl)methane serves as the entry point for the preparation of a tetrabenzimidazole-based binucleating ligand. A cupric complex of the former compound was prepared to compare its properties to those of the dicopper complexes of the tetrabenzimidazole derivative. In the latter case, the reaction of the binucleating ligand with cupric trifluoromethylsulfonate in air results in intramolecular C H activation with concomitant hydroxylation, presumably by an in situ formed copper-oxygen reactive intermediate. This reactivity highlights the relevance of benzimidazole-based scaffolds in biologically inspired copper-oxygen systems. [ABSTRACT FROM AUTHOR]

In this paper, we propose a novel autocovariance-based plant-model mismatch estimation approach for linear MPC MIMO control loops with changing setpoints and measurable disturbances. Assuming a noise model is available and that there are of periods of operating data where the active set of the controller is fixed and the plant-model mismatch is invariant, we establish an explicit relation between the autocovariance matrices of the mean-centered process outputs and the plant-model mismatch. We then formulate the mismatch estimation problem as an optimization aimed at minimizing the difference between the theoretical autocovariance, computed from the established relation, and actual output autocovariances, calculated from the plant data. We elaborate our results for step-response models typically used in MPC, as well as for parametric (transfer function models) in both continuous time and discrete time. A simulation case study for an unconstrained MPC controller with measurable disturbances is used to illustrate the theoretical results. [ABSTRACT FROM AUTHOR]

A new macrocycle bearing tyramine arms through amide linkages, 2,2′-(2,9-dioxo-1,4,7,10-tetraazacyclotridecane-4,7-diyl)bis( N -(4-hydroxyphenethyl)acetamide) abbreviated as L13Tyra, has been synthesized with amide-coupling agents in a microwave reactor. This macrocycle involves two potential metal-coordinating and bioactive sites, i.e ., the tetraaza-macrocyclic ring (with a low basicity of the amino nitrogen) and the pendant phenol arms (with a small p K a 8.6). The Cu 2+ complex has different compositions in solid and in solution. An X-ray crystal study shows that a mononuclear complex [Cu(L13Tyra – 2H)] 0 is formed with a square coordination of two deprotonated amide nitrogen and two amino nitrogen atoms of the macrocyclic ring; a carbonyl oxygen atom from a pendant arm occupies an axial site to construct a square pyramid. UV–Vis spectrometric titrations in aqueous solutions indicate the formation of a binuclear complex [Cu 2 (L13Tyra – 4H)(H 2 O) x ] 0 in which phenolate oxygen atoms of the tyramine arms coordinate a Cu 2+ ion in addition to the coordination of the macrocyclic chelate; such a binuclear structure is maintained only in solution. The uncoordinated ligand has a high antioxidant capacity with a TEAC (Trolox equivalent antioxidant capacity) assay comparable to that of ascorbic acid, thanks to the phenolic OH of the tyramine arms. Copper(II) ion works as an inhibitor against the activity; the TEAC assay of the binuclear complex is as small as one-twentieth that of the uncoordinated ligand. Antiproliferative and cytotoxic assays with normal and cancer cell lines show no toxicity for both the ligand and its Cu 2+ complex. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of polydentate amine-S-arythiocarbamates was tested by directed ortho-lithiation of 2,4-disubstituted thiophenols, or the corresponding O- and S-arylthiocarbamates by deprotonation or lithium–bromine exchange, followed by addition of the electrophiles N(CH2CH2X)3 (X=Br, I). In the case of the thiophenol, deprotonation resulted in a trithioether-amine upon addition of the electrophile. With the O- and S-thiocarbamates, the reactions resulted in the migration of the thiocarbamoyl group to the ortho-position (Fries rearrangement), or nucleophilic attack of the carbonyl group by butyllithium, respectively. An alternative route employed 2,4-disubstituted phenols to obtain the corresponding salicylaldehydes, and subsequently the O-arylthiocarbamates for Newman–Kwart thermal rearrangement (NKR). Finally, the formyl group on the S-arylthiocarbamates allowed reductive amination to assemble polytopic compounds with amine and S-thiocarbamate groups. [Copyright &y& Elsevier]

Abstract: An extension of the method for the regioselective introduction of nitrogen-containing heterocycles at the 1,5-phenolic positions of p-tert-butylcalix[8]arene previously described for 2,6-bis(chloromethyl)pyridine allowed the use of 2,9-bis(bromomethyl)-1,10-phenanthroline as a selective 1,5-dialkylating agent. The 1,5-dimethylpyridine derivative was previously characterized as a relatively rigid dicesium complex [1(4H)2−·2Cs+], its metal-free counterpart 1(6H) is herein described as a fluxional species in solution, as evidenced by VT–NMR and theoretical studies. The 1,5-[2,9-bis(methylene)-1,10-phenanthroline]-p-tert-butylcalix[8]arene analogue 2(6H) was characterized spectroscopically in solution as a relatively rigid cone conformer at 390K. The identity of both metal-free 1(6H) and the monocesium complex [2(5H)−·Cs+] was established in the solid state by X-ray crystallography, confirming the 1,5-substitution of the latter. The conformational behavior of 1(6H) and 2(6H) in solution is described in terms of the enthalpic and entropic contributions by semiempirical methods. [Copyright &y& Elsevier]

Abstract: Plasmodium, the parasite which causes malaria in humans multiplies in the liver and then infects circulating erythrocytes. Thus, the role of the erythrocyte cell membrane in antimalarial drug activity and resistance has key importance. The effects of the antiplasmodial N 6-(4-methoxybenzyl)quinazoline-2,4,6-triamine (M4), and its inclusion complex (M4/HPβCD) with 2-hydroxypropyl-β-cyclodextrin (HPβCD) on human erythrocytes and on cell membrane molecular models are herein reported. This work evidences that M4/HPβCD interacts with red cells as follows: a) in scanning electron microscopy (SEM) studies on human erythrocytes induced shape changes at a 10μM concentration; b) in isolated unsealed human erythrocyte membranes (IUM) a concentration as low as 1μM induced sharp DPH fluorescence anisotropy decrease whereas increasing concentrations produced a monotonically decrease of DPH fluorescence lifetime at 37°C; c) X-ray diffraction studies showed that 200μM induced a complete structural perturbation of dimyristoylphosphatidylcholine (DMPC) bilayers whereas no significant effects were detected in dimyristoylphosphatidylethanolamine (DMPE) bilayers, classes of lipids present in the outer and inner monolayers of the human erythrocyte membrane, respectively; d) fluorescence spectroscopy data showed that increasing concentrations of the complex interacted with the deep hydrophobic core of DMPC large unilamellar vesicles (LUV) at 18°C. All these experiments are consistent with the insertion of M4/HPβCD in the outer monolayer of the human erythrocyte membrane; thus, it can be considered a promising and novel antimalarial agent. [Copyright &y& Elsevier]

Abstract: Endocannabinoids (eCBs) are endogenous neuromodulators of synaptic transmission. Their dysfunction may cause debilitating disorders of diverse clinical manifestation. For example, drug addiction, lack of sex desire, eating disorders, such as anorexia or bulimia and dyssomnias. eCBs also participate in the regulation of core temperature and pain perception. In this context, it is important to recognize the utility of cannabinoid receptor 1 (CB1R) agonists, natural as Δ9-tetrahydrocannabinol (THC) or synthetic as Nabilone as useful drugs to alleviate this kind of patients’ suffering. Therefore, we have developed a new drug, (R,Z)-18-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-18-oxooctadec-9-en-7-yl phenylacetate (PhAR-DBH-Me), that appears to bind and activate the CB1R. This diazabicyclic amide was synthesized from phenylacetylricinoleic acid and (1S,4S)-2,5-diazabicyclo[2.2.1]heptane. To test its cannabinergic properties we evaluated its effects on core temperature, pain perception, and the sleep-waking cycle of rats. Results indicate that 20 and 40mg/kg of PhAR-DBH-Me readily reduced core temperature and increased pain perception threshold. In addition, 20mg/kg increased REM sleep in otherwise normal rats. All these effects were prevented or attenuated by AM251, a CB1R antagonist. Place preference conditioning studies indicated that this molecule does not produce rewarding effects. These results strongly support that PhAR-DBH-Me possesses cannabinoid activity without the reinforcement effects. [Copyright &y& Elsevier]

Abstract: The Newman–Kwart thermal rearrangement of two 2,4-disubstituted O-arylthiocarbamates, prepared from the corresponding phenols, is reported. Clean conversion to the S-arylthiocarbamates in high yields was observed. The rearrangement appears to be facilitated by the presence of electron-withdrawing substituents in the 2- and 4-positions of the aromatic ring. [Copyright &y& Elsevier]

• A statistical learning procedure for Dow data challenge problem (Braun et al., 2020) is presented that integrates process knowledge in all steps from pre-processing and model interpretation. • An accurate inferential sensor model is built with online bias learning based on new data to predict the impurity in the product stream with apparent drifts. • Least angle regression solution (LARS) is shown to select only one variable among a set of collinear variables. • We report the detection of an equipment-switching operation in the data and interpolations found in the impurity data, which leads to unique data pre-processing measures. • Using a softplus function, we propose a method to deal with non-negative physical property modeling. In this paper, we propose a statistical learning procedure that integrates process knowledge for the Dow data challenge problem presented in Braun et al. (2020). The task is to build an accurate inferential sensor model to predict the impurity in the product stream with apparent drifts. The proposed method consists of i) process data exploratory analysis, ii) a method for variable selection, iii) a method to deal with non-negative physical property modeling using a softplus function; and iv) a method for online bias updating based on known data. We make use of process operation knowledge in all steps of data analytics, including exploratory analysis and feature selection. We report the detection of equipment-switching operations in the data and interpolations found in the impurity data. Partial least squares (PLS) and least angle regression solution (LARS) are adopted to model the data with strong collinearity. Pros and cons of LARS and PLS are given with practical implications. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relationship between polymorphisms in the gene encoding the β1-adrenergic receptor (β1-AR) and clinical response to betaxolol hydrochloride 0.25% in a small pilot study of normal volunteers. Design: Prospective nonrandomized comparative trial. Participants: Forty-eight consecutive normal volunteers who met all eligibility requirements for inclusion into this study. Methods: Baseline intraocular pressure (IOP) was recorded. Subjects began treatment with betaxolol (1 drop both eyes twice daily) and underwent follow-up IOP recordings at 3 and 6 weeks. Peripheral blood was obtained for genetic analysis. Main Outcome Measures: Response to betaxolol was calculated as the change in mean IOP from baseline (averaged between both eyes and averaged between both follow-up visits). The β1-AR genotype was determined by polymerase chain reaction with restriction fragment length polymorphisms at codons 49 (serine [Ser] or glycine [Gly]) and 389 (arginine [Arg] or Gly). Results: There were 32 Ser49 homozygotes and 16 Gly49 carriers. There were no statistically significant differences between the Ser49 homozygotes and the Gly49 carriers with respect to baseline IOP or response to betaxolol therapy. There were 25 Arg389 homozygotes and 23 Gly389 carriers (22 heterozygotes and 1 Gly389 homozygote). As compared with Gly389 carriers, the Arg389 homozygotes had a higher baseline IOP (15.8 mmHg vs. 13.7 mmHg; P = 0.009) and a greater magnitude of response to betaxolol therapy (−3.4 mmHg vs. −1.5 mmHg; P = 0.0009). The Ser49 homozygote genotype was not independently associated with baseline IOP (P = 0.47) or with a response to betaxolol (P = 0.99). The Arg389 homozygote genotype was independently associated with a higher baseline IOP (P = 0.03) and a greater response to betaxolol (P = 0.03), even after adjusting for baseline IOP. Conclusions: In this small pilot series, a single nucleotide polymorphism at codon 389 in the β1-AR seems to correlate with a response to betaxolol therapy in normal, nonglaucomatous volunteers. There was no such correlation at codon 49. The polymorphism at codon 389 may predict short-term response to betaxolol and may serve as a determinant of response to betaxolol and other adrenergic agents in glaucomatous eyes requiring treatment. [Copyright &y& Elsevier]

Four new nickel (II) complexes with bis(benzimidazole)thio- and selenoether-based ligands have been synthesized and characterized in the solid state by elemental analysis, IR, magnetic susceptibility and X-ray crystallography, and in solution by FAB+ mass spectrometry, UV–vis spectroscopy and cyclic voltammetry. Single-crystal X-ray diffraction analysis of the compounds revealed octahedral geometries for all nickel centers. Three of the four complexes are dimers with chloride bridges between the two Ni(II) ions. However, in solution all complexes have a monomeric formulation, based on mass spectrometry and osmometry measurements. The complexes were also screened for their cytotoxic activity on human cell lines (HeLa, SK-LU-1 and HEK-293), and compared with a related Cu(II) complex. Bis(benzimidazole)thio- and selenoether ligands afford mono- and bimetallic Ni(II) complexes in the solid state, with monometallic behavior in solution. They show moderate cytotoxic activity towards cancer cell lines, in some cases with better selectivity than a Cu(II) analog. Unlabelled Image • Synthesis of 4 Ni(II) complexes with bis(benzimidazole)thio/selenoether ligands. • All Ni(II) complexes were characterized by X-ray crystallography. • Mass spectrometry confirms in all cases monomeric species in solution. • In vitro cytotoxicity of the complexes against cancer cell lines was studied. • One Ni(II) complex exhibits greater selectivity than its Cu(II)-based analog. [ABSTRACT FROM AUTHOR]

Abstract: Reaction of the chiral ligands (1S,4S)-2,5-bis(6-methylpyridyl)-diazabicyclo[2.2.1]heptane (L 1 ), and (1S,4S)-2,5-bis(2-methylbenzimidazolyl)-diazabicyclo[2.2.1]heptane (L 2 ) with copper(II) acetate results in the hydroxo-bridged dicopper complexes [(L 1 )Cu2(μ-OH)(H2O)(OAc)2Cl] (1-Cl·H2O), and [(L 2 )Cu(μ-OH)(H2O)(MeOH)(OAc)2]OAc (2 .H2O,MeOH). Both chiral complexes were characterized spectroscopically, as well as in the solid state by X-ray crystallography. [Copyright &y& Elsevier]

Abstract: Reaction of bispicolyl-p-tert-butylcalix[4]arene (L 1 ) functionalized in alternate phenolic positions with dimeric copper(II) acetate resulted in the formation of a hybrid organic–inorganic polymer. In the solid state, dicopper fragments are bridged by the bidentante ligand [Cu2(μ-O2CCH3)4(μ-L 1 )·C4H8O] n , with one molecule of tetrahydrofuran in the asymmetric unit. The two independent Cu(II) ions possess square pyramidal coordination geometries defined by the four acetate ligands, and a picolyl group in the axial position. [Copyright &y& Elsevier]