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To treat the novel COronaVIrus Disease (COVID), comparatively fewer medicines have been approved. Due to the global pandemic status of COVID, several medicines are being developed to treat patients. The modern COVID medicines development process has various challenges, including predicting and detecting hazardous COVID medicine responses. Moreover, correctly predicting harmful COVID medicine reactions is essential for health safety. Significant developments in computational models in medicine development can make it possible to identify adverse COVID medicine reactions. Since the beginning of the COVID pandemic, there has been significant demand for developing COVID medicines. Therefore, this paper presents the transfer‐learning methodology and a multilabel convolutional neural network for COVID (MLCNN‐COV) medicines development model to identify negative responses of COVID medicines. For analysis, a framework is proposed with five multilabel transfer‐learning models, namely, MobileNetv2, ResNet50, VGG19, DenseNet201, and Inceptionv3, and an MLCNN‐COV model is designed with an image augmentation (IA) technique and validated through experiments on the image of three‐dimensional chemical conformer of 17 number of COVID medicines. The RGB color channel is utilized to represent the feature of the image, and image features are extracted by employing the Convolution2D and MaxPooling2D layer. The findings of the current MLCNN‐COV are promising, and it can identify individual adverse reactions of medicines, with the accuracy ranging from 88.24% to 100%, which outperformed the transfer‐learning model's performance. It shows that three‐dimensional conformers adequately identify negative COVID medicine responses. [ABSTRACT FROM AUTHOR]

A series of three biphenyl‐based Knoevenagel products (denoted 1a, 1b, 1c) with active methylene groups has been synthesized. Compounds 1a and 1b show strong solid‐state fluorescence, whereas 1c displays low emission. Effects of substituent groups in condensed phase packing of the molecules have been investigated and correlated with their photophysical properties. Interestingly, compound 1a exhibits mechanofluorochromism with emission color changes from yellow to green (wavelength shift of 40 nm) after mechanical grinding. Furthermore, fluorescence of 1a and 1b is turned off under alkaline conditions, making them potential candidates for aggregation‐enhanced emission‐based pH sensors. [ABSTRACT FROM AUTHOR]

Complete photoemission experiments, enabling measurement of the full quantum set of the photoelectron final state, are in high demand for studying materials and nanostructures whose properties are determined by strong electron and spin correlations. Here the implementation of the new spin polarimeter VESPA (Very Efficient Spin Polarization Analysis) at the APE-NFFA beamline at Elettra is reported, which is based on the exchange coupling between the photoelectron spin and a ferromagnetic surface in a reflectometry setup. The system was designed to be integrated with a dedicated Scienta-Omicron DA30 electron energy analyzer allowing for two simultaneous reflectometry measurements, along perpendicular axes, that, after magnetization switching of the two targets, allow the three-dimensional vectorial reconstruction of the spin polarization to be performed while operating the DA30 in high-resolution mode. VESPA represents the very first installation for spin-resolved ARPES (SPARPES) at the Elettra synchrotron in Trieste, and is being heavily exploited by SPARPES users since autumn 2015. [ABSTRACT FROM AUTHOR]

An extinct hydrothermal barite-silica chimney from the Franklin Seamount of the Woodlark Basin, in the southwestern Pacific Ocean, was investigated for mineral distribution and geochemical composition. Six layers on either side of the orifice of a chimney show significant disparity in color, mineral assemblage and major element composition. Electron microscope (SEM) images reveal that the peripheral wall of the chimney is composed of colloform silica, suggesting that incipient precipitation of silica-saturated hydrothermal fluid initiated the development of the chimney wall. Intermediate layers, between the exterior wall and the inner fluid-orifice, dominate with barite and sulfides. Low Sr-to-Ba ratios (SrO/BaO = 0.015-0.017) indicate restricted fluid-seawater mixing, which causes relatively high-temperature formation of the intermediate layers. Whereas the innermost layer bordering the chimney orifice is characterized by more silica and a higher Sr-to-Ba ratio (SrO/BaO = 0.023), could have formed due to a paragenetic shift from a high-temperature active phase to a cooler waning stage of formation. A paragenetic shift is also probably responsible for the change in mineral formation mechanism that resulted in the textural variation of barite and colloform silica developed during different growth phases of this barite-silica chimney. [ABSTRACT FROM AUTHOR]

The Central Indian Ocean Basin (CIOB) basalts are plagioclase-rich, while olivine and pyroxene are very few. The analyses of 41 samples reveal high FeOT (∼10-18 wt%) and TiO2 (∼1.4-2.7 wt%) indicating a ferrobasaltic composition. The basalts have high incompatible elements (Zr 63-228 ppm; Nb ∼1-5 ppm; Ba ∼15-78 ppm; La ∼3-16 ppm), a similar U/Pb (0.02-0.4) ratio as the normal mid-oceanic basalt (0.16±0.07) but the Ba/Nb (12.5-53) ratio is much larger than that of the normal mid-oceanic ridge basalt (∼5.7) and Primitive Mantle (9.56). Interestingly almost all of the basalts have a significant negative Eu anomaly (Eu/Eu*=0.78-1.00) that may have been a result of the removal of feldspar and pyroxene during crystal fractionation. These compositional variations suggest that the basalts were derived through fractional crystallization together with low partial melting of a shallow seated magma. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) may be introduced into aquatic ecosystems because of their widespread use as antimicrobial agents. However, few studies have investigated the impacts of AgNPs on natural aquatic microbial activity in an environmentally relevant context. In this study, bacterioplankton were collected from nine aquatic habitats and exposed to six concentrations of carboxy-functionalized AgNP (ViveNano, 10-nm particle size, 20% Ag w/w) over 48 h. After 1 h of exposure, bacterial production and extracellular alkaline phosphatase affinity were significantly reduced in all AgNP-exposed samples. However, across a 48-h exposure, extracellular aminopeptidase affinity was not consistently impacted by AgNPs. After 48 h, bacterial production recovered by 40 to 250% at low AgNP nominal concentrations (0.05 and 0.1 mg/L) but remained inhibited at the two highest AgNP nominal concentrations (1 and 10 mg/L). In contrast, AgNO3 additions between 0.01 to 2 mg Ag/L fully inhibited bacterial production over the 48-h exposure. At 48-h exposure, the lowest observed effective concentrations and average median effective concentration for bacterial production ranged from 8 to 66 and 15 to 276 µg Ag/L, respectively. Thus, in natural aquatic systems, AgNP concentrations in the nanogram per liter range are unlikely to negatively impact aquatic biogeochemical cycles. Instead, exposures in the low microgram per liter range would likely be required to negatively impact natural aquatic bacterioplankton processes. Environ. Toxicol. Chem. 2012;31:122-130. © 2011 SETAC [ABSTRACT FROM AUTHOR]

Intracardiac echocardiography (ICE) broadens the spectrum of available echocardiographic techniques and provides the operator direct visualization of cardiac structures in real time. ICE has clear advantages over fluoroscopy, transthoracic echocardiography, and transesophageal echocardiography as the imaging modality of choice in the cardiac catheterization and electrophysiological laboratories. With the development of steerable phased array catheters with low frequency and Doppler qualities, there is marked improvement in visualization of left-sided structures from the right heart. Appropriate utilization of ICE is likely to maximize safety and efficacy of complex interventional procedures and may improve patient outcomes. Future advances in ICE imaging will further improve the ease of device guidance and, in combination with new imaging modalities, could dramatically improve other applications of echocardiography which may result in improved patient outcomes. This review describes the technical evolution of ICE, the use of ICE in guiding percutaneous interventional procedures and possible future applications of ICE in the ever-growing field of interventional cardiology. (Echocardiography 2011;28:582-590) [ABSTRACT FROM AUTHOR]

The accelerated migration of Langerhans cells (LCs) out of the epidermis and up-regulation of maturation markers, upon treatment with subtoxic concentrations of chemicals, were used as the criteria to determine the potential of allergenic chemicals capable of inducing a hapten-specific delayed-type hypersensitivity reaction. Here we report the findings of a study in which seven chemicals, coded and tested in a blind fashion, were classified as contact allergens or non-allergens using the human organotypic skin explant culture (hOSEC) model. All chemicals that were identified as a contact sensitizer on decoding induced a definite decrease in the number of CD1a and HLA-DR-positive epidermal LCs in the epidermis of the skin explants, as determined by both semiquantitative immunohistochemistry and quantitative flow cytometric analysis. A significant increase in the number of CD83+ cells was accompanied by up-regulation of activation molecules in the epidermis of hOSEC exposed specifically to contact allergens. In contrast, there were only minor alterations in epidermal LC numbers, expression of CD83 and other activation markers by LCs when the biopsies were treated with non-toxic concentrations of non-allergenic irritants and vehicles. The data suggest that an increased epidermal LC migration and maturation accompanied by increased expression of activation markers could be used as end-point determinants to screen allergens in a non-animal alternative hOSEC model. [ABSTRACT FROM AUTHOR]

Skin irritants and contact allergens reduce the number of Langerhans cells (LCs). It has been assumed that this reduction is due their migration to the draining lymph node (LN) for initiating immune sensitization in a host. Skin irritation, however, as opposed to contact allergy is not considered to be an immunological disease. Nevertheless, skin irritants are also known for their adjuvant-like effects on contact allergy, resulting in skin hypersensitivity reactions like toxic dermatitis. The human organotypic skin explant culture (hOSEC) model is used to study the characteristics of chemical-induced migration of CD1a+ LCs out of the epidermis in relation to irritancy or toxicity. We analysed cells emigrating out of hOSEC for CD1a+ LCs, CD83+ mature dendritic cells (DCs) and CCR7+ LN homing cells. After exposure to a toxic concentration of a non-immunogenic irritant, an increase of CD1a+CD83+ LCs was found in the culture medium. A non-toxic concentration of an sensitizer induced an increase of CD1a+ cells. About 50% of skin emigrating CD1a+ LCs were CD83– (immature) but all were CCR7+. Skin irritation by both non-allergenic and allergenic compounds induces LC migration and maturation. In contrast, only allergenic compounds induced LC migration with partial maturation at subtoxic concentration. This effectively demonstrates that irritation is physiologically needed stimuli for inducing LC maturation. [ABSTRACT FROM AUTHOR]

Ivanova K, van den Wijngaard R, Gerzer R, Lamers WH, Das PK. Non-lesional vitiliginous melanocytes are not characterized by an increased proneness to nitric oxide-induced apoptosis.Nitric oxide (NO) is a reactive endogenous molecule with multiple functions including inflammation and immunity. NO stimulates melanogenesis by activating soluble guanylyl cyclase (sGC) resulting in increases in intracellular guanosine 3′,5′-cyclic monophosphate (cGMP).In vitroexperiments showed that NO could inhibit thede novoattachment of melanocytes to extracellular matrix (ECM) suggesting that NO-induced aberrant perturbation of melanocyte–ECM interaction could be a reason for melanocyte loss in vitiliginous lesions. Here, we examined whether there might be differences between normal melanocytes and vitiliginous melanocytes (VMs) with respect to NO-induced detachment from ECM and whether cGMP is involved. We used the direct NO donor (Z)-1-[ N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate and the peroxynitrite donor 3-morpholino-sydnonimine for the present studies. These donors induced detachment of both normal melanocytes and non-lesional VMs in a time- and concentration-dependent manner with comparable susceptibility and similar expression profile of sGC. Treatment of melanocytes with caspase inhibitors reduced cell detachment, indicating that a major part of the detachment is due to apoptosis. The NO-induced detachment but not apoptosis was partly inhibited in the presence of sGC and cGMP-dependent protein kinase inhibitors. In addition, the membrane-permeable cGMP analog 8-(4-chlorophenyethio/guanosine-3′,5′-cyclic monophosphate (PCPT) cGMP was not able to induce apoptosis in melanocytes, suggesting that NO-induced detachment of melanocytes via apoptosis is cGMP-independent. The present results also indicate that there are no apparent differences between NO-induced detachment of non-lesional vitiliginous and normal melanocytes from ECM. [ABSTRACT FROM AUTHOR]

Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3′,5′-cyclic monophosphate (cGMP) plays an important role in human melanocyte functions and different guanylyl cyclase isoforms are responsible for cGMP synthesis in human non-metastatic and metastatic melanoma cells, we investigated the effects of hypergravity on the regulation of cGMP levels in cultured human melanocytes and in melanoma cell lines with different metastatic potentials. Hypergravity was produced by horizontal centrifugal acceleration. Here we report that long-term application of hypergravity (up to 5 gfor 24 h) stimulated cGMP efflux in cultured melanocytes and in non-metastatic melanoma cells in the presence of 0.1 mM 3-isobutyl-1-methylxanthine (IBMX), a non-selective phosphodiesterase (PDE) inhibitor. Under these conditions, cAMP synthesis and melanin production were up-regulated in pigmented melanocytes and non-metastatic melanoma cells. Hypergravity also stimulated cGMP transport in the presence of 1 μM trequinsin, an inhibitor of cGMP-binding PDE (PDE5) and of transport by multidrug resistance proteins MRP4/5, whereas 50 μM trequinsin partially inhibited cGMP transport. Transport was further inhibited by probenecid, an inhibitor of endogenous non-selective transporters as well as of MRP4/5 and by cycloheximide as an inhibitor of de novo protein synthesis. In contrast, hypergravity did not affect cGMP efflux in metastatic melanoma cells, which might be related to an up-regulated cGMP efflux at 1 g. The results of the present study indicate that hypergravity may stimulate cGMP efflux in melanocytes and in non-metastatic melanoma cells most probably by an enhanced expression of endogenous transporters and/or MRP4/5. Thus, an altered acceleration vector may induce signaling events in melanocytic cells. [ABSTRACT FROM AUTHOR]

The appearance of depigmentation during the course of malignant melanoma has been considered a good prognostic sign. Is it only a side-effect, informative of the immune system's response to the treatment, or does it act as a necessary amplifier of these clinically important anti-tumor responses? The current review will attempt to tackle this question by reviewing the current literature, as well as by posing some novel hypotheses. Understanding the nature of humoral and cellular immune responses directed against normal melanocytes and their malignant counterparts may lead to the design of improved therapeutic strategies relevant to both vitiligo and melanoma. [ABSTRACT FROM AUTHOR]

In vivo, melanocytes were detected in epidermis from human tissue of 6.5 weeks estimated gestinational age (EGA) and older. We have successfully established melanocyte monocultures from tissue of 9 to 10 weeks EGA. To our knowledge, this is the first report on physiology of human foetal melanocytes in monoculture. In culture, such melanocytes retained foetal characteristics. Proliferation rates noted were markedly higher (approximately 2.7-fold) when compared to those in cultures of neonatal melanocytes. Moreover, when analyzing cellular phenotypes by markers for cells of the melanocytic lineage, foetal cells isolated from tissue of 9 weeks EGA reproducibly showed expression of the high molecular weight (HMW) antigen and c-kit to an extent intermediate to that found in neonatal melanocytes and M14 melanoma cells. Such differential expression was not observed if cells were isolated from tissue of 10 weeks EGA, indicating that the foetal environment provides essential differentiation stimuli during the 10th week of gestation. Moreover, these results are supportive of the theory that malignant transformation involves a process of dedifferentiation. In all, human foetal melanocyte culture provides a useful model to investigate pigment cell differentiation. [ABSTRACT FROM AUTHOR]

An ex vivo model system was developed to investigate melanocyte migration. Within this model system, melanocytes migrate among other epidermal cells in the epibolic outgrowth of skin explants. This process is initiated by loss of contact inhibition of epidermal cells at the rim of the explants and by locally produced chemotactic factors. Punch biopsies provided explants of reproducible diameter. Optimal culture conditions include medium consisting of Dulbecco's Minimal Essential Medium containing 10% inactivated normal human serum and placement of explants epidermal side up at the air-liquid interphase. Within 7 days, epidermal cells completely surround the explant. Approximately 3 days after the onset of keratinocyte migration, melanocytes distribute themselves within the newly formed epidermis. Throughout the 7-day culture period, melanocytes and keratinocytes show maintenance of subcellular morphology, and the dermo-epidermal junction remains intact. Melanocyte migration was quantified using immunoperoxidase staining in combination with light microscopy and computer-aided image analysis. Preliminary results using the model system to compare migration in control and nonlesional vitiligo skin indicate that no inherent migration defect is responsible for impaired repigmentation of vitiligo lesions. The organotypic culture model system allows for investigations on melanocytes within their environment of autologous epidermal and dermal components, closely resembling in vivo circumstances in human skin. [ABSTRACT FROM AUTHOR]

The article presents information on tetraalkylammonium bromate catalyzed cyclodehydration and the synthesis of 2,3-dihydro-1h-1,5-benzodiazepine in aqueous methanol.

Diethylammonium hydrogensulfate as an ionic liquid catalyst in the microwave-assisted one-pot three-component reaction between arylamines (I), benzaldehydes (II) or (V) and phenylhydrazine (III) furnishes the formazans (IV) and (VI) in highs yield following a volatile-organic-compound- and solvent-free green protocol. [ABSTRACT FROM AUTHOR]

Among three ionic liquids tested, propylammoniumhydrogensulfate is found to be the most efficient promoter for the synthesis of title compounds (III), (V), and (VI). [ABSTRACT FROM AUTHOR]

The article presents a chemical equation related to the article "Tetraethylammonium Bromate Mediated Synthesis of 2-Arylbenzothiazole" by researchers P.J. Das and S. Sarkar published in the journal "Indian Journal of Chemistry" in 2013.

A diagram is presented which explains the environmentally benign source of bromine for trans-bromination of alkenes.