Efficient dataset extension using generative networks for assessing degree of coating degradation around scribe.

A novel methodology for dataset augmentation in the semantic segmentation of coil-coated surface degradation is presented in this study. Deep convolutional generative adversarial networks (DCGAN) are employed to generate synthetic input-target pairs, which closely resemble real-world data, with the goal of expanding an existing dataset. These augmented datasets are used to train two state-of-the-art models, U-net, and DeepLabV3, for the precise detection of degradation areas around scribes.

How the Presence of Crystalline Phase Affects Structural Relaxation in Molecular Liquids: The Case of Amorphous Indomethacin.

The influence of partial crystallinity on the structural relaxation behavior of low-molecular organic glasses is, contrary to, e.g., polymeric materials, a largely unexplored territory.

N-acetylcysteine Can Induce Massive Oxidative Stress, Resulting in Cell Death with Apoptotic Features in Human Leukemia Cells.

N-acetylcysteine (NAC), often used as an antioxidant-scavenging reactive oxygen species (ROS) in vitro, was recently shown to increase the cytotoxicity of other compounds through ROS-dependent and ROS-independent mechanisms. In this study, NAC itself was found to induce extensive ROS production in human leukemia HL-60 and U937 cells. The cytotoxicity depends on ROS-modulating enzyme expression.

New End-to-End Strategy Based on DeepLabv3+ Semantic Segmentation for Human Head Detection.

In the field of computer vision, object detection consists of automatically finding objects in images by giving their positions. The most common fields of application are safety systems (pedestrian detection, identification of behavior) and control systems. Another important application is head/person detection, which is the primary material for road safety, rescue, surveillance, etc.

Heat Shock Protein Inhibitor 17-Allyamino-17-Demethoxygeldanamycin, a Potent Inductor of Apoptosis in Human Glioma Tumor Cell Lines, Is a Weak Substrate for ABCB1 and ABCG2 Transporters.

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and has a poor prognosis. Complex genetic alterations and the protective effect of the blood-brain barrier (BBB) have so far hampered effective treatment. Here, we investigated the cytotoxic effects of heat shock protein 90 (HSP90) inhibitors, geldanamycin (GDN) and 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), in a panel of glioma tumor cell lines with various genetic alterations.

Preformulation design of PLGA particulate system for multi-day drug delivery of the antidepressant mirtazapine.

In this experimental study, the biodegradable polylactide-co-glycolide (PLGA) microparticles (MP) loaded with the insoluble antidepressant mirtazapine were prepared by the simple o/w solvent evaporation method. The formation involved intrinsic variables, such as the content of polymer (700, 900 or 1200 mg), dichloromethane (5 or 10 ml) and/or drug (200 or 400 or 600 mg), and the volume of the aqueous emulsion phase (400, 600 or 800 ml). The influence of these parameters on the size and morphology of microparticles, encapsulation efficiency, and drug release behavior was observed.

Multivariate analysis in the development of bioequivalent tablets containing bicalutamide.

The pharmaceutical industry has to tackle the explosion of high amounts of poorly soluble APIs. This phenomenon leads to numerous sophisticated solutions. These include the use of multifactorial data analysis identifying correlations between the components and dosage form properties, laboratory and production process parameters with respect to the API liberation Example of such API is bicalutamide.

Lysosomal Fusion: An Efficient Mechanism Increasing Their Sequestration Capacity for Weak Base Drugs without Apparent Lysosomal Biogenesis.

Lysosomal sequestration of anticancer therapeutics lowers their cytotoxic potential, reduces drug availability at target sites, and contributes to cancer resistance. Only recently has it been shown that lysosomal sequestration of weak base drugs induces lysosomal biogenesis mediated by activation of transcription factor EB (TFEB) which, in turn, enhances their accumulation capacity, thereby increasing resistance to these drugs. Here, we addressed the question of whether lysosomal biogenesis is the only mechanism that increases lysosomal sequestration capacity.

The Lysosomal Sequestration of Tyrosine Kinase Inhibitors and Drug Resistance.

The Lysosomal sequestration of weak-base anticancer drugs is one putative mechanism for resistance to chemotherapy but it has never been directly proven. We addressed the question of whether the lysosomal sequestration of tyrosine kinase inhibitors (TKIs) itself contributes to the drug resistance in vitro. Our analysis indicates that lysosomal sequestration of an anticancer drug can significantly reduce the concentration at target sites, only when it simultaneously decreases its extracellular concentration due to equilibrium, since uncharged forms of weak-base drugs freely diffuse across cellular membranes.

Estimation of ABCB1 concentration in plasma membrane.

The interaction between ABCB1 transporter and its substrates takes place in cell membranes but the available data precludes quantitative analysis of the interaction between transporter and substrate molecules. Further, the amount of transporter is usually expressed as a number of ABCB1 molecules per cell. In contrast, the substrate concentration in cell membranes is estimated by determination of substrate-lipid partition coefficient, as examples.

Apoptosis Induced by the Curcumin Analogue EF-24 Is Neither Mediated by Oxidative Stress-Related Mechanisms nor Affected by Expression of Main Drug Transporters ABCB1 and ABCG2 in Human Leukemia Cells.

The synthetic curcumin analogue, 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone (EF-24), suppresses NF-κB activity and exhibits antiproliferative effects against a variety of cancer cells in vitro. Recently, it was reported that EF-24-induced apoptosis was mediated by a redox-dependent mechanism. Here, we studied the effects of -acetylcysteine (NAC) on EF-24-induced cell death.

Reversal of ABCB1 mediated efflux by imatinib and nilotinib in cells expressing various transporter levels.

Recently, it has been suggested that imatinib (IM) and nilotinib (NIL) could be studied beyond their original application, as inhibitors of the drug efflux pump ABCB1 (P-glycoprotein, MDR1). Since the reversal of ABCB1-mediated resistance has never been successfully demonstrated in the clinic, we addressed the question of whether IM and NIL may actually serve as efficient inhibitors of ABCB1. Here we define an efficient inhibitor as a compound that achieves full (90-100%) reversal of drug efflux at a concentration that does not exhibit significant off-target toxicity in vitro.

Robust Grape Detector Based on SVMs and HOG Features.

Detection of grapes in real-life images is a serious task solved by researchers dealing with precision viticulture. In the case of white wine varieties, grape detectors based on SVMs classifiers, in combination with a HOG descriptor, have proven to be very efficient. Simplified versions of the detectors seem to be the best solution for practical applications.

Buccal films as a dressing for the treatment of aphthous lesions.

Background: Buccal flexible films in the form of solid, thin, mucoadhesive patches can be used as dressings separating aphthous lesions from the environment of the oral cavity, which can in turn shorten the treatment period and reduce the pain perception.

Methods: The clinical study was performed on 36 volunteers suffering from aphthous lesions. The first group was treated using standard means-by application of an oral gel containing cholin salicylate (Mundisal) on the aphthous lesion.

The influence of thermal treatment and type of insoluble poly(meth)acrylates on dissolution behavior of very soluble drug from hypromellose matrix tablets evaluated by multivariate data analysis.

Hypromellose matrices exhibit extended burst effect immediately after contact with aqueous medium, especially when a water-soluble drug is incorporated. The objective of this study was to reduce burst effect and maintain complete dissolution of a very soluble levetiracetam over 12 h period from hypromellose K4M matrices to obtain zero-order kinetics. Desired changes were achieved by applying water dispersions of insoluble Eudragits (NE, NM, RL, RS) as a granulation liquid to the drug/microcrystalline cellulose mixture during high-shear granulation (non-thermal treated set) and consequently by thermally treating granules or final tablets (TT), respectively.

Quality by design approach: antioxidant activity of the tablets containing cornelian cherry fruits in relation to their composition and physical properties.

The aim of this study was to prepare tablets containing ground fruits of cornelian cherry (Cornus mas L.) with high antioxidant capacity. The experiment was planned and evaluated on Design of Experiment (DoE) principle using Multivariate Data Analysis (MVA) as modern tools used in Quality by Design (QbD) approach.

The effect of superdisintegrants on the properties and dissolution profiles of liquisolid tablets containing rosuvastatin.

Context: The preparation of liquisolid systems (LSS) represents a promising method for enhancing a dissolution rate and bioavailability of poorly soluble drugs. The release of the drug from LSS tablets is affected by many factors, including the disintegration time.

Objective: The evaluation of differences among LSS containing varying amounts and types of commercially used superdisintegrants (Kollidon® CL-F, Vivasol® and Explotab®).

Loss of mitochondrial transmembrane potential and glutathione depletion are not sufficient to account for induction of apoptosis by carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone in human leukemia K562 cells.

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), an uncoupler of mitochondrial oxidative phosphorylation, inhibits cell proliferation and induces cell death with apoptotic features. It was reported that the cytotoxic effects of FCCP are preceded by a rapid glutathione (GSH) depletion with a subsequent loss of mitochondrial transmembrane potential (ΔΨ). The GSH depletion was suggested as the cause of apoptosis in FCCP treated cells.

Formulation of Novel Layered Sodium Carboxymethylcellulose Film Wound Dressings with Ibuprofen for Alleviating Wound Pain.

Effective assessment and management of wound pain can facilitate both improvements in healing rates and overall quality of life. From a pharmacological perspective, topical application of nonsteroidal anti-inflammatory drugs in the form of film wound dressings may be a good choice. Thus, the aim of this work was to develop novel layered film wound dressings containing ibuprofen based on partially substituted fibrous sodium carboxymethylcellulose (nonwoven textile Hcel NaT).

Carmellose Mucoadhesive Oral Films Containing Vermiculite/Chlorhexidine Nanocomposites as Innovative Biomaterials for Treatment of Oral Infections.

Infectious stomatitis represents the most common oral cavity ailments. Current therapy is insufficiently effective because of the short residence time of topical liquid or semisolid medical formulations. An innovative application form based on bioadhesive polymers featuring prolonged residence time on the oral mucosa may be a solution to this challenge.

Influence of different formulations and process parameters during the preparation of drug-loaded PLGA microspheres evaluated by multivariate data analysis.

The main objective of this study was to evaluate the influence of the formulation and process parameters on PLGA microparticles containing a practically insoluble model drug (ibuprofen) prepared by the o/w solvent evaporation method. Multivariate data analysis was used. The effects of altered stirring speed of a mechanical stirrer (600, 1000 rpm), emulsifier concentrations (PVA concentration 0.

Long-term controlled release of PLGA microparticles containing antidepressant mirtazapine.

The aim of the study was to prepare PLGA microparticles for prolonged release of mirtazapine by o/w solvent evaporation method and to evaluate effects of PVA concentration and organic solvent choice on microparticles characteristics (encapsulation efficiency, drug loading, burst effect, microparticle morphology). Also in vitro drug release tests were performed and the results were correlated with kinetic model equations to approximate drug release mechanism. It was found that dichloromethane provided microparticles with better qualities (encapsulation efficiency 64.

Can the assessment of ABCB1 gene expression predict its function in vitro?

Increased expression of the ABCB1 gene in cancer cells is usually connected with occurrence of multidrug resistance (MDR) and poor prognosis. However, the correlation between ABCB1 expression and MDR phenotype is difficult to prove in clinical samples. Most of the researchers believe that these difficulties are due to the poor reliability and sensitivity of assays for detection of ABCB1 expression in clinical samples.

Influence of process parameters on content uniformity of a low dose active pharmaceutical ingredient in a tablet formulation according to GMP.

The article describes the development and production of tablets using direct compression of powder mixtures. The aim was to describe the impact of filler particle size and the time of lubricant addition during mixing on content uniformity according to the Good Manufacturing Practice (GMP) process validation requirements. Processes are regulated by complex directives, forcing the producers to validate, using sophisticated methods, the content uniformity of intermediates as well as final products.

Evaluation of the influence of formulation and process variables on mechanical properties of oral mucoadhesive films using multivariate data analysis.

Oral mucosa is an attractive region for the local and systemic application of many drugs. Oral mucoadhesive films are preferred for their prolonged time of residence, the improved bioavailability of the drug they contain, their painless application, their protection against lesions, and their nonirritating properties. This work was focused on preparation of nonmedicated carmellose-based films using both solvent casting and impregnation methods, respectively.