Concise Synthesis of Pseudane IX, Its N-Oxide, and Novel Carboxamide Analogs with Antibacterial Activity.

A four-step synthesis of the natural product pseudane IX, starting from 3-oxododecanoic acid phenylamide and including only one chromatographic purification, was accomplished with an overall yield of 52%. The same synthetic sequence, but with a controlled partial reduction of a nitro group in the penultimate intermediate, led to the N-oxide of pseudane IX (NQNO). A shortened three-step variation of the synthesis allowed for the preparation of novel carboxamide analogs of the natural product. An agar diffusion assay against six different bacterial strains revealed significant antibacterial activity of the novel analogs against S. aureus at a concentration of 100 µg/mL. One of the novel compounds showed a remarkably broad spectrum of antibacterial activity, comparable to that of the positive control NQNO.

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common ß-keto amide precursors.

ß-Keto amides were used as convenient precursors to both 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides. The utility of this approach is demonstrated with the synthesis of fourteen novel and four known quinolone derivatives, including natural products of microbial origin such as HHQ and its C5-congener. Two compounds with high activity against S. aureus have been identified among the newly obtained quinolones, with MICs ≤ 3.12 and ≤ 6.25 µg/mL, respectively.

Ensemble-Based Bounding Box Regression for Enhanced Knuckle Localization.

The knuckle creases present on the dorsal side of the human hand can play significant role in identifying the offenders of serious crime, especially when evidence images of more recognizable biometric traits, such as the face, are not available. These knuckle creases, if localized appropriately, can result in improved identification ability. This is attributed to ambient inclusion of the creases and minimal effect of background, which lead to quality and discerning feature extraction. This paper presents an ensemble approach, utilizing multiple object detector frameworks, to localize the knuckle regions in a functionally appropriate way. The approach leverages from the individual capabilities of the popular object detectors and provide a more comprehensive knuckle region localization. The investigations are completed with two large-scale public hand databases which consist of hand-dorsal images with varying backgrounds and finger positioning. In addition to that, effectiveness of the proposed approach is also tested with a novel proprietary unconstrained multi-ethnic hand dorsal dataset to evaluate its generalizability. Several novel performance metrics are tailored to evaluate the efficacy of the proposed knuckle localization approach. These metrics aim to measure the veracity of the detected knuckle regions in terms of their relation with the ground truth. The comparison of the proposed approach with individual object detectors and a state-of-the-art hand keypoint detector clearly establishes the outperforming nature of the proposed approach. The generalization of the proposed approach is also corroborated through the cross-dataset framework.

Synthesis of functionalised ß-keto amides by aminoacylation/domino fragmentation of ß-enamino amides.

Ethylenediamine-derived ß-enamino amides are used as equivalents of amide enolate synthons in C-acylation reactions with N-protected amino acids. Domino fragmentation of the obtained intermediates leads to functionalised ß-keto amides, bearing a protected amino group in their side chain.

IRootLab: a free and open-source MATLAB toolbox for vibrational biospectroscopy data analysis.

SUMMARY: IRootLab is a free and open-source MATLAB toolbox for vibrational biospectroscopy (VBS) data analysis. It offers an object-oriented programming class library, graphical user interfaces (GUIs) and automatic MATLAB code generation. The class library contains a large number of methods, concepts and visualizations for VBS data analysis, some of which are introduced in the toolbox. The GUIs provide an interface to the class library, including a module to merge several spectral files into a dataset. Automatic code allows developers to quickly write VBS data analysis scripts and is a unique resource among tools for VBS. Documentation includes a manual, tutorials, Doxygen-generated reference and a demonstration showcase. IRootLab can handle some of the most popular file formats used in VBS. License: GNU-LGPL. AVAILABILITY: Official website: http://irootlab.googlecode.com/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Extracting biological information with computational analysis of Fourier-transform infrared (FTIR) biospectroscopy datasets: current practices to future perspectives.

Applying Fourier-transform infrared (FTIR) spectroscopy (or related technologies such as Raman spectroscopy) to biological questions (defined as biospectroscopy) is relatively novel. Potential fields of application include cytological, histological and microbial studies. This potentially provides a rapid and non-destructive approach to clinical diagnosis. Its increase in application is primarily a consequence of developing instrumentation along with computational techniques. In the coming decades, biospectroscopy is likely to become a common tool in the screening or diagnostic laboratory, or even in the general practitioner's clinic. Despite many advances in the biological application of FTIR spectroscopy, there remain challenges in sample preparation, instrumentation and data handling. We focus on the latter, where we identify in the reviewed literature, the existence of four main study goals: Pattern Finding; Biomarker Identification; Imaging; and, Diagnosis. These can be grouped into two frameworks: Exploratory; and, Diagnostic. Existing techniques in Quality Control, Pre-processing, Feature Extraction, Clustering, and Classification are critically reviewed. An aspect that is often visited is that of method choice. Based on the state-of-art, we claim that in the near future research should be focused on the challenges of dataset standardization; building information systems; development and validation of data analysis tools; and, technology transfer. A diagnostic case study using a real-world dataset is presented as an illustration. Many of the methods presented in this review are Machine Learning and Statistical techniques that are extendable to other forms of computer-based biomedical analysis, including mass spectrometry and magnetic resonance.

Biomimetic synthesis, antibacterial activity and structure-activity properties of the pyroglutamate core of oxazolomycin.

Biomimetic intramolecular aldol reactions on oxazolidine templates derived from serine may be used to generate densely functionalised pyroglutamates, which are simpler mimics of the right hand side of oxazolomycin. Some of the compounds from this sequence exhibit in vivo activity against S. aureus and E. coli, suggesting that pyroglutamate scaffolds may be useful templates for the development of novel antibacterials, and cheminformatic analysis has been used to provide some structure-activity data.

A Semi-Supervised Deep Rule-Based Approach for Complex Satellite Sensor Image Analysis.

Large-scale (large-area), fine spatial resolution satellite sensor images are valuable data sources for Earth observation while not yet fully exploited by research communities for practical applications. Often, such images exhibit highly complex geometrical structures and spatial patterns, and distinctive characteristics of multiple land-use categories may appear at the same region. Autonomous information extraction from these images is essential in the field of pattern recognition within remote sensing, but this task is extremely challenging due to the spectral and spatial complexity captured in satellite sensor imagery. In this research, a semi-supervised deep rule-based approach for satellite sensor image analysis (SeRBIA) is proposed, where large-scale satellite sensor images are analysed autonomously and classified into detailed land-use categories. Using an ensemble feature descriptor derived from pre-trained AlexNet and VGG-VD-16 models, SeRBIA is capable of learning continuously from both labelled and unlabelled images through self-adaptation without human involvement or intervention. Extensive numerical experiments were conducted on both benchmark datasets and real-world satellite sensor images to comprehensively test the validity and effectiveness of the proposed method. The novel information mining technique developed here can be applied to analyse large-scale satellite sensor images with high accuracy and interpretability, across a wide range of real-world applications.

Particle Swarm Optimized Autonomous Learning Fuzzy System.

The antecedent and consequent parts of a first-order evolving intelligent system (EIS) determine the validity of the learning results and overall system performance. Nonetheless, the state-of-the-art techniques mostly stress on the novelty from the system identification point of view but pay less attention to the optimality of the learned parameters. Using the recently introduced autonomous learning multiple model (ALMMo) system as the implementation basis, this article introduces a particle swarm-based approach for the EIS optimization. The proposed approach is able to simultaneously optimize the antecedent and consequent parameters of ALMMo and effectively enhance the system performance by iteratively searching for optimal solutions in the problem spaces. In addition, the proposed optimization approach does not adversely influence the "one pass" learning ability of ALMMo. Once the optimization process is complete, ALMMo can continue to learn from new data to incorporate unseen data patterns recursively without full retraining. The experimental studies with a number of real-world benchmark problems validate the proposed concept and general principles. It is also verified that the proposed optimization approach can be applied to other types of EISs with similar operating mechanisms.

Harnessing the Power of Smart and Connected Health to Tackle COVID-19: IoT, AI, Robotics, and Blockchain for a Better World.

As COVID-19 hounds the world, the common cause of finding a swift solution to manage the pandemic has brought together researchers, institutions, governments, and society at large. The Internet of Things (IoT), artificial intelligence (AI)-including machine learning (ML) and Big Data analytics-as well as Robotics and Blockchain, are the four decisive areas of technological innovation that have been ingenuity harnessed to fight this pandemic and future ones. While these highly interrelated smart and connected health technologies cannot resolve the pandemic overnight and may not be the only answer to the crisis, they can provide greater insight into the disease and support frontline efforts to prevent and control the pandemic. This article provides a blend of discussions on the contribution of these digital technologies, propose several complementary and multidisciplinary techniques to combat COVID-19, offer opportunities for more holistic studies, and accelerate knowledge acquisition and scientific discoveries in pandemic research. First, four areas, where IoT can contribute are discussed, namely: 1) tracking and tracing; 2) remote patient monitoring (RPM) by wearable IoT (WIoT); 3) personal digital twins (PDTs); and 4) real-life use case: ICT/IoT solution in South Korea. Second, the role and novel applications of AI are explained, namely: 1) diagnosis and prognosis; 2) risk prediction; 3) vaccine and drug development; 4) research data set; 5) early warnings and alerts; 6) social control and fake news detection; and 7) communication and chatbot. Third, the main uses of robotics and drone technology are analyzed, including: 1) crowd surveillance; 2) public announcements; 3) screening and diagnosis; and 4) essential supply delivery. Finally, we discuss how distributed ledger technologies (DLTs), of which blockchain is a common example, can be combined with other technologies for tackling COVID-19.

Syrian hamster embryo (SHE) assay (pH 6.7) coupled with infrared spectroscopy and chemometrics towards toxicological assessment.

The Syrian hamster embryo (SHE) assay (pH 6.7) is an in vitro candidate to replace in vivo carcinogenicity tests. However, the conventional method of visual scoring of foci (non-transformed vs. transformed colonies) can be time-consuming and is open to subjectivity. Infrared (IR) spectroscopy has the potential to provide objective assessment of such SHE colonies with the added advantage of potentially providing mechanistic information. In this study, SHE cells were treated with one of eight different chemical regimens, allowed in culture to attach and form foci on IR-reflective glass slides; these were subsequently interrogated by attenuated total reflection (ATR) Fourier-transform IR (FTIR) spectroscopy. Derived mid-IR spectra (n = 13,406) were subjected to chemometric analysis focusing primarily on the extraction of biochemical information related to test agent treatment and/or morphological transformation. The use of ATR-FTIR spectroscopy with chemometrics to analyze the SHE assay is a novel approach to toxicological assessment.

Robust classification of low-grade cervical cytology following analysis with ATR-FTIR spectroscopy and subsequent application of self-learning classifier eClass.

Although the UK cervical screening programme has reduced mortality associated with invasive disease, advancement from a high-throughput predictive methodology that is cost-effective and robust could greatly support the current system. We combined analysis by attenuated total reflection Fourier-transform infrared spectroscopy of cervical cytology with self-learning classifier eClass. This predictive algorithm can cope with vast amounts of multidimensional data with variable characteristics. Using a characterised dataset [set A: consisting of UK cervical specimens designated as normal (n = 60), low-grade (n = 60) or high-grade (n = 60)] and one further dataset (set B) consisting of n = 30 low-grade samples, we set out to determine whether this approach could be robustly predictive. Variously extending the training set consisting of set A with set B data produced good classification rates with three two-class cascade classifiers. However, a single three-class classifier was equally efficient, producing a user-friendly, applicable methodology with improved interpretability (i.e., better classification with only one set of fuzzy rules). As data from set B were added incrementally to the training set, the model learned and evolved. Additionally, monitoring of results of the set B low-grade specimens (known to be low-grade cervical cytology specimens) provided the opportunity to explore the possibility of distinguishing patients likely to progress towards invasive disease. eClass exhibited a remarkably robust predictive power in a user-friendly fashion (i.e., high throughput, ease of use) compared to other classifiers (k-nearest neighbours, support vector machines, artificial neural networks). Development of eClass to classify such datasets for applications such as screening exhibits robustness in identifying a dichotomous marker of invasive disease progression.

Towards explainable deep neural networks (xDNN).

In this paper, we propose an elegant solution that is directly addressing the bottlenecks of the traditional deep learning approaches and offers an explainable internal architecture that can outperform the existing methods, requires very little computational resources (no need for GPUs) and short training times (in the order of seconds). The proposed approach, xDNN is using prototypes. Prototypes are actual training data samples (images), which are local peaks of the empirical data distribution called typicality as well as of the data density. This generative model is identified in a closed form and equates to the pdf but is derived automatically and entirely from the training data with no user- or problem-specific thresholds, parameters or intervention. The proposed xDNN offers a new deep learning architecture that combines reasoning and learning in a synergy. It is non-iterative and non-parametric, which explains its efficiency in terms of time and computational resources. From the user perspective, the proposed approach is clearly understandable to human users. We tested it on challenging problems as the classification of different lighting conditions for driving scenes (iROADS), object detection (Caltech-256, and Caltech-101), and SARS-CoV-2 identification via computed tomography scan (COVID CT-scans dataset). xDNN outperforms the other methods including deep learning in terms of accuracy, time to train and offers an explainable classifier.

Scalable Database Indexing and Fast Image Retrieval Based on Deep Learning and Hierarchically Nested Structure Applied to Remote Sensing and Plant Biology.

Digitalisation has opened a wealth of new data opportunities by revolutionizing how images are captured. Although the cost of data generation is no longer a major concern, the data management and processing have become a bottleneck. Any successful visual trait system requires automated data structuring and a data retrieval model to manage, search, and retrieve unstructured and complex image data. This paper investigates a highly scalable and computationally efficient image retrieval system for real-time content-based searching through large-scale image repositories in the domain of remote sensing and plant biology. Images are processed independently without considering any relevant context between sub-sets of images. We utilize a deep Convolutional Neural Network (CNN) model as a feature extractor to derive deep feature representations from the imaging data. In addition, we propose an effective scheme to optimize data structure that can facilitate faster querying at search time based on the hierarchically nested structure and recursive similarity measurements. A thorough series of tests were carried out for plant identification and high-resolution remote sensing data to evaluate the accuracy and the computational efficiency of the proposed approach against other content-based image retrieval (CBIR) techniques, such as the bag of visual words (BOVW) and multiple feature fusion techniques. The results demonstrate that the proposed scheme is effective and considerably faster than conventional indexing structures.

Synthesis, spectroscopic and structural elucidation of 3-ethylamino-2-(4-nitro-benzoyl)-but-2-enoic acid phenylamide.

3-Ethylamino-2-(4-nitro-benzoyl)-but-2-enoic acid phenylamide is synthesized, isolated, spectroscopical and structural characterized by means of linear-polarized IR-spectroscopy (IR-LD) of oriented solids as a colloidal suspension in nematic liquid crystal. The experimental IR-band assignment and structural information are supported by quantum chemical calculations at MP2 and B3LYP level of theory and 6-311++G** basis set. The geometry is characterized by two inramolecular hydrogen bonds of NH...O=C with bond lengths of 2.589 and 3.449 angstroms. The NHO angles are 142.1(3) degrees and 125.8(4) degrees , respectively. A transoide configuration of amide fragments is predicted with a torsion NH-C=O angle of 150.6 degrees . Phenyl fragments are mutually perpendicular oriented closing an angle of 92.6 degrees .

A Generalized Methodology for Data Analysis.

Based on a critical analysis of data analytics and its foundations, we propose a functional approach to estimate data ensemble properties, which is based entirely on the empirical observations of discrete data samples and the relative proximity of these points in the data space and hence named empirical data analysis (EDA). The ensemble functions include the nonparametric square centrality (a measure of closeness used in graph theory) and typicality (an empirically derived quantity which resembles probability). A distinctive feature of the proposed new functional approach to data analysis is that it does not assume randomness or determinism of the empirically observed data, nor independence. The typicality is derived from the discrete data directly in contrast to the traditional approach, where a continuous probability density function is assumed a priori. The typicality is expressed in a closed analytical form that can be calculated recursively and, thus, is computationally very efficient. The proposed nonparametric estimators of the ensemble properties of the data can also be interpreted as a discrete form of the information potential (known from the information theoretic learning theory as well as the Parzen windows). Therefore, EDA is very suitable for the current move to a data-rich environment, where the understanding of the underlying phenomena behind the available vast amounts of data is often not clear. We also present an extension of EDA for inference. The areas of applications of the new methodology of the EDA are wide because it concerns the very foundation of data analysis. Preliminary tests show its good performance in comparison to traditional techniques.

Study of 3-Ethylamino-but-2-enoic acid phenylamide as a new ligand for preconcentration of lanthanides from aqueous media by liquid-liquid extraction prior to ICP-MS analysis.

In the present work the potential of a new ligand 3-Ethylamino-but-2-enoic acid phenylamide (representing the class of enaminones) for selective preconcentration of lanthanides (La, Ce, Eu, Gd and Er) from aqueous medium is examined. Liquid-liquid extraction parameters, such as pH of the water phase, type and volume of organic solvent, quantity of ligand and reaction time are optimized on model solutions. Recovery of lanthanides by re-extraction with nitric acid makes the LLE procedure compatible with Inductively Coupled Plasma Mass Spectrometry. Spectral and non-spectral interferences are studied. Two isotopes per element are measured (with exception of La) for dynamic evaluation of the potential risk of spectral interference in variable real samples. The selectivity of complex formation reaction towards concomitant alkali and alkali-earth elements eliminates the interferences from sample matrix. Subjecting the standards to the optimized extraction procedure in combination with Re as internal standard is recommended as calibration strategy. The accuracy of developed method is approved by analysis of CRM Bush branches and leaves (NCS DC 73348) and recovery of spiked water and plant samples. The method's limits of detection for both studied objects are in the ranges from 0.2 ((158)Gd) to 3.7 ((139)La) ngl(-1) and 0.02 ((158)Gd) to 0.37((139)La) ngg(-1) for waters and plants respectively. The studied compound is an effective new ligand for preconcentration/separation of lanthanides from aqueous medium by LLE and subsequent determination by ICP-MS.

Synthesis of some novel 11b-substituted pyrimido[6,1-a]-isoquinoline derivatives.

A series of novel 11b-substituted 1,6,7,11b-tetrahydropyrimido[6,1-a]- isoquinoline-2,4-diones and 4-thioxo-1,3,4,6,7,11b-hexahydropyrimido[6,1-a]isoquinolin-2- ones were synthesized, utilizing two alternative strategies for ring closure of tetrahydroisoquinoline intermediates obtained from N-phenethyl enaminones.

An approach to online identification of Takagi-Sugeno fuzzy models.

An approach to the online learning of Takagi-Sugeno (TS) type models is proposed in the paper. It is based on a novel learning algorithm that recursively updates TS model structure and parameters by combining supervised and unsupervised learning. The rule-base and parameters of the TS model continually evolve by adding new rules with more summarization power and by modifying existing rules and parameters. In this way, the rule-base structure is inherited and up-dated when new data become available. By applying this learning concept to the TS model we arrive at a new type adaptive model called the Evolving Takagi-Sugeno model (ETS). The adaptive nature of these evolving TS models in combination with the highly transparent and compact form of fuzzy rules makes them a promising candidate for online modeling and control of complex processes, competitive to neural networks. The approach has been tested on data from an air-conditioning installation serving a real building. The results illustrate the viability and efficiency of the approach. The proposed concept, however, has significantly wider implications in a number of fields, including adaptive nonlinear control, fault detection and diagnostics, performance analysis, forecasting, knowledge extraction, robotics, behavior modeling.

DEC: dynamically evolving clustering and its application to structure identification of evolving fuzzy models.

Identification of models from input-output data essentially requires estimation of appropriate cluster centers. In this paper, a new online evolving clustering approach for streaming data is proposed. Unlike other approaches that consider either the data density or distance from existing cluster centers, this approach uses cluster weight and distance before generating new clusters. To capture the dynamics of the data stream, the cluster weight is defined in both data and time space in such a way that it decays exponentially with time. It also applies concepts from computational geometry to determine the neighborhood information while forming clusters. A distinction is made between core and noncore clusters to effectively identify the real outliers. The approach efficiently estimates cluster centers upon which evolving Takagi-Sugeno models are developed. The experimental results with developed models show that the proposed approach attains results at par or better than existing approaches and significantly reduces the computational overhead, which makes it suitable for real-time applications.