Chemometric Tools to Point Out Benchmarks and Chromophores in Pigments through Spectroscopic Data Analyses

Spectral preprocessing data and chemometric tools are analytical methods widely applied in several scientific contexts i.e., in archaeometric applications. A systematic classification of natural powdered pigments of organic and inorganic nature through Principal Component Analysis with a multi-instruments spectroscopic study is presented here. The methodology allows the access to elementary and molecular unique benchmarks to guide and speed up the identification of an unknown pigment and its recipe. This study is conducted on a set of 48 powdered pigments and tested on a real-case sample from the wall painting in S. Maria Delle Palate di Tusa (Messina, Italy). Four spectroscopic techniques (X-ray Fluorescence, Raman, Attenuated Total Reflectance and Total Reflectance Infrared Spectroscopies) and six different spectrometers are tested to evaluate the impact of different setups. The novelty of the work is to use a systematic approach on this initial dataset using the entire spectroscopic energy range without any windows selection to solve problems linked with the manipulation of large analytes/materials to find an indistinct property of one or more spectral bands opening new frontiers in the dataset spectroscopic analyses.

Towards a Unified Dispositional Framework for Realizable Entities

Realizable entities are properties that can be realized in processes of specific correlated types in which the bearer participates. It will be valuable to create a systematic classification of realizable entities because they are useful for various modeling purposes in ontologies. In this paper we outline a unifying framework for realizable entities (including dispositions and roles) in the upper ontology Basic Formal Ontology (BFO) that is theoretically underpinned by J. McKitrick’s pragmatic approach to dispositions. In particular, we develop a formal ontological account of “extrinsic dispositions” and illustrate its potential applications with clarification of functions and roles in BFO.

Investigating the Suitability of Different Routing Strategies In Specific VANET Application Class

Vehicular Adhoc Network (VANET), is an emerging technology that holds the opportunity to create potential applications that directly impact peoples' lives, traffic management, and infotainment services. Understanding VANET applications and the available routing protocols can help to infer the most suitable protocols that satisfy VANET application requirements. This paper develops a systematic classification methodology to classify VANET applications from a routing perspective, each application class has different network requirements which are laid down by VANET Projects conducted in different countries. Some of these requirements are related to the routing aspects and need to be satisfied by the selected routing strategies (proactive and reactive). The paper identifies routing strategies performance metrics related to each application class requirement, to efficiently guide the development of these routing strategies towards guaranteeing satisfactory performance for the applications under a wide variety of realistic VANET scenarios. It is also worth mentioning that minimum delay is a requirement needed by time and event-driven application classes. However, high reliability is a requirement needed by on-demand applications. The paper aims to provide a comparative study on the performance of routing strategies in different VANET application classes, to identify which routing strategies have better performance in specific VANET applications class. End-to-end delay is employed as a performance metric to evaluate the short delay requirement, while, the Routing Overhead (RO) is used to assess the reliability requirement. Simulation results showed that proactive routing protocol has a lower delay, which means that it is suitable for delay-sensitive applications such as time-driven and event-driven applications. The result also showed that the reactive routing protocol outperforms the proactive routing protocol in terms of RO, which means that reactive routing protocols can be nominated as proper routing strategies to satisfy the reliability requirement of the On-demand driven applications.

Division, Syllogistic, and Science in Prior Analytics I.31

In the first book of the Prior Analytics, Aristotle sets out, for the first time in Greek philosophy, a logical system. After this, Aristotle compares this method with Plato’s method of division, a procedure designed to find essences of natural kinds through systematic classification. This critical comparison in APr I.31 raises an interpretive puzzle: how can Aristotle reasonably juxtapose two methods that differ so much in their aims and approach? What can be gained by doing so? Previous interpreters have failed to show how this comparison is legitimate or what important point Aristotle is making. The goal of this paper is to resolve the puzzle. In resolving this puzzle we not only learn more about the relationship between division and the syllogistic in Aristotle. We will also learn something about the motivation for the syllogistic itself, by seeing the role that it plays in his philosophy of science.

Polyphenol utilization proteins in human gut microbiome

Dietary polyphenols can significantly benefit human health, but their bioavailability is metabolically controlled by human gut microbiota. To facilitate the study of polyphenol metabolism for human gut health, we have manually curated experimentally characterized polyphenol utilization proteins (PUPs) from published literature. This resulted in 60 experimentally characterized PUPs (named seeds) with various metadata, such as species and substrate. Further database search found 107,851 homologs of the seeds from UniProt and UHGP (Unified Human Gastrointestinal Protein) databases. All PUP seeds and homologs were classified into protein classes, families and subfamilies based on Enzyme Commission (EC) numbers, Pfam (protein family) domains and sequence similarity networks. By locating PUP homologs in the genomes of UHGP, we have identified 1,074 physically linked PUP gene clusters (PGCs), which are potentially involved in polyphenol metabolism in the human gut. The gut microbiome of Africans was consistently ranked the top in terms of the abundance and prevalence of PUP homologs and PGCs among all geographical continents. This reflects the fact that dietary polyphenols are more commonly consumed by African population than other populations such as Europeans and North Americans. A case study of the Hadza hunter-gatherer microbiome verified the feasibility of using dbPUP to profile metagenomic data for biologically meaningful discovery, suggesting an association between diet and PUP abundance. A Pfam domain enrichment analysis of PGCs identified a number of putatively novel PUP families. Lastly, a user-friendly web interface ( https://bcb.unl.edu/dbpup/ ) provides all the data online to facilitate the research of polyphenol metabolism for improved human health. Importance Long-term consumption of polyphenol-rich foods have been shown to lower the risk of various human diseases such as cardiovascular diseases, cancers, and metabolic diseases. Raw polyphenols are often enzymatically processed by gut microbiome, which encode various polyphenol utilization proteins (PUPs) to produce metabolites with much higher bioaccessibility to gastrointestinal cells. This study delivered dbPUP as an online database for experimentally characterized PUPs and their homologs in human gut microbiome. This work also performed a systematic classification of PUPs into enzyme classes, families, and subfamilies. The signature Pfam domains were identified for PUP families, enabling conserved domain-based PUP annotation. This standardized sequence similarity-based PUP classification system offered a guideline for the future inclusion of new experimentally characterized PUPs and the creation of new PUP families. An in-depth data analysis was further conducted on PUP homologs and physically linked PUP gene clusters (PGCs) in gut microbiomes of different human populations.

Classification of Companion Diagnostics: A New Framework for Biomarker-Driven Patient Selection

Background Modern personalized medicine strategies builds on therapy companion diagnostics to stratify patients into subgroups with differential benefit/risk. In general, stratification for drug response implies a treatment-by-subgroup interaction. This interaction is usually suggested by the drug’s mechanism of action and investigated in pharmacological research or in clinical studies. In these candidate genes or pathway approaches, either biological reasons for a differential benefit/risk or statistical interaction regarding a pharmacological or clinical endpoint or both may be given. For successful drug approval, demonstration of a positive benefit/risk balance in the intended patient population is required. This also applies to situations with biomarker-selected populations. However, further regulatory considerations relate to the usefulness and plausibility of the selected patients and benefit/risk extrapolations or alternative therapy options in biomarker-negative populations. Methods To facilitate the specification of regulatory requirements and support the design of clinical development programmes, a systematic classification of biomarker-drug pairs is needed, in particular with regard to the expected underlying molecular mechanism and the clinical evidence. Results A classification of five biomarker-drug categories is proposed related to increasing evidence on the biomarker’s predictive value in relation to a specific drug. We classified biomarkers into five ascending categories with increasing evidence on the predictive nature of the biomarker in relation to a specific drug according to the comparative pharmacological and clinical evidence. Conclusions The proposed classification will facilitate regulatory decision-making and support drug development with respect to biomarker-related subgrouping, both, during clinical programme and at the time of marketing authorization application, since the grade of evidence on the differential power of the biomarker can be considered as an indicator for the usefulness of a biomarker-related subgrouping.

Progress in the Application of Immune Checkpoint Inhibitor-Based Immunotherapy for Targeting Different Types of Colorectal Cancer

Colorectal cancer (CRC), a common malignant disease, has the second highest mortality rate among all cancer types. Due to the diversity and heterogeneity of CRC, few effective treatment strategies have been developed in recent years, except for surgical resection. As immunotherapy has become a revolutionary treatment after surgery, along with chemoradiotherapy and targeted therapy, numerous basic research studies and clinical trials have been conducted on CRC. Therefore, immune checkpoint inhibitor (ICI) therapy has become the main anti-CRC immunotherapy method used at present. With the rapid development of biotechnology and cell research, an increasing number of monotherapy or combination therapy strategies using ICIs for CRC have been designed in recent years. Methods to classify and review ICI strategies for different types of CRC to better guide treatment are continuously investigated. However, the identification of why the ICIs would be more effective in targeting particular subtypes of CRC such as high microsatellite instability (MSI-H) is more important because of the different immune backgrounds in patients. This review intends to classify different subtypes of CRC and summarizes the basic and clinical studies on ICIs for each subtype of CRC currently available. In addition, we also attempt to briefly discuss the progress in immunotherapy methods other than ICI therapy, such as chemoimmunotherapy strategy, chimeric antigen receptor-modified T (CAR-T) cells, or immunotherapy based on oncolytic viruses. Finally, we provide a perspective on the development of immunotherapy in the treatment of CRC and attempt to propose a new systematic classification of CRC based on immunological strategies, which may improve guidance for the selection of immunotherapy strategies for different subtypes of CRC in the future.

Epilepsy-Related Mortality in Children and Young Adults in Denmark: A Nationwide Cohort Study

Background and Objectives:Mortality is increased in epilepsy, but the important issue is that a proportion of epilepsy-related death is potentially preventable by optimized therapy and needs therefore to be identified. A new systematic classification of epilepsy-related mortality has been suggested by Devinsky et al. in 2016 to identify these preventable deaths. We applied this classification to an analysis of premature mortality in persons with epilepsy younger than 50 years.Methods:The study was a population-based retrospective cohort of all Danish citizens with and without epilepsy aged 1–49 years during 2007–2009. Information on all deaths was retrieved from the Danish Cause of Death Registry, autopsy reports, death certificates, and the Danish National Patient Registry. The primary cause of death in persons with epilepsy was evaluated independently by three neurologist, one neuro-pediatrician, and two cardiologists. In case of uncertainty a pathologist was consulted. All deaths were classified as either epilepsy- or not-epilepsy-related, and the underlying causes or modes of death were compared between persons with and without epilepsy.Results:During the study period 700 deaths were identified in persons with epilepsy, and 440 (62.9%) of these were epilepsy-related, hereof, 169 (38%) directly related to seizures and 181 (41%) due to an underlying neurological disease. SUDEP accounted for 80% of deaths directly related to epilepsy. Aspiration pneumonia was the cause of death in 80% of cases indirectly related to epilepsy.Compared with the background population, persons with epilepsy had a nearly four-fold increased all-cause mortality (adjusted mortality hazard ratio of 3.95 [95% CI 3.64–4.27], p<0.0001) and a higher risk of dying from various underlying causes including alcohol-related conditions (hazard ratio of 2.91 [95% CI 2.23–3.80], p<0.0001) and suicide (hazard ratio of 2.10 [95% CI 1.18–3.73], p=0.01).Discussion:The newly proposed classification for mortality in persons with epilepsy was useful in an unselected nationwide cohort. It helped classifying unnatural causes of death as epilepsy-related or not, and it helped identifying potentially preventable deaths. The leading causes of premature mortality in persons younger than 50 years were related to epilepsy and were thus potentially preventable by good seizure control.

Stone Works Valuation within Immovable Cultural Heritage Monuments Restoration

Historic buildings and their stone parts represent both specific functional architectural features of constructions and important aspects of the cultural heritage. They provide important and valuable proof of development, style, and architecture, level of decorative art, and material processing techniques. However, these historic buildings need restoration so that their legacy can be preserved for future generations. The quality of restoration work tends to be closely related to work price. At present, however, prices for the restoration of stone parts of historic buildings are determined intuitively, based on their complexity, uniqueness, and specificity of restoration work. The valuation of restoration work is therefore carried out mainly by the private sector, based on the experience of individual budgeters and restorers. Due to the fact that the limits of the maximum and minimum scope of individual actions are not set, incorrect valuation can occur, which, in the case of subsequent implementation, may damage, or even in fact damages, the restoration activity as such. Based on this, the article deals with valuation of stone works restoration in real historic structures. It introduces and describes the proposal for systematic classification of these types of work, the procedure for setting standards for time units and consequently the proposal of formula structure for calculating costs and prices. The aim of the article is to introduce the use of standardised procedures for pricing of stone works restoration and thereby create a comparative and cost bases in order to make a qualified choice of restoration specialists.

Classification of digital stitch lines in machine embroidery

Despite the large application of the machine embroidery in textile and apparel design and high-tech clothing items, there is а lack of systematic arrangement of the digital stitch lines, used by embroidery machines and embroidery designers. Since 2010 information on embroidery stitch lines could be mostly found in the web sites of the embroidery machine manufacturers and software product manuals. However, in the instruction manuals the instruments for creating various embroidery objects are simply described without providing systematic information on the types of the stitch lines. Even more, different names of the stitch lines and different ways to achieve the same design are observed. Single authors offer their own classifications based entirely and logically on the stitches of the hand embroidery. Another group of authors relied on already developed techniques and strategies for digitizing stitches in various software products or took into account the final appearance of the stitch lines or their application. Our study aimed to develop a detailed and systematic classification of the digital stitch lines in the machine embroidery, which has not been presented in the literature.