bluuebunny/crossref_metadata_2025 huggingface dataset:
Coexistence of thought types as an attentional state during a sustained attention task
Authors: Shinagawa Kazushi , Itagaki Yu , Umeda Satoshi
Published: January 2023

Some studies have asked participants about attentional state on a scale from on-task to off-task, which set the middle option as attention focused on both, including the possibility of the coexistence of thoughts. In addition, studies using multidimensional probes explicitly assumed coexistence within spontaneous thoughts and task-focus dimensions. Although several studies have assumed the coexistence of some thought dimensions, none has explored whether these are different types of thoughts (task-focus, mind-wandering, task-related, external stimuli-related). To examine whether this coexistence of thought types occurred, we used thought probes to determine the degree of immersion in each. The participants responded to probes presented at random during a sustained attention task. The results revealed a mixture of thought types in many self-reports. In addition, the state of attentional allocation behind self-reports was estimated using the hidden Markov model. We observed the following attentional states: task-focused, task-unrelated, task-related, external stimuli-focused, and task-focused—but also focused on other thoughts. These results suggest that individuals can simultaneously allocate attention to thought types and discriminate between reporting. In some cases, probe options should also be considered for this coexistence. We also examined the relationship between self-reports and behavioral indexes, and discussed the necessity of separately measuring the degree of immersion for each thought type.
A quality-by-design eco-friendly UV-HPLC method for the determination of four drugs used to treat symptoms of common cold and COVID-19
Authors: Abdallah Nora A. , Fathy Mona E. , Tolba Manar M. , El-Brashy Amina M. , Ibrahim Fawzia A.
Published: January 2023

An optimization approach based on full factorial design was employed for developing an HPLC–UV method for simultaneous determination of a quaternary mixture used for the treatment of symptoms related to common cold and COVID-19. The quaternary mixture is composed of paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride. The developed technique is a green, fast and simple method that uses isocratic elution of mobile phase consisting of 20:5:75 (v/v) of ethanol: acetonitrile: 2.5 mM heptane-1-sulphonic acid sodium salt at pH 6.5 $$\pm$$
±
0.02. The chromatographic separation was carried out using Hypersil BDS Cyano LC Column (250 × 4.6 mm, 5 μm) with 230 nm UV detection and 1.0 mL/min. flow rate. Avoiding the routine methodology and resorting to the modern technology—represented in the usage of experimental design—allows rapid determination of the four drugs using the optimum quantity of chemicals to avoid any waste of resources. The quaternary mixture was eluted in less than 9 min., where retention times of paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride were found to be 2.2, 3.8, 6.6 and 8.8 min., respectively. The calibration graphs of the four drugs were linear over concentration ranges of 50.0–500.0, 0.5–20.0, 0.5–20.0 and 0.5–100.0 µg/mL for paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride, respectively with correlation coefficients higher than 0.999. The method is accurate with mean recoveries between 99.87 and 100.04%, precise, as %RSD for the intraday and interday precision were between 0.61 and 1.64% and very sensitive with limit of detections (LOD)’s between 29 and 147 ng/mL and limit of quantification (LOQ)’s between 95 and 485 ng/mL. The proposed method was successfully applied for the analysis of the four drugs either in raw materials or in prepared tablet with the least amount of chemicals within short time. It is also validated following International Conference on Harmonization Guidelines. The proposed method was found to be green according to the most common greenness assessment tools; NEMI, GAPI, Analytical Eco-Scale and AGREE methods. The advantages of the proposed method qualify it for routine analysis of the studied drugs either in single or co-formulated dosage form in quality control labs.
Dietary fatty acids and mortality risk from heart disease in US adults: an analysis based on NHANES
Authors: Wang Yutang , Fang Yan , Witting Paul K. , Charchar Fadi J. , Sobey Christopher G. , Drummond Grant R. , Golledge Jonathan
Published: January 2023

We investigated the association of dietary intake of major types of fatty acids with heart disease mortality in a general adult cohort with or without a prior diagnosis of myocardial infarction (MI). This cohort study included US adults who attended the National Health and Nutrition Examination Surveys from 1988 to 2014. Heart disease mortality was ascertained by linkage to the National Death Index records through 31 December 2015. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of fatty acid intake for heart disease mortality. This cohort included 45,820 adults among which 1,541 had a prior diagnosis of MI. Participants were followed up for 532,722 person-years (mean follow-up, 11.6 years), with 2,313 deaths recorded from heart disease being recorded. Intake of saturated (SFAs) and monounsaturated fatty acids (MUFAs) was associated with heart disease mortality after adjustment for all the tested confounders. In contrast, a 5% higher calorie intake from polyunsaturated fatty acids (PUFAs) was associated with a 9% (HR, 0.91; 95% CI 0.83–1.00; P = 0.048) lower multivariate-adjusted risk of heart disease mortality. Sub-analyses showed that this inverse association was present in those without a prior diagnosis of MI (HR,0.89; 95% CI 0.80–0.99) but not in those with the condition (HR, 0.94; 95% CI 0.75–1.16). The lack of association in the MI group could be due to a small sample size or severity and procedural complications (e.g., stenting and medication adherence) of the disease. Higher PUFA intake was associated with a favourable lipid profile. However, further adjustment for plasma lipids did not materially change the inverse association between PUFAs and heart disease mortality. Higher intake of PUFAs, but not SFAs and MUFAs, was associated with a lower adjusted risk of heart disease mortality in a large population of US adults supporting the need to increase dietary PUFA intake in the general public.
Xpert MTB/RIF Ultra CT value provides a rapid measure of sputum bacillary burden and predicts smear status in patients with pulmonary tuberculosis
Authors: Martin-Higuera M. C. , Rivas G. , Rolo M. , Muñoz-Gallego I. , Lopez-Roa Paula
Published: January 2023

Traditionally, smear microscopy has been used to estimate bacillary burden in order to assess infectiousness in tuberculosis (TB) patients. Since Xpert MTB assays might replace smear microscopy as the first-line diagnostic test for pulmonary tuberculosis, an alternative measure of bacillary load that correlates with smear positivity is needed. This study assessed the correlation between CT (with and without normalization), smear status, culture time-to-positivity (TTP), and clinical factors in patients with Xpert ultra positive sputum during a four-year period. A cut-off CT value for smear positivity was also estimated. 204 samples were included. Strong correlation between both Xpert Ultra CT values (raw and normalized) and smear status was obtained (r = 0.78 and − 0.79, respectively). The association between Raw-CT and TTP was weaker than normalized-CT (N-CT) and TTP (r = 0.50 and r = − 0.70, respectively). A Raw-CT cut-off value of 21.4 was identified with 85.7% (95% CI 65.4–95) sensitivity and 92.9% (95% CI 84.3–96.9) specificity. A N-CT cut-off value of 5.2 yielded a sensitivity of 94.3% (95% CI 86.2–97.8) and specificity of 85.7% (95% CI 65.4–95). Our study demonstrates that Xpert Ultra CT value correlates well with other measures of bacillary load such as smear status or TTP. The correlation with TTP is stronger when the CT value is normalized using the internal control. The proposed N-CT cut-off value of 5.2 shows a better sensitivity than the Raw-CT when predicting smear positive status.
Sustaining a network by controlling a fraction of nodes
Authors: Sanhedrai Hillel , Havlin Shlomo
Published: January 2023

Multi-stability is a widely observed phenomenon in real complex networked systems, such as technological infrastructures, ecological systems, gene regulation, transportation and more. Thus, even if the system is at equilibrium in a normal functional state, there might exist also a potential stable state having abnormal activity, into which the system might transition due to an external perturbation. Such a system can be regarded as unsustainable, due to the danger of falling into the potential undesired abnormal state. Here we explore, analytically and via simulations, how supporting the activity of a small fraction of nodes can turn an unsustainable system to become sustainable by eliminating the undesired potential stable state. We unveil a sustaining phase diagram in the presence of a fraction of controlled nodes. This phase diagram could provide how many controlled nodes are required for sustaining a given network as well as how strong the connectivity of the network should be for a given fraction of controllable nodes.
A general urban spreading pattern of COVID-19 and its underlying mechanism
Authors: Zhang Hongshen , Zhang Yongtao , He Shibo , Fang Yi , Cheng Yanggang , Shi Zhiguo , Shao Cunqi , Li Chao , Ying Songmin , Gong Zhenyu , Liu Yu , Dong Lin , Sun Youxian , Jia Jianmin , Stanley H. Eugene , Chen Jiming
Published: January 2023

Currently, the global situation of COVID-19 is aggravating, pressingly calling for efficient control and prevention measures. Understanding the spreading pattern of COVID-19 has been widely recognized as a vital step for implementing non-pharmaceutical measures. Previous studies explained the differences in contagion rates due to the urban socio-political measures, while fine-grained geographic urban spreading pattern still remains an open issue. Here, we fill this gap by leveraging the trajectory data of 197,808 smartphone users (including 17,808 anonymous confirmed cases) in nine cities in China. We find a general spreading pattern in all cities: the spatial distribution of confirmed cases follows a power-law-like model and the spreading centroid human mobility is time-invariant. Moreover, we reveal that long average traveling distance results in a high growth rate of spreading radius and wide spatial diffusion of confirmed cases in the fine-grained geographic model. With such insight, we adopt the Kendall model to simulate the urban spreading of COVID-19 which can well fit the real spreading process. Our results unveil the underlying mechanism behind the spatial-temporal urban evolution of COVID-19, and can be used to evaluate the performance of mobility restriction policies implemented by many governments and to estimate the evolving spreading situation of COVID-19.
Analytical Overview of Drug Detection: Civil Aviation
Authors: Dowdall Nigel P.
Published: January 2023

This chapter addresses the issue of substance abuse in the aviation sector, including recreational flying and the public transport and commercial industries. The evidence for the small but significant role of substance abuse in aviation accidents is reviewed, including data that have been collected from accident investigations. The international regulatory framework of the International Civil Aviation Organization is described, including the proposals to change medical assessments of licence holders to give greater emphasis to aspects of preventative medicine and behavioural issues. The current national regulatory requirements of several of the leading aviation nations, including the UK and the USA, are discussed, with an emphasis on the authorities’ approaches to the detection and management of substance misuse. The final section examines the opportunities and tools for identifying and managing individuals within the sector who have problems of substance abuse or dependency. Evidence suggests that the prevalence of substance abuse and dependency within the sector is lower than that of the general population. Nevertheless, there have been recent calls for the extension of drug and alcohol testing, particularly random testing, and the evidence for any potential benefit is reviewed. Other measures that are considered include the role of screening questionnaires performed at periodic medical examinations, the identification by law enforcement agencies, health professionals and whistle-blowers of individuals who may be of concern and the role of peer intervention programmes in both identifying and managing individuals with problems of substance abuse or dependency.
Detection of Misused Drugs: Natural and Synthetic Cathinones
Authors: Helander Anders
Published: January 2023

Cathinone is a naturally occurring monoamine alkaloid that is considered to be the main active ingredient of khat, a plant that grows wild in East Africa and the Arabian Peninsula and is used for its psychostimulant effects. In recent years, a large number of synthetic substituted cathinone derivatives have been introduced onto the recreational drugs market mainly through sale on the Internet, in addition to hundreds of other psychoactive compounds of various drug classes (e.g. cannabinoids, opioids, dissociatives and benzodiazepines). Such new drugs of abuse, commonly referred to as new psychoactive substances (NPSs), represent a growing health hazard due to their unknown adverse effects, and they have been involved in many cases of severe intoxication and fatalities. Substituted cathinones and other NPSs also represent an analytical challenge for drug testing laboratories, because standard routines for drug testing based on initial immunoassay screening followed by confirmatory analysis by mass spectrometry (MS) only focuses on the classical drugs panel. For laboratory testing of the large and increasing number of NPSs, new routines involving MS-based screening methods have to be employed.
Detection of Misused Drugs: Psychoactive Piperazines
Authors: Schep L. J. , Poulsen H. A. , Gee P.
Published: January 2023

In recent years, a new class of psychoactive drugs, predominantly causing adrenergic-like effects, has emerged in the market. They are identified by their piperazine backbone, possess a bridge to either a phenyl or benzyl group and are loosely defined as phenyl- and benzyl-piperazines, respectively. Detection of these drugs has traditionally focused on gas chromatography mass spectrometry assays, but these are being replaced by various liquid chromatography mass spectrometers, which enable greater resolution of the ion transition fragments and allow the identification of a wider range of recreational drugs. In contrast, there are, however, no known immunoassays (IAs) for the routine assessment of psychoactive piperazines, and evidence suggests routine IAs for amphetamine may cross-react with these piperazines. There is a variety of methods to extract, derivatise and identify piperazine moieties in biological matrices, as well as powders and tablets with a wide range of limits of detection and limits of quantitation, which are dependent on the methodology used and the technology available. When applied to identifying and quantifying analogues in powders and tablets, research has shown inconsistencies in both stated doses and the presence of unreported agents within a variety of different formulations. The analyses of biological matrices, obtained from autopsies or patients attending emergency departments, show evidence of elevated concentrations of various piperazines that may span several orders of magnitude.
The Usefulness of Metabolites in the Interpretation of Drug Test Results
Authors: Scott-Ham Michael
Published: January 2023

Many drugs are extensively metabolised in the body and consideration of these, in addition to the parent drugs, is often of great significance to providing the most useful information to the commissioner of the analytical testing. Many other factors affect the usefulness of the results of this testing, including sample type, the presence or absence of preservatives, sampling site, sample storage and analytical procedures, and all of these should be considered when interpreting these results. Examples of various illicit and medicinal drugs are given in order to provide a flavour of these issues, but also to highlight the potential usefulness of the inclusion of metabolites in drug testing of toxicological samples.
Neurohypophyseal Hormones and Drugs of Misuse
Authors: Johnson Jacinta L. , Johnson Michaela E. , Buisman-Pijlman Femke
Published: January 2023

A growing body of evidence suggests that neurohypophyseal hormones like oxytocin are able to modulate drug taking and susceptibility to addiction through interactions with a number of key neurobiological systems that are implicated in addiction processes. This chapter will describe the synthesis and role of these hormones and will examine the advantages and disadvantages of the methods of detection of oxytocin and vasopressin in humans. It will also describe the evidence relating to the relationship between peripheral and central concentrations of oxytocin and vasopressin. Lastly, it will highlight the relationship between the neurohypophyseal hormones and drugs of abuse. All studies associating neurohypophyseal hormones with behaviour rely upon accurate quantitation of peptide concentrations. Following extensive discussion in the field, the debate is ongoing as to which are the most appropriate methods for sample collection and analysis. This chapter will pull together the evidence in order to provide a current overview of the options and opportunities.
Molecular Cloning and DNA Sequencing
Authors: Rapley Ralph
Published: January 2023

Important advances in the understanding of gene structure, function and regulation have advanced the field of mutation analysis beyond recognition in a very short space of time. Much of this has been through the analysis and manipulation of nucleic acids using gene cloning and DNA sequencing. This has been accelerated through the discovery of DNA-manipulating enzymes, such as DNA polymerase, DNA ligase and reverse transcriptase. In particular, restriction endonucleases provided not only a turning point for the analysis of DNA but also the means to develop recombinant DNA technology as well as key methods for gene library production, molecular cloning and DNA sequencing. This chapter provides the detail of the techniques of cDNA and genomic library production and the identification of specific DNA fragments. In addition the key technology of DNA sequencing, which has allowed the development of the field of genomics, is presented, together with an overview of the newer technologies of second- and third-generation sequencing.
Microbial Proteomics
Authors: Patel Hershna , Whitehouse David B.
Published: January 2023

Proteomics is the large-scale and high-throughput study of proteins. A proteome is the population of all proteins expressed by the genome in a specific cell type, tissue or biological fluid at a particular time and under specific conditions. Any tissue, cell type or extracellular fluid is amenable to proteomic analysis. This chapter addresses the principles and practice of proteomics, focusing on microbial pathogens. An introduction to protein chemistry and analytical separation techniques is followed by a discussion of the technologies, approaches and applications of proteomics in the microbiology laboratory. Although the potential of proteomics for bacterial identification and characterisation remains to be fully realised, it is clear that this rapidly evolving science has already paved the way to aspects of cell biology and molecular pathology that were previously unattainable.
Introductory Bioinformatics
Authors: Whitehouse David , Rapley Ralph
Published: January 2023

Increasing amounts of molecular sequence data has produced challenges for computational biology and database management. This chapter introduces some of the key bioinformatics database resources and programs that have become pivotal to the progression of many branches of biological and medical sciences. Primary nucleic acid and amino acid sequence databases, such as GenBank and UniProt, are described along with more specialised databases, such as COSMIC and InterPro, that have been developed to address specific areas, such as cancer biology and protein family analysis. Parallel developments in textual knowledgebases, such as OMIM, and search tools, such as PubMed, enable the ready integration of experimental data with current medical and basic research and applications. Analytical software suites, such as BLAST and Align, are described which enable DNA or amino acid sequences to be searched against all known molecular sequences. Applied bioinformatics in the research laboratory is discussed in the context of the PCR. All of the database resources and software tools described in the chapter are freely available and generally simple to use.
Rare Disease Genomics and Clinical Diagnostics
Authors: Gouw Arvin M. , Pal Lipika R. , Varon Debora , Fumagalli Danielle C. , Chacko Anita
Published: January 2023

Rare diseases are not rare, and many of them have an underlying genetic cause. This chapter provides an overview of the history of sequencing technologies and how they are used in rare disease research. More specifically, challenges and opportunities for the use of genomics analyses in rare disease research and clinical practice are discussed. Last but not least, organizational efforts in rare disease genomics have had great successes and such collaborative efforts are the key to success in implementing genomics in rare disease research and diagnostics.
Molecular Microbial Diagnostics
Authors: Kalland Karl-Henning , Kommedal Øyvind , Ulvestad Elling
Published: January 2023

The suffering and deaths caused by infections and epidemics remain unsurpassed by any other malady afflicting the human species. Fortunately, a revolution has happened and is ongoing concerning laboratory diagnosis of infectious agents, including viruses, bacteria, fungi and parasites. Foremost amongst the new methods are tests based on analyses of nucleic acids – including DNA and RNA – from the causative microbial agents. Not only are these techniques orders of magnitude faster than the older techniques, they are also more sensitive and specific, and enable the detection of non-cultivable microbes. This chapter reviews the methodological basis of nucleic acid amplification, hybridization and sequencing methods that have now become established in modern diagnostic microbiology laboratories. The new molecular methods assist the medical doctor in agent identification, choice of correct therapy, monitoring of therapeutic effect and discovery of drug resistance. The new methods are used to discover and monitor epidemics. The future potential is great for automation, miniaturization, increased capacity, speed, reliability and user friendliness, whilst relative roles of nucleic acid amplification, next-generation sequencing and novel innovations remain undetermined. What is certain is that nucleic-acid-based techniques will continue to revolutionize the way we diagnose and treat infections.
Parasite Genomes and Diagnostics
Authors: Polley Spencer D.
Published: January 2023

The diagnosis of parasitic infections has, until recently, remained firmly grounded in the traditional methodologies of microscopic analysis of parasites in clinical samples coupled with the detection of anti-parasite antibodies in human serum. Over the last decade a significant shift has taken place in the uptake of diagnostic technologies based around the parasites' genome and even its transcriptome. This time period has also seen the development of these assays from in-house diagnostics to commercially released CE-marked assays. Nucleic-acid-based assays offer a significant improvement in analytical sensitivity in many scenarios compared with traditional techniques. In addition they allow for pathologists to determine the presence of live parasites (especially relevant in reinfections or post-treatment samples), differentiate between morphologically identical parasites and look for drug-resistance loci. The commonality in the technologies used between different disciplines has also allowed for the development of syndromic assays to analyse samples for multiple pathogens simultaneously, whilst reducing the specialist knowledge required to do so.
Next-Generation Molecular Markers: Challenges, Applications and Future Perspectives
Authors: Verma Mukesh , Barh Debmalya , Hassan Syed Shah
Published: January 2023

In this chapter we discuss the challenges in cancer biomarkers discovery. Furthermore, we discuss next-generation molecular markers and their applications in diagnostic screening, early diagnosis, risk assessment, prognosis and pharmacogenomics of immune diseases, cardiovascular diseases, metabolomic diseases, infectious diseases, neurological diseases and cancers. Additionally, we give brief accounts of therapeutic biomarkers for these selected diseases. Finally, we conclude the chapter with a future perspective on molecular biomarkers.
Transgenesis
Authors: Liu Wei , Wang Xin , Cartwright Elizabeth J.
Published: January 2023

Transgenesis is a term to describe an array of techniques used to modify the genomes of intact organisms including those of plants, insects, invertebrates, amphibians, fish and small and large mammals. To increase our knowledge of human health and disease, it is essential that we elucidate the function of the 21 000 genes in the mammalian genome. The mouse is the most commonly used mammalian model in which to explore gene function owing to the relative ease with which its genome can be modified. In the mouse, gene function can be altered in a number of ways, including over-expressing a gene, expressing a foreign gene, knocking out or deleting single or multiple genes, introducing point mutations and altering gene expression in a specific tissue or at a specific point in time. This chapter describes how the different techniques are used to introduce this wide range of gene modifications.
The Biotechnology and Molecular Biology of Yeast
Authors: Curran Brendan P. G. , Bugeja Virginia C.
Published: January 2023

The yeast Saccharomyces cerevisiae plays a central role both in biotechnology, the profitable exploitation of biological systems by humans, and in molecular biology, the study and manipulation of biological systems at the molecular level. Its contribution to biotechnology extends back over 2000 years; its contribution to molecular biology, although more recent, is equally impressive because it is currently the most molecularly characterised eukaryotic organism on the planet.
Antibody Engineering and Immunotherapeutics
Authors: Rapley Ralph
Published: January 2023

Antibodies have been known for many years to be a powerful therapeutic molecule and have given rise to the ‘magic bullet’ approach to targeted therapy of disease. Significant advances in the discovery and development of monoclonal antibodies and hybridoma technology led to the first engineered antibody in 1984. Since then, hundreds of antibodies are now being used for treatment and many more are in clinical trials. This chapter focuses on the production of hybridomas, the development of antibody humanisation techniques, surface display strategies and transgenic techniques that all play a major role in monoclonal antibody production for use in immunotherapeutics. The ability to conjugate antibodies to toxins and drugs to allow the delivery of potent molecules to disease targets and the potential to produce antibody fragments such as scFvs and nanobodies is also introduced. Furthermore, advances in CDR (complementarity-determining region) analysis and the molecular techniques that allow the fine tuning of antibody specificity and affinity are also covered. There is no doubt that the new generation of biological therapeutics will continue to have a profound impact on the present and future treatment of disease and a number of examples are presented within the chapter.
Introduction to Bioinformatics
Authors: Rapley Ralph , Whitehouse David B.
Published: January 2023

Bioinformatics is now an essential area in its own right in the biosciences and is now fully integrated into mainstream molecular biology and biotechnology in addition to many other areas, including immunology, microbiology, agriculture and medicine. There are a number of bioinformatic databases such as GenBank that contain many different types of biological information that can be accessed and analysed online using numerous resources such as the National Center for Biotechnology Information (NCBI) resource. It also encompasses an array of multidisciplinary approaches and is pivotal to all the areas of bioscience that are associated with the analysis of massive datasets and forms the basis of all genome project data management The fields within the area comprise biocomputation from analysis of molecular protein interactions to small-molecule library analysis in pharmacology studies, in addition to DNA and protein data analysis and similarity studies, among many other areas. Many species have dedicated databases and programs for their analysis and there are also many dedicated resources for the analysis of biological data in health and disease.
Nanotechnology in Medicine
Authors: Seriah Sara , Efthimiadou Eleni , Braoudaki Maria
Published: January 2023

Nanotechnology is a field that encompasses several disciplines and the exploitation of its nanoscale properties is growing at a rapid pace. In nanomedicine in particular, nanoparticles are used in a variety of applications, including the prevention, diagnosis and treatment of severe diseases such as cancer. There are different types of nanoparticles, mainly divided into organic, inorganic and hybrid types. Each type affords several properties that can be manipulated upon synthesis to suit the intended application and to achieve optimal results.
Biosensors
Authors: Chaplin Martin F.
Published: January 2023

Biosensors are analytical devices that convert biological actions into electrical signals to quantify them. In this chapter, biosensors that make use of the specificity of biological processes are described, that is, the recognition of enzymes for their substrates or other ligands, antibodies for their antigens, lectins for carbohydrates and nucleic acids or peptide nucleic acids for their complementary sequences. Biosensor science is interdisciplinary, bringing together chemistry, physics, biology, electronics and engineering to solve real-world analytical problems such as the sudden great need to test for coronavirus in the 2020–21 pandemic.
Vaccine Design Strategies: Pathogens to Genomes
Authors: McMullan Niall
Published: January 2023

Vaccines are undoubtedly one of the great triumphs of medical science. The global eradication of smallpox, once one of the most devastating infectious diseases of humankind, and the extensive control of various other infectious diseases bear testimony to the efficacy of vaccines. Much of this success employed classical vaccine designs, namely live attenuated vaccines as used for smallpox, measles, mumps and rubella (MMR), the BCG tuberculosis vaccine and the Sabin polio vaccine, and inactivated vaccines such as the Salk polio vaccine. Since then, subunit vaccines based on isolated macromolecules, including toxoid vaccines against tetanus, diphtheria and pertussis and conjugate vaccines against several forms of bacterial meningitis, have been developed. The advent of recombinant DNA technology and the first recombinant protein vaccine, the hepatitis B vaccine introduced in the 1980s, heralded a paradigm shift in vaccine design – no longer was it necessary to culture the pathogen. This millennium saw the introduction of recombinant protein vaccines against human papillomavirus (HPV) and meningitis B (MenB). Despite these successes, the persistence of malaria, HIV/AIDS and hepatitis C along with the emergence of novel zoonotic infections such as the devastating outbreaks of Ebola virus disease and the coronavirus outbreaks, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and Covid-19, serve as a reminder of the need for new vaccine technologies. At the forefront of this are recombinant vector vaccines and nucleic acid vaccines supported by dedicated bioinformatics tools. This chapter provides an overview of the immunology of vaccines and the range of vaccine design strategies currently being employed.
Phage-mediated Detection of Biological Threats
Authors: Ripp Steven
Published: January 2023

Bacteriophage, or bacterial viruses, are obligate intracellular parasites that rely upon compatible bacterial host cells for their survival and propagation. Since bacteriophage posses a means to very specifically identify the particular host cells to which they can attach and subsequently infect, this powerful recognition capacity can be exploited to create assays for defined detection and monitoring of bacterial targets. This chapter provides an overview of the various bacteriophage-mediated reporter and sensor systems that have been developed for the detection of priority biological agents.
Site-directed Chemical Modification of Phage Particles
Authors: Saleh Lana , Noren Christopher J.
Published: January 2023

The ability to chemically modify the surface of bacteriophage bypasses the functional limitations imposed by the standard biosynthetically incorporated amino acids that comprise the phage coat. Appended functionalities can include fluorescent or other reporter groups, inorganic materials, cytotoxic agents, and pharmacophores. Applications include incorporating the modification in the context of a displayed random peptide library prior to panning as a route to chimeric semisynthetic peptide ligands, use of phage as a template for construction of novel nanomaterials, direct mechanical manipulation of phage, use of phage particles as medical imaging reagents, and catalysis-based screening for novel enzyme activities.

Site-specific modification of phage in the context of the forest of competing functional groups that make up the phage coat requires a uniquely reactive chemical group specifically placed in the coat protein. The so-called “21st amino acid” selenocysteine (Sec) is found in all three kingdoms of life and is co-translationally incorporated via a context-dependent opal suppression mechanism. The lower pKa of Sec (5.2 vs. 8.3 for cysteine) permits modification by direct nucleophilic substitution at low pH values, where other nucleophilic amino acids are essentially unreactive. Incorporation of Sec-insertion signals into the phage coat protein gene gIII results in quantitative site-specific incorporation of Sec, which can, in principle, be modified with any novel chemical group. The use of phage-displayed selenopeptides for chimeric library screening, enzyme evolution, and direct mechanical manipulation of phage will be discussed in this chapter.
What is Pharmacology?
Authors: Rang Humphrey
Published: January 2023

Pharmacology is the study of the action of drugs on living systems – neatly paraphrased as the chemical control of physiology and pathology. It lies at the interface of chemistry and biology. Drugs, in this context, are chemicals of known structure that are administered as external agents – whether deliberately or accidentally – to the organism, and produce an observable effect on its function. This chapter provides an introduction to pharmacology, describing a brief history of the discipline.
The Pharmacological Analysis of Drug Activity in Receptor Systems
Authors: Kenakin Terry
Published: January 2023

Pharmacology is the only discipline that deals with the fact that because drugs interact with complex organs with basal activities and sensitivities, they can demonstrate different pharmacological and physiological behaviors. This chapter outlines the various pharmacological procedures available to convert descriptive activity (what is seen in the experiment) to predictive activity (indices that can predict behaviors in all tissues). This is essential since drugs are discovered and tested in surrogate test systems and rarely in the therapeutic system. A major division for drug activity is direct effect (agonism) and interference with a physiological effect (antagonism). The former uses methods that apply the Black/Leff operational model of agonism and deals with pluridimensional efficacy (a drug can have multiple efficacies) and biased signaling (an agonist may emphasize certain pathways in cells). Antagonism can be divided into orthosteric mechanisms (steric hindrance) and allosteric mechanisms (the antagonist binds to a separate site on the receptor). All of these procedures are designed to furnish system-independent parameters of drug activity that should describe what a drug can do in all physiological system; these data are essential for optimal choice of new drug candidates for progression in discovery programs.
Structure-based Drug Discovery and Advances in Protein Receptor Crystallography
Authors: Congreve Miles , Marshall Fiona H.
Published: January 2023

In this chapter we describe recent developments in the practice of structure-based drug design (SBDD) and the computational methods that can be applied across a diversity of target classes. Recent technological advances are discussed that have enabled breakthroughs in membrane crystallography in particular in the field of G protein-coupled receptors. This review describes recent examples of SBDD applied to four specific target classes, kinases, proteases, protein–protein interactions and GPCRs. Overall, this is a large and rapidly moving field that is significantly impacting on drug development pipelines and the future success of the pharmaceutical industry. It is likely that a significant proportion of drugs in the future will be derived from structure- and fragment-based methods that can be used to complement other strategies in drug discovery.
Actions of Drugs on the Autonomic Nervous System
Authors: Blackburn Thomas P.
Published: January 2023

The autonomic nervous system (ANS) is a network of neurones that innervate the organs of the body through branches of the sympathetic and parasympathetic nervous system. Chemical signals between neurones of both systems interact with associated receptors by which cells in the body communicate with one another and are the target of drugs that affect chemical transmission between cells and body organs (e.g., heart, kidney, GI system and the brain/CNS). Stimulation of the body's sympathetic system in general depresses all physiological function, except those that prepare the body to cope with the challenge of an emergency situation, the so-called “fight or flight” response to physical exertion. In contrast, the parasympathetic system, with a few exceptions opposes the effect of sympathetic stimulation and controls those physiological functions that conserve the body's energy stores, although neither is universally “stimulating” or “depressing”. Thus, the focus of this section is to understand the pharmacology of how drugs exert control of chemical transmission in the peripheral autonomic nervous system, with the same general principles applying to the central nervous system (see Chapter 5).
Actions of Drugs on The Brain and CNS Disorders
Authors: Blackburn Thomas P.
Published: January 2023

The psychiatric and neurological drugs reviewed in this section include anxiolytics, antidepressants, antipsychotics, sedative-hypnotics, anticonvulsants, and general and local anaesthetics. The pharmacology and chemistry for various classes of CNS drugs show several commonalities. For example, sedative-hypnotics also possess anxiolytic and anticonvulsant properties and at higher concentrations are general anaesthetics. Antipsychotics, also possess sedative-like/anxiolytic properties, but are unique in that they ameliorate the positive or negative thought disorders of schizophrenia. The structural similarities of the many CNS compounds are associated with allosteric or nonspecific binding to receptor proteins, where hydrophobic groups attach to a semipolar group that are capable of acting as a protein donor or acceptor – a common structural chemotype with CNS agents, that has stymied therapeutic advances over recent decades, thus, accelerating the need for breakthrough innovative approaches in medicinal chemistry, neuropharmacology/neuroscience and the formation of international collaborations like the Human Brain Project. This project, together with significant advances in imaging technologies (e.g. optogenetics – which uses light to control neurones in the brain) and gene editing (CRISPR/Cas9), are game changes in our understanding of how CNS agents interact with neurotransmitters, neuronal brain circuits, to unmask specific pathophysiological states associated with CNS disorders and pave the way for the development of new psychiatric and neurological drugs over the next decade. This chapter reviews recent progress in neuropharmacology for several CNS disease targets.
Clean Chemistry – The Science Behind Cleansing Products
Authors: Rolls Edward
Published: January 2023

If one word could sum up the cosmetics industry, one word that the majority of cosmetic and toiletries could not do without, then that word is ‘surfactant’. It is the basis of all cleansing products, it is responsible for the structure of creams and lotions. This chapter concentrates on its use in cleansing products by describing how it can turn water into an effective cleansing product. We will learn how we build on that simple addition to give a huge range of products that are now available and how the science of surfactants is adapting with current trends of natural, organic and sustainability.
Good Hair Day: The Science Behind Hair-care Products
Authors: Cornwell P. , Lim J.
Published: January 2023

Hair, for many of us, defines who we are and is our ‘crowning glory’. This chapter provides an overview of the science that underpins product development in the hair-care category. It describes the structure of the hair fibre and the processes involved in hair growth. It then shows how things can ‘go wrong’, resulting in hair damage, greying, hair loss or combinations of these effects. The chapter also covers the chemistry that is used to create the products that we use every day and the measurement techniques used to test product performance.
Oral Care – A Mouthful of Chemistry
Authors: Roberts Eleanor , Mason Stephen
Published: January 2023

Hard enamel on the outside of teeth is supported by softer underlying dentine and pulp. Enamel is mostly composed of hydroxyapatite, formed from calcium and phosphate. Enamel can be weakened if the oral environment becomes too acidic (pH<5.5), but hydroxyapatite can be re-formed from salivary minerals. However, if this environment is too acidic for too long, enamel can be permanently lost, leading to tooth erosion and/or dentine hypersensitivity. Teeth, and gums, can also be affected by oral bacteria, especially in the form of plaque, which can lead to caries and gum disease, and by deposits of calculus. Fluoride toothpaste, delivered via a suitable toothbrush and brushing technique, can help with enamel remineralization and limit bacterial growth. Abrasives in toothpaste, along with chemical agents, can remove dental plaque and stained pellicle, the layer that forms over enamel. Additional ingredients, alongside different fluoride preparations, include those that can help with dentine hypersensitivity or gum disease, can limit calculus build-up or can whiten teeth. Formulation considerations must balance all of these ingredients and pack them in a toothpaste that not only works, with any product benefit claims being substantiated, but also tastes and feels good to use twice per day, every day.
More Than a Smudge of Colour – The Science Behind Colour Cosmetics
Authors: Summers Claire , Dubois Pauline
Published: January 2023

The science behind colour cosmetics explains how colour is perceived by our eyes and how, as a result, an object will appear coloured. Changing the interactions between the body surfaces and the visible electromagnetic spectrum is how the cosmetic scientist creates the great variety of coloured cosmetic products – from lipsticks, eyeshadows and foundations to hair colourants. This chapter explores the many types of colourants that are available to us and their endless combinations. The options range from organic and inorganic for intensity through to pearlescent pigments, which can be used to achieve effects ranging from shimmer to sparkle, in addition to being able to create colour from light, which is referred to as interference. A question often asked is whether these colourants are chemicals, and the simple answer is ‘yes’. We need then to understand how and when to use them and also how to disperse them to achieve the desired effect. Colouring our formulations is then possible as it is both an art and a science.
The Inside Story – The Science Behind Active Ingredients
Authors: Metcalfe C. , Causer T.
Published: January 2023

This chapter covers a wide range of active ingredients and product types, demonstrating how specific ingredients work in your products and why they are used. The chapter takes a look both at ingredients that are widely used in products to deliver ‘everyday’ functions, such as antioxidants and preservatives, and at some of the industry's ‘special’ palette of active ingredients, such as peptides and vitamins.
Paper
Authors: Daniels V.
Published: January 2023

Paper is made from cellulose fibres which can be derived from many kinds of plants. Huge amounts of paper have been manufactured and very large amounts of paper can be found in public collections. Paper is present in everyday life in many forms with surfaces embellished with writing or decorative features. The basic principles behind the formation of paper will be discussed as well as the common additives. The stability of well-stored paper can be decreased by two chemical mechanisms, acid-catalysed hydrolysis and oxidation. The causes for the acceleration of decay by these mechanisms are reviewed as well as the various conservation processes and storage conditions which can be used to slow down degradation. Paper often discolours on ageing and although some of the ageing products can be removed with water, bleaching can be used to restore the original hue. Paper interacts with water causing chemical and physical changes, some of which are of vital importance to the proper care and conservation of the paper. There are many analytical techniques that can be used on paper ranging from very simple “spot” tests to those involving large instrumental systems; the most useful of each kind are described. Methods of testing the strength of paper are also very useful. A case study of a research project on the washing of paper is given to illustrate how basic information on the properties of discoloured paper has been obtained.