The Noble and Often Nobel Role Played by Insulin-Focused Research in Modern Medicine

Since diabetes was first described over 3,000 years ago, clinicians and scientists alike have sought ever improving treatments en route to a cure. As we approach the 100th anniversary of insulin’s first therapeutic use, this article will recount the glorious history associated with research surrounding insulin’s isolation, purification, cloning, and subsequent modification. The discovery path we will relate tells the story of many relentless and passionate investigators pursuing ground-breaking research. The fruits of their labor include several Nobel Prizes, new technology, and, more importantly, ever improving treatments for one of humankind’s greatest medical scourges.

The structural basis of mRNA recognition and binding by eukaryotic pseudouridine synthase PUS1

The chemical modification of RNA bases represents a ubiquitous activity that spans all domains of life. The formation of pseudouridine is the most common RNA modification and is observed within tRNA, rRNA, ncRNA and mRNAs. The catalysts of pseudouridylation, termed pseudouridine synthase or PUS enzymes, include those that rely on guide RNA molecules and others that function as stand-alone enzymes. Among the latter, up to ten are encoded in eukaryotic genomes, including several that modify uracil within mRNA transcripts. Neither the biological purpose of mRNA pseudouridylation, nor the mechanism by which individual mRNA bases are targeted, are well understood. In this study, we describe the high-resolution crystal structure of yeast PUS1 bound to an RNA target that we identified as being a hot spot for recognition, binding, and activity within a model mRNA. The enzyme recognizes RNA structural features corresponding to a base-paired duplex, which appears to act as a docking site leading to subsequent modification of the transcript. The study also allows us to visualize the divergence of related PUS-1 enzymes and their corresponding RNA target specificities, and to speculate on the basis by which this single PUS enzyme can bind and modify mRNA or tRNA substrates.

Influence of the Addition of Blast Furnace Slag to Alkali-Activated Mixtures Based on Natural Zeolites

This study focuses on a comparison of alkali-activated materials based on natural zeolites without and with the addition of blast furnace slag and their subsequent modification by acid leaching. The addition of slag to alkali-activated mixtures is generally used to increase the strength. The subsequent modification of its chemical, textural and mechanical properties by acid leaching makes this material usable in other industries, especially in the chemical industry. This study aimed to examine the influence of the addition of blast furnace slag to alkali-activated mixtures based on natural zeolites and observe the effect of subsequent acid leaching on the chemical, textural and mechanical properties and CO2 adsorption capacity of these materials. The modification of alkali-activated materials was carried out by acid leaching using 0.1 M HCl and then using 3 M HCl. The properties of these materials were determined using N2 physisorption, Hg porosimetry, XRF, XRD, DRIFT, TGA and strength measurements. The results showed that the addition of blast furnace slag significantly increased the cutting-edge strength of the obtained materials and affected the textural properties, especially in leached samples. The presence of blast furnace slag generated a higher proportion of mesopores, which are attributed to the presence of the calcium silicate hydrate (C–S–H) phase and are easily removed by leaching, as shown by the XRF results. The obtained data showed an improvement in properties and extension of the potential applicability of these materials in the chemical industry, especially for catalytic and adsorption applications.

The Effect of Atmospheric Corrosion on Steel Structures: A State-of-the-Art and Case-Study

Atmospheric corrosion can seriously affect the performance of steel structures over long periods of time; thus, it is essential to evaluate the rate of corrosion and subsequent modification of dynamic properties of a structure over different time periods. Standards and codes represent the general guidelines and suggest general protection techniques to prevent structures from corrosion damage. The available models in the literature propose the thickness reduction method that accounts for the exposure time of structures in corrosive environments. The purpose of this study is to review the existing corrosion models in the literature and report as well as compare their effectiveness in low (C2 level), medium (C3 level) and high (C4 level) corrosivity class in accordance with the ISO standard. Furthermore, the influence of corrosion loss during the lifetime of a structure is studied through a realistic case study model using FEM (finite element method) in both linear and nonlinear regions. The results showed that the corrosion can considerably affect the dynamic characteristics of the structure. For instance, the vibration period rose up to 15% for the C4 class and 100-year lifespan. Additionally, the corroded structure presented higher acceleration and drift demand, and the base reaction forces were reduced up to 60% for the same class and time period.

Post-acquisition CO2 Inhalation Enhances Fear Memory and Depends on ASIC1A

A growing body of evidence suggests that memories of fearful events may be altered after initial acquisition or learning. Although much of this work has been done in rodents using Pavlovian fear conditioning, it may have important implications for fear memories in humans such as in post-traumatic stress disorder (PTSD). A recent study suggested that cued fear memories, made labile by memory retrieval, were made additionally labile and thus more vulnerable to subsequent modification when mice inhaled 10% carbon dioxide (CO2) during retrieval. In light of this finding, we hypothesized that 10% CO2 inhalation soon after fear acquisition might affect memory recall 24 h later. We found that both cue and context fear memory were increased by CO2 exposure after fear acquisition. The effect of CO2 was time-dependent, as CO2 inhalation administered 1 or 4 h after cued fear acquisition increased fear memory, whereas CO2 inhalation 4 h before or 24 h after cued fear acquisition did not increase fear memory. The ability of CO2 exposure following acquisition to enhance fear memory was not a general consequence of stress, as restraining mice after acquisition did not alter cued fear memory. The memory-enhancing action of CO2 may be relatively specific to fear conditioning as novel object recognition was impaired by post-training CO2 inhalation. To explore the molecular underpinnings of these effects, we tested if they depended on the acid-sensing ion channel-1a (ASIC1A), a proton-gated cation channel that mediates other effects of CO2, likely via its ability to sense acidosis induced during CO2 inhalation. We found that CO2 inhalation did not alter cued or context fear memory in Asic1a–/– mice, suggesting that this phenomenon critically depends on ASIC1A. These results suggest that brain acidosis around the time of a traumatic event may enhance memory of the trauma, and may thus constitute an important risk factor for developing PTSD. Moreover, preventing peritraumatic acidosis might reduce risk of PTSD.

PRINCIPLES FOR DEVELOPMENT OF PROGRAM INTERFACES IN INDUSTRIAL INFORMATION, MEASURING, AND CONTROLLING SYSTEMS

Industrial information, measuring, and controlling systems have a program module designed to convert measurement results into data for display and control signals. A program module interconnected to other modules by program interfaces. In this case, data transformations are necessary when they are sent between modules. Object-oriented design patterns can be used when programming data transformations. When converting measurement results to objects, the Adapter design pattern can be applied. Programming the Command pattern is intended for converting objects into control signals. Data processing should be separated from their representation, storage and transmission. Functions between modules can be divided using the Model–View–Controller pattern. The use of design patterns reduces the development time and subsequent modification of software for both information, measuring, and control systems, as well as systems in other subjects of science and economics.

4 Optimisation of shared learning between critical care teams during the early stages of the COVID-19 pandemic

IntroductionIn anticipation of an uplift in critical care acuity due to COVID-19, staffing at JHG (SE) ICU was reconfigured into six discreet teams. At that time, there was no dedicated mechanism for shared learning and development of SOPs to occur in a horizontal fashion across teams. The aim of this project was to develop a tool that would enable the expanding knowledge base of each individual team to be captured, refined and rapidly disseminated to the rest of the department.MethodsA ‘Virtual Whiteboard’ was created consisting of an electronic feedback form accessible via smartphone. Individual team feedback was collated and then reviewed by a designated consultant. Subsequent modification of SOPs was disseminated across all teams via group email.ResultsThe Virtual White Board proved of particular use in the first few weeks of the new COVID-19 rota. Specific changes which occurred as a consequence of the project included improved efficiency in the use of personal protective equipment, increased clinical support to nursing staff from trainees and the development of new SOPs relating to more timely completion of death certificates.ConclusionsThe Virtual Whiteboard contributed to the ability of JHG (SE) Critical Care Unit to adapt rapidly and cohesively in the context of a fast-changing clinical environment.

Neural and Molecular Mechanisms of Biological Embedding of Social Interactions

Animals operate in complex environments, and salient social information is encoded in the nervous system and then processed to initiate adaptive behavior. This encoding involves biological embedding, the process by which social experience affects the brain to influence future behavior. Biological embedding is an important conceptual framework for understanding social decision-making in the brain, as it encompasses multiple levels of organization that regulate how information is encoded and used to modify behavior. The framework we emphasize here is that social stimuli provoke short-term changes in neural activity that lead to changes in gene expression on longer timescales. This process, simplified—neurons are for today and genes are for tomorrow—enables the assessment of the valence of a social interaction, an appropriate and rapid response, and subsequent modification of neural circuitry to change future behavioral inclinations in anticipation of environmental changes. We review recent research on the neural and molecular basis of biological embedding in the context of social interactions, with a special focus on the honeybee.

MODIFICATION OF PLA FOR 3D PRINTING AND ITS APPLICATION IN APPAREL PACKAGING

The application of biodegradable polylactic acid (PLA) in the field of 3D printing packaging was explored according to its properties and modification methods, and a new direction was proposed for the subsequent modification research and market application. In this paper, the structure and characteristics of PLA materials, modification methods and the application of 3D printing PLA materials in the packaging field are introduced in detail. With the advantages of high transparency and degradability of PLA material, the toughness, heat resistance, barrier and electrical conductivity of PLA material can be further improved, and the production cost can be reduced, so that PLA material can be used more widely in packaging field.

Liquid Based Cytology versus Conventional Cytology for Evaluation of Cervical PAP Smear

The cervix is the narrow inferior segment of the uterus which projects into the vaginal vault. Conventional cervical cytology is a simple, cost effective method that has been in use for more than 50 years and is still a highly effective cervical cancer screening procedure. Liquid-based, thin-layer preparation of cervical cytology specimens was a subsequent modification in technique. The present study was split-sample study was to compare Thin Prep Liquid-based Cytology with Conventional Pap Smear, relying on a laboratory with long term experience of the former. In our study most of the Conventional preparations showed cell overlapping, inflammatory cells, blood and mucus that obscure the epithelial cell morphology which was much reduced in Liquid based preparations.