Exploratory Investigations Research Articles

Introducing SuFEx click chemistry into aliphatic polycarbonates: a novel toolbox/platform for post-modification as biomaterials.

As a biodegradable and biocompatible biomaterial, aliphatic polycarbonates (APCs) have attracted substantial attention in terms of post-polymerization modification (PPM) for functionalization. A strategy for the introduction of sulfur(VI)-fluoride exchange (SuFEx) click chemistry into APCs for PPM is proposed for the first time in this work. 4'-(Fluorosulfonyl)benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate (FMC) was designed as a SuFEx clickable cyclic carbonate for APCs via ring-opening polymerization (ROP), and an operational and nontoxic synthetic route was achieved. FMC managed to undergo both ROP and PPM through the SuFEx click chemistry organocatalytically without constraining or antagonizing each other, using 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) as a co-organocatalyst here. Its ROP was systematically investigated, and density functional theory (DFT) calculations were performed to understand the acid-base catalytic mechanism in the anionic ROP. Exploratory investigations into PPM by SuFEx of poly(FMC) were conducted as biomaterials, and the one-pot strategies to achieve both ROP and SuFEx were confirmed.

A GIS-Agriflux Modeling and AHP Techniques for Groundwater Potential Zones Mapping

Groundwater is considered as the main portion of the water supply in arid and semi-arid regions. The Sfax plain area is part of the arid/semi-arid areas of Tunisia that are subject to the impact of climatic and human pressures. Water scarcity in combination with groundwater exploitation is a major concern in this region. Therefore, sustainable management and protection of groundwater resources, it necessary. The delineation of groundwater potential (GP) zones becomes an increasingly important tool for implementing successful management programs. The purpose of the present paper is to assess the potential zone of groundwater resources in the study area. An efficient approach using geographical information system (GIS), hydrological modelling and analytical hierarchy process (AHP) was developed. At first, six groundwater parameters that affect groundwater occurrences are derived from the spatial geodatabase. Those parameters are: Infiltration rate estimated from a GIS linked model, lineament density, drainage density, slope, rainfall and Land use/land cover. Then, the assigned weights of thematic layers based on expert knowledge were normalized by eigenvector technique of AHP. The parameter layers were integrated and modeled using a weighted linear combination (WLC). The resulting map was classified into four categories: very low, low, good, and excellent. The results showed that about 26% of the study area falls under very-low-potential zone, with 30% on low-potential zone, 21% with good potential zone, and 23% falling under excellent zone. The results of the analysis were validated using pumping rate data and curve trend of sensitivity classes theory validation of outcomes indicated a good prediction accuracy. The results of the present study can serve to prepare a comprehensive groundwater development and management plans proving its efficacy in this art of exploratory investigations.

Magnetic Abrasive Polishing of Stainless Steel SS304 with Diamond-Based Sintered Magnetic Abrasives

The most critical phase of all the stages needed for quality sample preparation for microscopic study is perhaps surface polishing. Magnetic abrasive polishing is a nonconventional finishing operation that can finish different materials and produce nano-finished surfaces. This study emphasizes the fabrication of a magnetic abrasive polishing setup for metallurgical polishing of specimens. Utilizing this test arrangement, exploratory investigations have been conducted to analyze the impact of five significant interaction factors, specifically the gap between the magnetic pole and the workpiece ([Formula: see text]), the quantity of diamond-based sintered magnetic abrasives ([Formula: see text]), the rotational speed of the magnetic pole (RPM), the grit size of sintered magnetic abrasives ([Formula: see text]), and machining time ([Formula: see text]). The abrasives used in this study were diamond-based sintered magnetic abrasives. The percentage change in surface roughness (PCSR) of the stainless steel SS304 workpiece is the response variable. From the results of the ANOVA study, the most important factor affecting the PCSR of the stainless steel SS304 workpiece is the abrasive grit size (49.49%), and the least important factor is the machining time (4.89%). The differences in scanning electron microscopy (SEM) images and surface profiles of workpieces demonstrate that the developed setup can polish stainless steel SS304 plane workpieces.

The Effect of Irradiated Riboflavin in Human Tenon’s Fibroblast – A Study on Cellular Viability

ABSTRACT Purpose/ Aim The main purpose of this work is to study the cellular viability effect of irradiated riboflavin in cultured human tenon fibroblasts. Materials and Methods The tenon tissue was harvested from a patient undergoing strabismus surgery. The human tenon fibroblast cell culture and isolation were performed according to the standard laboratory cell culturing protocol. The cells were divided into three groups: control, treatment with irradiated and non-irradiated riboflavin. There were five different concentrations (0.00156%, 0.003125%, 0.00625%, 0.0125%, 0.025%) in each group of riboflavin. The fibroblasts were treated with riboflavin and the cellular viability was assessed at 24-hour and 48-hour post treatment with MTT 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide colorimetric assay. The absorbance values were analysed using Magellan microplate reader data analysis. A triplicate of readings was taken. The data were presented as mean ± standard deviation of the triplicates. Statistical analysis was performed with Statistical Package for Social Sciences (SPSS) analysis version 23. Results Irradiated riboflavin caused a concentration-dependent cell death in human tenon fibroblast cell culture (p < .05). The antiproliferative difference between irradiated and non-irradiated riboflavin was significant up to 48 hours (p < .05). Post hoc multiple comparisons showed higher concentrations of irradiated riboflavin (0.0125% and 0.025%) caused more reduction in cellular viability in human tenon fibroblast cells (p < .05). The duration of treatment is not a causative factor in this study. Conclusions This pilot experiment demonstrated that irradiated riboflavin induced cell death in human tenon fibroblast culture in a concentration-dependent manner, but is not time-dependent. Further exploratory investigations should be performed to determine the mechanism of cell death. We postulate that apoptosis occurred in these irradiated riboflavin-treated cells.

A Note of Caution on Distorted Visual Feedback as a Treatment for Functional Movement Disorders.

A Note of Caution on Distorted Visual Feedback as a Treatment for Functional Movement Disorders.

A Model in Female Rats With Phenotypic Features Similar to Interstitial Cystitis/Bladder Pain Syndrome.

This report describes methodological and exploratory investigations of the zymosan-induced neonatal bladder inflammation (NBI) model of interstitial cystitis/bladder pain syndrome (IC/BPS) in female rats. These results validate and extend the currently employed model by evaluating critical timepoints for obtaining treatment effects and identified that a second insult as an adult including repeat intravesical zymosan, intravesical lipopolysaccharide, acute footshock stress, neuropathic nociception (facial) or somatic inflammation (hindpaw) all resulted in magnified visceromotor responses to urinary bladder distension (UBD) in rats which had experienced NBI when compared with their controls. NBI also resulted in increased tone and reactivity of pelvic floor musculature to UBD, as well as increased responsiveness to intravesical potassium chloride solutions, abnormal anxiety measures (elevated plus maze) and an increased number of submucosal petechial hemorrhages following 30 min of hydrodistension of the bladder. These phenotypic findings have correlates to the clinical features of IC/BPS in humans and so support use of this model system to examine mechanisms of and treatments for IC/BPS.

Unravelling protein turnover in Duchenne muscular dystrophy: one protein at a time.

Unravelling protein turnover in Duchenne muscular dystrophy: one protein at a time.

Comprehensive modeling of mineral potential mapping by integration of multiset geosciences data

This work has evaluated the functionality of various fuzzy-based fusion methods in the mineral potential mapping (MPM), by which a multi-criteria decision-making problem was solved to design a layout for drilling complementary boreholes through a comprehensive analysis of geospatial datasets. The novel methods employed were fuzzy c-means clustering, fuzzy gamma operator, fuzzy inference system (FIS), fuzzy outranking, and fuzzy ordered weighted averaging (FOWA). Kahang porphyry Cu-Mo deposit in the Isfahan province of Iran was chosen as a case study to examine the performance of these fuzzy methods in MPM. Extracted geospatial indicator layers for assessing the potential of porphyry-type mineralization were derived from four criteria, namely geology (rock units and faults), remote sensing (alteration map), geochemistry (Cu, Mo, and factor maps), and geophysics (reduced to the pole and analytical signal of magnetic data). The concentration-area multifractal method was utilized to reclassify each synthesized fuzzy favorability map into five classes. To appraise and compare the efficiency of each employed method, a productivity measure assumed as a cumulative summation of Cu grade multiplied by its thickness above an economical cut-off value of 0.2% was calculated along with each drilling (totally 33 ones). According to fuzzy favorability maps derived from running all fuzzy methods, the FIS and FOWA had the highest efficiency with 80 and 78% of accuracy, respectively. Eventually, taking all fuzzy maps into account led to the delineation of some new favorable zones, whereby further exploratory investigations are envisioned for determining their mining potential.

Designer nanoparticles for plant cell culture systems: Mechanisms of elicitation and harnessing of specialized metabolites.

Plant cell culture systems have become an attractive and sustainable approach to produce high-value and commercially significant metabolites under controlled conditions. Strategies involving elicitor supplementation into plant cell culture media are employed to mimic natural conditions for increasing the metabolite yield. Studies on nanoparticles (NPs) that have investigated elicitation of specialized metabolism have shown the potential of NPs to be a substitute for biotic elicitors such as phytohormones and microbial extracts. Customizable physicochemical characteristics allow the design of monodispersed-, stimulus-responsive-, and hormone-carrying-NPs of precise geometries to enhance their elicitation capabilities based on target metabolite/plant cell culture type. We contextualize advances in NP-mediated elicitation, especially stimulation of specialized metabolic pathways, the underlying mechanisms, impacts on gene regulation, and NP-associated cytotoxicity. The novelty of the concept lies in unleashing the potential of designer NPs to enhance yield, harness metabolites, and transform nanoelicitation from exploratory investigations to a commercially viable strategy.

Growing theory for practice: empirical multimodality beyond the case study

Abstract Many studies investigating the use and effectiveness of multimodal communication are now confronting the need to engage with larger bodies of data in order to achieve more empirically robust accounts, moving beyond the earlier prevalence of small-scale ‘case studies’. In this article, I briefly characterise how recent developments in the theory of multimodality can be drawn upon to encourage and support this change in both scale and breadth. In particular, the contribution will show how refinements in the degree of formality of definitions of the core multimodal constructs of ‘semiotic mode’ and ‘materiality’ can help bridge the gap between exploratory investigations of complex multimodal practices and larger-scale corpus studies.

Some features of prospecting work in the oil and gas region of Ganja

Extensive exploratory investigations and borehole surveys have confirmed the high prospect of oil and gas potential of the Upper Cretaceous-Maikop deposits in numerous structures in the Ganja oil and gas region. The structures identified in the OGR have a complex structure and are also complicated by multidirectional fractures. Although the regularity of field formation has been clarified, an individual approach to prospecting and exploration operations at each block is necessary. It is necessary to direct prospecting and exploration operations to obtain direct geophysical parameters representing oil and gas potential in other blocks, taking into account the results of recent comprehensive geophysical surveys at the Gazanbulag-Chaily and Naftalan-Godakboz fields. Taking into account the available geophysical data and using appropriate geophysical complexes for predicting of oil and gas potential in anticlinal and non-anticlinal structures, determination of their boundaries and depths, elements of traps and stratigraphic affiliation is an effective way for further exploration of oil and gas. Keywords: seismic survey; refracted wave; gravity-magnetic survey; seismic and gravimetric anomaly; trap; oil and gas field; upper Cretaceous-Maikop.

Off-the-shelf thermoluminescent silica glass media for use in medical diagnostic dosimetry applications

In respect of radiation exposure assessments, thermoluminescent dosimeters (TLD) represent a notable and important subset of passive detector technology, gaining widespread use over a period of many decades, not least for medical applications. TLDs are available in a range of physical and chemical forms, in particular the popularity of phosphor-based commercial products arising from features that include availability down to low mm dimensions, soft-tissue equivalence in some cases, and relatively low TL fading. Novel doped silica glass TL material fabricated as fibres also offer favourable responses, recent developments in co-doping leading to their ability to also provide for diagnostic radiology applications, adding to the attractive features of being impervious to water, of good sensitivity, and generally offering wide dynamic range. Thus said, doping and fibre fabrication involve relatively high costs. Accordingly, herein exploratory investigations are made of the cost-effective colourless silica-based glass medium from which marbles are made, reduced into chip form for ease of application, examining sensitivity to dose. In particular, the study focuses on the computerised tomography clinical application regime, 80- to 140 kVp, with excellent response being shown for doses within the range 2- to 50 mGy.

Unearthing trends in environmental science and engineering research: Insights from a probabilistic topic modeling literature analysis

Academic contributions in environmental science and engineering (ESE) research are needed to ensure a cleaner, productive, and environmentally conscious society. Hence, an understanding of the critical trends, topics, and research developments in the field is crucial towards facilitating the identification, communication, and improved research collaboration of nascent and increasingly complex environmental problems. As a deeper analysis of the broader trend evolution of ESE research is lacking in the literature, we employ a more robust content analysis approach in the form of a topic modeling computational text analysis method to unearth key temporal and regional insights in the field. As such, we apply a latent Dirichlet allocation (LDA) model on abstract metadata based on 3572 articles procured from reputable journals that published subject matter related to ESE research from 2005 to 2019 inclusive. We analyze the statistical composition of each inferred topic in the form of word clouds and uncover general research trends, such as topics related to environmental impact assessments, improved clean cookstoves, solid waste management, and environmental lead pollution. We also perform temporal analysis experiments across each respective journal and observe a high degree of consistency and variance among topic focuses. Moreover, whilst quantifying trends at the regional level, we detect that certain countries display clearly discernible patterns, suggesting that research communities in ESE from various countries tend to focus on different sub-fields. The main contribution of our work is the application of a more refined computer-assisted content analysis method in ESE trend analysis research that can serve as the foundation for future exploratory trend analysis investigations in ESE and other related fields.

A direct test of the similarity assumption — Focusing on differences as compared with similarities decreases automatic imitation

Individuals automatically imitate a wide range of different behaviors. Previous research suggests that imitation as a social process depends on the similarity between interaction partners. However, some of the experiments supporting this notion could not be replicated and all of the supporting experiments manipulated not only similarity between actor and observer, but also other features. Thus, the existing evidence leaves open whether similarity as such moderates automatic imitation. To directly test the similarity account, in four experiments, we manipulated participants' focus on similarities or differences while holding the stimulus material constant. In Experiment 1, we presented participants with a hand and let them either focus on similarities, differences, or neutral aspects between their own hand and the other person's hand. The results indicate that focusing on similarities increased perceived similarity between the own and the other person's hand. In Experiments 2 to 4, we tested the hypothesis that focusing on similarities, as compared with differences, increases automatic imitation. Experiment 2 tested the basic effect and found support for our prediction. Experiment 3 and 4 replicated this finding with higher-powered samples. Exploratory investigations further suggest that it is a focus on differences that decreases automatic imitation, and not a focus on similarities that increases automatic imitation. Theoretical implications and future directions are discussed.

Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK2140944)

BackgroundWith increasing concerns about the impact of frequent antibiotic usage on the human microbiome, it is important to characterize the potential for such effects in early antibiotic drug development clinical trials. In a randomised Phase 2a clinical trial study that evaluated the pharmacokinetics of repeated oral doses of gepotidacin, a first-in-chemical-class triazaacenaphthylene antibiotic with a distinct mechanism of action, in adult females with uncomplicated urinary tract infections for gepotidacin (GSK2140944) we evaluated the potential changes in microbiome composition across multiple time points and body-sites (ClinicalTrials.gov: NCT03568942).ResultsSamples of gastrointestinal tract (GIT), pharyngeal cavity and vaginal microbiota were collected with consent from 22 patients at three time points relative to the gepotidacin dosing regimen; Day 1 (pre-dose), Day 5 (end of dosing) and Follow-up (Day 28 ± 3 days). Microbiota composition was determined by DNA sequencing of 16S rRNA gene variable region 4 amplicons. By Day 5, significant changes were observed in the microbiome diversity relative to pre-dose across the tested body-sites. However, by the Follow-up visit, microbiome diversity changes were reverted to compositions comparable to Day 1. The greatest range of microbiome changes by body-site were GIT followed by the pharyngeal cavity then vagina. In Follow-up visit samples we found no statistically significant occurrences of pathogenic taxa.ConclusionOur findings suggest that gepotidacin alteration of the human microbiome after 5 days of dosing is temporary and rebound to pre-dosing states is evident within the first month post-treatment. We recommend that future antibiotic drug trials include similar exploratory investigations into the duration and context of microbiome modification and recovery.Trial registrationNCT03568942. Registered 26 June 2018.

PNS33 Recommendations for the Design and Implementation of an Early Feasibility Studies Program in Italy

Early Feasibility Studies (EFS) are limited exploratory clinical investigations taking place early in the development of devices, in small number of patients, typically before the device design has been finalized, when further non-clinical testing is not possible or meaningful. An EFS program was introduced by the US Food and Drug Administration (FDA) in 2013 to accelerate access of American patients to medical technologies and recoup a leading role in the pre-market research. The aim of this study was to explore perceptions of relevant stakeholders about the desirability and feasibility of an EFS program in Italy and of critical factors favoring or hampering its implementation.

Repurposing bromocriptine for Aβ metabolism in Alzheimer’s disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer’s disease with presenilin 1 (PSEN1) mutations

IntroductionAlzheimer’s disease (AD) is one of the most common causes of dementia. Pathogenic variants in the presenilin 1 (PSEN1) gene are the most frequent cause of early-onset AD. Medications for...

Graphite sheets in study of radiation dosimetry and associated investigations of damage

Present work builds upon prior investigations concerning the novel use of graphite-rich polymer pencil-lead for passive radiation dosimetry. Working with photon-mediated interactions at levels of dose familiar in radiotherapy, exploratory investigations have now been made using graphite produced commercially in the form of 50 μm thick sheets. Focusing on the relationship between absorbed radiation energy and induced material changes, investigations have been made of thermo- and photoluminescence dose dependence, also of alterations in Raman spectroscopic features. Photoluminescence studies have focused on the degree of structural order of the samples when exposed to incident MeV energy gamma-radiation, supported by crystallite size evaluations. The results are consistent and evident of structural alterations, radiation-driven thermal annealing also being observed. The results, supportive of previous TL, Raman and photoluminescence studies, are readily understood to arise from irradiation changes occurring at the microscopic level. Notwithstanding the non-linearities observed in the conduct of Raman and photoluminescence studies there is clear potential for applications in use of the defect-dependent methods herein, providing sensitive detection of radiation damage in graphite and from it dose determination. Most specifically, the readily available thin graphite sheets can provide the basis of a low-cost yet highly effective system for studies of radiation-driven changes in carbon (and/or carbon based composites), also as a dosimetric probe of skin dose, its atomic number closely matching with the effective atomic number of soft tissues.

Revival of Traditional Cascade Tanks for Achieving Climate Resilience in Drylands of South India

Traditional tanks in arid regions of India have been working to address water demands of the public for more than 2000 years. However, recent decade is witnessing growing domestic and agricultural water demand coupled with rising encroachment and ignorance toward tanks; consequently, intensifying water shortage issues. While climate change is impacting at alarming rates, local agencies have forgotten these tanks that have aided in sustainable water supply solutions for decades apart from municipal water supply. This research, for the first time, estimates water supply-demand for an arid region in South India (Madurai) and lists out the benefits if tanks were managed and desilted. Exploratory investigations for documenting seasonal domestic and agricultural unmet water demand were conducted followed by their validation through ground-truthing across the study period 2002–2019. Results indicated high unmet domestic water demand, estimating ~73% [maximum 365 thousand cubic meters (TCM)] for summer (March to May) and ~33% (maximum 149 TCM) for winter (January and February), and high unmet agricultural water demand estimating ~90% (maximum 5,424 TCM) during North-East monsoon (October to December), and ~95% (maximum 5,161 TCM) during South-West monsoon (June to September). Erratic rainfall pattern was identified as a major cause for higher fluctuations in water availability inside tanks ranging 0–50%, while lack of ownership resulted in increased siltation load ranging 30–70% of the tank's volume. The study found that the major portion of the unmet water demand can be accounted for through rehabilitation of the tanks, as under the rehabilitated tank irrigation scenario the tank storage could attain 200–400% more water than the estimated agricultural water demand. It was concluded that if the cascade tanks were managed appropriately, they could have positive impacts by reducing floods and providing water for drought seasons.

Finding Freedom: Exploratory Archaeological Investigations at the Free African American Site of Pandenarium (36ME253), 1854–1930s

In 1854, 63 free African Americans arrived at Pandenarium (36ME253) in northwestern Pennsylvania. Archaeological investigations at the site bring to light the narrative of the freed African Americans who settled there, often countering local stories of its history. Supplementing archaeological methods of inquiry, earlier historical research with analysis of light-detection and ranging (LiDAR) data, aerial photography, and historical mapping developed a more robust context in which to understand better the people of Pandenarium. Collection of ground-penetrating radar (GPR) data, shovel test-pit excavation, and test-unit excavations uncovered the remains of multiple generations living in a place of changing meanings and spatial layout. Landscape and ceramic analyses highlighted the lives of African Americans living at Pandenarium, helping us to move beyond earlier narratives built on secondhand accounts inferring the inhabitants’ inadequacy and race as key factors in the dissolution of the community. Resumen En el ano 1854, 63 afroamericanos libres llegaron a Pandenarium (36ME253) en el noroeste de Pensilvania. Las investigaciones arqueologicas en el sitio sacan a la luz la narrativa de los afroamericanos liberados que se establecieron alli, a menudo contrarrestando los cuentos locales de su historia. Al complementar los metodos arqueologicos de investigacion, la investigacion historica anterior, combinada con el analisis de datos de deteccion y alcance de la luz (LiDAR, por sus siglas en ingles), fotografia aerea y mapeo historico, se desarrollo un contexto mas solido para comprender mejor a la gente de Pandenarium. Con la recopilacion de datos de radar de penetracion de suelos (GPR, por sus siglas en ingles), la excavacion de pozos de prueba con pala y las excavaciones de unidades de prueba, se descubrieron los restos de varias generaciones que vivian en un lugar de disposicion espacial y significados cambiantes. Los analisis de paisajes y ceramica revelaron mas sobre las vidas de los afroamericanos que vivian en Pandenarium, ayudandonos a ir mas alla de las narrativas anteriores construidas sobre relatos de segunda mano que infieren la insuficiencia y la raza de los habitantes como factores clave en la disolucion de la comunidad. Resume En 1854, 63 Africains-americains libres arriverent a Pandenarium (36ME253) dans le Nord-Ouest de la Pennsylvanie. Les fouilles archeologiques sur le site mettent en lumiere le recit des Africains-americains liberes qui se sont installes ici, venant souvent contredire les anecdotes locales sur leur histoire. Les methodes archeologiques complementaires d'enquete, la recherche historique anterieure, en combinaison avec l'analyse des donnees de detection de la lumiere et de mesure a distance (LiDAR, light-detection and ranging) et la photographie aerienne, ont conduit au developpement d'un contexte plus solide dans lequel on peut mieux comprendre la population de Pandenarium. La collecte de donnees georadar (GPR, ground-penetrating radar), le sondage a la pelle et les fouilles de perimetre-test ont mis a jour les vestiges de generations nombreuses ayant vecu sur un site dont les significations et l'amenagement de l'espace montrent une evolution. Les analyses de terrain et de ceramiques ont mis en lumiere l'existence des Africains-americains ayant vecu a Pandenarium, nous permettant ainsi de passer outre les narrations precedentes faconnees a partir de recits de seconde main suggerant que les insuffisances et la race des habitants sont des facteurs cles dans la dissolution de la communaute.