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Tooth eruption comprises a highly coordinated cascade of complex cellular and molecular interactions resulting in axial movement of the tooth germ from an intra-osseous position to its functional occlusion. Odontogenesis is under genetic control, governed by more than 300 genes, with environmental factors playing a comparatively minor role. Delayed tooth eruption (DTE) describes the most frequently encountered deviation from normal eruption and can be the solitary materialization of local or systemic pathology. Where local pathology has been excluded, the dentist should be aware of the multitude of systemic conditions that may be contributing, and liaise with relevant medical colleagues. This article provides a review of the literature regarding the systemic causes of DTE.CPD/Clinical Relevance:Systemic conditions can be aetiological factors in delayed tooth eruption.

ABSTRACTThis study explores two unique aspects of diversity, equity, and inclusion (DEI) from the perspective of gender diversity in the field of motion pictures and the dimension of inclusion utilizing the Bechdel-Wallace Test (BWT). A production may pass the BWT if a conversation between two women is not about men, hence the conversation is deemed meaningful. Using a consumer-driven data set, we find a positive effect of the BWT on international and total box office sales. The results also show a unique result in the years following the modern #MeToo movement, leading to enhanced box office returns for domestic, international, and total box office sales. Therefore, in addition to contributing to efforts to better understanding the impact of the addition of gender diversity and inclusion on motion picture performance, female characters’ meaningful conversation with other females will likely lead to higher return on producers’ investment in motion pictures. Practical implications and contributions to feminist film theory and theory of planned behavior are discussed.

Craniofacial microsomia (CFM) is a congenital facial condition that affects the structures derived from the first and second pharyngeal arches. It results in underdevelopment of facial structures, most commonly causing abnormal mandibular growth and morphology. Part 1 of this two-part series outlined the aetiology, classification systems and clinical features of CFM. In this article, we explore the management pathway and treatment approaches that may be undertaken. We highlight the dental and orthodontic involvement in managing patients with CFM.CPD/Clinical Relevance:For patients with CFM, having an understanding of the overall facial and dental management helps the clinician to plan for dental and orthodontic care.

Diffusion-ordered nuclear magnetic resonance (NMR) spectroscopy is widely used for the analysis of mixtures, dispersing the signals of different species in a two-dimensional spectrum according to their diffusion coefficients. However, interpretation of these diffusion coefficients is typically purely qualitative, for example, to deduce which species are bigger or smaller. In studies of proteins in solution, important questions concern the molecular weight of the proteins, the presence or absence of aggregation, and the degree of folding. The Stokes–Einstein Gierer–Wirtz estimation (SEGWE) method has been previously developed to simplify the complex relationship between diffusion coefficient and molecular mass, allowing the prediction of a species’ diffusion coefficient in a pure solvent based on its molecular weight. Here, we show that SEGWE can be extended to successfully predict both peptide and protein diffusion coefficients in mixed protiated–deuteriated water samples and, hence, distinguish effectively between globular and disordered proteins.

‘This article gives an overview of craniofacial microsomia (CFM), its diagnostic features and relevant classification systems. Craniofacial microsomia is the most common facial anomaly after cleft lip and palate. It has a wide phenotypic variance and requires a multidisciplinary approach for comprehensive management. We outline both the facial and dental manifestations and orthodontic implications.CPD/Clinical Relevance:CFM patients often require comprehensive dental and orthodontic care and it is necessary for the clinician to be aware of the clinical challenges in treating this cohort of patients. By having a thorough understanding of the aetiology and clinical features, it can help direct appropriate clinical care.

Introduction: SHORT syndrome is a rare autosomal dominant condition described by its acronym of short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger abnormality, and teething delay. Individuals have a distinct progeroid craniofacial appearance with a triangular face, frontal bossing, hypoplastic or thin alae nasi, large low-set ears, and mandibular retrognathia.Objectives: To systematically appraise the literature and update the clinical phenotype with emphasis on the dental condition.Design: A systematic literature search was carried out to update the clinical phenotype, identifying reports of individuals with SHORT syndrome published after August 2015. The same search strategy but not limited to publication date was carried out to identify reports of the dental phenotype. Two independent reviewers screened 1937 articles with 55 articles identified for full-text review.Results: Nineteen individuals from 11 families were identified. Facial dysmorphism including ocular depression, triangular shaped face, frontal bossing, large low-set ears, and micrognathia were the most consistent features followed by lipodystrophy, insulin resistance, and intrauterine growth restriction. Teething delay, microdontia, hypodontia, and enamel hypoplasia have all been reported.Conclusion: Features that comprise the SHORT acronym do not accurately or completely describe the clinical phenotype. The craniofacial appearance is one of the most consistent features. Lipodystrophy and insulin resistance may also be considered cardinal features. After teething delay, enamel hypoplasia and microdontia are the most common dental manifestations. We present recommendations for the dental and orthodontic/orthognathic management of individuals with SHORT syndrome.

ABSTRACTThis paper presents statistical evidence of roadside vegetation’s contribution to pavement roughness progression rates. Detailed statistical and regression analysis of the roadside vegetation data collected via satellite imageries and road roughness data collected via high speed road profiler was performed. Elaborative investigation on interaction between roadside vegetation and waveband roughness progression has provided a clear indication of tree variable’s contribution on road deterioration. Statistical parameters such as moderate Pearson correlation coefficient (r) values, low mean squared error (MSE), root mean squared error (RMSE), mean absolute error (MAE) values, high Willmott’s index of agreement (d) were obtained for training and validation datasets, that depicted the potentiality of tree variables as predictors in pavement roughness progression rate modelling. Statistical evidence showed that effect of trees on road deterioration was more noticeable on long wavelength roughness progression rates. This can be justified via prevailing soil moisture interaction in expansive soil deposits subjected to moisture withdrawal of deciduous trees in arid climate conditions. Overall, the findings of this paper exemplify on the necessity of considering the presence of roadside vegetation in road deterioration analysis, and suggesting the scope of improvement for prediction performance.

Amyloidogenic processing of the amyloid precursor protein (APP) forms the amyloid-β peptide (Aβ) component of pathognomonic extracellular plaques of AD. Additional early cortical changes in AD include neuroinflammation and elevated iron levels. Activation of the innate immune system in the brain is a neuroprotective response to infection; however, persistent neuroinflammation is linked to AD neuropathology by uncertain mechanisms. Non-parametric machine learning analysis on transcriptomic data from a large neuropathologically characterised patient cohort revealed the acute phase protein lactoferrin (Lf) as the key predictor of amyloid pathology. In vitro studies showed that an interaction between APP and the iron-bound form of Lf secreted from activated microglia diverted neuronal APP endocytosis from the canonical clathrin-dependent pathway to one requiring ADP ribosylation factor 6 trafficking. By rerouting APP recycling to the Rab11-positive compartment for amyloidogenic processing, Lf dramatically increased neuronal Aβ production. Lf emerges as a novel pharmacological target for AD that not only modulates APP processing but provides a link between Aβ production, neuroinflammation and iron dysregulation.

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Planning disputes are sites of contestation in which science-based regulations come into conflict with the place-based knowledge of local communities. The procedural and often technical nature of these regulations means that these controversies are marked by an asymmetry of resources that is often experienced by community groups as an asymmetry in credibility. In short, the expertise of developers is generally accepted as such, whilst the knowledge claimed by citizens is dismissed as ‘anecdotal’ or ‘NIMBYism’. In this article, we make the argument that the asymmetries of expertise are less stark than the current system typically allows and that recognising and accommodating this would improve the planning system by enhancing the representation and inclusion of community voices. We explore this position by using a case study of the construction of a Energy-from-Biomass plant in South Wales. Drawing from 30 qualitative interviews, we maintain that the planning process has the potential to function as one of a network of ‘trading zones’ in which different communities enact their rights and have their claims to knowledge and expertise recognised. Crucial to this argument is understanding that the levels and kinds of expertise that different parties bring to the interactions are more than just matters of attribution: community groups can have genuine expertise.

Early medieval thinkers often conceived of God in legal terms, especially when they interpreted contemporary disasters as God's ‘just judgement’. Modern scholars have emphasized the importance of these ideas for motivating early medieval reform and legislation and for interpreting history itself. This article explores how these ideas were used in Carolingian legislation and history writing and argues that God's judgement was not as straightforward a theme as it first appears. God's judgement, for example, was not nearly as important for Carolingian historians as it had been for their predecessors. Similarly, in both legal and historical texts, there was great variety in how God's judgement or punishment was expressed, both in how that punishment fell and on whom (whether on the audience or on their enemies). Across these works, however, it is clear that God's judgement was almost never referred to apart from his continuing mercy and help towards to the audiences of these texts. This shows the importance of the various aspects of God's character for early medieval churches and their attitudes to law and history.

Polyacrylamide (PAM) has been shown to enhance strength, stiffness and durability characteristics of granular materials, in addition to providing lower carbon footprints when compared to traditional stabilisers. In this study, the responses of granular subbase materials for flexible pavements, under simulated traffic loading, have been investigated using repeat load triaxial (RLT) testing. Three types of granular materials treated with PAM have been tested to assess changes in engineering performance and responses to simulated traffic. Untreated materials were also tested for comparison. The engineering performance of these materials (treated and untreated) in terms of strength and stiffness were assessed by conducting unconfined compressive strength (UCS) and RLT tests. Results indicate that samples treated with PAM yield higher UCS and resilient modulus values than the untreated samples, with the magnitude of the resilient modulus being dependent on compaction effort. Data related to response under simulated loads has also been collected and used to calibrate an existing model to predict resilient modulus response for each soil type from its physical and engineering properties. The calibrated models were found to satisfactorily simulate the resilient modulus response of the RLT experimental test data.

Among the multiple properties exhibited by lactoferrin (Lf), its involvement in bone regeneration processes is of great interest at the present time. A series of in vitro and in vivo studies have revealed the ability of Lf to promote survival, proliferation and differentiation of osteoblast cells and to inhibit bone resorption mediated by osteoclasts. Although the mechanism underlying the action of Lf in bone cells is still not fully elucidated, it has been shown that its mode of action leading to the survival of osteoblasts is complemented by its mitogenic effect. Activation of several signalling pathways and gene expression, in an LRPdependent or independent manner, has been identified. Unlike the effects on osteoblasts, the action on osteoclasts is different, with Lf leading to a total arrest of osteoclastogenesis. Due to the positive effect of Lf on osteoblasts, the potential use of Lf alone or in combination with different biologically active compounds in bone tissue regeneration and the treatment of bone diseases is of great interest. Since the bioavailability of Lf in vivo is poor, a nanotechnology- based strategy to improve the biological properties of Lf was developed. The investigated formulations include incorporation of Lf into collagen membranes, gelatin hydrogel, liposomes, loading onto nanofibers, porous microspheres, or coating onto silica/titan based implants. Lf has also been coupled with other biologically active compounds such as biomimetic hydroxyapatite, in order to improve the efficacy of biomaterials used in the regulation of bone homeostasis. This review aims to provide an up-to-date review of research on the involvement of Lf in bone growth and healing and on its use as a potential therapeutic factor in bone tissue regeneration.

To establish, and isolate, the influence of different chemical functional groups on the aggregation of polyaromatic hydrocarbons, a series of triphenylene-based compounds were investigated using a combined experimental and computational approach. Containing alkoxy side chains of varying lengths or amide appendages, both with and without a terminating carboxylic acid, their aggregation structures, sizes, and kinetics in toluene were studied over several length scales, using a combination of dynamic light scattering and diffusion-ordered nuclear magnetic resonance spectroscopy, complemented with molecular dynamics simulations. There is a strong correlation between molecular architecture and aggregation mechanisms: the addition of polar functional groups and heteroatoms resulted in compounds that are more prone to aggregation and form large, micrometer-sized clusters, while the increased steric hindrance imposed by alkoxy side chains led to stable nanometer-sized aggregates. These conclusions underline the strong structure–function relationship of polyaromatic hydrocarbons, such as asphaltenes, examined here over multiple length scales in a single solvent. We also demonstrate the importance of using complementary techniques to study the aggregation process of polyaromatic hydrocarbons that could form aggregates of various sizes over different time scales.

This article explores the ways in which histories were used in the moral and doctrinal education of Christian elites in the West from the late Roman to the Carolingian periods. In the sixth century, Cassiodorus wrote that histories, whether Christian or not, were useful for ‘instructing the minds of readers in heavenly matters’. How far was this characteristic of the period? Traditionally, scholars have emphasized either the apologetic purpose or the moral of specific histories, such as Orosius's Historiaeor Bede's Historia Ecclesiastica. Few modern scholars, however, have examined the long-term development of history writing as a vehicle for Christian education during the transformation of the Roman world. Those who have done, such as Karl-Ferdinand Werner and Hans-Werner Goetz, have emphasized continuity rather than change. The article sketches some of the changes and continuities across the period. In particular, it demonstrates that there was a shift from the apologetic concerns of the fifth-century historians, writing to educate Christians from pagan backgrounds, to the doctrinal (as much as moral) concerns of Frankish historians, emerging from the Carolingian Renaissance.

Understanding the biosynthesis of cofactors is fundamental to the life sciences, yet to date a few important pathways remain unresolved. One example is the redox cofactor pyrroloquinoline quinone (PQQ), which is critical for C1 metabolism in many microorganisms, a disproportionate number of which are opportunistic human pathogens. While the initial and final steps of PQQ biosynthesis, involving PqqD/E and PqqC, have been elucidated, the precise nature and order of the remaining transformations in the pathway are unknown. Here we show evidence that the remaining essential biosynthetic enzyme PqqB is an iron-dependent hydroxylase catalyzing oxygen-insertion reactions that are proposed to produce the quinone moiety of the mature PQQ cofactor. The demonstrated reactions of PqqB are unprecedented within the metallo β-lactamase protein family and expand the catalytic repertoire of nonheme iron hydroxylases. These new findings also generate a nearly complete description of the PQQ biosynthetic pathway.

Patients with syndromic craniosynostosis have a molecularly identified genetic cause for the premature closure of their cranial sutures and associated facial and extra-cranial features. Their clinical complexity demands comprehensive management by an extensive multidisciplinary team. This review aims to marry genotypic and phenotypic knowledge with clinical presentation and management of the craniofacial syndromes presenting most frequently to the craniofacial unit at Great Ormond Street Hospital for Children NHS Foundation Trust.

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Hydrogen bonding plays a role in the microphase separation behavior of many block copolymers, such as those used in lithography, where the stronger interactions due to hydrogen bonding can lead to a smaller period for the self-assembled structures, allowing the production of higher resolution templates. However, current statistical thermodynamic models used in descriptions of microphase separation, such as the Flory–Huggins approach, do not take into account some important properties of hydrogen bonding, such as site specificity and cooperativity. In this combined theoretical and experimental study, a step is taken toward the development of a more complete theory of hydrogen bonding in polymers, using polyacrylamide as a model system. We begin by developing a set of association models to describe hydrogen bonding in amides. Both models with one association constant and two association constants are considered. This theory is used to fit IR spectroscopy data from acrylamide solutions in chloroform, thereby determining the model parameters. We find that models with two constants give better predictions of bond energy in the acrylamide dimer and more realistic asymptotic behavior of the association constants in the limit of high temperatures. At the end of the paper, we briefly discuss the question of the determination of the Flory–Huggins parameter for a diblock copolymer with one self-associating hydrogen bonding block and one non-hydrogen bonding block by means of fitting the scattering function in a disordered state.

The maxillary canine is commonly displaced or impacted. Monitoring the normal development of the dentition is important to identify and treat potential problems and hence minimise the need for later, more complex therapy. This paper discusses some problems that may occur and the subsequent treatment of these problems, by illustration with five case reports.

Bacteria colonize highly diverse and complex environments, from gastrointestinal tracts to soil and plant surfaces. This colonization process is controlled in part by the intracellular signal cyclic di-GMP, which regulates bacterial motility and biofilm formation. To interrogate cyclic di-GMP signaling networks, a variety of fluorescent biosensors for live cell imaging of cyclic di-GMP have been developed. However, the need for external illumination precludes the use of these tools for imaging bacteria in their natural environments, including in deep tissues of whole organisms and in samples that are highly autofluorescent or photosensitive. The need for genetic encoding also complicates the analysis of clinical isolates and environmental samples. Toward expanding the study of bacterial signaling to these systems, we have developed the first chemiluminescent biosensors for cyclic di-GMP. The biosensor design combines the complementation of split luciferase (CSL) and bioluminescence resonance energy transfer (BRET) approaches. Furthermore, we developed a lysate-based assay for biosensor activity that enabled reliable high-throughput screening of a phylogenetic library of 92 biosensor variants. The screen identified biosensors with very large signal changes (∼40- and 90-fold) as well as biosensors with high affinities for cyclic di-GMP (KD< 50 nM). These chemiluminescent biosensors then were applied to measure cyclic di-GMP levels in E. coli. The cellular experiments revealed an unexpected challenge for chemiluminescent imaging in Gram negative bacteria but showed promising application in lysates. Taken together, this work establishes the first chemiluminescent biosensors for studying cyclic di-GMP signaling and provides a foundation for using these biosensors in more complex systems.

Lime stabilisation is a commonly used method for improving the properties of expansive clay subgrades around the world. This paper investigates the effect of curing on the behaviour of lime-stabilised basaltic expansive subgrade. The effect of the presence of low levels of organic material in the surface clay on change in pH of the mixture is also investigated. This leads to a better understanding of the impact of curing duration on the process of lime stabilisation when dealing with these clays. In this study, Braybrook and Whittlesea (a western and a northern suburb of Melbourne, Australia) expansive clays were stabilised using different percentages of hydrated lime. Physical properties of untreated samples and those treated with 2%, 3%, 4%, 6%, and 8% lime were evaluated. A suite of tests was conducted to investigate the behaviour of the stabilised basaltic expansive clay over the curing period and to find the optimum lime content (OLC). These tests included pH concentration at various curing periods (at 1.5 h and at 7, 28, and 57 days), Atterberg limit, linear shrinkage (LS) strain (without curing), swelling potential, and unconfined compressive strength (UCS) (under curing periods of 7 and 28 days). Furthermore, X-ray diffraction (XRD) and scanning electron microscopy (SEM) were conducted on Braybrook soil to investigate the mechanism of soil–lime reaction. The suitability of Eades and Grim [1966. A quick test to determine lime requirements for lime stabilisation. Highway Research Record, 139, 61–72] method in determining OLC is also discussed. Test results of these soils indicated that the longer the curing time, the larger the drop in pH concentration. While the swelling potential results suggest an OLC of 4% (for Braybrook) and 6% (for Whittlesea), UCS tests, plasticity indices, and LS suggest an OLC of 6% for Braybrook soil, while it is about 8% for Whittlesea soil according to UCS tests. However, according to the Eades and Grim (1966) procedure, OLC is about 2.64% and 4% for Braybrook and Whittlesea soils, respectively. This paper suggests a modification of Eades and Grim (1966) method to measure the OLC for basaltic expansive clays to take into account the dropping of pH concentration during curing. The mechanism of lime stabilisation and the analysis of the above tests were the major factors to establish this modification. This modification depends on measuring pH concentration at different lime contents and curing periods. The results contribute to a better understanding of the impact of curing and low levels of organic matters on the stabilisation of expansive clays, which can ultimately lead to a simplified procedure in the determination of OLC.

Fine particles may migrate in the preexisting pores of an internally unstable soil matrix caused by water flow. This migration changes the fine particle distribution and content at different zones and can affect the mechanical properties of these soils. Due to the different roles that fine particles can play in the force chains of an internally unstable soil, the available geometrical assessment methods do not predict post-erosion behavior of the soil. The fine particles may sit loose in the voids, provide lateral support for the primary soil matrix, or participate directly in stress transfer. This will depend on the fine content, particle size distribution, constriction size, relative density, stress path, and particle shape. However, to evaluate the post-erosion behavior accurately, computational modelling or experimental investigation needs to be conducted. A modified triaxial apparatus connected to a water supply system and collection tank was developed to investigate the post-erosion behavior of an internally unstable cohesionless soil under different loading patterns in undrained conditions. This system allowed all test phases to be completed, including erosion inside the triaxial chamber to remove any possible impact of specimen disturbance. The results suggest that the undrained shear strength of the eroded specimen increased at small vertical strains (0–4 %) under monotonic and cyclic loadings, whereas the initial modulus of elasticity remained unchanged. Also, the eroded specimen showed much higher resistance against cyclic loadings, whereas the non-eroded specimen was liquefied during less than five cycles of loading. This improvement was due to a better interlock between coarse particles due to erosion of fine particles. The hardening strain behavior of the non-eroded specimen changed to limited flow deformation due to a decrease in the fine content. The flow deformation of the eroded specimen at medium strain may be due to the local increase in lubrication effect of fine particles in the eroded specimen.

Biosynthesis of the ribosomally synthesized and post-translationally modified peptide (RiPP), pyrroloquinoline quinone (PQQ), is initiated when the precursor peptide, PqqA, is recognized and bound by the RiPP precursor peptide recognition element (RRE), PqqD, for presentation to the first enzyme in the pathway, PqqE. Unlike other RiPP-producing, postribosomal peptide synthesis (PRPS) pathways in which the RRE is a component domain of the first enzyme, PqqD is predominantly a separate scaffolding protein that forms a ternary complex with the precursor peptide and first tailoring enzyme. As PqqD is a stable, independent RRE, this makes the PQQ pathway an ideal PRPS model system for probing RRE interactions using nuclear magnetic resonance (NMR). Herein, we present both the solution NMR structure of Methylobacterium extorquensPqqD and results of 1H–15N HSQC binding experiments that identify the PqqD residues involved in binding the precursor peptide, PqqA, and the enzyme, PqqE. The reported structural model for an independent RRE, along with the mapped binding surfaces, will inform future efforts both to understand and to manipulate PRPS pathways.