Spectral theory of some non-selfadjoint linear differential operators

We give a characterisation of the spectral properties of linear differential operators with constant coefficients, acting on functions defined on a bounded interval, and determined by general linear boundary conditions. The boundary conditions may be such that the resulting operator is not selfadjoint. We associate the spectral properties of such an operator $S$ with the properties of the solution of a corresponding boundary value problem for the partial differential equation $\partial_t q \pm iSq=0$. Namely, we are able to establish an explicit correspondence between the properties of the family of eigenfunctions of the operator, and in particular whether this family is a basis, and the existence and properties of the unique solution of the associated boundary value problem. When such a unique solution exists, we consider its representation as a complex contour integral that is obtained using a transform method recently proposed by Fokas and one of the authors. The analyticity properties of the integrand in this representation are crucial for studying the spectral theory of the associated operator.Comment: 1 figur

The origins of intensive marine fishing in medieval Europe: the English evidence

The catastrophic impact of fishing pressure on species such as cod and herring is well documented. However, the antiquity of their intensive exploitation has not been established. Systematic catch statistics are only available for ca. 100 years, but large-scale fishing industries existed in medieval Europe and the expansion of cod fishing from the fourteenth century (first in Iceland, then in Newfoundland) played an important role in the European colonization of the Northwest Atlantic. History has demonstrated the scale of these late medieval and post-medieval fisheries, but only archaeology can illuminate earlier practices. Zooarchaeological evidence shows that the clearest changes in marine fishing in England between AD 600 and 1600 occurred rapidly around AD 1000 and involved large increases in catches of herring and cod. Surprisingly, this revolution predated the documented post-medieval expansion of England's sea fisheries and coincided with the Medieval Warm Period-when natural herring and cod productivity was probably low in the North Sea. This counterintuitive discovery can be explained by the concurrent rise of urbanism and human impacts on freshwater ecosystems. The search for 'pristine' baselines regarding marine ecosystems will thus need to employ medieval palaeoecological proxies in addition to recent fisheries data and early modern historical records

Success in periodontology: An evolutive concept

AimThe purpose of this editorial was to discuss a definition of success after periodontal therapy based on the retention of natural dentition.Materials and MethodsBased on topic and relevance, references were collected and then divided into four categories: (a) the influence of available therapeutic techniques on the definition of hopeless teeth, (b) the longâ term rate of tooth loss during supportive periodontal therapy, (c) the duration of time that the treatment outcomes may be considered stable and (d) patientsâ perception and satisfaction of periodontal therapy.ResultsPeriodontal therapy can change the prognosis of hopeless teeth, making them maintainable in the long term. The rate of tooth loss can be minimized in a way that a period of 10 years or more is needed to evaluate further periodontal breakdown. In addition, patientsâ perception and satisfaction of the treatment should be considered as the main therapeutic endpoints of the provided periodontal therapy.ConclusionsDefinition of success is linked to the available therapeutic tools. Due to the recent advancement of treatment modalities, periodontally hopeless teeth can now be treated and maintained for a long period of time with health, function and patient satisfaction.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150541/1/jcpe13150.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150541/2/jcpe13150_am.pd

Distinct roles for the IIId2 sub-domain in pestivirus and picornavirus internal ribosome entry sites.

Viral internal ribosomes entry site (IRES) elements coordinate the recruitment of the host translation machinery to direct the initiation of viral protein synthesis. Within hepatitis C virus (HCV)-like IRES elements, the sub-domain IIId(1) is crucial for recruiting the 40S ribosomal subunit. However, some HCV-like IRES elements possess an additional sub-domain, termed IIId2, whose function remains unclear. Herein, we show that IIId2 sub-domains from divergent viruses have different functions. The IIId2 sub-domain present in Seneca valley virus (SVV), a picornavirus, is dispensable for IRES activity, while the IIId2 sub-domains of two pestiviruses, classical swine fever virus (CSFV) and border disease virus (BDV), are required for 80S ribosomes assembly and IRES activity. Unlike in SVV, the deletion of IIId2 from the CSFV and BDV IRES elements impairs initiation of translation by inhibiting the assembly of 80S ribosomes. Consequently, this negatively affects the replication of CSFV and BDV. Finally, we show that the SVV IIId2 sub-domain is required for efficient viral RNA synthesis and growth of SVV, but not for IRES function. This study sheds light on the molecular evolution of viruses by clearly demonstrating that conserved RNA structures, within distantly related RNA viruses, have acquired different roles in the virus life cycles

Prevalence and correlates of self-reported state of teeth among schoolchildren in Kerala, India

BACKGROUND: Oral health status in India is traditionally evaluated using clinical indices. There is growing interest to know how subjective measures relate to outcomes of oral health. The aims of the study were to assess the prevalence and correlates of self-reported state of teeth in 12-year-old schoolchildren in Kerala, India. METHODS: Cross-sectional survey data were used. The sample consisted of 838 12-year-old schoolchildren. Data was collected using clinical examination and questionnaire. The clinical oral health status was recorded using Decayed, Missing and Filled Teeth (DMFT) and Oral Hygiene Index – Simplified (OHI-S). The questionnaire included questions on sociodemographics, self reports of behaviour, knowledge and oral problems and a single-item measuring self-reported state and satisfaction with appearance of teeth. The Kappa values for test-retest of the questionnaire ranged from 0.55 to 0.97. RESULTS: Twenty-three per cent of the schoolchildren reported the state of teeth as bad. Multivariate logistic regression showed significant associations between schoolchildren who reported to have bad teeth and poor school performance (Odds Ratio (OR) = 2.5), having bad breath (OR = 2.4), food impaction (OR = 1.7) dental visits (OR = 1.6), being dissatisfied with appearance of teeth (OR = 4.2) and caries experience (OR = 1.7). The explained variance was highest when the variables dental visits, bleeding gums, bad breath, food impaction and satisfaction with appearance were introduced into the model (19%). CONCLUSION: A quarter of 12-year-olds reported having bad teeth. The self-reported bad state of teeth was associated with poor school performance, having bad breath and food impaction, having visited a dentist, being dissatisfied with teeth appearance and having caries experience. Information from self-reports of children might help in planning effective strategies to promote oral health

The Batten disease protein CLN3 is important for stress granules dynamics and translational activity

The assembly of membrane-less organelles such as stress granules (SGs) is emerging as central in helping cells rapidly respond and adapt to stress. Following stress sensing, the resulting global translational shutoff leads to the condensation of stalled mRNAs and proteins into SGs. By reorganizing cytoplasmic contents, SGs can modulate RNA translation, biochemical reactions, and signaling cascades to promote survival until the stress is resolved. While mechanisms for SG disassembly are not widely understood, the resolution of SGs is important for maintaining cell viability and protein homeostasis. Mutations that lead to persistent or aberrant SGs are increasingly associated with neuropathology and a hallmark of several neurodegenerative diseases. Mutations in CLN3 are causative of juvenile neuronal ceroid lipofuscinosis, a rare neurodegenerative disease affecting children also known as Batten disease. CLN3 encodes a transmembrane lysosomal protein implicated in autophagy, endosomal trafficking, metabolism, and response to oxidative stress. Using a HeLa cell model lacking CLN3, we now show that CLN3KO is associated with an altered metabolic profile, reduced global translation, and altered stress signaling. Furthermore, loss of CLN3 function results in perturbations in SG dynamics, resulting in assembly and disassembly defects, and altered expression of the key SG nucleating factor G3BP1. With a growing interest in SG-modulating drugs for the treatment of neurodegenerative diseases, novel insights into the molecular basis of CLN3 Batten disease may reveal avenues for disease-modifying treatments for this debilitating childhood disease

Design and evaluation of the immunogenicity and efficacy of a biomimetic particulate formulation of viral antigens

Subunit viral vaccines are typically not as efficient as live attenuated or inactivated vaccines at inducing protective immune responses. This paper describes an alternative 'biomimetic' technology; whereby viral antigens were formulated around a polymeric shell in a rationally arranged fashion with a surface glycoprotein coated on to the surface and non-structural antigen and adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP and IAV groups following the booster immunisation. IFN-γ responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups. We observed that the protection afforded by the particulate vaccine was comparable to the licenced IAV formulation. In conclusion, the biomimetic particulates showed a promising immunogenicity and efficacy profile that may be improved by virtue of being a customisable mode of delivery

Organizational and Supervisory Apology Effectiveness: Apology Giving in Work Settings

We synthesize the interdisciplinary literature into a heuristic for crafting effective organizational and supervisory apologies (the OOPS four-component apology). In the first experiment, we demonstrate how an offense committed by an organization is perceived to be more egregious than an offense committed by a friend or supervisor. Furthermore, results did not support that OOPS apologies are unequally effective if issued by a friend, supervisor, or organization. In the second experiment, we test OOPS apology-training effectiveness. Results indicated that trained participants crafted more effective apologies. Our apology heuristic is an innovation for training business communicators how to apologize effectively.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Structure–function analysis of the equine hepacivirus 5′ untranslated region highlights the conservation of translational mechanisms across the hepaciviruses

Equine hepacivirus (EHcV) (now also classified as hepacivirus A) is the closest genetic relative to hepatitis C virus (HCV) and is proposed to have diverged from HCV within the last 1000years. The 5′ untranslated regions (UTRs) of both HCV and EHcV exhibit internal ribosome entry site (IRES) activity, allowing cap-independent translational initiation, yet only the HCV 5′UTR has been systematically analysed. Here, we report a detailed structural and functional analysis of the EHcV 5′UTR. The secondary structure was determined using selective 2′ hydroxyl acylation analysed by primer extension (SHAPE), revealing four stem–loops, termed SLI, SLIA, SLII and SLIII, by analogy to HCV. This guided a mutational analysis of the EHcV 5′UTR, allowing us to investigate the roles of the stem–loops in IRES function. This approach revealed that SLI was not required for EHcV IRES-mediated translation. Conversely, SLIII was essential, specifically SLIIIb, SLIIId and a GGG motif that is conserved across the Hepaciviridae. Further SHAPE analysis provided evidence that this GGG motif mediated interaction with the 40S ribosomal subunit, whilst a CUU sequence in the apical loop of SLIIIb mediated an interaction with eIF3. In addition, we showed that a microRNA122 target sequence located between SLIA and SLII mediated an enhancement of translation in the context of a subgenomic replicon. Taken together, these results highlight the conservation of hepaciviral translation mechanisms, despite divergent primary sequences

Modal Analysis and Coupling in Metal-Insulator-Metal Waveguides

This paper shows how to analyze plasmonic metal-insulator-metal waveguides using the full modal structure of these guides. The analysis applies to all frequencies, particularly including the near infrared and visible spectrum, and to a wide range of sizes, including nanometallic structures. We use the approach here specifically to analyze waveguide junctions. We show that the full modal structure of the metal-insulator-metal (MIM) waveguides--which consists of real and complex discrete eigenvalue spectra, as well as the continuous spectrum--forms a complete basis set. We provide the derivation of these modes using the techniques developed for Sturm-Liouville and generalized eigenvalue equations. We demonstrate the need to include all parts of the spectrum to have a complete set of basis vectors to describe scattering within MIM waveguides with the mode-matching technique. We numerically compare the mode-matching formulation with finite-difference frequency-domain analysis and find very good agreement between the two for modal scattering at symmetric MIM waveguide junctions. We touch upon the similarities between the underlying mathematical structure of the MIM waveguide and the PT symmetric quantum mechanical pseudo-Hermitian Hamiltonians. The rich set of modes that the MIM waveguide supports forms a canonical example against which other more complicated geometries can be compared. Our work here encompasses the microwave results, but extends also to waveguides with real metals even at infrared and optical frequencies.Comment: 17 pages, 13 figures, 2 tables, references expanded, typos fixed, figures slightly modifie