Toward more rational criteria for determination of design earthquake forces

The preliminary design of most buildings is based on equivalent static forces specified by the governing building code. The height wise distribution of these static forces seems to be based implicitly on the elastic vibration modes. Therefore, the employment of such a load pattern in seismic design of normal structures does not guarantee the optimum use of materials. This paper presents a new method for optimization of dynamic response of structures subjected to seismic excitation. This method is based on the concept of uniform distribution of deformation. In order to obtain the optimum distribution of structural properties, an iterative optimization procedure has been adopted. In this approach, the structural properties are modified so that inefficient material is gradually shifted from strong to weak areas of a structure. This process is continued until a state of uniform deformation is achieved. It is shown that the seismic performance of such a structure is optimal, and behaves generally better than those designed by conventional methods. By conducting this algorithm on shear-building models with various dynamic characteristics subjected to 20 earthquake ground motions, more adequate load patterns are introduced with respect to the period of the structure and the target ductility demand. © 2005 Elsevier Ltd. All rights reserved

Caffeine suppresses homologous recombination through interference with RAD51-mediated joint molecule formation

Caffeine is a widely used inhibitor of the protein kinases that play a central role in the DNA damage response. We used chemical inhibitors and genetically deficient mouse embryonic stem cell lines to study the role of DNA damage response in stable integration of the transfected DNA and found that caffeine rapidly, efficiently and reversibly inhibited homologous integration of the transfected DNA as measured by several homologous recombination-mediated gene-targeting assays. Biochemical and structural biology experiments revealed that caffeine interfered with a pivotal step in homologous recombination, homologous joint molecule formation, through increasing interactions of the RAD51 nucleoprotein filament with non-homologous DNA. Our results suggest that recombination pathways dependent on extensive homology search are caffeine-sensitive and stress the importance of considering direct checkpoint-independent mechanisms in the interpretation of the effects of caffeine on DNA repair

Transcriptomic Analysis of Host Immune and Cell Death Responses Associated with the Influenza A Virus PB1-F2 Protein

Airway inflammation plays a major role in the pathogenesis of influenza viruses and can lead to a fatal outcome. One of the challenging objectives in the field of influenza research is the identification of the molecular bases associated to the immunopathological disorders developed during infection. While its precise function in the virus cycle is still unclear, the viral protein PB1-F2 is proposed to exert a deleterious activity within the infected host. Using an engineered recombinant virus unable to express PB1-F2 and its wild-type homolog, we analyzed and compared the pathogenicity and host response developed by the two viruses in a mouse model. We confirmed that the deletion of PB1-F2 renders the virus less virulent. The global transcriptomic analyses of the infected lungs revealed a potent impact of PB1-F2 on the response developed by the host. Thus, after two days post-infection, PB1-F2 invalidation severely decreased the number of genes activated by the host. PB1-F2 expression induced an increase in the number and level of expression of activated genes linked to cell death, inflammatory response and neutrophil chemotaxis. When generating interactive gene networks specific to PB1-F2, we identified IFN-γ as a central regulator of PB1-F2-regulated genes. The enhanced cell death of airway-recruited leukocytes was evidenced using an apoptosis assay, confirming the pro-apoptotic properties of PB1-F2. Using a NF-kB luciferase adenoviral vector, we were able to quantify in vivo the implication of NF-kB in the inflammation mediated by the influenza virus infection; we found that PB1-F2 expression intensifies the NF-kB activity. Finally, we quantified the neutrophil recruitment within the airways, and showed that this type of leukocyte is more abundant during the infection of the wild-type virus. Collectively, these data demonstrate that PB1-F2 strongly influences the early host response during IAV infection and provides new insights into the mechanisms by which PB1-F2 mediates virulence

Ductility of wide-beam RC frames as lateral resisting system

[EN] Some Mediterranean seismic codes consider wide-beam reinforced concrete moment resisting frames (WBF) as horizontal load carrying systems that cannot guarantee high ductility performances. Conversely, Eurocode 8 allows High Ductility Class (DCH) design for such structural systems. Code prescriptions related to WBF are systematically investigated. In particular, lesson learnt for previous earthquakes, historical reasons, and experimental and numerical studies underpinning specific prescriptions on wide beams in worldwide seismic codes are discussed. Local and global ductility of WBF are then analytically investigated through (1) a parametric study on chord rotations of wide beams with respect to that of deep beams, and (2) a spectral-based comparison of WBF with conventional reinforced concrete moment resisting frames (i.e. with deep beams). Results show that the set of prescriptions given by modern seismic codes provides sufficient ductility to WBF designed in DCH. In fact, global capacity of WBF relies more on the lateral stiffness of the frames and on the overstrength of columns rather than on the local ductility of wide beams, which is systematically lower with respect to that of deep beams.Gómez-Martínez, F.; Alonso Durá, A.; De Luca, F.; Verderame, GM. (2016). Ductility of wide-beam RC frames as lateral resisting system. Bulletin of Earthquake Engineering. 14(6):1545-1569. doi:10.1007/s10518-016-9891-xS15451569146ACI (1989) Building code requirements for reinforced concrete (ACI 318-89). ACI Committee 318, American Concrete Institute, Farmington Hills, Michigan, USAACI (2008) Building code requirements for structural concrete (ACI 318-08) and commentary (318-08). ACI Committee 318, American Concrete Institute, Farmington Hills, Michigan, USAACI-ASCE (1991) Recommendations for design of beam-column connections in monolithic reinforced concrete structures (ACI 352R-91). Joint ACI-ASCE Committee 352, American Concrete Institute, Farmington Hills, Michigan, USAACI-ASCE (2002) Recommendations for design of beam-column connections in monolithic reinforced concrete structures (ACI 352R-02). Joint ACI-ASCE Committee 352, American Concrete Institute, Farmington Hills, Michigan, USAArslan MH, Korkmaz HH (2007) What is to be learned from damage and failure of reinforced concrete structures during recent earthquakes in Turkey? Eng Fail Anal 14(1):1–22ASCE (2007) Seismic Rehabilitation of Existing Buildings, ASCE/SEI 41-06. American Society of Civil Engineers, RestonASCE (2010) Minimum Design Loads for Building and Other Structures, ASCE/SEI 7-10. American Society of Civil Engineers, RestonBenavent-Climent A (2007) Seismic behavior of RC side beam-column connections under dynamic loading. J Earthquake Eng 11:493–511Benavent-Climent A, Zahran R (2010) An energy-based procedure for the assessment of seismic capacity of existing frames: application to RC wide beam systems in Spain. Soil Dyn Earthq Eng 30:354–367Benavent-Climent A, Cahís X, Zahran R (2009) Exterior wide beam-column connections in existing RC frames subjected to lateral earthquake loads. Eng Struct 31:1414–1424Benavent-Climent A, Cahís X, Vico JM (2010) Interior wide beam-column connections in existing RC frames subjected to lateral earthquake loading. Bull Earthq Eng 8:401–420BHRC (2004) Iranian Code of Practice for Seismic Resistant Design of Buildings. Standard Nº 2800, 3rd edn. Building and Housing Research Center, TehranBorzi B, Elnashai AS (2000) Refined force reduction factors for seismic design. Eng Struct 22:1244–1260Borzi B, Pinho R, Crowley H (2008) Simplified pushover-based vulnerability analysis for large-scale assessment of RC buildings. Eng Struct 30:804–820BSI (2004) Eurocode 2: Design of concrete structures: Part 1-1: General rules and rules for buildings. British Standards Institutions, LondonCalvi GM (1999) A displacement-based approach for vulnerability evaluation of classes of buildings. J Earthquake Eng 3(3):411–438CDSC (1994) Seismic construction code, NCSR-94. Committee for the Development of Seismic Codes, Spanish Ministry of Construction, Madrid, Spain (in Spanish)CDSC (2002) Seismic construction code, NCSE-02. Committee for the Development of Seismic Codes, Spanish Ministry of Construction, Madrid, Spain (in Spanish)CEN (2004) Eurocode 8: design of structures for earthquake resistance—part 1: general rules, seismic actions and rules for buildings. European Standard EN 1998-1:2003—Comité Européen de Normalisation, Brussels, BelgiumCEN (2005) Eurocode 8: design of structures for earthquake resistance—part 3: assessment and retrofitting of buildings. European Standard EN 1998-1:2005—Comité Européen de Normalisation, Brussels, BelgiumCheung PC, Paulay T, Park R (1991) Mechanisms of slab contributions in beam-column subassemblages. ACI Spec Publ 123Cosenza E, Manfredi G, Polese M, Verderame GM (2005) A multilevel approach to the capacity assessment of existing RC buildings. J Earthquake Eng 9(1):1–22Crowley H, Pinho R (2010) Revisiting Eurocode 8 formulae for periods of vibration and their employment in linear seismic analysis. Earthquake Eng Struct Dynam 39:223–235CS.LL.PP (2009) Instructions for the application of the technique code for the Constructions. Official Gazette of the Italian Republic, 47, Regular Supplement no. 27 (in Italian)De Luca F, Vamvatsikos D, Iervolino I (2013) Near-optimal piecewise linear fits of static pushover capacity curves for equivalent SDOF analysis. Earthquake Eng Struct Dynam 42(4):523–543De Luca F, Verderame GM, Gómez-Martínez F, Pérez-García A (2014) The structural role played by masonry infills on RC building performances after the 2011 Lorca, Spain, earthquake. Bull Earthq Eng 12(5):1999–2026Decanini LD, Mollaioli F (2000) Analisi di vulnerabilità sismica di edifici in cemento armato pre-normativa. In: Cosenza E (ed) Comportamento sismico di edifici in cemento armato progettati per carichi verticali. CNR—Gruppo Nazionale per la Difesa dei Terremoti, Rome (in Italian)Dolšek M, Fajfar P (2004) IN2—a simple alternative for IDA. In: Proceedings of the 13th World conference on Earthquake Engineering. August 1–6, Vancouver, Canada. Paper 3353Domínguez D, López-Almansa F, Benavent-Climent A (2014) Comportamiento para el terremoto de Lorca de 11-05-2011, de edificios de vigas planas proyectados sin tener en cuenta la acción sísmica. Informes de la Construcción 66(533):e008 (in Spanish)Domínguez D, López-Almansa F, Benavent-Climent A (2016) Would RC wide-beam buildings in Spain have survived Lorca earthquake (11-05-2011)? Eng Struct 108:134–154Dönmez C (2013) Seismic Performance of Wide-Beam Infill-Joist Block RC Frames in Turkey. J Perform Constr Facil 29(1):04014026Fadwa I, Ali TA, Nazih E, Sara M (2014) Reinforced concrete wide and conventional beam-column connections subjected to lateral load. Eng Struct 76:34–48Fardis MN (2009) Seismic design, assessment and retrofitting of concrete, Buildings edn. Springer, LondonGentry TR, Wight JK (1992) Reinforced concrete wide beam-column connections under earthquake-type loading. Report no. UMCEE 92-12. Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USAGómez-Martínez F (2015) FAST simplified vulnerability approach for seismic assessment of infilled RC MRF buildings and its application to the 2011 Lorca (Spain) earthquake. Ph.D. Thesis, Polytechnic University of Valencia, SpainGómez-Martínez F, Pérez García A, De Luca F, Verderame GM (2015a) Comportamiento de los edificios de HA con tabiquería durante el sismo de Lorca de 2011: aplicación del método FAST. Informes de la Construcción 67(537):e065 (in Spanish)Gómez-Martínez F, Pérez-García A, Alonso Durá A, Martínez Boquera A, Verderame GM (2015b) Eficacia de la norma NCSE-02 a la luz de los daños e intervenciones tras el sismo de Lorca de 2011. In: Proceedings of Congreso Internacional sobre Intervención en Obras Arquitectónicas tras Sismo: L’Aquila (2009), Lorca (2011) y Emilia Romagna (2012), May 13–14, Murcia, Spain (in Spanish)Gómez-Martínez F, Verderame GM, De Luca F, Pérez-García A, Alonso-Durá, A (2015c). High ductility seismic performances of wide-beam RC frames. In; XVI Convegno ANIDIS. September 13–17, L'Aquila, ItalyHawkins NM, Mitchell D (1979) Progressive collapse of flat plate structures. ACI J 76(7):775–808Iervolino I, Manfredi G, Polese M, Verderame GM, Fabbrocino G (2007) Seismic risk of RC building classes. Eng Struct 29(5):813–820Inel M, Ozmen HB, Akyol E (2013) Observations on the building damages after 19 May 2011 Simav (Turkey) earthquake. Bull Earthq Eng 11(1):255–283Kurose Y, Guimaraes GN, Zuhua L, Kreger ME, Jirsa JO (1991) Evaluation of slab-beam-column connections subjected to bidirectional loading. ACI Spec Publ 123:39–67LaFave JM, Wight JK (1997) Behavior of reinforced exterior wide beam-column-slab connections subjected to lateral earthquake loading. Report no. UMCEE 97-01. Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USALaFave JM, Wight JK (1999) Reinforced concrete exterior wide beam-column-slab connections subjected to lateral earthquake loading. ACI Struct J 96(4):577–586LaFave JM, Wight JK (2001) Reinforced concrete wide-beam construction vs. conventional construction: resistance to lateral earthquake loads. Earthq Spectra 17(3):479–505Li B, Kulkarni SA (2010) Seismic behavior of reinforced concrete exterior wide beam-column joints. J Struct Eng (ASCE) 136(1):26–36López-Almansa F, Domínguez D, Benavent-Climent A (2013) Vulnerability analysis of RC buildings with wide beams located in moderate seismicity regions. Eng Struct 46:687–702Masi A, Santarsiero G, Nigro D (2013a) Cyclic tests on external RC beam-column joints: role of seismic design level and axial load value on the ultimate capacity. J Earthquake Eng 17(1):110–136Masi A, Santarsiero G, Mossucca A, Nigro D (2013b) Seismic behaviour of RC beam-column subassemblages with flat beam. In: Proceedings of XV Convegno della Associazione Nazionale Italiana di Ingegneria Sismica, ANIDIS. Padova, ItalyMazzolani FM, Piluso V (1997) Plastic design of seismic resistant steel frames. Earthquake Eng Struct Dynam 26:167–191MEPP (2000a) Greek earthquake resistant design code, EAK 2000. Ministry of Environment, Planning and Public Works, AthensMEPP (2000b) Greek code for the design and construction of concrete works, EKOS 2000. Ministry of Environment, Planning and Public Works, Athens (in Greek)Miranda E, Bertero VV (1994) Evaluation of strength reduction factors for earthquake-resistant design. Earthq Spectra 10(2):357–379MPWS (2007) Specifications for buildings to be built in seismic areas. Turkish Standards Institution, Ministry of Public Works and Settlement, Ankara (in Turkish)Mwafy AM, Elnashai AS (2002) Calibration of force reduction factors of RC buildings. J Earthquake Eng 6(2):239–273NZS (2004) Structural design actions. Part 5: earthquake actions, NZS 1170.5. New Zealand Standards, WellingtonNZS (2006) Concrete structures standard: part 1—the design of concrete structures, NZS 3101 part 1. New Zealand Standards, WellingtonPan A, Moehle JP (1989) Lateral displacement ductility of reinforced concrete flat plates. ACI Struct J 86(3):250–258Panagiotakos TB, Fardis MN (2001) Deformations of reinforced concrete members at yielding and ultimate. ACI Struct J 98(2):135–148 [and Appendix 1 (69 pp)]Paulay T, Priestley MJN (1992) Seismic design of concrete and masonry structures. Wiley, New York, USAQuintero-Febres CG, Wight JK (1997) Investigation on the seismic behavior of RC interior wide beam-column connections. Report no. UMCEE 97-15. Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USAQuintero-Febres CG, Wight JK (2001) Experimental study of Reinforced concrete interior wide beam-column connections subjected to lateral loading. ACI Struct J 98(4):572–582Serna-Ros P, Fernández-Prada MA, Miguel-Sosa P, Debb OAR (2001) Influence of stirrup distribution and support width on the shear strength of reinforced concrete wide beams. Mag Concr Res 54(00):1–11Shuraim AB (2012) Transverse stirrup configurations in RC wide shallow beams supported on narrow columns. J Struct Eng 138(3):416–424Siah WL, Stehle JS, Mendis P, Goldsworthy H (2003) Interior wide beam connections subjected to lateral earthquake loading. Eng Struct 25:281–291Tore E, Demiral T (2014) A parametric study of code-based performance limits for wide beams. e-GFOS 5(8):1–11Vamvatsikos D, Cornell CA (2002) Incremental Dynamic Analysis. Earthquake Eng Struct Dynam 31:491–514Vidic T, Fajfar P, Fischinger M (1994) Consistent inelastic design spectra: strength and displacement. Earthquake Eng Struct Dynam 23:507–521Vielma JC, Barbat AH, Oller S (2010) Seismic safety of low ductility structures used in Spain. Bull Earthq Eng 8:135–15

Air pollution trends in the EMEP region between 1990 and 2012

The present report synthesises the main features of the evolution over the 1990-2012 time period of the concentration and deposition of air pollutants relevant in the context of the Convention on Long-range Transboundary Air Pollution: (i) ozone, (ii) sulfur and nitrogen compounds and particulate matter, (iii) heavy metals and persistent organic pollutants. It is based on observations gathered in State Parties to the Convention within the EMEP monitoring network of regional background stations, as well as relevant modelling initiatives. Joint Report of: EMEP Task Force on Measurements and Modelling (TFMM), Chemical Co-ordinating Centre (CCC), Meteorological Synthesizing Centre-East (MSC-E), Meteorological Synthesizing Centre-West (MSC-W)

IlsA, A Unique Surface Protein of Bacillus cereus Required for Iron Acquisition from Heme, Hemoglobin and Ferritin

The human opportunistic pathogen Bacillus cereus belongs to the B. cereus group that includes bacteria with a broad host spectrum. The ability of these bacteria to colonize diverse hosts is reliant on the presence of adaptation factors. Previously, an IVET strategy led to the identification of a novel B. cereus protein (IlsA, Iron-regulated leucine rich surface protein), which is specifically expressed in the insect host or under iron restrictive conditions in vitro. Here, we show that IlsA is localized on the surface of B. cereus and hence has the potential to interact with host proteins. We report that B. cereus uses hemoglobin, heme and ferritin, but not transferrin and lactoferrin. In addition, affinity tests revealed that IlsA interacts with both hemoglobin and ferritin. Furthermore, IlsA directly binds heme probably through the NEAT domain. Inactivation of ilsA drastically decreases the ability of B. cereus to grow in the presence of hemoglobin, heme and ferritin, indicating that IlsA is essential for iron acquisition from these iron sources. In addition, the ilsA mutant displays a reduction in growth and virulence in an insect model. Hence, our results indicate that IlsA is a key factor within a new iron acquisition system, playing an important role in the general virulence strategy adapted by B. cereus to colonize susceptible hosts

Carbon-nitrogen interactions in European forests and semi-natural vegetation - Part 1: Fluxes and budgets of carbon, nitrogen and greenhouse gases from ecosystem monitoring and modelling

The impact of atmospheric reactive nitrogen (N$_{r}$) deposition on carbon (C) sequestration in soils and biomass of unfertilized, natural, semi-natural and forest ecosystems has been much debated. Many previous results of this dC/dN response were based on changes in carbon stocks from periodical soil and ecosystem inventories, associated with estimates of N$_{r}$ deposition obtained from large-scale chemical transport models. This study and a companion paper (Flechard et al., 2020) strive to reduce uncertainties of N effects on C sequestration by linking multi-annual gross and net ecosystem productivity estimates from 40 eddy covariance flux towers across Europe to local measurement-based estimates of dry and wet N$_{r}$ deposition from a dedicated collocated monitoring network. To identify possible ecological drivers and processes affecting the interplay between C and N$_{r}$ inputs and losses, these data were also combined with in situ flux measurements of NO, N$_{2}$O and CH$_{4}$ fluxes; soil NO$_{3}$̅ leaching sampling; and results of soil incubation experiments for N and greenhouse gas (GHG) emissions, as well as surveys of available data from online databases and from the literature, together with forest ecosystem (BASFOR) modelling. Multi-year averages of net ecosystem productivity (NEP) in forests ranged from -70 to 826 gCm$^{-2}$ yr$^{-1}$ at total wet+dry inorganic N$_{r}$ deposition rates (N$_{dep}$) of 0.3 to 4.3 gNm$^{-2}$ yr$^{-1}$ and from -4 to 361 g Cm$^{-2}$ yr$^{-1}$ at N$_{dep}$ rates of 0.1 to 3.1 gNm$^{-2}$ yr$^{-1}$ in short semi-natural vegetation (moorlands, wetlands and unfertilized extensively managed grasslands). The GHG budgets of the forests were strongly dominated by CO$_{2}$ exchange, while CH$_{4}$ and N$_{2}$O exchange comprised a larger proportion of the GHG balance in short semi-natural vegetation. Uncertainties in elemental budgets were much larger for nitrogen than carbon, especially at sites with elevated N$_{dep}$ where N$_{r}$ leaching losses were also very large, and compounded by the lack of reliable data on organic nitrogen and N$_{2}$ losses by denitrification. Nitrogen losses in the form of NO, N$_{2}$O and especially NO$_{3}$̅ were on average 27%(range 6 %–54 %) of N$_{dep}$ at sites with N$_{dep}$ 3 gNm$^{-2}$ yr$^{-1}$. Such large levels of N$_{r}$ loss likely indicate that different stages of N saturation occurred at a number of sites. The joint analysis of the C and N budgets provided further hints that N saturation could be detected in altered patterns of forest growth. Net ecosystem productivity increased with N$_{r}$ deposition up to 2–2.5 gNm$^{-2}$ yr$^{-1}$, with large scatter associated with a wide range in carbon sequestration efficiency (CSE, defined as the NEP = GPP ratio). At elevated N$_{dep}$ levels (> 2.5 gNm$^{-2}$ yr$^{-1}$), where inorganic N$_{r}$ losses were also increasingly large, NEP levelled off and then decreased. The apparent increase in NEP at low to intermediate N$_{dep}$ levels was partly the result of geographical cross-correlations between N$_{dep}$ and climate, indicating that the actual mean dC/dN response at individual sites was significantly lower than would be suggested by a simple, straightforward regression of NEP vs. N$_{dep}$

Two Chromogranin A-Derived Peptides Induce Calcium Entry in Human Neutrophils by Calmodulin-Regulated Calcium Independent Phospholipase A2

Background: Antimicrobial peptides derived from the natural processing of chromogranin A (CgA) are co-secreted with catecholamines upon stimulation of chromaffin cells. Since PMNs play a central role in innate immunity, we examine responses by PMNs following stimulation by two antimicrobial CgA-derived peptides. Methodology/Principal Findings: PMNs were treated with different concentrations of CgA-derived peptides in presence of several drugs. Calcium mobilization was observed by using flow cytometry and calcium imaging experiments. Immunocytochemistry and confocal microscopy have shown the intracellular localization of the peptides. The calmodulin-binding and iPLA2 activating properties of the peptides were shown by Surface Plasmon Resonance and iPLA2 activity assays. Finally, a proteomic analysis of the material released after PMNs treatment with CgA-derived peptides was performed by using HPLC and Nano-LC MS-MS. By using flow cytometry we first observed that after 15 s, in presence of extracellular calcium, Chromofungin (CHR) or Catestatin (CAT) induce a concentration-dependent transient increase of intracellular calcium. In contrast, in absence of extra cellular calcium the peptides are unable to induce calcium depletion from the stores after 10 minutes exposure. Treatment with 2-APB (2-aminoethoxydiphenyl borate), a store operated channels (SOCs) blocker, inhibits completely the calcium entry, as shown by calcium imaging. We also showed that they activate iPLA2 as the two CaM-binding factors (W7 and CMZ) and that the two sequences can be aligned with the two CaMbinding domains reported for iPLA2. We finally analyzed by HPLC and Nano-LC MS-MS the material released by PMNs following stimulation by CHR and CAT. We characterized several factors important for inflammation and innate immunity. Conclusions/Significance: For the first time, we demonstrate that CHR and CAT, penetrate into PMNs, inducing extracellular calcium entry by a CaM-regulated iPLA2 pathway. Our study highlights the role of two CgA-derived peptides in the active communication between neuroendocrine and immune systems

Review of nanomaterials in dentistry: interactions with the oral microenvironment, clinical applications, hazards, and benefits.

Interest in the use of engineered nanomaterials (ENMs) as either nanomedicines or dental materials/devices in clinical dentistry is growing. This review aims to detail the ultrafine structure, chemical composition, and reactivity of dental tissues in the context of interactions with ENMs, including the saliva, pellicle layer, and oral biofilm; then describes the applications of ENMs in dentistry in context with beneficial clinical outcomes versus potential risks. The flow rate and quality of saliva are likely to influence the behavior of ENMs in the oral cavity, but how the protein corona formed on the ENMs will alter bioavailability, or interact with the structure and proteins of the pellicle layer, as well as microbes in the biofilm, remains unclear. The tooth enamel is a dense crystalline structure that is likely to act as a barrier to ENM penetration, but underlying dentinal tubules are not. Consequently, ENMs may be used to strengthen dentine or regenerate pulp tissue. ENMs have dental applications as antibacterials for infection control, as nanofillers to improve the mechanical and bioactive properties of restoration materials, and as novel coatings on dental implants. Dentifrices and some related personal care products are already available for oral health applications. Overall, the clinical benefits generally outweigh the hazards of using ENMs in the oral cavity, and the latter should not prevent the responsible innovation of nanotechnology in dentistry. However, the clinical safety regulations for dental materials have not been specifically updated for ENMs, and some guidance on occupational health for practitioners is also needed. Knowledge gaps for future research include the formation of protein corona in the oral cavity, ENM diffusion through clinically relevant biofilms, and mechanistic investigations on how ENMs strengthen the tooth structure