Component Of Susceptibility Research Articles

A large-scale genomic investigation of susceptibility to infection and its association with mental disorders in the Danish population

Infections and mental disorders are two of the major global disease burdens. While correlations between mental disorders and infections have been reported, the possible genetic links between them have not been assessed in large-scale studies. Moreover, the genetic basis of susceptibility to infection is largely unknown, as large-scale genome-wide association studies of susceptibility to infection have been lacking. We utilized a large Danish population-based sample (N = 65,534) linked to nationwide population-based registers to investigate the genetic architecture of susceptibility to infection (heritability estimation, polygenic risk analysis, and a genome-wide association study (GWAS)) and examined its association with mental disorders (comorbidity analysis and genetic correlation). We found strong links between having at least one psychiatric diagnosis and the occurrence of infection (P = 2.16 × 10−208, OR = 1.72). The SNP heritability of susceptibility to infection ranged from ~2 to ~7% in samples of differing psychiatric diagnosis statuses (suggesting the environment as a major contributor to susceptibility), and polygenic risk scores moderately but significantly explained infection status in an independent sample. We observed a genetic correlation of 0.496 (P = 2.17 × 10−17) between a diagnosis of infection and a psychiatric diagnosis. While our GWAS did not identify genome-wide significant associations, we found 90 suggestive (P ≤ 10−5) associations for susceptibility to infection. Our findings suggest a genetic component in susceptibility to infection and indicate that the occurrence of infections in individuals with mental illness may be in part genetically driven.

Second-harmonic generation in gold crescent- and comma-like nanostructures.

Anisotropic metal nanostructures reveal unique optical properties providing new optical effects. Here we study experimentally the nonlinear-optical response of planar arrays of gold comma-like and crescent-like nanostructures made by colloidal lithography. We show that anisotropy of the nonlinear-optical response is defined not only by the shape of the particles, but also by the relative phase of second-order susceptibility components, which are found to be spectrally sensitive. High values of circular dichroism in the second-harmonic generation response up to 70% are observed in comma-like nanostructures.

Dielectric properties of vapor-deposited propylbenzenes.

Dielectric susceptibility data of vapor-deposited films of iso-propylbenzene (IPB) and n-propylbenzene (NPB) have been recorded across a wide range of deposition temperatures, Tdep, mostly below the glass transition temperature, Tg. The results for the real and imaginary components of dielectric susceptibility are compared with recently published results for 2-methyltetrahydrofuran (MTHF). Common to all three systems are the following: (i) increased kinetic stability seen as higher onset temperature for the transformation to the liquid state for Tdep ≈ 0.85Tg; (ii) the reduction of the dielectric loss (χ″) for as-deposited glasses, a signature of increased packing density that is maximal for Tdep ≈ 0.85Tg; and (iii) a reduced level of the storage component (χ') for as-deposited glasses, an effect that is almost deposition temperature invariant for Tdep < Tg. Material specific behavior is observed when heating the as-deposited films to 1.2Tg: IPB and NPB transform directly into the ordinary liquid state if judged on the basis of dielectric susceptibility, whereas MTHF has been reported to enter an unusual liquid state prior to a liquid-liquid transition at higher temperatures. These results are discussed in the context of the curious scattering results reported by Ishii et al. for some benzene derivatives, which hint at a liquid-liquid transformation.

Second harmonic generation in monolithic lithium niobate metasurfaces.

Second-order nonlinear metasurfaces have proven their ability to efficiently convert the frequency of incident signals over subwavelength thickness. However, the availability of second-order nonlinear materials for such metasurfaces has so far been limited to III-V semiconductors, which have low transparency in the visible and impose constraints on the excitation geometries due to the lack of diagonal second-order susceptibility components. Here we propose a new design concept for second-order nonlinear metasurfaces on a monolithic substrate, which is not limited by the availability of thin crystalline films and can be applied to any non-centrosymmetric material. We exemplify this concept in a monolithic Lithium Niobate metasurface with cylinder-shaped corrugations for enhanced field confinement. By optimizing the geometrical parameters, we show enhanced second harmonic generation from a near-infrared pump beam with conversion efficiency above 10-5 using 1 GW/cm2 pump intensity. Our approach enables new opportunities for practical designs of generic metasurfaces for nonlinear and quantum light sources.

Environmental and health inequalities in England (2000-2015)

Background: Environmental factors, including deprivation, account for 23% of global deaths. Deprivation is believed to magnify differences in the exposure levels (exposure differential), and in the population’s susceptibility to develop health outcomes given an exposure (susceptibility differential). We aimed to examine exposure and susceptibility differentials to various environmental exposures, such as PM2.5 and NO2, across England (2000-2015). Methods: Population-weighted mean concentrations of the studied exposures were assigned to 2011 Lower Super Output Area, LSOA (1,000-3,000 population) and each LSOA was classified in deciles of Index of Multiple Deprivation (IMD), 2015. To assess the exposure differential component, exposure gradients across IMD deciles were investigated. To evaluate the differential susceptibility component, we used sex- and age-specific all-cause mortality. Age-standardized death rates were investigated by exposure levels across IMD deciles. Finally, we regressed mortality rates to exposure levels adjusting for main confounders and stratifying by deprivation decile. Results: Mean concentration of PM2.5 and NO2 were 14.01µg/m3 and 29.13µg/m3, respectively. Preliminary results show a positive gradient of concentration by IMD decile, suggesting an exposure differential by deprivation. Between 2000 and 2015, there were an average of 488,511 deaths per annum. Of these, ~11% and ~8% occurred in the top most and least deprived IMD deciles, respectively. After fitting basic regression models, our preliminary results show no difference in the effect of PM2.5 and NO2 on all-cause mortality risk by deprivation decile. More sophisticated statistical approaches are currently being explored in order to account for spatial dependency and other confounders that could be creating noise in our data. Conclusion: This national study provides up to date evidence on the exposure differential by area deprivation in relation to environmental exposures (e.g. PM2.5 and NO2) across England. It also explores the role of deprivation in the mortality effects of these environmental exposures.

Influence of signal bandwidth and phase delay on complex susceptibility based magnetic particle imaging

In this paper, the influences of signal bandwidth and phase delay on the spatial resolution of complex susceptibility based magnetic particle imaging (csMPI) are investigated by modeling the transfer function of the measurement circuit. Based on the simulation and experimental results, it is found that the signal bandwidth and the phase delay will significantly impact on the spatial resolution of csMPI. To avoid the influence of narrow signal bandwidth and phase delay of measurement circuit on csMPI, a resonance measurement circuit with −3 dB bandwidth of 2.3 kHz (much larger than the signal bandwidth of the desired csMPI signal) and resonance frequency of 12.8 kHz is adopted to measure the weak nonlinear magnetization of the magnetic nanoparticles; a phase compensation is used when calculating the real and the imaginary components of ac magnetic susceptibility.

Complex Susceptibilities and Chiroptical Effects of Collagen Measured with Polarimetric Second-Harmonic Generation Microscopy

Nonlinear optical properties of collagen type-I are investigated in thin tissue sections of pig tendon as a research model using a complete polarimetric second-harmonic generation (P-SHG) microscopy technique called double Stokes-Mueller polarimetry (DSMP). Three complex-valued molecular susceptibility tensor component ratios are extracted. A significant retardance is observed between the chiral susceptibility component and the achiral components, while the achiral components appear to be in phase with each other. The DSMP formalism and microscopy measurements are further used to explain and experimentally validate the conditions required for SHG circular dichroism (SHG-CD) of collagen to occur. The SHG-CD can be observed with the microscope when: (i) the chiral second-order susceptibility tensor component has a non-zero value, (ii) a phase retardance is present between the chiral and achiral components of the second-order susceptibility tensor and (iii) the collagen fibres are tilted out of the image plane. Both positive and negative areas of SHG-CD are observed in microscopy images, which relates to the anti-parallel arrangement of collagen fibres in different fascicles of the tendon. The theoretical formalism and experimental validation of DSMP imaging technique opens new opportunities for ultrastructural characterisation of chiral molecules, in particular collagen, and provides basis for the interpretation of SHG-CD signals. The nonlinear imaging of chiroptical parameters offers new possibilities to further improve the diagnostic sensitivity and/or specificity of nonlinear label-free histopathology.

A Double‐Armed, Hydrophilic Transition Metal Complex as a Paramagnetic NMR Probe

AbstractSynthetic metal complexes can be used as paramagnetic probes for the study of proteins and protein complexes. Herein, two transition metal NMR probes (TraNPs) are reported. TraNPs are attached through two arms to a protein to generate a pseudocontact shift (PCS) using cobalt(II), or paramagnetic relaxation enhancement (PRE) with manganese(II). The PCS analysis of TraNPs attached to three different proteins shows that the size of the anisotropic component of the magnetic susceptibility depends on the probe surroundings at the surface of the protein, contrary to what is observed for lanthanoid‐based probes. The observed PCS are relatively small, making cobalt‐based probes suitable for localized studies, such as of an active site. The obtained PREs are stronger than those obtained with nitroxide spin labels and the possibility to generate both PCS and PRE offers advantages. The properties of TraNPs in comparison with other cobalt‐based probes are discussed.

A Double-Armed, Hydrophilic Transition Metal Complex as a Paramagnetic NMR Probe.

Synthetic metal complexes can be used as paramagnetic probes for the study of proteins and protein complexes. Herein, two transition metal NMR probes (TraNPs) are reported. TraNPs are attached through two arms to a protein to generate a pseudocontact shift (PCS) using cobalt(II), or paramagnetic relaxation enhancement (PRE) with manganese(II). The PCS analysis of TraNPs attached to three different proteins shows that the size of the anisotropic component of the magnetic susceptibility depends on the probe surroundings at the surface of the protein, contrary to what is observed for lanthanoid‐based probes. The observed PCS are relatively small, making cobalt‐based probes suitable for localized studies, such as of an active site. The obtained PREs are stronger than those obtained with nitroxide spin labels and the possibility to generate both PCS and PRE offers advantages. The properties of TraNPs in comparison with other cobalt‐based probes are discussed.

Computational Bottom-Up Vulnerability Indicator for Low-Income Flood-Prone Urban Areas

This study presents the implementation of a methodology for the formulation of a vulnerability indicator for low-income urban territories in flood-prone areas, for two flood types: Sudden and slow. The methodology developed a computational assessment tool based on the Multiple Correspondence Analysis and the framework for vulnerability analysis in sustainable science. This approach uses participatory mapping and on-site data. The data collection was easily implemented with free software tools to facilitate its use in low-income urban territories. The method combines the evaluation of experts using the of the traditional approach for the qualification of the variables of vulnerability in its three components (exposure, susceptibility, and resilience), and incorporates a computational method of the correspondence analysis family to formulate the indicators of vulnerability. The results showed that the multiple correspondence analysis is useful for the identification of the most representative variables in the vulnerability assessment, used for the construction of spatial disaggregated vulnerability indicators and therefore the development of vulnerability maps that will help in the short term in disaster risk management, urban planning, and infrastructure protection. In addition, the variables of the susceptibility component are the most representative regardless of the type of flooding, followed by the variables of the exposure component, for sudden flood-prone territories, and the resilience component for slow flood-prone territories. Our findings and the computational tool can facilitate the prioritization of improvement projects and flood risk management on a household, neighborhood, and municipal level.

Estimation of economic damages caused by the flood risk

In recent years, we have become increasingly aware of the importance of factoring the risk to people, property, the overall economy and the environment from flooding into the planning system, and the role that good planning has in avoiding and reducing such risk that could otherwise arise in the future need to pro-actively manage flood risk. There are many areas, including towns and cities that are already at risk from periodic flooding. One of them is Jijia hydrographic basin is characterized by frequent and sharp variations of flow volumes and levels which lead to floods and flooding throughout the basin. Dorohoi town is located in this basin and experienced a significant flooding from a heavy rainfall event in June 2010. The article describes the undergoing work on model development to estimate the damage that was produced by this flash flood. Different land-use data sets have been used to represent the uncertainties in the exposure, value and susceptibility components. For the flood hazard component, inundation depth has been varied systematically to estimate the sensitivity of flood damage estimations to this component.

The effects of electron–phonon interaction on anisotropic RKKY interaction in graphene nanoribbon

We study the Ruderman–Kittle–Kasuya–Yosida (RKKY) interaction in doped armchair graphene nanoribbon. The effects of both external magnetic field and electron-Holstein phonon on RKKY interaction have been addressed. RKKY interaction as a function of distance between localized moments has been analyzed. It has been shown that a magnetic field along the z-axis mediates an anisotropic interaction which corresponds to a XXZ model interaction between two magnetic moments. In order to calculate the exchange interaction along arbitrary direction between two magnetic moments, we should obtain both transverse and longitudinal static spin susceptibilities of armchair graphene nanoribbon in the presence of electron-phonon coupling and magnetic field. The spin susceptibility components are calculated using the spin dependent Green’s function approach for Holstein model Hamiltonian. The effects of spin polarization on the dependence of exchange interaction on distance between moments are investigated via calculating correlation function of spin density operators. Our results show the influences of magnetic field on the spatial behavior of in-plane and longitudinal RKKY interactions are different in the presence of magnetic field.

Untangling electronic, optical and bonding properties of hexagonal bismuth borate SrBi2B2O7 crystal for ultraviolet opto-electronic applications: An ab initio study

To realize the efficient frequency conversion, the nonlinear ultraviolet crystal must exhibit strong second harmonic generation and possible phase-matching condition. The current first principles calculations predict that SrBi2B2O7 represents potentially a new class of materials with such characteristics. For this aim, we present the first analysis of dynamical, bonding, linear and nonlinear optical properties of the SrBi2B2O7 single crystal. To untangle such properties, both density functional theory calculation and topological analysis were used. It is found that the compound exhibits a wide indirect band gap and an interesting bonding motif. In particular, the distortion caused by the stereochemically active lone pair of the s-state in the Bi3+ unit favors the enhancement of local dipole moment. In addition, the refraction index, absorption spectrum, phase matching and second harmonic properties were calculated and analyzed. According to the results, SrBi2B2O7 has a large d33 s-order susceptibility component which makes it a very promising UV nonlinear optical material.

Magnetic susceptibility and phase transitions in LiNiPO4

Detailed studies of specific heat, magnetization, and magnetic torque of a single crystal of ${\mathrm{LiNiPO}}_{4}$ olivine are presented. Olivines attract attention as promising for application as cathodes in Li-ion batteries and exhibiting a unique set of properties. ${\mathrm{LiNiPO}}_{4}$ is the unique olivine, in which antiferromagnetic order develops in two steps, i.e., at 21.8 K, the second-order transition to an incommensurate phase and then, at 20.9 K, the first-order transition to a commensurate phase appears. Specific heat studies, supplemented by the ``slope analysis procedure,'' revealed a splitting of the specific heat anomaly accompanying the first-order transition, which suggests that actually, these are two coupled transitions, one of which can be the ferroelectric one. The specific heat was measured as a function of temperature for a series of fixed external magnetic field $B$ values. As the result, analytical equations describing the phase transition lines in the $T\text{\ensuremath{-}}B$ plane were determined and evolution of a shape of the specific heat anomalies accompanying the phase transitions, observed in the powder sample under influence of $B$, was modeled. Angular dependence of magnetic torque and of magnetization for $B$ rotating within the $a\text{\ensuremath{-}}c$ and $b\text{\ensuremath{-}}c$ crystalline planes was measured for several fixed temperature and $B$ values. Based on these results, we found a new effect, that we called ``off-diagonal nonlinear magnetic susceptibility,'' i.e., we found that for each main crystallographic axis $(a,b$, and $c)$, an additional component of magnetic susceptibility, proportional to the square of the perpendicular to this axis component of $B$, exists. A phenomenological model of this effect, describing the experimental results correctly, was proposed.

Influences of Ga Doping on Crystal Structure and Polarimetric Pattern of SHG in ZnO Nanofilms.

The second-harmonic generation (SHG) in gallium doped ZnO (GZO) nanofilms was studied. The Ga doping in GZO nanofilms influenced the crystal structure of the films, which affected SHG characteristics of the nanofilms. In our experiments, a strong SHG response was obtained in GZO nanofilms, which was excited by 790 nm femtosecond laser. It was observed that the Ga doping concentrations affected, not only the intensity, but also the polarimetric pattern of SHG in GZO nanofilms. For 5.0% doped GZO films, the SHG intensity increased about 70%. The intensity ratio of SHG between the incident light polarization angle of 90° and 0°changed with the Ga doping concentrations. It showed the most significant increase for 7.3% doped GZO films, with an increased ratio of c/a crystal constants. This result was attributed to the differences of the ratios of d33/d31 (the second-order nonlinear susceptibility components) induced by the crystal distortion. The results are helpful to investigate nanofilms doping levels and crystal distortion by SHG microscopy, which is a non-destructive and sensitive method.

Surface-wave dispersion retrieval method and synthesis technique for bianisotropic metasurfaces

We propose a surface-wave dispersion retrieval method and synthesis technique that applies to bianisotropic metasurfaces that are embedded in symmetric or asymmetric environments. Specifically, we use general zero-thickness sheet transition conditions to relate the propagation constants of surface-wave modes to the bianisotropic susceptibility components of the metasurface, which can themselves be directly related to its scattering parameters. It is then possible to either obtain the metasurface dispersion diagram from its known susceptibilities or, alternatively, compute the susceptibilities required to achieve a desired surface-wave propagation. The validity of the method is demonstrated by comparing its results to those obtained with exact dispersion relations of well known structures such as the propagation of surface plasmons on thin metallic films. In particular, this work reveals that it is possible to achieve surface-wave propagation only on one side of the metasurface either by superposition of symmetric and asymmetric modes in the case of anisotropic metasurfaces or by completely forbidding the existence of the surface wave on one side of the structure using bianisotropic metasurfaces.

Protist communities are more sensitive to nitrogen fertilization than other microorganisms in diverse agricultural soils

BackgroundAgricultural food production is at the base of food and fodder, with fertilization having fundamentally and continuously increased crop yield over the last decades. The performance of crops is intimately tied to their microbiome as they together form holobionts. The importance of the microbiome for plant performance is, however, notoriously ignored in agricultural systems as fertilization disconnects the dependency of plants for often plant-beneficial microbial processes. Moreover, we lack a holistic understanding of how fertilization regimes affect the soil microbiome. Here, we examined the effect of a 2-year fertilization regime (no nitrogen fertilization control, nitrogen fertilization, and nitrogen fertilization plus straw amendment) on entire soil microbiomes (bacteria, fungi, and protist) in three common agricultural soil types cropped with maize in two seasons.ResultsWe found that the application of nitrogen fertilizers more strongly affected protist than bacterial and fungal communities. Nitrogen fertilization indirectly reduced protist diversity through changing abiotic properties and bacterial and fungal communities which differed between soil types and sampling seasons. Nitrogen fertilizer plus straw amendment had greater effects on soil physicochemical properties and microbiome diversity than nitrogen addition alone. Moreover, nitrogen fertilization, even more together with straw, increased soil microbiome network complexity, suggesting that the application of nitrogen fertilizers tightened soil microbiomes interactions.ConclusionsTogether, our results suggest that protists are the most susceptible microbiome component to the application of nitrogen fertilizers. As protist communities also exhibit the strongest seasonal dynamics, they serve as the most sensitive bioindicators of soil changes. Changes in protist communities might have long-term effects if some of the key protist hubs that govern microbiome complexities as top microbiome predators are altered. This study serves as the stepping stone to promote protists as promising agents in targeted microbiome engineering to help in reducing the dependency on exogenous unsustainably high fertilization and pesticide applications.

Functional variation at an expressed MHC class IIβ locus associates with Ranavirus infection intensity in larval anuran populations.

Infectious diseases are causing catastrophic losses to global biodiversity. Iridoviruses in the genus Ranavirus are among the leading causes of amphibian disease-related mortality. Polymorphisms in major histocompatibility complex (MHC) genes are significantly associated with variation in amphibian pathogen susceptibility. MHC genes encode two classes of polymorphic cell-surface molecules that can recognize and bind to diverse pathogen peptides. While MHC class I genes are the classic mediators of viral-acquired immunity, larval amphibians do not express them. Consequently, MHC class II gene diversity may be an important predictor of Ranavirus susceptibility in larval amphibians, the life stage most susceptible to Ranavirus. We surveyed natural populations of larval wood frogs (Rana sylvatica), which are highly susceptible to Ranavirus, across 17 ponds and 2years in Maryland, USA. We sequenced the peptide-binding region of an expressed MHC class IIβ locus and assessed allelic and genetic diversity. We converted alleles to functional supertypes and determined if supertypes or alleles influenced host responses to Ranavirus. Among 381 sampled individuals, 26% were infected with Ranavirus. We recovered 20 unique MHC class IIβ alleles that fell into two deeply diverged clades and seven supertypes. MHC genotypes were associated with Ranavirus infection intensity, but not prevalence. Specifically, MHC heterozygotes and supertype ST1/ST7 had significantly lower Ranavirus infection intensity compared to homozygotes and other supertypes. We conclude that MHC class IIβ functional genetic variation is an important component of Ranavirus susceptibility. Identifying immunogenetic signatures linked to variation in disease susceptibility can inform mitigation strategies for combatting global amphibian declines.

Imaging Regional Geology and Au – Sulphide mineralization over Dhanjori greenstone belt: Implications from 3-D Inversion of Audio Magnetotelluric data and Petrophysical Characterization

The 2.1-Ga-old Paleoproterozoic Dhanjori Group of rocks covers 800 sq. km area within the Singhbhum Crustal province of eastern India, and is composed of siliciclastic metasedimentary sequence interlayered with mafic to ultramafic rocks. The meta-volcanosedimentary sequence is deformed and is of low-grade greenschist metamorphic facies. The gold occurrences within the study area are confined to the sulphide hosted mafic/ultramafic volcanic rocks and also in the basal quartz pebble conglomerates (QPC) within the Dhanjori Formation. Gold mineralization within the mafic/ultramafic meta-volcanics formations occurs within the quartz ± carbonate vein i.e. lode gold and as detrital gold within the QPC (0.5−7 ppm) of Phuljhari Formations. Regional Audio Magnetotelluric (AMT) measurements across the geological domains of Dhanjori Group and Iron Ore Group (IOG) were carried out in the frequency range of 10 kHz–10 Hz. This work discusses the conductivity model from 3-D inversion along with geology and petrophysical properties in mapping the regional geological features, associated sulphide mineralization and influence of texture, grain and bulk properties on mineralization. Dimensionality and strike analysis of the AMT data indicate complex conductivity structures. 3-D inversion of off-diagonal component of impedance was performed for obtaining an optimum value of uniform half space initial resistivity and error floor for off-diagonal component of impedance data. These were used to perform 3-D inversion of full impedance to produce a conductivity model of the study area. The conductivity model delineated major geological boundaries and the sulphide bearing mineralized zone. A major conductor is observed which extends to a depth of ∼250 m within meta-volcanics. On comparison with the available borehole adjacent to this, it is confirmed that the conductor corresponds to sulphide mineralization. The resistivity low at a depth of 150 m coincides with metabasalts (pyrite present which extends to 159 m with arsenopyrite). Another mineralized zone is observed at the boundary of iron ore group volcanics and Proterozoic-gabbro-anorthosite-ultramafics (PGAU), it starts appearing from a depth of ∼400 m and can be seen which extends to a depth of ∼800 m. It is worth mentioning that there lies Kundarkocha gold mine in the same geological domain. In addition, near surface conductor to a maximum depth of ∼50 m is observed all along the AMT profile. The sediments and fluids could account for this conducting feature. This is in agreement with available Electrical Resistivity Tomography section. The borehole within Dhanjori Volcanics also detected sulphide mineralization for ∼50 m. Thus, it can be inferred that the near surface conductor indicates the presence of gold in association with other sulphide minerals. The petrophysical studies helped to estimate the concentration of minerals within the rocks. High density and low susceptibilities in the area is an indicative of low-grade metamorphism and low level of serpentenization. Combined density and susceptibility scatter diagram and component proportion phase diagram suggests 20 vol%, 78 vol% and 2 vol% of haematite/sulphides, barren rocks and magnetite respectively. The high value of chargeability and negligible value of susceptibility indicates the presence of disseminated sulphides rather than haematites and/or massive sulphides in the rocks. Ternary plot suggest that the mineralization is controlled by texture and grain properties. Petrophysical analysis suggests that the lithotypes of the study area are similar to those of greenstone terrain in the Abitibi Subprovince. Integrating inverted section, geology and petrophysical properties has a substantial impact on the study area in terms of predicting the mineralization prospect and at the same time substantially reduces the drilling cost. Thus, the study provides a new orientation and advancement to the exploration strategy for deeper deposits.

Probabilistic seismic assessment of as-built and retrofitted old and newly designed skewed multi-frame bridges

This paper presents a probabilistic seismic assessment of older and newly-designed skewed multi-frame reinforced concrete box-girder bridges in California. The overall system and individual components fragility curves were developed for both older and new bridges with different skewness angles across four different damage states. Moreover, the effectiveness of two retrofit strategies: restrainer cables and shear keys at both in-span hinges and abutments was explored for mitigating the seismic fragility of multi-frame bridges and contributing to the nation's effort in maintaining the deteriorating infrastructure. The results indicate that the bridge system and different component fragilities are affected by the design details chronological changes, deck skewness, and the choice of the retrofit components. Deck unseating at the in-span hinge is shown to be the most sensitive component to the retrofit measures and design chronological changes. The retrofit measures are also shown to reduce the vulnerability of older bridges and have a negligible effect on newly designed bridges. On the other hand, the bearing pads damage of both old and new bridges is the most susceptible component to the deck skewness. For completeness, the results of this study are compared to fragility medians suggested by HAZUS-MH, and a significant underestimation of vulnerability for both old and new skewed multi-frame bridge is shown.