Background and purpose
Previous studies suggested that the overall burden of prior infections contributes to cardiovascular diseases and stroke. In the present study, the association between ...infectious burden (IB) and Alzheimer's disease (AD) was examined.
Methods
Antibody titers to common infectious pathogens including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV‐1), Borrelia burgdorferi, Chlamydophila pneumoniae and Helicobacter pylori were measured by enzyme‐linked immunosorbent assay in 128 AD patients and 135 healthy controls. IB was defined as a composite serological measure of exposure to these common pathogens.
Results
Seropositivities toward zero−two, three and four−five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini‐Mental State Examination scores were negatively correlated with IB in all cases. Serum beta‐amyloid protein (Aβ) levels (i.e. Aβ40, Aβ42 and total Aβ) and inflammatory cytokines (i.e. interferon‐γ, tumor necrosis factor α, interleukin‐1β and interleukin‐6) in individuals exposed to four−five infectious pathogens were significantly higher than those exposed to zero−two or three pathogens.
Conclusions
IB consisting of CMV, HSV‐1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.
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Four metallic metamaterials with tailorable mechanical properties are designed using bi-material star-shaped re-entrant planar lattice structures, which do not involve pins, adhesive, welding or ...pressure-fit joints and can be fabricated through laser-based additive manufacturing. Three length parameters, one angle parameter and three material combinations are used as adjustable design parameters to explore structure-property relations. For each of the four designed metamaterials, the effects of the design parameters on the Poisson’s ratio (PR), coefficient of thermal expansion (CTE), Young’s modulus and relative density are systematically investigated using unit cell-based finite element simulations that incorporate periodic boundary conditions. It is found that the bi-material lattice structures can be tailored to obtain 3-D printable metallic metamaterials with positive, near-zero or negative PR and CTE together with an uncompromised Young’s modulus. In particular, it is shown that metamaterial # 1 can exhibit both a negative PR and a non-positive CTE simultaneously. These metallic metamaterials can find applications in structures or devices such as antennas and precision instruments to reduce thermomechanical stresses and extend service lives.
A new Timoshenko beam model is developed using a modified couple stress theory and a surface elasticity theory. A variational formulation based on Hamilton’s principle is employed, which leads to the ...simultaneous determination of the equations of motion and complete boundary conditions for a Timoshenko beam. The new model contains a material length scale parameter accounting for the microstructure effect in the bulk of the beam and three surface elasticity constants describing the mechanical behavior of the beam surface layer. The inclusion of these additional material constants enables the new model to capture the microstructure-and surface energy-dependent size effect. In addition, both bending and axial deformations are considered, and the Poisson effect is incorporated in the current model, unlike existing Timoshenko beam models. The new beam model includes the models considering only the microstructure dependence or the surface energy effect as limiting cases and recovers the Bernoulli–Euler beam model incorporating the two effects as a special case. Also, the current model reduces to the classical Timoshenko beam model when the microstructure dependence, surface energy and Poisson’s effect are all suppressed. To demonstrate the new model, the static bending and free vibration problems of a simply supported beam are analytically solved by directly applying the general formulas derived. The numerical results for the static bending problem reveal that both the deflection and rotation of the simply supported beam predicted by the new model are smaller than those predicted by the classical Timoshenko beam model. In addition, the differences in both the deflection and rotation predicted by the two models are very large when the beam thickness is small, but they are diminishing with the increase of the beam thickness. Similar trends are observed for the free vibration problem, where it is shown that the natural frequency predicted by the new model is higher than that given by the classical model, with the difference between them being significantly large for very thin beams. These predicted trends of the size effect in beam bending at the micron scale agree with those observed experimentally.
•Four types of three-dimensional (3-D) metallic metamaterials with tailorable thermo-mechanical properties are designed. For the first three types, the structure-property relations are studied by ...adjusting design parameters including two length parameters, one angle parameter and two material combinations. For the fourth type, one additional angle parameter is involved.•It is shown that each of the four types of metamaterials designed exhibits the cubic symmetry and thus needs three independent elastic constants to characterize its elastic behavior and one coefficient of thermal expansion to describe its isotropic thermal expansion.•The effects of the design parameters on the effective Poisson's ratio (PR), coefficient of thermal expansion (CTE), Young's modulus, shear modulus and the relative density are systematically investigated for each of the four types of designed metamaterials by using unit cell-based finite element simulations that incorporate periodic boundary conditions.•It is found that 3-D metallic metamaterials with positive, near-zero or negative PR and CTE can be obtained by tailoring the bi-material lattice structures and material combinations. Also, it is revealed that metamaterial # 1 can achieve both a negative PR and a non-positive CTE while maintaining a high stiffness and a low relative density (and thus a lightweight).•The good tunability of thermo-mechanical properties of the four types of metamaterials provides an avenue of enabling the expansion of Ashby's material chart to produce more material options for engineering applications.
Four types of three-dimensional (3-D) metallic metamaterials with tailorable thermo-mechanical properties are designed. For the first three types, the structure-property relations are studied by adjusting design parameters including two length parameters, one angle parameter and two material combinations. For the fourth type, one additional angle parameter is involved. It is shown that each of the four types of metamaterials designed exhibits the cubic symmetry and thus needs three independent elastic constants to characterize its elastic behavior and one coefficient of thermal expansion to describe its isotropic thermal expansion. The effects of the design parameters on the effective Poisson's ratio (PR), coefficient of thermal expansion (CTE), Young's modulus, shear modulus and the relative density are systematically investigated for each of the four types of designed metamaterials by using unit cell-based finite element simulations that incorporate periodic boundary conditions. It is found that 3-D metallic metamaterials with positive, near-zero or negative PR and CTE can be obtained by tailoring the bi-material lattice structures and material combinations. Also, it is revealed that metamaterial # 1 can achieve both a negative PR and a non-positive CTE while maintaining a high stiffness and a low relative density (and thus a lightweight). The good tunability of thermo-mechanical properties of the four types of metamaterials provides an avenue of enabling the expansion of Ashby's material chart to produce more material options for engineering applications.
Double neutron star (DNS) merger events are promising candidates of short gamma-ray burst (sGRB) progenitors as well as high-frequency gravitational wave (GW) emitters. On August 17, 2017, such a ...coinciding event was detected by both the LIGO-Virgo gravitational wave detector network as GW170817 and Gamma-Ray Monitor on board NASA's Fermi Space Telescope as GRB 170817A. Here, we show that the fluence and spectral peak energy of this sGRB fall into the lower portion of the distributions of known sGRBs. Its peak isotropic luminosity is abnormally low. The estimated event rate density above this luminosity is at least Formula: see text Gpc
yr
, which is close to but still below the DNS merger event rate density. This event likely originates from a structured jet viewed from a large viewing angle. There are similar faint soft GRBs in the Fermi archival data, a small fraction of which might belong to this new population of nearby, low-luminosity sGRBs.
•A new analytical model is developed for three types of 2-D periodic star-shaped re-entrant lattice structures that possess the orthotropic symmetry and exhibit negative Poisson's ...ratios.•Contributions from both the re-entrant and connection struts are considered using an energy method based on Castigliano's second theorem. Each re-entrant strut is treated as a Timoshenko beam, and stretching, transverse shearing and bending deformations are all incorporated in the formulation.•Unlike existing studies, the overlapping of struts at joints is included in determining the relative density, which is analytically expressed for each lattice type.•Closed-form formulas are derived for the effective Young's moduli and Poisson's ratios of each type of lattice structure, which contains three non-dimensional length ratios, two re-entrant angles, one shear correction factor, and Young's modulus and Poisson's ratio of the strut material.•The new analytical model is validated against finite element simulations conducted in the current study and two existing analytical models for simpler square lattice structures without re-entrant struts.•It is demonstrated that through a proper selection of the geometrical parameters, vertex connections and strut material, it is possible to tailor the effective Poisson's ratios and Young's moduli of each type of lattice structure over wide ranges to satisfy different needs in various applications.
A new analytical model is developed for three types of 2-D periodic star-shaped re-entrant lattice structures that possess the orthotropic symmetry and exhibit negative Poisson's ratios. Contributions from both the re-entrant and connection struts are considered using an energy method based on Castigliano's second theorem. Each re-entrant strut is treated as a Timoshenko beam, and stretching, transverse shearing and bending deformations are all incorporated in the formulation. Unlike existing studies, the overlapping of struts at joints is included in determining the relative density, which is analytically expressed for each lattice type. Closed-form formulas are derived for the effective Young's moduli and Poisson's ratios of each type of lattice structure, which contain three non-dimensional length ratios, two re-entrant angles, one shear correction factor, and Young's modulus and Poisson's ratio of the strut material. The new analytical model is validated against finite element simulations conducted in the current study and two existing analytical models for simpler square lattice structures without re-entrant struts. To illustrate the newly developed analytical model, a parametric study is conducted to quantitatively show the effects of the five geometrical parameters on the effective properties of each type of lattice structure. It is found that for the effective Poisson's ratios the key controlling parameters are the two re-entrant angles, while for the effective Young's moduli all of the geometrical parameters can have significant effects except for the external connection length ratio. It is demonstrated that through a proper selection of the geometrical parameters, vertex connections and strut material, it is possible to tailor the effective Poisson's ratios and Young's moduli of each type of lattice structure over wide ranges to satisfy different needs in various applications.
Display omitted A new analytical model is developed for three types of 2-D periodic star-shaped re-entrant, lattice structures (with their unit cells shown in Fig. 1) that possess the orthotropic symmetry and, exhibit negative Poisson's ratios.
Summary
Background
Vitiligo is an autoimmune chronic depigmentation disorder caused by melanocyte loss. Previous studies found that CD4+CD25+ regulatory T‐cell (Treg) dysfunction was involved in the ...pathogenesis of vitiligo and that gene polymorphisms in forkhead box P3 (FOXP3) – a master regulator of Treg development and function – were associated with susceptibility to some autoimmune disorders. Therefore, we hypothesized that functional polymorphisms of the FOXP3 gene might be associated with vitiligo via dysregulation of Treg cells.
Objectives
To evaluate whether FOXP3 polymorphisms are associated with vitiligo risk.
Material and methods
In this hospital‐based case–control study of 682 patients with vitiligo and 682 vitiligo‐free age‐ and sex‐matched controls, we genotyped three single nucleotide polymorphisms (SNPs) of the FOXP3 gene – rs2232365, rs3761548 and rs5902434 – by performing polymerase chain reaction with sequence‐specific primers (PCR‐SSP).
Results
Significantly increased vitiligo risk was associated with the rs2232365 GG odds ratio (OR) 1·68, 95% confidence interval (CI) 1·17–2·39, P = 0·004 and rs3761548 AA (OR 1·82, 95% CI 1·10–3·01, P = 0·033) genotypes compared with the rs2232365 AA and rs3761548 CC genotypes. On combined analysis of these three variant alleles, we found that individuals carrying 2–6 variant alleles had significantly increased vitiligo risk (OR 1·34, 95% CI 1·08–1·66). This risk was more pronounced in the following subgroups: age > 20 years, male sex, active vitiligo, nonsegmental vitiligo and other accompanying autoimmune diseases.
Conclusions
FOXP3 gene polymorphisms contributed to vitiligo risk in a Han Chinese population.
What's already known about this topic?
Previous findings have suggested that forkhead box P3 (FOXP3) is a master regulator of regulatory T cells (Tregs) for maintaining immune tolerance and abrogating autoimmune diseases.
Dysfunction of Tregs is involved in the autoimmune mechanism of vitiligo.
FOXP3 polymorphisms negatively affect the expression and functions of FOXP3 as well as of its target genes.
What does this study add?
Our study suggests an association between FOXP3 gene polymorphisms and vitiligo susceptibility.
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