skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Mathematical Models of Early Hepatitis B Virus Dynamics in Humanized Mice
Abstract Analyzing the impact of the adaptive immune response during acute hepatitis B virus (HBV) infection is essential for understanding disease progression and control. Here we developed mathematical models of HBV infection which either lack terms for adaptive immune responses, or assume adaptive immune responses in the form of cytolytic immune killing, non-cytolytic immune cure, or non-cytolytic-mediated block of viral production. We validated the model that does not include immune responses against temporal serum hepatitis B DNA (sHBV) and temporal serum hepatitis B surface-antigen (HBsAg) experimental data from mice engrafted with human hepatocytes (HEP). Moreover, we validated the immune models against sHBV and HBsAg experimental data from mice engrafted with HEP and human immune system (HEP/HIS). As expected, the model that does not include adaptive immune responses matches the observed high sHBV and HBsAg concentrations in all HEP mice. By contrast, while all immune response models predict reduction in sHBV and HBsAg concentrations in HEP/HIS mice, the Akaike Information Criterion cannot discriminate between non-cytolytic cure (resulting in a class of cells refractory to reinfection) and antiviral block functions (of up to$$99\%$$ 99 % viral production 1–3 weeks following peak viral load). We can, however, reject cytolytic killing, as it can only match the sHBV and HBsAg data when we predict unrealistic levels of hepatocyte loss.  more » « less
Award ID(s):
2051820
PAR ID:
10499624
Author(s) / Creator(s):
; ;
Publisher / Repository:
Springer Science + Business Media
Date Published:
Journal Name:
Bulletin of Mathematical Biology
Volume:
86
Issue:
5
ISSN:
0092-8240
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Given$$g \in \mathbb N \cup \{0, \infty \}$$ g N { 0 , } , let$$\Sigma _g$$ Σ g denote the closed surface of genusgwith a Cantor set removed, if$$g<\infty $$ g < ; or the blooming Cantor tree, when$$g= \infty $$ g = . We construct a family$$\mathfrak B(H)$$ B ( H ) of subgroups of$${{\,\textrm{Map}\,}}(\Sigma _g)$$ Map ( Σ g ) whose elements preserve ablock decompositionof$$\Sigma _g$$ Σ g , andeventually like actlike an element ofH, whereHis a prescribed subgroup of the mapping class group of the block. The group$$\mathfrak B(H)$$ B ( H ) surjects onto an appropriate symmetric Thompson group of Farley–Hughes; in particular, it answers positively. Our main result asserts that$$\mathfrak B(H)$$ B ( H ) is of type$$F_n$$ F n if and only ifHis. As a consequence, for every$$g\in \mathbb N \cup \{0, \infty \}$$ g N { 0 , } and every$$n\ge 1$$ n 1 , we construct a subgroup$$G <{{\,\textrm{Map}\,}}(\Sigma _g)$$ G < Map ( Σ g ) that is of type$$F_n$$ F n but not of type$$F_{n+1}$$ F n + 1 , and which contains the mapping class group of every compact surface of genus$$\le g$$ g and with non-empty boundary. 
    more » « less
  2. Abstract The electricE1 and magneticM1 dipole responses of the$$N=Z$$ N = Z nucleus$$^{24}$$ 24 Mg were investigated in an inelastic photon scattering experiment. The 13.0 MeV electrons, which were used to produce the unpolarised bremsstrahlung in the entrance channel of the$$^{24}$$ 24 Mg($$\gamma ,\gamma ^{\prime }$$ γ , γ ) reaction, were delivered by the ELBE accelerator of the Helmholtz-Zentrum Dresden-Rossendorf. The collimated bremsstrahlung photons excited one$$J^{\pi }=1^-$$ J π = 1 - , four$$J^{\pi }=1^+$$ J π = 1 + , and six$$J^{\pi }=2^+$$ J π = 2 + states in$$^{24}$$ 24 Mg. De-excitation$$\gamma $$ γ rays were detected using the four high-purity germanium detectors of the$$\gamma $$ γ ELBE setup, which is dedicated to nuclear resonance fluorescence experiments. In the energy region up to 13.0 MeV a total$$B(M1)\uparrow = 2.7(3)~\mu _N^2$$ B ( M 1 ) = 2.7 ( 3 ) μ N 2 is observed, but this$$N=Z$$ N = Z nucleus exhibits only marginalE1 strength of less than$$\sum B(E1)\uparrow \le 0.61 \times 10^{-3}$$ B ( E 1 ) 0.61 × 10 - 3  e$$^2 \, $$ 2 fm$$^2$$ 2 . The$$B(\varPi 1, 1^{\pi }_i \rightarrow 2^+_1)/B(\varPi 1, 1^{\pi }_i \rightarrow 0^+_{gs})$$ B ( Π 1 , 1 i π 2 1 + ) / B ( Π 1 , 1 i π 0 gs + ) branching ratios in combination with the expected results from the Alaga rules demonstrate thatKis a good approximative quantum number for$$^{24}$$ 24 Mg. The use of the known$$\rho ^2(E0, 0^+_2 \rightarrow 0^+_{gs})$$ ρ 2 ( E 0 , 0 2 + 0 gs + ) strength and the measured$$B(M1, 1^+ \rightarrow 0^+_2)/B(M1, 1^+ \rightarrow 0^+_{gs})$$ B ( M 1 , 1 + 0 2 + ) / B ( M 1 , 1 + 0 gs + ) branching ratio of the 10.712 MeV$$1^+$$ 1 + level allows, in a two-state mixing model, an extraction of the difference$$\varDelta \beta _2^2$$ Δ β 2 2 between the prolate ground-state structure and shape-coexisting superdeformed structure built upon the 6432-keV$$0^+_2$$ 0 2 + level. 
    more » « less
  3. Abstract A search for exotic decays of the Higgs boson ($$\text {H}$$ H ) with a mass of 125$$\,\text {Ge}\hspace{-.08em}\text {V}$$ Ge V to a pair of light pseudoscalars$$\text {a}_{1} $$ a 1 is performed in final states where one pseudoscalar decays to two$${\textrm{b}}$$ b quarks and the other to a pair of muons or$$\tau $$ τ leptons. A data sample of proton–proton collisions at$$\sqrt{s}=13\,\text {Te}\hspace{-.08em}\text {V} $$ s = 13 Te V corresponding to an integrated luminosity of 138$$\,\text {fb}^{-1}$$ fb - 1 recorded with the CMS detector is analyzed. No statistically significant excess is observed over the standard model backgrounds. Upper limits are set at 95% confidence level ($$\text {CL}$$ CL ) on the Higgs boson branching fraction to$$\upmu \upmu \text{ b } \text{ b } $$ μ μ b b and to$$\uptau \uptau \text{ b } \text{ b },$$ τ τ b b , via a pair of$$\text {a}_{1} $$ a 1 s. The limits depend on the pseudoscalar mass$$m_{\text {a}_{1}}$$ m a 1 and are observed to be in the range (0.17–3.3) $$\times 10^{-4}$$ × 10 - 4 and (1.7–7.7) $$\times 10^{-2}$$ × 10 - 2 in the$$\upmu \upmu \text{ b } \text{ b } $$ μ μ b b and$$\uptau \uptau \text{ b } \text{ b } $$ τ τ b b final states, respectively. In the framework of models with two Higgs doublets and a complex scalar singlet (2HDM+S), the results of the two final states are combined to determine upper limits on the branching fraction$${\mathcal {B}}(\text {H} \rightarrow \text {a}_{1} \text {a}_{1} \rightarrow \ell \ell \text{ b } \text{ b})$$ B ( H a 1 a 1 b b ) at 95%$$\text {CL}$$ CL , with$$\ell $$ being a muon or a$$\uptau $$ τ lepton. For different types of 2HDM+S, upper bounds on the branching fraction$${\mathcal {B}}(\text {H} \rightarrow \text {a}_{1} \text {a}_{1} )$$ B ( H a 1 a 1 ) are extracted from the combination of the two channels. In most of the Type II 2HDM+S parameter space,$${\mathcal {B}}(\text {H} \rightarrow \text {a}_{1} \text {a}_{1} )$$ B ( H a 1 a 1 ) values above 0.23 are excluded at 95%$$\text {CL}$$ CL for$$m_{\text {a}_{1}}$$ m a 1 values between 15 and 60$$\,\text {Ge}\hspace{-.08em}\text {V}$$ Ge V
    more » « less
  4. Abstract Using proton–proton collision data corresponding to an integrated luminosity of$$140\hbox { fb}^{-1}$$ 140 fb - 1 collected by the CMS experiment at$$\sqrt{s}= 13\,\text {Te}\hspace{-.08em}\text {V} $$ s = 13 Te V , the$${{{\Lambda }} _{\text {b}}^{{0}}} \rightarrow {{\text {J}/\uppsi }} {{{\Xi }} ^{{-}}} {{\text {K}} ^{{+}}} $$ Λ b 0 J / ψ Ξ - K + decay is observed for the first time, with a statistical significance exceeding 5 standard deviations. The relative branching fraction, with respect to the$${{{\Lambda }} _{\text {b}}^{{0}}} \rightarrow {{{\uppsi }} ({2\textrm{S}})} {{\Lambda }} $$ Λ b 0 ψ ( 2 S ) Λ decay, is measured to be$$\mathcal {B}({{{\Lambda }} _{\text {b}}^{{0}}} \rightarrow {{\text {J}/\uppsi }} {{{\Xi }} ^{{-}}} {{\text {K}} ^{{+}}} )/\mathcal {B}({{{\Lambda }} _{\text {b}}^{{0}}} \rightarrow {{{\uppsi }} ({2\textrm{S}})} {{\Lambda }} ) = [3.38\pm 1.02\pm 0.61\pm 0.03]\%$$ B ( Λ b 0 J / ψ Ξ - K + ) / B ( Λ b 0 ψ ( 2 S ) Λ ) = [ 3.38 ± 1.02 ± 0.61 ± 0.03 ] % , where the first uncertainty is statistical, the second is systematic, and the third is related to the uncertainties in$$\mathcal {B}({{{\uppsi }} ({2\textrm{S}})} \rightarrow {{\text {J}/\uppsi }} {{{\uppi }} ^{{+}}} {{{\uppi }} ^{{-}}} )$$ B ( ψ ( 2 S ) J / ψ π + π - ) and$$\mathcal {B}({{{\Xi }} ^{{-}}} \rightarrow {{\Lambda }} {{{\uppi }} ^{{-}}} )$$ B ( Ξ - Λ π - )
    more » « less
  5. Abstract A search for supersymmetry involving the pair production of gluinos decaying via off-shell third-generation squarks into the lightest neutralino$$(\tilde{\chi }^0_1)$$ ( χ ~ 1 0 ) is reported. It exploits LHC proton–proton collision data at a centre-of-mass energy$$\sqrt{s} = 13$$ s = 13 TeV with an integrated luminosity of 139 fb$$^{-1}$$ - 1 collected with the ATLAS detector from 2015 to 2018. The search uses events containing large missing transverse momentum, up to one electron or muon, and several energetic jets, at least three of which must be identified as containingb-hadrons. Both a simple kinematic event selection and an event selection based upon a deep neural-network are used. No significant excess above the predicted background is found. In simplified models involving the pair production of gluinos that decay via off-shell top (bottom) squarks, gluino masses less than 2.44 TeV (2.35 TeV) are excluded at 95% CL for a massless$$\tilde{\chi }^0_1.$$ χ ~ 1 0 . Limits are also set on the gluino mass in models with variable branching ratios for gluino decays to$$b\bar{b}\tilde{\chi }^0_1,$$ b b ¯ χ ~ 1 0 , $$t\bar{t}\tilde{\chi }^0_1$$ t t ¯ χ ~ 1 0 and$$t\bar{b}\tilde{\chi }^-_1/\bar{t}b\tilde{\chi }^+_1.$$ t b ¯ χ ~ 1 - / t ¯ b χ ~ 1 + .  
    more » « less