scholarly journals Estimating the Impact of Vaccination on Acute Simian-Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections

2008 ◽  
Vol 82 (23) ◽  
pp. 11589-11598 ◽  
Author(s):  
Janka Petravic ◽  
Ruy M. Ribeiro ◽  
Danilo R. Casimiro ◽  
Joseph J. Mattapallil ◽  
Mario Roederer ◽  
...  
Keyword(s):  
Animal Models ◽  
Standard Model ◽  
Acute Infection ◽  
Virus Infections ◽  
Immunodeficiency Virus ◽  
The Standard Model ◽  
Peak Viral Load ◽  
Siv Infection ◽  
The Impact

ABSTRACT The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, for the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in SHIV and SIV infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3- and 2-fold, respectively. This method allows the comparison of vaccination efficacies among different viral strains and animal models in vivo.

scholarly journals Downregulation of Robust Acute Type I Interferon Responses Distinguishes Nonpathogenic Simian Immunodeficiency Virus (SIV) Infection of Natural Hosts from Pathogenic SIV Infection of Rhesus Macaques

2010 ◽  
Vol 84 (15) ◽  
pp. 7886-7891 ◽  
Author(s):  
Levelle D. Harris ◽  
Brian Tabb ◽  
Donald L. Sodora ◽  
Mirko Paiardini ◽  
Nichole R. Klatt ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Acute Infection ◽  
Type I ◽  
Acute Type ◽  
Type I Ifn ◽  
Immunodeficiency Virus ◽  
Natural Hosts ◽  
Siv Infection

ABSTRACT The mechanisms underlying the AIDS resistance of natural hosts for simian immunodeficiency virus (SIV) remain unknown. Recently, it was proposed that natural SIV hosts avoid disease because their plasmacytoid dendritic cells (pDCs) are intrinsically unable to produce alpha interferon (IFN-α) in response to SIV RNA stimulation. However, here we show that (i) acute SIV infections of natural hosts are associated with a rapid and robust type I IFN response in vivo, (ii) pDCs are the principal in vivo producers of IFN-α/β at peak acute infection in lymphatic tissues, and (iii) natural SIV hosts downregulate these responses in early chronic infection. In contrast, persistently high type I IFN responses are observed during pathogenic SIV infection of rhesus macaques.

scholarly journals Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques

Blood ◽  
2011 ◽  
Vol 118 (10) ◽  
pp. 2763-2773 ◽  
Author(s):  
Suefen Kwa ◽  
Sunil Kannanganat ◽  
Pragati Nigam ◽  
Mariam Siddiqui ◽  
Ravi Dyavar Shetty ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Activation ◽  
Rhesus Macaques ◽  
Virus Infections ◽  
Natural Hosts ◽  
Siv Infection ◽  
Gastrointestinal Tissue ◽  
The Impact

AbstractIn SIV/HIV infection, the gastrointestinal tissue dominates as an important site because of the impact of massive mucosal CD4 depletion and immune activation-induced tissue pathology. Unlike AIDS-susceptible rhesus macaques, natural hosts do not progress to AIDS and resolve immune activation earlier. Here, we examine the role of dendritic cells (DCs) in mediating immune activation and disease progression. We demonstrate that plasmacytoid DCs (pDCs) in the blood up-regulate β7-integrin and are rapidly recruited to the colorectum after a pathogenic SIV infection in rhesus macaques. These pDCs were capable of producing proinflammatory cytokines and primed a T cytotoxic 1 response in vitro. Consistent with the up-regulation of β7-integrin on pDCs, in vivo blockade of α4β7-integrin dampened pDC recruitment to the colorectum and resulted in reduced immune activation. The up-regulation of β7-integrin expression on pDCs in the blood also was observed in HIV-infected humans but not in chronically SIV-infected sooty mangabeys that show low levels of immune activation. Our results uncover a new mechanism by which pDCs influence immune activation in colorectal tissue after pathogenic immunodeficiency virus infections.

scholarly journals The Impact of Excited Neutrinos onνν¯→γγProcess

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
S. C. İnan ◽  
M. Köksal
Keyword(s):  
Standard Model ◽  
Ultrahigh Energy ◽  
The Standard Model ◽  
The Impact

We examine the effect of excited neutrinos on the annihilation of relic neutrinos with ultrahigh energy cosmic neutrinos for theνν¯→γγprocess. The contributions of the excited neutrinos to the neutrino-photon decoupling temperature are calculated. We see that photon-neutrino decoupling temperature can be significantly reduced below the obtained value of the Standard Model with the impact of excited neutrinos.

A Note on Licenses in the Presence of Corruption

2017 ◽  
Vol 14 (3) ◽  
Author(s):  
Amy Farmer ◽  
Fabio Méndez ◽  
Andrew Samuel
Keyword(s):  
Standard Model ◽  
Regulatory Policies ◽  
The Standard Model ◽  
The Impact

Abstract We study the effectiveness of licenses in environments with corruption. We expand the standard model so that bribery is feasible not only when licenses are granted but also when enforced or verified. This modification alters many prior results on bribery and licensing significantly. Specifically, we show that in some cases penalties for bribery at the license-granting stage complement penalties for bribery at the permit-enforcement stage. In other cases, they act as substitutes for each other. These results are especially important for often used regulatory policies in which licenses are used in conjunction with some form of subsequent license verification. Thus, our model suggests that studying the impact of bribery at the license-granting stage should not be conducted without simultaneously studying bribery at the permit verification stage.

scholarly journals Flavor physics: Precision as an avenue to discovery

2020 ◽  
Vol 35 (01) ◽  
pp. 1930018
Author(s):  
Diego Guadagnoli
Keyword(s):  
Cp Violation ◽  
Standard Model ◽  
Flavor Physics ◽  
Standard Model Prediction ◽  
New Physics ◽  
Effective Theory ◽  
Theory Approach ◽  
Long Distance ◽  
The Standard Model ◽  
The Impact

This paper describes the work pursued in the years 2008–2013 on improving the Standard Model prediction of selected flavor-physics observables. The latter includes: (1) [Formula: see text], that quantifies indirect CP violation in the [Formula: see text] system and (2) the very rare decay [Formula: see text], recently measured at the LHC. Concerning point (1), the paper describes our reappraisal of the long-distance contributions to [Formula: see text],[Formula: see text] that have permitted to unveil a potential tension between CP violation in the [Formula: see text]- and [Formula: see text]-system. Concerning point (2), the paper gives a detailed account of various systematic effects pointed out in Ref. 4 and affecting the Standard Model [Formula: see text] decay rate at the level of 10% — hence large enough to be potentially misinterpreted as nonstandard physics, if not properly included. The paper further describes the multifaceted importance of the [Formula: see text] decays as new physics probes, for instance how they compare with [Formula: see text]-peak observables at LEP, following the effective-theory approach of Ref. 5. Both cases (1) and (2) offer clear examples in which the pursuit of precision in Standard Model predictions offered potential avenues to discovery. Finally, this paper describes the impact of the above results on the literature, and what is the further progress to be expected on these and related observables.

scholarly journals Testing lepton flavour universality with (semi)-leptonic $$\varvec{D_{(s)}}$$ decays

2020 ◽  
Vol 80 (2) ◽  
Author(s):  
Robert Fleischer ◽  
Ruben Jaarsma ◽  
Gabriël Koole
Keyword(s):  
Standard Model ◽  
Branching Ratios ◽  
Current Data ◽  
Leptonic Decays ◽  
Independent Analysis ◽  
The Standard Model ◽  
Model Independent ◽  
Pseudo Scalar ◽  
The Impact ◽  
Lepton Flavour

Abstract Data in B-meson decays indicate violations of lepton flavour universality, thereby raising the question about such phenomena in the charm sector. We perform a model-independent analysis of NP contributions in (semi)-leptonic decays of $$D_{(s)}$$D(s) mesons which originate from $$c \rightarrow d \bar{{\ell }} \nu _l$$c→dℓ¯νl and $$c \rightarrow s \bar{{\ell }} \nu _{\ell }$$c→sℓ¯νℓ charged-current interactions. Starting from the most general low-energy effective Hamiltonian containing four-fermion operators and the corresponding short-distance coefficients, we explore the impact of new (pseudo)-scalar, vector and tensor operators and constrain their effects through the interplay with current data. We pay special attention to the elements $$|V_{cd}|$$|Vcd| and $$|V_{cs}|$$|Vcs| of the Cabibbo–Kobayashi–Maskawa matrix and extract them from the $$D_{(s)}$$D(s) decays in the presence of possible NP decay contributions, comparing them with determinations utilizing unitarity. We find a picture in agreement with the Standard Model within the current uncertainties. Using the results from our analysis, we make also predictions for leptonic $$D_{(s)}^+ \rightarrow e^+ \nu _e$$D(s)+→e+νe modes which could be hugely enhanced with respect to their tiny Standard Model branching ratios. It will be interesting to apply our strategy at the future high-precision frontier.

scholarly journals Upregulation of human immunodeficiency virus-1 in chronically infected monocytic cell line by both contact with endothelial cells and cytokines

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1567-1572 ◽  
Author(s):  
ST Fan ◽  
K Hsia ◽  
TS Edgington
Keyword(s):  
Human Immunodeficiency Virus ◽  
Endothelial Cells ◽  
Viral Gene ◽  
Target Cells ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

Abstract Cells of monocytic lineage (Mo) persistently infected with human immunodeficiency virus (HIV) have been suspected to be a major reservoir for in vivo transmission of virus to susceptible target cells. Cellular events and mechanisms that upregulate viral gene expression in such cells are important issues. Because the traffic of such cells is central to biodistribution of HIV, we have explored the impact of interaction of endothelium with HIV-1-infected U1 promonocytic cells. Coculturing of U1 with human umbilical endothelial cells (HUVEC) for 24 to 72 hours in the absence of stimulation induced HIV-1 p24 biosynthesis significantly. Antibody-blocking experiments indicated that CD11/CD18 integrins play a role in upregulation of HIV expression elicited by interaction with HUVEC. Engagement of CD11b/CD18 by adherence of U1 to surfaces coated with either the cognate ligand fibrinogen or monoclonal antibody specific for CD11b/CD18 also enhanced p24 biosynthesis. Furthermore, endothelial cells were found to constitutively synthesize and secrete soluble factors that enhanced HIV- 1 synthesis. The enhancing factors, of estimated size 10 to 45 kD, were induced in HUVEC to high levels by monokines or by lipopolysaccharide, resulting in markedly enhanced HIV-1 expression by U1. These endothelial cell-derived HIV-1-enhancing factors consist of, among others, interleukin-6 (IL-6), IL-1 beta, and granulocyte-macrophage CSF (GM-CSF). Our results suggest that activation of HIV biosynthesis in infected Mo via interaction with endothelium may impact significantly on the tissue distribution and pathogenesis of HIV infections.

SEARCHING FOR AXIONS AND OTHER EXOTICS WITH DARK MATTER DETECTORS

2010 ◽  
Vol 25 (02n03) ◽  
pp. 564-572
Author(s):  
MAXIM POSPELOV
Keyword(s):  
Dark Matter ◽  
Standard Model ◽  
Cold Dark Matter ◽  
Direct Detection ◽  
Annual Modulation ◽  
The Standard Model ◽  
Detection Capabilities ◽  
The Impact ◽  
Particle Decays ◽  
O 10

I consider models of light super-weakly interacting cold dark matter, with [Formula: see text] mass, focusing on bosonic candidates such as pseudoscalars and vectors. I analyze the cosmological abundance, the γ-background created by particle decays, the impact on stellar processes due to cooling, and the direct detection capabilities in order to identify classes of models that pass all the constraints. In certain models, variants of photoelectric (or axioelectric) absorption of dark matter in direct-detection experiments can provide a sensitivity to the superweak couplings to the Standard Model which is superior to all existing indirect constraints. In all models studied, the annual modulation of the direct-detection signal is at the currently unobservable level of O(10-5).

scholarly journals Intrinsic Susceptibility of Rhesus Macaque Peripheral CD4+ T Cells to Simian Immunodeficiency Virus In Vitro Is Predictive of In Vivo Viral Replication

2000 ◽  
Vol 74 (20) ◽  
pp. 9388-9395 ◽  
Author(s):  
Simoy Goldstein ◽  
Charles R. Brown ◽  
Houman Dehghani ◽  
Jeffrey D. Lifson ◽  
Vanessa M. Hirsch
Keyword(s):  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
Rank Order ◽  
Rhesus Macaques ◽  
Target Cells ◽  
Plasma Viremia ◽  
Immunodeficiency Virus ◽  
Siv Infection

ABSTRACT Previous studies with simian immunodeficiency virus (SIV) infection of rhesus macaques suggested that the intrinsic susceptibility of peripheral blood mononuclear cells (PBMC) to infection with SIV in vitro was predictive of relative viremia after SIV challenge. The present study was conducted to evaluate this parameter in a well-characterized cohort of six rhesus macaques selected for marked differences in susceptibility to SIV infection in vitro. Rank order relative susceptibility of PBMC to SIVsmE543-3-infection in vitro was maintained over a 1-year period of evaluation. Differential susceptibility of different donors was maintained in CD8+T-cell-depleted PBMC, macrophages, and CD4+ T-cell lines derived by transformation of PBMC with herpesvirus saimiri, suggesting that this phenomenon is an intrinsic property of CD4+target cells. Following intravenous infection of these macaques with SIVsmE543-3, we observed a wide range in plasma viremia which followed the same rank order as the relative susceptibility established by in vitro studies. A significant correlation was observed between plasma viremia at 2 and 8 weeks postinoculation and in vitro susceptibility (P < 0.05). The observation that the two most susceptible macaques were seropositive for simian T-lymphotropic virus type 1 may suggests a role for this viral infection in enhancing susceptibility to SIV infection in vitro and in vivo. In summary, intrinsic susceptibility of CD4+ target cells appears to be an important factor influencing early virus replication patterns in vivo that should be considered in the design and interpretation of vaccine studies using the SIV/macaque model.

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