37 research outputs found
Mixing of Active and Sterile Neutrinos
We investigate mixing of neutrinos in the MSM (neutrino Minimal Standard
Model), which is the MSM extended by three right-handed neutrinos. Especially,
we study elements of the mixing matrix between three
left-handed neutrinos () and two sterile
neutrinos () which are responsible to the seesaw mechanism
generating the suppressed masses of active neutrinos as well as the generation
of the baryon asymmetry of the universe (BAU). It is shown that
can be suppressed by many orders of magnitude compared with
and , when the Chooz angle is large in the
normal hierarchy of active neutrino masses. We then discuss the neutrinoless
double beta decay in this framework by taking into account the contributions
not only from active neutrinos but also from all the three sterile neutrinos.
It is shown that and give substantial, destructive contributions
when their masses are smaller than a few 100 MeV, and as a results receive no stringent constraint from the current bounds on such decay.
Finally, we discuss the impacts of the obtained results on the direct searches
of in meson decays for the case when are lighter than pion
mass. We show that there exists the allowed region for with such
small masses in the normal hierarchy case even if the current bound on the
lifetimes of from the big bang nucleosynthesis is imposed. It is also
pointed out that the direct search by using and might miss such since the branching ratios can be
extremely small due to the cancellation in , but the search by
can cover the whole allowed region by improving the
measurement of the branching ratio by a factor of 5.Comment: 30 pages, 32 figure
The mu problem and sneutrino inflation
We consider sneutrino inflation and post-inflation cosmology in the singlet
extension of the MSSM with approximate Peccei-Quinn(PQ) symmetry, assuming that
supersymmetry breaking is mediated by gauge interaction. The PQ symmetry is
broken by the intermediate-scale VEVs of two flaton fields, which are
determined by the interplay between radiative flaton soft masses and higher
order terms. Then, from the flaton VEVs, we obtain the correct mu term and the
right-handed(RH) neutrino masses for see-saw mechanism. We show that the RH
sneutrino with non-minimal gravity coupling drives inflation, thanks to the
same flaton coupling giving rise to the RH neutrino mass. After inflation,
extra vector-like states, that are responsible for the radiative breaking of
the PQ symmetry, results in thermal inflation with the flaton field, solving
the gravitino problem caused by high reheating temperature. Our model predicts
the spectral index to be n_s\simeq 0.96 due to the additional efoldings from
thermal inflation. We show that a right dark matter abundance comes from the
gravitino of 100 keV mass and a successful baryogenesis is possible via
Affleck-Dine leptogenesis.Comment: 27 pages, no figures, To appear in JHE
Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin
Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al
StopCOVID cohort : An observational study of 3,480 patients admitted to the Sechenov University hospital network in Moscow city for suspected COVID-19 infection
© 2020 Oxford University Press. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Clinical Infectious Diseases following peer review. The version of record is available online at: https://doi.org/10.1093/cid/ciaa1535.BACKGROUND: The epidemiology, clinical course, and outcomes of COVID-19 patients in the Russian population are unknown. Information on the differences between laboratory-confirmed and clinically-diagnosed COVID-19 in real-life settings is lacking. METHODS: We extracted data from the medical records of adult patients who were consecutively admitted for suspected COVID-19 infection in Moscow, between April 8 and May 28, 2020. RESULTS: Of the 4261 patients hospitalised for suspected COVID-19, outcomes were available for 3480 patients (median age 56 years (interquartile range 45-66). The commonest comorbidities were hypertension, obesity, chronic cardiac disease and diabetes. Half of the patients (n=1728) had a positive RT-PCR while 1748 were negative on RT-PCR but had clinical symptoms and characteristic CT signs suggestive of COVID-19 infection.No significant differences in frequency of symptoms, laboratory test results and risk factors for in-hospital mortality were found between those exclusively clinically diagnosed or with positive SARS-CoV-2 RT-PCR.In a multivariable logistic regression model the following were associated with in-hospital mortality; older age (per 1 year increase) odds ratio [OR] 1.05 (95% confidence interval (CI) 1.03 - 1.06); male sex (OR 1.71, 1.24 - 2.37); chronic kidney disease (OR 2.99, 1.89 - 4.64); diabetes (OR 2.1, 1.46 - 2.99); chronic cardiac disease (OR 1.78, 1.24 - 2.57) and dementia (OR 2.73, 1.34 - 5.47). CONCLUSIONS: Age, male sex, and chronic comorbidities were risk factors for in-hospital mortality. The combination of clinical features were sufficient to diagnoseCOVID-19 infection indicating that laboratory testing is not critical in real-life clinical practice.Peer reviewe
Tailored ß-Cyclodextrin Blocks the Translocation Pores of Binary Exotoxins from C. Botulinum and C. Perfringens and Protects Cells from Intoxication
International audienceBackgroundClostridium botulinum C2 toxin and Clostridium perfringens iota toxin are binary exotoxins, which ADP-ribosylate actin in the cytosol of mammalian cells and thereby destroy the cytoskeleton. C2 and iota toxin consists of two individual proteins, an enzymatic active (A-) component and a separate receptor binding and translocation (B-) component. The latter forms a complex with the A-component on the surface of target cells and after receptor-mediated endocytosis, it mediates the translocation of the A-component from acidified endosomal vesicles into the cytosol. To this end, the B-components form heptameric pores in endosomal membranes, which serve as translocation channels for the A-components.Here we demonstrate that a 7-fold symmetrical positively charged ß-cyclodextrin derivative, per-6-S-(3-aminomethyl)benzylthio-ß-cyclodextrin, protects cultured cells from intoxication with C2 and iota toxins in a concentration-dependent manner starting at low micromolar concentrations. We discovered that the compound inhibited the pH-dependent membrane translocation of the A-components of both toxins in intact cells. Consistently, the compound strongly blocked transmembrane channels formed by the B-components of C2 and iota toxin in planar lipid bilayers in vitro. With C2 toxin, we consecutively ruled out all other possible inhibitory mechanisms showing that the compound did not interfere with the binding of the toxin to the cells or with the enzyme activity of the A-component.Conclusions/SignificanceThe described ß-cyclodextrin derivative was previously identified as one of the most potent inhibitors of the binary lethal toxin of Bacillus anthracis both in vitro and in vivo, implying that it might represent a broad-spectrum inhibitor of binary pore-forming exotoxins from pathogenic bacteria
Higgs field in cosmology
The accelerated expansion of the early universe is an integral part of modern
cosmology and dynamically realized by the mechanism of inflation. The simplest
theoretical description of the inflationary paradigm is based on the assumption
of an additional propagating scalar degree of freedom which drives inflation -
the inflaton. In most models of inflation the fundamental nature of the
inflaton remains unexplained. In the model of Higgs inflation, the inflaton is
identified with the Standard Model Higgs boson and connects cosmology with
elementary particle physics. A characteristic feature of this model is a
non-minimal coupling of the Higgs boson to gravity. I review and discuss
several phenomenological and fundamental aspects of this model, including the
impact of quantum corrections and the renormalization group, the derivation of
initial conditions for Higgs inflation in a quantum cosmological framework and
the classical and quantum equivalence of different field parametrizations.Comment: 36 pages, 9 figures; references added, typos corrected. Invited
contribution to the Heraeus-Seminar "Hundred Years of Gauge Theory", 30 July
- 3 August 2018, Physikzentrum Bad Honnef, organized by Silvia De Bianchi and
Claus Kiefer. To appear in the proceedings "100 Years of Gauge Theory. Past,
present and future perspectives" in the series `Fundamental Theories of
Physics' (Springer
QCD and strongly coupled gauge theories : challenges and perspectives
We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe