Molecular dynamics simulations of the Johari-Goldstein relaxation in a molecular liquid

Molecular dynamics simulations (mds) were carried out to investigate the reorientational motion of a rigid (fixed bond length), asymmetric diatomic molecule in the liquid and glassy states. In the latter the molecule reorients via large-angle jumps, which we identify with the Johari-Goldstein (JG) dynamics. This relaxation process has a broad distribution of relaxation times, and at least deeply in the glass state, the mobility of a given molecule remains fixed over time; that is, there is no dynamic exchange among molecules. Interestingly, the JG relaxation time for a molecule does not depend on the local density, although the non-ergodicity factor is weakly correlated with the packing efficiency of neighboring molecules. In the liquid state the frequency of the JG process increases significantly, eventually subsuming the slower alpha-relaxation. This evolution of the JG-motion into structural relaxation underlies the correlation of many properties of the JG- and alpha-dynamics.Comment: 12 pages, 6 figure

Connection between dynamics and thermodynamics of liquids on the melting line

The dynamics of a large number of liquids and polymers exhibit scaling properties characteristic of a simple repulsive inverse power law (IPL) potential, most notably the superpositioning of relaxation data as a function of the variable TV{\gamma}, where T is temperature, V the specific volume, and {\gamma} a material constant. A related scaling law, TmVm{\Gamma}, with the same exponent {\Gamma}={\gamma}, links the melting temperature Tm and volume Vm of the model IPL liquid; liquid dynamics is then invariant at the melting point. Motivated by a similar invariance of dynamics experimentally observed at transitions of liquid crystals, we determine dynamic and melting point scaling exponents {\gamma} and {\Gamma} for a large number of non-associating liquids. Rigid, spherical molecules containing no polar bonds have {\Gamma}={\gamma}; consequently, the reduced relaxation time, viscosity and diffusion coefficient are each constant along the melting line. For other liquids {\gamma}>{\Gamma} always; i.e., the dynamics is more sensitive to volume than is the melting point, and for these liquids the dynamics at the melting point slows down with increasing Tm (that is, increasing pressure).Comment: 20 pages, 8 figures, 1 tabl

Isomorphs in model molecular liquids

Isomorphs are curves in the phase diagram along which a number of static and dynamic quantities are invariant in reduced units. A liquid has good isomorphs if and only if it is strongly correlating, i.e., the equilibrium virial/potential energy fluctuations are more than 90% correlated in the NVT ensemble. This paper generalizes isomorphs to liquids composed of rigid molecules and study the isomorphs of two systems of small rigid molecules, the asymmetric dumbbell model and the Lewis-Wahnstrom OTP model. In particular, for both systems we find that the isochoric heat capacity, the excess entropy, the reduced molecular center-of-mass self part of the intermediate scattering function, the reduced molecular center-of-mass radial distribution function to a good approximation are invariant along an isomorph. In agreement with theory, we also find that an instantaneous change of temperature and density from an equilibrated state point to another isomorphic state point leads to no relaxation. The isomorphs of the Lewis-Wahnstrom OTP model were found to be more approximative than those of the asymmetric dumbbell model, which is consistent with the OTP model being less strongly correlating. For both models we find "master isomorphs", i.e., isomorphs have identical shape in the virial/potential energy phase diagram.Comment: 20 page

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Models for Heavy-tailed Asset Returns

Many of the concepts in theoretical and empirical finance developed over the past decades – including the classical portfolio theory, the Black-Scholes-Merton option pricing model or the RiskMetrics variance-covariance approach to VaR – rest upon the assumption that asset returns follow a normal distribution. But this assumption is not justified by empirical data! Rather, the empirical observations exhibit excess kurtosis, more colloquially known as fat tails or heavy tails. This chapter is intended as a guide to heavy-tailed models. We first describe the historically oldest heavy-tailed model – the stable laws. Next, we briefly characterize their recent lighter-tailed generalizations, the so-called truncated and tempered stable distributions. Then we study the class of generalized hyperbolic laws, which – like tempered stable distributions – can be classified somewhere between infinite variance stable laws and the Gaussian distribution. Finally, we provide numerical examples

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. METHODS: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany ((n) = 135), Spain ((n) = 133), Switzerland ((n) = 20) and the United States ((n) = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). FINDINGS: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted (p)-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. INTERPRETATION: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2