Warming Up Density Functional Theory

Density functional theory (DFT) has become the most popular approach to electronic structure across disciplines, especially in material and chemical sciences. Last year, at least 30,000 papers used DFT to make useful predictions or give insight into an enormous diversity of scientific problems, ranging from battery development to solar cell efficiency and far beyond. The success of this field has been driven by usefully accurate approximations based on known exact conditions and careful testing and validation. In the last decade, applications of DFT in a new area, warm dense matter, have exploded. DFT is revolutionizing simulations of warm dense matter including applications in controlled fusion, planetary interiors, and other areas of high energy density physics. Over the past decade or so, molecular dynamics calculations driven by modern density functional theory have played a crucial role in bringing chemical realism to these applications, often (but not always) with excellent agreement with experiment. This chapter summarizes recent work from our group on density functional theory at non-zero temperatures, which we call thermal DFT. We explain the relevance of this work in the context of warm dense matter, and the importance of quantum chemistry to this regime. We illustrate many basic concepts on a simple model system, the asymmetric Hubbard dimer

When Less Is Best: Female Brown-Headed Cowbirds Prefer Less Intense Male Displays

Sexual selection theory predicts that females should prefer males with the most intense courtship displays. However, wing-spread song displays that male brown-headed cowbirds (Molothrus ater) direct at females are generally less intense than versions of this display that are directed at other males. Because male-directed displays are used in aggressive signaling, we hypothesized that females should prefer lower intensity performances of this display. To test this hypothesis, we played audiovisual recordings showing the same males performing both high intensity male-directed and low intensity female-directed displays to females (N = 8) and recorded the females' copulation solicitation display (CSD) responses. All eight females responded strongly to both categories of playbacks but were more sexually stimulated by the low intensity female-directed displays. Because each pair of high and low intensity playback videos had the exact same audio track, the divergent responses of females must have been based on differences in the visual content of the displays shown in the videos. Preferences female cowbirds show in acoustic CSD studies are correlated with mate choice in field and captivity studies and this is also likely to be true for preferences elucidated by playback of audiovisual displays. Female preferences for low intensity female-directed displays may explain why male cowbirds rarely use high intensity displays when signaling to females. Repetitive high intensity displays may demonstrate a male's current condition and explain why these displays are used in male-male interactions which can escalate into physical fights in which males in poorer condition could be injured or killed. This is the first study in songbirds to use audiovisual playbacks to assess how female sexual behavior varies in response to variation in a male visual display

Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease

Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB

Nitrated α–Synuclein Immunity Accelerates Degeneration of Nigral Dopaminergic Neurons

The neuropathology of Parkinson's disease (PD) includes loss of dopaminergic neurons in the substantia nigra, nitrated alpha-synuclein (N-alpha-Syn) enriched intraneuronal inclusions or Lewy bodies and neuroinflammation. While the contribution of innate microglial inflammatory activities to disease are known, evidence for how adaptive immune mechanisms may affect the course of PD remains obscure. We reasoned that PD-associated oxidative protein modifications create novel antigenic epitopes capable of peripheral adaptive T cell responses that could affect nigrostriatal degeneration.Nitrotyrosine (NT)-modified alpha-Syn was detected readily in cervical lymph nodes (CLN) from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice. Antigen-presenting cells within the CLN showed increased surface expression of major histocompatibility complex class II, initiating the molecular machinery necessary for efficient antigen presentation. MPTP-treated mice produced antibodies to native and nitrated alpha-Syn. Mice immunized with the NT-modified C-terminal tail fragment of alpha-Syn, but not native protein, generated robust T cell proliferative and pro-inflammatory secretory responses specific only for the modified antigen. T cells generated against the nitrated epitope do not respond to the unmodified protein. Mice deficient in T and B lymphocytes were resistant to MPTP-induced neurodegeneration. Transfer of T cells from mice immunized with N-alpha-Syn led to a robust neuroinflammatory response with accelerated dopaminergic cell loss.These data show that NT modifications within alpha-Syn, can bypass or break immunological tolerance and activate peripheral leukocytes in draining lymphoid tissue. A novel mechanism for disease is made in that NT modifications in alpha-Syn induce adaptive immune responses that exacerbate PD pathobiology. These results have implications for both the pathogenesis and treatment of this disabling neurodegenerative disease

Role of Synucleins in Alzheimer’s Disease

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common causes of dementia and movement disorders in the elderly. While progressive accumulation of oligomeric amyloid-β protein (Aβ) has been identified as one of the central toxic events in AD leading to synaptic dysfunction, accumulation of α-synuclein (α-syn) resulting in the formation of oligomers has been linked to PD. Most of the studies in AD have been focused on investigating the role of Aβ and Tau; however, recent studies suggest that α-syn might also play a role in the pathogenesis of AD. For example, fragments of α-syn can associate with amyloid plaques and Aβ promotes the aggregation of α-syn in vivo and worsens the deficits in α-syn tg mice. Moreover, α-syn has also been shown to accumulate in limbic regions in AD, Down’s syndrome, and familial AD cases. Aβ and α-syn might directly interact under pathological conditions leading to the formation of toxic oligomers and nanopores that increase intracellular calcium. The interactions between Aβ and α-syn might also result in oxidative stress, lysosomal leakage, and mitochondrial dysfunction. Thus, better understanding the steps involved in the process of Aβ and α-syn aggregation is important in order to develop intervention strategies that might prevent or reverse the accumulation of toxic proteins in AD

High Z ions in hot, dense matter

International audienceCurrent and proposed experiments on high-energy density matter include conditions for high Z ions in fully ionized plasmas. A semi-classical description is proposed whereby the classical Coulomb interactions are `regularized' at short distances to account for quantum diffraction effects. One motivation for this approach is to allow application of classical molecular dynamics (MID) simulation methods. Here, attention is focused on energy transfer between a heavy-impurity ion at low velocities and an electron gas. The relationship between the mobility, diffusion, and stopping power is noted and clarified. Some examples of MD simulation to explore the dependence on charge number of the impurity are given for an impurity in an electron gas

Electric field dynamics at a charged point

International audienceThe autocorrelation function for the electric field at an impurity ion in a plasma is considered. A simple model is constructed that preserves the exact short time dynamics and the long time global constraint of a given self-diffusion coefficient. The input required is the initial value of the autocorrelation function and its derivatives, and the self-diffusion coefficient. These are calculated from the hypernetted chain equations for correlation functions and a `'disconnected'' approximation for the self-diffusion coefficient. A comparison of the predictions of the model for the electric field autocorrelation function with results from molecular dynamics simulation shows good agreement over a wide range of plasma coupling, impurity ion charge, and impurity ion mass. This provides justification for a simple interpretation of electric field dynamics in terms of three collective modes

Charge correlation effects in electron broadening of ion emitters in hot and dense plasmas

International audienceElectron broadening for ion emitters is investigated with a molecular dynamics based spectral line shape simulation. A regularized, Coulomb potential that removes the divergence at short distances is used for the ion-electron interaction. The method presented here allows one to account for all the correlations between charged particles, which is in distinction to the standard electron broadening of the impact approximation. Two cases are considered: first, a single ion impurity embedded into an electron gas is considered; and second, a two-component ion-electron plasma is studied. Simulations show non-negligible charge correlation effects on line shapes opening new possibilities to improve line shape models and interpretations of experiments. (C) 2003 Elsevier Science Ltd. All rights reserved