A Note on Solid-State Maxwell Demon

Starting from 2002, at least two kinds of laboratory-testable, solid-state Maxwell demons have been proposed that utilize the electric field energy of an open-gap n-p junction and that seem to challenge the validity of the Second Law of Thermodynamics. In the present paper we present some arguments against the alleged functioning of such devices.Comment: 9 pages, 4 figures. Foundations of Physics, forthcoming. arXiv admin note: substantial text overlap with arXiv:1101.505

Efficient and Accurate Modeling of Conformational Transitions in Proteins: The Case of c-Src Kinase

The theoretical computational modeling of large conformational transitions occurring in biomolecules still represents a challenge. Here, we present an accurate "in silico" description of the activation and deactivation mechanisms of human c-Src kinases, a fundamental process regulating several crucial cell functions. Our results clearly show that by applying an efficient and automated algorithm able to drive the molecular dynamics (MD) sampling along the pathway between the two c-Src conformational states - the active state and the inactive state - it is possible to accurately describe, at reduced computational costs, the molecular mechanism underlying these large conformational rearrangements. This procedure, combining the MD simulations with the sampling along the well-defined principal motions connecting the two conformational states, allows to provide a description well beyond the present computational limits, and it is easily applicable to different systems where the structures of both the initial and final states are known

Canonical equilibrium distribution derived from Helmholtz potential

Plastino and Curado [Phys. Rev. E 72, 047103 (2005)] recently determined the equilibrium probability distribution for the canonical ensemble using only phenomenological thermodynamical laws as an alternative to the entropy maximization procedure of Jaynes. In the current paper we present another alternative derivation of the canonical equilibrium probability distribution, which is based on the definition of the Helmholtz free energy (and its being constant at the equilibrium) and the assumption of the uniqueness of the equilibrium probability distribution. Noting that this particular derivation is applicable for all trace-form entropies, we also apply it to the Tsallis entropy showing that the Tsallis entropy yields genuine inverse power laws.Comment: 7 pages. Accepted for publication in Physica

ERAP1 and ERAP2 Haplotypes Influence Suboptimal HLA-B*27:05-Restricted Anti-Viral CD8+ T Cell Responses Cross-Reactive to Self-Epitopes

The human leukocyte antigen (HLA)-B*27 family of alleles is strongly associated with ankylosing spondylitis (AS), a chronic inflammatory disorder affecting the axial and peripheral joints, yet some HLA-B*27 variants not associated with AS have been shown. Since no major differences in the ligandome of associated compared to not-associated alleles have emerged, a plausible hypothesis is that the quantity rather than the quality of the presented epitopes makes the difference. In addition, the Endoplasmic Reticulum AminoPeptidases (ERAPs) 1 and 2, playing a crucial role in shaping the HLA class I epitopes, act as strong AS susceptibility factors, suggesting that an altered peptidome might be responsible for the activation of pathogenic CD8+ T cells. In this context, we have previously singled out a B*27:05-restricted CD8+ T cell response against pEBNA3A (RPPIFIRRL), an EBV peptide lacking the B*27 classic binding motif. Here, we show that a specific ERAP1/2 haplotype negatively correlates with such response in B*27:05 subjects. Moreover, we prove that the B*27:05 allele successfully presents peptides with the same suboptimal N-terminal RP motif, including the self-peptide, pDYNEIN (RPPIFGDFL). Overall, this study underscores the cooperation between the HLA-B*27 and ERAP1/2 allelic variants in defining CD8+ T cell reactivity to suboptimal viral and self-B*27 peptides and prompts further investigation of the B*27:05 peptidome composition

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects

Unravelling polar lipids dynamics during embryonic development of two sympatric brachyuran crabs (Carcinus maenas and Necora puber) using lipidomics

Embryogenesis is an important stage of marine invertebrates with bi-phasic life cycles, as it conditions their larval and adult life. Throughout embryogenesis, phospholipids (PL) play a key role as an energy source, as well as constituents of biological membranes. However, the dynamics of PL during embryogenesis in marine invertebrates is still poorly studied. The present work used a lipidomic approach to determine how polar lipid profiles shift during embryogenesis in two sympatric estuarine crabs, Carcinus maenas and Necora puber. The combination of thin layer chromatography, liquid chromatography – mass spectrometry and gas chromatography – mass spectrometry allowed us to achieve an unprecedented resolution on PL classes and molecular species present on newly extruded embryos (stage 1) and those near hatching (stage 3). Embryogenesis proved to be a dynamic process, with four PL classes being recorded in stage 1 embryos (68 molecular species in total) and seven PL classes at stage 3 embryos (98 molecular species in total). The low interspecific difference recorded in the lipidomic profiles of stage 1 embryos appears to indicate the existence of similar maternal investment. The same pattern was recorded for stage 3 embryos revealing a similar catabolism of embryonic resources during incubation for both crab species

Unveiling the Excited State Dynamics of Indole in Solution

In this paper, wereconstruct in detail the dynamicsof the emittingelectronic excited state of aqueous indole, investigating its relaxationmechanism and kinetics to be related to the time-dependent fluorescencesignal. Taking advantage of the results shown in a very recent paper,we were able to model the relaxation process in solution in termsof the transitions between two gas-phase singlet electronic states(L-1(a) and L-1(b)), subsequentlyirreversibly relaxing to the gas-phase singlet dark state ((1)pi sigma*). A comparison of the results with the availableexperimental data shows that the relaxation mechanism we obtain byour theoretical-computational model is reliable, reproducing ratheraccurately all the experimental observables