The second law and beyond in microscopic quantum setups

The Clausius inequality (CI) is one of the most versatile forms of the second law. Although it was originally conceived for macroscopic steam engines, it is also applicable to quantum single particle machines. Moreover, the CI is the main connecting thread between classical microscopic thermodynamics and nanoscopic quantum thermodynamics. In this chapter, we study three different approaches for obtaining the CI. Each approach shows different aspects of the CI. The goals of this chapter are: (i) To show the exact assumptions made in various derivations of the CI. (ii) To elucidate the structure of the second law and its origin. (iii) To discuss the possibilities each approach offers for finding additional second-law like inequalities. (iv) To pose challenges related to the second law in nanoscopic setups. In particular, we introduce and briefly discuss the notions of exotic heat machines (X machines), and "lazy demons".Comment: As a chapter of: F. Binder, L. A. Correa, C. Gogolin, J. Anders, and G. Adesso (eds.), "Thermodynamics in the quantum regime - Recent Progress and Outlook", (Springer International Publishing). v1 does not include references to other book chapter

Continuum Molecular Simulation of Large Conformational Changes during Ion–Channel Gating

A modeling framework was developed to simulate large and gradual conformational changes within a macromolecule (protein) when its low amplitude high frequency vibrations are not concerned. Governing equations were derived as alternative to Langevin and Smoluchowski equations and used to simulate gating conformational changes of the Kv7.1 ion-channel over the time scale of its gating process (tens of milliseconds). The alternative equations predict the statistical properties of the motion trajectories with good accuracy and do not require the force field to be constant over the diffusion length, as assumed in Langevin equation. The open probability of the ion–channel was determined considering cooperativity of four subunits and solving their concerted transition to the open state analytically. The simulated open probabilities for a series of voltage clamp tests produced current traces that were similar to experimentally recorded currents

Consistent approximation of epidemic dynamics on degree-heterogeneous clustered networks

Realistic human contact networks capable of spreading infectious disease, for example studied in social contact surveys, exhibit both significant degree heterogeneity and clustering, both of which greatly affect epidemic dynamics. To understand the joint effects of these two network properties on epidemic dynamics, the effective degree model of Lindquist et al. [28] is reformulated with a new moment closure to apply to highly clustered networks. A simulation study comparing alternative ODE models and stochastic simulations is performed for SIR (Susceptible–Infected–Removed) epidemic dynamics, including a test for the conjectured error behaviour in [40], providing evidence that this novel model can be a more accurate approximation to epidemic dynamics on complex networks than existing approaches

Effect of a multi-faceted quality improvement intervention on inappropriate antibiotic use in children with non-bloody diarrhoea admitted to district hospitals in Kenya

BACKGROUND: There are few reports of interventions to reduce the common but irrational use of antibiotics for acute non-bloody diarrhoea amongst hospitalised children in low-income settings. We undertook a secondary analysis of data from an intervention comprising training of health workers, facilitation, supervision and face-to-face feedback, to assess whether it reduced inappropriate use of antibiotics in children with non-bloody diarrhoea and no co-morbidities requiring antibiotics, compared to a partial intervention comprising didactic training and written feedback only. This outcome was not a pre-specified end-point of the main trial. METHODS: Repeated cross-sectional survey data from a cluster-randomised controlled trial of an intervention to improve management of common childhood illnesses in Kenya were used to describe the prevalence of inappropriate antibiotic use in a 7-day period in children aged 2-59 months with acute non-bloody diarrhoea. Logistic regression models with random effects for hospital were then used to identify patient and clinician level factors associated with inappropriate antibiotic use and to assess the effect of the intervention. RESULTS: 9, 459 admission records of children were reviewed for this outcome. Of these, 4, 232 (44.7%) were diagnosed with diarrhoea, with 130 of these being bloody (dysentery) therefore requiring antibiotics. 1, 160 children had non-bloody diarrhoea and no co-morbidities requiring antibiotics-these were the focus of the analysis. 750 (64.7%) of them received antibiotics inappropriately, 313 of these being in the intervention hospitals vs. 437 in the controls. The adjusted logistic regression model showed the baseline-adjusted odds of inappropriate antibiotic prescription to children admitted to the intervention hospitals was 0.30 times that in the control hospitals (95%CI 0.09-1.02). CONCLUSION: We found some evidence that the multi-faceted, sustained intervention described in this paper led to a reduction in the inappropriate use of antibiotics in treating children with non-bloody diarrhoea. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register ISRCTN42996612

An overview of animal prion diseases

Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy of primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, animal prion diseases have basically occurred via the acquisition of infection from contaminated feed or via the exposure to contaminated environment. Scrapie and chronic wasting disease are naturally sustaining epidemics. The transmission of BSE to human has caused more than 200 cases of variant Cruetzfeldt-Jacob disease and has raised serious public health concerns. The present review discusses the epidemiology, clinical neuropathology, transmissibility and genetics of animal prion diseases

The Spatial Association of Gene Expression Evolves from Synchrony to Asynchrony and Stochasticity with Age

For multicellular organisms, different tissues coordinate to integrate physiological functions, although this systematically and gradually declines in the aging process. Therefore, an association exists between tissue coordination and aging, and investigating the evolution of tissue coordination with age is of interest. In the past decade, both common and heterogeneous aging processes among tissues were extensively investigated. The results on spatial association of gene changes that determine lifespan appear complex and paradoxical. To reconcile observed commonality and heterogeneity of gene changes among tissues and to address evolution feature of tissue coordination with age, we introduced a new analytical strategy to systematically analyze genome-wide spatio-temporal gene expression profiles. We first applied the approach to natural aging process in three species (Rat, Mouse and Drosophila) and then to anti-aging process in Mouse. The results demonstrated that temporal gene expression alteration in different tissues experiences a progressive association evolution from spatial synchrony to asynchrony and stochasticity with age. This implies that tissue coordination gradually declines with age. Male mice showed earlier spatial asynchrony in gene expression than females, suggesting that male animals are more prone to aging than females. The confirmed anti-aging interventions (resveratrol and caloric restriction) enhanced tissue coordination, indicating their underlying anti-aging mechanism on multiple tissue levels. Further, functional analysis suggested asynchronous DNA/protein damage accumulation as well as asynchronous repair, modification and degradation of DNA/protein in tissues possibly contributes to asynchronous and stochastic changes of tissue microenvironment. This increased risk for a variety of age-related diseases such as neurodegeneration and cancer that eventually accelerate organismal aging and death. Our study suggests a novel molecular event occurring in aging process of multicellular species that may represent an intrinsic molecular mechanism of aging

Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG

Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity. Methodology and Principal Findings: We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16. F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation. Conclusions: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B-and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clini