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

Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways

Signal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKKɛ, requires interaction with adapter proteins such as TRAF associated NF-κB activator (TANK). Although increased expression or dysregulation of both kinases has been described for a variety of human cancers, this study shows that deregulated expression of the TANK protein is frequently occurring in glioblastomas (GBMs). The functional relevance of TANK was analyzed in a panel of GBM-derived cell lines and revealed that knockdown of TANK arrests cells in the S-phase and prohibits tumor cell migration. Deregulated TANK expression affects several signaling pathways controlling cell proliferation and the inflammatory response. Interference with stoichiometrically assembled signaling complexes by overexpression or silencing of TANK prevented constitutive interferon-regulatory factor 3 (IRF3) phosphorylation. Knockdown of TANK frequently prevents constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). TANK-mediated ERK1/2 activation is independent from the canonical MAP kinase or ERK kinase (MEK) 1/2-mediated pathway and utilizes an alternative pathway that uses a TBK1/IKKɛ/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity.Peer reviewe

CLINICAL AND IMMUNOLOGICAL EFFICIENCY OF MURAMYL DIPEPTIDE IN THE TREATMENT OF ATOPIC DISEASES

Increased incidence of allergic diseases worldwide reflects some mangles of the existing pharmacotherapy concept which ignores some etiopathogenetic aspects of clinical atopy. Meanwhile, understanding cellular and molecular mechanisms of allergy may create prerequisites for development of new therapeutic areas, in order to effectively influence pathogenesis points of allergic inflammation and, thus, leading to therapeutic success. The review article concerns an antagonism between the two populations of T-helper cells (Th1 and Th2) carried out mainly by the action of IFNγ produced by activated Th1, and IL-4 secreted by activated Th2 which is at the heart of modern concept on the regulation of adaptive immunity. The prospects of immunotherapy of allergic diseases based on the polarization of the immune response are discussed, i.e., an activation of Th1 responses and Th2 suppression. This functional polarization can be mediated by the innate immune receptor agonist, i.e., synthetic and natural minimally-sized biologically active fragments (MBAF) with pathogen-associated molecular patterns. In this respect, a very promising drug registered in Russia is based on the synthetic MBAF, glucosaminylmuramyldipeptide (GMDP), The liсopid immunomodulator. This is due to the fact that GMDP, being an active substance of Liсopid, is a highly specific ligand for the NOD2 receptor of innate immunity factors; it may cause activation of the NF-kB transcription factor, and production of multiple immunoregulatory cytokines. Clinical and immunological efficacy of Licopid application in conventional therapy of atopic allergic diseases (asthma, atopic dermatitis, atopic variant of acute obstructive bronchitis) is presented as an overview of pre-clinical and clinical trials

CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms

Although clinically tested JAK inhibitors reduce splenomegaly and systemic symptoms, molecular responses are not observed in most myeloproliferative neoplasm (MPN) patients. We previously demonstrated that MPN cells become persistent to type I JAK inhibitors that bind the active conformation of JAK2. We investigated whether CHZ868, a type II JAK inhibitor, would demonstrate activity in JAK inhibitor persistent cells, murine MPN models, and MPN patient samples. JAK2 and MPL mutant cell lines were sensitive to CHZ868, including type I JAK inhibitor persistent cells. CHZ868 showed significant activity in murine MPN models and induced reductions in mutant allele burden not observed with type I JAK inhibitors. These data demonstrate that type II JAK inhibition is a viable therapeutic approach for MPN patients