On the Role of the Immunoproteasome in Protein Homeostasis

Numerous cellular processes are controlled by the proteasome, a multicatalytic protease in the cytosol and nucleus of all eukaryotic cells, through regulated protein degradation. The immunoproteasome is a special type of proteasome which is inducible under inflammatory conditions and constitutively expressed in hematopoietic cells. MECL-1 (β2i), LMP2 (β1i), and LMP7 (β5i) are the proteolytically active subunits of the immunoproteasome (IP), which is known to shape the antigenic repertoire presented on major histocompatibility complex (MHC) class I molecules. Furthermore, the immunoproteasome is involved in T cell expansion and inflammatory diseases. In recent years, targeting the immunoproteasome in cancer, autoimmune diseases, and transplantation proved to be therapeutically effective in preclinical animal models. However, the prime function of standard proteasomes and immunoproteasomes is the control of protein homeostasis in cells. To maintain protein homeostasis in cells, proteasomes remove proteins which are not properly folded, which are damaged by stress conditions such as reactive oxygen species formation, or which have to be degraded on the basis of regular protein turnover. In this review we summarize the latest insights on how the immunoproteasome influences protein homeostasis.

Spicing Wine at the Symposion: Fact or Fiction? Some Critical Thoughts on Material Aspects of Commensality in the Early Iron Age and Archaic Mediterranean World

Interpretations of metal graters and pottery tripod bowls as Leitfossils of a trans-Mediterranean ‘orientalizing’ culture of spiced-wine consumption have of late become a staple of scholarship on sympotic banqueting, shaping our perception of ancient wine-drinking and its role in cross-cultural interaction in the first half of the first millennium BC. Yet a closer look at the evidence for spiced wine and the use of graters casts serious doubt on assumptions of a widespread practice of adding ‘spices’ to wine during the Greek symposion and of the use of graters or tripod grinding bowls for such a purpose in the Mediterranean and Near Eastern world. A more plausible scenario, it is argued, arises from the well-attested association of graters with cheese and other primarily culinary commodities. It sees the grater’s prime function and symbolic significance shift from a use in Early Iron Age ‘Homeric’ hospitality to becoming a tool in the increasingly complex cuisines associated with the Archaic and Classical banquet – an indicator of evolving Mediterranean commensality with no less of an international horizon, but a commensality that involved interaction and shared consumption beyond the narrowly sympotic.

The Prime Function, the Fay Trisecant Identity, and the van der Pauw Method

The van der Pauw method is a well-known experimental technique in the applied sciences for measuring physical quantities such as the electrical conductivity or the Hall coefficient of a given sample. Its popularity is attributable to its flexibility: the same method works for planar samples of any shape provided they are simply connected. Mathematically, the method is based on the cross-ratio identity. Much recent work has been done by applied scientists attempting to extend the van der Pauw method to samples with holes (“holey samples”). In this article we show the relevance of two new function theoretic ingredients to this area of application: the prime function associated with the Schottky double of a multiply connected planar domain and the Fay trisecant identity involving that prime function. We focus here on the single-hole (doubly connected, or genus one) case. Using these new theoretical ingredients we are able to prove several mathematical conjectures put forward in the applied science literature.

A Structural and Dynamic Analysis of the Partially Disordered Polymerase-Binding Domain in RSV Phosphoprotein

The phosphoprotein P of Mononegavirales (MNV) is an essential co-factor of the viral RNA polymerase L. Its prime function is to recruit L to the ribonucleocapsid composed of the viral genome encapsidated by the nucleoprotein N. MNV phosphoproteins often contain a high degree of disorder. In Pneumoviridae phosphoproteins, the only domain with well-defined structure is a small oligomerization domain (POD). We previously characterized the differential disorder in respiratory syncytial virus (RSV) phosphoprotein by NMR. We showed that outside of RSV POD, the intrinsically disordered N-and C-terminal regions displayed a structural and dynamic diversity ranging from random coil to high helical propensity. Here we provide additional insight into the dynamic behavior of PCα, a domain that is C-terminal to POD and constitutes the RSV L-binding region together with POD. By using small phosphoprotein fragments centered on or adjacent to POD, we obtained a structural picture of the POD–PCα region in solution, at the single residue level by NMR and at lower resolution by complementary biophysical methods. We probed POD–PCα inter-domain contacts and showed that small molecules were able to modify the dynamics of PCα. These structural properties are fundamental to the peculiar binding mode of RSV phosphoprotein to L, where each of the four protomers binds to L in a different way.

The Schottky–Klein prime function and counting functions for Fenchel double crosses

We relate the classical nineteenth century Schottky–Klein function in complex analysis to a counting problem for pairs of geodesics in hyperbolic geometry studied by Fenchel. We then solve the counting problem using ideas from ergodic theory and thermodynamic formalism.

Fay meets van der Pauw: the trisecant identity and the resistivity of holey samples

The van der Pauw method is commonly used in the applied sciences to find the resistivity of a simply connected, two-dimensional conducting laminate. Given the usefulness of this ‘4-point probe’ method there has been much recent interest in trying to extend it to holey, that is, multiply connected, samples. This paper introduces two new mathematical tools to this area of investigation—the prime function on the Schottky double of a planar domain and the Fay trisecant identity—and uses them to show how the van der Pauw method can be extended to find the resistivity of a sample with a hole. We show that an integrated form of the Fay trisecant identity provides valuable information concerning the appearance of ‘envelopes’ observed in the case of holey samples by previous authors. We find explicit formulae for these envelopes, as well as an approximate formula relating two pairs of resistance measurements to the sample resistivity that is expected to be valid when the hole is sufficiently small and not too close to the outer boundary. We describe how these new mathematical tools have enabled us to prove certain conjectures recently made in the engineering literature.

A calculus for flows in periodic domains

Purpose: We present a constructive procedure for the calculation of 2-D potential flows in periodic domains with multiple boundaries per period window.Methods: The solution requires two steps: (i) a conformal mapping from a canonical circular domain to the physical target domain, and (ii) the construction of the complex potential inside the circular domain. All singly periodic domains may be classified into three distinct types: unbounded in two directions, unbounded in one direction, and bounded. In each case, we use conformal mappings to relate the target periodic domain to a canonical circular domain with an appropriate branch structure.Results: We then present solutions for a range of potential flow phenomena including flow singularities, moving boundaries, uniform flows, straining flows and circulatory flows.Conclusion: By using the transcendental Schottky-Klein prime function, the ensuing solutions are valid for an arbitrary number of obstacles per period window. Moreover, our solutions are exact and do not require any asymptotic approximations.

Time response of FOPID controlled PV based cascaded landsman converter-inverter fed induction motor and electric drives applications

Time Response enhancement utilizing photovoltaic based cascaded Landsman Converter (LC) structure is one of the soft strategies in the recent scenario. The prime function of a DC-DC Landsman converter is to optimize the output power of the photovoltaic array and reduce the output voltage ripples. This paper reveals the demonstration and simulation of the Cascaded Landsman Converter Inverter System (CLCIS) with a PV source. MATLAB Simulink-model for CLCIS has been created utilizing the components of Simulink and closed-loop examinations are performed with PI and Fractional-Order-PID (FOPID) Controllers. The present work deal with the comparison of transient and steady-state time responses of CLCIS with PI and FOPID controllers. The outcomes demonstrate that dynamic reaction is enhanced by utilizing FOPID controller.

The Motion of a Point Vortex in Multiply-Connected Polygonal Domains

We study the motion of a single point vortex in simply- and multiply-connected polygonal domains. In the case of multiply-connected domains, the polygonal obstacles can be viewed as the cross-sections of 3D polygonal cylinders. First, we utilize conformal mappings to transfer the polygonal domains onto circular domains. Then, we employ the Schottky-Klein prime function to compute the Hamiltonian governing the point vortex motion in circular domains. We compare between the topological structures of the contour lines of the Hamiltonian in symmetric and asymmetric domains. Special attention is paid to the interaction of point vortex trajectories with the polygonal obstacles. In this context, we discuss the effect of symmetry breaking, and obstacle location and shape on the behavior of vortex motion.