Potential for therapeutic manipulation of the UPR in disease

Increased endoplasmic reticulum (ER) stress and the activated unfolded protein response (UPR) signaling associated with it play key roles in physiological processes as well as under pathological conditions. The UPR normally protects cells and re-establishes cellular homeostasis, but prolonged UPR activation can lead to the development of various pathologies. These features make the UPR signaling pathway an attractive target for the treatment of diseases whose pathogenesis is characterized by chronic activation of this pathway. Here, we focus on the molecular signaling pathways of the UPR and suggest possible ways to target this response for therapeutic purposes

LIPIcs, Volume 248, ISAAC 2022, Complete Volume

LIPIcs, Volume 248, ISAAC 2022, Complete Volum

B+-tree Index Optimization by Exploiting Internal Parallelism of Flash-based Solid State Drives

Previous research addressed the potential problems of the hard-disk oriented design of DBMSs of flashSSDs. In this paper, we focus on exploiting potential benefits of flashSSDs. First, we examine the internal parallelism issues of flashSSDs by conducting benchmarks to various flashSSDs. Then, we suggest algorithm-design principles in order to best benefit from the internal parallelism. We present a new I/O request concept, called psync I/O that can exploit the internal parallelism of flashSSDs in a single process. Based on these ideas, we introduce B+-tree optimization methods in order to utilize internal parallelism. By integrating the results of these methods, we present a B+-tree variant, PIO B-tree. We confirmed that each optimization method substantially enhances the index performance. Consequently, PIO B-tree enhanced B+-tree's insert performance by a factor of up to 16.3, while improving point-search performance by a factor of 1.2. The range search of PIO B-tree was up to 5 times faster than that of the B+-tree. Moreover, PIO B-tree outperformed other flash-aware indexes in various synthetic workloads. We also confirmed that PIO B-tree outperforms B+-tree in index traces collected inside the Postgresql DBMS with TPC-C benchmark.Comment: VLDB201

Gluino Stransverse Mass

We introduce a new observable, 'gluino stransverse mass', which is an application of the Cambridge $m_{T2}$ variable to the process where gluinos are pair produced in proton-proton collision and each gluino subsequently decays into two quarks and one LSP, $i.e. \tilde{g}\tilde{g} \to qq\tilde\chi_1^0\ qq\tilde\chi_1^0$. We show that the gluino stransverse mass can be utilized to measure the gluino and the lightest neutralino masses separately, and also the (1st and 2nd generation) squark masses if lighter than the gluino mass, thereby providing a good first look at the pattern of sparticle masses experimentally.Comment: Typos corrected, Some discussions and one reference adde

The Guidelines of Material Design and Process Control on Hybrid Fiber Metal Laminate for Aircraft Structures

Fiber metal laminate (FML) is a hybrid material system that consists of thin metal sheets bonded into a laminate with intermediate thin fiber reinforced composite layers. The aerospace industry has recently increased their use of FMLs due to the considerable weight reduction and consequent benefits for critical load-carrying locations in commercial aircraft, such as upper fuselage skin panels. All FML materials and their processes should be qualified through enough tests and fabrication trials to demonstrate reproducible and reliable design criteria. In particular, proper surface treatment technologies are prerequisite for achieving long-term service capability through the adhesive bonding process. This chapter introduces a brief overview of design concept, material properties and process control methodologies to provide detailed background information with engineering practices and to help ensure stringent quality controls and substantiation of structure integrity. The guidelines and information found in this chapter are meant to be a documentation of current knowledge and an application of sound engineering principles to the FML part development for aerospace usage

M_T2-assisted on-shell reconstruction of missing momenta and its application to spin measurement at the LHC

We propose a scheme to assign a 4-momentum to each WIMP in new physics event producing a pair of mother particles each of which decays to an invisible weakly interacting massive particle (WIMP) plus some visible particle(s). The transverse components are given by the value that determines the event variable M_T2, while the longitudinal component is determined by the on-shell condition on the mother particle. Although it does not give the true WIMP momentum in general, this M_T2-assisted on-shell reconstruction of missing momenta provides kinematic variables well correlated to the true WIMP momentum, and thus can be useful for an experimental determination of new particle properties. We apply this scheme to some processes to measure the mother particle spin, and find that spin determination is possible even without a good knowledge of the new particle masses.Comment: 11 pages, 10 figures, typos are corrected, figures are replace

Probing resonance decays to two visible and multiple invisible particles

We consider the decay of a generic resonance to two visible particles and any number of invisible particles. We show that the shape of the invariant mass distribution of the two visible particles is sensitive to both the mass spectrum of the new particles, as well as the decay topology. We provide the analytical formulas describing the invariant mass shapes for the nine simplest topologies (with up to two invisible particles in the final state). Any such distribution can be simply categorized by its endpoint, peak location and curvature, which are typically sufficient to discriminate among the competing topologies. In each case, we list the effective mass parameters which can be measured by experiment. In certain cases, the invariant mass shape is sufficient to completely determine the new particle mass spectrum, including the overall mass scale.Comment: Added new figures, conclusions unchanged, published versio

Divergent roles of the regulatory subunits of class IA PI3K

The regulatory subunit of phosphatidylinositol 3-kinase (PI3K), known as p85, is a critical component in the insulin signaling pathway. Extensive research has shed light on the diverse roles played by the two isoforms of p85, namely p85α and p85β. The gene pik3r1 encodes p85α and its variants, p55α and p50α, while pik3r2 encodes p85β. These isoforms exhibit various activities depending on tissue types, nutrient availability, and cellular stoichiometry. Whole-body or liver-specific deletion of pik3r1 have shown to display increased insulin sensitivity and improved glucose homeostasis; however, skeletal muscle-specific deletion of p85α does not exhibit any significant effects on glucose homeostasis. On the other hand, whole-body deletion of pik3r2 shows improved insulin sensitivity with no significant impact on glucose tolerance. Meanwhile, liver-specific double knockout of pik3r1 and pik3r2 leads to reduced insulin sensitivity and glucose tolerance. In the context of obesity, upregulation of hepatic p85α or p85β has been shown to improve glucose homeostasis. However, hepatic overexpression of p85α in the absence of p50α and p55α results in increased insulin resistance in obese mice. p85α and p85β have distinctive roles in cancer development. p85α acts as a tumor suppressor, but p85β promotes tumor progression. In the immune system, p85α facilitates B cell development, while p85β regulates T cell differentiation and maturation. This review provides a comprehensive overview of the distinct functions attributed to p85α and p85β, highlighting their significance in various physiological processes, including insulin signaling, cancer development, and immune system regulation