A reevaluation of the role of the unfolded protein response in islet dysfunction: maladaptation or a failure to adapt?

Endoplasmic reticulum (ER) stress caused by perturbations in ER homeostasis activates an adaptive response termed the unfolded protein response (UPR) whose function is to resolve ER stress. If unsuccessful, the UPR initiates a proapoptotic program to eliminate the malfunctioning cells from the organism. It is the activation of this proapoptotic UPR in pancreatic β-cells that has been implicated in the onset of type 2 diabetes and thus, in this context, is considered a maladaptive response. However, there is growing evidence that β-cell death in type 2 diabetes may not be caused by a maladaptive UPR but by the inhibition of the adaptive UPR. In this review, we discuss the evidence for a role of the UPR in β-cell dysfunction and death in the development of type 2 diabetes and ask the following question: Is β-cell dysfunction the result of a maladaptive UPR or a failure of the UPR to adequately adapt? The answer to this question is critically important in defining potential therapeutic strategies for the treatment and prevention of type 2 diabetes. In addition, we discuss the potential role of the adaptive UPR in staving off type 2 diabetes by enhancing β-cell mass and function in response to insulin resistance

Managing Water under Uncertainty and Risk: The United Nations World Water Development Report 4

This report introduces new aspects of water issues: 1) it reintroduces the 12 challenge area reports that provided the foundation for the first two World Water Development Reports (WWDR); 2) 4 new reports on water quality, groundwater, gender, and desertification, land degradation and drought; 3) in recognition that the global challenges of water can vary considerably across countries and regions, a series of 5 regional reports have been included; 4) a deeper analysis of the main external forces of freshwater resources and possibilities for their future evolution; 5) managing water under uncertainty and risk

Differences in telomere length between sporadic and familial cutaneous melanoma

BACKGROUND: Several pieces of evidence indicate that a complex relationship exists between constitutional telomere length (TL) and the risk of cutaneous melanoma. Although the general perception is that longer telomeres increase melanoma risk, some studies do not support this association. We hypothesise that discordant data are due to the characteristics of the studied populations. OBJECTIVES: To evaluate the association of telomere length with familial and sporadic melanoma. METHODS: TL was measured by multiplex quantitative PCR in leukocytes from 310 melanoma patients according to familial/sporadic and single/multiple cancers and 216 age-matched controls. RESULTS: Patients with sporadic melanoma were found to have shorter telomeres as compared to those with familial melanoma. In addition, shorter telomeres, while tending to reduce the risk of familial melanoma regardless of single or multiple tumors, nearly trebled the risk of single sporadic melanoma. CONCLUSIONS: This is the first time that TL has been correlated to opposite effects on melanoma risk according to the presence or absence of familial predisposition. Individual susceptibility to melanoma should be taken into account when assessing the role of TL as a risk factor. This article is protected by copyright. All rights reserved

Polarized Proton Beams from Laser-induced Plasmas

We report on the concept of an innovative source to produce polarized proton/deuteron beams of a kinetic energy up to several GeV from a laser-driven plasma accelerator. Spin effects have been implemented into the PIC simulation code VLPL to make theoretical predictions about the behavior of proton spins in laser-induced plasmas. Simulations of spin-polarized targets show that the polarization is conserved during the acceleration process. For the experimental realization, a polarized HCl gas-jet target is under construction using the fundamental wavelength of a Nd:YAG laser system to align the HCl bonds and simultaneously circular polarized light of the fifth harmonic to photo-dissociate, yielding nuclear polarized H atoms. Subsequently, their degree of polarization is measured with a Lamb-shift polarimeter. The final experiments, aiming at the first observation of a polarized particle beam from laser-generated plasmas, will be carried out at the 10 PW laser system SULF at SIOM/Shanghai.Comment: 7 pages, 7 figure

Algorithmic Government: Automating Public Services and Supporting Civil Servants in using Data Science Technologies

The data science technologies of artificial intelligence (AI), Internet of Things (IoT), big data and behavioral/predictive analytics, and blockchain are poised to revolutionize government and create a new generation of GovTech start-ups. The impact from the ‘smartification’ of public services and the national infrastructure will be much more significant in comparison to any other sector given government’s function and importance to every institution and individual. Potential GovTech systems include Chatbots and intelligent assistants for public engagement, Robo-advisors to support civil servants, real-time management of the national infrastructure using IoT and blockchain, automated compliance/regulation, public records securely stored in blockchain distributed ledgers, online judicial and dispute resolution systems, and laws/statutes encoded as blockchain smart contracts. Government is potentially the major ‘client’ and also ‘public champion’ for these new data technologies. This review paper uses our simple taxonomy of government services to provide an overview of data science automation being deployed by governments world-wide. The goal of this review paper is to encourage the Computer Science community to engage with government to develop these new systems to transform public services and support the work of civil servants

Актуальні проблеми розвитку виноградства та виноробства

В статті розглянуто сучасні тенденції та проблеми розвитку виноградарства та виноробства України. Надано рекомендації щодо пріоритетних напрямків розвитку виноробних підприємств.The modern tendencies and development problems of Ukraine viticulture and winemaking industry are considered in the article. The regards priority areas recommendations of winemaking enterprises development are given

X-GRL: An Empirical Assessment of Explainable GNN-DRL in B5G/6G Networks

The rapid development of artificial intelligence (AI) techniques has triggered a revolution in beyond fifth-generation (B5G) and upcoming sixth-generation (6G) mobile networks. Despite these advances, efficient resource allocation in dynamic and complex networks remains a major challenge. This paper presents an experimental implementation of deep reinforcement learning (DRL) enhanced with graph neural networks (GNNs) on a real 5G testbed. The method addresses the explainability of GNNs by evaluating the importance of each edge in determining the model's output. The custom sampling functions feed the data into the proposed GNN-driven Monte Carlo policy gradient (REINFORCE) agent to optimize the gNodeB (gNB) radio resources according to the specific traffic demands. The demo demonstrates real-time visualization of network parameters and superior performance compared to benchmarks.Comment: 3 pages, 8 figure

Data-driven urban management: Mapping the landscape

Big data analytics and artificial intelligence, paired with blockchain technology, the Internet of Things, and other emerging technologies, are poised to revolutionise urban management. With massive amounts of data collected from citizens, devices, and traditional sources such as routine and well-established censuses, urban areas across the world have – for the first time in history – the opportunity to monitor and manage their urban infrastructure in real-time. This simultaneously provides previously unimaginable opportunities to shape the future of cities, but also gives rise to new ethical challenges. This paper provides a transdisciplinary synthesis of the developments, opportunities, and challenges for urban management and planning under this ongoing ‘digital revolution’ to provide a reference point for the largely fragmented research efforts and policy practice in this area. We consider both top-down systems engineering approaches and the bottom-up emergent approaches to coordination of different systems and functions, their implications for the existing physical and institutional constraints on the built environment and various planning practices, as well as the social and ethical considerations associated with this transformation from non-digital urban management to data-driven urban management

On the computations of interatomic Coulombic decay widths with R-matrix method

Interatomic Coulombic Decay (ICD) is a general mechanism in which an excited atom can transfer its excess energy to a neighbor which is thus ionized. ICD belongs to the family of Feshbach resonance processes, and, as such, states undergoing ICD are characterized by their energy width. In this work, we investigate the computations of ICD widths using the R-matrix method as implemented in the UKRmol package. Helium dimer is used here as a benchmark system. The results are compared with those obtained with the well established Fano-Algebraic Diagrammatic Construction method. It is shown that the R-matrix method in its present implementation provides accurate total and partial widths if the kinetic energy of the ICD electron is lower than 10 eV. Advantages and limitations of the R-matrix method on the computations of ICD widths are discussed

Morphology and Tensile Properties of Multigraft Copolymers with Regularly Spaced Tri-, Tetra-, and Hexafunctional Junction Points

The effect of chain architecture on the morphological and tensile properties of series of multigraft copolymers, with regularly spaced tri-, tetra-, and hexafunctional junction points, was investigated using transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and tensile testing. The materials were synthesized by coupling difunctional polyisoprene (PI) spacers and living polystyrene (PS) branches, made by anionic polymerization, with chlorosilanes of different functionalities. Since the coupling process is a step-growth polymerization, yielding polydisperse products, fractionation was utilized to separate each material into three fractions (high, middle, and low molecular weight), each of low polydispersity. All three fractions have the same chain architecture on a per junction point basis but differ in the number of junction point units per molecule. By applying the constituting block copolymer concept, the physical behavior of these molecules was compared with current theories. It was found that morphological behavior of these graft copolymers can be predicted using theoretical approaches and is independent on the number of junction points. The number of the junction points, however, greatly influences the long-range order of microphase separation. Additionally, two new parameters for adjusting mechanical properties of multigraft copolymers were found in this investigation: (1) functionality of the graft copolymerstri-, tetra-, or hexafunctionals and (2) number of junction points per molecule. An increase in functionality causes a change in morphology, resulting in a high level of tensile strength for tetrafunctional (cylindrical) and hexafunctional (lamellae) multigraft copolymers, leading to about the twice the strength of the spherical trifunctional multigrafts of similar overall composition. Tetrafunctional multigraft copolymers show a surprisingly high strain at break, far exceeding that of commercial block copolymer thermoplastic elastomers (TPEs). Strain at break and tensile strength increase linearly with the number of junction points per molecule. Hysteresis experiments at about 300-900% deformation demonstrate that multifunctional multigraft copolymers have improved high elasticity as compared to commercial TPEs like Kraton or Styroflex