Catastrophe risk-based bonds are used by governments, financial institutions and (re)insurers to transfer the financial risk associated to the occurrence of catastrophic events, such as earthquakes, ...to the capital market. In this study, we show how municipalities prone to earthquakes can use this type of insurance-linked security to protect their building stock and communities from economic losses, and ultimately increase their earthquake resilience. We consider Benevento, a middle-sized historical town in southern Italy, as a case study, although the same approach is applicable to other urban areas in seismically active regions. One of the crucial steps in pricing catastrophe bonds is the computation of aggregate losses. We compute direct economic losses for each exposed asset based on high spatial resolution hazard and exposure models. Finally, we use the simulated loss data to price two types of catastrophe bonds (zero-coupon and coupon bonds) for different thresholds and maturity times. Although the present application focuses on earthquakes, the framework can potentially be applied to other natural disasters, such as hurricanes, floods, and other extreme weather events.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Risk-based catastrophe bonds require the estimation of losses from the convolution of hazard, exposure and vulnerability models. These models are affected by different uncertainties that arise from ...the definition of their input parameters. In this paper, we propose a stochastic approach to treat the uncertainty in the asset location and attributes of the exposure model. The proposed method uses the Monte Carlo sampling approach to generate a stochastic exposure database, where each asset location is generated randomly within the geometric bound of the administration, while the asset attributes (i.e. construction type and material, number of storey, building activity type and number of dwelling) are sampled from distributions built from census data. Finally, a sensitivity analysis is performed to investigate the influence of the spatial resolution of the exposure model on the average annual losses (AAL) and catastrophe bond prices. To this end, we implement four exposure models, with spatial resolution at the asset, municipality and province levels, on a study region comprising ten provinces in southern Italy. Compared to the proposed model, the exposure model where assets are relocated and aggregated at the geometric centroid of the municipality underestimates AAL by
8
%
, while a higher difference (up to
20
%
) is observed for the exposure model where assets are relocated and aggregated at the geometric centroid of the province. We also consider an exposure model whose asset locations are extracted from publicly available building footprints. Yet, this latter model was incomplete for some provinces resulting in underestimation of AAL up to
90
%
. Differences in catastrophe bond prices obtained from the four exposure models are less evident, with the exposure model built based on the building footprints showing a difference up to
9.5
%
.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Number sense, the ability to decipher quantity, forms the foundation for mathematical cognition. How number sense emerges with learning is, however, not known. Here we use a biologically-inspired ...neural architecture comprising cortical layers V1, V2, V3, and intraparietal sulcus (IPS) to investigate how neural representations change with numerosity training. Learning dramatically reorganized neuronal tuning properties at both the single unit and population levels, resulting in the emergence of sharply-tuned representations of numerosity in the IPS layer. Ablation analysis revealed that spontaneous number neurons observed prior to learning were not critical to formation of number representations post-learning. Crucially, multidimensional scaling of population responses revealed the emergence of absolute and relative magnitude representations of quantity, including mid-point anchoring. These learnt representations may underlie changes from logarithmic to cyclic and linear mental number lines that are characteristic of number sense development in humans. Our findings elucidate mechanisms by which learning builds novel representations supporting number sense.
One of the most important atomic properties governing an element's chemical behavior is the energy required to remove its least-bound electron, referred to as the first ionization potential. For the ...heaviest elements, this fundamental quantity is strongly influenced by relativistic effects which lead to unique chemical properties. Laser spectroscopy on an atom-at-a-time scale was developed and applied to probe the optical spectrum of neutral nobelium near the ionization threshold. The first ionization potential of nobelium is determined here with a very high precision from the convergence of measured Rydberg series to be 6.626 21±0.000 05 eV. This work provides a stringent benchmark for state-of-the-art many-body atomic modeling that considers relativistic and quantum electrodynamic effects and paves the way for high-precision measurements of atomic properties of elements only available from heavy-ion accelerator facilities.
Full text
Available for:
CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Steps stabilize water adsorption on metal surfaces, providing favorable binding sites for water during wetting or ice nucleation, but there is limited understanding of the local water arrangements ...formed on such surfaces. Here we describe the structural evolution of water on the stepped Pt(211) surface using thermal desorption, low-energy electron diffraction, and scanning tunneling microscopy to probe the water structure. At low coverage water forms linear structures comprising zigzag chains along the steps that are decorated by H-bonded rings every one or two units along the terrace. Simple 2-coordinate H-bonded chains are not observed, indicating the Pt step binds too weakly to compensate entirely for a low water H-bond coordination number. As the coverage increases, water chains assemble into a disordered (2 × 1) structure, likely made up of the same narrow water chains along the steps with little or no H-bonding between adjacent structures. The chain structure disappears as water adsorption saturates the surface to form an incommensurate, disordered network of water rings of different size. Although the steps on Pt(211) clearly stabilize water adsorption and direct growth, the surface does not support the simple 1D chains previously proposed or an ordered 2D network such as seen on other surfaces. We discuss reasons for this and the factors that determine the behavior of the first water layer on stepped metal surfaces.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Reactive oxygen species have emerged as key participants in a broad range of physiological and pathophysiological processes, not least within the vascular system. Diverse cellular functions which ...have been attributed to some of these pro-oxidants within the vasculature include the regulation of blood pressure, neovascularisation and vascular inflammation. We here highlight the emerging roles of the enzymatically-generated reaction oxygen species, O2- and H2O2, in the regulation of the functions of the gaseous signalling molecules: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulphide (H2S). These gasotransmitters are produced on demand from distinct enzymatic sources and in recent years it has become apparent that they are capable of mediating a number of homeostatic processes within the cardiovascular system including enhanced vasodilation, angiogenesis, wound healing and improved cardiac function following myocardial infarction. In common with O2- and/or H2O2 they signal by altering the functions of target proteins, either by the covalent modification of thiol groups or by direct binding to metal centres within metalloproteins, most notably haem proteins. The regulation of the enzymes which generate NO, CO and H2S have been shown to be influenced at both the transcriptional and post-translational levels by redox-dependent mechanisms, while the activity and bioavailability of the gasotransmitters themselves are also subject to oxidative modification. Within vascular cells, the family of nicotinamide adenine dinucleotide phosphate oxidases (NAPDH oxidases/Noxs) have emerged as functionally significant sources of regulated O2- and H2O2 production and accordingly, direct associations between Nox-generated oxidants and the functions of specific gasotransmitters are beginning to be identified. This review focuses on the current knowledge of the redox-dependent mechanisms which regulate the generation and activity of these gases, with particular reference to their roles in angiogenesis.
Display omitted
•Reactive Oxygen Species and Gasotransmitters are critical regulators of angiogenesis and are involved in processes both upstream and downstream of VEGF expression.•The enzymes which generate NO, CO and H2S are redox regulated at the levels of their transcription, translation, activity and bioavailability.•NAPDH oxidases are functionally significant sources of superoxide and hydrogen peroxide that can direct the functions of specific gasotransmitters.•The products of the chemical interactions of reactive oxygen species and the gasotransmitters are emerging as novel biomolecules that may be exploited therapeutically.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Glucocerebrosidase 1 (
) mutations responsible for Gaucher disease (GD) are the most common genetic risk factor for Parkinson's disease (PD). Although the genetic link between GD and PD is well ...established, the underlying molecular mechanism(s) are not well understood. We propose that glucosylsphingosine, a sphingolipid accumulating in GD, mediates PD pathology in
-associated PD. We show that, whereas GD-related sphingolipids (glucosylceramide, glucosylsphingosine, sphingosine, sphingosine-1-phosphate) promote α-synuclein aggregation
, glucosylsphingosine triggers the formation of oligomeric α-synuclein species capable of templating in human cells and neurons. Using newly generated GD/PD mouse lines of either sex
mutant (N370S, L444P, KO) crossed to α-synuclein transgenics, we show that
mutations predispose to PD through a loss-of-function mechanism. We further demonstrate that glucosylsphingosine specifically accumulates in young GD/PD mouse brain. With age, brains exhibit glucosylceramide accumulations colocalized with α-synuclein pathology. These findings indicate that glucosylsphingosine promotes pathological aggregation of α-synuclein, increasing PD risk in GD patients and carriers.
Parkinson's disease (PD) is a prevalent neurodegenerative disorder in the aging population. Glucocerebrosidase 1 mutations, which cause Gaucher disease, are the most common genetic risk factor for PD, underscoring the importance of delineating the mechanisms underlying mutant
-associated PD. We show that lipids accumulating in Gaucher disease, especially glucosylsphingosine, play a key role in PD pathology in the brain. These data indicate that ASAH1 (acid ceramidase 1) and GBA2 (glucocerebrosidase 2) enzymes that mediate glucosylsphingosine production and metabolism are attractive therapeutic targets for treating mutant
-associated PD.
Chronic inflammation including B-cell activation is commonly observed in both inherited (Gaucher disease GD) and acquired disorders of lipid metabolism. However, the cellular mechanisms underlying ...B-cell activation in these settings remain to be elucidated. Here, we report that β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), 2 major sphingolipids accumulated in GD, can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells. Human βGL1-22– and LGL1-reactive CD1d tetramer–positive T cells have a distinct T-cell receptor usage and genomic and cytokine profiles compared with the classical type I NKT cells. In contrast to type I NKT cells, βGL1-22– and LGL1-specific NKT cells constitutively express T-follicular helper (TFH) phenotype. Injection of these lipids leads to an increase in respective lipid-specific type II NKT cells in vivo and downstream induction of germinal center B cells, hypergammaglobulinemia, and production of antilipid antibodies. Human βGL1-22– and LGL1-specific NKT cells can provide efficient cognate help to B cells in vitro. Frequency of LGL1-specific T cells in GD mouse models and patients correlates with disease activity and therapeutic response. Our studies identify a novel type II NKT-mediated pathway for glucosphingolipid-mediated dysregulation of humoral immunity and increased risk of B-cell malignancy observed in metabolic lipid disorders.
•A new subset of human and murine type II NKT-TFH cells against Gaucher lipids that regulate B-cell immunity.•A novel pathway for B-cell help providing a mechanism underlying chronic B-cell activation and gammopathy in metabolic lipid disorders.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Lysosomal storage disorders (LSD) are rare diseases, caused by inherited deficiencies of lysosomal enzymes/transporters, that affect 1 in 7000 to 1 in 8000 newborns. Individuals with LSDs face long ...diagnostic journeys during which debilitating and life-threatening events can occur. Clinical trials and classical descriptions of LSDs typically focus on common manifestations, which are not representative of the vast phenotypic heterogeneity encountered in real-world experience. Additionally, recognizing that there was a limited understanding of the natural history, disease progression, and real-world clinical outcomes of rare LSDs, a collaborative partnership was pioneered 30 years ago to address these gaps. The Rare Disease Registries (RDR) (for Gaucher, Fabry, Mucopolysaccharidosis type I, and Pompe), represent the largest observational database for these LSDs. Over the past thirty years, data from the RDRs have helped to inform scientific understanding and the development of comprehensive monitoring and treatment guidelines by creating a framework for data collection and establishing a standard of care, with an overarching goal to improve the quality of life of affected patients. Here, we highlight the history, process, and impact of the RDRs, and discuss the lessons learned and future directions.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
