Hurricane Matthew in 2100: effects of extreme sea level rise scenarios on a highly valued coastal area (Palm Beach, FL, USA)

Sea-level rise represents a severe hazard for populations living within low-elevation coastal zones and is already largely affecting coastal communities worldwide. As sea level continues to rise following unabated greenhouse gas emissions, the exposure of coastal communities to inundation and erosion will increase exponentially. These impacts will be further magnified under extreme storm conditions. In this paper, we focus on one of the most valuable coastal real estate markets globally (Palm Beach, FL). We use XBeach, an open-source hydro and morphodynamic model, to assess the impact of a major tropical cyclone (Hurricane Matthew, 2016) under three different sea-level scenarios. The first scenario (modern sea level) serves as a baseline against which other model runs are evaluated. The other two runs use different 2100 sea-level projections, localized to the study site: (i) IPCC RCP 8.5 (0.83 m by 2100) and (ii) same as (i), but including enhanced Antarctic ice loss (1.62 m by 2100). Our results show that the effective doubling of future sea level under heightened Antarctic ice loss amplifies flow velocity and wave height, leading to a 46% increase in eroded beach volume and the overtopping of coastal protection structures. This further exacerbates the vulnerability of coastal properties on the island, leading to significant increases in parcel inundation

Framework for selecting manufacturing simulation software in industry 4.0 environment

Even though the use of simulation software packages is widespread in industrial and manufacturing companies, the criteria and methods proposed in the scientific literature to evaluate them do not adequately help companies in identifying a package able to enhance the efficiency of their production system. Hence, the main objective of this paper is to develop a framework to guide companies in choosing the most suitable manufacturing simulation software package. The evaluation framework developed in this study is based on two different multi-criteria methods: analytic hierarchy process (AHP) integrated with benefits, opportunities, costs, risks (BOCR) analysis and the best-worst method (BWM). The framework was developed on the basis of the suggestions from the literature and from a panel of experts, both from academia and industry, trying to capture all the facets of the software selection problem. For testing purposes, the proposed approach was applied to a mid-sized enterprise located in the south of Italy, which was facing the problem of buying an effective simulation software for Participatory Design. From a practical perspective, the application showed that the framework is effective in identifying the most suitable simulation software package according to the needs of the company. From a theoretical point of view, the multi-criteria methods suggested in the framework have never been applied to the problem of selecting simulation software; their usage in this context could bring some advantages compared to other decision-making tools

Oral liquid L-thyroxine (L-t4) may be better absorbed compared to L-T4 tablets following bariatric surgery.

Drug malabsorption is a potential concern after bariatric surgery. We present four case reports of hypothyroid patients who were well replaced with thyroxine tablets to euthyroid thyrotropin (TSH) levels prior to Roux-en-Y gastric bypass surgery. These patients developed elevated TSH levels after the surgery, the TSH responded reversibly to switching from treatment with oral tablets to a liquid formulation

Acute hepatitis caused by minocycline.

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Measurement of the Fermi Constant by FAST

An initial measurement of the lifetime of the positive muon to a precision of 16 parts per million (ppm) has been performed with the FAST detector at the Paul Scherrer Institute. The result is tau_mu = 2.197083 (32) (15) microsec, where the first error is statistical and the second is systematic. The muon lifetime determines the Fermi constant, G_F = 1.166353 (9) x 10^-5 GeV^-2 (8 ppm).Comment: 15 pages, 6 figure

Microsatellite instability and defects in mismatch repair proteins: a new aetiology for Sertoli cell‐only syndrome

Microsatellite instability is characteristic of certain types of cancer, and is present in rodents lacking specific DNA mismatch repair proteins. These azoospermic mice exhibit spermatogenic defects similar to some human testicular failure patients. Therefore, we hypothesized that microsatellite instability due to deficiencies in mismatch repair genes might be an unrecognized aetiology of human testicular failure. Because these azoospermic patients are candidates for testicular sperm extraction and ICSI, transmission of mismatch repair defects to the offspring is possible. Seven microsatellite loci were analysed for instability in specimens from 41 testicular failure patients and 20 controls. Blood and testicular DNA were extracted from patient and control specimens, and amplified by PCR targeting seven microsatellite loci. DNA fragment length was analysed with an ABI Prism 310 Genotyping Machine and GeneScan software. Immunohistochemistry was performed on paraffinized testis biopsy sections and cultured testicular fibroblasts from each patient to determine if expression of the mismatch repair proteins hMSH2 and hMLH1 was normal in both somatic and germline cells. Results demonstrate that microsatellite instability and DNA mismatch repair protein defects are present in some azoospermic men, predominantly in Sertoli cell‐only patients (P < 0.01 and P < 0.05 respectively). This provides evidence of a previously unrecognized aetiology of testicular failure that may be associated with cancer predispositio

Role of the Cysteine in R3 Tau Peptide in Copper Binding and Reactivity

Tau is a widespread neuroprotein that regulates the cytoskeleton assembly. In some neurological disorders, known as tauopathies, tau is dissociated from the microtubule and forms insoluble neurofibrillary tangles. Tau comprises four pseudorepeats (R1-R4), containing one (R1, R2, R4) or two (R3) histidines, that potentially act as metal binding sites. Moreover, Cys291 and Cys322 in R2 and R3, respectively, might have an important role in protein aggregation, through possible disulfide bond formation, and/or affecting the binding and reactivity of redox-active metal ions, as copper. We, therefore, compare the interaction of copper with octadeca-R3-peptide (R3C) and with the mutant containing an alanine residue (R3A) to assess the role of thiol group. Spectrophotometric titrations allow to calculate the formation constant of the copper(I) complexes, showing a remarkable stronger interaction in the case of R3C (log K-f = 13.4 and 10.5 for copper(I)-R3C and copper(I)-R3A, respectively). We also evaluate the oxidative reactivity associated to these copper complexes in the presence of dopamine and ascorbate. Both R3A and R3C peptides increase the capability of copper to oxidize catechols, but copper-R3C displays a peculiar mechanism due to the presence of cysteine. HPLC-MS analysis shows that cysteine can form disulfide bonds and dopamine-Cys covalent adducts, with potential implication in tau aggregation process

DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function

Parkinson's disease is a neurodegenerative disorder characterized by the death of dopaminergic neurons and by accumulation of alpha-synuclein (aS) aggregates in the surviving neurons. The dopamine catabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is a highly reactive and toxic molecule that leads to aS oligomerization by covalent modifications to lysine residues. Here we show that DOPAL-induced aS oligomer formation in neurons is associated with damage of synaptic vesicles, and with alterations in the synaptic vesicles pools. To investigate the molecular mechanism that leads to synaptic impairment, we first aimed to characterize the biochemical and biophysical properties of the aS-DOPAL oligomers; heterogeneous ensembles of macromolecules able to permeabilise cholesterol-containing lipid membranes. aS-DOPAL oligomers can induce dopamine leak in an in vitro model of synaptic vesicles and in cellular models. The dopamine released, after conversion to DOPAL in the cytoplasm, could trigger a noxious cycle that further fuels the formation of aS-DOPAL oligomers, inducing neurodegeneration