An input-output hydro-economic model to assess the economic pressure on water resources

This study develops a hydroeconomic input-output (IO) model to evaluate the pressures that economic activities exert on water resources. For a better understanding of the sectoral and total impacts, three innovations are incorporated with respect to previous literature: i) the development of a methodology for disaggregating the extended water demand (blue water plus grey water) by economic sector, ii) the use of the IO side of the model to reclassify water demand by “extracting” and “demanding” sectors, and iii) the proposition of an improved indicator of pressure on water resources based on a “feasible” measure of water supply. Empirically tested in the Tuscany region (Italy), our findings reveal significant changes in the structure of economic pressures when adopting the proposed approach. When assessing direct total water withdrawals, agriculture accounts for 61% and manufacture for 20% of regional pressures. However, when considering only the demand for water resources exposed to scarcity reclassified by demanding sectors, agriculture falls to 5% and manufacture rises to 54%. By incorporating grey water in water demand and a “feasible” measure of supply, the regional water exploitation indicator increases from 0.05 to 0.19, and can even reach 0.30 with dry hydrological conditions, beyond the threshold for moderate scarcity (0.20). The unbalance between water supply and demand worsen even more when considering the balance of surface waters only (1.16). The proposed model can support an in-depth analysis of an economy’s water footprint, allowing impacts to be mapped from specific industries to particular water bodies. This information can support decisions about sustainable water management at the national and regional levels

Low energy electron-phonon effective action from symmetry analysis

Based on a detailed symmetry analysis, we state the general rules to build up the effective low energy field theory describing a system of electrons weakly interacting with the lattice degrees of freedom. The basic elements in our construction are what we call the "memory tensors", that keep track of the microscopic discrete symmetries into the coarse-grained action. The present approach can be applied to lattice systems in arbitrary dimensions and in a systematic way to any desired order in derivatives. We apply the method to the honeycomb lattice and re-obtain the by now well-known effective action of Dirac fermions coupled to fictitious gauge fields. As a second example, we derive the effective action for electrons in the kagom\'e lattice, where our approach allows to obtain in a simple way the low energy electron-phonon coupling terms.Comment: 18 pages, one figur

High Sensitivity of Human Translesion DNA Synthesis Polymerase κ to Variation in O6-Carboxymethylguanine Structures

Carboxymethylation of DNA, including the formation of the DNA adduct O6-carboxymethylguanine (O6-CMG), is associated with lifestyle factors, such as diet. It can impede replicative polymerases (Pols) and lead to replication fork stalling, or an alternative means for replication to proceed by translesion DNA synthesis (TLS). TLS requires specialized DNA Pols characterized by open and preformed active sites capable of preferential bypass of alkylated DNA adducts but that have high error rates, leading to mutations. Human TLS Pols can bypass O6-CMG with varying degrees of accuracy, but it is not known how the chemical structure of the O6-CMG adduct influences polymerase proficiency or fidelity. To better understand how adduct structure determines dNTP selection at lesion sites, we prepared DNA templates with a series of O6-CMG structural analogs and compared the primer extension patterns of Y- and X-family Pols in response to these modifications. The results indicate that the structure of the DNA adduct had a striking effect on dNTP selection by Pol κ and that an increased steric size influences the fidelity of Pol η, whereas Pol ι and β function were only marginally affected. To test the hypothesis that specific hydrogen bonding interactions between the templating base and the incoming dNTP are a basis of this selection, we modeled the structural analogs with incoming dNTP in the Pol κ active site. These data indicate that the base pairing geometry and stabilization by a dense hydrogen bonding network are important molecular features for dNTP incorporation, providing a basis for understanding error-free bypass of O6-CMG by Pol κ

Case report: Personalized transcatheter approach to mid-aortic syndrome by in vitro simulation on a 3-dimensional printed model

An 8-year-old girl, diagnosed with mid-aortic syndrome (MAS) at the age of 2 months and under antihypertensive therapy, presented with severe systemic hypertension (>200/120 mmHg). Computed tomography (CT) examination revealed aortic aneurysm between severe stenoses at pre- and infra-renal segments, and occlusion of principal splanchnic arteries with peripheral collateral revascularization. Based on CT imaging, preoperative three-dimensional (3D) anatomy was reconstructed to assess aortic dimensions and a dedicated in vitro planning platform was designed to investigate the feasibility of a stenting procedure under fluoroscopic guidance. The in vitro system was designed to incorporate a translucent flexible 3D-printed patient-specific model filled with saline. A covered 8-zig 45-mm-long Cheatham-Platinum (CP) stent and a bare 8-zig, 34-mm-long CP stent were implanted with partial overlap to treat the stenoses (global peak-to-peak pressure gradient > 60 mmHg), excluding the aneurysm and avoiding risk of renal arteries occlusion. Percutaneous procedure was successfully performed with no residual pressure gradient and exactly replicating the strategy tested in vitro. Also, as investigated on the 3D-printed model, additional angioplasty was feasible across the frames of the stent to improve bilateral renal flow. Postoperative systemic pressure significantly reduced (130/70 mmHg) as well as dosage of antihypertensive therapy. This is the first report demonstrating the use of a 3D-printed model to effectively plan percutaneous intervention in a complex pediatric MAS case: taking full advantage of the combined use of a patient-specific 3D model and a dedicated in vitro platform, feasibility of the stenting procedure was successfully tested during pre-procedural assessment. Hence, use of patient-specific 3D-printed models and in vitro dedicated platforms is encouraged to assist pre-procedural planning and personalize treatment, thus enhancing intervention success

Novel effects of strains in graphene and other two dimensional materials

The analysis of the electronic properties of strained or lattice deformed graphene combines ideas from classical condensed matter physics, soft matter, and geometrical aspects of quantum field theory (QFT) in curved spaces. Recent theoretical and experimental work shows the influence of strains in many properties of graphene not considered before, such as electronic transport, spin-orbit coupling, the formation of Moir\'e patterns, optics, ... There is also significant evidence of anharmonic effects, which can modify the structural properties of graphene. These phenomena are not restricted to graphene, and they are being intensively studied in other two dimensional materials, such as the metallic dichalcogenides. We review here recent developments related to the role of strains in the structural and electronic properties of graphene and other two dimensional compounds.Comment: 75 pages, 15 figures, review articl

LANCL1 binds abscisic acid and stimulates glucose transport and mitochondrial respiration in muscle cells via the AMPK/PGC-1α/Sirt1 pathway

Objective: Abscisic acid (ABA) is a plant hormone also present and active in animals. In mammals, ABA regulates blood glucose levels by stimulating insulin-independent glucose uptake and metabolism in adipocytes and myocytes through its receptor LANCL2. The objective of this study was to investigate whether another member of the LANCL protein family, LANCL1, also behaves as an ABA receptor and, if so, which functional effects are mediated by LANCL1. Methods: ABA binding to human recombinant LANCL1 was explored by equilibrium-binding experiments with [3H]ABA, circular dichroism, and surface plasmon resonance. Rat L6 myoblasts overexpressing either LANCL1 or LANCL2, or silenced for the expression of both proteins, were used to investigate the basal and ABA-stimulated transport of a fluorescent glucose analog (NBDG) and the signaling pathway downstream of the LANCL proteins using Western blot and qPCR analysis. Finally, glucose tolerance and sensitivity to ABA were compared in LANCL2−/− and wild-type (WT) siblings. Results: Human recombinant LANCL1 binds ABA with a Kd between 1 and 10 μM, depending on the assay (i.e., in a concentration range that lies between the low and high-affinity ABA binding sites of LANCL2). In L6 myoblasts, LANCL1 and LANCL2 similarly, i) stimulate both basal and ABA-triggered NBDG uptake (4-fold), ii) activate the transcription and protein expression of the glucose transporters GLUT4 and GLUT1 (4-6-fold) and the signaling proteins AMPK/PGC-1α/Sirt1 (2-fold), iii) stimulate mitochondrial respiration (5-fold) and the expression of the skeletal muscle (SM) uncoupling proteins sarcolipin (3-fold) and UCP3 (12-fold). LANCL2−/− mice have a reduced glucose tolerance compared to WT. They spontaneously overexpress LANCL1 in the SM and respond to chronic ABA treatment (1 μg/kg body weight/day) with an improved glycemia response to glucose load and an increased SM transcription of GLUT4 and GLUT1 (20-fold) of the AMPK/PGC-1α/Sirt1 pathway and sarcolipin, UCP3, and NAMPT (4- to 6-fold). Conclusions: LANCL1 behaves as an ABA receptor with a somewhat lower affinity for ABA than LANCL2 but with overlapping effector functions: stimulating glucose uptake and the expression of muscle glucose transporters and mitochondrial uncoupling and respiration via the AMPK/PGC-1α/Sirt1 pathway. Receptor redundancy may have been advantageous in animal evolution, given the role of the ABA/LANCL system in the insulin-independent stimulation of cell glucose uptake and energy metabolism

Bypass of mutagenic O 6 -Carboxymethylguanine DNA Adducts by Human Y- and B-Family Polymerases

The generation of chemical alkylating agents from nitrosation of glycine and bile acid conjugates in the gastrointestinal tract is hypothesized to initiate carcinogenesis. O6-carboxymethylguanine (O6-CMG) is a product of DNA alkylation derived from nitrosated glycine. Although the tendency of the structurally related adduct O6-methylguanine to code for the misincoporation of TTP during DNA replication is well-established, the impact of the presence of the O6-CMG adduct in a DNA template on the efficiency and fidelity of translesion DNA synthesis (TLS) by human DNA polymerases (Pols) has hitherto not been described. Herein, we characterize the ability of the four human TLS Pols η, ι, κ, and ζ and the replicative Pol δ to bypass O6-CMG in a prevalent mutational hot-spot for colon cancer. The results indicate that Pol η replicates past O6-CMG, incorporating dCMP or dAMP, whereas Pol κ incorporates dCMP only, and Pol ι incorporates primarily dTMP. Additionally, the subsequent extension step was carried out with high efficiency by TLS Pols η, κ, and ζ, while Pol ι was unable to extend from a terminal mismatch. These results provide a first basis of O6-CMG-promoted base misincorporation by Y- and B-family polymerases potentially leading to mutational signatures associated with colon cancer

Association Between Colchicine Treatment and Clinical Outcomes in Patients with Coronary Artery Disease: Systematic Review and Meta-analysis

Background: The authors examined the association between colchicine treatment and clinical outcomes in patients with coronary artery disease. Methods: They performed a meta-analysis of randomised controlled trials (RCTs) involving patients with coronary artery disease receiving add-on colchicine to standard treatment compared with standard treatment. They used a mixed-effects Poisson regression model with random intervention effects to estimate the pooled incidence rate ratios (IRR) with 95% CI. Results: Ten RCTs were identified, including 12,819 participants followed up for a median of 6 months. Colchicine was associated with a lower risk of major adverse cardiovascular events (IRR 0.69; 95% CI [0.60–0.79]; number needed to treat for an additional beneficial outcome [NNTB] = 28); MI (IRR 0.77; 95% CI [0.64–0.93]; NNTB = 95) and ischaemic stroke (IRR 0.48; 95% CI [0.30–0.76]; NNTB = 155) and with a higher risk of gastrointestinal adverse events (IRR 1.69; 95% CI [1.12–2.54]; number needed to treat for an additional harmful outcome [NNTH] = 10). Colchicine did not affect all-cause death (IRR 1.09; 95% CI [0.85–1.40]), or cardiovascular death (IRR 0.75; 95% CI [0.51–1.12]), while it was associated with a higher risk of non-cardiovascular death (IRR 1.45; 95% CI [1.04–2.02]; NNTH = 396). Conclusion: The meta-analysis showed that the relative and absolute beneficial treatment effects of colchicine on cardiovascular outcomes outweigh the potential harm for non-cardiovascular mortality. Registration: PROSPERO 2021 CRD42021248874

Fluid-structure interaction simulation of prosthetic aortic valves : comparison between immersed boundary and arbitrary Lagrangian-Eulerian techniques for the mesh representation

In recent years the role of FSI (fluid-structure interaction) simulations in the analysis of the fluid-mechanics of heart valves is becoming more and more important, being able to capture the interaction between the blood and both the surrounding biological tissues and the valve itself. When setting up an FSI simulation, several choices have to be made to select the most suitable approach for the case of interest: in particular, to simulate flexible leaflet cardiac valves, the type of discretization of the fluid domain is crucial, which can be described with an ALE (Arbitrary Lagrangian-Eulerian) or an Eulerian formulation. The majority of the reported 3D heart valve FSI simulations are performed with the Eulerian formulation, allowing for large deformations of the domains without compromising the quality of the fluid grid. Nevertheless, it is known that the ALE-FSI approach guarantees more accurate results at the interface between the solid and the fluid. The goal of this paper is to describe the same aortic valve model in the two cases, comparing the performances of an ALE-based FSI solution and an Eulerian-based FSI approach. After a first simplified 2D case, the aortic geometry was considered in a full 3D set-up. The model was kept as similar as possible in the two settings, to better compare the simulations' outcomes. Although for the 2D case the differences were unsubstantial, in our experience the performance of a full 3D ALE-FSI simulation was significantly limited by the technical problems and requirements inherent to the ALE formulation, mainly related to the mesh motion and deformation of the fluid domain. As a secondary outcome of this work, it is important to point out that the choice of the solver also influenced the reliability of the final results