Resolvent Analysis: With or Without Eddy Viscosity?

International audienceIn this study, estimations of the spatio-temporal power cross-spectral density based on the resolvent operator are compared to those obtained by direct numerical simulation (DNS) in the turbulent plane channel flow at Re τ = 1007 by analysing separately the contribution of each temporal frequency ω. The comparison is performed for spatial scales characteristic of buffer-layer and large-scale motions. Good agreement between the resolvent-based estimates and the statistics obtained by DNS is found when the resolvent operator is based on a linear model which includes the effect of an eddy-viscosity modelling the effect of turbulent Reynolds stresses. The agreement is further improved when a colored noise matching the measures is used instead of white noise in the forcing modelling. Such a good agreement is not observed when the eddy-viscosity terms are not included in the linear model. In this case, the estimation based on the resolvent is unable to select the right peak frequency and wall-normal location of buffer-layer motions

Recurrence Analysis of Vegetation Indices for Highlighting the Ecosystem Response to Drought Events: An Application to the Amazon Forest

Forests are important in sequestering CO2 and therefore play a significant role in climate change. However, the CO2 cycle is conditioned by drought events that alter the rate of photosynthesis, which is the principal physiological action of plants in transforming CO2 into biological energy. This study applied recurrence quantification analysis (RQA) to describe the evolution of photosynthesis-related indices to highlight disturbance alterations produced by the Atlantic Multidecadal Oscillation (AMO, years 2005 and 2010) and the El Niño-Southern Oscillation (ENSO, year 2015) in the Amazon forest. The analysis was carried out using Moderate Resolution Imaging Spectroradiometer (MODIS) images to build time series of the enhanced vegetation index (EVI), the normalized difference water index (NDWI), and the land surface temperature (LST) covering the period 2001–2018. The results did not show significant variations produced by AMO throughout the study area, while a disruption due to the global warming phase linked to the extreme ENSO event occurred, and the forest was able to recover. In addition, spatial differences in the response of the forest to the ENSO event were found. These findings show that the application of RQA to the time series of vegetation indices supports the evaluation of the forest ecosystem response to disruptive events. This approach provides information on the capacity of the forest to recover after a disruptive event and, therefore is useful to estimate the resilience of this particular ecosystem

Inquinamento microbiologico delle sale operatorie: analisi critica di due decenni di sorveglianza

Obiettivo dello studio è stato quello di analizzare i risultati delle campagne di monitoraggio microbiologico delle sale operatorie effettuate negli ultimi due decenni presso il Policlinico di Roma, al fine di descrivere l’andamento nel tempo dei livelli di contaminazione riscontrati e di valutare eventuali cambiamenti significativi. Sono stati presi in esame i campionamenti microbiologici dell’aria effettuati all’interno di 14 blocchi operatori tra il 1992 ed il 2010. I risultati dei campionamenti sono stati aggregati in quattro periodi di tempo (1992-1996; 1996-2000; 2001-2005; 2006-2010) ed è stato analizzata la distribuzione nel tempo dei risultati dei campionamenti rispetto al limite proposto all'ISPESL per le sale at-rest (≤35 UFC/mc). La stessa analisi è stata ripetuta dopo la stratificazione per livello di rischio delle sale operatorie (AR e BR). Al fine di verificare il livello di significatività delle variazioni temporali nelle distribuzioni dei risultati si è fatto ricorso al test del x2 per il trend. Si è osservato un significativo trend in diminuzione del numero di sale con livelli di contaminazione superiori a quello indicato (x2 per trend=8,94; p<0,025). Tale riduzione ha riguardato soprattutto le sale operatorie AR (x2 per trend=7,33; p<0,05). I risultati ottenuti fanno ritenere che le misure adottate nelle sale ad AR siano risultate efficaci. Una maggiore attenzione dovrà essere posta alle sale operatorie a BR

Nanoscale Assembly of Functional Peptides with Divergent Programming Elements

Self-assembling peptides are being applied both in the biomedical area and as building blocks in nanotechnology. Their applications are closely linked to their modes of self-assembly, which determine the functional nanostructures that they form. This work brings together two structural elements that direct nanoscale self-association in divergent directions: proline as a β-breaker and the β-structure-associated diphenylalanine motif, into a single tripeptide sequence. Amino acid chirality was found to resolve the tension inherent to these conflicting self-assembly instructions. Stereoconfiguration determined the ability of each of the eight possible Pro-Phe-Phe stereoisomers to self-associate into diverse nanostructures, including nanoparticles, nanotapes, or fibrils, which yielded hydrogels with gel-to-sol transition at a physiologically relevant temperature. Three single-crystal structures and all-atom molecular dynamics simulations elucidated the ability of each peptide to establish key interactions to form long-range assemblies (i,e., stacks leading to gelling fibrils), medium-range assemblies (i.e., stacks yielding nanotapes), or short-range assemblies (i.e., dimers or trimers that further associated into nanoparticles). Importantly, diphenylalanine is known to serve as a binding site for pathological amyloids, potentially allowing these heterochiral systems to influence the fibrillization of other biologically relevant peptides. To probe this hypothesis, all eight Pro-Phe-Phe stereoisomers were tested in vitro on the Alzheimer's disease-associated Aβ(1-42) peptide. Indeed, one nonfibril-forming stereoisomer effectively inhibited Aβ fibrillization through multivalent binding between diphenylalanine motifs. This work thus defined heterochirality as a useful feature to strategically develop future therapeutics to interfere with pathological processes, with the additional value of resistance to protease-mediated degradation and biocompatibility

Heterochirality and Halogenation Control Phe-Phe Hierarchical Assembly

Diphenylalanine is an amyloidogenic building block that can form a versatile array of supramolecular materials. Its shortcomings, however, include the uncontrolled hierarchical assembly into microtubes of heterogeneous size distribution and well-known cytotoxicity. This study rationalized heterochirality as a successful strategy to address both of these pitfalls and it provided an unprotected heterochiral dipeptide that self-organized into a homogeneous and optically clear hydrogel with excellent ability to sustain fibroblast cell proliferation and viability. Substitution of one l-amino acid with its d-enantiomer preserved the ability of the dipeptide to self-organize into nanotubes, as shown by single-crystal XRD analysis, whereby the pattern of electrostatic and hydrogen bonding interactions of the backbone was unaltered. The effect of heterochirality was manifested in subtle changes in the positioning of the aromatic side chains, which resulted in weaker intermolecular interactions between nanotubes. As a result, d-Phe-l-Phe self-organized into homogeneous nanofibrils with a diameter of 4 nm, corresponding to two layers of peptides around a water channel, and yielded a transparent hydrogel. In contrast with homochiral Phe-Phe stereoisomer, it formed stable hydrogels thermoreversibly. d-Phe-l-Phe displayed no amyloid toxicity in cell cultures with fibroblast cells proliferating in high numbers and viability on this biomaterial, marking it as a preferred substrate over tissue-culture plastic. Halogenation also enabled the tailoring of d-Phe-l-Phe self-organization. Fluorination allowed analogous supramolecular packing as confirmed by XRD, thus nanotube formation, and gave intermediate levels of bundling. In contrast, iodination was the most effective strategy to augment the stability of the resulting hydrogel, although at the expense of optical transparency and biocompatibility. Interestingly, iodine presence hindered the supramolecular packing into nanotubes, resulting instead into amphipathic layers of stacked peptides without the occurrence of halogen bonding. By unravelling fine details to control these materials at the meso- A nd macro-scale, this study significantly advanced our understanding of these systems

Hospital admissions for hypertensive crisis in the Emergency Departments: a large multicenter Italian study

Epidemiological data on the impact of hypertensive crises (emergencies and urgencies) on referral to the Emergency Departments (EDs) are lacking, in spite of the evidence that they may be life-threatening conditions. We performed a multicenter study to identify all patients aged 18 years and over who were admitted to 10 Italian EDs during 2009 for hypertensive crises (systolic blood pressure ≥220 mmHg and/or diastolic blood pressure ≥120 mmHg). We classified patients as affected by either hypertensive emergencies or hypertensive urgencies depending on the presence or the absence of progressive target organ damage, respectively. Logistic regression analysis was then performed to assess variables independently associated with hypertensive emergencies with respect to hypertensive urgencies. Of 333,407 patients admitted to the EDs over the one-year period, 1,546 had hypertensive crises (4.6/1,000, 95% CI 4.4-4.9), and 23% of them had unknown hypertension. Hypertensive emergencies (n = 391, 25.3% of hypertensive crises) were acute pulmonary edema (30.9%), stroke (22.0%,), myocardial infarction (17.9%), acute aortic dissection (7.9%), acute renal failure (5.9%) and hypertensive encephalopathy (4.9%). Men had higher frequency than women of unknown hypertension (27.9% vs 18.5%, p<0.001). Even among known hypertensive patients, a larger proportion of men than women reported not taking anti-hypertensive drug (12.6% among men and 9.4% among women (p<0.001). Compared to women of similar age, men had higher likelihood of having hypertensive emergencies than urgencies (OR = 1.34, 95% CI 1.06-1.70), independently of presenting symptoms, creatinine, smoking habit and known hypertension. This study shows that hypertensive crises involved almost 5 out of 1,000 patients-year admitted to EDs. Sex differences in frequencies of unknown hypertension, compliance to treatment and risk of hypertensive emergencies might have implications for public health programs

Severe hematopoietic stem cell inflammation compromises chronic granulomatous disease gene therapy

X-linked chronic granulomatous disease (CGD) is associated with defective phagocytosis, life-threatening infections, and inflammatory complications. We performed a clinical trial of lentivirus-based gene therapy in four patients (NCT02757911). Two patients show stable engraftment and clinical benefits, whereas the other two have progressively lost gene-corrected cells. Single-cell transcriptomic analysis reveals a significantly lower frequency of hematopoietic stem cells (HSCs) in CGD patients, especially in the two patients with defective engraftment. These two present a profound change in HSC status, a high interferon score, and elevated myeloid progenitor frequency. We use elastic-net logistic regression to identify a set of 51 interferon genes and transcription factors that predict the failure of HSC engraftment. In one patient, an aberrant HSC state with elevated CEBPβ expression drives HSC exhaustion, as demonstrated by low repopulation in a xenotransplantation model. Targeted treatments to protect HSCs, coupled to targeted gene expression screening, might improve clinical outcomes in CGD

Changes in hemostasis parameters in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia complicated by endocarditis or thromboembolic events : a prospective gender-age adjusted cohort study

The aim of this study was to examine the changes in hemostasis parameters in endocarditis and thromboembolic events in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia (MS-SAB) - a topic not evaluated previously. In total, 155 patients were recruited and were categorized according to the presence of endocarditis or thromboembolic events with gender-age adjusted controls. Patients who deceased within 90 days or patients not chosen as controls were excluded. SAB management was supervised by an infectious disease specialist. Patients with endocarditis (N = 21), compared to controls (N = 21), presented lower antithrombin III at day 4 (p <0.05), elevated antithrombin III at day 90 (p <0.01), prolonged activated partial thromboplastin time at days 4 and 10 (p <0.05), and enhanced thrombin-antithrombin complex at day 4 (p <0.01). Thromboembolic events (N = 8), compared to controls (N = 34), significantly increased thrombin-antithrombin complex at day 4 (p <0.05). In receiver operating characteristic analysis, the changes in these hemostasis parameters at day 4 predicted endocarditis and thromboembolic events (p <0.05). No differences in hemoglobin, thrombocyte, prothrombin fragment, thrombin time, factor VIII, D-dimer or fibrinogen levels were observed between cases and controls. The results suggest that nonfatal MS-SAB patients present marginal hemostasis parameter changes that, however, may have predictability for endocarditis or thromboembolic events. Larger studies are needed to further assess the connection of hemostasis to complications in SAB.Peer reviewe

Sotatercept, a novel transforming growth factor beta ligand trap, improves anemia in beta-thalassemia: a phase 2, open-label, dose-finding study

\u3b2-thalassemia, a hereditary blood disorder caused by defective synthesis of hemoglobin \u3b2 globin chains, leads to ineffective erythropoiesis and chronic anemia that may require blood transfusions. Sotatercept (ACE-011) acts as a ligand trap to inhibit negative regulators of late-stage erythropoiesis in the transforming growth factor beta superfamily, correcting ineffective erythropoiesis. In this phase II, open-label, dose-finding study, 16 patients with transfusion-dependent \u3b2-thalassemia and 30 patients with non-transfusion-dependent \u3b2 thalassemia were enrolled at 7 centers in 4 countries from November 2012 to November 2014. Patients were treated with sotatercept at 0.1, 0.3, 0.5, 0.75, or 1.0 mg/kg to determine a safe and effective dose. Doses were administered by subcutaneous injection every 3 weeks. Patients were treated for 6422 months. Response was assessed as a 6520% reduction in transfusion burden sustained for 24 weeks in transfusion-dependent \u3b2-thalassemia patients, and an increase in hemoglobin level of 651.0 g/dL sustained for 12 weeks in non-transfusion-dependent \u3b2-thalassemia patients. Sotatercept was well tolerated. After a median treatment duration of 14.4 months (range 0.6-35.9), no severe life-threatening adverse events were observed; 13% of patients reported serious but manageable adverse events. The active dose of sotatercept was 650.3 mg/kg for non-transfusion-dependent \u3b2-thalassemia and 650.5 mg/kg for transfusion-dependent \u3b2-thalassemia patients. Of 30 non-transfusion-dependent \u3b2-thalassemia patients treated with 650.1 mg/kg sotatercept, 18 (60%) achieved a mean hemoglobin increase 651.0 g/dL, and 11 (37%) an increase 651.5 g/dL, sustained for 6512 weeks. Four (100%) transfusion-dependent \u3b2-thalassemia patients treated with 1.0 mg/kg sotatercept achieved a transfusion-burden reduction of 6520%. Sotatercept was effective and well tolerated in patients with \u3b2-thalassemia. Most non-transfusion-dependent \u3b2-thalassemia patients treated with higher doses achieved sustained increases in hemoglobin level. Transfusion-dependent \u3b2-thalassemia patients treated with higher doses of sotatercept achieved notable reductions in transfusion requirement. The registration number at ClinicalTrials.gov was NCT01571635

All-Photonic Multifunctional Molecular Logic Device

Photochromes are photoswitchable, bistable chromophores which, like transistors, can implement binary logic operations. When several photochromes are combined in one molecule, interactions between them such as energy and electron transfer allow design of simple Boolean logic gates and more complex logic devices with all-photonic inputs and outputs. Selective isomerization of individual photochromes can be achieved using light of different wavelengths, and logic outputs can employ absorption and emission properties at different wavelengths, thus allowing a single molecular species to perform several different functions, even simultaneously. Here, we report a molecule consisting of three linked photochromes that can be configured as AND, XOR, INH, half-adder, half-subtractor, multiplexer, demultiplexer, encoder, decoder, keypad lock, and logically reversible transfer gate logic devices, all with a common initial state. The system demonstrates the advantages of light-responsive molecules as multifunctional, reconfigurable nanoscale logic devices that represent an approach to true molecular information processing units