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Using first-principle numerical simulations, we find a new spatially inhomogeneous phase in rigidly rotating Nc=3 gluon plasma. This mixed phase simultaneously possesses both confining and deconfining phases in thermal equilibrium. Unexpectedly, the local critical temperature of the phase transition at the rotation axis does not depend on the angular frequency within a few percent accuracy. Even more surprisingly, an analytic continuation of our results to the domain of real angular frequencies indicates a profound breaking of the Tolman-Ehrenfest law in the vicinity of the phase transition, with the confining (deconfining) phase appearing far (near) the rotation axis.

A new derivatization reagent, phthalylglycyl chloride (PG-Cl), for the analysis of urinary amino acids was demonstrated using reversed-phase ultra-high performance liquid chromatography coupled to electrospray ionization-quadrupole-time-of-flight mass spectrometer. The study compares the limits of detection and quantification for different sample preparation techniques with the commonly used and effective method of derivatization using dansyl chloride. The stability of the derivatives was investigated, and the study includes an example of urinary amino acid analysis using PG-Cl derivatization. The optimal values for pH, temperature, and concentration of the derivatization reagent were established. Limits of quantification in the range of 0.5–500 µg/mL were obtained for different amino acids. The possibility of phthalylglycyl chloride usage for non-target screening applications and targeted analysis of amino acids in urine was discussed. An advantages and issues of PG-Cl in comparison with commonly used acyl-chlorides (FMOC-Cl and DNS-Cl) provided and discussed.

Using first-principle numerical simulations of the lattice SU(3) gauge theory, we calculate the isothermal moment of inertia of the rigidly rotating gluon plasma. We find that the moment of inertia unexpectedly takes a negative value below the “supervortical temperature” Ts=1.50(10)Tc, vanishes at T=Ts, and becomes a positive quantity at higher temperatures. The negative moment of inertia indicates a thermodynamic instability of rigid rotation. We derive the condition of thermodynamic stability of the vortical plasma and show how it relates to the scale anomaly and the magnetic gluon condensate. The rotational instability of gluon plasma shares a striking similarity with the rotational instabilities of spinning Kerr and Myers-Perry black holes.

This work presents a new approach to enhance EMI shielding efficiency of nanocomposites of dielectric polymers, multiwalled carbon nanotubes (MWCNTs) and intrinsically conducting polymers for account of using core-shell morphology for conducting components. To realize this approach new ternary nanocomposites of poly(vinylidene fluoride) (PVDF), MWCNTs and poly(3-methylthiophene) doped by Cl− anions (P3MT) were prepared through synthesis of thermally stable core/shell nanocomposites PVDF/P3MT and MWCNT/P3MT. These binary nanocomposites were mixed with pure MWCNTs or PVDF followed by compression molding to prepare the ternary nanocomposites of different morphology to discriminate their EMI shielding properties in a wide frequency range (1–67 GHz). Values of the tangent of dielectric loss angle, the efficiency of transmission, reflection and absorption of microwave radiation, and shielding efficiency (SE) of the specified materials were found from analysis of spectral dependences of their complex dielectric constants. It was shown that while the melt mixing of the binary PVDF/P3MT nanocomposite with MWCNTs both in a pure state and in the binary nanocomposite (MWCNT/P3MT) expectedly strongly enhances SE of the former, this effect is non-linear and depends on presence/absence of the P3MT shell on the MWCNT core. The ternary nanocomposite PVDF/P3MT/MWCNT made of the binary polymer-polymer nanocomposite PVDF/P3MT and pure MWCNTs showed highest SE values at the frequencies above 4.5 GHz up to 68.4 dB at 67 GHz in the case of the 1 mm thickness sample. However, below 4.5 GHz the SE was higher in the case of the ternary nanocomposites containing core/shell MWCNT/P3MT nanocomposite instead of pure MWCNT.

The supersymmetry (SUSY) breaking mechanism inevitably predicts the existence of the sgoldstinos, which can play the role of wave-like dark matter. Due to the ubiquitous coupling to the electromagnetic fields, the light scalar sgoldstino dark matter can lead to the variance of the fine-structure constant. With the precise atomic clock data, we find the SUSY breaking scale F can be probed up to the GUT scale in the sgoldstino mass range of 10−22 eV

The electrochemical conversion of biobased levulinic acid (LA) into renewable chemicals and biofuel precursors represents an important and reasonable alternative to the high temperature conventional catalytic processes of great importance for the development of a sustainable and cost-effective biorefinery. The establishment of the mechanism of levulinic acid reduction is a promising strategy in choosing the optimal electrocatalyst for the redox-transformation of biobased substrates. Herein, we report a new approach to study an electrochemical reduction mechanism of levulinic acid using of proton-deficient non-aqueous reaction media. The electrochemical reduction of levulinic acid to γ-valerolactone (GVL) and valeric acid (VA) in aqueous and organic solutions on various electrodes (glassy carbon, graphite, Al, Pb) was studied. The mechanism of LA electrochemical reduction and major reaction products significantly was found to depend on the solvent, the presence of proton donors, the material of cathode, and the magnitude of the applied potential. In an aqueous solution the process proceeded with the formation of valeric acid on all the electrodes studied. In acetonitrile in the presence of protons, the electrochemical reduction of LA proceeded by various mechanisms, both with the participation of atomic hydrogen and the protonated form of LA, and led to the formation of GVL and/or VA. The difference (ΔE1/2) between the reduction half-wave potential of protons and levulinic acid was found to play an important role in the reduction pathway of LA carbonyl group. At a large ΔE1/2, as in the case of the GC electrode, the LA reduction resulted in the GVL formation. LA can be completely reduced to VA by transferring four electrons due to the close reduction potentials of protons and LA (a low ΔE1/2), as on a Pb electrode. The pathway depends on the conditions of the reduction process and can be estimated based on electrochemical data obtained in the study of reaction products in organic media.

We report the case of a 46-year-old patient who, after renal cancer surgery, developed a recurrent urinary tract infection that lasted for more than 2 years. Despite repeated antibiotic courses, including broad-spectrum drugs chosen using conventional antibiotic susceptibility testing, multiple reinfections followed. The patient was successfully treated once antibiotics were selected with AtbFinder. Unlike routine antimicrobial susceptibility methods, which select antibiotics effective only against a “lead bacterial pathogen,” AtbFinder identifies antibiotics that target the mixture of bacteria at the infection site. This case demonstrates the ability of AtbFinder to successfully select antibiotics for the treatment of relapsing urinary tract infections.

Biological activity of monoaryl furazanopyrazines (FPs), known as high-energy molecules, is scarcely explored. A series of monoaryl FPs was synthesized by condensation of arylglyoxals with diaminofurazane. The targeted compounds at low micromolar concentrations inhibited growth of human cancer cells in NCI60 screen. Further evaluation using a sea urchin embryo model revealed that antiproliferative activity of monoaryl FPs could be associated with targeting tubulin and microtubule destabilization, systemic (nonspecific) toxicity, or both. Introduction of hydroxy group into pyrazine ring of monoaryl FPs yielded inactive molecules.

OncoboxPD (Oncobox pathway databank) available at https://open.oncobox.com is the collection of 51 672 uniformly processed human molecular pathways. Superposition of all pathways formed interactome graph of protein–protein interactions and metabolic reactions containing 361 654 interactions and 64 095 molecular participants. Pathways are uniformly classified by biological processes, and each pathway node is algorithmically functionally annotated by specific activator/repressor role. This enables online calculation of statistically supported pathway activation levels (PALs) with the built-in bioinformatic tool using custom RNA/protein expression profiles. Each pathway can be visualized as static or dynamic graph, where vertices are molecules participating in a pathway and edges are interactions or reactions between them. Differentially expressed nodes in a pathway can be visualized in two-color mode with user-defined color scale. For every comparison, OncoboxPD also generates a graph summarizing top up- and downregulated pathways.

ABSTRACT: The intensification of innovation processes in Russia is a challenging task that requires a continuous search for solutions to make possible the many required changes in economics. We consider the major factors needed to advance an innovative activity at all levels in the national economy to have a freely exchanged flow of innovative ideas between all actors involved. As practice shows, the currently existing models in the country to deal with open innovations are mostly based on a cluster development approach, which is still limited. The authors propose synergizing the cluster approach with an ecosystem innovation model, which should ensure an effective collaboration and an accelerated rate for the diffusion of innovations between various actors while involving various regions. The purpose of the study was to develop a conceptual model for implementing open proposals from participants in the innovation economy. The research methodology is based on numerous works in the field of open innovation theory, cluster and ecosystem approaches. The study utilizes empirical and dialectical methods of scientific knowledge. The methodological toolkit covers information processing with historical analysis, a literature review using the Russian Citation Index and Scopus databases, analysis and diagnostics of innovative activity in domestic regions, the comparison method, modeling and correlation analysis. We concluded that the interaction of participants in the Russian regions through implementing the cluster model is not sufficiently effective and requires the development of new methodological approaches. Therefore, we propose combining the cluster approach with the ecosystem innovation model, which should ensure an effective cooperation and accelerate the rate of innovation dissemination among various subjects involving several regions. To determine the approach’s efficiency, the proposed concept should be tested in one or more regions.

Icosahedral Al65Cu23Fe12 and decagonal Al73Cu11Cr16 quasicrystalline powders were synthesized by the mechanical alloying and subsequent annealing. Morphology evolution at mechanical alloying of Al-based powders was found to be determined by competition between cold welding and fracture mechanisms. Mechanical alloying results in formation of coarse agglomerates consisting of fine particles. The chemical binding between the polymer matrix and quasicrystals, destruction of agglomerated at extrusion, and the uniform distribution of quasicrystals over the polymer melt were provided by surface treatment of quasicrystalline particles with silanes. The highly filled (up to 60 wt%) ethylene-vinyl acetate/quasicrystals composites were obtained, and their rheological characteristics were studied. It was shown that the fluidity of the melt is retained at a high level providing uniform distribution of quasicrystalline particles over the polymer. Keywords: Quasicrystals, Ethylene-vinyl acetate, Silanes, Mechanical alloying, Extrusion

Fe90-xLaxZr10 (x = 1 and 2) rapidly quenched ribbons with thickness of about 15 μm were prepared by the melt-spinning method. X-ray diffraction analysis shows that the structure of the ribbons is mostly amorphous. The Curie temperature, TC, of the alloy considerably increased, from ∼262 K for x = 1 to ∼302 K for x = 2, with increasing La-concentration. The maximum magnetic entropy change, |ΔSm|max, of the alloy is about 1.1 J∙kg−1K−1 for a magnetic field change ΔH = 12 kOe. A quite large refrigerant capacity (RC ∼ 74 J∙kg−1 for ΔH = 12 kOe) near the room temperature region is obtained for the alloy. A thorough analysis on critical exponents around the ferromagnetic-paramagnetic phase transition, using the Arrott–Noakes plots and Kouvel–Fisher method, sheds light on the critical magnetic behavior and its association with the magnetocaloric effect in the Fe-La based alloys. Keywords: Magnetocaloric effect, Magnetic refrigerant, Critical parameter, Magnetic entropy change, Melt-spinning method

Mapping Asia Plants (MAP) is a comprehensive project that aims to build a detailed infrastructure for integrating Asian plant distribution data a global-scale array of knowledge for plant biodiversity conservation. Here, we provide a brief historical review of botanical research in Southwest Asia – an understudied botanical region with high conservation priority. Nineteen countries were included in this study (from west to east): Turkey, Cyprus, Palestine, Israel, Jordan, Saudi Arabia, Lebanon, Syria, Iraq, Georgia, Yemen, Armenia, Iran, Azerbaijan, Kuwait, Bahrain, Qatar, United Arab Emirates, and Oman. We reviewed 132 resources comprising 125 Floras and Checklists, of which we describe in some detail at least one of the most important Floras or Checklists for each country. Complete and published national Floras exist for 13 countries; three countries (Jordan, Israel and Bahrain) do not have a Flora but have annotated Checklists, and national Floras are at different stages of completion for Iran, Iraq and Georgia. Where present, online resources are also given for references. We found major gaps in species concepts and taxonomic classification systems, and that many up-to-date Flora revisions remained unresolved, i.e. taxon ranks and species concepts varied among different countries, different systems were adopted or followed in the taxonomic treatments in the Floras and Checklists, and some of the current Floras are out of date. Floras are the first necessary step for many fields, including evolutionary biology, ecology, biogeography, and systematics, as well as environmental research and conservation of biodiversity at national and international levels. Here, we provide the progress updates on the main published floristic works of Southwest Asia, which continue to serve as references for the Flora of Southwest Asia, and will be the foundation of the MAP project.

North Asia – the Asian part of Russia – is a vast territory that occupies 1/3 of Asia, or about 13 100 000 sq. km. Floristic exploration of North Asia was bolstered in the first half of the 18th century when the emperor Peter I the Great founded the Academy of Sciences (currently, the Russian Academy of Sciences). The first complete flora of the Russian Empire was published in the middle of the 19th century by C.F. von Ledebour, and a wealth of North Asian floristic data had accumulated by the beginning of the 20th century. Under the guidance of the Botanical Institute in Leningrad (St. Petersburg), the “Flora of the USSR” (1944–1964) was initiated to consolidate this vast body of floristic knowledge. Following this Flora, two modern interregional compendia (“Vascular Plants of the Soviet Far East” and “Flora of Siberia”) were published in the 1980s and 1990s, which serve as the taxonomic foundation for the newest regional floras and checklists of the last twenty years. According to our statistics, which are expansive but not comprehensive, there are at least 300 books devoted to the flora of different regions of North Asia. The newest “Checklist of the Flora of Asian Russia” published in 2012 listed 6961 species and subspecies of vascular plants. Here, we provide a short review of the main references on vascular flora within all 27 administrative regions of North Asia.

The study of the transformation of retail chain stores (RCS) due to the impact of digitalization on them is a new problem. The main part of modern scientific research is devoted to separate directions of digitalization and does not consider conceptual aspects of these processes. The purpose of this article is to fill the existing research gap through the development of a new system concept of the digitalization impact on RCS transformations. The study shows the need to clarify the understanding of RCS strategic transformation caused by the drivers of different digitalization processes, which are not well understood today and are not taken into account when developing digitalization strategies. This situation has an extremely negative effect on the quality of RCS development and its competitiveness. The article consistently examines insufficiently covered problems in scientific literature and offers a new conceptual approach to the impact of digitalization on companies with regard to RCS transformation. New digitalization trends and their drivers have a deep impact on RCS transformations. A new system model is needed that integrates superdrivers and the impact of digitalization on the RCS transformation. Causal and heuristic forecasts of prospects, trends and results of digitalization, including contradictory results of AI development are included. We used materials from large retail chains “Magnit”, “Perekrestok” and “M.Video-Eldorado Group”. The research methods used were system modelling, cause and effect links building and heuristic forecasting based on logical models. The main results will be useful for researchers, managers, entrepreneurs and students in developing a clear understanding of digitalization development and its impacts, in order to better work out digitalization strategies and for the development of new directions of scientific research.

The aerodynamic focusing in the coaxial nozzle and deposition on substrates of silver nanoparticles beams at the high subsonic speeds has been studied. The multi-spark discharge generator was used as a source of silver nanoparticles. We established that controlling the high-speed sheath flow allows to provide the minimization of the aerosol beam diameter for 4 times and printing of silver lines with width up to 60 μm using a nozzle 100 μm in outlet diameter. It was realized due to usage of high-speed beams of silver nanoparticle agglomerates, with the size of 25–110 nm, consisting of the primary particles with diameter of 5–10 nm. The agglomeration effect of aerosol nanoparticles plays a positive role providing particle deposition onto a substrate and substantially reducing diffusion broadening of an aerosol beam.

A method for determining the critical values of the flow speed and the flow constriction degree characteristic of the alignment of cylindrical nano-objects in a flowing suspension is proposed. Previously, the alignment process of cylindrical nano-objects in suspensions was investigated by using birefringence of the polarized light and the small-angle X-ray scattering. While both methods are suitable for measuring the alignment degree of cylindrical nano-objects in suspensions diluted down to low concentrations, they are restricted for the application to undiluted concentrated suspensions because of non-transparency and multiple scattering of X-rays. In addition, the use of the second method requires an expensive synchrotron equipment. We present a simple and faster method based on the direct ultrasound attenuation measurements of longitudinal viscosity of a suspension containing cylindrical nano-objects, which decreases monotonically, approaching its asymptotic value with increase in the flow speed and the flow constriction degree. The principle and advantages of the proposed method are as follows: • The cylindrical nano-objects align along an accelerated flow at overcritical values of the flow speed and the constriction degree. • The critical values correspond to the state of a suspension possessing viscosity close to the asymptotic value. • The method is applicable to undiluted concentrated suspensions, including opaque ones.

Background: Enzyme replacement therapy (ERT) with recombinant human α-galactosidase has been available for the treatment of Fabry disease since 2001 in Europe and 2003 in the USA. Treatment outcomes with ERT are dependent on baseline patient characteristics, and published data are derived from heterogeneous study populations. Methods: We conducted a comprehensive systematic literature review of all original articles on ERT in the treatment of Fabry disease published up until January 2017. This article presents the findings in adult male patients. Results: Clinical evidence for the efficacy of ERT in adult male patients was available from 166 publications including 36 clinical trial publications. ERT significantly decreases globotriaosylceramide levels in plasma, urine, and in different kidney, heart, and skin cell types, slows the decline in estimated glomerular filtration rate, and reduces/stabilizes left ventricular mass and cardiac wall thickness. ERT also improves nervous system, gastrointestinal, pain, and quality of life outcomes. Conclusions: ERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment. Keywords: Fabry disease, agalsidase alfa, agalsidase beta, systematic literature review, enzyme replacement therapy, adult male patients

The data presented in this article are related to the research article entitled “One of the possible mechanisms of amyloid fibrils formation based on the sizes of primary and secondary folding nuclei of Aβ40 and Aβ42” (Dovidchenko et al., 2016) [1]. Aβ peptide is one of the most intensively studied amyloidogenic peptides. Despite the huge number of articles devoted to studying different fragments of Aβ peptide there are only several papers with correct kinetics data, also there are a few papers with X-ray data, especially for Aβ42. Our data present X-ray diffraction patterns both for Aβ40 and Aβ42 as well for Tris–HCl and wax. Moreover, our data provide kinetics of amyloid formation by recombinant Аβ40 and synthetic Аβ42 peptides by using electron microscopy.

Proper control of DNA replication is essential to ensure faithful transmission of genetic material and prevent chromosomal aberrations that can drive cancer progression and developmental disorders. DNA replication is regulated primarily at the level of initiation and is under strict cell-cycle regulation. Importantly, DNA replication is highly influenced by developmental cues. In Drosophila, specific regions of the genome are repressed for DNA replication during differentiation by the SNF2 domain-containing protein SUUR through an unknown mechanism. We demonstrate that SUUR is recruited to active replication forks and mediates the repression of DNA replication by directly inhibiting replication fork progression instead of functioning as a replication fork barrier. Mass spectrometry identification of SUUR-associated proteins identified the replicative helicase member CDC45 as a SUUR-associated protein, supporting a role for SUUR directly at replication forks. Our results reveal that control of eukaryotic DNA copy number can occur through the inhibition of replication fork progression.

Epigenetic alterations, particularly in DNA methylation, are ubiquitous in cancer, yet the molecular origins and the consequences of these alterations are poorly understood. CTCF, a DNA-binding protein that regulates higher-order chromatin organization, is frequently altered by hemizygous deletion or mutation in human cancer. To date, a causal role for CTCF in cancer has not been established. Here, we show that Ctcf hemizygous knockout mice are markedly susceptible to spontaneous, radiation-, and chemically induced cancer in a broad range of tissues. Ctcf+/− tumors are characterized by increased aggressiveness, including invasion, metastatic dissemination, and mixed epithelial/mesenchymal differentiation. Molecular analysis of Ctcf+/− tumors indicates that Ctcf is haploinsufficient for tumor suppression. Tissues with hemizygous loss of CTCF exhibit increased variability in CpG methylation genome wide. These findings establish CTCF as a prominent tumor-suppressor gene and point to CTCF-mediated epigenetic stability as a major barrier to neoplastic progression.

Ultrasound attenuates when propagating through aqueous dispersions of carbon nanotubes. We established a significant difference in the ultrasound attenuation frequency spectra for the nanotubes oriented either along or across the ultrasound beam. This effect can be used for calculating geometrical and rheological properties of nanofiber materials dispersed in liquids. Keywords: Ultrasound attenuation, Carbon nanotubes, Nanofibers

This research aims to investigate and quantify potential damage resulting from induced superficial defects on the surface of wires use on tensile armor of flexible pipes. Different values of kt factors and H2S concentration in aggressive gas mixtures with CO2, were analysed to determine the operational conditions that do not result in rupture of the tensile reinforcement during service, under the conditions studied. The tests were based on NACE TM0316 standard, using a 4-point bend test. Two superficial notches were created, which generated known stress concentration factor Kt values of 1.5 and 2.0, and three gaseous concentrations (220, 700, and 1100 ppm of H2S in CO2) were used. After bending tests, the samples were evaluated by metallographic and fractographic analysis, weight loss and liquid penetrant inspection. The results were then analysed using analysis of variance (ANOVA). Only the samples exposed to 220 ppm of H2S in CO2 did not rupture at both Kt values. However, for the Kt value of 2.0, cracks were observed in the longitudinal direction of the wires, originating from the machined notch. Additionally, the samples exposed to 700 ppm and 1100 ppm of H2S had a significantly higher damage score (approximately 15x) than the samples exposed to 220 ppm, regardless of the Kt value.

Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

Within the adult mouse subventricular zone (SVZ), neural stem cells (NSCs) produce neuroblasts and oligodendrocyte precursor cells (OPCs). T3, the active thyroid hormone, influences renewal and commitment of SVZ progenitors. However, how regulators of T3 availability affect these processes is less understood. Using Mct8/Dio2 knockout mice, we investigated the role of MCT8, a TH transporter, and DIO2, the T3-generating enzyme, in regulating adult SVZ-neurogliogenesis. Single-cell RNA-Seq revealed Mct8 expression in various SVZ cell types in WT mice, while Dio2 was enriched in neurons, astrocytes, and quiescent NSCs. The absence of both regulators in the knockout model dysregulated gene expression, increased the neuroblast/OPC ratio and hindered OPC differentiation. Immunostainings demonstrated compromised neuroblast migration reducing their supply to the olfactory bulbs, impairing interneuron differentiation and odor discrimination. These findings underscore the pivotal roles of MCT8 and DIO2 in neuro- and oligodendrogenesis, offering targets for therapeutic avenues in neurodegenerative and demyelinating diseases.

The article introduces a novel weakly-partitioned numerical coupling method implemented to analyze the wind-induced response of low-damped structures incorporating a Tuned Liquid Damper (TLD). The proposed methodology integrates the meshless Vortex-Particle Method (VPM) for wind flow and Smoothed Particle Hydrodynamics (SPH) for liquid sloshing flow, along with a structural dynamics solver, to simulate the complex coupled interactions of wind-sensitive structures. The numerical coupling framework includes time domain simulation by solving dynamic equations of motion that integrate stepwise external forces to account for (i) the wind effect and (ii) the hydrodynamic forces resulting from the sloshing damper. The complexity of this coupling method lies in precisely updating the boundary conditions during each simulation step to accurately model the flow-induced forces and coupled structural response phenomena. The presented wind–structure–damper interaction framework is employed for a two-dimensional case by using a circular cross-section equipped with a TLD to mitigate wind-induced vibrations. Comparative numerical analyses are presented for both vortex-induced vibration response of a single dynamic structure and wake-buffeting response of downstream moving structure influenced by a nearby standing section. In both scenarios, a unidirectional sloshing damper is considered across the wind. The dynamic analyses reveal a noteworthy reduction in structural response when employing the TLD in both cases. The study aims to underscore the applicability of CFD models for TLD predesign, specifically in modeling nonlinear sloshing forces in response to nonlinear resonant wind behavior, as a viable alternative to large-scale experiments.

Frailty and sarcopenia are well-recognized factors related to worse outcomes in patients with cirrhosis, including liver transplant (LT) candidates. Implications of pre-LT functional and muscle deterioration also affect post-LT outcomes. Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have a lower survival rate, both before and after LT. There is a need to better identify those patients with ACLF who would benefit from LT. This review aims to present the available data about frailty and sarcopenia in patients with ACLF in the LT setting. An exhaustive review of the published literature was conducted. Data regarding frailty and sarcopenia in LT candidates with ACLF are scarce and heterogeneous. Studies evaluating frailty and sarcopenia in critically ill patients outside the liver literature are also presented in this review to enrich the knowledge of this field in expansion. Frailty and sarcopenia seem to contribute to worse outcomes in LT candidates with ACLF, both before and after LT. Sarcopenia evaluation may be the most prudent approach for those very sick patients. Skeletal muscle index assessed by computed tomography is recommended to evaluate sarcopenia. The role of muscle ultrasound and bioelectrical impedance analysis is to be determined. Frailty and sarcopenia are crucial factors to consider on a case-by-case basis in LT candidates with ACLF to improve patient outcomes.

Many studies propose a significant shift in the tectonic and paleogeographic evolution of the Andes in south-central Chile and Argentina during the Late Cretaceous. It has been proposed that the preceding Jurassic-Early Cretaceous extensional regime that resulted in a low-relief volcanic arc and the backarc Neuquén basin came to an end, giving way to shortening and Andean growth from the Late Cretaceous onward. Nevertheless, there are disagreements regarding the timing and nature of this transition to Andean orogenesis. To address these issues, we conducted geochronologic (U–Pb and 40Ar/39Ar), sedimentologic, and structural studies on Mesozoic-Cenozoic sedimentary and volcanic rocks in the Río Maule area (Principal Cordillera, Chile, 36°S). From our findings and prior analyses, we propose the following tectono-stratigraphic evolution of the region. (1) Marine deposition of the Tithonian-Hauterivian Baños del Flaco Formation took place in an extensional backarc basin. (2) After a ∼ 40 Myr hiatus, fluvial deposits of the Colimapu Formation and volcanic rocks of the Plan de los Yeuques Formation accumulated during the Cenomanian-Danian. Whereas the Colimapu Formation displays evidence of syndepositional shortening, the Plan de los Yeuques Formation exhibits synextensional growth strata. Contrary to other studies, our results suggest that the Chilean part of the Principal Cordillera was largely a zone of active deposition rather than an elevated fold-thrust belt during the Late Cretaceous. We propose that sedimentation occurred within a series of relatively stable intermontane subbasins generated by shortening, followed by extension. (3) After a ∼ 20 Myr hiatus, middle Eocene to early Miocene (Lutetian-Aquitanian) accumulation of a thick succession of andesitic lavas and minor clastic sediments of the Abanico Formation occurred in an intraarc extensional basin. (4) Finally, major shortening and uplift of previously deposited Mesozoic-Cenozoic rocks took place throughout the Neogene. This phase constituted the primary contractional deformation in the Andes of south-central Chile and Argentina. In terms of the transition to early Andean deformation, we propose that structural deformation did not generate a major, regional-scale fold-thrust belt during the late Albian-Santonian. Modest extension, tectonic quiescence, or low-magnitude shortening seem to have dominated during the early to middle Cenozoic.

Background: The immunomodulatory imide drugs (IMiDs) thalidomide, lenalidomide and pomalidomide may exhibit therapeutic efficacy in the prostate. In lower urinary tract symptoms (LUTS), voiding and storage disorders may arise from benign prostate hyperplasia, or overactive bladder. While current therapeutic options target smooth muscle contraction or cell proliferation, side effects are mostly cardiovascular. Therefore, we investigated effects of IMiDs on human detrusor and porcine artery smooth muscle contraction, and growth-related functions in detrusor smooth muscle cells (HBdSMC). Methods: Cell viability was assessed by CCK8, and apoptosis and cell death by flow cytometry in cultured HBdSMC. Contractions of human detrusor tissues and porcine interlobar and coronary arteries were induced by contractile agonists, or electric field stimulation (EFS) in the presence or absence of an IMID using an organ bath. Proliferation was assessed by EdU assay and colony formation, cytoskeletal organization by phalloidin staining, Results: Depending on tissue type, IMiDs inhibited cholinergic contractions with varying degree, up to 50 %, while non-cholinergic contractions were inhibited up to 80 % and 60 % for U46619 and endothelin-1, respectively, and EFS-induced contractions up to 75 %. IMiDs reduced viable HBdSM cells in a time-dependent manner. Correspondingly, proliferation was reduced, without showing pro-apoptotic effects. In parallel, IMiDs induced cytoskeletal disorganization. Conclusions: IMiDs exhibit regulatory functions in various smooth muscle-rich tissues, and of cell proliferation in the lower urinary tract. This points to a novel drug class effect for IMiDs, in which the molecular mechanisms of action of IMiDs merit further consideration for the application in LUTS.

Summary: Background: The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Methods: Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E] ≤ 4) were used for hierarchical clustering to identify patients with similar signatures. Findings: Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Interpretation: Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. Funding: CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke.