bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turbulent Scales Observed in a River Plume Entering a Fjord
Authors: McPherson R. A. , Stevens C. L. , O'Callaghan J. M. 
Published: November 2019

AbstractObservations of turbulent mixing are quantified in the near‐field region (first several kilometers) of a controlled river flow entering Doubtful Sound, New Zealand. Measurement techniques include direct turbulence measurements using microstructure profilers in both Eulerian and quasi‐Lagrangian perspectives and turbulent overturn analysis. Over 500 profiles of vertical microstructure were collected within the inner fjord. With high flow speeds of the surface plume over 2 m/s and some of the strongest stratification (N2∼10−1 s−2) recorded in the coastal ocean, turbulent overturning (Thorpe, LT) scales are used to indirectly infer turbulence dissipation rates (ϵ) and compared with direct measurements in a quasi‐idealized laboratory setting. There exists an inverse relationship between directly measured estimates of ϵ and distance from the plume discharge point. Peak values of ϵ>10−2 W/kg are observed within 500 m from the discharge point, among the highest turbulence dissipation rates recorded in oceanic shear flows. Thorpe scales range from below 1 cm in the pycnocline to a few meters in the weakly stratified ambient water below the plume. Stratification within the surface layer constrains the vertical dimension, limiting LT. Therefore, LT is an unreliable estimator of L0, where LO is the Ozmidov scale and is used to infer ϵ. Care must thus be taken when applying this method of overturn analysis in an environment where stratification or physical boundaries limit the vertical extent of overturns.
Multidecadal Changes in Meteorological Drought Severity and Their Drivers in Mainland China
Authors: Apurv Tushar , Xu Yue‐Ping , Wang Zhuo , Cai Ximing 
Published: November 2019

AbstractThis study analyzes the multidecadal changes in the severity of extreme meteorological droughts at the regional scale in China during 1951–2017. Dominance analysis is applied to multiple linear regression models to quantify the relative influence of global warming and internal variability on the meteorological drought severity in nine climate regions of China to understand which drivers are the most significant for each region and how they are likely to influence the severity of droughts in the near future (10–20 years). The influence of internal variability is represented by the Pacific Decadal Oscillation (PDO) and the Atlantic Multidecadal Oscillation (AMO). The PDO and global warming are found to have a stronger influence on the multidecadal variability of drought severity in China than the AMO. Global warming is found to be the more dominant driver of multidecadal variability of drought severity in the western parts of China, whereas the PDO is found to have a more dominant influence in the eastern parts of China. In the near future, global warming and the PDO are both likely to contribute to reduction of drought severity in Xinjiang, Northwest, and Tibet regions. The positive phase of the PDO is also expected to reduce the severity of droughts in Inner Mongolia and South China. On the other hand, both the PDO and global warming are expected to contribute to increase in drought severity in North and Southwest China in the near future.
Pre-clinical activity of combined LSD1 and mTORC1 inhibition in MLL-translocated acute myeloid leukaemia
Authors: Deb Gauri , Wingelhofer Bettina , Amaral Fabio M. R. , Maiques-Diaz Alba , Chadwick John A. , Spencer Gary J. , Williams Emma L. , Leong Hui-Sun , Maes Tamara , Somervaille Tim C. P. 
Published: November 2019

AbstractThe histone demethylase lysine-specific demethylase 1 (LSD1 or KDM1A) has emerged as a candidate therapeutic target in acute myeloid leukaemia (AML); tranylcypromine-derivative inhibitors induce loss of clonogenic activity and promote differentiation, in particular in the MLL-translocated molecular subtype of AML. In AML, the use of drugs in combination often delivers superior clinical activity. To identify genes and cellular pathways that collaborate with LSD1 to maintain the leukaemic phenotype, and which could be targeted by combination therapies, we performed a genome-wide CRISPR-Cas9 dropout screen. We identified multiple components of the amino acid sensing arm of mTORC1 signalling—RRAGA, MLST8, WDR24 and LAMTOR2—as cellular sensitizers to LSD1 inhibition. Knockdown of mTORC1 components, or mTORC1 pharmacologic inhibition, in combination with LSD1 inhibition enhanced differentiation in both cell line and primary cell settings, in vitro and in vivo, and substantially reduced the frequency of clonogenic primary human AML cells in a modelled minimal residual disease setting. Synergistic upregulation of a set of transcription factor genes associated with terminal monocytic lineage differentiation was observed. Thus, dual mTORC1 and LSD1 inhibition represents a candidate combination approach for enhanced differentiation in MLL-translocated AML which could be evaluated in early phase clinical trials.
Childhood intelligence attenuates the association between biological ageing and health outcomes in later life
Authors: Stevenson Anna J. , McCartney Daniel L. , Hillary Robert F. , Redmond Paul , Taylor Adele M. , Zhang Qian , McRae Allan F. , Spires-Jones Tara L. , McIntosh Andrew M. , Deary Ian J. , Marioni Riccardo E. 
Published: November 2019

AbstractThe identification of biomarkers that discriminate individual ageing trajectories is a principal target of ageing research. Some of the most promising predictors of biological ageing have been developed using DNA methylation. One recent candidate, which tracks age-related phenotypes in addition to chronological age, is ‘DNAm PhenoAge’. Here, we performed a phenome-wide association analysis of this biomarker in a cohort of older adults to assess its relationship with a comprehensive set of both historical, and contemporaneously-measured, phenotypes. Higher than expected DNAm PhenoAge compared with chronological age, known as epigenetic age acceleration, was found to associate with a number of blood, cognitive, physical fitness and lifestyle variables, and with mortality. Notably, DNAm PhenoAge, assessed at age 70, was associated with cognitive ability at age 11, and with educational attainment. Adjusting for age 11 cognitive ability attenuated the majority of the cross-sectional later-life associations between DNAm PhenoAge and health outcomes. These results highlight the importance of early life factors on healthy older ageing.
Sleep EEG slow-wave activity in medicated and unmedicated children and adolescents with attention-deficit/hyperactivity disorder
Authors: Furrer Melanie , Jaramillo Valeria , Volk Carina , Ringli Maya , Aellen Robert , Wehrle Flavia M. , Pugin Fiona , Kurth Salome , Brandeis Daniel , Schmid Markus , Jenni Oskar G. , Huber Reto 
Published: November 2019

AbstractSlow waves (1–4.5 Hz) are the most characteristic oscillations of deep non-rapid eye movement sleep. The EEG power in this frequency range (slow-wave activity, SWA) parallels changes in cortical connectivity (i.e., synaptic density) during development. In patients with attention-deficit/hyperactivity disorder (ADHD), prefrontal cortical development was shown to be delayed and global gray matter volumes to be smaller compared to healthy controls. Using data of all-night recordings assessed with high-density sleep EEG of 50 children and adolescents with ADHD (mean age: 12.2 years, range: 8–16 years, 13 female) and 86 age- and sex-matched healthy controls (mean age: 12.2 years, range: 8–16 years, 23 female), we investigated if ADHD patients differ in the level of SWA. Furthermore, we examined the effect of stimulant medication. ADHD patients showed a reduction in SWA across the whole brain (−20.5%) compared to healthy controls. A subgroup analysis revealed that this decrease was not significant in patients who were taking stimulant medication on a regular basis at the time of their participation in the study. Assuming that SWA directly reflects synaptic density, the present findings are in line with previous data of neuroimaging studies showing smaller gray matter volumes in ADHD patients and its normalization with stimulant medication.
The Penrose Effect and its acceleration by the war on drugs: a crisis of untranslated neuroscience and untreated addiction and mental illness
Authors: Grecco Gregory G. , Andrew Chambers R. 
Published: November 2019

AbstractIn 1939, British psychiatrist Lionel Penrose described an inverse relationship between mental health treatment infrastructure and criminal incarcerations. This relationship, later termed the ‘Penrose Effect’, has proven remarkably predictive of modern trends which have manifested as reciprocal components, referred to as ‘deinstitutionalization’ and ‘mass incarceration’. In this review, we consider how a third dynamic—the criminalization of addiction via the ‘War on Drugs’, although unanticipated by Penrose, has likely amplified the Penrose Effect over the last 30 years, with devastating social, economic, and healthcare consequences. We discuss how synergy been the Penrose Effect and the War on Drugs has been mediated by, and reflects, a fundamental neurobiological connection between the brain diseases of mental illness and addiction. This neuroscience of dual diagnosis, also not anticipated by Penrose, is still not being adequately translated into improving clinical training, practice, or research, to treat patients across the mental illness-addictions comorbidity spectrum. This failure in translation, and the ongoing fragmentation and collapse of behavioral healthcare, has worsened the epidemic of untreated mental illness and addictions, while driving unsustainable government investment into mass incarceration and high-cost medical care that profits too exclusively on injuries and multi-organ diseases resulting from untreated addictions. Reversing the fragmentation and decline of behavioral healthcare with decisive action to co-integrate mental health and addiction training, care, and research—may be key to ending criminalization of mental illness and addiction, and refocusing the healthcare system on keeping the population healthy at the lowest possible cost.
In vivo delivery of VEGF RNA and protein to increase osteogenesis and intraosseous angiogenesis
Authors: Rumney Robin M. H. , Lanham Stuart A. , Kanczler Janos M. , Kao Alexander P. , Thiagarajan Lalitha , Dixon James E. , Tozzi Gianluca , Oreffo Richard O. C. 
Published: November 2019

AbstractDeficient bone vasculature is a key component in pathological conditions ranging from developmental skeletal abnormalities to impaired bone repair. Vascularisation is dependent upon vascular endothelial growth factor (VEGF), which drives both angiogenesis and osteogenesis. The aim of this study was to examine the efficacy of blood vessel and bone formation following transfection with VEGF RNA or delivery of recombinant human VEGF165 protein (rhVEGF165) across in vitro and in vivo model systems. To quantify blood vessels within bone, an innovative approach was developed using high-resolution X-ray computed tomography (XCT) to generate quantifiable three-dimensional reconstructions. Application of rhVEGF165 enhanced osteogenesis, as evidenced by increased human osteoblast-like MG-63 cell proliferation in vitro and calvarial bone thickness following in vivo administration. In contrast, transfection with VEGF RNA triggered angiogenic effects by promoting VEGF protein secretion from MG-63VEGF165 cells in vitro, which resulted in significantly increased angiogenesis in the chorioallantoic (CAM) assay in ovo. Furthermore, direct transfection of bone with VEGF RNA in vivo increased intraosseous vascular branching. This study demonstrates the importance of continuous supply as opposed to a single high dose of VEGF on angiogenesis and osteogenesis and, illustrates the potential of XCT in delineating in 3D, blood vessel connectivity in bone.
Insights into the 400 million-year-old eyes of giant sea scorpions (Eurypterida) suggest the structure of Palaeozoic compound eyes
Authors: Schoenemann Brigitte , Poschmann Markus , Clarkson Euan N. K. 
Published: November 2019

AbstractSea scorpions (Eurypterida, Chelicerata) of the Lower Devonian (~400 Mya) lived as large, aquatic predators. The structure of modern chelicerate eyes is very different from that of mandibulate compound eyes [Mandibulata: Crustacea and Tracheata (Hexapoda, such as insects, and Myriapoda)]. Here we show that the visual system of Lower Devonian (~400 Mya) eurypterids closely matches that of xiphosurans (Xiphosura, Chelicerata). Modern representatives of this group, the horseshoe crabs (Limulidae), have cuticular lens cylinders and usually also an eccentric cell in their sensory apparatus. This strongly suggests that the xiphosuran/eurypterid compound eye is a plesiomorphic structure with respect to the Chelicerata, and probably ancestral to that of Euchelicerata, including Eurypterida, Arachnida and Xiphosura. This is supported by the fact that some Palaeozoic scorpions also possessed compound eyes similar to those of eurypterids. Accordingly, edge enhancement (lateral inhibition), organised by the eccentric cell, most useful in scattered light-conditions, may be a very old mechanism, while the single-lens system of arachnids is possibly an adaptation to a terrestrial life-style.
Reassessment of a juvenile Daspletosaurus from the Late Cretaceous of Alberta, Canada with implications for the identification of immature tyrannosaurids
Authors: Voris Jared T. , Zelenitsky Darla K. , Therrien François , Currie Philip J. 
Published: November 2019

AbstractDaspletosaurus is a large tyrannosaurine found in upper Campanian deposits of Alberta and Montana. Although several large subadult and adult individuals of this taxon are known, only one juvenile individual, TMP 1994.143.1, has been identified. This specimen has played a key role in the idea that juvenile tyrannosaurid individuals are difficult to differentiate among species. Here the taxonomic affinity of TMP 1994.143.1 is reassessed in light of a juvenile tyrannosaurine postorbital recently discovered in the Dinosaur Park Formation of Alberta. Anatomical comparisons and phylogenetic analyses reveal that TMP 1994.143.1 is referable to the albertosaurine Gorgosaurus libratus, whereas the new postorbital belongs to a small juvenile Daspletosaurus. This taxonomic reassignment of TMP 1994.143.1 results in the juvenile ontogenetic stage of Daspletosaurus being known only from two isolated cranial elements. The new postorbital provides insights into early Daspletosaurus ontogeny, revealing that the cornual process developed earlier or faster than in other tyrannosaurids. Although some ontogenetic changes in the postorbital are found to be unique to Daspletosaurus, overall changes are most consistent with those of other large tyrannosaurines. Our results also show that diagnostic features develop early in ontogeny, such that juveniles of different tyrannosaurid species are easier to differentiate than previously thought.
The influence of urban form on the grid integration of renewable energy technologies and distributed energy systems
Authors: Perera A. T. D. , Coccolo Silvia , Scartezzini Jean-Louis 
Published: November 2019

AbstractStandard and newly designed building blocks for complex urban sites– also designated by urban archetypes - are used in this study to quantify the influence of urban forms on their energy demand and energy systems design. An energy hub, which consists on a multi-carrier energy system involving multiple energy conversion, storage and/or network technologies, is employed to quantify the impact of the urban morphology on the energy system requirements. This study reveals that urban archetypes have a notable influence on the heating and cooling energy demands of city districts that can be characterized using form factors and floor area ratio. However, the influence on demand profiles cannot be assessed based on the aforementioned indicators. The cost of energy systems can increase up to 50% due to the impact of urban forms that are well beyond the increase of peak and/or annual energy demands. In addition, renewable energy integration to the grid as well its utilization in districts is influenced by urban forms. This makes it essential to consider energy system design as a part of the urban planning process moving even beyond building simulation.
Engineering of chimeric peptides as antagonists for the G protein-coupled receptor, RXFP4
Authors: Praveen Praveen , Bathgate Ross A. D. , Hossain Mohammed Akhter 
Published: November 2019

AbstractInsulin-like peptide 5 (INSL5) is a very important pharma target for treating human conditions such as anorexia and diabetes. However, INSL5 with two chains and three disulfide bridges is an extremely difficult peptide to assemble by chemical or recombinant means. In a recent study, we were able to engineer a simplified INSL5 analogue 13 which is a relaxin family peptide receptor 4 (RXFP4)-specific agonist. To date, however, no RXFP4-specific antagonist (peptide or small molecule) has been reported in the literature. The focus of this study was to utilize the non-specific RXFP3/RXFP4 antagonist ΔR3/I5 as a template to rationally design an RXFP4 specific antagonist. Unexpectedly, we demonstrated that ΔR3/I5 exhibited partial agonism at RXFP4 when expressed in CHO cells which is associated with only partial antagonism of INSL5 analogue activation. In an attempt to improve RXFP4 specificity and antagonist activity we designed and chemically synthesized a series of analogues of ΔR3/I5. While all the chimeric analogues still demonstrated partial agonism at RXFP4, one peptide (Analogue 17) exhibited significantly improved RXFP4 specificity. Importantly, analogue 17 has a simplified structure which is more amenable to chemical synthesis. Therefore, analogue 17 is an ideal template for further development into a specific high affinity RXFP4 antagonist which will be an important tool to probe the physiological role of RXFP4/INSL5 axis.
Cu(II) and magnetite nanoparticles decorated melamine-functionalized chitosan: A synergistic multifunctional catalyst for sustainable cascade oxidation of benzyl alcohols/Knoevenagel condensation
Authors: Alirezvani Zahra , Dekamin Mohammad G. , Valiey Ehsan 
Published: November 2019

AbstractThe uniform decoration of Cu(II) species and magnetic nanoparticles on the melamine-functionalized chitosan afforded a new supramolecular biopolymeric nanocomposite (Cs-Pr-Me-Cu(II)-Fe3O4). The morphology, structure, and catalytic activity of the Cs-Pr-Me-Cu(II)-Fe3O4 nanocomposite have been systematically investigated. It was found that Cs-Pr-Me-Cu(II)-Fe3O4 nanocomposite can smoothly promote environmentally benign oxidation of different benzyl alcohol derivatives by tert-butyl hydroperoxide (TBHP) to their corresponding benzaldehydes and subsequent Knoevenagel condensation with malononitrile, as a multifunctional catalyst. Interestingly, Fe3O4 nanoparticles enhance the catalytic activity of Cu(II) species. The corresponding benzylidenemalononitriles were formed in high to excellent yields at ambient pressure and temperature. The heterogeneous Cs-Pr-Me-Cu(II)-Fe3O4 catalyst was also very stable with almost no leaching of the Cu(II) species into the reaction medium and could be easily recovered by an external magnet. The recycled Cs-Pr-Me-Cu(II)-Fe3O4 was reused at least four times with slight loss of its activity. This is a successful example of the combination of chemo- and bio-drived materials catalysis for mimicing biocatalysis as well as sustainable and one pot multistep synthesis.
The α1-adrenoceptor inhibitor ρ-TIA facilitates net hunting in piscivorous Conus tulipa
Authors: Dutt Mriga , Giacomotto Jean , Ragnarsson Lotten , Andersson Åsa , Brust Andreas , Dekan Zoltan , Alewood Paul F. , Lewis Richard J. 
Published: November 2019

AbstractCone snails use separately evolved venoms for prey capture and defence. While most use a harpoon for prey capture, the Gastridium clade that includes the well-studied Conus geographus and Conus tulipa, have developed a net hunting strategy to catch fish. This unique feeding behaviour requires secretion of “nirvana cabal” peptides to dampen the escape response of targeted fish allowing for their capture directly by mouth. However, the active components of the nirvana cabal remain poorly defined. In this study, we evaluated the behavioural effects of likely nirvana cabal peptides on the teleost model, Danio rerio (zebrafish). Surprisingly, the conantokins (NMDA receptor antagonists) and/or conopressins (vasopressin receptor agonists and antagonists) found in C. geographus and C. tulipa venom failed to produce a nirvana cabal-like effect in zebrafish. In contrast, low concentrations of the non-competitive adrenoceptor antagonist ρ-TIA found in C. tulipa venom (EC50 = 190 nM) dramatically reduced the escape response of zebrafish larvae when added directly to aquarium water. ρ-TIA inhibited the zebrafish α1-adrenoceptor, confirming ρ-TIA has the potential to reverse the known stimulating effects of norepinephrine on fish behaviour. ρ-TIA may act alone and not as part of a cabal, since it did not synergise with conopressins and/or conantokins. This study highlights the importance of using ecologically relevant animal behaviour models to decipher the complex neurobiology underlying the prey capture and defensive strategies of cone snails.
1H NMR study of the interaction of trans-resveratrol with soybean phosphatidylcholine liposomes
Authors: Cardia Maria Cristina , Caddeo Carla , Lai Francesco , Fadda Anna Maria , Sinico Chiara , Luhmer Michel 
Published: November 2019

AbstractResveratrol (RSV) is a well-known natural derivative with a wide range of biological and pharmacological activities. Despite of these demonstrated properties, it exhibits low both aqueous solubility and chemical stability and therefore low bioavailability. Consequently, the major concern of the technological research is to exploit delivery systems able to overcome bioavailability problems. In the recent past liposomes have been successfully studied for these purposes. In this paper, 1H-NMR spectroscopy, Nuclear Overhauser Spectroscopy (NOESY) as well as Paramagnetic Relaxation Enhancements (PRE) experiments have been carried out to quantitatively investigate the incorporation of resveratrol, at both the liposome preparation stage and by preformed liposomes, also with the aim to characterize resveratrol- soybean phosphatidylcholine (P90G) lipid bilayer interactions. Overall results of 1H NMR spectroscopy analysis suggest that RSV is located nearby the phosphocholine headgroups and also provide quantitative data on the incorporation of RSV (5% w/w), which corresponds to a 150-fold increase with respect to the solubility of RSV in water. Beside, considering that the same level of RSV incorporation was obtained via spontaneous uptake by preformed P90G liposomes, it can be concluded that RSV easily diffuses through the lipid bilayer.