bluuebunny/crossref_metadata_2025 huggingface dataset:
Coastal wetlands reduce property damage during tropical cyclones
Authors: Sun Fanglin , Carson Richard T.
Published: March 2020

Coastal wetlands dampen the impact of storm surge and strong winds. Studies on the economic valuation of this protective service provided by wetland ecosystems are, however, rare. Here, we analyze property damage caused by 88 tropical storms and hurricanes hitting the United States between 1996 and 2016 and show that counties with more wetland coverage experienced significantly less property damage. The expected economic value of the protective effects of wetlands varies widely across coastal US counties with an average value of about $1.8 million/km
2
per year and a median value of $91,000/km
2
. Wetlands confer relatively more protection against weaker storms and in states with weaker building codes. Recent wetland losses are estimated to have increased property damage from Hurricane Irma by $430 million. Our results suggest the importance of considering both natural and human factors in coastal zone defense policy.
In situ healing of dendrites in a potassium metal battery
Authors: Hundekar Prateek , Basu Swastik , Fan Xiulin , Li Lu , Yoshimura Anthony , Gupta Tushar , Sarbada Varun , Lakhnot Aniruddha , Jain Rishabh , Narayanan Shankar , Shi Yunfeng , Wang Chunsheng , Koratkar Nikhil
Published: March 2020

Significance

Historically, battery self-heating has been viewed negatively as an undesirable attribute. However, we report that battery self-heat, if properly controlled, can smoothen dendritic features in potassium metal batteries. This could open the door to high gravimetric and volumetric energy density potassium-ion batteries that could offer a sustainable and low-cost alternative to the incumbent lithium-ion technology.
Triacylglycerol and phytyl ester synthesis in
Synechocystis
sp. PCC6803
Authors: Aizouq Mohammed , Peisker Helga , Gutbrod Katharina , Melzer Michael , Hölzl Georg , Dörmann Peter
Published: March 2020

Significance

Cyanobacteria harbor a photosynthetic apparatus related to plant chloroplasts. The lipid compositions of the thylakoids that harbor the photosynthetic complexes in cyanobacteria and chloroplasts are highly similar. Chloroplasts contain triacylglycerol (storage oil) and wax esters; the latter are composed of phytol derived from chlorophyll and fatty acids (phytyl esters). However, the existence of these lipids in cyanobacteria in general remained unclear. Here we show that the cyanobacterium
Synechocystis
contains triacylglycerol and phytyl esters. A mutant, Δslr2103, was generated, which lacked these two lipids but showed no obvious growth defect. The
slr2103
gene encodes a diacylglycerol acyltransferase different from known enzymes of triacylglycerol synthesis in bacteria. This pathway can be employed to produce oil for biotechnological applications in cyanobacteria.
Biphasic chemotaxis of
Escherichia coli
to the microbiota metabolite indole
Authors: Yang Jingyun , Chawla Ravi , Rhee Kathy Y. , Gupta Rachit , Manson Michael D. , Jayaraman Arul , Lele Pushkar P.
Published: March 2020

Significance

Chemotaxis to microbial metabolites in the GI tract plays a key role in regulating bacterial colonization and pathogenesis. Chemotaxis to indole, one of the prominent GI-tract metabolites, remains poorly understood. In this work, we describe how two major chemoreceptors, Tar and Tsr, mediate opposite responses to indole. The difference in the kinetics of these responses causes an inversion from a repellent to an attractant response over time. Cells migrated toward regions of high indole concentration only if they had previously adapted to indole. Otherwise, they were repelled. Thus, indole has the potential to segregate cells based on their state of adaptation. This bipartite response to indole may shape the development of microbial communities in the GI tract.
Experimental observation of the marginal glass phase in a colloidal glass
Authors: Hammond Andrew P. , Corwin Eric I.
Published: March 2020

Significance

Glass is one of the easiest materials to work with, capable of forming complex and sophisticated structures with relative ease in the hands of a glass blower. However, the underlying physical principles that allow glass to slowly melt and flow are among the least understood. Recent theoretical breakthroughs hope to reveal a new kind of underlying simplicity within glasses, one that might extend to all manner of disordered and complex materials. By studying the formation of a model glass system at extremely short time scales and small length scales, we have proven the central prediction of these theories, that glasses undergo an extremely subtle transition while forming, which controls their physical properties.
Conformational control of small GTPases by AMPylation
Authors: Barthelmes Katja , Ramcke Evelyn , Kang Hyun-Seo , Sattler Michael , Itzen Aymelt
Published: March 2020

Posttranslational modifications (PTMs) are important physiological means to regulate the activities and structures of central regulatory proteins in health and disease. Small GTPases have been recognized as important molecules that are targeted by PTMs during infections of mammalian cells by bacterial pathogens. The enzymes DrrA/SidM and AnkX from
Legionella pneumophila
AMPylate and phosphocholinate Rab1b during infection, respectively. Cdc42 is AMPylated by IbpA from
Histophilus somni
at tyrosine 32 or by VopS from
Vibrio parahaemolyticus
at threonine 35. These modifications take place in the important regulatory switch I or switch II regions of the GTPases. Since Rab1b and Cdc42 are central regulators of intracellular vesicular trafficking and of the actin cytoskeleton, their modifications by bacterial pathogens have a profound impact on the course of infection. Here, we addressed the biochemical and structural consequences of GTPase AMPylation and phosphocholination. By combining biochemical experiments and NMR analysis, we demonstrate that AMPylation can overrule the activity state of Rab1b that is commonly dictated by binding to guanosine diphosphate or guanosine triphosphate. Thus, PTMs may exert conformational control over small GTPases and may add another previously unrecognized layer of activity control to this important regulatory protein family.
The functional activity of E-cadherin controls tumor cell metastasis at multiple steps
Authors: Na Tae-Young , Schecterson Leslayann , Mendonsa Alisha M. , Gumbiner Barry M.
Published: March 2020

Significance

The expression of E-cadherin has been implicated in tumor metastasis, often as a tumor suppressor, but also as a promoter of growth and metastasis. We have shown that the functional activity of E-cadherin at the cell surface is often modified in response to environmental factors, and have developed monoclonal antibodies (mAbs) that activate E-cadherin adhesive function. These activating mAbs inhibit the metastasis of endogenous genetically driven mammary tumors in mice, and we dissect the process to show that these mAbs work at multiple steps of the metastatic cascade, including local invasion, intravasation, cell survival, and extravasation into the target organ. Thus, the functional state of E-cadherin is an important determinant of metastatic potential beyond whether the gene is expressed.
Context-dependent operation of neural circuits underlies a navigation behavior in
Caenorhabditis elegans
Authors: Ikeda Muneki , Nakano Shunji , Giles Andrew C. , Xu Linghuan , Costa Wagner Steuer , Gottschalk Alexander , Mori Ikue
Published: March 2020

The nervous system evaluates environmental cues and adjusts motor output to ensure navigation toward a preferred environment. The nematode
Caenorhabditis elegans
navigates in the thermal environment and migrates toward its cultivation temperature by moving up or down thermal gradients depending not only on absolute temperature but on relative difference between current and previously experienced cultivation temperature. Although previous studies showed that such thermal context-dependent opposing migration is mediated by bias in frequency and direction of reorientation behavior, the complete neural pathways—from sensory to motor neurons—and their circuit logics underlying the opposing behavioral bias remain elusive. By conducting comprehensive cell ablation, high-resolution behavioral analyses, and computational modeling, we identified multiple neural pathways regulating behavioral components important for thermotaxis, and demonstrate that distinct sets of neurons are required for opposing bias of even single behavioral components. Furthermore, our imaging analyses show that the context-dependent operation is evident in sensory neurons, very early in the neural pathway, and manifested by bidirectional responses of a first-layer interneuron AIB under different thermal contexts. Our results suggest that the contextual differences are encoded among sensory neurons and a first-layer interneuron, processed among different downstream neurons, and lead to the flexible execution of context-dependent behavior.
Association of Cl with C
2
H
2
by unified variable-reaction-coordinate and reaction-path variational transition-state theory
Authors: Zhang Linyao , Truhlar Donald G. , Sun Shaozeng
Published: March 2020

Significance

A key issue in chemical kinetics is advancing the theoretical framework to handle reactions beyond the domain of textbook transition-state theory by including––for example––anharmonicity, barrierless transition states, transition states in series, and the effect of conformational flexibility on equilibrium constants. Other key issues are validating affordable electronic structure methods for direct dynamics and the direct calculation of high-pressure limiting rate constants, which are often obtainable experimentally only by extrapolation. The present article addresses all these issues for a prototype radical–molecule association reaction and thereby demonstrates how to combine improved theoretical methods to provide rate constants in cases where experimental data are uncertain or missing.
RNA extension drives a stepwise displacement of an initiation-factor structural module in initial transcription
Authors: Li Lingting , Molodtsov Vadim , Lin Wei , Ebright Richard H. , Zhang Yu
Published: March 2020

All organisms—bacteria, archaea, and eukaryotes—have a transcription initiation factor that contains a structural module that binds within the RNA polymerase (RNAP) active-center cleft and interacts with template-strand single-stranded DNA (ssDNA) in the immediate vicinity of the RNAP active center. This transcription initiation-factor structural module preorganizes template-strand ssDNA to engage the RNAP active center, thereby facilitating binding of initiating nucleotides and enabling transcription initiation from initiating mononucleotides. However, this transcription initiation-factor structural module occupies the path of nascent RNA and thus presumably must be displaced before or during initial transcription. Here, we report four sets of crystal structures of bacterial initially transcribing complexes that demonstrate and define details of stepwise, RNA-extension-driven displacement of the “σ-finger” of the bacterial transcription initiation factor σ. The structures reveal that—for both the primary σ-factor and extracytoplasmic (ECF) σ-factors, and for both 5′-triphosphate RNA and 5′-hydroxy RNA—the “σ-finger” is displaced in stepwise fashion, progressively folding back upon itself, driven by collision with the RNA 5′-end, upon extension of nascent RNA from ∼5 nt to ∼10 nt.
Cyp2c44 regulates prostaglandin synthesis, lymphangiogenesis, and metastasis in a mouse model of breast cancer
Authors: Kesavan Rushendhiran , Frömel Timo , Zukunft Sven , Laban Hebatullah , Geyer Alexandra , Naeem Zumer , Heidler Juliana , Wittig Ilka , Elwakeel Eiman , Brüne Bernhard , Weigert Andreas , Popp Rüdiger , Fleming Ingrid
Published: March 2020

Arachidonic acid epoxides generated by cytochrome P450 (CYP) enzymes have been linked to increased tumor growth and metastasis, largely on the basis of overexpression studies and the application of exogenous epoxides. Here we studied tumor growth and metastasis in Cyp2c44
−/−
mice crossed onto the polyoma middle T oncogene (PyMT) background. The resulting PyMT
2c44
mice developed more primary tumors earlier than PyMT mice, with increased lymph and lung metastasis. Primary tumors from Cyp2c44-deficient mice contained higher numbers of tumor-associated macrophages, as well as more lymphatic endothelial cells than tumors from PyMT mice. While epoxide and diol levels were comparable in tumors from both genotypes, prostaglandin (PG) levels were higher in the PyMT
Δ2c44
tumors. This could be accounted for by the finding that Cyp2c44 metabolized the PG precursor, PGH
2
to 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT), thus effectively reducing levels of effector PGs (including PGE
2
). Next, proteomic analyses revealed an up-regulation of WD repeating domain FYVE1 (WDFY1) in tumors from PyMT
Δ2c44
mice, a phenomenon that was reproduced in Cyp2c44-deficient macrophages as well as by PGE
2
. Mechanistically, WDFY1 was involved in Toll-like receptor signaling, and its down-regulation in human monocytes attenuated the LPS-induced phosphorylation of IFN regulatory factor 3 and nuclear factor-κB. Taken together, our results indicate that Cyp2c44 protects against tumor growth and metastasis by preventing the synthesis of PGE
2
. The latter eicosanoid influenced macrophages at least in part by enhancing Toll-like receptor signaling via the up-regulation of WDFY1.
Mechanism of proton transfer in class A β-lactamase catalysis and inhibition by avibactam
Authors: Pemberton Orville A. , Noor Radwan E. , Kumar M. V. Vasantha , Sanishvili Ruslan , Kemp M. Trent , Kearns Fiona L. , Woodcock H. Lee , Gelis Ioannis , Chen Yu
Published: March 2020

Gram-negative bacteria expressing class A β-lactamases pose a serious health threat due to their ability to inactivate all β-lactam antibiotics. The acyl–enzyme intermediate is a central milestone in the hydrolysis reaction catalyzed by these enzymes. However, the protonation states of the catalytic residues in this complex have never been fully analyzed experimentally due to inherent difficulties. To help unravel the ambiguity surrounding class A β-lactamase catalysis, we have used ultrahigh-resolution X-ray crystallography and the recently approved β-lactamase inhibitor avibactam to trap the acyl–enzyme complex of class A β-lactamase CTX-M-14 at varying pHs. A 0.83-Å-resolution CTX-M-14 complex structure at pH 7.9 revealed a neutral state for both Lys73 and Glu166. Furthermore, the avibactam hydroxylamine-
O
-sulfonate group conformation varied according to pH, and this conformational switch appeared to correspond to a change in the Lys73 protonation state at low pH. In conjunction with computational analyses, our structures suggest that Lys73 has a perturbed acid dissociation constant (pK
a
) compared with acyl–enzyme complexes with β-lactams, hindering its function to deprotonate Glu166 and the initiation of the deacylation reaction. Further NMR analysis demonstrated Lys73 pK
a
to be ∼5.2 to 5.6. Together with previous ultrahigh-resolution crystal structures, these findings enable us to follow the proton transfer process of the entire acylation reaction and reveal the critical role of Lys73. They also shed light on the stability and reversibility of the avibactam carbamoyl acyl–enzyme complex, highlighting the effect of substrate functional groups in influencing the protonation states of catalytic residues and subsequently the progression of the reaction.
Clonemate cotransmission supports a role for kin selection in a puppeteer parasite
Authors: Criscione Charles D. , van Paridon Bradley J. , Gilleard John S. , Goater Cameron P.
Published: March 2020

Significance

The lancet flukeDicrocoelium dendriticumcan precisely manipulate its ant host to facilitate transmission to its ungulate host. However, the sole parasite manipulator in the ant brain is presumed not infective to its next host whereas the parasites in the abdomen of the same ant are infective. We conducted a test of genetic relatedness between the brain fluke to those flukes in the abdomen. Our data show that clonemates (i.e. genetically identical individuals) are cotransmitted into ants and that the brain fluke is often a clonemate of flukes in the abdomen. Hence, our study provides empirical evidence that supports a role for kin selection in the evolution of a host-manipulating behavior.
Learning how to communicate in infancy
Authors: Matthews Danielle
Published: March 2020

Just like other baby apes, human infants make it their business to stay in safe contact with their caregivers. The difference is that humans do this not just by holding on for dear life, but by ensuring their caregivers are in psychological contact with them. To this end, many of the most important communicative developments take place within the first two years of life. In this chapter we will review how physical mutual responsiveness gives way to the back-and-forth of proto-conversation, where caregivers respond to hiccups, coos and sneezes as if they were speech. Infants discover that they can make sounds and gestures in order to engage others and take turns. They become able to make demands of people, bring things to their attention and ask questions of them. Once they have mastered doing so non-verbally, they soon learn that they can use words for the same purposes (even though they don’t understand words as intersubjectively agreed symbols until sometime later). These communicative developments far outstrip those of any other animal on the planet. And yet it seems that it is precisely the relatively slow development of human infants that affords our species unique mode of communication. Newborns, equipped with a desire to be with others and some basic attentional preferences, are set up to learn from their social environment and thereby guarantee their entry into human culture.
Heads, shoulders, knees and toes
Authors: Twomey Katherine E. , Cangelosi Angelo
Published: March 2020

Decades of research have brought us a long way in understanding the many factors that affect language acquisition. However, while a wealth of empirical studies have characterised children’s language learning behaviours, from pre-speech to syntax, until relatively recently researchers have been unable to explicitly test developmental mechanisms. However, advances in computational modelling and in particular in developmental robotics have allowed researchers to implement and test developmental theories, specifying explicitly the knowledge and cognitive computations assumed to be at play during language development. The current chapter reviews a series of developmental robotics models of the early stages of language development, illustrating (a) the importance for future theory development of cross-disciplinary collaboration and (b) an emerging new view of language acquisition in which nonlinguistic – as well as linguistic – input drives language development.
Understanding the cross-linguistic pattern of verb-marking error in typically developing children and children with Developmental Language Disorder
Authors: Pine Julian M. , Freudenthal Daniel , Gobet Fernand
Published: March 2020

Verb-marking errors such as ‘*That go there’ and ‘*We make this yesterday’ are a characteristic feature of children’s early language. In this chapter, we review work on the cross-linguistic pattern of verb-marking error that suggests that these errors reflect the incorrect use of non-finite forms in finite contexts (often referred to as ‘Optional Infinitive (OI) errors’). The vast majority of this research has been conducted within the generativist tradition and has assumed that OI errors reflect an underlying maturational difference between the child and the adult grammar. However, we show that a detailed analysis of the cross-linguistic data reveals patterns that are difficult to explain in these terms, and can be more readily explained under the assumption that OI errors are learned directly from the input as a result of weaknesses in the child’s ability to process longer utterances. The implication is that the cross-linguistic pattern of verb-marking errors in children’s early language can only be properly understood by focusing on the relation between the kind of errors that young children make and the semantic-distributional properties of the language to which they have been exposed.
Lessons from studying language development in bilingual children
Authors: Serratrice Ludovica
Published: March 2020

The chapter starts by providing an overview of the many factors that contribute to children’s bilingual experience including the societal context and the social status of the two languages, the household composition and the access to native speakers, the age of first exposure, the distance between the two languages and patterns of code-switching. The second half of the chapter homes in on three areas of language development where bilingualism shapes the relationship with the input, plays a role in the relationship between processing skills and pragmatic skills, and affects representations across two languages. Within-language and across-language relationships in the first three years of word learning highlight the language-specific nature of the role of the input. The interaction between pragmatic skills, vocabulary size and lexical learning in a comparative monolingual-bilingual framework further unpack how much is language-specific in the course of early development. The final section moves beyond the lexicon to investigate the extent to which syntactic representations are shared across languages and how this affects cross-linguistic influence at the syntactic level in older pre-school children.
Language disorders and autism
Authors: Abbot-Smith Kirsten
Published: March 2020

Usage-based theories explain language development in terms of the specific characteristics of language input in combination with a child’s own inherent ability to engage in shared intentionality and statistical learning. In this chapter, I discuss these mechanisms in relation to evidence from Developmental Language Disorders (DLD) and Autism. First, there is evidence for the role of language input in both conditions. The specific patterns of morpho-syntax impairments in DLD are clearly affected by the relative perceptual salience, frequency and complexity of morpho-syntax in the specific language a child is acquiring. Regarding autism, the grammatical complexity of parental child-directed utterances predicts child vocabulary and morpho-syntactic skills at later time-points. Nonetheless, both conditions are highly heritable, raising questions about the child-internal mechanisms leading to language learning difficulties. Impairments in statistical learning could potentially account for morpho-syntactic difficulties in DLD. However, any firm conclusions await assessments of statistical learning which have good test – retest reliability. Autistic children might plausibly tend to have difficulties with – or lack motivation for – engaging in shared intentionality. If verified, this could account for patterns of relatively spared nuts-and-bolts (structural, core) language in the face of pragmatic language difficulties. However, to date studies of autistic difficulties with shared intentionality have not stringently ruled out alternative explanations. Both DLD and autism are likely to exist on a continuum with the neuro-typical population. Future research needs to move towards designs which can more fully accommodate the vast heterogeneity that exists within both DLD and autism.
Chromosomes function as a barrier to mitotic spindle bipolarity in polyploid cells
Authors: Goupil Alix , Nano Maddalena , Letort Gaëlle , Gemble Simon , Edwards Frances , Goundiam Oumou , Gogendeau Delphine , Pennetier Carole , Basto Renata
Published: March 2020

Ploidy variations such as genome doubling are frequent in human tumors and have been associated with genetic instability favoring tumor progression. How polyploid cells deal with increased centrosome numbers and DNA content remains unknown. Using Drosophila neuroblasts and human cancer cells to study mitotic spindle assembly in polyploid cells, we found that most polyploid cells divide in a multipolar manner. We show that even if an initial centrosome clustering step can occur at mitotic entry, the establishment of kinetochore-microtubule attachments leads to spatial chromosome configurations, whereby the final coalescence of supernumerary poles into a bipolar array is inhibited. Using in silico approaches and various spindle and DNA perturbations, we show that chromosomes act as a physical barrier blocking spindle pole coalescence and bipolarity. Importantly, microtubule stabilization suppressed multipolarity by improving both centrosome clustering and pole coalescence. This work identifies inhibitors of bipolar division in polyploid cells and provides a rationale to understand chromosome instability typical of polyploid cancer cells.
Study of the parameter dependence of laser-accelerated protons from a hydrogen cluster source
Authors: Aurand B , Schwind KM , Toncian T , Aktan E , Cerchez M , Lessmann L , Mannweiler C , Prasad R , Khoukaz A , Willi O
Published: March 2020

We present a study on laser-driven proton acceleration from a hydrogen cluster target. Aiming for the optimisation of the proton source, we performed a detailed parametric scan of the interaction conditions by varying different laser and the target parameters. While the underlying process of a Coulomb-explosion delivers moderate energies, in the range of 100 s of keV, the use of hydrogen as target material comes with the benefit of a debris-free, single-species proton acceleration scheme, enabling high repetition-rate experiments, which are very robust against shot-to-shot fluctuations.
Topological order on the Bloch sphere
Authors: Liss Rotem , Mor Tal , Orús Román
Published: March 2020

A Bloch sphere is the geometrical representation of an arbitrary two-dimensional Hilbert space. Possible classes of entanglement and separability for the pure and mixed states on the Bloch sphere were suggested by [Boyer et al 2017 PRA 95 032 308]. Here we construct a Bloch sphere for the Hilbert space spanned by one of the ground states of Kitaev’s toric code model and one of its closest product states. We prove that this sphere contains only one separable state, thus belonging to the fourth class suggested by the said paper. We furthermore study the topological order of the pure states on its surface and conclude that, according to conventional definitions, only one state (the toric code ground state) seems to present non-trivial topological order. We conjecture that most of the states on this Bloch sphere are neither ‘trivial’ states (namely, they cannot be generated from a product state using a trivial circuit) nor topologically ordered. In addition, we show that the whole setting can be understood in terms of Grover rotations with gauge symmetry, akin to the quantum search algorithm.
Locally-triggered hydrophobic collapse induces global interface self-cleaning in van-der-Waals heterostructures at room-temperature
Authors: Wakolbinger Stefan , Geisenhof Fabian R , Winterer Felix , Palmer Samuel , Crimmann Juri G , Watanabe Kenji , Taniguchi Takashi , Trixler Frank , Weitz R Thomas
Published: March 2020

Mutual relative orientation and well defined, uncontaminated interfaces are the key to obtain van-der-Waals heterostacks with defined properties. Even though the van-der-Waals forces are known to promote the ‘self-cleaning’ of interfaces, residue from the stamping process, which is often found to be trapped between the heterostructure constituents, can interrupt the interlayer interaction and therefore the coupling. Established interfacial cleaning methods usually involve high-temperature steps, which are in turn known to lead to uncontrolled rotations of layers within fragile heterostructures. Here, we present an alternative method feasible at room temperature. Using the tip of an atomic force microscope (AFM), we locally control the activation of interlayer attractive forces, resulting in the global removal of contaminants from the interface (i.e. the contaminants are also removed in regions several µm away from the line touched by the AFM tip). By testing combinations of various hydrophobic van-der-Waals materials, mild temperature treatments, and by observing the temporal evolution of the contaminant removal process, we identify that the AFM tip triggers a dewetting-induced hydrophobic collapse and the van-der-Waals interaction is driving the cleaning process. We anticipate that this process is at the heart of the known ‘self-cleaning’ mechanism. Our technique can be utilized to controllably establish interlayer close coupling between a stack of van-der-Waals layers, and additionally allows to pattern and manipulate heterostructures locally for example to confine material into nanoscopic pockets between two van-der-Waals materials.
Cu2FeSnS4 nanoparticles: potential photovoltaic absorption materials for solar cell application
Authors: Deepika R , Meena P
Published: March 2020

Quaternary semiconductor Cu2FeSnS4 (CFTS) nanoparticle powder have been prepared by a simple chemical technique. The synthesized CFTS nanoparticles have been characterized via powder XRD analysis, Raman spectra, FE-SEM-EDS, UV-Visible absorption spectroscopy, thermal analysis and electrochemical characterization. Powder XRD and Raman spectroscopy confirm the phase and structure of the prepared nanoparticles. The optical absorption studies reveal that the CFTS nanoparticles have a direct optimal band gap in the range from 1.32 to 1.5 eV, which indicates that these nanoparticles are potential absorber materials for thin-film photovoltaic application. The synthesized CFTS nanoparticles were transformed to the ink form and the obtained nanoparticle ink coated on a FTO conducting substrate (surface resistivity-13 Ω sq−1). The catalytic activity of the substrate was analyzed by electrochemical impedance spectroscopy (EIS) and cyclic voltammogram (CV) curves. The appropriate optical band gap and stable electrical properties indicate that Cu2FeSnS4 Nanoparticles are potential materials for thin-film photovoltaic application.
Suppressing spinodal decomposition by incorporation of reduced graphene oxide into (Sn0.5Ti0.5)O2 solid solution
Authors: Choi Yun-Hyuk
Published: March 2020

Here, it is found that the incorporation of rGO into (Sn0.5Ti0.5)O2 solid solution suppresses spinodal decomposition via two characteristic routes. First, the addition of rGO to the solid solution leads to the compositional change from (Sn0.5Ti0.5)O2 to (Sn0.1Ti0.9)O2 moving out of the miscibility gap at SnO2-TiO2 phase diagram, which suppresses spinodal decomposition. The results indicate that addition of rGO promotes reduction and evaporation of SnO2 during heat treatment. Secondly, the incorporation of rGO is found to produce the solid solution with lower Sn and Ti valences and more oxygen vacancies, which can also suppress spinodal decomposition.
Piezoelectric 3D bioprinting for ophthalmological applications: process development and viability analysis of the technology
Authors: Hoehne Juliana Lopes , Carlstron Regina , Dernorwsek Janaína , Cristovam Priscila Cardoso , Bachiega Helder Luiz , Abensur Silvia Itzcovici , Schor Paulo
Published: March 2020

Piezoelectric inkjet 3D bioprinting technology is a viable technique for ophthalmological applications. It provides versatility, high sensibility and accuracy, required in ophthalmological procedures. A process flow for biofabrication was described in detail and validated, using piezoelectric inkjet technology, for ophthalmological applications, in vitro and in situ, based on complex images. Ophthalmological problems were documented by diagnostic examinations and were fed to the flow as complex images. The Concept Mapping methodology and the Conceptual Design approach were utilized to elaborate the 3D bioprinting process flow. It was developed a bioink with corneal epithelial cells. To simulate an in situ bioprinting process, eyes of pigs were selected as the substrate to print the cells. Print scripts used the digitally treated images. In order to print on predefined locations, alignment devices and sample holders were built. The proposed process flow has shown to be a potential tool for the biofabrication of ophthalmological solutions.
Factor, Concurrent and Predictive Validity of the Readiness to Change Questionnaire [Treatment Version] Among Non-Treatment-Seeking Individuals
Authors: Richards Dylan K , Morera Osvaldo F , Cabriales José A , Smith Juliana Cardoso , Field Craig A
Published: March 2020

Aims

This study assessed the factor, concurrent and predictive validity of the revised Readiness to Change Questionnaire [Treatment Version] (RCQ[TV]) among non-treatment-seeking individuals.

Methods

Non-treatment-seeking patients (Mage = 34.8, SD = 12.4) who screened positive for alcohol misuse were recruited from three urban Level I Trauma Centers and completed the RCQ[TV] (Heather et al. [(1999) Development of a treatment version of the Readiness to Change Questionnaire. Addict Res7, 63–83]).

Results

A confirmatory factor analysis supported the three-factor structure of the RCQ[TV]. Observed scores for precontemplation, contemplation and action demonstrated concurrent validity, as they were correlated with drinking and alcohol-related problems prior to baseline assessment. Finally, RCQ[TV] scores at baseline added to the predictability of an alcohol consumption composite score at a 3-month follow-up after controlling for baseline alcohol consumption and randomization to treatment arm.

Conclusions

The results of the present study suggest that the RCQ[TV] has desirable psychometric properties and supports the use of the RCQ[TV] among non-treatment-seeking patients with alcohol misuse.
Changes in Alkaline Phosphatase and 5'-Nucleotidase Multiple Forms After Surgical Management of Biliary Obstruction
Authors: Novo F J , Tutor J C
Published: March 2020

Serial measurements of alkaline phosphatase and 5'-nucleotidase multiple forms in two patients undergoing surgical procedures to release biliary obstruction suggested an inverse relationship between high-M(r) isoforms and serum bile acids concentrations. Furthermore, the study of several groups of patients with cholestatic disorders confirmed this inverse correlation. Mechanisms responsible for these observations are discussed.
A case report of recurrent transient ischaemic attacks on dabigatran for atrial fibrillation: real-world insight into treatment failure
Authors: Huynh Ronald , Anderson Stephanie , Chen Vivien M , Yeoh Thomas
Published: March 2020

Background 

Non-valvular atrial fibrillation (AF) is an important risk factor for acute ischaemic stroke. There has been an increase in the use of direct-acting oral anticoagulants (DOAC therapy) in stroke prophylaxis due to their convenience and rapid action of onset. However, there is a lack of information in the literature regarding management options and possible mechanisms with the apparent failure of DOAC therapy.

Case summary 

We present a clinical case of a 51-year-old man presenting with transient ischaemic attacks on a background of AF on therapeutic doses of dabigatran. His medication box suggested 100% compliance and his admission coagulation studies showed a marginally prolonged activated partial thromboplastin time and thrombin time (TT). While in hospital, our patient had supervised doses of dabigatran (150 mg b.i.d.). Despite this, his peak dabigatran level was undetectable (<40 ng/mL). With the apparent failure of therapy, he was switched to apixaban 5 mg b.i.d., which showed subsequent peak levels in the target range.

Discussion 

There are a number of isolated case reports of DOAC failure in stroke prophylaxis and management has simply involved switching to another DOAC or warfarin. This case is unique as we have discovered undetectable levels of dabigatran providing a mechanism for failure.
Atrial myxomas arise from multipotent cardiac stem cells
Authors: Scalise Mariangela , Torella Michele , Marino Fabiola , Ravo Maria , Giurato Giorgio , Vicinanza Carla , Cianflone Eleonora , Mancuso Teresa , Aquila Iolanda , Salerno Luca , Nassa Giovanni , Agosti Valter , De Angelis Antonella , Urbanek Konrad , Berrino Liberato , Veltri Pierangelo , Paolino Donatella , Mastroroberto Pasquale , De Feo Marisa , Viglietto Giuseppe , Weisz Alessandro , Nadal-Ginard Bernardo , Ellison-Hughes Georgina M , Torella Daniele
Published: March 2020

Aims

Cardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumours are a valuable research model because of the rarity of cardiac tumours, their clinical presentation and uncertain origin. Here, we assessed whether multipotent cardiac stem/progenitor cells (CSCs) give rise to atrial myxoma tissue.

Methods and results

Twenty-three myxomas were collected and analysed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos/CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately ≤10% of the c-kitpos/CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing, and sphere forming while exhibiting an abortive cardiac differentiation potential. Myxoma-derived CSCs possess a mRNA and microRNA transcriptome overall similar to normal myocardium-derived c-kitpos/CD45neg/CD31negCSCs , yet showing a relatively small and relevant fraction of dysregulated mRNA/miRNAs (miR-126-3p and miR-335-5p, in particular). Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumours in xenograft’s in immunodeficient NOD/SCID mice.

Conclusion

Myxoma-derived c-kitpos/CD45neg/CD31neg CSCs fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg/CD31neg CSCs. Taken together the data presented here suggest that human myxomas could be the first-described CSC-related human heart disease.
Using photography to explore people with diabetes’ perspectives on food environments in urban and rural South Africa
Authors: Spires Mark , Delobelle Peter , Sanders David , Puoane Thandi
Published: March 2020

Diabetes, a serious disease resulting in significant morbidity and early mortality, is currently on the rise globally. A major contributor to this observed increase in low- and middle-income countries, such as South Africa, has been the observed change in diet at the population level—a shift from a traditional diet, to one consisting of more energy-dense, processed foods, with more added sugar, salt and fat. Implicated in this degradation of diet are changing local food environments. Participant-generated digital photographs and facilitated focus group discussion-style workshops were utilized to better understand diabetic community members’ perspectives on their food environments in both an urban and rural setting in South Africa, and what (and how) aspects of these physical environments influence their food acquisition behaviours and diet. Qualitative data were analysed using a deductive thematic analysis approach. The resulting predominant themes of accessibility, availability and affordability are outlined and discussed. Findings from this study have implications beyond the self-management of diabetes and extend to the self-management and reduction of all diet-related non-communicable diseases.
Single cell transcriptome profiling of the human alcohol-dependent brain
Authors: Brenner Eric , Tiwari Gayatri R , Kapoor Manav , Liu Yunlong , Brock Amy , Mayfield R Dayne
Published: March 2020

Alcoholism remains a prevalent health concern throughout the world. Previous studies have identified transcriptomic patterns in the brain associated with alcohol dependence in both humans and animal models. But none of these studies have systematically investigated expression within the unique cell types present in the brain. We utilized single nucleus RNA sequencing (snRNA-seq) to examine the transcriptomes of over 16 000 nuclei isolated from the prefrontal cortex of alcoholic and control individuals. Each nucleus was assigned to one of seven major cell types by unsupervised clustering. Cell type enrichment patterns varied greatly among neuroinflammatory-related genes, which are known to play roles in alcohol dependence and neurodegeneration. Differential expression analysis identified cell type-specific genes with altered expression in alcoholics. The largest number of differentially expressed genes (DEGs), including both protein-coding and non-coding, were detected in astrocytes, oligodendrocytes and microglia. To our knowledge, this is the first single cell transcriptome analysis of alcohol-associated gene expression in any species and the first such analysis in humans for any addictive substance. These findings greatly advance the understanding of transcriptomic changes in the brain of alcohol-dependent individuals.
International Relations Theory and the Future of European Integration
Authors: Maher Richard
Published: March 2020

What are the prospects and likely future direction of European integration? Will it be marked by resilience and perhaps even deepening integration among European Union (EU) member states, or will it encounter further instability that could lead to fragmentation and disintegration? The answers to these questions are currently unknown but are important not just for the citizens and countries of the EU but for world politics more broadly. Scholars and other observers have advanced a range of arguments to answer these questions, many of which are derived from the three mainstream theoretical paradigms of contemporary International Relations (IR): realism, liberalism, and constructivism. These arguments reveal disagreement both within and across paradigms over the question of the EU's future. While it is commonly thought that realists are generally pessimistic and liberals and constructivists broadly optimistic regarding the EU's future prospects, it is possible to identify arguments derived from liberal IR theory that the EU faces possibly fatal challenges and realists who see powerful reasons for the EU to stick together, while there are constructivists who think it can go either way. There are thus six basic positions on the future of the EU derived from IR theory. This paper identifies and evaluates a broad range of causal forces that will affect the future of European integration. The paper concludes by discussing the enduring role and value of theory in the study of international relations.
Grazoprevir/elbasvir for the immediate treatment of recently acquired HCV genotype 1 or 4 infection in MSM
Authors: Boyd Anders , Miailhes Patrick , Chas Julie , Valantin Marc-Antoine , Yazdanpanah Yazdan , Rosenthal Eric , Chevaliez Stephane , Piroth Lionel , Rougier Hayette , Peytavin Gilles , Pialoux Gilles , Girard Pierre-Marie , Lacombe Karine
Published: March 2020

Background

In Europe, increases in HCV infection have been observed over the last two decades in MSM, making them a key population for recently acquired HCV. Alternative combinations of direct-acting antiviral agents against early HCV infection need to be assessed.

Patients and methods

In this pilot trial, MSM with recently acquired genotype 1 or 4 HCV infection were prospectively included and received 8 weeks of oral grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination administered once daily. The primary endpoint was sustained virological response evaluated 12 weeks after the end of treatment (EOT) (SVR12). Secondary endpoints were the virological characterization of failures, the quality of life before, during and after treatment and the rate of reinfection.

Results

In a 15 month period, 30 patients were enrolled, all of whom were MSM. Of the 29 patients completing follow-up, 28 (96%, 95% CI = 82%–99%) achieved SVR12. One patient interrupted follow-up (suicide) but had undetectable plasma HCV RNA at EOT. One patient with suboptimal adherence confirmed by plasma drug monitoring relapsed and developed NS3, NS5A and NS5B resistance-associated substitutions (V36M, M28V and S556G). The most common adverse events related to study drug were diarrhoea (n = 4, 13%), insomnia (n = 2, 7%) and fatigue (n = 2, 7%), although no patient discontinued treatment. No HIV RNA breakthrough was reported in the 28 patients with HIV coinfection. At Week 48, reinfection was diagnosed in three patients.

Conclusions

Our data support the use of grazoprevir/elbasvir for immediate treatment against HCV in order to reduce HCV transmission in MSM.
8 The Adoption of Rescue Colloid During Resuscitation Decreases Fluid Administered and Returns End Organ Perfusion
Authors: Comish Paul , Castillo-Angeles Manuel , Carlson Deborah , Phelan Herb , Arnoldo Brett , Kubasiak John
Published: March 2020

Introduction

Traditionally lactated ringers (LR) has been utilized for the resuscitation of thermally injured patients. Both the Parkland and Brooke formula’s include the addition of albumin as part of their ongoing resuscitation after the initial 24 hours. Over the last five years, the addition of albumin to current protocols has been reported to decrease fluid creep. Our institution has adopted these practices and here we present our findings during the adoption phase of rescue albumin during resuscitation.

Methods

A prospectively collected burn registry was queried for patients greater than 18 years, between July 2017 and December 2018, who sustained a thermal injury and required a formal resuscitation. Patients were included in the rescue albumin group if the treating team administered 25% albumin for a sustained urine output less than 0.5ml/kg over 2–3 hours. Our primary outcome was a total volume of resuscitation ml LR/%TBSA/kg. Our secondary outcomes were the change in resuscitation rate and the change in urine output three hours before and three hours after the administration of albumin normalized to %TBSA/kgs. Finally, we compared clinical outcomes of ICU days and length of stay (LOS) between the rescue albumin and no rescue albumin group.

Results

A total of 92 patients with thermal injuries were included: median age was 40 (IQR 31–57), 73% were male, and 30 patients received rescue albumin. The TBSA was increased in those who received rescue albumin (47% vs 38% p=0.02). Despite a higher TBSA in the albumin group the total LR given during resuscitation normalized to TBSA and KG was not significantly different (ml LR/%TBSA/kg: 3.66 vs. 4.31, p=0.149). Similarly, the total urine output (UOP) and the adjusted UOP showed no significant difference, total UOP 1,781 ml no albumin vs 1,483ml rescue albumin (p=0.149) and UOP/kg 21.7ml no albumin vs 18.9 ml rescue albumin (p=0.341). But our secondary outcomes did demonstrate there was a decrease in the LR rate by -0.06 ml/%TBSA/kg/hr (SD 0.13) and an increase in the UOP by 1.61 ml/kg/hr (SD 3.25), see Figure 1.

Conclusions

Rescue albumin administration decreases the amount of fluid administered during resuscitation, and increases end organ function as evidenced by increase UOP. This was observed in patients who sustained larger burns and were failing traditional increases in resuscitation LR. These findings are the basis for a modification to our current protocol and a prospective study of the clinical outcomes.

Applicability of Research to Practice

We believe these findings support the limited use of albumin in patients who fail a conventional LR based resuscitation.