bluuebunny/crossref_metadata_2025 huggingface dataset:
A Facile Approach to 3,4‐Oxepino‐Fused Tricyclic Indoles from MBH‐Acetates of Acetylenic Aldehydes via Successive Allylic Substitution/Intramolecular [3+2] Annulation†
Authors: Reddy Chada Raji , Sathish Puppala , Valleti Reddi Rani
Published: July 2019

Herein, we present our findings on the synthesis of 3,4‐oxepino‐fused indoles by a two‐step reaction sequence involving an initial allylic substitution followed by Rh(III)‐catalyzed intramolecular [3+2] annulation via C−H activation starting from Morita‐Baylis‐Hillman (MBH) acetates of acetylenic aldehydes. The strategy is amenable to broad range of MBH acetates providing a facile access to 3,4‐oxepino‐fused indoles in good yield.
Scenario Analyses for By‐Products Reuse in Integrated Steelmaking Plants by Combining Process Modeling, Simulation, and Optimization Techniques
Authors: Matino Ismael , Branca Teresa Annunziata , Fornai Barbara , Colla Valentina , Romaniello Lea
Published: July 2019

Steel industry consumes resources and produces important amounts of by‐products. Process modeling, simulation, and optimization can address field tests for maximizing by‐products reuse. The improvements of a long‐lasting research activity on slag reuse by deepening aspects, only marginally considered in the past, are presented herein. An Aspen Plus‐based model is developed to assess different basic oxygen furnace slag pretreatment configurations or involved techniques. A previously developed superstructure is upgraded, considering more slag pretreatments and qualities. A simplified Aspen Plus‐based model of mixing of the different pretreated by‐products is applied to evaluate the chemical composition of pellets in each scenario, starting from the computed mixtures. The developed tools are exploited to get a holistic view of steelmaking by‐products reuse and make multiobjective optimization studies which provide different results. For instance, the mixture to be pelletized completely changes if final product quality is (or not) considered in the optimization. Regarding the optimization combining all the considered objective functions, the best slag treatment includes a wet high‐intensity magnetic separation stage, and only some slag qualities are considered in the pellet mixture. A preliminary economic analysis confirms that an optimal combination of internal and external recoveries of by‐products can produce noteworthy revenues.
Mathematical Analysis of the Touching Inclusions Parameters at the Tundish Free Surface to Predict More Realistic Inclusion Removal Rates
Authors: Gutiérrez Enif , Garcia-Hernandez Saúl , Barreto José de Jesús
Published: July 2019

Steel cleanliness is an essential assignment during steelmaking practice to improve the steel quality; this means that the inclusions count during the casting operations must be low. Inclusions removal in the tundish is mainly studied by simulation, assuming that “if an inclusion touches the tundish free surface, it is considered removed,” predicting high removal rates for all sizes and showing large discrepancies when compared with the experimental results. Searching for a realistic accordance between inclusions removal rates obtained by mathematical modeling and the experimental results, this work has the main purpose to predict the inclusion removal count at the free surface in a more realistic fashion in a tundish using flow‐control devices. The results show an over‐estimation up to 80% on the reported removal rates for small inclusions, which is attributed to the use of the Random Walk Model (RWM); however, if the RWM is not used, the inclusions behavior and its removal distribution show severe inconsistencies related to the fluid dynamics. Due to this, a new removal criterion used along with the RWM is applied, predicting more realistic removal rates in agreement with the experimental results and theoretical limits.
Modern management of diverticular disease in men
Authors: Oakland Kathryn , Dorudi Sina
Published: July 2019

The presentation of diverticular disease and its complications are varied: it is common and most people with diverticulosis are asymptomatic. In this article the authors review the burden of diverticular disease and its causes, and present two clinical cases of complicated diverticulitis with a urology theme.
Leptospirosis, one neglected disease in rural Senegal
Authors: Roqueplo Cédric , Kodjo Angeli , Demoncheaux Jean‐Paul , Scandola Pierre , Bassene Hubert , Diatta Georges , Sokhna Cheikh , Raoult Didier , Davoust Bernard , Mediannikov Oleg
Published: July 2019

A serological study was carried out in two Senegalese villages located in the Sine‐Saloum region in order to estimate the presence of anti‐leptospiral antibodies in humans and animals, and to identify the predominant serogroups. Seven hundred and forty‐nine serum samples were collected from humans (n = 545), dogs (n = 33), donkeys (n = 20), goats (n = 52), sheep (n = 43) and N’Dama cattle (n = 56), all originated from Dielmo and Ndiop villages. All samples were tested for different serovars of pathogenic Leptospira species by the microscopic agglutination test. Considering titres ≥ 1:100, 7.7% [CI 95:5.5 to 9.9] on the 545 human blood samples tested and 42.2% [CI95:35.4 to 48.9] on the 204 animal blood samples tested were found to be positive to one or more serovars. The results obtained indicate that the Australis serogroup is the most prevalent serogroup in human (67.3%) and cattle (27.3%). Serogroup Icterohaemorhagiae is the most frequent serogroup in goat (55.6%) and donkey (37.5%). Canicola (23.4%), Icterohaemorhagiae (21.1%) and Australis (12.5%) serogroups are the most prevalent serogroups in dogs. This study shows that diverse Leptospira serovars occur in a wide range of wild and domestic mammal species, as well as in humans in Senegal. However, further studies are needed to better understand the complexity of Leptospira epidemiology in Africa, identify the reservoirs of different serogroups and estimate its impact on livestock. Understanding the multi‐host epidemiology of leptospirosis is essential to control and prevent the disease.
Building flat space-time from information exchange between quantum fluctuations
Authors: Karlsson Anna
Published: July 2019

Abstract

We consider a hypothesis in which classical space-time emerges from information exchange (interactions) between quantum fluctuations in the gravity theory. In this picture, a line element would arise as a statistical average of how frequently particles interact, through an individual rate dt ∼ 1/f

t
and spatially interconnecting rates dl ∼ c/f . The question is if space-time can be modelled consistently in this way. The ansatz would be opposite to the standard treatment of space-time as insensitive to altered physics at event horizons (disrupted propagation of information) but by extension relate to the connection of space-time to entanglement (interactions) through the gauge/gravity duality. We make a first, rough analysis of the implications this type of quantization would have on the classical structure of flat space-time, and of what would be required of the interactions. Seeing no obvious reason for why the origin would be unrealistic, we comment on expected effects in the presence of curvature.
Limited by our limitations
Authors: Ross Paula T. , Zaidi Nikki L. Bibler
Published: July 2019

Study limitations represent weaknesses within a research design that may influence outcomes and conclusions of the research. Researchers have an obligation to the academic community to present complete and honest limitations of a presented study. Too often, authors use generic descriptions to describe study limitations. Including redundant or irrelevant limitations is an ineffective use of the already limited word count. A meaningful presentation of study limitations should describe the potential limitation, explain the implication of the limitation, provide possible alternative approaches, and describe steps taken to mitigate the limitation. This includes placing research findings within their proper context to ensure readers do not overemphasize or minimize findings. A more complete presentation will enrich the readers’ understanding of the study’s limitations and support future investigation.
The blood that remains: card collections from the colonial anthropological missions
Authors: ROQUE RICARDO
Published: July 2019

In this paper I discuss the history of colonial collections through a focus on the social life of a set of blood group cards held by Portuguese institutions since the 1950s. Between the 1940s and 1960s, a series of anthropological field expeditions were organized by the Portuguese Overseas Science Research Board to the then Portuguese colonies in Africa and Asia. A large number of samples of indigenous blood were collected on blood group paper cards in the course of these campaigns. The cards were then stored in Portugal and used for racial serological studies until the 1980s. Thereafter, the collection survived various institutional deaths. Throughout its post-colonial existence in Portuguese institutions, the cards seem to have moved ambivalently between a condition of valued asset and one of obsolete material. And yet they revealed a resilient capacity to mediate conceptions of historical time. Thus the essay asks what it might mean to approach these collections as colonial ‘chronotope’ – devices for connecting space and time – and how and why they endured through various ends, culminating as a genetically contaminated museum object.
AN ENGLISHWOMAN IN THE ALENTEJO: EDITH GUEST AND THE STUDY OF MEGALITHISM IN PORTUGAL IN THE 1930s
Authors: Ávila de Melo Ana , Cardoso João Luís
Published: July 2019

In 1934 English archaeologist Edith Guest (1873–1942) visited the Alentejo region in south-central Portugal. Though not of the first rank of famous archaeologists, Guest made a contribution to archaeology in the first half of the twentieth century, assisting such luminaries as Margaret Murray (1863–1963) and Gertrude Caton-Thompson (1888–1985) in their excavations in the Mediterranean. But why did Guest visit the megaliths in the Alentejo region of Portugal in 1934? Based on unpublished contemporary sources, such as diaries, letters and photographs, this paper suggests that Guest’s presence on the Iberian Peninsula was linked to the ambitions of Manuel Heleno (1894–1970), the second director of the National Archaeological Museum in Lisbon. Studies on megalithic Alentejo were at this time still in their infancy, and Heleno hoped to raise the profile of such studies and the museum with an enterprising schedule of excavations that would attract notable archaeologists and the ensuing publicity. Heleno’s aspirations were successful: archaeologists such as Hugo Obermaier, Vera and Georg Leisner and, of course, Edith Guest took an interest in the fieldwork, helping to bring it to wider attention in Portugal and elsewhere.
HELICONIAN NYMPHS, OEDIPUS’ ANCESTRY AND WILAMOWITZ'S CONJECTURE (SOPH.OT1108)
Authors: Mojsik Tomasz
Published: July 2019

The third stasimon ofOedipus Rex(OT) is the climax of the play, separating the conversation with the Corinthian messenger from the interrogation of the shepherd, so crucial for the narrative. Indeed, the question τίς σε, τέκνον, τίς σ’ ἔτικτε, critical for the plot, comes right at the beginning of its antistrophe. Sophocles, however, offers no easy answer to it. Instead, he provides yet another narrative misdirection, one that—for the last time—suggests that the paths of the king of Thebes and of his predecessor may have been divergent: the possibility that Oedipus’ divine ancestry would question the prophecy of Apollo. After enumerating Pan, Hermes and Apollo himself as possible parents, the song also mentions Dionysus and the ‘Heliconian nymphs’. The reference to Helicon has perplexed the readers for many years, since the text seems to focus on Cithaeron as the ‘birthplace’. As a result, editions and translations prefer the conjecture ἑλικωπίδων (Νυμφᾶν) proposed by U. von Wilamowitz-Moellendorff in 1879, over Ἑλικωνί(α)δων, the form present in all manuscripts. In this paper I argue that an analysis of our sources for Heliconian cults, an assessment of the performative context, and a close reading of the stasimon and its place in the narrative, all suggest that the manuscript reading should be retained.
Examining the relationship between vowel quality and voice quality
Authors: Esposito Christina M. , Sleeper Morgan , Schäfer Kevin
Published: July 2019

The majority of studies on phonation types have focused on low vowels due to the minimal effects of their first formant on harmonic amplitude. In studies of multiple vowel qualities, reports on the relationship between vowel and voice quality are mixed: some show similar formant frequencies across phonation types (e.g. Abramson, Nye & Luangthongkum 2007, Khan 2012), while others show different formant frequencies depending on voice quality (e.g. Ren 1992, Kuang 2011). Results differ as to whether the degree of non-modal phonation varies (Andruski & Ratliff 2000, Kuang 2011) or does not vary (Esposito 2012, Khan 2012) across different vowel qualities. The present study draws on innovations which allow for more accurate corrections for the effects of formant frequencies on spectral measures (i.e. Hanson 1995, Iseli, Shue & Alwan 2007) to examine the relationship between vowel quality and voice quality, in eight languages – !Xóõ, Burmese, Gujarati, Jalapa de Díaz Mazatec, Mon, Santa Ana del Valle Zapotec, White Hmong, and Yi. While no significant difference in the degree of non-modal phonation due to vowel quality was found, results showed a crosslinguistic pattern in the relationship between vowel quality and voice quality: vowels with higher log(F1) and log(F2) values tended to be produced with creakier phonation, while vowels with lower log(F1) and log(F2) values tended to be produced with breathier phonation, but only on the measure H1*-H2*.
On Komlós’ tiling theorem in random graphs
Authors: Nenadov Rajko , Škorić Nemanja
Published: July 2019

Given graphs G and H, a family of vertex-disjoint copies of H in G is called an H-tiling. Conlon, Gowers, Samotij and Schacht showed that for a given graph H and a constant γ>0, there exists C>0 such that if
$p \ge C{n^{ - 1/{m_2}(H)}}$
, then asymptotically almost surely every spanning subgraph G of the random graph 𝒢(n, p) with minimum degree at least
$\delta (G) \ge (1 - \frac{1}{{{\chi _{{\rm{cr}}}}(H)}} + \gamma )np$
contains an H-tiling that covers all but at most γn vertices. Here, χcr(H) denotes the critical chromatic number, a parameter introduced by Komlós, and m2(H) is the 2-density of H. We show that this theorem can be bootstrapped to obtain an H-tiling covering all but at most
$\gamma {(C/p)^{{m_2}(H)}}$
vertices, which is strictly smaller when
$p \ge C{n^{ - 1/{m_2}(H)}}$
. In the case where H
= K3, this answers the question of Balogh, Lee and Samotij. Furthermore, for an arbitrary graph H we give an upper bound on p for which some leftover is unavoidable and a bound on the size of a largest H -tiling for p below this value.
An overview of word and sense similarity
Authors: Navigli Roberto , Martelli Federico
Published: July 2019

Over the last two decades, determining the similarity between words as well as between their meanings, that is, word senses, has been proven to be of vital importance in the field of Natural Language Processing. This paper provides the reader with an introduction to the tasks of computing word and sense similarity. These consist in computing the degree of semantic likeness between words and senses, respectively. First, we distinguish between two major approaches: the knowledge-based approaches and the distributional approaches. Second, we detail the representations and measures employed for computing similarity. We then illustrate the evaluation settings available in the literature and, finally, discuss suggestions for future research.
Adapting antiquity: using tiered texts to increase Latin reading proficiency
Authors: Sears Lindsay L. , Ballestrini Kevin
Published: July 2019

It's the first day of instruction following the holiday break, and you and your students are eagerly anticipating returning to the lengthy Latin reading required for the springtime exams. You take a step back to observe how your students are approaching a new text for the first time as they turn the page to the next selection from one of the canonical Roman authors. Each student dutifully has laid out before them the Latin text, their notebook, a pencil, a Latin dictionary, and any other references or charts they might find valuable in the moment.
Isolated High‐Density Structures in Magnetic Anomaly Regions of the Martian Lower Ionosphere
Authors: Mohanamanasa P. , Venkateswara Rao N. , Leelavathi V. , Rao S. V. B.
Published: July 2019

The occurrence of density structures in magnetic anomaly regions is one of the prominent features of the Martian ionosphere. These structures, in general, occur at altitudes above the main peak. In the present study, we analyze four cases of unusually strong oblique echoes that occur in magnetic anomaly regions and are observed by the Mars Express MARSIS instrument. An in‐depth analysis suggests that these strong oblique echoes, in fact, correspond to the density structures. After correcting for dispersion effects, these structures are found to occur in the lower ionosphere at altitudes as low as 88 km. Ray propagation simulations carried out in this study demonstrate that the density structures can be modeled as Gaussian shapes distributed along planetary latitude. The density of these structures decreases with an increase in altitude. Accordingly, the density structures at higher altitudes are associated with iso‐density contours of the background ionosphere. In the lower ionosphere, however, the density structures are found to immerse in a background ionosphere whose density is much smaller than those of the density structures. The possible causes and consequences of such low altitude density structures are discussed. The results of this study are combined with those of previously reported studies to produce a comprehensive picture of these magnetically controlled density structures.
Magnetotelluric Apparent Resistivity Tensors for Improved Interpretations and 3‐D Inversions
Authors: Hering P. , Brown C. , Junge A.
Published: July 2019

The complex magnetotelluric (MT) apparent resistivity tensor can be decomposed into two real tensors, the apparent resistivity and the resistivity phase tensors, which represent relationships between the observed electric field at a point on the Earth's surface and an associated apparent current density. We explain the differences between these tensors and conventional estimates of apparent resistivity and phase for simple resistivity environments and demonstrate, using canonical models in 1‐D and 2‐D environments, that both tensors are more sensitive to vertical and horizontal resistivity gradients than their conventional counterparts. The properties of the new tensors are explained using electromagnetic induction theory and the effects of associated charges at resistivity boundaries. We introduce a new way to plot tensor ellipses, which brings significant improvements to the interpretation of MT data, using appropriate visualization software. The apparent resistivity tensor gives information about the magnitude and direction of apparent resistivity subsurface structures and has a strong response to vertical resistivity contrasts. The resistivity phase tensor is highly sensitive to vertical boundaries and the associated fields in the TM mode. It is also free from static distortions under the same conditions implied for the conventional phase tensor. These findings have prompted a study in the potential of the new tensors for 3‐D inversions. The results from a 3‐D inversion of a canonical oblique conductor straddling two quarter spaces show distinct improvements in resolving the boundaries of the conductor and open a promising field for future studies.
Origin of Serpentinization Patterns Beneath the S‐Reflector Detachment Fault in the Galicia Margin, Offshore Spain
Authors: Schuba C. N. , Gray G. G. , Morgan J. K. , Schuba J. P. , Sawyer D. S.
Published: July 2019

Serpentinization of exhumed mantle peridotite is thought to influence the mechanics and evolution of hyperextended rifted margins. The Galicia margin is an example of where this may have occurred. New constraints on the 3‐D seismic velocities in the upper mantle beneath the Galicia S‐reflector detachment fault suggest heterogeneously distributed serpentinization (0–90%). To the first order, areas with high degrees of serpentinization correspond with the intersections of crust‐cutting normal faults and the S‐reflector detachment, suggesting that these faults served as conduits transporting fluids to the upper mantle. The role of temperature on alteration was also investigated, as it is a key condition for serpentinization. Estimated paleotemperatures ranged from 55 to 140 °C along the S‐reflector detachment. This temperature range may have played a role in the heterogeneity of alteration. These broader patterns of both high and low mantle alteration correspond to areas of thick and thin overburden immediately postrift, respectively. Several areas that are estimated to lie within the favorable paleotemperature range, and that have crust‐cutting fault intersections, exhibit unusually low degrees of serpentinization. This is possibly due to locally reduced fault permeability. The preservation of relationships between the degree of serpentinization and the occurrence of crust‐cutting fault intersections and postrift overburden thickness implies that volumetrically significant amounts of mantle serpentinization occurred after movement ceased on the detachment. Serpentinization‐related volume increases may have caused postrift uplift of the detachment fault surface. Thus, the current morphology of this detachment surface may be due largely to heterogenous postkinematic processes, rather than primary fault‐related processes.
Hemispheric Asymmetry of Tropical Expansion Under CO2 Forcing
Authors: Watt‐Meyer O. , Frierson D. M. W. , Fu Q.
Published: July 2019

The degree of Hadley cell expansion under global warming will have a substantial impact on changing rainfall patterns. Most previous studies have quantified changes in total tropical width, focused on the Southern Hemisphere Hadley cell or considered each hemisphere's response to a multitude of anthropogenic forcings. It is shown here that under exclusive CO2 forcing, climate models predict twice as much Hadley cell expansion in the Southern Hemisphere relative to the Northern Hemisphere. This asymmetry is present in the annual mean expansion and all seasons except boreal autumn. It is robust across models and Hadley cell edge definitions. It is surprising since asymmetries in simulated Hadley cell expansion are typically attributed to stratospheric ozone depletion or aerosol emission. Its primary cause is smaller sensitivity of the Northern Hemisphere Hadley cell to static stability changes. The pattern of sea surface warming and the CO2 direct radiative effect also contribute to the asymmetry.
Towards a Harmonized Long‐Term Spaceborne Record of Far‐Red Solar‐Induced Fluorescence
Authors: Parazoo Nicholas C. , Frankenberg Christian , Köhler Philipp , Joiner Joanna , Yoshida Yasuko , Magney Troy , Sun Ying , Yadav Vineet
Published: July 2019

Far‐red solar‐induced chlorophyll fluorescence (SIF) has been retrieved from multiple satellites with nearly continuous global coverage since 1996. Multiple official and research‐grade retrievals provide a means for cross validation across sensors and algorithms, but produces substantial variation across products due to differences in instrument characteristics and retrieval algorithm. The lack of a consistent, calibrated SIF data set hampers scientific interpretation of planetary photosynthesis. NASA's Orbiting Carbon Observatory 2 (OCO‐2) offers small sampling footprints, high data acquisition, and repeating spatially resolved targets at bioclimatically diverse locations, providing a unique benchmark for spaceborne sensors traceable to ground data. We leverage overlap between the longer running Global Ozone Monitoring Instrument version 2 (GOME‐2) SIF time series, and more recent state‐of‐the‐art OCO‐2 and TROPOspheric Monitoring Instrument (TROPOMI) data, in a first attempt to reconcile inconsistencies in the long‐term record. After screening and correcting for key instrument differences (time of day, wavelength, Sun‐sensor geometry, cloud effects, footprint area), we find that Global Ozone Monitoring Instrument version 2 and TROPOspheric Monitoring Instrument perform exceedingly well in capturing spatial, seasonal, and interannual variability across OCO‐2 targets. However, Global Ozone Monitoring Instrument version 2 retrieval methods differ by up to a factor of 2 in signal‐to‐noise and magnitude. Magnitude differences are largely attributed to retrieval window choice, with wider windows producing higher magnitudes. The assumed SIF spectral shape has negligible effect. Substantial research is needed to understand remaining sensitivities to atmospheric absorption and reflectance. We conclude that OCO‐2 and TROPOspheric Monitoring Instrument have opened up the possibility to produce a multidecadal SIF record with well‐characterized uncertainty and error quantification for overlapping instruments, enabling back‐calibration of previous instruments and production of a consistent, research‐grade, harmonized time series.
Postobductional Kinematic Evolution and Geomorphology of a Major Regional Structure—The Semail Gap Fault Zone (Oman Mountains)
Authors: Scharf A. , Mattern F. , Moraetis D. , Callegari I. , Weidle C.
Published: July 2019

The Semail Gap/Semail Gap Fault Zone is one of the most prominent tectonic features in the Oman Mountains and is located between the Jabal Akhdar Dome in the west and the Saih Hatat Dome to the east. The two domes were uplifted during the Late Eocene to Early Miocene. Uplift led to monoclinal bending with a “fold axis” parallel to the Semail Gap. Subsequently, dextral transtensional faulting along the Semail Gap Fault Zone ensued. This fault zone follows a major preexisting fault, which explains the distribution differences of Neoproterozoic and Phanerozoic sedimentary formations (partly omissions) across this structure. The vertical and horizontal displacements along the Semail Gap amount to up to ~5.5 and ≤2 km, respectively. Vertical displacement may be a combination of monoclinal bending and later faulting along the Semail Gap Fault Zone. Its latest activity mainly preceded the Quaternary because there is only minor faulting of Quaternary deposits. Despite ongoing uplift of the Oman Mountains, which may amount to ≤50 m during the Quaternary based on incision of wadi/alluvial terraces, only insignificant seismicity is observed and attributed to minor movements along this fault zone. The transtensional deformation is a result of uplift and orogenic/gravitational collapse of the Jabal Akhdar/Saih Hatat domes. The neighboring two hanging wall blocks of each dome moved downward, ESE/SE and SSW/SW, which explains dextral transtension along the Semail Gap Fault Zone. The Semail Gap Fault Zone has a sinistral transtensional counterpart at the southwestern margin of the Nakhl Subdome/Saih Hatat Dome.
Analysis of polygenic risk score usage and performance in diverse human populations
Authors: Duncan L. , Shen H. , Gelaye B. , Meijsen J. , Ressler K. , Feldman M. , Peterson R. , Domingue B.
Published: July 2019

A historical tendency to use European ancestry samples hinders medical genetics research, including the use of polygenic scores, which are individual-level metrics of genetic risk. We analyze the first decade of polygenic scoring studies (2008–2017, inclusive), and find that 67% of studies included exclusively European ancestry participants and another 19% included only East Asian ancestry participants. Only 3.8% of studies were among cohorts of African, Hispanic, or Indigenous peoples. We find that predictive performance of European ancestry-derived polygenic scores is lower in non-European ancestry samples (e.g. African ancestry samples: t = −5.97, df = 24, p = 3.7 × 10−6), and we demonstrate the effects of methodological choices in polygenic score distributions for worldwide populations. These findings highlight the need for improved treatment of linkage disequilibrium and variant frequencies when applying polygenic scoring to cohorts of non-European ancestry, and bolster the rationale for large-scale GWAS in diverse human populations.
Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing
Authors: Cheng Zhi-xue , Guo Chang , Chen Zhuang-gui , Yang Tian-ci , Zhang Jian-ying , Wang Jie , Zhu Jia-xin , Li Dan , Zhang Tian-tuo , Li Hui , Peng Bo , Peng Xuan-xian
Published: July 2019

Serum resistance is a poorly understood but common trait of some difficult-to-treat pathogenic strains of bacteria. Here, we report that glycine, serine and threonine catabolic pathway is down-regulated in serum-resistantEscherichia coli, whereas exogenous glycine reverts the serum resistance and effectively potentiates serum to eliminate clinically-relevant bacterial pathogens in vitro and in vivo. We find that exogenous glycine increases the formation of membrane attack complex on bacterial membrane through two previously unrecognized regulations: 1) glycine negatively and positively regulates metabolic flux to purine biosynthesis and Krebs cycle, respectively. 2) α-Ketoglutarate inhibits adenosine triphosphate synthase, which in together promote the formation of cAMP/CRP regulon to increase the expression of complement-binding proteins HtrE, NfrA, and YhcD. The results could lead to effective strategies for managing the infection with serum-resistant bacteria, an especially valuable approach for treating individuals with weak acquired immunity but a normal complement system.
JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma
Authors: Wong Matthew , Sun Yuting , Xi Zhichao , Milazzo Giorgio , Poulos Rebecca C. , Bartenhagen Christoph , Bell Jessica L. , Mayoh Chelsea , Ho Nicholas , Tee Andrew E. , Chen Xiaoqiong , Li Yang , Ciaccio Roberto , Liu Pei Y. , Jiang Chen C. , Lan Qing , Jayatilleke Nisitha , Cheung Belamy B. , Haber Michelle , Norris Murray D. , Zhang Xu D. , Marshall Glenn M. , Wang Jenny Y. , Hüttelmaier Stefan , Fischer Matthias , Wong Jason W. H. , Xu Hongxi , Perini Giovanni , Dong Qihan , George Rani E. , Liu Tao
Published: July 2019

Chromosome 17q21-ter is commonly gained in neuroblastoma, but it is unclear which gene in the region is important for tumorigenesis. TheJMJD6gene at 17q21-ter activates gene transcription. Here we show that JMJD6 forms protein complexes with N-Myc and BRD4, and is important for E2F2, N-Myc and c-Myc transcription. Knocking down JMJD6 reduces neuroblastoma cell proliferation and survival in vitro and tumor progression in mice, and high levels of JMJD6 expression in human neuroblastoma tissues independently predict poor patient prognosis. In addition,JMJD6gene is associated with transcriptional super-enhancers. Combination therapy with the CDK7/super-enhancer inhibitor THZ1 and the histone deacetylase inhibitor panobinostat synergistically reduces JMJD6, E2F2, N-Myc, c-Myc expression, induces apoptosis in vitro and leads to neuroblastoma tumor regression in mice, which are significantly reversed by forced JMJD6 over-expression. Our findings therefore identify JMJD6 as a neuroblastoma tumorigenesis factor, and the combination therapy as a treatment strategy.
IFN-γ selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate macrophage activation
Authors: Kang Kyuho , Bachu Mahesh , Park Sung Ho , Kang Keunsoo , Bae Seyeon , Park-Min Kyung-Hyun , Ivashkiv Lionel B.
Published: July 2019

Activation of macrophage proinflammatory and antimicrobial phenotypes is regulated by IFN-γ and LPS via synergistic induction of canonical, inflammatory NF-κB target genes. However, whether IFN-γ negatively regulates components of the LPS response, and how this may affect macrophage activation, is still unclear. Here we use combined transcriptomic and epigenomic approaches to find that IFN-γ selectively abrogates LPS-induced feedback and alters macrophage metabolic pathways by suppressing TLR4-mediated gene activation. In contrast to superinduction of inflammatory genes via enhancers that bind IRF1 and STAT1, IFN-γ represses target enhancers that bind STAT3. TLR4-activated but IFN-γ-suppressed enhancers comprise two subsets discernable by differential regulation of histone acetylation and recruitment of STAT3, CDK8 and cohesin. Our findings thus show that IFN-γ suppresses feedback inhibitory and metabolic components of TLR responses to enhance macrophage activation; they also provide insights for IFN-γ-mediated selective inhibition of TLR4-induced transcription. Such inhibition can contribute to severe and sustained inflammatory responses.
KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants
Authors: Herholz Marija , Cepeda Estela , Baumann Linda , Kukat Alexandra , Hermeling Johannes , Maciej Sarah , Szczepanowska Karolina , Pavlenko Victor , Frommolt Peter , Trifunovic Aleksandra
Published: July 2019

Most manipulations that extend lifespan also increase resistance to various stress factors and environmental cues in a range of animals from yeast to mammals. However, the underlying molecular mechanisms regulating stress resistance during aging are still largely unknown. Here we identify Krüppel-like factor 1 (KLF-1) as a mediator of a cytoprotective response that dictates longevity induced by reduced mitochondrial function. A redox-regulated KLF-1 activation and transfer to the nucleus coincides with the peak of somatic mitochondrial biogenesis that occurs around a transition from larval stage L3 to D1. We further show that KLF-1 activates genes involved in the xenobiotic detoxification programme and identified cytochrome P450 oxidases, the KLF-1 main effectors, as longevity-assurance factors of mitochondrial mutants. Collectively, these findings underline the importance of the xenobiotic detoxification in the mitohormetic, longevity assurance pathway and identify KLF-1 as a central factor in orchestrating this response.
3D-structured supports create complete data sets for electron crystallography
Authors: Wennmacher Julian T. C. , Zaubitzer Christian , Li Teng , Bahk Yeon Kyoung , Wang Jing , van Bokhoven Jeroen A. , Gruene Tim
Published: July 2019

3D electron crystallography has recently attracted much attention due to its complementarity to X-ray crystallography in determining the structure of compounds from submicrometre sized crystals. A big obstacle lies in obtaining complete data, required for accurate structure determination. Many crystals have a preferred orientation on conventional, flat sample supports. This systematically shades some part of the sample and prevents the collection of complete data, even when several data sets are combined. We introduce two types of three-dimensional sample supports that enable the collection of complete data sets. In the first approach the carbon layer forms coils on the sample support. The second approach is based on chaotic nylon fibres. Both types of grids disrupt the preferred orientation as we demonstrate with a well suited crystal type of MFI-type zeolites. The easy-to-obtain three-dimensional sample supports have different features, ensuring a broad spectrum of applications for these 3D support grids.
Isostructural Mott transition in 2D honeycomb antiferromagnet V0.9PS3
Authors: Coak Matthew J. , Son Suhan , Daisenberger Dominik , Hamidov Hayrullo , Haines Charles R. S. , Alireza Patricia L. , Wildes Andrew R. , Liu Cheng , Saxena Siddharth S. , Park Je-Geun
Published: July 2019

The MPX3 family of magnetic van-der-Waals materials (M denotes a first row transition metal and X either S or Se) are currently the subject of broad and intense attention for low-dimensional magnetism and transport and also for novel device and technological applications, but the vanadium compounds have until this point not been studied beyond their basic properties. We present the observation of an isostructural Mott insulator–metal transition in van-der-Waals honeycomb antiferromagnet V0.9PS3 through high-pressure x-ray diffraction and transport measurements. We observe insulating variable-range-hopping type resistivity in V0.9PS3, with a gradual increase in effective dimensionality with increasing pressure, followed by a transition to a metallic resistivity temperature dependence between 112 and 124 kbar. The metallic state additionally shows a low-temperature upturn we tentatively attribute to the Kondo effect. A gradual structural distortion is seen between 26 and 80 kbar, but no structural change at higher pressures corresponding to the insulator–metal transition. We conclude that the insulator–metal transition occurs in the absence of any distortions to the lattice—an isostructural Mott transition in a new class of two-dimensional material, and in strong contrast to the behavior of the other MPX3 compounds.
Production of Polyunsaturated Fatty Acids and Lipids from Autotrophic, Mixotrophic and Heterotrophic cultivation of Galdieria sp. strain USBA-GBX-832
Authors: López Gina , Yate Camilo , Ramos Freddy A. , Cala Mónica P. , Restrepo Silvia , Baena Sandra
Published: July 2019

A search for extremophile organisms producing bioactive compounds led us to isolate a microalga identified as Galdieria sp. USBA-GBX-832 from acidic thermal springs. We have cultured Galdieria sp. USBA-GBX-832 under autotrophic, mixotrophic and heterotrophic conditions and determined variations of its production of biomass, lipids and PUFAs. Greatest biomass and PUFA production occurred under mixotrophic and heterotrophic conditions, but the highest concentration of lipids occurred under autotrophic conditions. Effects of variations of carbon sources and temperature on biomass and lipid production were evaluated and factorial experiments were used to analyze the effects of substrate concentration, temperature, pH, and organic and inorganic nitrogen on biomass production, lipids and PUFAs. Production of biomass and lipids was significantly dependent on temperature and substrate concentration. Greatest accumulation of PUFAs occurred at the lowest temperature tested. PUFA profiles showed trace concentrations of arachidonic acid (C20:4) and eicosapentaenoic acid (C20:5). This is the first time synthesis of these acids has been reported in Galdieria. These findings demonstrate that under heterotrophic conditions this microalga’s lipid profile is significantly different from those observed in other species of this genus which indicates that the culture conditions evaluated are key determinants of these organisms’ responses to stress conditions and accumulation of these metabolites.
Small Neotropical primates promote the natural regeneration of anthropogenically disturbed areas
Authors: Heymann Eckhard W. , Culot Laurence , Knogge Christoph , Smith Andrew C. , Tirado Herrera Emérita R. , Müller Britta , Stojan-Dolar Mojca , Lledo Ferrer Yvan , Kubisch Petra , Kupsch Denis , Slana Darja , Koopmann Mareike Lena , Ziegenhagen Birgit , Bialozyt Ronald , Mengel Christina , Hambuckers Julien , Heer Katrin
Published: July 2019

Increasingly large proportions of tropical forests are anthropogenically disturbed. Where natural regeneration is possible at all, it requires the input of plant seeds through seed dispersal from the forest matrix. Zoochorous seed dispersal – the major seed dispersal mode for woody plants in tropical forests – is particularly important for natural regeneration. In this study, covering a period of more than 20 years, we show that small New World primates, the tamarins Saguinus mystax and Leontocebus nigrifrons, increase their use of an anthropogenically disturbed area over time and disperse seeds from primary forest tree species into this area. Through monitoring the fate of seeds and through parentage analyses of seedlings of the legume Parkia panurensis from the disturbed area and candidate parents from the primary forest matrix, we show that tamarin seed dispersal is effective and contributes to the natural regeneration of the disturbed area.
AAV GCG-EGFP, a new tool to identify glucagon-secreting α-cells
Authors: Tudurí Eva , Glavas Maria M. , Asadi Ali , Baker Robert K. , Ellis Cara E. , Soukhatcheva Galina , Philit Marjolaine , Huynh Frank K. , Johnson James D. , Bruce Verchere C. , Kieffer Timothy J.
Published: July 2019

The study of primary glucagon-secreting α-cells is hampered by their low abundance and scattered distribution in rodent pancreatic islets. We have designed a double-stranded adeno-associated virus containing a rat proglucagon promoter (700 bp) driving enhanced green fluorescent protein (AAV GCG-EGFP), to specifically identify α-cells. The administration of AAV GCG-EGFP by intraperitoneal or intraductal injection led to EGFP expression selectively in the α-cell population. AAV GCG-EGFP delivery to mice followed by islet isolation, dispersion and separation by FACS for EGFP resulted in an 86% pure population of α-cells. Furthermore, the administration of AAV GCG-EGFP at various doses to adult wild type mice did not significantly alter body weight, blood glucose, plasma insulin or glucagon levels, glucose tolerance or arginine tolerance. In vitro experiments in transgene positive α-cells demonstrated that EGFP expression did not alter the intracellular Ca2+ pattern in response to glucose or adrenaline. This approach may be useful for studying purified primary α-cells and for the in vivo delivery of other genes selectively to α-cells to further probe their function or to manipulate them for therapeutic purposes.
Disruption of NOTCH signaling by a small molecule inhibitor of the transcription factor RBPJ
Authors: Hurtado Cecilia , Safarova Alena , Smith Michael , Chung Raeeun , Bruyneel Arne A. N. , Gomez-Galeno Jorge , Oswald Franz , Larson Christopher J. , Cashman John R. , Ruiz-Lozano Pilar , Janiak Philip , Suzuki Teri , Mercola Mark
Published: July 2019

NOTCH plays a pivotal role during normal development and in congenital disorders and cancer. γ-secretase inhibitors are commonly used to probe NOTCH function, but also block processing of numerous other proteins. We discovered a new class of small molecule inhibitor that disrupts the interaction between NOTCH and RBPJ, which is the main transcriptional effector of NOTCH signaling. RBPJ Inhibitor-1 (RIN1) also blocked the functional interaction of RBPJ with SHARP, a scaffold protein that forms a transcriptional repressor complex with RBPJ in the absence of NOTCH signaling. RIN1 induced changes in gene expression that resembled siRNA silencing of RBPJ rather than inhibition at the level of NOTCH itself. Consistent with disruption of NOTCH signaling, RIN1 inhibited the proliferation of hematologic cancer cell lines and promoted skeletal muscle differentiation from C2C12 myoblasts. Thus, RIN1 inhibits RBPJ in its repressing and activating contexts, and can be exploited for chemical biology and therapeutic applications.
Birth weight prediction models for the different gestational age stages in a Chinese population
Authors: Li Chunhui , Peng Yang , Zhang Bin , Ji Weiying , Li Li , Gong Jianhua , Xia Wei , Li Yuanyuan , Jin Shuna , Song Ranran , Wang Youjie , Xu Shunqing
Published: July 2019

The study aims to develop new birth weight prediction models for different gestational age stages using 2-dimensional (2D) ultrasound measurements in a Chinese population. 2D ultrasound was examined in pregnant women with normal singleton within 3 days prior to delivery (28–42 weeks’ gestation). A total of 19,310 fetuses were included in the study and randomly split into the training group and the validation group. Gestational age was divided into five stages: 28–30, 31–33, 34–36, 37–39 and 40–42 weeks. Multiple linear regression (MLR), fractional polynomial regression (FPR) and volume-based model (VM) were used to develop birth weight prediction model. New staged prediction models (VM for 28–36 weeks, MLR for 37–39 weeks, and FPR for 40–42 weeks) provided lower systematic errors and random errors than previously published models for each gestational age stage in the training group. The similar results were observed in the validation group. Compared to the previously published models, new staged models had the lowest aggregate systematic error (0.31%) and at least a 19.35% decrease; at least a 4.67% decrease for the root-mean-square error (RMSE). The prediction rates within 5% and 10% of birth weight for new staged models were higher than those for previously published models, which were 54.47% and 85.10%, respectively. New staged birth weight prediction models could improve the accuracy of birth weight estimation for different gestational age stages in a Chinese population.
Emission-wavelength-dependent photoluminescence decay lifetime of N-functionalized graphene quantum dot downconverters: Impact on conversion efficiency of Cu(In, Ga)Se2 solar cells
Authors: Khan Firoz , Kim Jae Hyun
Published: July 2019

Graphene quantum dots (GQDs) have several advantages over inorganic quantum dots owing to their beneficial properties. Recently, GQDs have been used as downconverters in photovoltaic devices. However, the application of GQDs in most emergent thin-film-based Cu(In, Ga)Se2 (CIGS) photovoltaic cells is limited because of either low photoluminescence (PL) quantum yield (QY) or a small Stokes shift (Δλ). Therefore, GQDs with an ultrahigh QY and large Δλ are essential to realizing the two emergent fields, i.e., the application of GQDs in CIGS photovoltaic solar cells. In this regard, we synthesized nitrogen-functionalized GQDs (NGQDs) with an ultrahigh QY (77–99%) and a large Δλ (95–155 nm) via tailoring of the nitrogen and oxygen moieties. The NGQDs were applied in CIGS solar cells to evaluate their downconversion efficiency. Our study shows that the emission wavelength (λem)-dependent photoluminescence decay lifetime (τem) determines the down-conversion efficiency of the nitrogen-functionalized graphene quantum dots. With the increase in τem at λem > 500 nm, the conversion efficiencies of the NGQDs coated-CIGS solar cells increased by 12.22%. Thus, the increase in τem at λem > 500 nm significantly increased the maximum current output and thus enhanced the solar-cell performance.
Polarization independent dielectric metasurface for infrared beam steering applications
Authors: Abdelsalam Mostafa , Mahmoud Ahmed M. , Swillam Mohamed A.
Published: July 2019

Over the past years, metasurfaces have been of great interest due to their ability manipulate optical wavefront by introducing a phase gradient across the transverse directions of the wave. This phase gradient was usually realized using plasmonic resonators which had high intrinsic losses. Here, we demonstrate, numerically, a proof of principle of an all-dielectric silicon based metasurface at the infrared (IR) range that manipulates the wave front and achieves beam steering with significantly high transmission. The proposed cross-shaped unit cell design shows high transmission with the ability to fully control the phase of the transmitted wave from 0 to 2π. The metasurface is made of silicon cross resonators, arranged to have a linear phase gradient, on SiO2 substrate which makes the device compatible with most standard semiconductor fabrication techniques.