bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipopolysaccharide Alters Thermogenic and Inflammatory Genes in White Adipose Tissue in Mice Fed Diets with Distinct 18‐Carbon Fatty‐Acid Composition
Authors: Shin Sunhye , Ajuwon Kolapo M.
Published: November 2018

Fatty acids are involved in the regulation of inflammatory responses in obesity. However, despite being the largest dietary fatty‐acid class, effects of 18‐carbon fatty acids with different degrees of saturation on inflammatory, metabolic, and thermogenic markers have not been well studied. Therefore, the objective of this study was to test if diets with different 18‐carbon fatty‐acid profiles differentially regulate inflammatory and metabolic genes. Male C57BL/6 mice were fed one of the four different diets: a control diet (CON) containing 5.6% kcal fat from lard and 4.4% kcal fat from soybean oil (CON) or three high‐fat diets (HFD) containing 25% kcal fat from lard and 20% kcal fat from either shea butter oil (saturated fatty‐acid‐rich fat; shea butter [SHB]), olive oil (monounsaturated fatty‐acid‐rich fat; olive oil [OO]), or soybean oil (polyunsaturated fatty‐acid‐rich fat; soybean oil [SBO]) ad libitum for 4 weeks with or without a terminal 4‐h lipopolysaccharide (LPS) treatment. Compared to CON, HFD‐fed mice had higher weight gain and fat accumulation. The OO group had the highest brown adipose tissue (BAT) mass while the SBO group had higher Il6 and lower Cpt1a expression in white adipose tissue (WAT) than other HFD groups. Treatment with LPS upregulated expression of proinflammatory cytokines, and this was associated with downregulation of thermogenic gene expression. However, the diets did not have differential effects on inflammatory response to LPS. These data indicate that the saturation degree of 18‐C fatty acids is not an important factor on response to LPS with regard to metabolic and inflammatory indicators.
Texture as an imaging biomarker for disease severity in golden retriever muscular dystrophy
Authors: Eresen Aydin , Alic Lejla , Birch Sharla M. , Friedeck Wade , Griffin John F. , Kornegay Joe N. , JI Jim X.
Published: November 2018

Introduction: Golden retriever muscular dystrophy (GRMD), an X‐linked recessive disorder, causes similar phenotypic features to Duchenne muscular dystrophy (DMD). There is currently a need for a quantitative and reproducible monitoring of disease progression for GRMD and DMD.Methods: To assess severity in the GRMD, we analyzed texture features extracted from multi‐parametric MRI (T1w, T2w, T1m, T2m, and Dixon images) using 5 feature extraction methods and classified using support vector machines.Results: A single feature from qualitative images can provide 89% maximal accuracy. Furthermore, 2 features from T1w, T2m, or Dixon images provided highest accuracy. When considering a tradeoff between scan‐time and computational complexity, T2m images provided good accuracy at a lower acquisition and processing time and effort.Conclusions: The combination of MRI texture features improved the classification accuracy for assessment of disease progression in GRMD with evaluation of the heterogenous nature of skeletal muscles as reflection of the histopathological changes.Muscle Nerve59:380–386, 2019
Fabrication of durable superhydrophobic coating on fabrics surface for oil/water separation
Authors: Ji Qiang , Xiao Xinyan , Ye Zhihao , Yu Nanlin
Published: November 2018

A superhydrophobic fabric coating with hierarchical structure was fabricated by a dip coating, in which dodecyltrimethoxysilane (DTMS)‐modified alumina (Al2O3) was used as modifier and polydimethylsiloxane (PDMS) as additive. The effects of the amounts of Al2O3 nano‐sized particles and PDMS on the water contact angle (WCA) and the sliding angle (SA) of the as‐prepared fabrics coating samples were studied. The surface morphology of the as‐prepared samples was characterized by SEM, and the abrasion resistance and chemical resistance experiments were performed by abrasion resistance test, tape tear test, and chemical soaking test. The results show that WCA and SA of the superhydrophobic fabrics coating are 158° and 6°, respectively. With the increasing addition of PDMS, the abrasion resistance of hydrophobic fabrics coating is improved. The WCA value of the as‐prepared fabrics coating is still >150° after five abrasion cycles. The obtained fabrics exhibit excellent superhydrophobicity and oleophilicity due to the hydrophobic modification of DTMS for Al2O3 nano‐sized particles. And the separation efficiency of the as‐prepared superhydrophobic fabrics coating for n‐dodecane and water system can reach 99.98%. POLYM. COMPOS., 2018. © 2018 Society of Plastics Engineers
Effect of random vibration processing on void content in composite laminates
Authors: Yang Xiaobo , Zhan Lihua , Jiang Chengbiao , Zhao Xing , Guan Chenglong
Published: November 2018

The presence of voids and delamination are common structural defects in the manufacturing process of carbon fiber‐reinforced plastics (CFRPs) structures. The reduction of manufacturing quality and mechanical properties caused by such defects will restrict the extensive application of composite materials in engineering field. Therefore, this work reports the experimental research and analysis on the effect of random vibration applied to the curing system of CFRP laminates, mainly aiming at the reduction of the void content and improvement of mechanical performances under low cure pressures. Range of vibration acceleration was from 5 to 20 g, for different periods of random vibration. For the sake of porosity and property comparison, the autoclave process with different cure pressures was designed as the experimental control groups. Based on the method of mathematical statistics, the content, equivalent diameter and aspect ratio of the voids in the specimens were calculated, and the effect of vibration on the morphological characteristics of pores was clarified. All composite laminates were subjected to the short‐beam three point bending test to determine their interlaminar shear strength (ILSS). Then the influence of random mechanical vibration on the ILSS between the composite layers was analyzed. The research showed that the low porosity and high quality CFRP laminates could be produced at low cure pressures by introducing the random vibration into the forming process. POLYM. COMPOS., 40:3122–3130, 2019. © 2018 Society of Plastics Engineers
Creep deformation and its correspondence to the microstructure of different polyester industrial yarns at room temperature
Authors: Chen Kang , Yu Jinchao , Liu Yanping , Song Minggen , Jiang Quan , Ji Hong , Zou Jiaxiong , Zhang Yumei , Wang Huaping
Published: November 2018

The room temperature creep behaviors and related microstructural changes of a high‐tenacity (HT) poly(ethylene terephthalate) (PET) industrial yarn and a super‐low‐shrinkage (SLS) PET industrial yarn were investigated and compared by using wide‐angle X‐ray scattering (WAXS), small‐angle X‐ray scattering (SAXS), birefringence measurements and Fourier transform infrared spectroscopy (FTIR) in order to identify their respective underlying creep mechanisms. The crystal structure including crystalline orientation and crystallinity of fibers did not show obvious changes after the creep process, while the amorphous structures varied with creep stress. The HT yarn creep deformation was mainly elastic, and its creep recovery ratio was high. The amorphous orientation, amorphous layer thickness and degree of conformation change fromgauchetotransconformers showed a slight increase. The mechanism of this slight change is that the coiled molecular chains are oriented under tensile loading and most of the extended chains are disoriented under offloading in the small amorphous region. By contrast, the SLS yarn underwent plastic creep deformation with a low recovery ratio. After the creep test, the amorphous orientation and lamellar thickness both increased but the crystallinity remained unchanged. The creep mechanism for the SLS yarn is that the molecular chains in the large amorphous domain are easily extended and oriented subjected to tensile loading, while conformation transition fromgauchetotransconformers and the formation of irreversible mesophase take place. © 2018 Society of Chemical Industry
Insights into the excited state dynamical process for 3‐hydroxy‐2‐(5‐(5‐(5‐(3‐hydroxy‐4‐oxo‐4H‐chromen‐2‐yl)thiophen‐2‐yl)thiophen‐2‐yl)thiophen‐2‐yl)‐4H‐chromen‐4‐one
Authors: Wang Yusheng , Yang Guang , Jia Min , Song Xiaoyan , Zhang Qiaoli , Yang Dapeng
Published: November 2018

In this present work, we theoretically investigate a novel system 3‐hydroxy‐2‐(5‐(5‐(5‐(3‐hydroxy‐4‐oxo‐4H‐chromen‐2‐yl)thiophen‐2‐yl)thiophen‐2‐yl)thiophen‐2‐yl)‐4H‐chromen‐4‐one (FT) based on density functional theory (DFT) and time‐dependent DFT (TDDFT) methods. Via calculating the reduced density gradient (RDG) versus sign(λ2) ρ, we firstly verify the formation of the dual intramolecular hydrogen bonds (O1─H2···O3 and O4─H5···O6) for FT form in the S0 state. Then comparing the primary structural parameters and corresponding infrared (IR) vibrational spectra involved in hydrogen bonds between S0 and S1 state, we demonstrate that these two intramolecular hydrogen bonds should be strengthened in the S1 state. Insights into the vertical excitation process, our theoretical results reproduced experimental absorption nature, which confirms that the theoretical level (B3LYP/TZVP) is reasonable and effective in this work. And frontier molecular orbitals (MOs) depict the nature of electronically excited state and support the excited‐state intramolecular proton transfer (ESIPT) reaction. According to the calculated results of potential energy curves along stepwise and synergetic O1─H2 and O4─H5 coordinates, we verify that only the excited‐state single‐proton transfer could occur for FT molecule in the S1 state, although it possesses two intramolecular hydrogen bonds. We not only investigate the detail excited‐state behaviors for FT system and elaborate the ESIPT mechanism but also explain previous experimental results.
Crystal structure of human vaccinia‐related kinase 1 in complex with AMP‐PNP, a non‐hydrolyzable ATP analog
Authors: Ngow Yeen Shian , Rajan Sreekanth , Ye Hong , Yoon Ho Sup
Published: November 2018

Vaccinia‐related kinase 1 (VRK1), a serine/threonine mitotic kinase, is widely over‐expressed in dividing cells and regarded as a cancer drug target primarily due to its function as an early response gene in cell proliferation. However, the mechanism of VRK1 phosphorylation and substrate activation is not well understood. More importantly even the molecular basis of VRK1 interaction with its cofactor, adenosine triphosphate (ATP), is unavailable to‐date. As designing specific inhibitors remains to be the major challenge in kinase research, such a molecular understanding will enable us to design ATP‐competitive specific inhibitors of VRK1. Here we report the molecular characterization of VRK1 in complex with AMP‐PNP, a non‐hydrolyzable ATP‐analog, using NMR titration followed by the co‐crystal structure determined upto 2.07 Å resolution. We also carried out the structural comparison of the AMP‐PNP bound‐form with its apo and inhibitor‐bound counterparts, which has enabled us to present our rationale toward designing VRK1‐specific inhibitors.
N domain of the Lon AAA+ protease controls assembly and substrate choice
Authors: Brown Breann L. , Vieux Ellen F. , Kalastavadi Tejas , Kim SaRa , Chen James Z. , Baker Tania A.
Published: November 2018

Abstract: The protein quality control network (pQC) plays critical roles in maintaining protein and cellular homeostasis, especially during stress. Lon is a major pQC AAA+ protease, conserved from bacteria to human mitochondria. It is the principal enzyme that degrades most unfolded or damaged proteins. Degradation by Lon also controls cellular levels of several key regulatory proteins. Recently, our group determined that Escherichia coli Lon, previously thought to be an obligate homo‐hexamer, also forms a dodecamer. This larger assembly has decreased ATPase activity and displays substrate‐specific alterations in degradation compared with the hexamer. Here we experimentally probe the physical hexamer–hexamer interactions and the biological roles of the Lon dodecamer. Using structure prediction methods coupled with mutagenesis, we identified a key interface and specific residues within the Lon N domain that participates in an intermolecular coiled coil unique to the dodecamer. With this knowledge, we made a Lon variant (LonVQ) that forms a dodecamer with increased stability, as determined by analytical ultracentrifugation and electron microscopy. Using this altered Lon, we characterize the Lon dodecamer's activities using a panel of substrates. Lon dodecamers are clearly functional, and complement critical lon‐ phenotypes but also exhibit altered substrate specificity. For example, the small heat shock proteins IbpA and IbpB are only efficiently degraded well by the hexamer. Thus, by elucidating the intermolecular contacts connecting the hexamers, we are starting to illuminate how dodecamer formation versus disassembly can alter Lon function under conditions where controlling specific activities and substrate preferences of this key protease may be advantageous.
The Tension between 10D Supergravity and dS Uplifts
Authors: Gautason F. F. , Van Hemelryck V. , Van Riet T.
Published: November 2018

We elaborate on the recent work of Moritz et al. where it is argued that anti‐brane uplifting in KKLT models never leads to dS vacua. This is due to flattening effects in the effective potential found when treating the gaugino condensate energy momentum in ten‐dimensional supergravity. We point out that the Silverstein‐Saltman uplift, which effectively dissolves the anti‐brane in 3‐form fluxes, is a conceptually simpler setting in which flattening effects can be present, without requiring assumptions about UV/IR mixings. Along the way we revise and improve on the arguments of Moritz et al. and discuss various subleties when studying gaugino condensates from a ten‐dimensional point‐of‐view. In particular, the “no dS” argument is slightly weaker and we emphasize a technical loophole that might allow dS vacua. Finally we suggest that AdS vacua which are parametrically controlled from these flattening effects belong to the Swampland. We comment on the relation with the recent refined dS Swampland inequalities.
Para‐Hermitian Geometry, Dualities and Generalized Flux Backgrounds
Authors: Marotta Vincenzo E. , Szabo Richard J.
Published: November 2018

We survey physical models which capture the main concepts of double field theory on para‐Hermitian manifolds. We show that the geometric theory of Lagrangian and Hamiltonian dynamical systems is an instance of para‐Kähler geometry which extends to a natural example of a Born geometry. The corresponding phase space geometry belongs to the family of natural almost para‐Kähler structures which we construct explicitly as deformations of the canonical para‐Kähler structure by non‐linear connections. We extend this framework to a class of non‐Lagrangian dynamical systems which naturally encodes the notion of fluxes in para‐Hermitian geometry. In this case we describe the emergence of fluxes in terms of weak integrability defined by the D‐bracket, and we extend the construction to arbitrary cotangent bundles where we reproduce the standard generalized fluxes of double field theory. We also describe the para‐Hermitian geometry of Drinfel'd doubles, which gives an explicit illustration of the interplay between fluxes, D‐brackets and different polarizations. The left‐invariant para‐Hermitian structure on a Drinfel'd double in a Manin triple polarization descends to a doubled twisted torus, which we use to illustrate how changes of polarizations give rise to different fluxes and string backgrounds in para‐Hermitian geometry.
Prelude to molecular dynamics: Topography‐driven gaussian charge models
Authors: Albuquerque Johnross Virgil , Shirsat Rajendra Nivrutti
Published: November 2018

A new strategy to develop Gaussian charge models (GCMs) for molecules like ammonia, water, ethene, hydrogen sulfide, formaldehyde and benzene is presented. These molecular models comprising of positive point charges and negative Gaussian charge distributions (GCDs), which represent nuclei and continuous electron charge distribution, are found to correctly represent the ab initio Molecular Electrostatic Potential (MESP) and reproduce its essential topographical features of corresponding molecules. The models use optimized parameters: positive charges at nuclei, negative charges on GCDs, Gaussian exponent and centers. The Potential Energy Surface (PES) of water dimer has been explored using water GCMs. A good agreement has been found between PES obtained using GCMs and wave function. The Gaussian models correctly predict structure of benzene‐water complex. It is thus recommended to use GCMs for molecular dynamic simulations.
Channel forms and vegetation adjustment to damming in a Mediterranean gravel‐bed river (Serpis River, Spain)
Authors: Sanchis‐Ibor Carles , Segura‐Beltrán Francisca , Navarro‐Gómez Angel
Published: November 2018

This paper focuses on the analysis of changes observed in channel morphology in the Serpis River (Alicante, Spain), a gravel‐bed river dammed since 1958. The paper analyses flow series and several aerial images, prior and subsequent to dam construction, to analyse changes in channel morphology and vegetation colonisation using Geographical Information Systems (GIS) techniques. Results show a concatenation of morphological changes throughout an adjustment sequence (60 years), which started with the transformation from wandering to single thread channel pattern, was followed by a slow vegetation encroachment, and culminated with the stabilization of channel migration. The role of vegetation (particularly Salicaceae species) has been critical in controlling floods' effectiveness, reducing river mobility and shifting, and consolidating a channel planform model adapted to the post‐dam flow conditions.
Mapping with confidence; delineating seagrass habitats using Unoccupied Aerial Systems (UAS)
Authors: Nahirnick Natasha K. , Reshitnyk Luba , Campbell Marcus , Hessing‐Lewis Margot , Costa Maycira , Yakimishyn Jennifer , Lee Lynn
Published: November 2018

There is growing interest in the use of Unoccupied Aerial Systems (UAS) for mapping and monitoring of seagrass habitats. UAS provide flexibility with timing of imagery capture, are relatively inexpensive, and obtain very high spatial resolution imagery compared to imagery acquired from sensors mounted on satellite or piloted aircraft. However, research to date has focused on UAS applications for exposed intertidal areas or clear tropical waters. In contrast, submerged seagrass meadows in temperate regions are subject to high cloud cover and water column turbidity, which may limit the application of UAS imagery for coastal habitat mapping. To test the constraints on UAS seagrass mapping, we examined the effects of five environmental conditions at the time of UAS image acquisition (sun angle, tidal height, cloud cover, Secchi depth and wind speed) and five site characteristics (eelgrass patchiness and density, presence and density of non‐eelgrass submerged aquatic vegetation, sediment tone, eelgrass deep edge and site exposure) at 26 eelgrass (Zostera marina) monitoring sites in British Columbia, Canada. Eelgrass was delineated in UAS orthomosaics using object‐based image analysis, combining image segmentation with manual classification. Each site was ranked according to the analysts’ confidence in the delineated eelgrass. Robust Linear Regression revealed sun angle and ‘theoretical visibility’ (an aggregate of tidal height, Secchi depth, and eelgrass deep edge conditions) to be the most important variables affecting mapping confidence. In general, ideal environmental conditions to obtain high confidence eelgrass mapping included: (1) sun angles below 40°; (2) positive theoretical visibility with Secchi depths >5 m; (3) cloud cover conditions of <10% or >90%; and (4) wind speeds less than 5 km h−1. Additionally, high mapping confidence was achieved for sites with dense, continuous, and homogeneous eelgrass meadows. The results of this analysis will guide implementation of UAS mapping technologies in coastal temperate regions.
The effect of surface pretreatment on the corrosion behaviour of silanated AA2198‐T851 Al‐Cu‐Li alloy
Authors: Donatus Uyime , Klumpp Rafael Emil , Mogili Naga Vishnu Vardan , Altobelli Antunes Renato , Milagre Mariana Xavier , Costa Isolda
Published: November 2018

The corrosion behaviour of silanated AA2198‐T851 alloy substrates with and with no manufacturing‐process induced near‐surface deformed layer (MPI‐NSDL) has been investigated. Two methods (alkaline etching + desmutting and mechanical polishing) were employed in removing the MPI‐NSDL. Silanization was performed using 2‐bis‐triethoxysilylethane. Electrochemical impedance spectroscopy (EIS), salt spray test, and microscopy techniques were employed in the investigation of the corrosion behaviours. The studies revealed that polishing appeared to be the best silanating pre‐treatment (compared with degreasing and etching + desmutting) for the new generation AA2198‐T851 Al‐Cu‐Li alloy, and this was reflected in the EIS spectra. The etched + desmutted and the degreased surface with MPI‐NSDL did not respond well to silanization and presented more pitting sites per square millimeter. However, the severity of corrosion per pit was more on the polished sample compared with the other two. Also, the corrosion mechanisms were different for the three cases.
Bioinspired Photonic Barcodes with Graphene Oxide Encapsulation for Multiplexed MicroRNA Quantification
Authors: Bian Feika , Wu Jindao , Wang Huan , Sun Lingyu , Shao Changmin , Wang Yu , Li Zhiyang , Wang Xuehao , Zhao Yuanjin
Published: November 2018

Multiplexed microRNA (miRNA) quantification has a demonstrated value in clinical diagnosis. In this paper, novel mussel‐inspired photonic crystal (PhC) barcodes with graphene oxide (GO) encapsulation for multiplexed miRNA detection are presented. Using the excellent adhesion capability of polydopamine, the dispersed GO particles can be immobilized on the surfaces of the PhC barcodes to form an additional functional layer. The GO‐decorated PhC barcodes have constant characteristic reflection peaks because the GO immobilization process not only maintains their periodic microstructure but also enhances their stability and anti‐incoherent light‐scattering capability. The immobilized GO particles are shown to enable high‐sensitivity miRNA screening on the surface of the PhC barcodes by integration with a hybridization chain reaction amplification strategy. Because the PhC barcodes have stable encoding reflection peaks, multiplexed low‐abundance miRNA quantification can also be achieved rapidly, accurately, and reproducibly by employing different GO‐decorated PhC barcodes. These features should make GO‐encapsulated PhC barcodes ideal for many practical applications.
Cytotoxic and morphological effects of microcystin‐LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2
Authors: Gutiérrez‐Praena Daniel , Guzmán‐Guillén Remedios , Pichardo Silvia , Moreno Francisco Javier , Vasconcelos Vitor , Jos Ángeles , Cameán Ana María
Published: November 2018

Cylindrospermopsin (CYN) and Microcystin‐LR (MC‐LR) are toxins produced by different cyanobacterial species, which are found mainly in freshwater reservoirs. Both of them can induce, separately, toxic effects in humans and wildlife. However, little is known about the toxic effects of the combined exposure, which could likely happen, taking into account the concomitant occurrence of the producers. As both cyanotoxins are well known to induce hepatic damage, the human hepatocellular HepG2 cell line was selected for the present study. Thus, the cytotoxicity of both pure cyanotoxins alone (0–5 μg/mL CYN and 0–120 μg/mL MC‐LR) and in combination for 24 and 48 h was assayed, as long as the cytotoxicity of extracts from CYN‐producing and nonproducing cyanobacterial species. The potential interaction of the combination was evaluated by the isobologram or Chou–Talalay's method, which provides a combination index as a quantitative measure of the two cyanotoxins interaction's degree. Moreover, a morphological study of the individual pure toxins and their combinations was also performed. Results showed that CYN was the most toxic pure cyanotoxin, being the mean effective concentrations obtained ≈4 and 90 μg/mL for CYN and MC‐LR, respectively after 24 h. However, the simultaneous exposure showed an antagonistic effect. Morphologically, autophagy, at low concentrations, and apoptosis, at high concentrations were observed, with affectation of the rough endoplasmic reticulum and mitochondria. These effects were more pronounced with the combination. Therefore, it is important to assess the toxicological profile of cyanotoxins combinations in order to perform more realistic risk evaluations.
High Frequency of Symptoms Suggestive of Endometriosis in a Clinic‐Based Sample of Low‐Income Women in Mexico City
Authors: Harris Courtney , Willie Tiara C. , Cardoso Lauren F. , Campos Rivera Paola A. , Diaz Olavarrieta Claudia , Pollack Anna Z. , Gupta Jhumka
Published: November 2018

Endometriosis affects an estimated 10 percent of women and girls globally, yet little is known about symptoms and awareness among women in low‐ and middle‐income countries. This commentary presents a descriptive secondary analysis of baseline data from a clinic‐based intervention study with low‐income women in Mexico City who experienced intimate partner violence in the past year (N = 754). The secondary analysis examined symptoms that may be suggestive of endometriosis as well as endometriosis awareness. Over half of participants reported at least one symptom suggestive of endometriosis (59.3 percent), while 12.5 percent of those reporting a symptom had ever heard of the disease. Pain‐related symptoms were classified as pain with menses disrupting household chores, pain with menses disrupting work or social gatherings, and/or pelvic pain outside of menses disrupting daily activities. Fewer women who reported pain‐related symptoms had heard of the disease compared to those who reported a history of infertility (11.4 vs. 15.7 percent, respectively). This study documents levels of awareness of endometriosis among women in Mexico City and underscores the importance of integrating endometriosis education into broader global reproductive health agendas.
3‐Bromopyruvate as a potent anticancer therapy in honor and memory of the late Professor André Goffeau
Authors: Ko Young H. , Niedźwiecka Katarzyna , Casal Margarida , Pedersen Peter L. , Ułaszewski Stanisław
Published: November 2018

3‐Bromopyruvate (3BP) is a small, highly reactive molecule formed by bromination of pyruvate. In the year 2000, the antitumor properties of 3BP were discovered. Studies using animal models proved its high efficacy for anticancer therapy with no apparent side effects. This was also found to be the case in a limited number of cancer patients treated with 3BP. Due to the “Warburg effect,” most tumor cells exhibit metabolic changes, for example, increased glucose consumption and lactic acid production resulting from mitochondrial‐bound overexpressed hexokinase 2. Such alterations promote cell migration, immortality via inhibition of apoptosis, and less dependence on the availability of oxygen. Significantly, these attributes also make cancer cells more sensitive to agents, such as 3BP that inhibits energy production pathways without harming normal cells. This selectivity of 3BP is mainly due to overexpressed monocarboxylate transporters in cancer cells. Furthermore, 3BP is not a substrate for any pumps belonging to the ATP‐binding cassette superfamily, which confers resistance to a variety of drugs. Also, 3BP has the capacity to induce multiple forms of cell death, by, for example, ATP depletion resulting from inactivation of both glycolytic and mitochondrial energy production pathways. In addition to its anticancer property, 3BP also exhibits antimicrobial activity. Various species of microorganisms are characterized by different susceptibility to 3BP inhibition. Among tested strains, the most sensitive was found to be the pathogenic yeast‐like fungus Cryptococcus neoformans. Significantly, studies carried out in our laboratories have shown that 3BP exhibits a remarkable capacity to eradicate cancer cells, fungi, and algae.
Sollten Pflegeroboter auch sexuelle Assistenzfunktionen bieten?
Authors: Döring Nicola
Published: November 2018

Pflege und Pflegeroboter zielen darauf ab, Menschen mit Pflegebedarf zu betreuen, Krankheiten zu verhüten und Gesundheit zu fördern. Das umfasst die ganzheitliche Sorge um das Wohlbefinden und schließt auch das sexuelle Wohlbefinden als wichtigen Gesundheitsfaktor und als Menschenrecht mit ein. Der Beitrag behandelt zunächst den Stellenwert des sexuellen Wohlbefindens und konkretisiert die sexuellen Anliegen von Menschen mit Pflegebedarf. Die bisherigen Angebote der Sexualassistenz für Menschen mit Pflegebedarf werden beschrieben. Auf dieser Grundlage plädiert der Beitrag dafür, im Sinne einer besseren Förderung sexuellen Wohlbefindens von Menschen mit Pflegebedarf in Zukunft auch Konzepte der robotischen Sexualassistenz zu entwickeln und zu evaluieren. Dabei werden drei Entwicklungspfade aufgezeigt, nämlich die Nutzung von Sexrobotern und Sexpuppen, die Ausstattung von multifunktionalen Pflegerobotern mit sexuellen Assistenzfunktionen sowie der Einsatz spezialisierter sexueller Assistenzgeräte. In allen drei Szenarien sollte robotische Sexualassistenz jeweils durch professionelle Sexualberatung begleitet werden. Angesichts der Tatsache, dass in der Allgemeinbevölkerung das Interesse an und die Nutzung von sexuellen Artefakten wie Sexspielzeugen und Sexmaschinen weit verbreitet und positiv mit sexueller Gesundheit verknüpft ist, sind Menschen mit Pflegebedarf von dieser Entwicklung nicht auszuschließen. Möglichen Gefahren robotischer Sexualassistenz gilt es im Zuge einer interdisziplinär informierten Entwicklung der Technik und ihrer Einsatzszenarien entgegenzuwirken.
Bewertung von AAL-Ambient-Assisted-Living-Systemen bei Personen mit kognitiver Schädigung: Match vs. Mismatch
Authors: Hauer Klaus
Published: November 2018

Die Entwicklung von Robotern im Gesundheitsbereich oder AAL-System folgt ethischen wie auch technischen Grundsätzen. Ein Schwerpunkt in der ethischen Bewertung wie auch der zielführenden technischen Entwicklung von Unterstützungssystemen ist die Passung (Match) von technischen Funktionen mit den Ressourcen, Wünschen und Bedürfnissen der Zielgruppe (Nutzerperspektive), für die das System entwickelt wird. Eine Nichtbeachtung einer solchen Passung (Mismatch) hat vielerlei negative Konsequenzen von der Nichtbenutzung solcher Systeme bis hin zu Überforderung, Gefährdung oder negativen psychosozialen Konsequenzen. Besonders vulnerable Gruppen wie Menschen mit kognitiver Schädigung (MKS) sind betroffen und erfordern besondere Strategien und Bewertungs-/Entwicklungskriterien, um den limitierten, aber auch verbliebenen Ressourcen dieser speziellen Zielgruppe gerecht zu werden. Am Beispiel des Vergleiches zweier Teilfunktionen eines intelligenten Mobilitätsunterstützungssystems (MOBOT) soll im Beitrag untersucht werden, wie eine passende mit einer eher unpassenden Entwicklung gestaltbar und klassifizierbar ist.
Wege zu verantwortungsvoller Forschung und Entwicklung im Bereich der Pflegerobotik: Die ambivalente Rolle der Ethik
Authors: Kehl Christoph
Published: November 2018

Obwohl die Entwicklungsarbeiten an Pflegerobotern bis in die 1980er Jahre zurückreichen, waren die bisherigen Bemühungen nicht von größeren Erfolgen gekrönt. Zwar wurde eine Vielzahl an Produktvisionen und Prototypen hervorgebracht, diese haben jedoch in aller Regel noch nicht den Weg in den Pflegemarkt gefunden. Dies hängt nicht nur mit technischen Schwierigkeiten zusammen, sondern lässt sich auch auf die bislang stark technikfokussierte Ausrichtung der Forschungs- und Entwicklungspraxis zurückführen: Offenbar ist es noch nicht gelungen, Angebote zu entwickeln, die von Kostenträgern und Endkunden ausreichend akzeptiert werden. Vor diesem Hintergrund geht der Beitrag der Frage nach, wie sich eine verantwortungsvolle Forschungs- und Entwicklungspraxis gestalten lässt, die den hohen Anforderungen an Serviceroboter-Anwendungen im Pflegebereich gerecht wird. Mit Blick auf neuere politische Konzepte zur Technology Governance wird dargelegt, dass neben einer bedarfsorientierten Vorgehensweise vor allem der angemessene Umgang mit normativen Fragen und Unsicherheiten heraussticht, was auf die zentrale Bedeutung ethischer Reflexion verweist. Die Schwierigkeiten, die sich bei der ethischen Bewertung der robotischen Pflegeanwendungen ergeben, werden beleuchtet, und es wird schließlich die ambivalente Rolle der Ethik bei der Governance der Pflegerobotik herausgearbeitet.
Light-ray operators in conformal field theory
Authors: Kravchuk Petr , Simmons-Duffin David
Published: November 2018

Abstract

We argue that every CFT contains light-ray operators labeled by a continuous spin J. When J is a positive integer, light-ray operators become integrals of local operators over a null line. However for non-integer J , light-ray operators are genuinely nonlocal and give the analytic continuation of CFT data in spin described by Caron-Huot. A key role in our construction is played by a novel set of intrinsically Lorentzian integral transforms that generalize the shadow transform. Matrix elements of light-ray operators can be computed via the integral of a double-commutator against a conformal block. This gives a simple derivation of Caron-Huot’s Lorentzian OPE inversion formula and lets us generalize it to arbitrary four-point functions. Furthermore, we show that light-ray operators enter the Regge limit of CFT correlators, and generalize conformal Regge theory to arbitrary four-point functions. The average null energy operator is an important example of a light-ray operator. Using our construction, we find a new proof of the average null energy condition (ANEC), and furthermore generalize the ANEC to continuous spin.
Phenomenology of the generalised scotogenic model with fermionic dark matter
Authors: Hagedorn Claudia , Herrero-García Juan , Molinaro Emiliano , Schmidt Michael A.
Published: November 2018

Abstract

We study a simple extension of the Standard Model that accounts for neutrino masses and dark matter. The Standard Model is augmented by two Higgs doublets and one Dirac singlet fermion, all charged under a new dark global symmetry. It is a generalised version of the Scotogenic Model with Dirac fermion dark matter. Masses for two neutrinos are generated radiatively at one-loop level. We study the case where the singlet fermion constitutes the dark matter of the Universe. We study in depth the phenomenology of the model, in particular the complementarity between dark matter direct detection and charged lepton flavour violation observables. Due to the strong limits from the latter, dark matter annihilations are suppressed and the relic abundance is set by coannihilations with (and annihilations of) the new scalars if the latter and the Dirac fermion are sufficiently degenerate in mass. We discuss how different ratios of charged lepton flavour violating processes can be used to test the model. We also discuss the detection prospects of the charged scalars at colliders. In some cases these leave ionising tracks and in others have prompt decays, depending on the flavour in the final state and neutrino mass orderings.
Electroweak vacuum lifetime in two Higgs doublet models
Authors: Branchina V. , Contino F. , Ferreira P. M.
Published: November 2018

Abstract

We study the stability of neutral electroweak vacua in two Higgs doublet models, and calculate the lifetime of these states when the parameters are such that they are false vacua. As the two Higgs doublet model is invariant under a sign change of both doublets, degenerate true vacua exist. It is shown that this degeneracy, despite the fact that each of these minima locally describes the same physics, can immensely affect their lifetime. We apply these calculations to the parameter space of the models which is allowed by recent LHC searches, and infer combinations of parameters which should be excluded on grounds of a tunneling time inferior to the age of the universe.
One-point functions in β-deformed $$ \mathcal{N}=4 $$ SYM with defect
Authors: Widén Erik
Published: November 2018

Abstract

We generalize earlier results on one-point functions in

$$ \mathcal{N}=4 $$

N
=
4

SYM with a codimension one defect, dual to the D3-D5-brane setup in type IIB string theory on AdS
5 ×S
5, to a similar setup in the β-deformed version of the theory. The treelevel vacuum expectation values of single-trace operators in the two-scalar-subsector are expressed as overlaps between a matrix product state (MPS) and Bethe states in the corresponding twisted spin-chain picture. We comment on the properties of this MPS and present the simplest analytical overlaps and their behavior in a certain limit (of large k). Importantly, we note that the deformation alters earlier interpretations of the MPS as an integrable boundary state, seemingly obstructing simplifications of the overlaps analogous to the compact determinant formula found in the non-deformed theory. The results are supplemented with some supporting numerical results for operators of length eight with four excitations.
Bone Mineral Density as a Risk Factor for Patients Undergoing Surgery for Hepatocellular Carcinoma
Authors: Miyachi Yosuke , Kaido Toshimi , Yao Siuan , Shirai Hisaya , Kobayashi Atsushi , Hamaguchi Yuhei , Kamo Naoko , Yagi Shintaro , Uemoto Shinji
Published: November 2018

Background

We have reported the impact of sarcopenia and body composition on patients undergoing hepatectomy for hepatocellular carcinoma (HCC). However, the impact of bone mineral density (BMD) on outcomes after hepatectomy for HCC and correlation with other parameters including sarcopenia are unclear.

Methods

We retrospectively analyzed 465 patients who underwent primary hepatectomy for HCC between April 2005 and March 2015. We analyzed the plain CT images at the level of the eleventh thoracic vertebra with the region of interest and defined as preoperative BMD.

Results

In this cohort, male (n = 367) and female (n = 98) patients showed significant heterogeneity in age, body composition markers, tumor factors, peri‐operative parameters and so on. The median preoperative BMD in male and female patients was 155 and 139 HU, respectively (P = 0.005). BMD was negatively correlated with age in female (r = −0.590, P < 0.001) and intramuscular adipose tissue content in both male and female (r = −0.332 and −0.359, respectively, P < 0.001). For males, BMD < 160 HU was associated with worse cancer‐specific survival post‐hepatectomy (P = 0.015). In contrast, females were not (P = 0.135). For male patients, multivariate analysis identified low BMD as an independent risk factor for death (hazard ratio 1.720, 95% confidence interval 1.038–2.922, P = 0.035) after hepatectomy for HCC.

Conclusion

Preoperative low BMD was an independent risk factor for cancer‐specific mortality after hepatectomy for HCC.
Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase
Authors: Maffioli Sonia I , Sosio Margherita , Ebright Richard H , Donadio Stefano
Published: November 2018

Pseudouridimycin (PUM) is a novel pseudouridine-containing peptidyl-nucleoside antibiotic that inhibits bacterial RNA polymerase (RNAP) through a binding site and mechanism different from those of clinically approved RNAP inhibitors of the rifamycin and lipiarmycin (fidaxomicin) classes. PUM was discovered by screening microbial fermentation extracts for RNAP inhibitors. In this review, we describe the discovery and characterization of PUM. We also describe the RNAP-inhibitory and antibacterial properties of PUM. Finally, we review available information on the gene cluster and pathway for PUM biosynthesis and on the potential for discovering additional novel pseudouridine-containing nucleoside antibiotics by searching bacterial genome and metagenome sequences for sequences similar to pumJ, the pseudouridine-synthase gene of the PUM biosynthesis gene cluster.
Female Migration to ISIS: Conclusions and Recommendations
Authors: Viano Emilio C.
Published: November 2018

To effectively address/counter/neutralize the areas in which ISIS/ISIL/IS/DAESH has had
success in its strategy, operation and tactics, the international community must deal with
the following three issues: (A) multifaceted recruitment counter-efforts; (B) looking at
women as survivors of ISIS on a continuum from free agent to victim; (C) the need to
investigate and monitor the movement of people with concern and respect for human rights and
international treaties. The role of different actors is examined in detail. The need for
international efforts and coordination is also addressed. Concrete recommendations are
provided. The list of members of the International Task Force that worked on this
Conclusions and Recommendations is given.
2288 Neural correlates of face processing in autism spectrum disorder: A quantitative meta-analysis of current literature and future directions
Authors: Ammons Carla J. , Winslett Mary-Elizabeth , Kana Rajesh K.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Autism spectrum disorder (ASD) affects 1 in 68 people and includes restricted, repetitive behavior, and social communication deficits. Aspects of face processing (i.e., identity, emotion perception) are impaired in some with ASD. Neuroimaging studies have shown aberrant patterns of brain activation and connectivity of face processing regions. However, small sample sizes and inconsistent results have hindered clinical utility of these findings. The study aims to establish consistent patterns of brain responses to faces in ASD and provide directions for future research. METHODS/STUDY POPULATION: Neuroimaging studies were identified through a multi-database search according to PRISMA guidelines. In total, 23 studies were retained for a sample size of 383 healthy controls and 345 ASD. Peak coordinates were extracted for activation likelihood estimation (ALE) in GingerALE v2.3.6. Follow-up ALE analyses investigated directed Versus undirected gaze, static Versus dynamic, emotional Versus neutral, and familiar Versus unfamiliar faces. RESULTS/ANTICIPATED RESULTS: Faces produced bilateral activation of the fusiform gyrus (FG) in healthy controls (−42 −52 −20; 22 −74 −12, p<0.05, FDR) and left FG activation in ASD (−42 −54 −16, p<0.05, FDR). Activation in both groups was lateral to the mid-fusiform sulcus. Follow-up results pending. DISCUSSION/SIGNIFICANCE OF IMPACT: Reduced right FG activation to faces may inform biomarker or response to intervention studies. Mid-fusiform sulcus proved a reliable predictor of functional divides should be investigated on a subject-specific level.
2520 Proteomics in the early diagnosis of metabolic syndrome in a Hispanic pre-teen cohort
Authors: Viera Guillermo T. , Candales Ángel L. , Rivera Horacio S.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The objective of the present study is to determine if decreased adiponectin and increased leptin levels are associated with the development of MetS and identifiable endothelial dysfunction in a cohort of Hispanic pre-pubertal children. To do so we propose the following aims: (1) To measure expression of adiponectin and leptin levels in a Hispanic pre-pubertal cohort and determine their correlation with features of the MetS. (2) To perform proteomic analysis in a Hispanic pre-pubertal cohort. (3) Evaluate early onset of endothelial dysfunction and its correlation with expression of adiponectin and leptin levels in a Hispanic pre-pubertal cohort. METHODS/STUDY POPULATION: A cross-sectional pilot study will obtain a random representative sampling of children aged 6–12 years from all geographical areas of Puerto Rico. Children will be assessed regarding pre-pubertal status through Tanner staging and later divided into pre-MetS Versus MetS groups as well as controls. MetS will include children meeting 3 or more of the current International Diabetes Federation (IDF) criteria. Pre-MetS will include children with at least 1 criterion for MetS. Anthropometric data, blood pressure readings, ultrasound-based noninvasive testing for endothelial dysfunction, and laboratory assays will be performed to the study population and data analyzed for correlation. Total adiponectin and leptin levels will be measured using a commercially available quantitative sandwich enzyme-linked immunoassay test. The study will be submitted to the University of Puerto Rico Medical Sciences Campus’ Institutional Review Board (IRB) for approval. Written consent and assent will be obtained from parents and children respectively to ensure patient anonymity. RESULTS/ANTICIPATED RESULTS: We hypothesize that low levels of adiponectin and high levels of leptin will correlate with features of the MetS as defined by the IDF consensus statement, as well as with clinical features of MetS in undiagnosed Hispanic pre-pubertal youth. We also hypothesize that non-invasive testing of endothelial function will correlate both with clinical features of the MetS and with low levels of adinopectin and high levels of leptin. DISCUSSION/SIGNIFICANCE OF IMPACT: The correlation of findings suggestive of endothelial dysfunction and biomarker expression (mainly adiponectin and leptin levels) in a pre-pubertal cohort has yet to be established and could also provide information regarding early atherogenesis in otherwise unidentified youth at risk. Therefore, by using a proteomic approach, this study aims to measure associations between clinical features of the MetS and expression of proteins associated with an adverse cardiometabolic profile in a Hispanic pre-pubertal population. We will concurrently measure the degree of endothelial dysfunction and evaluate whether a correlation exists between previously mentioned protein expression and early onset of dysfunction.
2482 Reward-based learning as a function of the severity of substance abuse risk in drug-naïve youth
Authors: Parvaz Muhammad A. , Kim Kristen , Froudist-Walsh Sean , Newcorn Jeffrey H. , Ivanov Iliyan
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Deficits in reward-based learning have been shown in youth at risk for developing substance use disorders (SUD). Here, we investigated whether computational models can be used to more precisely delineate the additive effects of such risk loading (i.e., the comparison between youth with ADHD, and those with ADHD and familial SUD) on reward-based learning in youth. METHODS/STUDY POPULATION: In total, 41 drug-naïve youth, stratified into 3 groups based on ADHD diagnosis and parental SUD: healthy controls (HC, n=13; neither ADHD nor parental SUD), low risk (LR, n=13; ADHD only), and high risk (HR, n=15; both ADHD and parental SUD), performed a reward task. Learning rates, prediction and congruence t-scores were computed using a reinforcement learning model and analyzed via a multivariate ANOVA. RESULTS/ANTICIPATED RESULTS: The analyses showed a significant linear effect in task accuracy, which decreased with increasing risk profiles. Analyses of the model-derived variables also showed similar significant linear effects in learning rates and the congruence t-score, but not in the prediction t-score. These effects were primarily driven by significantly higher learning rate and congruence t-score in HC compared with HR youth. DISCUSSION/SIGNIFICANCE OF IMPACT: These results show most profound deficits in reward-learning in HR youth. These findings also show that computational analyses can offer added value over conventional behavioral analyses by more precisely evaluating group differences in relation to SUD risk.