bluuebunny/crossref_metadata_2025 huggingface dataset:
“We are all republicans”: Political Articulation and the Production of Nationhood in France's Face Veil Debate
Authors: Laxer Emily
Published: October 2018

In July 2010, following a year-long nationwide debate over Islamic veiling, the French government passed a law prohibiting facial coverings in all public spaces. Prior research attributes this and other restrictive laws to France's republican secular tradition. This article takes a different approach. Building on literature that sees electoral politics as a site for articulating, rather than merely reflecting, social identities, I argue that the 2010 ban arose in significant part out of political parties’ struggles to demarcate the boundaries of legitimate politics in the face of an ultra-right electoral threat. Specifically, I show that in seeking to prevent the ultra-right National Front party from monopolizing the religious signs issue, France's major right and left parties agreed to portray republicanism as requiring the exclusion of face veiling from public space. Because it was forged in conflict, however, the consensus thus generated is highly fractured and unstable. It conceals ongoing conflict, both between and within political parties, over the precise meaning(s) of French republican nationhood. The findings thus underscore the relationship between boundary-drawing in the political sphere and the process of demarcating the cultural and political boundaries of nationhood in contexts of immigrant diversity.
Rustic Reich: The Local Meanings of (Trans)National Socialism among Paraguay's Mennonite Colonies
Authors: Eicher John
Published: October 2018

This article compares two German-speaking Mennonite colonies in Paraguay and their encounters with Nazism during the 1930s. It focuses on their understandings of the Nazi bid for transnationalvölkischunity. Latin America presents a unique context for studying the Nazis’ relationship to German-speakers abroad because it held the allure of being the last prospect for German cultural and economic expansion, but was simultaneously impossible for the German state to invade. The Menno Colony was made up of voluntary migrants from Canada who arrived in Paraguay in the 1920s. The Fernheim Colony was composed of refugees from the Soviet Union who settled alongside the Menno Colony in the 1930s. Both groups shared a history in nineteenth-century Russia as well as a common faith and culture. Nevertheless, they developed radically different opinions aboutvölkischnationalism. The Menno Colony's communal understanding of Germanness madevölkischpropaganda about Hitler's “New Germany” unappealing to their local sensibilities. They rejected all forms of nationalism as worldly attempts to thwart their cultural-religious isolationism. The refugees of Fernheim Colony, by contrast, shared little communal unity since they originated from diverse settlements across the Soviet Union. They viewed Germanness as a potential bridge to an imagined German homeland and believed that the highest goal ofvölkischunity was to promote communal unity. Resembling other German-speaking communities in Latin America, the two colonies—which seemed identical to Nazi observers—held vastly different interpretations ofvölkischnationalism at the height of the Nazi bid to establish transnational German unity in Latin America.
Integration and Identities: The Effects of Time, Migrant Networks, and Political Crises on Germans in the United States
Authors: Krawatzek Félix , Sasse Gwendolyn
Published: October 2018

This article offers the first large-scale analysis of the interlinked dynamics of integration and belonging based on perceptions of “ordinary” German-speaking migrants in the United States in the nineteenth and twentieth centuries. Our analysis draws on a corpus of over a thousand letters from the North American Letter Collection held at the Forschungsbibliothek Gotha in Germany. Through computer-assisted text analysis, framed by research on transnationalism and immigrant integration, we explore patterns in integration and identities over time. We show how the migrants continuously redefine their identities vis-à-vis their homeland and the host society, and their letters thereby shape the image of the United States and the homeland for their recipients. Our analysis establishes more comprehensively than have previous historical and social science studies that integration into a host society is a non-linear process. Immigrant identities are influenced less by the time they have spent in the receiving country than by critical political events that affect both the country of origin and that of destination. Such events can reactivate migrant's identifications with their homeland. Immigrant networks filter this dual process in that they can facilitate migrants’ integration while also reminding them of people and places left behind.
The effects of systemic steroid therapy on macrophage migration inhibitory factor concentrations in patients with nasal polyps
Authors: Ekinci A
Published: October 2018

Objectives

This study aimed to compare serum macrophage migration inhibitory factor concentrations before and after oral steroid therapy in nasal polyps patients, and determine whether there is a difference between pre-treatment macrophage migration inhibitory factor concentrations and healthy individuals.

Methods

The study included 24 patients with nasal polyps and 25 healthy individuals. The patient group received 1 mg/kg oral steroid.

Results

The mean macrophage migration inhibitory factor concentration before oral steroid therapy was 3889.79 pg/ml in the patient group and 2334.52 pg/ml in the control group. Macrophage migration inhibitory factor concentrations were statistically significantly higher in the pre-oral steroid therapy patient group than in the control group (p= 0.017). The mean pre- and post-oral steroid therapy serum macrophage migration inhibitory factor concentrations were 3889.79 pg/ml and 2451.25 pg/ml, respectively. The reduction in macrophage migration inhibitory factor concentrations was statistically significant (p= 0.010).

Conclusion

These findings suggest that concentrations of macrophage migration inhibitory factor may play a role in the pathogenesis of nasal polyps.
Quantity-based reasoning in the broader autism phenotype: A web-based study
Authors: VAN TIEL BOB , KISSINE MIKHAIL
Published: October 2018

We conducted a web-based study investigating whether the probability of deriving four types of pragmatic inferences depends on the degree to which one has traits associated with the autism spectrum, as measured by the autism spectrum quotient test (Baron-Cohen, Wheelwright, Skinner, Martin, & Clubley, 2001). In line with previous research, we show that, independently of their autism spectrum quotient, participants are likely to derive those pragmatic inferences that can be derived by reasoning solely about alternatives that the speaker could have used. However, if the derivation of the pragmatic inference draws upon more complex counterfactual reasoning about what the speaker could have said, the probability that it is derived decreases significantly with one’s autism quotient. We discuss the consequences for theories of pragmatics in autism and for linguistic theorizing in general.
Prospective Evaluation of Point-of-Care Ultrasound at a Remote, Multi-Day Music Festival
Authors: Prager Ross , Sedgwick Colin , Lund Adam , Kim Daniel , Ho Ben , Stachura Maja , Gutman Samuel
Published: October 2018

Introduction

Point-of-Care Ultrasound (POCUS) has become an important diagnostic tool for hospital-based clinicians. This study assesses the role of POCUS at Pemberton Music Festival 2016 (Pemberton, British Columbia [BC], Canada), a remote mass gathering where physicians face limited resources, complex disposition decisions, and a dynamic clinical environment.

Objectives

This study prospectively evaluated the impact of POCUS on patient diagnosis, management, and disposition based on the self-report of the study physicians. The authors hypothesized that having ultrasound available for use would aid in diagnostic and management decisions and would reduce the need to transfer patients off-site to other health care facilities, reducing impact on the acute health services in the host community.

Methods

A handheld ultrasound was available for use by physicians in the main medical tent. All participating physicians self-reported their training and comfort using POCUS. After each POCUS scan, physicians completed a survey and recorded the indication for use, scans performed, and impact on patient diagnosis, management, and disposition.

Results

In total, POCUS was used on 28 of the 686 patients treated in the main medical tent; POCUS was reported to narrow the differential diagnosis in 64% of cases and altered the working diagnosis in 21% of cases. Its use changed the management plan in 39% of patients. Its use was reported to reduce the burden on broader health care resource utilization in 46% of cases and prevented ambulance transport off-site in 32% of cases (nine cases in total). This corresponded to an absolute risk reduction of 1.3% for the percentage of patients transferred to hospital (PPTH; relative risk reduction of 53%).

Conclusion:

Physicians reported that POCUS improved the diagnosis, management, and disposition of select patients at a remote, multi-day music festival. Also, POCUS reduced ambulance transfers off-site and reduced the perceived burden on broader health care utilization.

PragerR, SedgwickC, LundA, KimD, HoB, StachuraM, GutmanS. Prospective evaluation of point-of-care ultrasound at a remote, multi-day music festival. Prehosp Disaster Med. 2018;33(5):484–489.
Insights on the Japanese Subduction Megathrust Properties From Depth and Lateral Variability of Observed Ground Motions
Authors: Piña‐Valdés J. , Socquet A. , Cotton F.
Published: October 2018

Two ground motion prediction equation models for subduction zones have been tested using a public ground motion database of the KiK‐net records obtained by automated processing protocols (Dawood et al., 2016, https://doi.org/10.1193/071214EQS106). The database contains records of more than 700 interface earthquakes that occurred on the Japan subduction between 1998 and 2012. The Zhao et al. (2006, https://doi.org/10.1785/0120050122) ground motion prediction equation was shown to be the best suited model for the region. It was then used as backbone to analyze the variability of ground motion records. The residuals between observed and predicted ground motions have been analyzed to study the spatial variation of the earthquakes' ground motion frequency content on the Japan megathrust. This analysis revealed a depth dependency of generated ground motions consistent with the downdip segmentation proposed for subduction interfaces (Lay et al., 2012, https://doi.org/10.1029/2011JB009133), a regional ground motion dependency that may be related with lateral variations of the mechanical properties of the subduction interface and a high‐frequency radiations drop in the earthquake sequence that preceded the Tohoku‐Oki earthquake Mw 9.0. The regional ground motion dependency suggests the existence of different domains along trench of the Japan subduction megathrust that control the ground motions and the wave radiation patterns of interface earthquakes. The location of their boundaries is consistent with the extension of the rupture of the 2011 Tohoku‐Oki earthquake, with pre‐Tohoku interseismic coupling, and with the free air gravity anomalies.
Coupled Numerical Modeling of Gas Hydrate‐Bearing Sediments: From Laboratory to Field‐Scale Analyses
Authors: Sánchez Marcelo , Santamarina Carlos , Teymouri Mehdi , Gai Xuerui
Published: October 2018

Methane hydrates are ice‐like compounds made of gas methane and water. Hydrates are stable under low‐temperature and high‐pressure conditions constraining their occurrence in sediments to marine and permafrost settings. A shift from the stability condition triggers an endothermic hydrate dissociation with the associated release of gas and water, impacting (among others) on sediment pore pressure, temperature, and deformations. Therefore, the behavior of hydrate‐bearing sediments (HBS) is controlled by strongly coupled thermo‐hydro‐chemo‐mechanical actions. The analysis of available data from past field and laboratory experiments and the optimization of future field production studies require a formal and robust numerical framework able to capture the complex behavior of this type of soil. In this paper we used a fully coupled thermo‐hydro‐mechanical framework to study different problems involving HBS, from laboratory experiments involving natural hydrate samples to gas production tests. We also develop an analytical solution for the case of gas production via radial depressurization from a confined HBS reservoir. The analyses show the complexity of the thermo‐hydro‐mechanical phenomena associated with this type of system and contribute to better understand the behavior of HBS.
Geochemical Characterization of Two Ferruginous Meromictic Lakes in the Upper Midwest, USA
Authors: Lambrecht Nicholas , Wittkop Chad , Katsev Sergei , Fakhraee Mojtaba , Swanner Elizabeth D.
Published: October 2018

To elucidate the role of (bio)geochemical processes that fueled iron and carbon cycling in early Earth oceans, modern environments with similar geochemical conditions are needed. As the range of chemical, physical, and biological attributes of the Precambrian oceans must have varied in time and space, lakes of different compositions are useful to ask and answer different questions. Tropical Lake Matano (Indonesia), the largest known ferruginous lake, and Lake Pavin (France), a meromictic crater lake, are the two best studied Precambrian ocean analogs. Here we present seasonal geochemical data from two glacially formed temperate ferruginous lakes: Brownie Lake (MN) and Canyon Lake (MI) in the Upper Midwest, USA. The results of seasonal monitoring over multiple years indicate that (1) each lake is meromictic with a dense, anoxic monimolimnion, which is separated from the less dense, oxic mixolimnion by a sharp chemocline; (2) below this chemocline are ferruginous waters, with maximum dissolved iron concentrations >1 mM; (3) meromixis in Brownie Lake is largely anthropogenic, whereas in Canyon Lake it is natural; (4) the shallow chemocline of Brownie Lake and high phosphorus reservoir make it an ideal analog to study anoxygenic photosynthesis, elemental ratios, and mineralogy; and (5) a deep penetrating suboxic zone in Canyon Lake may support future studies of suboxic microbial activity or mineral transformation.
Powerful turbidity currents driven by dense basal layers
Authors: Paull Charles K. , Talling Peter J. , Maier Katherine L. , Parsons Daniel , Xu Jingping , Caress David W. , Gwiazda Roberto , Lundsten Eve M. , Anderson Krystle , Barry James P. , Chaffey Mark , O’Reilly Tom , Rosenberger Kurt J. , Gales Jenny A. , Kieft Brian , McGann Mary , Simmons Steve M. , McCann Mike , Sumner Esther J. , Clare Michael A. , Cartigny Matthieu J.
Published: October 2018

Seafloor sediment flows (turbidity currents) are among the volumetrically most important yet least documented sediment transport processes on Earth. A scarcity of direct observations means that basic characteristics, such as whether flows are entirely dilute or driven by a dense basal layer, remain equivocal. Here we present the most detailed direct observations yet from oceanic turbidity currents. These powerful events in Monterey Canyon have frontal speeds of up to 7.2 m s−1, and carry heavy (800 kg) objects at speeds of ≥4 m s−1. We infer they consist of fast and dense near-bed layers, caused by remobilization of the seafloor, overlain by dilute clouds that outrun the dense layer. Seabed remobilization probably results from disturbance and liquefaction of loose-packed canyon-floor sand. Surprisingly, not all flows correlate with major perturbations such as storms, floods or earthquakes. We therefore provide a new view of sediment transport through submarine canyons into the deep-sea.
Bone protection by inhibition of microRNA-182
Authors: Inoue Kazuki , Deng Zhonghao , Chen Yufan , Giannopoulou Eugenia , Xu Ren , Gong Shiaoching , Greenblatt Matthew B. , Mangala Lingegowda S. , Lopez-Berestein Gabriel , Kirsch David G. , Sood Anil K. , Zhao Liang , Zhao Baohong
Published: October 2018

Targeting microRNAs recently shows significant therapeutic promise; however, such progress is underdeveloped in treatment of skeletal diseases with osteolysis, such as osteoporosis and rheumatoid arthritis (RA). Here, we identified miR-182 as a key osteoclastogenic regulator in bone homeostasis and diseases. Myeloid-specific deletion of miR-182 protects mice against excessive osteoclastogenesis and bone resorption in disease models of ovariectomy-induced osteoporosis and inflammatory arthritis. Pharmacological treatment of these diseases with miR-182 inhibitors completely suppresses pathologic bone erosion. Mechanistically, we identify protein kinase double-stranded RNA-dependent (PKR) as a new and essential miR-182 target that is a novel inhibitor of osteoclastogenesis via regulation of the endogenous interferon (IFN)-β-mediated autocrine feedback loop. The expression levels of miR-182, PKR, and IFN-β are altered in RA and are significantly correlated with the osteoclastogenic capacity of RA monocytes. Our findings reveal a previously unrecognized regulatory network mediated by miR-182-PKR-IFN-β axis in osteoclastogenesis, and highlight the therapeutic implications of miR-182 inhibition in osteoprotection.
A luminous blue kilonova and an off-axis jet from a compact binary merger at z = 0.1341
Authors: Troja E. , Ryan G. , Piro L. , van Eerten H. , Cenko S. B. , Yoon Y. , Lee S.-K. , Im M. , Sakamoto T. , Gatkine P. , Kutyrev A. , Veilleux S.
Published: October 2018

The recent discovery of a gamma-ray burst (GRB) coincident with the gravitational-wave (GW) event GW170817 revealed the existence of a population of low-luminosity short duration gamma-ray transients produced by neutron star mergers in the nearby Universe. These events could be routinely detected by existing gamma-ray monitors, yet previous observations failed to identify them without the aid of GW triggers. Here we show that GRB150101B is an analogue of GRB170817A located at a cosmological distance. GRB150101B is a faint short burst characterized by a bright optical counterpart and a long-lived X-ray afterglow. These properties are unusual for standard short GRBs and are instead consistent with an explosion viewed off-axis: the optical light is produced by a luminous kilonova, while the observed X-rays trace the GRB afterglow viewed at an angle of ~13°. Our findings suggest that these properties could be common among future electromagnetic counterparts of GW sources.
Graphene-enabled and directed nanomaterial placement from solution for large-scale device integration
Authors: Engel Michael , Farmer Damon B. , Azpiroz Jaione Tirapu , Seo Jung-Woo T. , Kang Joohoon , Avouris Phaedon , Hersam Mark C. , Krupke Ralph , Steiner Mathias
Published: October 2018

Directed placement of solution-based nanomaterials at predefined locations with nanoscale precision limits bottom-up integration in semiconductor process technology. We report a method for electric-field-assisted placement of nanomaterials from solution by means of large-scale graphene layers featuring nanoscale deposition sites. The structured graphene layers are prepared via either transfer or synthesis on standard substrates, and then are removed once nanomaterial deposition is completed, yielding material assemblies with nanoscale resolution that cover surface areas >1 mm2. In order to demonstrate the broad applicability, we have assembled representative zero-dimensional, one-dimensional, and two-dimensional semiconductors at predefined substrate locations and integrated them into nanoelectronic devices. Ultimately, this method opens a route to bottom-up integration of nanomaterials for industry-scale applications.
Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration
Authors: Meliani Amine , Boisgerault Florence , Hardet Romain , Marmier Solenne , Collaud Fanny , Ronzitti Giuseppe , Leborgne Christian , Costa Verdera Helena , Simon Sola Marcelo , Charles Severine , Vignaud Alban , van Wittenberghe Laetitia , Manni Giorgia , Christophe Olivier , Fallarino Francesca , Roy Christopher , Michaud Alicia , Ilyinskii Petr , Kishimoto Takashi Kei , Mingozzi Federico
Published: October 2018

Gene therapy mediated by recombinant adeno-associated virus (AAV) vectors is a promising treatment for systemic monogenic diseases. However, vector immunogenicity represents a major limitation to gene transfer with AAV vectors, particularly for vector re-administration. Here, we demonstrate that synthetic vaccine particles encapsulating rapamycin (SVP[Rapa]), co-administered with AAV vectors, prevents the induction of anti-capsid humoral and cell-mediated responses. This allows successful vector re-administration in mice and nonhuman primates. SVP[Rapa] dosed with AAV vectors reduces B and T cell activation in an antigen-selective manner, inhibits CD8+ T cell infiltration in the liver, and efficiently blocks memory T cell responses. SVP[Rapa] immunomodulatory effects can be transferred from treated to naive mice by adoptive transfer of splenocytes, and is inhibited by depletion of CD25+ T cells, suggesting a role for regulatory T cells. Co-administration of SVP[Rapa] with AAV vector represents a powerful strategy to modulate vector immunogenicity and enable effective vector re-administration.
Lateral inhibition by Martinotti interneurons is facilitated by cholinergic inputs in human and mouse neocortex
Authors: Obermayer Joshua , Heistek Tim S. , Kerkhofs Amber , Goriounova Natalia A. , Kroon Tim , Baayen Johannes C. , Idema Sander , Testa-Silva Guilherme , Couey Jonathan J. , Mansvelder Huibert D.
Published: October 2018

A variety of inhibitory pathways encompassing different interneuron types shape activity of neocortical pyramidal neurons. While basket cells (BCs) mediate fast lateral inhibition between pyramidal neurons, Somatostatin-positive Martinotti cells (MCs) mediate a delayed form of lateral inhibition. Neocortical circuits are under control of acetylcholine, which is crucial for cortical function and cognition. Acetylcholine modulates MC firing, however, precisely how cholinergic inputs affect cortical lateral inhibition is not known. Here, we find that cholinergic inputs selectively augment and speed up lateral inhibition between pyramidal neurons mediated by MCs, but not by BCs. Optogenetically activated cholinergic inputs depolarize MCs through activation of ß2 subunit-containing nicotinic AChRs, not muscarinic AChRs, without affecting glutamatergic inputs to MCs. We find that these mechanisms are conserved in human neocortex. Cholinergic inputs thus enable cortical pyramidal neurons to recruit more MCs, and can thereby dynamically highlight specific circuit motifs, favoring MC-mediated pathways over BC-mediated pathways.
Intestinal microbiome adjusts the innate immune setpoint during colonization through negative regulation of MyD88
Authors: Koch Bjørn E. V. , Yang Shuxin , Lamers Gerda , Stougaard Jens , Spaink Herman P.
Published: October 2018

Host pathways mediating changes in immune states elicited by intestinal microbial colonization are incompletely characterized. Here we describe alterations of the host immune state induced by colonization of germ-free zebrafish larvae with an intestinal microbial community or single bacterial species. We show that microbiota-induced changes in intestinal leukocyte subsets and whole-body host gene expression are dependent on the innate immune adaptor gene myd88. Similar patterns of gene expression are elicited by colonization with conventional microbiome, as well as mono-colonization with two different zebrafish commensal bacterial strains. By studying loss-of-function myd88 mutants, we find that colonization suppresses Myd88 at the mRNA level. Tlr2 is essential for microbiota-induced effects on myd88 transcription and intestinal immune cell composition.
Eye gaze patterns reveal how reasoning skills improve with experience
Authors: Guerra-Carrillo Belén C. , Bunge Silvia A.
Published: October 2018

Reasoning, our ability to solve novel problems, has been shown to improve as a result of learning experiences. However, the underlying mechanisms of change in this high-level cognitive ability are unclear. We hypothesized that possible mechanisms include improvements in the encoding, maintenance, and/or integration of relations among mental representations – i.e., relational thinking. Here, we developed several eye gaze metrics to pinpoint learning mechanisms that underpin improved reasoning performance. We collected behavioral and eyetracking data from young adults who participated in a Law School Admission Test preparation course involving word-based reasoning problems or reading comprehension. The Reasoning group improved more than the Comprehension group on a composite measure of four visuospatial reasoning assessments. Both groups improved similarly on an eyetracking paradigm involving transitive inference problems, exhibiting faster response times while maintaining high accuracy levels; nevertheless, the Reasoning group exhibited a larger change than the Comprehension group on an ocular metric of relational thinking. Across the full sample, individual differences in response time reductions were associated with increased efficiency of relational thinking. Accounting for changes in visual search and a more specific measure of relational integration improved the prediction accuracy of the model, but changes in these two processes alone did not adequately explain behavioral improvements. These findings provide evidence of transfer of learning across different kinds of reasoning problems after completing a brief but intensive course. More broadly, the high temporal precision and rich derivable parameters of eyetracking make it a powerful approach for probing learning mechanisms.
Unusual bidirectional frequency dependence of dynamical susceptibility in hexagonal intermetallic Pr2Ni0.95Si2.95
Authors: Pakhira Santanu , Mazumdar Chandan , Basu Abhik , Ranganathan R. , Bhowmik R. N. , Satpati Biswarup
Published: October 2018

In this study, the synthesis of a novel ternary intermetallic compound Pr2Ni0.95Si2.95 forming in single phase only by deliberately introducing vacancies in Ni/Si site is reported. The detailed studies on dc magnetization, heat capacity, ac magnetization & associated dynamical scaling, different types of non-equilibrium dynamical behaviour, viz., magnetic relaxation behaviour as a function of wait time and temperature, aging phenomena, and magnetic memory effect firmly establish that the compound exhibits spin freezing behaviour below 3.3 K (Tf). However, below Tf, temperature dependence of ac susceptibility data exhibit an additional peak that shows reverse frequency dependence to that generally observed in a glassy system. The unusual bidirectional frequency dependence in a single magnetic system is of significant interest and rarely reported in literature. Competing exchange interaction arising from c/a ~ 1 and crystallographic randomness driven magnetic phase separation has been argued to be responsible for such observation. The reverse frequency shift of the low temperature peak has been described on the basis of a simple phenomenological model proposed in this work.
Chemical transfer of dissolved organic matter from surface seawater to sea spray water-soluble organic aerosol in the marine atmosphere
Authors: Miyazaki Yuzo , Yamashita Youhei , Kawana Kaori , Tachibana Eri , Kagami Sara , Mochida Michihiro , Suzuki Koji , Nishioka Jun
Published: October 2018

It is critical to understand how variations in chemical composition in surface seawater (SSW) affect the chemistry of marine atmospheric aerosols. We investigated the sea-to-air transfer of dissolved organic carbon (DOC) via cruise measurements of both ambient aerosols and SSW in the Oyashio and its coastal regions, the western subarctic Pacific during early spring. Sea spray aerosols (SSAs) were selected based on the stable carbon isotope ratio of water-soluble organic carbon (WSOC) (δ13CWSOC) and concentrations of glucose as a molecular tracer in marine aerosols together with local surface wind speed data. For both SSA and SSW samples, excitation-emission matrices were obtained to examine the transfer of fluorescent organic material. We found that the ratios of fluorescence intensity of humic-like and protein-like substances in the submicrometer SSAs were significantly larger than those in the bulk SSW (~63%). This ratio was also larger for the supermicrometer SSAs than for the SSW. The results suggest significant decomposition of protein-like DOC on a timescale of <12–24 h and/or preferential production of humic-like substances in the atmospheric aerosols regardless of the particle size. This study provides unique insights into the complex transfer of DOC from the ocean surface to the atmosphere.
Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in Peyer’s patches of mice
Authors: Di Paola Monica , Bonechi Elena , Provensi Gustavo , Costa Alessia , Clarke Gerard , Ballerini Clara , De Filippo Carlotta , Passani M. Beatrice
Published: October 2018

The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation. When administered exogenously, OEA has beneficial effects in several cognitive paradigms; therefore, in all respects, OEA can be considered a hormone of the gut-brain axis. Here we report an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response. Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer’s patches. Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a “lean-like phenotype”, and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
Realizing multi-functional all-optical data processing on nanoscale SiC waveguides
Authors: Syu Shih-Chang , Cheng Chih-Hsien , Wang Huai-Yung , Chi Yu-Chieh , Wu Chih-I , Lin Gong-Ru
Published: October 2018

All-optical logics are realized on nanoscale SiC waveguides with add-drop micro-ring functionality, including the TE/TM polarized data decoding, the dual-port Kerr switching and gating beyond 12 Gbit/s. With employing the C-C bond enriched SiC thin film upon thermal oxide, the nonlinear refractive index of up to 2.44 × 10−12 cm2/W enables the asymmetric waveguide with polarization distinguishable transmission, which provides a polarization-selectivity to discreminate the TE/TM polarized data decoding with an nearly 9-dB extinction ratio. The TE/TM polarized decoding performance is comparable with a state-of-the-art fiberized in-line polarizer. The complementary transmission in the bus waveguide port facilitates the dual-port Kerr switching for data format conversion/inversion in both add/drop channels. Owing to the TE/TM polarization discriminated throughput, the asymmetric add-drop waveguide micro-ring also permits all-optical AND logic gating functions, where the ON-state outputs only if the pump bit is set at ON state and the probe bit with matched polarization. These results reveal the multi-functionality of the nanoscale SiC add-drop micro-ring waveguide for future photonic logics on chip.
Technology Transfer of the Microphysiological Systems: A Case Study of the Human Proximal Tubule Tissue Chip
Authors: Sakolish Courtney , Weber Elijah J. , Kelly Edward J. , Himmelfarb Jonathan , Mouneimne Roula , Grimm Fabian A. , House John S. , Wade Terry , Han Arum , Chiu Weihsueh A. , Rusyn Ivan
Published: October 2018

The adoption of a new technology into basic research, and industrial and clinical settings requires rigorous testing to build confidence in the reproducibility, reliability, robustness, and relevance of these models. Tissue chips are promising new technology, they have the potential to serve as a valuable tool in biomedical research, as well as pharmaceutical development with regards to testing for efficacy and safety. The principal goals of this study were to validate a previously established proximal tubule tissue chip model in an independent laboratory and to extend its utility to testing of nephrotoxic compounds. Here, we evaluated critical endpoints from the tissue chip developer laboratory, focusing on biological relevance (long-term viability, baseline protein and gene expression, ammoniagenesis, and vitamin D metabolism), and toxicity biomarkers. Tissue chip experiments were conducted in parallel with traditional 2D culture conditions using two different renal proximal tubule epithelial cell sources. The results of these studies were then compared to the findings reported by the tissue chip developers. While the overall transferability of this advanced tissue chip platform was a success, the reproducibility with the original report was greatly dependent on the cell source. This study demonstrates critical importance of developing microphysiological platforms using renewable cell sources.
Site-Specific Labelling of Multidomain Proteins by Amber Codon Suppression
Authors: Heil Christina S. , Rittner Alexander , Goebel Bjarne , Beyer Daniel , Grininger Martin
Published: October 2018

The access to information on the dynamic behaviour of large proteins is usually hindered as spectroscopic methods require the site-specific attachment of biophysical probes. A powerful emerging tool to tackle this issue is amber codon suppression. Till date, its application on large and complex multidomain proteins of MDa size has not been reported. Herein, we systematically investigate the feasibility to introduce different non-canonical amino acids into a 540 kDa homodimeric fatty acid synthase type I by genetic code expansion with subsequent fluorescent labelling. Our approach relies on a microplate-based reporter assay of low complexity using a GFP fusion protein to quickly screen for sufficient suppression conditions. Once identified, these findings were successfully utilized to upscale both the expression scale and the protein size to full-length constructs. These fluorescently labelled samples of fatty acid synthase were subjected to initial biophysical experiments, including HPLC analysis, activity assays and fluorescence spectroscopy. Successful introduction of such probes into a molecular machine such as fatty acid synthases may pave the way to understand the conformational variability, which is a primary intrinsic property required for efficient interplay of all catalytic functionalities, and to engineer them.
Contribution of SPI-1 bistability to Salmonella enterica cooperative virulence: insights from single cell analysis
Authors: Sánchez-Romero María Antonia , Casadesús Josep
Published: October 2018

Salmonella enterica pathogenicity island 1 (SPI-1) is a gene cluster that encodes a type III secretion system and effectors involved in epithelial cell invasion. SPI-1 undergoes bistable expression, with concomitant formation of SPI-1ON and SPI-1OFF lineages. This study describes single cell analysis of SP1-1 bistability and epithelial cell invasion, and reports the unsuspected observation that optimal invasion of epithelial cells requires the presence of both SPI-1ON and SPI-1OFF subpopulations. The contribution of SPI-1OFF cells to optimal invasion may rely on their ability to invade epithelial cells if a SPI-1ON subpopulation is present. In fact, Salmonella SPI-1 mutants are also able to invade epithelial cells in the presence of SPI-1ONSalmonellae, a phenomenon described in the 1990’s by Galán and co-workers. Invasion by SPI-1OFF cells does not seem to involve a diffusible factor. A small number of SPI-1ON cells is sufficient to endow the bacterial population with invasion capacity, a feature that may permit host colonization regardless of the bottlenecks encountered by Salmonella populations inside animals.
The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue
Authors: Komakula Sai Santosh Babu , Tumova Jana , Kumaraswamy Deeptha , Burchat Natalie , Vartanian Vladimir , Ye Hong , Dobrzyn Agnieszka , Lloyd R. Stephen , Sampath Harini
Published: October 2018

Obesity and related metabolic pathologies represent a significant public health concern. Obesity is associated with increased oxidative stress that damages genomic and mitochondrial DNA. Oxidatively-induced lesions in both DNA pools are repaired via the base-excision repair pathway, initiated by DNA glycosylases such as 8-oxoguanine DNA glycosylase (OGG1). Global deletion of OGG1 and common OGG1 polymorphisms render mice and humans susceptible to metabolic disease. However, the relative contribution of mitochondrial OGG1 to this metabolic phenotype is unknown. Here, we demonstrate that transgenic targeting of OGG1 to mitochondria confers significant protection from diet-induced obesity, insulin resistance, and adipose tissue inflammation. These favorable metabolic phenotypes are mediated by an increase in whole body energy expenditure driven by specific metabolic adaptations, including increased mitochondrial respiration in white adipose tissue of OGG1 transgenic (Ogg1Tg) animals. These data demonstrate a critical role for a DNA repair protein in modulating mitochondrial energetics and whole-body energy balance.
A new pharmacokinetic model for 90Y-ibritumomab tiuxetan based on 3-dimensional dosimetry
Authors: Morschhauser F. , Dekyndt B. , Baillet C. , Barthélémy C. , Malek E. , Fulcrand J. , Bigot P. , Huglo D. , Décaudin B. , Simon N. , Odou P.
Published: October 2018

Monoclonal antibodies (mAbs) are key components in several therapies for cancer and inflammatory diseases but current knowledge of their clinical pharmacokinetics and distribution in human tissues remains incomplete. Consequently, optimal dosing and scheduling in clinics are affected. With sequential radiolabeled mAb-based imaging, radiation dosing in tissues/organs can be calculated to provide a better assessment of mAb concentrations in tissues. This is the first pharmacokinetic model of 90Y-Ibritumomab tiuxetan (90Y-IT) in humans to be described, based on three-dimensional (3D) dosimetry using single-photon emission computed-tomography coupled with computed-tomography. 19 patients with follicular lymphoma were treated initially with 90Y-IT in the FIZZ trial. Based on a compartmental approach individualising the vascular compartment within studied organs, this study proposes a reliable pharmacokinetic (PK) five-compartment model replacing the currently used two-compartment model and constitutes a new direction for further research. This model provides exchange constants between the different tissues, Area Under the Curve of 111In-IT in blood (AUC) and Mean Residence Time (MRT) that have not been reported so far for IT. Finally, the elimination process appears to occur in a compartment other than the liver or the spleen and suggests the metabolism of mAbs may take place mainly on the vascular compartment level.
Developmental asynchrony and antagonism of sex determination pathways in a lizard with temperature-induced sex reversal
Authors: Whiteley Sarah L. , Weisbecker Vera , Georges Arthur , Gauthier Arnault Roger Gaston , Whitehead Darryl L. , Holleley Clare E.
Published: October 2018

Vertebrate sex differentiation follows a conserved suite of developmental events: the bipotential gonads differentiate and shortly thereafter sex specific traits become dimorphic. However, this may not apply to squamates, a diverse vertebrate lineage comprising of many species with thermosensitive sexual development. Of the three species with data on the relative timing of gonad differentiation and genital dimorphism, the females of two (Niveoscincus ocellatus and Barisia imbricata) exhibit a phase of temporary pseudohermaphroditism or TPH (gonads have differentiated well before genital dimorphism). We report a third example of TPH in Pogona vitticeps, an agamid with temperature-induced male to female sex reversal. These findings suggest that for female squamates, genital and gonad development may not be closely synchronised, so that TPH may be common. We further observed a high frequency of ovotestes, a usually rare gonadal phenotype characterised by a mix of male and female structures, exclusively associated with temperature-induced sex reversal. We propose that ovotestes are evidence of a period of antagonism between male and female sex-determining pathways during sex reversal. Female sexual development in squamates is considerably more complex than has been appreciated, providing numerous avenues for future exploration of the genetic and hormonal cues that govern sexual development.
Analysis of coupling between magnetic dipoles enhanced by metasurfaces for wireless power transfer efficiency improvement
Authors: Younesiraad Hemn , Bemani Mohammad
Published: October 2018

In this paper, we investigate the possibility of improving efficiency in non-radiative wireless power transfer (WPT) using metasurfaces embedded between two current varying coils and present a complete theoretical analysis of this system. We use a point-dipole approximation to calculate the fields of the coils. Based on this method, we obtain closed-form and analytical expressions which would provide basic insights into the possibility of efficiency improvement with metasurface. In our analysis, we use the equivalent two sided surface impedance model to analyze the metasurface and to show for which equivalent surface impedance the WPT efficiency will be maximized at the design frequency. Then, to validate our theory, we perform a full-wave simulation for analyzing a practical WPT system, including two circular loop antennas at 13.56 MHz. We then design a metasurface composed of single-sided CLSRRs to achieve a magnetic lensing based on the calculated equivalent surface impedance. The analytical results and full-wave simulations indicated non-radiative WPT efficiency improvement due to amplifying the near evanescent field which can be achieved through inserting the proposed metasurface.
Ankyrin Repeat Domain 1 Overexpression is Associated with Common Resistance to Afatinib and Osimertinib in EGFR-mutant Lung Cancer
Authors: Takahashi Akiko , Seike Masahiro , Chiba Mika , Takahashi Satoshi , Nakamichi Shinji , Matsumoto Masaru , Takeuchi Susumu , Minegishi Yuji , Noro Rintaro , Kunugi Shinobu , Kubota Kaoru , Gemma Akihiko
Published: October 2018

Overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is critical in combating EGFR-mutant non-small cell lung cancer (NSCLC). We tried to construct a novel therapeutic strategy to conquer the resistance to second-and third-generation EGFR-TKIs in EGFR-positive NSCLC patients. We established afatinib- and osimertinib-resistant lung adenocarcinoma cell lines. Exome sequencing, cDNA array and miRNA microarray were performed using the established cell lines to discover novel therapeutic targets associated with the resistance to second-and third-generation EGFR-TKIs. We found that ANKRD1 which is associated with the epithelial-mesenchymal transition (EMT) phenomenon and anti-apoptosis, was overexpressed in the second-and third-generation EGFR-TKIs-resistant cells at the mRNA and protein expression levels. When ANKRD1 was silenced in the EGFR-TKIs-resistant cell lines, afatinib and osimertinib could induce apoptosis of the cell lines. Imatinib could inhibit ANKRD1 expression, resulting in restoration of the sensitivity to afatinib and osimertinib of EGFR-TKI-resistant cells. In EGFR-mutant NSCLC patients, ANKRD1 was overexpressed in the tumor after the failure of EGFR-TKI therapy, especially after long-duration EGFR-TKI treatments. ANKRD1 overexpression which was associated with EMT features and anti-apoptosis, was commonly involved in resistance to second-and third-generation EGFR-TKIs. ANKRD1 inhibition could be a promising therapeutic strategy in EGFR-mutant NSCLC patients.
Electrochemical Preparation and Post-treatment of Composite Porous Foam NiZn Alloy Electrodes with High Activity for Hydrogen Evolution
Authors: Zhang Jingguo , Zhou Youzhi , Zhang Shaoming , Li Shuo , Hu Qiang , Wang Ligen , Wang Limin , Ma Fei
Published: October 2018

Composite porous foam NiZn alloy electrodes with nano pore structure were prepared by the combination of eletrodeposition, heat treatment and HCl etching. The morphology of the electrodes was examined by scanning electron microscopy (SEM). And the component of the electrodes was analyzed by Energy Dispersive Spectrum (EDS). The specific surface area and pore size of the electrode were investigated by nitrogen adsorption. The phase constituents were analyzed by X ray diffraction (XRD), and the electrocatalytic characteristics for hydrogen evolution reaction of the electrodes in 30% (mass fraction) KOH solution were investigated by cathode polarization curve. The experimental results showed that the pores were formed on surface of the foam NiZn alloy electrodes after heat treatment at 600 °C, and with the etching by 10% HCl, nano layered structure was formed on the surface of the porous skeleton. Compared with the nickel foam, the surface area of the NiZn foam alloy electrode became larger, and the nano pore structure had good catalytic activity. At current density of 200 mA·dm−2, the hydrogen evolution overpotential of the NiZn foam alloy electrodes were reduced by 222 mV and 276 mV, respectively, through heat treatment of 600 °C and etching in 10% HCl solution, which indicated that the hydrogen evolution overpotential was effectively reduced because of the composite nano porous structure, while the activity of hydrogen evolution of the electrodes was obviously improved.
Splenectomy modulates early immuno-inflammatory responses to trauma-hemorrhage and protects mice against secondary sepsis
Authors: Drechsler S. , Zipperle J. , Rademann P. , Jafarmadar M. , Klotz A. , Bahrami S. , Osuchowski M. F.
Published: October 2018

In polytrauma patients, the impact of splenectomy is equivocal, ranging from negative to protective. We investigated the impact of splenectomy on immune responses in the 1st-hit polytrauma alone and on survival in the post-traumatic sepsis (2nd hit). Female BALB/c mice underwent polytrauma (1st hit) consisting of either a) TH: femur fracture, hemorrhagic shock or b) TSH: splenectomy, femur fracture, hemorrhagic shock. Additionally, the polytrauma hit was followed by cecal ligation and puncture (CLP) 48 h later and compared to CLP alone. Splenectomy improved the 28-day survival in secondary sepsis to 92% (from 62%), while TH lowered it to 46% (p < 0.05). The improved survival was concurrent with lower release of inflammatory cytokines (IL-6, CXCL-1, MCP-1) and increase of C5a post-CLP. In the polytrauma hit alone, TSH induced stronger neutrophilia (1.9 fold) and lymphocytosis (1.7 fold) when compared to TH mice. Moreover, TSH resulted in a 41% rise of regulatory T-cells and reduced the median fluorescence intensity of MHC-2 on monocytes by 55% within 48 h (p < 0.05). Conversely, leukocyte phagocytic capacity was significantly increased by 4-fold after TSH despite a similar M1/M2 macrophage profile in both groups. Summarizing, splenectomy provoked both immuno-suppressive and immuno-stimulatory responses but was life-saving in secondary sepsis. Additionally, the polytrauma components in 2-hit models should be tested for their effects on outcome; the presumed end-effect of the 1st hit solely based on the common immuno-inflammatory parameters could be misleading.