bluuebunny/crossref_metadata_2025 huggingface dataset:
Wind tunnel quantification of dynamic stall on an S817 airfoil and its control using synthetic jet actuators
Authors: Rice Thomas T. , Taylor Keith , Amitay Michael
Published: September 2018

Wind tunnel experiments were performed to quantify the aerodynamic characteristics of the S817 airfoil in dynamic stall conditions, and the subsequent application of active flow control to modify the manner by which dynamic stall incepts. Both quasi‐2D and cantilevered finite span configurations were tested. Surface pressure, six‐component force‐torque sensor, and stereoscopic particle image velocimetry (SPIV) were used to quantify the baseline flow and the benefits of actuating synthetic jets (installed at x/c = 0.35, angled 45° into the flow, and at a momentum coefficient Cμ  =  0.012). The airfoil was pitched at reduced frequencies of kf = 0.025 and 0.05 and at shallow and deep stall. Vortex induced lift from dynamic stall was observed and was eliminated by the use of synthetic jets for nearly all conditions; pitching moment deviation was also observed to be significant, and was eliminated at shallow stall and significantly reduced during deep dynamic stall when the synthetic jets were actuated. Moreover, the activation of synthetic jets resulted in significant reduction in the hysteresis (area within the pitching up and pitching down load history) of the lift and pitching moment through all experimental conditions, as much as 41% and 85%, respectively. SPIV flow fields in shallow dynamic stall demonstrated that actuation of synthetic jets confined the separated region to the trailing edge, in both the instantaneous and time averaged sense. To further reduce the lift and pitching moment hysteresis at high angles of attack, a pulse modulation technique was used and showed a marked increase in synthetic jet performance compared with the continuously actuated case and achieved this result with approximately 65% less power consumption.
Transcriptomic and proteomic changes from medium supplementation and strain evolution in high-yielding Clostridium thermocellum strains
Authors: Papanek Beth , O’Dell Kaela B , Manga Punita , Giannone Richard J , Klingeman Dawn M , Hettich Robert L , Brown Steven D , Guss Adam M
Published: September 2018

Clostridium thermocellum is a potentially useful organism for the production of lignocellulosic biofuels because of its ability to directly deconstruct cellulose and convert it into ethanol. Previously engineered C. thermocellum strains have achieved higher yields and titers of ethanol. These strains often initially grow more poorly than the wild type. Adaptive laboratory evolution and medium supplementation have been used to improve growth, but the mechanism(s) by which growth improves remain(s) unclear. Here, we studied (1) wild-type C. thermocellum, (2) the slow-growing and high-ethanol-yielding mutant AG553, and (3) the faster-growing evolved mutant AG601, each grown with and without added formate. We used a combination of transcriptomics and proteomics to understand the physiological impact of the metabolic engineering, evolution, and medium supplementation. Medium supplementation with formate improved growth in both AG553 and AG601. Expression of C1 metabolism genes varied with formate addition, supporting the hypothesis that the primary benefit of added formate is the supply of C1 units for biosynthesis. Expression of stress response genes such as those involved in the sporulation cascade was dramatically over-represented in AG553, even after the addition of formate, suggesting that the source of the stress may be other issues such as redox imbalances. The sporulation response is absent in evolved strain AG601, suggesting that sporulation limits the growth of engineered strain AG553. A better understanding of the stress response and mechanisms of improved growth hold promise for informing rational improvement of C. thermocellum for lignocellulosic biofuel production.
End-of-life care in the Dutch medical curricula
Authors: De Bruin Josefien , Verhoef Mary-Joanne , Slaets Joris P. J. , Van Bodegom David
Published: September 2018

Introduction Future doctors must be trained in giving appropriate care to terminal patients. In several countries, medical curricula have been reviewed for the attention devoted to end-of-life care (ELC). In the Netherlands, no formal review had been performed. Therefore, the aim of this study was to provide an overview of the Dutch medical curricula regarding ELC.

Methods We formed a checklist based on international standards consisting of five domains of ELC education that are considered essential. Firstly, we studied the Dutch national blueprint on medical education. Secondly, using a questionnaire based on the checklist we studied the curricula of the eight medical faculties. A questionnaire was sent to all Dutch medical faculties to study the compulsory courses of the curricula. To assess the elective courses, we consulted the study guides.

Results The national blueprint included four of the five domains of ELC. None of the eight medical faculties taught all domains specifically on ELC; they were taught within other courses. Most attention was given to the domains on psychological, sociological, cultural and spiritual aspects; communication and conversational techniques; and juridical and ethical aspects. One faculty taught an elective course that included all essential aspects of the international standards.

Discussion Our study shows that ELC is currently insufficiently mentioned in the national blueprint and that none of the faculties fully integrated ELC as a part of their compulsory medical curricula.
Two-dimensional distributed strain sensing with an Archimedean spiral arrangement in optical frequency domain reflectometry
Authors: Guo Yamei , Ding Zhenyang , Liu Kun , Jiang Junfeng , Wang Chenhuan , Liu Tiegen
Published: September 2018

We demonstrate a distributed two-dimensional (2D) strain-sensing system in optical frequency domain reflectometry (OFDR) with an Archimedean spiral arrangement of the sensing fiber. The Archimedean spiral describes a simple relationship between the radial radius and polar angle, such that each circle (the polar angle from 0 to 2π) can sense the 2D strain in all directions. The strain between two adjacent circles can also be easily obtained because an Archimedean spiral facilitates sensing of every angle covering the full 2D range. Based on the mathematical relation of Archimedean spirals, we deduce the relationship between the one-dimensional position of the sensing fiber and 2D distribution in polar coordinates. The results of the experiment show that an Archimedean spiral arrangement system can achieve 2D strain sensing with different strain load angles.
Cavafy and Niketas Choniates: a possible source for ‘Waiting for the barbarians’
Authors: Pontani Filippomaria
Published: September 2018

This article suggests that a possible source of inspiration for Cavafy's poem ‘Waiting for the barbarians’ can be identified in a passage of the Byzantine historian Niketas Choniates concerning the arrival of German ambassadors at the court of Alexios III in Constantinople in 1196. The context of diplomacy, the city's decadent atmosphere, the emperor's self-humiliation and the unsuccessful ostentation of luxury and royal attire are prominent features linking both texts.
The Inequality of Low-Wage Migrant Labour: Reflections onPN v FRandOPT v Presteve Foods
Authors: Hastie Bethany
Published: September 2018

This article explores the inequality inhering to low-wage migrant labour and critically evaluates the current capacity of human rights law to account for and address this inequality. This article uses two recent human rights tribunal decisions as case studies through which to conduct this examination:PN v FR, 2015 BCHRT 60, andOPT v Presteve Foods Ltd, 2015 HRTO 675. While these cases establish the positive role of human rights law in accounting for the wider context in which inequality impacts on migrant labour, this role is also inherently limited by the purpose, scope, and function of the Tribunals. This article will identify and discuss issues illustrated in the cases that are reflective of deeper systemic and structural inequalities attending low-wage migrant labour, including: the underlying reasons motivating low-wage labour migration; the legal regulations governing migrant workers’ status and employment conditions; and, the racialization of migrant workers.
Temporary Labour Migration and the “Ceremony of Innocence” of Postwar Labour Law: Confronting “the South of the North”
Authors: Smith Adrian A.
Published: September 2018

The article considers the temporary labour migration program in Canada, which catapults workers from the global South into work and wider relations in the global North, in the context of debates swirling around Anglo-American labour law. There is widespread consensus that labour law is experiencing a sustained moment of crisis in the face of neoliberal globalization. Not widely considered is how this crisis relates to temporary labour migration and the global South-North relationship and, in turn, how this relationship may impact emergent approaches tasked with transforming or transcending the field. Critical interventions seeking to confront the “southern question” within the socio-legal imaginary have gone largely unnoticed by labour law scholars. Transnational labour law may hold potential for an alternative account of the racialized production of unfree migrant labour. But only if its adherents can truly confront the dynamic unfolding through temporary labour migration—that of the “South of the North.”
Travail non libre et rapports sociaux de sexe – À propos des programmes canadiens d’immigration temporaire
Authors: Galerand Elsa , Gallié Martin
Published: September 2018

L’analyse proposée ici défend la nécessité d’opérer un déplacement vis-à-vis des termes qui semblent dominer pour l’heure la réflexion sur les nouvelles formes d’esclavage ou de servitude pour y intégrer pleinement les rapports sociaux de sexe en tant que rapports sociaux de production et d’exploitation. Dans cette perspective, à partir de deux études sur le terrain réalisées auprès des travailleuses domestiques et des travailleurs agricoles soumis aux programmes canadiens d’immigration, il s’agit de chercher à voir comment les rapports de travail qui sont rassemblés sous les concepts « d’esclavage moderne » et de « travail non libre » produisent non seulement une classe de travailleurs exclue du salariat canonique, mais aussi et simultanément une main-d’œuvre racisée, intrinsèquement sexuée : des « non-ressortissants » qui sont aussi des hommes et des femmes dont les corps sont différemment mis au travail, exploités et marqués.
Managing Communist Enterprises: Poland, Hungary, and Czechoslovakia, 1945–1970
Authors: SCRANTON PHILIP
Published: September 2018

Business history for three generations has focused almost exclusively on capitalist firms, their managers, and their relations with markets, states, and rivals. However, enterprises on all scales also operated within communist nations “building socialism” in the wake of World War II. This article represents a first-phase exploration of business practices in three Central European states as Stalinism gave way to cycles of reform and retrenchment in the 1960s. Focusing chiefly on industrial initiatives, the study asks: How did socialist enterprises work and change across the first postwar generation, given their distinctive principles and political/economic contexts, and implicitly, what contrasts with capitalist activities are worth considering.
What Can We Learn from the Business History of Communist Enterprises?
Authors: GERMUSKA PÁL
Published: September 2018

This comment challenges two main points of Phil Scranton’s article: his periodization, and the adequacy of the utilized sources. His interpretation neglects the efforts of the de-Stalinization attempts in Eastern European socialist countries during the mid-1950s, though these measures established all subsequent reforms. He based his argumentation on contemporaneous articles from the 1950s and 1960s while an expanding fresh literature is available on socialist economies, thanks to the large-scale declassification of formerly top-secret documents. However, his article is an extremely important contribution to the business history of communism and a delightful point of departure for many kinds of future research in this field.
Whatever Happened to Dubai's Public Spaces?
Authors: Alawadi Khaled
Published: September 2018

As an ambitious city aspiring to become a major contributor to and player in the global world, Dubai often tends to be endeared to and affected by grand-scale urbanism and skyscraper skylines. The recent practice of architecture in Dubai is replete with examples of architectural monuments and miraculous constructions. Whilst the architectural feats required to raise grand structures for global branding and economic strategy are noteworthy, many other facets of urbanism also warrant adulation and exploration. One example is the narrative of human-scale urbanism—the pedestrian-driven places that put people at the center of the town. Due to its human-scale nature and morphology, the quotidian landscape, more than other existing settings, such as those modeled on “bigness” and dispersion successfully narrates a clear story about the essence of everyday urbanism: the nexus between the physical and the social, and the architecture and everyday life of the city's urban spaces. Life and culture in the UAE have evolved drastically, but in old communities where the quotidian landscape is still palpable, it has stayed the same—simple, open to everyone, and full of animation and affection.
Climate change and beef supply chain in Southern Brazil
Authors: Pereira P. R. R. X. , Hasenack H. , Pereira G. R. , Dewes H. , Canellas L. C. , Oliveira T. E. , Barcellos J. O. J.
Published: September 2018

The current study evaluated the uncertainty of beef cattle supply for slaughter due to the variable climate of Rio Grande do Sul, Brazil. The data included the numbers of cattle slaughtered, local live cattle prices, price and amount of exported beef, and the prices of the Brazilian beef futures market. Data were collected on the beef supply from January 1997 to March 2014. Climate data included El Niño (EN), La Niña (LN), South Atlantic Sub-tropical Dipole (SASD), Negative and Positive Atlantic Dipole (−AD and +AD), Tropical South and North Atlantic indices. Statistical analysis was performed by a multivariate regression of time series. It was observed that EN and SASD climatic variables increased the numbers of beef cattle slaughtered, with a 1 and 4-month lag, respectively. On the other hand, LN and -AD decreased the number of animals slaughtered, with 4 and 0 months’ lag, respectively, meaning that there was an immediate response to −AD, while there was a 4-month delay for LN. The amount of exported beef and live beef cattle prices were explained by the number of animals slaughtered in the state. Data suggested that the beef cattle market in RS was more strongly influenced by the occurrence of climate phenomena with LN and −AD than by economic variables such as the price paid to the producer for beef and the amount exported. The climate changes evaluated in the current study affect the livestock production system and consequently the beef market industry in Southern Brazil.
The Interwar Period as a Machine Age: Mechanics, the Machine, Mechanisms, and the Market in Discourse
Authors: Staley Richard
Published: September 2018

Argument

This paper examines some of the ways that machines, mechanisms, and the new mechanics were treated in post-World War I discourse. Spengler's 1919Decline of the Westand Hessen's 1931 study of Newton have usually been tied closely to Weimar culture in Germany, and Soviet politics. Linking them also to the writings of Rathenau, Simmel, Chase, Mumford, Hayek, and others, as well as to Dada and film studies of the city will indicate central features of a wide-ranging, international discourse on the machine and mechanization. I argue that machines were so thoroughly integrated into social and economic experience that we can treat this as a distinctive new phase in the cultural history of mechanics, what some contemporaries called the “machine age”: a period in which rather than the hand mill or steam engine, the city stands as an appropriate realization (and sometimes symbol) of the significance but also ambiguities and tensions of mechanical life; and concepts of mechanization were extended to encompass the economy and market mechanisms.
The Shaping of Interwar Physics by Technology: The Case of Piezoelectricity
Authors: Katzir Shaul
Published: September 2018

Argument

Concentrating on the important developments of quantum physics, historians have overlooked other significant forces that shaped interwar physics, like that of technology. Based on the case of piezoelectricity, I argue that interests of users of technics (i.e. devices of methods) channeled research in physics into particular fields and questions relevant for industrial companies and governmental agencies. To recognize the effects of such social forces on physics, one needs to study the content of the scientific activity (both experimental and theoretical) of the researchers within its social and disciplinary contexts. By examining paths of individual scientists along with a study of the research in the field as a whole this paper exposes a range of reasons that led researchers to studies pertinent to technics. In particular, it shows that commercial, social, and military powers shaped interwar research through institutions aimed at fostering technology, some of them newly founded, and by a general view that academic research should help technology, a position that became more common at the time.
Turbulence Research in the 1920s and 1930s between Mathematics, Physics, and Engineering
Authors: Eckert Michael
Published: September 2018

Argument

During the interwar period research on turbulence met with interest from different areas: in aeronautical engineering turbulence became a subject of experimental study in wind tunnels; in naval architecture and hydraulic engineering turbulence research was on the agenda because of its role for skin friction; applied mathematicians and theoretical physicists struggled with the problem to determine the onset of turbulence from the fundamental hydrodynamic equations; experimental physicists developed techniques to measure the velocity fluctuations of turbulent flows. In this paper I describe the rise of turbulence in the 1920s and 1930s as a research field under the label of applied mechanics. Although the focus is on Germany, the international development of this research field is illuminated by the role which Ludwig Prandtl played as its acknowledged “chief” (G. I. Taylor). I argue that the multifaceted character of this research field calls for an epistemology and historiography which intrinsically takes the interaction of science and engineering into account.
On the weak forms of the 2-part of Birch and Swinnerton-Dyer conjecture
Authors: ZHAI SHUAI
Published: September 2018

In this paper, we investigate the weak forms of the 2-part of the conjecture of Birch and Swinnerton-Dyer, and prove a lower bound for the 2-adic valuation of the algebraic part of the central value of the complexL-series for the family of quadratic twists of all optimal elliptic curves over${\mathbb Q}$.
Adaptation transculturelle en français du Edinburgh Feeding Evaluation in Dementia (EdFED) Scale : un questionnaire pour évaluer les difficultés à s’alimenter de personnes âgées présentant des troubles cognitifs en centre d’hébergement
Authors: Côté Claudia , Gagnon Cynthia , Payette Hélène
Published: September 2018

The Edinburgh Feeding Evaluation in Dementia (EdFED) Scale was designed to identify feeding difficulties for people with moderate to severe dementia. Its Canadian-French cross-cultural adaptation was carried out, as part of an experimental study, whose secondary objective was to document its construct validity. A back-translation method was followed. The EdFED-f was used during a meal with 26 elderly residents who had cognitive disorders. There was a significant correlation between EdFED-f scores and energy intakes calculated using a visual estimation of plate wash method (r=-0,50, p=0,009). EdFED-f scores also showed a significant difference according to the percentage of food consumed at meals (p=0,015). These results support the validity of the EdFED-f to assess feeding difficulties among elderly French-speaking Canadians living in residential and long-term care centers.
Past and present (and future) of parallel and distributed computation in (constraint) logic programming
Authors: FIORETTO FERDINANDO , PONTELLI ENRICO
Published: September 2018

Declarative languages offer unprecedented opportunities for the use of parallelism to speed up execution. A declarative language, being not procedural, removes the need to perform operations in a strict order and reduces the number of dependencies among operations, thus opening the doors for concurrent execution. The potential for transparent exploitation of parallelism in logic programming emerged almost immediately with the birth of the paradigm (Pollard 1981).
Time-domain analysis of compact dual band-notched slot antenna in indoor environments
Authors: Emadian Seyed Ramin , Ahmadi-Shokouh Javad
Published: September 2018

Frequency- and time-domain characteristics as well as indoor propagation channel impulse response of a compact dual band-notched ultra-wideband (UWB) slot antenna are investigated in this paper. The antenna consists of a narrow rectangular radiation patch and a rectangular wide slot in the modified ground plane. A pair of L-shaped stubs are connected to the radiation patch to obtain band-notched property in WLAN band and a narrow straight stub is placed on the back side of the substrate to create band-notched characteristics in X-band downlink satellite communication system. Moreover, two small parasitic strips are added to the radiation patch to enhance the bandwidth (BW) of the antenna up to 14 GHz. A comprehensive study on time-domain and indoor propagation channel characteristics of the proposed antenna is also presented throughout the paper. A ray-tracing approach based on geometrical optics is applied to analyze the indoor channel characteristics. The designed antenna not only has a wide BW and compact size but also has appropriate radiation and time-domain characteristics over the antenna operating BW. The measured and simulated results are in good agreement. These advantages make the proposed antenna as a desirable option for UWB impulse radio applications.
Global Distribution of ULF Waves During Magnetic Storms: Comparison of Arase, Ground Observations, and BATSRUS + CRCM Simulation
Authors: Takahashi Naoko , Seki Kanako , Teramoto Mariko , Fok Mei‐Ching , Zheng Yihua , Matsuoka Ayako , Higashio Nana , Shiokawa Kazuo , Baishev Dmitry , Yoshikawa Akimasa , Nagatsuma Tsutomu
Published: September 2018

Abstracts

During 26–29 March 2017 magnetic storm, the Arase satellite observed typical ultra low frequency (ULF) waves and acceleration of relativistic electrons. We simulate the global distribution of these ULF waves using CRCM with BATSRUS global magnetospheric magnetohydrodynamic model. The simulation can qualitatively reproduce the ULF waves observed by Arase at frequencies of 2–3 mHz. However, the simulated ULF wave power is 1–2 orders of magnitude smaller than the observation. The simulated ULF wave activity has a good correlation with the solar‐wind dynamic pressure variation, while the wave activity on the ground is enhanced even during the recovery phase, possibly due to the Kelvin‐Helmholtz instability and/or substorms. We also study the 3–6 April 2017 magnetic storm, in which low ULF wave activity and weak acceleration of relativistic electrons are seen. We suggest that the existence of ULF waves plays an important role in accelerating electrons up to relativistic energies.
Integrin α5β1-Ang1/Tie2 receptor cross-talk regulates brain endothelial cell responses following cerebral ischemia
Authors: Pang Defang , Wang Lu , Dong Jing , Lai Xiaoyin , Huang Qijuan , Milner Richard , Li Longxuan
Published: September 2018

We have previously demonstrated that in response to cerebral ischemia (CI), the growth factor angiopoietin-1 (Ang1) and α5β1 integrin are both induced in cerebral vessels, which likely provide positive signals driving the endogenous angiogenic response and vascular protection after CI. However, the precise relationship between endothelial Ang1 and α5β1 integrin after CI remains poorly understood. Here, we investigated the effects of the interaction between the Ang1/Tie2 system and α5β1 integrin on brain endothelial cells (BECs) under cerebral ischemic conditions in vivo and in vitro. Immunofluorescence analysis demonstrated that integrin α5β1 co-localized with Tie2/phosphorylated Tie2 on cerebral vessels in the penumbra. The in vitro study showed that oxygen–glucose deprivation/restoration (OGD/R) induced the expression of the Ang1 receptor Tie2 on BECs in a manner similar to that for integrin α5 and Ang1 in response to OGD/R, accompanied by increased activation of Tie2 and its downstream effectors focal adhesion kinase (FAK) and Akt. Knockdown of α5 integrin markedly suppressed OGD/R-induced Tie2 receptor activation in BECs, while in contrast, priming BECs with Ang1 promoted the expression of α5 integrin as well as the Tie2 downstream transcription factor Ets-1 in OGD-treated BECs. In line with this, Ets-1 knockdown significantly attenuated Ang1-mediated upregulation of α5 integrin. Functionally, Ang1 induced cell migration and tube formation of BECs after OGD, but this effect was inhibited by diminishment of the levels of α5 integrin in BECs. Taken together, our data indicate that the Ang1/Tie2 system cross-talks with integrin α5β1 in BECs after CI, which may contribute to the endogenous angiogenic vascular protective response following CI.
GWAS for Interleukin-1β levels in gingival crevicular fluid identifies IL37 variants in periodontal inflammation
Authors: Offenbacher Steven , Jiao Yizu , Kim Steven J. , Marchesan Julie , Moss Kevin L. , Jing Li , Divaris Kimon , Bencharit Sompop , Agler Cary S. , Morelli Thiago , Zhang Shaoping , Sun Lu , Seaman William T. , Cowley Dale , Barros Silvana P. , Beck James D. , Munz Matthias , Schaefer Arne S. , North Kari E.
Published: September 2018

There is no agnostic GWAS evidence for the genetic control of IL-1β expression in periodontal disease. Here we report a GWAS for “high” gingival crevicular fluid IL-1β expression among 4910 European-American adults and identify association signals in the IL37 locus. rs3811046 at this locus (p = 3.3 × 10−22) is associated with severe chronic periodontitis (OR = 1.50; 95% CI = 1.12–2.00), 10-year incident tooth loss (≥3 teeth: RR = 1.33; 95% CI = 1.09–1.62) and aggressive periodontitis (OR = 1.12; 95% CI = 1.01–1.26) in an independent sample of 4927 German/Dutch adults. The minor allele at rs3811046 is associated with increased expression of IL-1β in periodontal tissue. In RAW macrophages, PBMCs and transgenic mice, the IL37 variant increases expression of IL-1β and IL-6, inducing more severe periodontal disease, while IL-37 protein production is impaired and shows reduced cleavage by caspase-1. A second variant in the IL37 locus (rs2708943, p = 4.2 × 10−7) associates with attenuated IL37 mRNA expression. Overall, we demonstrate that IL37 variants modulate the inflammatory cascade in periodontal disease.
Glutamic acid is a carrier for hydrazine during the biosyntheses of fosfazinomycin and kinamycin
Authors: Wang Kwo-Kwang A. , Ng Tai L. , Wang Peng , Huang Zedu , Balskus Emily P. , van der Donk Wilfred A.
Published: September 2018

Fosfazinomycin and kinamycin are natural products that contain nitrogen–nitrogen (N–N) bonds but that are otherwise structurally unrelated. Despite their considerable structural differences, their biosynthetic gene clusters share a set of genes predicted to facilitate N–N bond formation. In this study, we show that for both compounds, one of the nitrogen atoms in the N–N bond originates from nitrous acid. Furthermore, we show that for both compounds, an acetylhydrazine biosynthetic synthon is generated first and then funneled via a glutamyl carrier into the respective biosynthetic pathways. Therefore, unlike other pathways to N–N bond-containing natural products wherein the N–N bond is formed directly on a biosynthetic intermediate, during the biosyntheses of fosfazinomycin, kinamycin, and related compounds, the N–N bond is made in an independent pathway that forms a branch of a convergent route to structurally complex natural products.
Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in Amyotrophic Lateral Sclerosis
Authors: Wang Haibo , Guo Wenting , Mitra Joy , Hegde Pavana M. , Vandoorne Tijs , Eckelmann Bradley J. , Mitra Sankar , Tomkinson Alan E. , Van Den Bosch Ludo , Hegde Muralidhar L.
Published: September 2018

Genome damage and defective repair are etiologically linked to neurodegeneration. However, the specific mechanisms involved remain enigmatic. Here, we identify defects in DNA nick ligation and oxidative damage repair in a subset of amyotrophic lateral sclerosis (ALS) patients. These defects are caused by mutations in the RNA/DNA-binding protein FUS. In healthy neurons, FUS protects the genome by facilitating PARP1-dependent recruitment of XRCC1/DNA Ligase IIIα (LigIII) to oxidized genome sites and activating LigIII via direct interaction. We discover that loss of nuclear FUS caused DNA nick ligation defects in motor neurons due to reduced recruitment of XRCC1/LigIII to DNA strand breaks. Moreover, DNA ligation defects in ALS patient-derived iPSC lines carrying FUS mutations and in motor neurons generated therefrom are rescued by CRISPR/Cas9-mediated correction of mutation. Our findings uncovered a pathway of defective DNA ligation in FUS-linked ALS and suggest that LigIII-targeted therapies may prevent or slow down disease progression.
Heterogeneous Catalytic Oxidation of Amides to Imides by Manganese Oxides
Authors: Biswas Sourav , Khanna Harshul S. , Nizami Quddus A. , Caldwell Donald R. , Cavanaugh Katherine T. , Howell Amy R. , Raman Sumathy , Suib Steven L. , Nandi Partha
Published: September 2018

Herein, we report a one-step peroxide mediated heterogeneous catalytic oxidation of amides to imides utilizing a series of manganese oxides. Among them, Cs/Mn2O3 was found to be the most active catalyst for the selective partial oxidation of N-benzylbenzamide to diphenyl imide. We have been able to apply an optimized oxidation method to other aromatic substrates. The feasibility of using air as an oxidant, the heterogeneous nature, inexpensive catalytic materials, respectable turnover numbers, and chemoselectivity to imides make this methodology an attractive choice for functional group transformations of amides to imides.
Surface structures with unconventional patterns and shapes generated by femtosecond structured light fields
Authors: JJ Nivas Jijil , Allahyari Elaheh , Cardano Filippo , Rubano Andrea , Fittipaldi Rosalba , Vecchione Antonio , Paparo Domenico , Marrucci Lorenzo , Bruzzese Riccardo , Amoruso Salvatore
Published: September 2018

We present an investigation on ultrashort laser surface structuring with structured light fields generated by various q-plates. In particular, q-plates with topological charges q = 1, 3/2, 2, 5/2 are used to generate femtosecond (fs) vector vortex beams, and form complex periodic surface structures through multi-pulse ablation of a solid crystalline silicon target. We show how optical retardation tuning of the q-plate offers a feasible way to vary the fluence transverse distribution of the beam, thus allowing the production of structures with peculiar shapes, which depend on the value of q. The features of the generated surface structures are compared with the vector vortex beam characteristics at the focal plane, by rationalizing their relationship with the local state of the laser light. Our experimental findings demonstrate how irradiation with fs complex light beams can offer a valuable route to design unconventional surface structures.
Visualisation and analysis of hepatitis C virus non-structural proteins using super-resolution microscopy
Authors: Bartlett Christopher , Curd Alistair , Peckham Michelle , Harris Mark
Published: September 2018

Hepatitis C virus (HCV) RNA replication occurs in the cytosol of infected cells within a specialised membranous compartment. How the viral non-structural (NS) proteins are associated and organised within these structures remains poorly defined. We employed a super-resolution microscopy approach to visualise NS3 and NS5A in HCV infected cells. Using single molecule localisation microscopy, both NS proteins were resolved as clusters of localisations smaller than the diffraction-limited volume observed by wide-field. Analysis of the protein clusters identified a significant difference in size between the NS proteins. We also observed a reduction in NS5A cluster size following inhibition of RNA replication using daclatasvir, a phenotype which was maintained in the presence of the Y93H resistance associated substitution and not observed for NS3 clusters. These results provide insight into the NS protein organisation within hepatitis C virus RNA replication complexes and the mode of action of NS5A inhibitors.
Identifying the early 2000s hiatus associated with internal climate variability
Authors: Dai Xin-Gang , Wang Ping
Published: September 2018

This study focuses on re-examining the early 2000s hiatus and the associated key components of the global mean surface temperature (GMST) using multiscale statistics for five well-known gridded surface temperature and two reanalysis datasets. The hiatus is characterized as a near-zero trend on the decadal scale corresponding to the maximum P-value via an F-test in statistics. The results reveal that the hiatus exists in both the GMST and global mean air temperature (GMAT) time series, rather than in global warming component, which has maintained an approximately constant rate of change of approximately 0.08 °C/decade over the past three decades. The hiatus’s duration is different from that of time series such as 2002–2012/2001–2013/2002–2014 in HadCRUT4, NOAA-old, ERA-Interim and NCEP-R2. The newly gridded datasets with data infilling or bias correction for interpreting the sea surface temperature (SST) measurement from the old versions show a slightly higher trend from 2002–2012 than the hiatus, which is thus regarded as a slowdown. Comparison suggests that the hiatus should be during the period 2002–2012. Orthogonal wavelet decomposition of the temperature time series shows that the hiatus was merely a decadal balance between cooling from interannual variability and global warming, in addition to weak warming from interdecadal and multidecadal climate oscillations. In addition, the evolutions of the GMST’s interannual composites are well coincided with Niño3.4 SST anomalies, which is consistent with the numerical simulation performed by Kosaka and Xie in 2013. Hence, it is the anomalous El Niño Southern Oscillation (ENSO) events in the early 2000s that caused the hiatus despite a constant rate of global warming and the maximum magnitude of the multidecadal composite that led to the limited contribution to the trend during this period. The multidecadal composite follows a downward path, which implies that future climate conditions will likely rely on competition between multidecadal cooling and global warming if the multidecadal climate cycle repeats, as was experienced during the second half of the twentieth century.
Naphthol Blue Black and 99mTc-Labeled Mannosylated Human Serum Albumin (99mTc-MSA) Conjugate as a Multimodal Lymph Node Mapping Nanocarrier
Authors: Lee Ji Youn , Kim Ho Young , Lee Yun-Sang , Jeong Jae Min
Published: September 2018

99mTc-labeled mannosylated human serum albumin (MSA) has been reported as a sentinel lymph node (SLN)-imaging agent by binding to macrophages in the LNs. By conjugating it with blue dye, we developed a new multimodal radio-nanocarrier by visual investigation, fluorescence imaging, and single photon emission computed tomography (SPECT)/computed tomography (CT). Binding affinities of seven blue dyes to MSA were tested. According to the spectroscopic study and visual inspection of MSA-bound dyes, naphthol blue black (NBB) was selected as the best candidate of multimodal agent. Thus, 99mTc-MSA-NBB conjugate was prepared and further investigated using mice. After footpad injection, it showed high popliteal LN accumulation at 1 h. SPECT/CT also showed high popliteal as well as inguinal LN uptakes at 10 min that sustained until 2 h. In conclusion, we prepared a multimodal SLN imaging radio-nanocarrier, 99mTc-MSA-NBB conjugate, and confirmed its excellency as a multimodal probe for SLN mapping.
Reconfiguration of the plastid genome in Lamprocapnos spectabilis: IR boundary shifting, inversion, and intraspecific variation
Authors: Park Seongjun , An Boram , Park SeonJoo
Published: September 2018

We generated a complete plastid genome (plastome) sequence for Lamprocapnos spectabilis, providing the first complete plastome from the subfamily Fumarioideae (Papaveraceae). The Lamprocapnos plastome shows large differences in size, structure, gene content, and substitution rates compared with two sequenced Papaveraceae plastomes. We propose a model that explains the major rearrangements observed, involving at least six inverted repeat (IR) boundary shifts and five inversions, generating a number of gene duplications and relocations, as well as a two-fold expansion of the IR and miniaturized small single-copy region. A reduction in the substitution rates for genes transferred from the single-copy regions to the IR was observed. Accelerated substitution rates of plastid accD and clpP were detected in the Lamprocapnos plastome. The accelerated substitution rate for the accD gene was correlated with a large insertion of amino acid repeat (AAR) motifs in the middle region, but the forces driving the higher substitution rate of the clpP gene are unclear. We found a variable number of AARs in Lamprocapnos accD and ycf1 genes within individuals, and the repeats were associated with coiled-coil regions. In addition, comparative analysis of three Papaveraceae plastomes revealed loss of rps15 in Papaver, and functional replacement to the nucleus was identified.
Differential effects of spinal motor neuron-derived and skeletal muscle-derived Rspo2 on acetylcholine receptor clustering at the neuromuscular junction
Authors: Li Jin , Ito Mikako , Ohkawara Bisei , Masuda Akio , Ohno Kinji
Published: September 2018

We recently reported that R-spondin 2 (Rspo2), a secreted activator of Wnt/β-catenin signaling, promotes acetylcholine receptor (AChR) clustering and neuromuscular junction (NMJ) formation via its receptor, Lgr5. Rspo2 is expressed highly in spinal motor neurons (SMNs) and marginally in the skeletal muscle, but the origin of Rspo2 at the NMJ remains elusive. We rescued Rspo2-deficient (Rspo2−/−) mice by specifically expressing Rspo2 in the skeletal muscle and SMNs. SMN-specific Rspo2 mitigated or over-corrected abnormal features of the NMJs and AChR clusters observed in Rspo2−/− mice including (i) abnormal broadening of enlarged AChR clusters, (ii) three of six abnormal ultrastructural features, and (iii) abnormal expression of nine genes in SMNs and the diaphragm. In contrast, muscle-specific Rspo2 normalized all six abnormal ultrastructural features, but it had no effect on AChR clustering and NMJ formation at the light microscopy level or on abnormal gene expression in SMNs and the diaphragm. These results suggest that SMN-derived Rspo2 plays a major role in AChR clustering and NMJ formation in the postsynaptic region, and muscle-derived Rspo2 also plays a substantial role in juxtaposition of the active zones and synaptic folds.
Natural variation among Arabidopsis thaliana accessions in tolerance to high magnesium supply
Authors: Niu Yaofang , Chen Ping , Zhang Yu , Wang Zhongwei , Hu Shikai , Jin Gulei , Tang Caixian , Guo Longbiao
Published: September 2018

High magnesium (Mg2+) in some extreme serpentine soils or semi-arid regions is an important factor affecting crop growth and development. Specific loci that form the genetic framework underlying high Mg2+ homeostasis, however, are not well understood. By using GWA mapping on 388 accessions of Arabidopsis thaliana selected from a worldwide collection and genotyped at approximately 250,00 SNPs, we successfully identified 109 and 74 putative genetic regions associated in nutrient traits under normal (1,000 µM) and high Mg2+ (10,000 µM), respectively. Above 90% SNPs associated with nutrients including Mg2+ and only two SNPs shared between normal and high Mg2+. A single strong peak of SNPs associated with Ca concentration corresponding to candidate gene At1g60420 ARABIDOPSIS NUCLEOREDOXIN (AtNRX1) under high Mg2+ was further determined. Compared with wildtype, mutants of Atnrx1-1 and Atnrx1-2 supplied with high Mg2+ had higher Ca concentrations in the plant, and higher cytosolic Ca2+ concentrations during root elongation, as well as higher fresh weight and lateral-root number. This suggests that AtNRX1 was a critical gene negatively regulating Ca uptake under high Mg2+ conditions. The discovery could help to breed/select crops that can adapt to high-Mg2+ soils such as serpentine soils (high ratio of Mg2+: Ca2+) or Mars soil with high levels of magnesium sulfate.
Anti-TNFR1 targeting in humanized mice ameliorates disease in a model of multiple sclerosis
Authors: Williams Sarah K. , Fairless Richard , Maier Olaf , Liermann Patricia C. , Pichi Kira , Fischer Roman , Eisel Ulrich L. M. , Kontermann Roland , Herrmann Andreas , Weksler Babette , Romero Nacho , Couraud Pierre-Olivier , Pfizenmaier Klaus , Diem Ricarda
Published: September 2018

Tumour necrosis factor (TNF) signalling is mediated via two receptors, TNF-receptor 1 (TNFR1) and TNF-receptor 2 (TNFR2), which work antithetically to balance CNS immune responses involved in autoimmune diseases such as multiple sclerosis. To determine the therapeutic potential of selectively inhibiting TNFR1 in mice with experimental autoimmune encephalomyelitis, we used chimeric human/mouse TNFR1 knock-in mice allowing the evaluation of antagonistic anti-human TNFR1 antibody efficacy. Treatment of mice after onset of disease with ATROSAB resulted in a robust amelioration of disease severity, correlating with reduced central nervous system immune cell infiltration. Long-term efficacy of treatment was achieved by treatment with the parental mouse anti-human TNFR1 antibody, H398, and extended by subsequent re-treatment of mice following relapse. Our data support the hypothesis that anti-TNFR1 therapy restricts immune cell infiltration across the blood-brain barrier through the down-regulation of TNF-induced adhesion molecules, rather than altering immune cell composition or activity. Collectively, we demonstrate the potential for anti-human TNFR1 therapies to effectively modulate immune responses in autoimmune disease.
Characterization of nitrogen deposition in a megalopolis by means of atmospheric biomonitors
Authors: Díaz-Álvarez Edison A. , de la Barrera Erick
Published: September 2018

An increase of nitrogen deposition resulting from human activities is not only a major threat for global biodiversity, but also for human health, especially in highly populated regions. It is thus important and in some instances legally mandated to monitor reactive nitrogen species in the atmosphere. The utilization of widely distributed biological species suitable for biomonitoring may be a good alternative. We assessed the suitability of an ensemble of atmospheric biomonitors of nitrogen deposition by means of an extensive sampling of a lichen, two mosses, and a bromeliad throughout the Valley of Mexico, whose population reaches 30 million, and subsequent measurements of nitrogen metabolism parameters. In all cases we found significant responses of nitrogen content, C:N ratio and the δ15N to season and site. In turn, the δ15N for the mosses responded linearly to the wet deposition. Also, the nitrogen content (R2 = 0.7), the C:N ratio (R2 = 0.6), and δ15N (R2 = 0.5) for the bromeliad had a linear response to NOx. However, the bromeliad was not found in sites with NOx concentrations exceeding 80 ppb, apparently of as a consequence of excess nitrogen. These biomonitors can be utilized in tandem to determine the status of atmospheric nitrogenous pollution in regions without monitoring networks for avoiding health problems for ecosystems and humans.
Bacillus velezensis A2 fermentation exerts a protective effect on renal injury induced by Zearalenone in mice
Authors: Wang Nan , Li Peng , Pan Jiawen , Wang Mingyang , Long Miao , Zang Jian , Yang Shuhua
Published: September 2018

Zearalenone (ZEN) is an estrogen-like mycotoxin occurring in food and feeds, and it can cause oxidative damage and apoptosis in the testis, liver, and kidney. A current concern for researchers is how to reduce the harm it causes to humans and animals. In this study, our aim was to isolate and identify a novel and efficient ZEN-detoxifying strain of bacteria, and we aimed to assess the protective effect of the isolated strain on kidney damage caused by ZEN in mice. Our results indicated that a strain of Bacillus velezensis (B. velezensis), named A2, could completely degrade ZEN (7.45 μg/mL) after three days of incubation at 37 °C in the Luria-Bertani (LB) medium. This fermentation broth of the B. velezensis A2 strain was given to mice. The histopathological analysis indicated that the fermentation broth from the B. velezensis A2 strain reduced the degree of renal injury that is induced by ZEN. Furthermore, it greatly reduced the increase in serum levels of creatinine (CRE), uric acid (UA), and urea nitrogen (BUN) caused by ZEN. In addition, B. velezensis A2 strain also significantly inhibited the increase of malonaldehyde (MDA) content, and reversed the decreases of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities caused by ZEN. Studies have shown that ZEN is involved in the regulation of mRNA and protein levels of genes involved in the ER stress-induced apoptotic pathway, such as heavy chain binding protein (BIP), C-/-EBP homologous protein (CHOP), cysteine Aspartate-specific protease-12 (Caspase-12), c-Jun N-terminal kinase (JNK), and BCL2-related X protein (Bcl-2 and Bax). However, when mice were administered the fermentation broth of the B. velezensis A2 strain, it significantly reversed the expressions of these genes in their kidney tissue. In conclusion, our results indicate that the newly identified strain of B. velezensis A2, has a protective effect from renal injury induced by ZEN in mice. This strain has a potential application in the detoxification of ZEN in feed and protects animals from ZEN poisoning.
Computational Approaches in the Development of Small-molecule Transcription Factor Inhibitors
Authors: Jackson Paul J. M. , Jamshidi Shirin , Farag Doaa B.
Published: September 2018

This chapter describes the use of computational methods in the development of small-molecule transcription factor inhibitors. Methodologies such as virtual screening, docking, quantitative structure–activity relationship (QSAR) and molecular dynamics simulation are discussed and specific examples of their use in the development of NF-κB and STAT3 inhibitors are outlined.