bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of gelling bath on the physical properties of alginate gel beads and the biological characteristics of entrapped HepG2 cells
Authors: Sun Dongsheng , Liu Yang , Wu Hao , Ren Ying , Ma Xiaojun , Wu Huijian , Sun Guangwei
Published: August 2017

Optimizing alginate gel beads is necessary to support the survival, proliferation, and function of entrapped hepatocytes. In this study, gelling bath was modified by decreasing calcium ion concentration and increasing sodium ion concentration. Alginate gel beads (using 36% G sodium alginate) prepared in the modified gelling bath had more homogeneous structure and better mass transfer properties compared with the traditional gelling bath that contains only calcium ions. Moreover, alginate gel beads generated in the modified gelling bath could significantly promote the HepG2 cell proliferation and the growth of cell spheroids, and maintain the albumin secretion ability similar to alginate gel beads prepared in the traditional gelling bath with only calcium ions. The mass transfer properties and cell proliferation were similar in ALG beads with different M/G ratio (36% G and 55% G) generated in the modified gelling bath, whereas they were significantly increased compared with alginate gel beads (55% G) in traditional gelling bath. These results indicated that adjusting the gelling bath was a simple and convenient method to enhance the mass transfer properties of alginate gel beads for 3D hepatocyte culture, which might provide more hepatocytes for the bioartificial liver support system.
The anti‐proliferative effects of oleanolic acid on A7r5 cells—Role of UCP2 and downstream FGF‐2/p53/TSP‐1
Authors: Han Yantao , Jiang Qixiao , Wang Yu , Li Wenqian , Geng Min , Han Zhiwu , Chen Xuehong
Published: August 2017

Vascular smooth muscle cell (VSMC) proliferation is a major contributor to atherosclerosis. This study investigated the inhibitory effects of oleanolic acid (OA) against oxidized low‐density lipoprotein (ox‐LDL)‐induced VSMC proliferation in A7r5 cells and explored underlying molecular mechanism. The cell proliferation was quantified with cell counting kit‐8 (CCK‐8), in which ox‐LDL significantly increased A7r5 cells proliferation, while OA pretreatment effectively alleviated such changes without inducing overt cytotoxicity, as indicated by lactate dehydrogenase (LDH) assay. Quantitative real‐time RT‐PCR (qRT‐PCR) and Western blotting revealed increased UCP2 and FGF‐2 expression levels as well as decreased p53 and TSP‐1 expression levels in A7r5 cells following ox‐LDL exposure, while OA pretreatment reversed such changes. Furthermore, inhibiting UCP2 with genipin remarkably reversed the changes in the expression levels of FGF‐2, p53, and TSP‐1 induced by ox‐LDL exposure; silencing FGF‐2 with siRNA did not significantly change the expression levels of UCP2 but effectively reversed the changes in the expression levels of p53 and TSP‐1, and activation of p53 with PRIMA‐1 only significantly affected the changes in the expression levels of TSP‐1, but not in UCP2 or FGF‐2, suggesting a UCP‐2/FGF‐2/p53/TSP‐1 signaling in A7r5 cells response to ox‐LDL exposure. Additionally, co‐treatment of OA and genipin exhibited similar effects to the expression levels of UCP2, FGF‐2, p53, and TSP‐1 as OA or genipin solo treatment in ox‐LDL‐exposed A7r5 cells, suggesting the involvement of UCP‐2/FGF‐2/p53/TSP‐1 in the mechanism of OA. In conclusion, OA inhibits ox‐LDL‐induced VSMC proliferation in A7r5 cells, the mechanism involves the changes in UCP‐2/FGF‐2/p53/TSP‐1.
Facile Solvothermal Synthesis of Pt4Co Multi‐dendrites: An Effective Electrocatalyst for Oxygen Reduction and Glycerol Oxidation
Authors: Jiang Liu‐Ying , Wang Ai‐Jun , Li Xin‐Sheng , Yuan Junhua , Feng Jiu‐Ju
Published: August 2017

In this work, hierarchical Pt4Co multi‐dendrites (MDs) with abundant active sites were synthesized by using a one‐pot solvothermal co‐reduction approach, where cetyltrimethylammonium chloride (CTAC), citric acid, and oleylamine served as the structure director, eco‐friendly reducing agent, and co‐reductant, respectively. The architectures were mainly characterized by using a series of characterization techniques, demonstrating the enlarged electrochemically active surface area of 28.27 m2 g−1, much enhanced mass activity and specific activity for oxygen reduction reaction (279.14 mA mg−1Pt and 0.89 mA cm−2) and glycerol oxidation reaction (1422.56 mA mg−1Pt, 4.58 mA cm−2) comparable with commercial Pt black, along with the superior durability. These results demonstrate the potential applications of the synthesized Pt4Co MDs catalyst in energy storage and transformation.
Online updating method with new variables for big data streams
Authors: Wang Chun , Chen Ming‐Hui , Wu Jing , Yan Jun , Zhang Yuping , Schifano Elizabeth
Published: August 2017

For big data arriving in streams online updating is an important statistical method that breaks the storage barrier and the computational barrier under certain circumstances. In the regression context online updating algorithms assume that the set of predictor variables does not change, and consequently cannot incorporate new variables that may become available midway through the data stream. A naive approach would be to discard all previous information and start updating with new variables from scratch. We propose a method that utilizes the information from earlier data in the online updating algorithm with bias corrections to improve efficiency. The method is developed for linear models first, and then extended to estimating equations for generalized linear models. Closed‐form expressions for the efficiency gain over the naive approach are derived in a particular linear model setting. We compare the performance of our proposed bias‐correcting approach and the naive approach in simulation studies with data generated from a normal linear model and a logistic regression model. The method is applied to a study on airline delay, where reasons for delays were only available more recently, starting in 2003. The Canadian Journal of Statistics 46: 123–146; 2018 © 2017 Statistical Society of Canada
Synthesis and Antibacterial Activity of Polymerizable Acryloyloxyalkyltriethyl Ammonium Salts
Authors: Mancuso Raffaella , Amuso Roberta , Armentano Biagio , Grasso Giuseppe , Rago Vittoria , Cappello Anna Rita , Galiano Francesco , Figoli Alberto , De Luca Giorgio , Hoinkis Jan , Gabriele Bartolo
Published: August 2017

Invited for this month's cover are the collaborating groups at the University of Calabria (Unical, Italy)—Department of Chemistry and Chemical Technologies (CTC) and Department of Pharmacy and Health and Nutritional Sciences (PHNS), at the National Research Council (CNR, Italy), Institute on Membrane Technology (ITM), and at the Karlsruhe University of Applied Sciences (HSKA, Germany), Institute of Applied Research (IAR), which cooperated in the framework of the European Union's Horizon 2020 project “VicInAqua”. The front cover shows the structure of an acryloxyalkyltrithylammonium (AATEA) cation, characterized by a polymerizable end, a long‐chain alkyl linker, and a quaternary ammonium moiety. The bromide salts (AATEABs) have been synthesized by a two‐step procedure carried out entirely under air without any need for chromatographic purifications. Some AATEABs have shown significant antimicrobial activity and represent useful precursors for the preparation of polymeric films with antimicrobial properties. Read the full text of the article at 10.1002/cplu.201700194.
Increased Systemic Exposure and Stronger Cardiovascular and Metabolic Adverse Reactions to Fenoterol in Individuals with Heritable OCT1 Deficiency
Authors: Tzvetkov Mladen V. , Matthaei Johannes , Pojar Sherin , Faltraco Frank , Vogler Sabrina , Prukop Thomas , Seitz Tina , Brockmöller Jürgen
Published: August 2017

Fenoterol is a widely used anti‐asthmatic and tocolytic agent, but high plasma concentrations of fenoterol may lead to severe and even fatal adverse reactions. We studied whether heritable deficiency of the liver organic cation transporter 1 (OCT1), a trait observed in 3% of Europeans and white Americans, affects fenoterol plasma concentrations and toxicity. OCT1 transported fenoterol with high affinity, and OCT1 inhibition in human hepatocytes reduced fenoterol uptake threefold. After administration of 180 µg of fenoterol to 39 healthy individuals, the OCT1‐deficient individuals (zero active OCT1 alleles; n = 5) showed 1.9‐fold greater systemic fenoterol exposure (P = 4.0 × 10−5) and 1.7‐fold lower volume of distribution (P = 8.0 × 10−5). Correspondingly, the OCT1‐deficient individuals had a 1.5‐fold stronger increase in heart rate (P = 0.002), a 3.4‐fold greater increase in blood glucose (P = 3.0 × 10−5), and significantly lower serum potassium levels. In conclusion, heritable OCT1 deficiency significantly increases plasma concentrations of fenoterol and may be an important factor underlying the excess mortality associated with fenoterol.
Boron‐Functionalized Phosphorescent Iridium(III) Complexes
Authors: Xu Wen‐Juan , Qin Yan‐Yan , Wei Liu‐Wei , Zhang Kenneth Yin , Liu Shu‐Juan , Zhao Qiang
Published: August 2017

Boron‐based motifs, introduced into π‐conjugated systems in various forms (e.g., triarylboranes, borate dyes, and boron clusters), have attracted much attention owing to their unique electronic and structural features. Recently, organoboron groups – mainly triarylboranes and boron clusters (carboranes) – that exhibit highly polarizable σ‐aromatic character and strongly electron‐withdrawing properties have been widely incorporated into phosphorescent IrIII complexes. These organoboron groups make significant contributions to the excited states of such IrIII complexes, allowing tuning of phosphorescence energy and quantum yields. A number of fascinating boron‐functionalized IrIII complexes have been synthesized to date, and some of them have been applied in various fields, including those of organic light‐emitting diodes, chemosensors, and biological probes. This microreview provides a summary of recent research into boron‐functionalized IrIII complexes, emphasizing the impact of organoboron groups on photophysical properties and their optoelectronic applications.
A Framework for the Dual Language Assessment of Young Dual Language Learners in the United States
Authors: Guzman‐Orth Danielle , Lopez Alexis A. , Tolentino Florencia
Published: August 2017

Dual language learners (DLLs) and the various educational programs that serve them are increasing in number across the country. This framework lays out a conceptual approach for dual language assessment tasks designed to measure the language and literacy skills of young DLLs entering kindergarten in the United States. Although our examples focus on Spanish–English DLLs, we anticipate that our recommendations could be broadly applied to other language combinations with appropriate adaptations for each language.
Natural Products as Inspiration for the Development of New Synthetic Methods
Authors: Ma Zhiqiang , Chen Chuo
Published: August 2017

Natural products have played an important role in shaping modern synthetic organic chemistry. In particular, their complex molecular skeletons have stimulated the development of many new synthetic methods. We highlight in this article some recent examples of synthetic designs inspired by the biosynthesis of natural products.
Spatial distribution of flow and oxygenation in the cerebral venous drainage system
Authors: De Vis Jill B. , Lu Hanzhang , Ravi Harshan , Hendrikse Jeroen , Liu Peiying
Published: August 2017

Purpose

To investigate the venous oxygenation and flow in the brain, and determine how they might change under challenged states.

Materials and Methods

Eight healthy human subjects (24–37 years) were studied. T2‐relaxation under spin tagging (TRUST) magnetic resonance imaging (MRI) and phase‐contrast MRI were performed to measure venous oxygenation and venous blood flow, respectively, in the superior sagittal sinus (SSS), the straight sinus (SS), and the internal jugular veins (IJVs). Venous oxygenation was assessed at room air (0.03%CO2, 21%O2) and under hyperoxia (O%CO2, 95%O2, and 5%N2) conditions. Venous blood flow was assessed at room air and under hypercapnia (5%CO2, 21%O2, and 74%N2) conditions. Whole‐brain blood flow was also measured at the four feeding arteries of the brain using phase‐contrast MRI. The changes in venous oxygenation and blood flow from room air to hyperoxia or hypercapnia conditions were tested using paired t‐tests.

Results

Venous oxygenation in the SSS, the SS, and the IJVs was 61 ± 4%, 64 ± 4%, and 62 ± 4%, respectively, at room air, and increased to 70 ± 3% (P < 0.01 compared to room air), 71 ± 5% (P = 0.59), and 68 ± 5% (P < 0.05) under hyperoxic condition. The SSS, SS, and IJV drained 46 ± 9%, 16 ± 4%, and 79 ± 1% of whole‐brain blood flow, respectively, and this flow distribution did not change under hypercapnic condition (P > 0.5).

Conclusion

The results found in this study provide insight into the venous oxygenation and venous flow distribution and its heterogeneity among different venous structures.

Level of Evidence: 1

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2018;47:1091–1098.
Toward Contingency in Scaffolding Reading Comprehension: Next Steps for Research
Authors: Reynolds Dan , Daniel Shannon
Published: August 2017

Although much research exists on scaffolding in reading instruction, confusion about the construct persists. In this commentary inspired by a recent article inReading Research Quarterly, we argue for the importance of contingency—that is, responsiveness to student thinking—in reading comprehension scaffolding. We begin by defining two sometimes nebulous constructs: scaffolding and comprehension. We then argue that the dynamic, contextual, and affective nature of comprehension calls for a focus on contingency in scaffolding interactions because the requisite assumptions of preplanned scaffolding can obscure students’ emergent comprehension. To focus on contingency, three implications for research follow. First, research designs could separate interactional scaffolding from planned scaffolding so as to directly investigate the construct. Second, collaboratively analyzing video data of scaffolding interactions is an effective tool for teacher educators and researchers. Finally, researchers should consider refining, building on, or comparing their findings with existing frameworks to illuminate both the transferable and the idiosyncratic dimensions of contingent scaffolding. This could also include studying students’ discursive moves in addition to teachers’ utterances, which might offer a new lens on how teachers adjust scaffolds in moment‐to‐moment interactions. These implications lay a foundation for a research agenda that goes beyond assumptions about students built into planned scaffolding and tackles the challenges of contingent comprehension scaffolding.
Fluorescence Resonance Energy Transfer of Monomer via Photoisomerization
Authors: Wang Jiangcai , Cao En , Lin Weihua , Song Peng , Zhou Qiao , Zhang Xiaofang , Sun Yinghui , Liang Wenjie , Sun Mengtao
Published: August 2017

We experimentally report a new photoisomerization mechanism of fluorescence resonance energy transfer (FRET) of monomer via photoisomerization. Firstly, a new photoisomerization was firstly report by us, in which trans, trans‐1,4‐Diphenyl‐1,3‐butadiene (tt‐DPB) is photoisomerized to D‐DPB (D stands for rotating double bond) by rotating double bond, evidenced by the three dimensional (3D) and 2D excitation‐emission mappings, and firmly supported by theoretical calculations on potential energy surfaces. Secondly, absorption energy of the photoisomerized D‐DPB is resonated with the fluorescence energy of tt‐DPB. By the electronic state excitation of tt‐DPB, the fluorescence of D‐DPB is observed, which provide evidence of the FRET of DPB via photoisomerization. Our results provide a new mechanism on FRET of monomer via photoisomerization.
Accidental Orthogonality Induced Weak Magnetic Coupling in a Dinuclear Copper(II) Complex: Exploration of Unconventional C‐H⋅⋅⋅π(SCN) Interactions and Catechol Oxidase Activity
Authors: Roy Sourav , Bhattacharyya Anik , Herrero Santiago , González‐Prieto Rodrigo , Frontera Antonio , Chattopadhyay Shouvik
Published: August 2017

Variable temperature magnetic susceptibility measurement of a thiocyanate/phenoxo bridged dinuclear copper(II) complex indicated the presence of weak antiferromagnetic interaction. DFT calculation showed perpendicular arrangement of magnetic orbitals, thereby rationalizing the lowJvalue. Unconventional C–H⋅⋅⋅π (SCN) interaction in solid state of the complex was estimated and analyzed by Bader's AIM theory. Catechol oxidase mimicking activity of the complex was also investigated.
Bombing the Marshall Islands
Authors: Parsons Keith M. , Zaballa Robert A.
Published: August 2017

During the Cold War, the United States conducted atmospheric tests of nuclear weapons in the Marshall Islands of the Pacific. The total explosive yield of these tests was 108 megatons, equivalent to the detonation of one Hiroshima bomb per day over nineteen years. These tests, particularly Castle Bravo, the largest one, had tragic consequences, including the irradiation of innocent people and the permanent displacement of many native Marshallese. Keith M. Parsons and Robert Zaballa tell the story of the development and testing of thermonuclear weapons and the effects of these tests on their victims and on the popular and intellectual culture. These events are also situated in their Cold War context and explained in terms of the prevailing hopes, fears, and beliefs of that age. In particular, the narrative highlights the obsessions and priorities of top American officials, such as Lewis L. Strauss, Chairman of the Atomic Energy Commission.
Globalization against Democracy
Authors: Wu Guoguang
Published: August 2017

Globalization has reconfigured both the external institutional framework and the intrinsic operating mechanisms of capitalism. The global triumph of capitalism implies the embracing of the market by the state in all its variants, and that global capitalism is not confined to the shell of nation-state democracy. Guoguang Wu provides a theoretical framework of global capitalism for specialists in political economy, political science, economics and international relations, for graduate and undergraduate courses on globalization, capitalism, development and democracy, as well as for the public who are interested in globalization. Wu examines the new institutional features of global capitalism and how they reframe movements of capital, labor and consumption. He explores how globalization has created a chain of connection in which capital depends on effective authoritarianism, while democracy depends on capital. Ultimately, he argues that the emerging state-market nexus has fundamentally shaken the existing institutional systems, harming democracy in the process.
Revisiting the Dominant Discourse on Conditionality in the EU: The Case of EU Spending Conditionality
Authors: VIŢĂ Viorica
Published: August 2017

This article maps the rise of EU spending conditionality in the 2014–20 financial period and shows how the study of this novel type of conditionality adds to the dominant legal discourse on conditionality in the EU. It also suggests that the rise of conditionality may signal more profound transformations in the deep tissue of the EU, expressed by a transition towards a conditionality-based culture within the EU internal relationships.
Pentameroid brachiopodKarlsorusnew genus from the upper Wenlock (Silurian) Slite Beds, Gotland, Sweden
Authors: Jin Jisuo , Holmer Lars E.
Published: August 2017

Karlsorusn. gen. is proposed in this study as a large, smooth-shelled pentameride brachiopod of the family Pentameridae, based onPentamerus gothlandicusLebedev, 1892, from the Wenlock (Silurian) Slite beds of Gotland, Sweden. This species is transferred fromPentamerusto the new genus because of the combination of aPentamerus-like shell shape and the development of a brachiophorium through fusion of the outer hinge plates in the middle portion, like a dorso-ventrally inversed cruralium. The first appearance of brachiophorium in pentamerids is in the late Wenlock, known also inBrooksina,Pentamerifera, and other related pentamerid genera, marking a significant stage in morphological transformation of dorsal internal structures, as part of the Silurian pentameride diversification in both level-bottom and reefal depositional environments.
Cardiovascular pre-participation screening in young athletes: Recommendations of the Association of European Paediatric Cardiology
Authors: Fritsch Peter , Dalla Pozza Robert , Ehringer-Schetitska Doris , Jokinen Eero , Herceg Vesna , Hidvegi Erzsebet , Oberhoffer Renate , Petropoulos Andreas
Published: August 2017

Sudden death in young competitive athletes can be avoided by implementation of pre-participation screening programmes. A screening programme should be performed only by trained physicians and should include the athlete’s personal and family history, physical examination results, and the readings from a 12-lead-electrocardiogram. The athlete should undergo this screening programme every second year to detect progressive diseases. In addition, the programme should include detailed instructions to the athletes to pause training during infections in order to prevent sudden death due to myocarditis.
Vitamin D supplementation and vitamin D status in children of immigrant background in Norway
Authors: Madar Ahmed A , Gundersen Thomas E , Haug Anne M , Meyer Haakon E
Published: August 2017

Objective

Sufficient vitamin D status during infancy is important for child health and development. Several initiatives for improving vitamin D status among immigrant children have been implemented in Norway. The present study aimed to evaluate the vitamin D status and its determinants in children of immigrant background in Oslo.

Design

Cross-sectional study.

Setting

Child health clinics in Oslo.

Subjects

Healthy children with immigrant background (n 102) aged 9–16 months were recruited at the routine one-year check-up from two child health clinics with high proportions of immigrant clients. Blood samples were collected using the dried blood spot technique and analysed for serum 25-hydroxyvitamin D (s-25(OH)D) concentration using LC–MS/MS.

Results

Mean s-25(OH)D was 52·3 (sd 16·7) nmol/l, with only three children below 25 nmol/l and none below 12·5 nmol/l. There was no significant gender, ethnic or seasonal variation in s-25(OH)D. However, compared with breast-fed children, s-25(OH)D concentration was significantly higher among children who were about 1 year of age and not breast-fed. About 38 % of the children were anaemic, but there was no significant correlation between s-25(OH)D and Hb (Pearson correlation, r=0·1, P=0·33).

Conclusions

Few children in the study had vitamin D deficiency, but about 47 % of the children in the study population were under the recommended s-25(OH)D sufficiency level of ≥50 nmol/l.
Protection and consolidation of stone heritage by self-inoculation with indigenous carbonatogenic bacterial communities
Authors: Jroundi Fadwa , Schiro Mara , Ruiz-Agudo Encarnación , Elert Kerstin , Martín-Sánchez Inés , González-Muñoz María Teresa , Rodriguez-Navarro Carlos
Published: August 2017

Enhanced salt weathering resulting from global warming and increasing environmental pollution is endangering the survival of stone monuments and artworks. To mitigate the effects of these deleterious processes, numerous conservation treatments have been applied that, however, show limited efficacy. Here we present a novel, environmentally friendly, bacterial self-inoculation approach for the conservation of stone, based on the isolation of an indigenous community of carbonatogenic bacteria from salt damaged stone, followed by their culture and re-application back onto the same stone. This method results in an effective consolidation and protection due to the formation of an abundant and exceptionally strong hybrid cement consisting of nanostructured bacterial CaCO3 and bacterially derived organics, and the passivating effect of bacterial exopolymeric substances (EPS) covering the substrate. The fact that the isolated and identified bacterial community is common to many stone artworks may enable worldwide application of this novel conservation methodology.
Synthesis of Saccharumoside-B analogue with potential of antiproliferative and pro-apoptotic activities
Authors: Rayavarapu Srinuvasarao , Yarla Nagendra Sastry , Kadiri Sunanda Kumari , Bishayee Anupam , Vidavalur Siddaiah , Tadikonda Ramu , Basha Mahaboob , Pidugu Vijaya Rao , Dowluru Kaladhar S. V. G. K. , Lakappa Dhananjaya Bhadrapura , Kamal Mohammad A. , Md Ashraf Ghulam , Tarasov Vadim V. , Chubarev Vladimir N. , Klochkov Sergey G. , Barreto George E. , Bachurin Sergey O. , Aliev Gjumrakch
Published: August 2017

A new series of phenolic glycoside esters, saccharumoside-B and its analogs (9b-9n, 10) have been synthesized by the Koenigs-Knorr reaction. Antiproliferative activities of the compounds (9b-9n, 10) were evaluated on various cancer cell lines including, MCF-7 breast, HL-60 leukemia, MIA PaCa-2 pancreatic, DU145 prostate, HeLa cervical and CaCo-2 colon, as well as normal human MCF10A mammary epithelial and human peripheral blood mononuclear cells (PBMC) by MTT assay. Compounds (9b-9n, 10) exhibited considerable antiproliferative effects against cancer cells with IC50 range of 4.43 ± 0.35 to 49.63 ± 3.59 µM, but they are less cytotoxic on normal cells (IC50 > 100 µM). Among all the compounds, 9f showed substantial antiproliferative activity against MCF-7 and HL-60 cells with IC50 of 6.13 ± 0.64 and 4.43 ± 0.35, respectively. Further mechanistic studies of 9f were carried out on MCF-7 and HL-60 cell lines. 9f caused arrest of cell cycle of MCF-7 and HL-60 cells at G0/G1 phase. Apoptotic population elevation, mitochondrial membrane potential loss, increase of cytosolic cytochrome c and Bax levels, decrease of Bcl-2 levels and enhanced caspases-9 and -3 activities were observed in 9f-treated MCF-7 and HL-60 cells. These results demonstrate anticancer and apoptosis-inducing potentials of 9f in MCF-7 and HL-60 cells via intrinsic pathway.
Loop quantum cosmology and singularities
Authors: Struyve Ward
Published: August 2017

Loop quantum gravity is believed to eliminate singularities such as the big bang and big crunch singularity. This belief is based on studies of so-called loop quantum cosmology which concerns symmetry-reduced models of quantum gravity. In this paper, the problem of singularities is analysed in the context of the Bohmian formulation of loop quantum cosmology. In this formulation there is an actual metric in addition to the wave function, which evolves stochastically (rather than deterministically as the case of the particle evolution in non-relativistic Bohmian mechanics). Thus a singularity occurs whenever this actual metric is singular. It is shown that in the loop quantum cosmology for a homogeneous and isotropic Friedmann-Lemaître-Robertson-Walker space-time with arbitrary constant spatial curvature and cosmological constant, coupled to a massless homogeneous scalar field, a big bang or big crunch singularity is never obtained. This should be contrasted with the fact that in the Bohmian formulation of the Wheeler-DeWitt theory singularities may exist.
Continuously wavelength-tunable passband-flattened fiber comb filter based on polarization-diversified loop structure
Authors: Jung Jaehoon , Lee Yong Wook
Published: August 2017

Continuous wavelength tuning of optical comb filters, which is an essential functionality for flexible signal processing in reconfigurable optical systems, has been challenging in high order filter structures with two birefringent elements (BEs) or more due to cumbersomeness in finding a combination of waveplates and BEs and complexity in determining their individual azimuthal orientations. Here, we propose a continuously tunable polarization-independent passband-flattened fiber comb filter with two BEs using a polarization-diversified loop structure for the first time. The proposed filter consists of a polarization beam splitter and two groups of a half-wave plate, quarter-wave plate, and polarization-maintaining fiber (PMF). The azimuthal orientation of PMF in the second group is fixed as 22.5°. Orientation angle sets of the four waveplates, which can induce an arbitrary phase shift from 0 to 2π in the passband-flattened transmittance function, are found from the filter transmittance derived using Jones matrix formulation. From theoretical spectral analysis, it is confirmed that passband-flattened comb spectra can be continuously tuned. Theoretical prediction is verified by experimental demonstration. Moreover, the wavelength-dependent evolution of the output state of polarization (SOP) of each PMF is investigated on the Poincare sphere, and the relationship between wavelength tuning and SOP evolution is also discussed.
Mammary Tumors Induce Central Pro-inflammatory Cytokine Expression, but Not Behavioral Deficits in Balb/C Mice
Authors: Walker II William H. , Borniger Jeremy C. , Surbhi  , Zalenski Abigail A. , Muscarella Stevie L. , Fitzgerald Julie A. , Zhang Ning , Gaudier-Diaz Monica M. , DeVries A. Courtney
Published: August 2017

Breast cancer survivors are more likely to develop mood disorders and cognitive deficits than women in the general population. Previous studies suggest that peripheral tumors elicit central pro-inflammatory cytokine production, in turn leading to depression and cognitive deficits. In the current study, two cohorts of female Balb/C mice received bilateral orthotopic injections of syngeneic 67NR, 4T07, or 4T1cells (1 × 105 cells per injection) to induce mammary tumors. Approximately three weeks later, learned fear (via fear conditioning) or depressive-like behavior (via tail suspension and forced swim test) was assessed. Proinflammatory cytokine levels were increased in the serum (IL-1β, TNFα, IFNγ) and livers (IL-1β, IL-6, TNFα) of mice with 4T07 or 4T1 tumors compared to 67NR tumors and the vehicle control. IL-1β was increased in both the hippocampus and cortex of mice injected with 4T07 or 4T1 cell lines relative to the other treatment groups. However, mammary tumors had no effect on hippocampal doublecortin + and did not alter depressive-like behavior or learned fear. These data demonstrate that similarly sized tumors can produce differential immune responses and that tumor-induced central pro-inflammatory cytokine production can exist in the absence of depressive-like behavior or cognitive deficits.
On the shape and likelihood of oceanic rogue waves
Authors: Benetazzo Alvise , Ardhuin Fabrice , Bergamasco Filippo , Cavaleri Luigi , Guimarães Pedro Veras , Schwendeman Michael , Sclavo Mauro , Thomson Jim , Torsello Andrea
Published: August 2017

We consider the observation and analysis of oceanic rogue waves collected within spatio-temporal (ST) records of 3D wave fields. This class of records, allowing a sea surface region to be retrieved, is appropriate for the observation of rogue waves, which come up as a random phenomenon that can occur at any time and location of the sea surface. To verify this aspect, we used three stereo wave imaging systems to gather ST records of the sea surface elevation, which were collected in different sea conditions. The wave with the ST maximum elevation (happening to be larger than the rogue threshold 1.25Hs) was then isolated within each record, along with its temporal profile. The rogue waves show similar profiles, in agreement with the theory of extreme wave groups. We analyze the rogue wave probability of occurrence, also in the context of ST extreme value distributions, and we conclude that rogue waves are more likely than previously reported; the key point is coming across them, in space as well as in time. The dependence of the rogue wave profile and likelihood on the sea state conditions is also investigated. Results may prove useful in predicting extreme wave occurrence probability and strength during oceanic storms.
Rapid and accurate in silico solubility screening of a monoclonal antibody library
Authors: Sormanni Pietro , Amery Leanne , Ekizoglou Sofia , Vendruscolo Michele , Popovic Bojana
Published: August 2017

Antibodies represent essential tools in research and diagnostics and are rapidly growing in importance as therapeutics. Commonly used methods to obtain novel antibodies typically yield several candidates capable of engaging a given target. The development steps that follow, however, are usually performed with only one or few candidates since they can be resource demanding, thereby increasing the risk of failure of the overall antibody discovery program. In particular, insufficient solubility, which may lead to aggregation under typical storage conditions, often hinders the ability of a candidate antibody to be developed and manufactured. Here we show that the selection of soluble lead antibodies from an initial library screening can be greatly facilitated by a fast computational prediction of solubility that requires only the amino acid sequence as input. We quantitatively validate this approach on a panel of nine distinct monoclonal antibodies targeting nerve growth factor (NGF), for which we compare the predicted and measured solubilities finding a very close match, and we further benchmark our predictions with published experimental data on aggregation hotspots and solubility of mutational variants of one of these antibodies.
Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality
Authors: Vavricka Christopher J. , Muto Chiaki , Hasunuma Tomohisa , Kimura Yoshinobu , Araki Michihiro , Wu Yan , Gao George F. , Ohrui Hiroshi , Izumi Minoru , Kiyota Hiromasa
Published: August 2017

The design, synthesis and application of N-acetylneuraminic acid-derived compounds bearing anomeric sulfo functional groups are described. These novel compounds, which we refer to as sulfo-sialic acid analogues, include 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid and its 4-deoxy-3,4-dehydrogenated pseudoglycal. While 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid contains no further modifications of the 2-deoxy-pyranose ring, it is still a more potent inhibitor of avian-origin H5N1 neuraminidase (NA) and drug-resistant His275Tyr NA as compared to the oxocarbenium ion transition state analogue 2,3-dehydro-2-deoxy-N-acetylneuraminic acid. The sulfo-sialic acid analogues described in this report are also more potent inhibitors of influenza NA (up to 40-fold) and bacterial NA (up to 8.5-fold) relative to the corresponding anomeric phosphonic acids. These results confirm that this novel anomeric sulfo modification offers great potential to improve the potency of next-generation NA inhibitors including covalent inhibitors.
Localization of photoperiod responsive circadian oscillators in the mouse suprachiasmatic nucleus
Authors: Yoshikawa Tomoko , Inagaki Natsuko F. , Takagi Seiji , Kuroda Shigeru , Yamasaki Miwako , Watanabe Masahiko , Honma Sato , Honma Ken-ichi
Published: August 2017

The circadian pacemaker in the suprachiasmatic nucleus (SCN) yields photoperiodic response to transfer seasonal information to physiology and behavior. To identify the precise location involved in photoperiodic response in the SCN, we analyzed circadianPeriod1and PERIOD2 rhythms in horizontally sectioned SCN of mice exposed to a long or short day. Statistical analyses of bioluminescence images with respective luciferase reporters on pixel level enabled us to identify the distinct localization of three oscillating regions; a large open-ring-shape region, the region at the posterior end and a sharply demarcated oval region at the center of the SCN. The first two regions are the respective sites for the so-called evening and morning oscillators, and the third region is possibly a site for mediating photic signals to the former oscillators. In these regions, there are two classes of oscillating cells in whichPer1andPer2could play differential roles in photoperiodic responses.
CO2 and temperature decoupling at the million-year scale during the Cretaceous Greenhouse
Authors: Barral Abel , Gomez Bernard , Fourel François , Daviero-Gomez Véronique , Lécuyer Christophe
Published: August 2017

CO2 is considered the main greenhouse gas involved in the current global warming and the primary driver of temperature throughout Earth’s history. However, the soundness of this relationship across time scales and during different climate states of the Earth remains uncertain. Here we explore how CO2 and temperature are related in the framework of a Greenhouse climate state of the Earth. We reconstruct the long-term evolution of atmospheric CO2 concentration (pCO2) throughout the Cretaceous from the carbon isotope compositions of the fossil conifer Frenelopsis. We show that pCO2 was in the range of ca. 150–650 ppm during the Barremian–Santonian interval, far less than what is usually considered for the mid Cretaceous. Comparison with available temperature records suggest that although CO2 may have been a main driver of temperature and primary production at kyr or smaller scales, it was a long-term consequence of the climate-biological system, being decoupled or even showing inverse trends with temperature, at Myr scales. Our analysis indicates that the relationship between CO2 and temperature is time scale-dependent at least during Greenhouse climate states of the Earth and that primary productivity is a key factor to consider in both past and future analyses of the climate system.
Totipotency segregates between the sister blastomeres of two-cell stage mouse embryos
Authors: Casser E. , Israel S. , Witten A. , Schulte K. , Schlatt S. , Nordhoff V. , Boiani M.
Published: August 2017

Following fertilization in mammals, it is generally accepted that totipotent cells are exclusive to the zygote and to each of the two blastomeres originating from the first mitotic division. This model of totipotency was inferred from a minority of cases in which blastomeres produced monozygotic twins in mice. Was this due to experimental limitation or biological constraint? Here we removed experimental obstacles and achieved reliable quantification of the prevalence of dual totipotency among mouse two-cell stage blastomeres. We separated the blastomeres of 1,252 two-cell embryos, preserving 1,210 of the pairs. Two classes of monozygotic twins became apparent at the blastocyst stage: 27% formed a functional epiblast in both members (concordant), and 73% did so in only one member of the pair (discordant) – a partition that proved insensitive to oocyte quality, sperm-entry point, culture environment and pattern of cleavage. In intact two-cell embryos, the ability of sister blastomeres to generate epiblast was also skewed. Class discovery clustering of the individual blastomeres’ and blastocysts’ transcriptomes points to an innate origin of concordance and discordance rather than developmental acquisition. Our data place constraints on the commonly accepted idea that totipotency is allocated equally between the two-cell stage blastomeres in mice.
Atomic-scale study of the amorphous-to-crystalline phase transition mechanism in GeTe thin films
Authors: Mantovan R. , Fallica R. , Mokhles Gerami A. , Mølholt T. E. , Wiemer C. , Longo M. , Gunnlaugsson H. P. , Johnston K. , Masenda H. , Naidoo D. , Ncube M. , Bharuth-Ram K. , Fanciulli M. , Gislason H. P. , Langouche G. , Ólafsson S. , Weyer G.
Published: August 2017

The underlying mechanism driving the structural amorphous-to-crystalline transition in Group VI chalcogenides is still a matter of debate even in the simplest GeTe system. We exploit the extreme sensitivity of 57Fe emission Mössbauer spectroscopy, following dilute implantation of 57Mn (T½ = 1.5 min) at ISOLDE/CERN, to study the electronic charge distribution in the immediate vicinity of the 57Fe probe substituting Ge (FeGe), and to interrogate the local environment of FeGe over the amorphous-crystalline phase transition in GeTe thin films. Our results show that the local structure of as-sputtered amorphous GeTe is a combination of tetrahedral and defect-octahedral sites. The main effect of the crystallization is the conversion from tetrahedral to defect-free octahedral sites. We discover that only the tetrahedral fraction in amorphous GeTe participates to the change of the FeGe-Te chemical bonds, with a net electronic charge density transfer of  ~ 1.6 e/a0 between FeGe and neighboring Te atoms. This charge transfer accounts for a lowering of the covalent character during crystallization. The results are corroborated by theoretical calculations within the framework of density functional theory. The observed atomic-scale chemical-structural changes are directly connected to the macroscopic phase transition and resistivity switch of GeTe thin films.
Mutations in the promoter, intron and CDS of two FAD2 generate multiple alleles modulating linoleic acid level in yellow mustard
Authors: Zeng Fangqin , Roslinsky Vicky , Cheng Bifang
Published: August 2017

Linoleic acid (C18:2) is an important polyunsaturated fatty acid in the seed oil of many crops. Here, we report that mutations in the promoter, intron and CDS of the FAD2 genes SalFAD2.LIA1 and SalFAD2.LIA2 generate three alleles LIA1a
, LIA
1b
and lia
1
and two alleles LIA2 and lia2, respectively, controlling the C18:2 variation (4.4–32.7%) in yellow mustard. The allelic effect on increasing C18:2 content is LIA
1a
 > LIA
1b
 > lia
1
, LIA2 > lia2, and LIA
1a
 > LIA2. The five FAD2 alleles each contain two exons, one intron and a promoter adjacent to exon 1. LIA1a
has a 1152 bp CDS, a 1221 bp intron with promoter function and a 607 bp promoter. Compared with LIA
1a
, the intron of LIA
1b
has reduced promoter activity and that of LIA2 and lia2 has no promoter function due to extensive SNP and indel mutations. lia1 differed from LIA1b
by having an insertion of 1223 bp retrotransposon in its intron. lia
2
with mutations in the promoter has reduced promoter activity compared with LIA
2
. This study revealed that complex quantitative variation of trait phenotype in plants could be modulated by multiple alleles of oligogenic loci resulting from mutations in the regulatory region and CDS.
A new method to investigate the catalytic mechanism of YhdE pyrophosphatase by using a pyrophosphate fluorescence probe
Authors: Shen Qingya , Tan Hongwei , Xing Guo-wen , Zheng Jimin , Jia Zongchao
Published: August 2017

YhdE is a Maf (multicopy associated filamentation) proteins from Escherichia coli which exhibits pyrophosphatase activity towards selected nucleotides, although its catalytic mechanism remains unclear. Herein we used a novel fluorescence probe (4-isoACBA–Zn(II) complex) to characterize the enzymatic properties of YhdE and its mutant, establishing a new method for assaying pyrophosphatase catalytic function. Our results reveal for the first time that the new fluorescence sensor confers high sensitivity and specificity and pyrophosphate (PPi) is the direct catalytic product of YhdE. Crystal structures of a mutant in the active-site loop (YhdE_E33A) show conformational flexibility implicated in the catalytic mechanism of YhdE. ITC experiments and computational docking further reveal that Asp70 and substrate dTTP coordinate Mn2+. Quantum mechanics calculations indicate that YhdE hydrolysis appears to follow a stepwise pathway in which a water molecule first attacks the α-phosphorus atom in the substrate, followed by the release of PPi from the pentavalent intermediate.
Interactions count: plant origin, herbivory and disturbance jointly explain seedling recruitment and community structure
Authors: Korell Lotte , Lang Birgit R. , Hensen Isabell , Auge Harald , Bruelheide Helge
Published: August 2017

Herbivory and disturbance are major drivers of biological invasions, but it is unclear how they interact to determine exotic vs. native seedling recruitment and what consequences arise for biodiversity and ecosystem functioning. Previous studies neglected the roles of different, potentially interacting, guilds of generalist herbivores such as rodents and gastropods. We therefore set up a full-factorial rodent exclusion x gastropod exclusion x disturbance x seed-addition experiment in a grassland community in Central Germany and measured early seedling recruitment, as well as species richness, species composition and aboveground biomass. Gastropod herbivory reduced the positive effect of disturbance on seedling recruitment, particularly for exotic species. Rodent herbivory had weak positive effects on seedling recruitment at undisturbed sites, irrespective of species origin. This effect was likely driven by their strong negative effect on productivity. Interactive effects between both herbivore guilds became only evident for species richness and composition. How many species established themselves depended on disturbance, but was independent of species origin. The fewer exotic species that established themselves increased productivity to a stronger extent compared to native species. Our study highlights that joint effects of disturbance, herbivory and species origin shape early recruitment, while they only weakly affect biodiversity and ecosystem functioning.
Overexpressed somatic alleles are enriched in functional elements in Breast Cancer
Authors: Restrepo Paula , Movassagh Mercedeh , Alomran Nawaf , Miller Christian , Li Muzi , Trenkov Chris , Manchev Yulian , Bahl Sonali , Warnken Stephanie , Spurr Liam , Apanasovich Tatiyana , Crandall Keith , Edwards Nathan , Horvath Anelia
Published: August 2017

Asymmetric allele content in the transcriptome can be indicative of functional and selective features of the underlying genetic variants. Yet, imbalanced alleles, especially from diploid genome regions, are poorly explored in cancer. Here we systematically quantify and integrate the variant allele fraction from corresponding RNA and DNA sequence data from patients with breast cancer acquired through The Cancer Genome Atlas (TCGA). We test for correlation between allele prevalence and functionality in known cancer-implicated genes from the Cancer Gene Census (CGC). We document significant allele-preferential expression of functional variants in CGC genes and across the entire dataset. Notably, we find frequent allele-specific overexpression of variants in tumor-suppressor genes. We also report a list of over-expressed variants from non-CGC genes. Overall, our analysis presents an integrated set of features of somatic allele expression and points to the vast information content of the asymmetric alleles in the cancer transcriptome.
Solid-state 31P and 1H chemical MR micro-imaging of hard tissues and biomaterials with magic angle spinning at very high magnetic field
Authors: Yon Maxime , Sarou-Kanian Vincent , Scheler Ulrich , Bouler Jean-Michel , Bujoli Bruno , Massiot Dominique , Fayon Franck
Published: August 2017

In this work, we show that it is possible to overcome the limitations of solid-state MRI for rigid tissues due to large line broadening and short dephasing times by combining Magic Angle Spinning (MAS) with rotating pulsed field gradients. This allows recordingex vivo31P 3D and 2D slice-selected images of rigid tissues and related biomaterials at very high magnetic field, with greatly improved signal to noise ratio and spatial resolution when compared to static conditions. Cross-polarization is employed to enhance contrast and to further depict spatially localized chemical variations in reduced experimental time. In these materials, very high magnetic field and moderate MAS spinning rate directly provide high spectral resolution and enable the use of frequency selective excitation schemes for chemically selective imaging. These new possibilities are exemplified with experiments probing selectively the 3D spatial distribution of apatitic hydroxyl protons inside a mouse tooth with attached jaw bone with a nominal isotropic resolution nearing 100 µm.