bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Spray‐Dried Flavonoid Microparticles on Oxidative Stability of Methyl Linoleate as Lipid Model System
Authors: Palma Manuel , Márquez‐Ruiz Gloria , García Paula , Holgado Francisca , Vergara Cristina , Giménez Begoña , Robert Paz
Published: November 2016

Microencapsulated quercetin (Q) and epicatechin (E) were prepared by spray‐drying using inulin (IN) as encapsulating agent (Q–IN and E–IN) as well as with Capsul (C) as channelizing agent (Q–IN–C and E–IN–C). Microparticles were added to methyl linoleate (ML) and results showed that Q microparticles markedly improved its oxidative stability by increasing the induction period values and delaying the formation of oxidation compounds, as determined by high‐performance size‐exclusion chromatography, with respect to E microparticles, thus suggesting the importance of flavonoid C‐ring substitution. Remaining levels of Q in the lipid system throughout oxidation of ML added with Q microparticles seemed to show two releasing zones: the first one corresponds to the equilibrium zone, when Q released from microparticles replaces Q that is being degraded; the second zone corresponds to the degradation of Q, when the release rate of the encapsulated Q is slower than its degradation rate. In contrast, E microparticles showed only one zone corresponding to the release of surface E. The end of the induction period was in line with the exhaustion of Q and E and the initiation of formation of advanced oxidation products (polymers). In conclusion, Q microparticles have a potential application to extend the shelf‐life of lipid matrixes.
Social Involvement and Consumption Motivation: Co-Creation of Magic in the Servicescape
Authors: McNeill Lisa , Mather Damien
Published: November 2016

In service experiences, customers often look to create their own magic in the service environment, through interaction with other customers, not the producer of the experience (the provider) at all. The current study examines the bar environment, where hedonically-driven service encounter experiences are constructed, not by the provider, but by the social interactions of the consumers of the environment. The study surveys 130 consumers, measuring experiential, situational and social involvement levels in relation to consumption motivation and overall experience evaluation. The research finds that, while bar consumers are likely to be highly socially involved, they still need the company of close friends to become fully involved in the bar service experience. In addition, where atmospheric theory discusses the value of extraordinary or surprising service environments, consumers in the already hedonic bar environment may indeed prefer environments which are simply comfortable and consistent with their expectations (in regard to motivations to consume and overall positive evaluations).
Blood‐based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic
Authors: O'Bryant Sid E. , Mielke Michelle M. , Rissman Robert A. , Lista Simone , Vanderstichele Hugo , Zetterberg Henrik , Lewczuk Piotr , Posner Holly , Hall James , Johnson Leigh , Fong Yiu‐Lian , Luthman Johan , Jeromin Andreas , Batrla‐Utermann Richard , Villarreal Alcibiades , Britton Gabrielle , Snyder Peter J. , Henriksen Kim , Grammas Paula , Gupta Veer , Martins Ralph , Hampel Harald ,   Biofluid Based Biomarker Professional Interest Area
Published: November 2016

The last decade has seen a substantial increase in research focused on the identification of blood‐based biomarkers that have utility in Alzheimer's disease (AD). Blood‐based biomarkers have significant advantages of being time‐ and cost‐efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood‐based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public‐private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases.
A Randomized Dose Escalation Study of Intravenous Baclofen in Healthy Volunteers: Clinical Tolerance and Pharmacokinetics
Authors: Schmitz Natalie S. , Krach Linda E. , Coles Lisa D. , Mishra Usha , Agarwal Suresh K. , Cloyd James C. , Kriel Robert L.
Published: November 2016

Background

Abrupt discontinuation of baclofen can result in a potentially severe withdrawal syndrome. The current treatment for baclofen withdrawal is inadequate, resulting in a critical need to develop an alternative method to prevent or treat this withdrawal syndrome.

Objective

To evaluate the safety profile and pharmacokinetics of oral (PO) and investigational intravenous (IV) baclofen formulations at clinically relevant doses.

Design

Randomized, open‐label, dose‐escalation, crossover study.

Setting

Contract Research Organization (CRO).

Methods

Three cohorts of 12 healthy adults received single doses of PO baclofen (10 mg, 15 mg or 20 mg) and 10‐minute infusions of IV baclofen (7.5 mg, 11.5 mg, or 15 mg) with a minimum 48‐hour wash‐out period. The third cohort also received a 60‐minute infusion of 15 mg IV baclofen after an additional 48‐hour wash‐out period.

Main Outcome Measures

Subjects were observed in a CRO for 24 hours after each dose of baclofen, and were assessed for nystagmus, ataxia, and sedation. Blood samples were collected from 0 to 24 hours and analyzed for baclofen concentration using high‐performance liquid chromatography−mass spectroscopy. Noncompartmental pharmacokinetic analyses were performed. Dose linearity and proportionality was assessed using 2‐way repeated‐measures analysis of variance and a power model analysis.

Results

None of the PO or IV doses resulted in significant sedation compared to baseline. All subjects could perform tandem gait after each baclofen dose. The most common side effect, transient mild nystagmus, was noted in 4 of 36 and in 13 of 36 subjects after PO and IV administration, respectively. This was likely related to increased maximum concentrations (Cmax). After the 20 mg PO and 15 mg IV doses, mean Cmax levels were 255 and 722 ng/mL and half‐lives were 5.24 and 5.79 hours for PO and IV baclofen, respectively. The mean oral bioavailability for the 20‐mg PO dose was approximately 80%.

Conclusions

All PO and IV doses of baclofen were well tolerated clinically. The 80% bioavailability suggests that a 20% reduction in IV dose will produce comparable total drug exposures to that of the PO dose. When PO therapy is interrupted, bridging with IV baclofen may be feasible.

Level of Evidence

II
Cenozoic history of topography in southeastern Gorny Altai: thermochronology and resistivity and gravity records
Authors: Dobretsov N.L. , Buslov M.M. , Vasilevsky A.N. , Vetrov E.V. , Nevedrova N.N.
Published: November 2016

The Central Asian Orogen was reactivated in the Cenozoic, which gave rise to mountain systems and sedimentary basins, strike-slip and thrust faults, ramps, and rift basins under the far-field effect of the India–Eurasia collision. Pre-Cenozoic structures, as well as the superposed Cenozoic deformation, are traceable in the gravity pattern. Analysis and correlation of stratigraphic, tectonic, geomorphological, and geophysical (resistivity and gravity) data from Gorny Altai and tectonic modeling on the basis of apatite fission-track thermochronology show that vertical motions have been the most active for the past 5 Ma. The uplift and subsidence produced, respectively, the Chulyshman and Ukok Plateaus with high mountains around and the the Kurai–Chuya basin between them. Gravity data suggest the existence of Late Carboniferous, Jurassic, and Cretaceous rocks found in tectonic wedges around the basin at the base of its sedimentary fill.
Geochemical, isotopic, and geochronological evidence for subsynchronous island-arc magmatism and terrigenous sedimentation (Predivinsk terrane of the Yenisei Ridge)
Authors: Nozhkin A.D. , Dmitrieva N.V. , Likhanov I.I. , Serov P.A. , Kozlov P.S.
Published: November 2016

In this study we present data on the geologic setting, geochemical and isotopic compositions, timing and P-T conditions of metamorphism of Neoproterozoic terrigenous metasediments, and associated island-arc metavolcanics of the Predivinsk terrane of the Yenisei Ridge. Relatively immature terrigenous rocks were eroded from a local source which is associated with island-arc magmatic complexes. The geochronological constraints indicate that the terrigenous rocks were eroded from juvenile crustal sources represented primarily by magmatic rocks, which are similar to those of the Predivinsk terrane. This is supported by a similar range of model ages, positive εNd values of terrigenous and magmatic rocks, and correspondence between the concordant ages of detrital zircons from metasedimentary rocks (610–640 Ma) and the U–Pb ages of zircons from rhyolites (ca. 620–640 Ma) from two suites within different sequences. The P-T conditions for volcanosedimentary rocks of the Predivinsk terrane correspond to the epidote-amphibolite facies and the transition from epidote-amphibolite to amphibolite facies. The most likely age of metamorphism due to Vendian accretion/collision events is given by Ar–Ar dates of 600–610 Ma.
Deep seismic structure of the boundary zone between the Eurasian and Okhotsk plates in eastern Russia (along the 3DV deep seismic sounding profile)
Authors: Solov’ev V.M. , Seleznev V.S. , Sal’nikov A.S. , Shibaev S.V. , Timofeev V.Yu. , Liseikin A.V. , Shenmaier A.E.
Published: November 2016

Analysis of geological and geophysical data on the boundary zones between the Eurasian plate and other plates shows poor knowledge of the deep structure of the region. This information will help to refine the position of the plate boundaries and the structure of the Earth’s crust and mantle. We present data on the seismicity and deep structure along the deep seismic sounding (DSS) profile running across the boundary between the Eurasian and Okhotsk plates. A comprehensive analysis of the DSS materials and seismic data shows a significant expression of this boundary zone both in the deep Earth’s crust structures and in the Moho. A zone of anomalous seismicity and deep structure extends along the DSS profile for several hundred kilometers. We have refined the position of the main boundary between the Eurasian and Okhotsk plates, which passes approximately along 144° E.
Evaluation of present-day deformations in the Amurian Plate and its surroundings, based on GPS data
Authors: Ashurkov S.V. , San’kov V.A. , Serov M.A. , Luk’yanov P.Yu. , Grib N.N. , Bordonskii G.S. , Dembelov M.G.
Published: November 2016

We analyze recent crustal movements, based on data of GPS measurements on the Amurian Plate and its margins. Most of the velocities were borrowed from scientific publications. Also, our new and updated data of periodic and permanent GPS observations are presented. A continuous field of strain rates has been constructed using the combined field of movement velocities. Dilatation rates and the directions and values of the main strain axes have been calculated. We have made a quantitative estimation of the maximum shear rates and their directions. Zones of background deformations in the inner part of the Amurian Plate have been revealed along with high-strain zones. Zones with intense tectonic activity, corresponding to areas of reduced lithosphere, often show manifestations of Late Cenozoic volcanism. Part of them can be interpreted as the present-day boundaries of intracontinental geoblocks and small lithospheric plates.
Random and cooperative accumulation of intra- and intergranular defects in granite subject to high-temperature impact fracture
Authors: Shcherbakov I.P. , Chmel A.E.
Published: November 2016

Acoustic emission (AE) from laboratory samples of coarse-grained granite hit by a dropped weight at temperatures from 20 to 500 °C is recorded within a frequency range of 80 kHz–4 MHz. The time series of AE signals bear information on the size of primary defects, since the AE frequency is proportional to the growth rate of microcracks and inversely proportional to their lengths. According to AE data obtained in this study, impact fracture of granite produces cracks at grain boundaries at temperatures below 400 °C and additional defects inside grains at 400 °C and higher. The reason is that overheated water–vapor inclusions increase pressure in the grain interior, which affects the mechanic behavior of granite.
The Preface to the Old English Bede: authorship, transmission, and connection with the West Saxon Genealogical Regnal List
Authors: Waite Greg
Published: November 2016

Lexical and stylistic features indicate that the Preface to the Old English Bede was composed by a writer different from the anonymous Mercian who translated the body of the text. The Preface, therefore, cannot be taken to reveal aspects of the original translator's aims or attitude to the text. Recently discovered collations of the burnt manuscript London, British Library, Cotton Otho B. xi, made by John Smith prior to the 1731 fire, provide further insight, indicating that a copy of the West Saxon Genealogical Regnal List was attached to the Preface by the mid-tenth century. Thus the origins of the Preface may lie in an Alfredian or post-Alfredian initiative to disseminate the translation at some time later than its actual creation.
Old English poetry, verse by verse
Authors: Weiskott Eric
Published: November 2016

Certain syntactical ambiguities in Old English poetry have been the focus of debate among students of metre and syntax. Proponents of intentional ambiguity must demonstrate that the passages in question exhibit, not an absence of syntactical clarity, but a presence of syntactical ambiguity. This article attempts such a demonstration. It does so by shifting the terms of the debate, from clauses to verses and from a spatial to a temporal understanding of syntax. The article proposes a new interpretation of many problematic passages that opens onto a new way of parsing and punctuating Old English poetry.

In this essay in the history of poetic style, I demonstrate that the sequence in time of Old English half-lines sometimes necessitates retrospective syntactical reanalysis, a state of affairs which modern punctuation is ill-equipped to capture, but in which Anglo-Saxon readers and listeners would have recognized specific literary effects. In the second section, I extrapolate two larger syntactical units, the half-line sequence and the verse paragraph, which differ in important ways from the clauses and sentences that modern editors impose on Old English poetic texts. Along the way, I improve the descriptive accuracy of Kuhn's Laws by reinterpreting them as governing half-line sequences rather than clauses. I conclude with a call for unpunctuated or minimally punctuated critical editions of Old English verse texts.
The date and authorship of the Vita Ædwardi regis
Authors: Licence Tom
Published: November 2016

Scholarly understanding of the reign of Edward the Confessor is hampered by doubt surrounding the date, authorship and purpose of the Vita Ædwardi regis, its chief biographical source. This article rejects readings that see it as a work written after the Conquest, arguing instead that it was begun in 1065–6 and tried to foresee what would happen in that time of upheaval by optimistic inspection of precedents from Godwine family history, tempered by anxious reflections on pagan Antiquity. Through the prophetic insights of history it finely balanced Edith's hopes and fears. The second part of the article considers evidence that helps us to identify an author.
A hoard from the reign of Cnut from Buckinghamshire: a preliminary report
Authors: Williams Gareth
Published: November 2016

A hoard of 5,248 silver pennies discovered at Lenborough in Buckinghamshire in December 2015 is one of the largest hoards of Anglo-Saxon coins ever found. Although the deposition of the hoard cannot be precisely dated, it must have been buried in the latter part of the reign of Cnut (1016–35). The hoard was wrapped in lead sheet, establishing without doubt that it represents a single deposit, but contains distinct parcels of coins from the reigns of Æthelred II (978–1016) and the latter part of the reign of Cnut, with a clear gap in between. The cataloguing of the hoard is ongoing, but this paper provides a preliminary description and interpretation of the hoard. While the hoard contains few coins of particular numismatic interest, it is argued that the hoard potentially provides important information for the administration of the late Anglo-Saxon coinage, and for changing patterns of monetary circulation in the reign of Cnut.
A Multidimensional View of Children’s School Readiness
Authors: Sassu Raluca , Roebers Claudia M.
Published: November 2016

Abstract. The present longitudinal study explores, on the one hand, the nature and strengths of the relation between cognitive and behavioral self-regulation, and, on the other hand, the impact of early social, cognitive, and self-regulatory skills on later school achievement and social school adjustment. Findings indicate that working memory is the most important predictor of academic achievement in the longitudinal perspective; individual differences in social school adjustment, in contrast, were mainly explained by earlier behavioral self-regulatory skills. Executive functions, however, may additionally help us to understand the developmental mechanisms responsible for the successes and failures of school adaptation, while behavioral self-regulation, based on its adaptive role, may be quintessential in supporting a child’s successful transition into formal schooling, including its social demands.
Environmental spread of microbes impacts the development of metabolic phenotypes in mice transplanted with microbial communities from humans
Authors: Zhang Li , Bahl Martin Iain , Roager Henrik Munch , Fonvig Cilius Esmann , Hellgren Lars I , Frandsen Henrik Lauritz , Pedersen Oluf , Holm Jens-Christian , Hansen Torben , Licht Tine Rask
Published: November 2016

Microbiota transplantation to germ-free animals is a powerful method to study involvement of gut microbes in the aetiology of metabolic syndrome. Owing to large interpersonal variability in gut microbiota, studies with broad coverage of donors are needed to elucidate the establishment of human-derived microbiotas in mice, factors affecting this process and resulting impact on metabolic health. We thus transplanted faecal microbiotas from humans (16 obese and 16 controls) separately into 64 germ-free Swiss Webster mice caged in pairs within four isolators, with two isolators assigned to each phenotype, thereby allowing us to explore the extent of microbial spread between cages in a well-controlled environment. Despite high group-wise similarity between obese and control human microbiotas, transplanted mice in the four isolators developed distinct gut bacterial composition and activity, body mass gain, and insulin resistance. Spread of microbes between cages within isolators interacted with establishment of the transplanted microbiotas in mice, and contributed to the transmission of metabolic phenotypes. Our findings highlight the impact of donor variability and reveal that inter-individual spread of microbes contributes to the development of metabolic traits. This is of major importance for design of animal studies, and indicates that environmental transfer of microbes between individuals may affect host metabolic traits.
In situ frequency gating and beam splitting of vacuum- and extreme-ultraviolet pulses
Authors: Rajeev Rajendran , Hellwagner Johannes , Schumacher Anne , Jordan Inga , Huppert Martin , Tehlar Andres , Niraghatam Bhargava Ram , Baykusheva Denitsa , Lin Nan , von Conta Aaron , Wörner Hans Jakob
Published: November 2016

Monochromatization of high-harmonic sources has opened fascinating perspectives regarding time-resolved photoemission from all phases of matter. Such studies have invariably involved the use of spectral filters or spectrally dispersive optical components that are inherently lossy and technically complex. Here we present a new technique for the spectral selection of near-threshold harmonics and their spatial separation from the driving beams without any optical elements. We discover the existence of a narrow phase-matching gate resulting from the combination of the non-collinear generation geometry in an extended medium, atomic resonances and absorption. Our technique offers a filter contrast of up to 104 for the selected harmonics against the adjacent ones and offers multiple temporally synchronized beamlets in a single unified scheme. We demonstrate the selective generation of 133, 80 or 56 nm femtosecond pulses from a 400-nm driver, which is specific to the target gas. These results open new pathways towards phase-sensitive multi-pulse spectroscopy in the vacuum- and extreme-ultraviolet, and frequency-selective output coupling from enhancement cavities.
Mfsd2a+ hepatocytes repopulate the liver during injury and regeneration
Authors: Pu Wenjuan , Zhang Hui , Huang Xiuzhen , Tian Xueying , He Lingjuan , Wang Yue , Zhang Libo , Liu Qiaozhen , Li Yan , Li Yi , Zhao Huan , Liu Kuo , Lu Jie , Zhou Yingqun , Huang Pengyu , Nie Yu , Yan Yan , Hui Lijian , Lui Kathy O. , Zhou Bin
Published: November 2016

Hepatocytes are functionally heterogeneous and are divided into two distinct populations based on their metabolic zonation: the periportal and pericentral hepatocytes. During liver injury and regeneration, the cellular dynamics of these two distinct populations remain largely elusive. Here we show that major facilitator super family domain containing 2a (Mfsd2a), previously known to maintain blood–brain barrier function, is a periportal zonation marker. By genetic lineage tracing of Mfsd2a+ periportal hepatocytes, we show that Mfsd2a+ population decreases during liver homeostasis. Nevertheless, liver regeneration induced by partial hepatectomy significantly stimulates expansion of the Mfsd2a+ periportal hepatocytes. Similarly, during chronic liver injury, the Mfsd2a+ hepatocyte population expands and completely replaces the pericentral hepatocyte population throughout the whole liver. After injury recovery, the adult liver re-establishes the metabolic zonation by reprogramming the Mfsd2a+-derived hepatocytes into pericentral hepatocytes. The evidence of entire zonation replacement during injury increases our understanding of liver biology and disease.
Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire
Authors: Yeung Yik Andy , Foletti Davide , Deng Xiaodi , Abdiche Yasmina , Strop Pavel , Glanville Jacob , Pitts Steven , Lindquist Kevin , Sundar Purnima D. , Sirota Marina , Hasa-Moreno Adela , Pham Amber , Melton Witt Jody , Ni Irene , Pons Jaume , Shelton David , Rajpal Arvind , Chaparro-Riggers Javier
Published: November 2016

Staphylococcus aureus is both an important pathogen and a human commensal. To explore this ambivalent relationship between host and microbe, we analysed the memory humoral response against IsdB, a protein involved in iron acquisition, in four healthy donors. Here we show that in all donors a heavily biased use of two immunoglobulin heavy chain germlines generated high affinity (pM) antibodies that neutralize the two IsdB NEAT domains, IGHV4-39 for NEAT1 and IGHV1-69 for NEAT2. In contrast to the typical antibody/antigen interactions, the binding is primarily driven by the germline-encoded hydrophobic CDRH-2 motifs of IGHV1-69 and IGHV4-39, with a binding mechanism nearly identical for each antibody derived from different donors. Our results suggest that IGHV1-69 and IGHV4-39, while part of the adaptive immune system, may have evolved under selection pressure to encode a binding motif innately capable of recognizing and neutralizing a structurally conserved protein domain involved in pathogen iron acquisition.
Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism
Authors: Tamura Tatsuya , Noda Hiroshi , Joyashiki Eri , Hoshino Maiko , Watanabe Tomoyuki , Kinosaki Masahiko , Nishimura Yoshikazu , Esaki Tohru , Ogawa Kotaro , Miyake Taiji , Arai Shinichi , Shimizu Masaru , Kitamura Hidetomo , Sato Haruhiko , Kawabe Yoshiki
Published: November 2016

Parathyroid hormone (PTH) is essential for calcium homeostasis and its action is mediated by the PTH type 1 receptor (PTHR1), a class B G-protein-coupled receptor. Hypoparathyroidism and osteoporosis can be treated with PTH injections; however, no orally effective PTH analogue is available. Here we show that PCO371 is a novel, orally active small molecule that acts as a full agonist of PTHR1. PCO371 does not affect the PTH type 2 receptor (PTHR2), and analysis using PTHR1–PTHR2 chimeric receptors indicated that Proline 415 of PTHR1 is critical for PCO371-mediated PTHR1 activation. Oral administration of PCO371 to osteopenic rats provokes a significant increase in bone turnover with limited increase in bone mass. In hypocalcemic rats, PCO371 restores serum calcium levels without increasing urinary calcium, and with stronger and longer-lasting effects than PTH injections. These results strongly suggest that PCO371 can provide a new treatment option for PTH-related disorders, including hypoparathyroidism.
One-volt-driven superfast polymer actuators based on single-ion conductors
Authors: Kim Onnuri , Kim Hoon , Choi U. Hyeok , Park Moon Jeong
Published: November 2016

The key challenges in the advancement of actuator technologies related to artificial muscles include fast-response time, low operation voltages and durability. Although several researchers have tackled these challenges over the last few decades, no breakthrough has been made. Here we describe a platform for the development of soft actuators that moves a few millimetres under 1 V in air, with a superfast response time of tens of milliseconds. An essential component of this actuator is the single-ion-conducting polymers that contain well-defined ionic domains through the introduction of zwitterions; this achieved an exceptionally high dielectric constant of 76 and a 300-fold enhancement in ionic conductivity. Moreover, the actuator demonstrated long-term durability, with negligible changes in the actuator stroke over 20,000 cycles in air. Owing to its low-power consumption (only 4 mW), we believe that this actuator could pave the way for cutting-edge biomimetic technologies in the future.
Minimal ingredients for orbital-texture switches at Dirac points in strong spin–orbit coupled materials
Authors: Waugh Justin A , Nummy Thomas , Parham Stephen , Liu Qihang , Zhang Xiuwen , Zunger Alex , Dessau Daniel S
Published: November 2016

Recent angle-resolved photoemission spectroscopy measurements on strong spin–orbit coupled materials have shown an in-plane orbital-texture switch at their respective Dirac points, regardless of whether they are topological insulators or ‘trivial’ Rashba materials. This feature has also been demonstrated in a few materials (Bi2Se3, Bi2Te3 and BiTeI) though DFT calculations. Here we present a minimal orbital-derived tight binding model to calculate the electron wavefunction in a two-dimensional crystal lattice. We show that the orbital components of the wavefunction demonstrate an orbital-texture switch in addition to the usual spin switch seen in spin polarised bands. This orbital-texture switch is determined by the existence of three main properties: local or global inversion symmetry breaking, strong spin–orbit coupling and non-local physics (the electrons are on a lattice). Using our model, we demonstrate that the orbital-texture switch is ubiquitous and to be expected in many real systems. The orbital hybridisation of the bands is the key aspect for understanding the unique wavefunction properties of these materials, and this minimal model helps to establish the quantum perturbations that drive these hybridisations.
Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy
Authors: Nakayama Taku , Otsuka Shimpei , Kobayashi Tatsuya , Okajima Hodaka , Matsumoto Kentaro , Hagiya Yuichiro , Inoue Keiji , Shuin Taro , Nakajima Motowo , Tanaka Tohru , Ogura Shun-ichiro
Published: November 2016

Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to drive the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), are in common clinical use. However, the tendency to accumulate PpIX is not well understood. Patients with cancer can develop recurrent metastatic disease with latency periods. This pause can be explained by cancer dormancy. Here we created uniformly sized PC-3 prostate cancer spheroids using a 3D culture plate (EZSPHERE). We demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner not only in spheroids but also in 2D culture. Dormant cancer cells accumulated high PpIX levels and were sensitive to ALA-PDT. In dormant cancer cells, transporter expressions of PEPT1, ALA importer, and ABCB6, an intermediate porphyrin transporter, were upregulated and that of ABCG2, a PpIX exporter, was downregulated. PpIX accumulation and ALA-PDT cytotoxicity were enhanced by G0/G1-phase arrestors in non-dormant cancer cells. Our results demonstrate that ALA-PDT would be an effective approach for dormant cancer cells and can be enhanced by combining with a cell-growth inhibitor.
High flux circularly polarized gamma beam factory: coupling a Fabry-Perot optical cavity with an electron storage ring
Authors: Chaikovska I. , Cassou K. , Chiche R. , Cizeron R. , Cornebise P. , Delerue N. , Jehanno D. , Labaye F. , Marie R. , Martens A. , Peinaud Y. , Soskov V. , Variola A. , Zomer F. , Cormier E. , Lhermite J. , Dolique V. , Flaminio R. , Michel C. , Pinard L. , Sassolas B. , Akagi T. , Araki S. , Honda Y. , Omori T. , Terunuma N. , Urakawa J. , Miyoshi S. , Takahashi T. , Yoshitama H.
Published: November 2016

We report and discuss high-flux generation of circularly polarized γ-rays by means of Compton scattering. The γ-ray beam results from the collision of an external-cavity-enhanced infrared laser beam and a low emittance relativistic electron beam. By operating a non-planar bow-tie high-finesse optical Fabry-Perot cavity coupled to a storage ring, we have recorded a flux of up to (3.5 ± 0.3) × 108 photons per second with a mean measured energy of 24 MeV. The γ-ray flux has been sustained for several hours. In particular, we were able to measure a record value of up to 400 γ-rays per collision in a full bandwidth. Moreover, the impact of Compton scattering on the electron beam dynamics could be observed resulting in a reduction of the electron beam lifetime correlated to the laser power stored in the Fabry-Perot cavity. We demonstrate that the electron beam lifetime provides an independent and consistent determination of the γ-ray flux. Furthermore, a reduction of the γ-ray flux due to intrabeam scattering has clearly been identified. These results, obtained on an accelerator test facility, warrant potential scaling and revealed both expected and yet unobserved effects. They set the baseline for further scaling of the future Compton sources under development around the world.
Robust signatures detection of Majorana fermions in superconducting iron chains
Authors: Chen Hua-Jun , Fang Xian-Wen , Chen Chang-Zhao , Li Yang , Tang Xu-Dong
Published: November 2016

We theoretically propose an optical means to detect Majorana fermions in superconducting iron (Fe) chains with a hybrid quantum dot-nanomechanical resonator system driven by two-tone fields, which is very different from the current tunneling spectroscopy experiments with electrical means. Based on the scheme, the phenomenon of Majorana modes induced transparency is demonstrated and a straightforward method to determine the quantum dot-Majorana fermions coupling strength is also presented. We further investigate the role of the nanomechanical resonator, and the resonator behaving as a phonon cavity enhances the exciton resonance spectrum, which is robust for detecting of Majorana fermions. The coherent optical spectrum affords a potential supplement to detecte Majorana fermions and supports Majorana fermions-based topological quantum computation in superconducting iron chains.
A van der Waals-like Transition Between Normal and Cancerous Phases in Cell Populations Dynamics of Colorectal Cancer
Authors: Qiu Kang , Wang Li-fang , Shen Jian , Yousif Alssadig A. M. , He Peng , Shao Dan-dan , Zhang Xiao-min , Kirunda John B. , Jia Ya
Published: November 2016

Based on a deterministic continuous model of cell populations dynamics in the colonic crypt and in colorectal cancer, we propose four combinations of feedback mechanisms in the differentiations from stem cells (SCs) to transit cells (TCs) and then to differentiated cells (DCs), the four combinations include the double linear (LL), the linear and saturating (LS), the saturating and linear (SL), and the double saturating (SS) feedbacks, respectively. The relative fluctuations of the population of SCs, TCs, and DCs around equilibrium states with four feedback mechanisms are studied by using the Langevin method. With the increasing of net growth rate of TCs, it is found that the Fano factors of TCs and DCs go to a peak in a transient phase, and then increase again to infinity in the cases of LS and SS feedbacks. The “up-down-up” characteristic on the Fano factor (like the van der Waals loop) demonstrates that there exists a transient phase between the normal and cancerous phases, our novel findings suggest that the mathematical model with LS or SS feedback might be better to elucidate the dynamics of a normal and abnormal (cancerous) phases.
Evaluation of promoters and ribosome binding sites for biotechnological applications in the unicellular cyanobacterium Synechocystis sp. PCC 6803
Authors: Englund Elias , Liang Feiyan , Lindberg Pia
Published: November 2016

For effective metabolic engineering, a toolbox of genetic components that enables predictable control of gene expression is needed. Here we present a systematic study of promoters and ribosome binding sites in the unicellular cyanobacterium Synechocystis sp. PCC 6803. A set of metal ion inducible promoters from Synechocystis were compared to commonly used constitutive promoters, by measuring fluorescence of a reporter protein in a standardized setting to allow for accurate comparisons of promoter activity. The most versatile and useful promoter was found to be PnrsB, which from a relatively silent expression could be induced almost 40-fold, nearly up to the activity of the strong psbA2 promoter. By varying the concentrations of the two metal ion inducers Ni2+ and Co2+, expression from the promoter was highly tunable, results that were reproduced with PnrsB driving ethanol production. The activities of several ribosomal binding sites were also measured, and tested in parallel in Synechocystis and Escherichia coli. The results of the study add useful information to the Synechocystis genetic toolbox for biotechnological applications.
GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A
Authors: Barcala Tabarrozzi Andres E. , Andreone Luz , Deckers Julie , Castro Carla N. , Gimeno María L. , Ariolfo Laura , Berguer Paula M. , Antunica-Noguerol María , Liberman Ana C. , Vettorazzi Sabine , Tuckermann Jan P. , De Bosscher Karolien , Perone Marcelo J.
Published: November 2016

Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties. We investigated the effects of CpdA on in vitro generated GM-CSF-conditioned bone marrow-derived DC (BMDC). CpdA-exposed BMDC exhibited low expression of cell-surface molecules and diminution of the release of proinflammatory cytokines upon LPS stimulation; processes associated with BMDC maturation and activation. CpdA-treated BMDC were inefficient at Ag capture via mannose receptor-mediated endocytosis and displayed reduced T-cell priming. CpdA prevented the LPS-induced rise in pErk1/2 and pP38, kinases involved in TLR4 signaling. CpdA fully inhibited LPS-induced pAktSer473, a marker associated with the generation of tolerogenic DC. We used pharmacological blockade and selective genetic loss-of-function tools and demonstrated GR-independent inhibitory effects of CpdA in BMDC. Mechanistically, CpdA-mediated inactivation of the NF-κB intracellular signaling pathway was associated with a short-circuiting of pErk1/2 and pP38 upstream signaling. Assessment of the in vivo function of CpdA-treated BMDC pulsed with the hapten trinitrobenzenesulfonic acid showed impaired cell-mediated contact hypersensitivity. Collectively, we provide evidence that CpdA is an effective BMDC modulator that might have a benefit for immune disorders, even when GR is not directly targeted.
Tree species, tree genotypes and tree genotypic diversity levels affect microbe-mediated soil ecosystem functions in a subtropical forest
Authors: Purahong Witoon , Durka Walter , Fischer Markus , Dommert Sven , Schöps Ricardo , Buscot François , Wubet Tesfaye
Published: November 2016

Tree species identity and tree genotypes contribute to the shaping of soil microbial communities. However, knowledge about how these two factors influence soil ecosystem functions is still lacking. Furthermore, in forest ecosystems tree genotypes co-occur and interact with each other, thus the effects of tree genotypic diversity on soil ecosystem functions merit attention. Here we investigated the effects of tree species, tree genotypes and genotypic diversity levels, alongside soil physicochemical properties, on the overall and specific soil enzyme activity patterns. Our results indicate that tree species identity, tree genotypes and genotypic diversity level have significant influences on overall and specific soil enzyme activity patterns. These three factors influence soil enzyme patterns partly through effects on soil physicochemical properties and substrate quality. Variance partitioning showed that tree species identity, genotypic diversity level, pH and water content all together explained ~30% variations in the overall patterns of soil enzymes. However, we also found that the responses of soil ecosystem functions to tree genotypes and genotypic diversity are complex, being dependent on tree species identity and controlled by multiple factors. Our study highlights the important of inter- and intra-specific variations in tree species in shaping soil ecosystem functions in a subtropical forest.
Observation selection bias in contact prediction and its implications for structural bioinformatics
Authors: Orlando G. , Raimondi D. , Vranken W. F.
Published: November 2016

Next Generation Sequencing is dramatically increasing the number of known protein sequences, with related experimentally determined protein structures lagging behind. Structural bioinformatics is attempting to close this gap by developing approaches that predict structure-level characteristics for uncharacterized protein sequences, with most of the developed methods relying heavily on evolutionary information collected from homologous sequences. Here we show that there is a substantial observational selection bias in this approach: the predictions are validated on proteins with known structures from the PDB, but exactly for those proteins significantly more homologs are available compared to less studied sequences randomly extracted from Uniprot. Structural bioinformatics methods that were developed this way are thus likely to have over-estimated performances; we demonstrate this for two contact prediction methods, where performances drop up to 60% when taking into account a more realistic amount of evolutionary information. We provide a bias-free dataset for the validation for contact prediction methods called NOUMENON.
Principles of proteome allocation are revealed using proteomic data and genome-scale models
Authors: Yang Laurence , Yurkovich James T. , Lloyd Colton J. , Ebrahim Ali , Saunders Michael A. , Palsson Bernhard O.
Published: November 2016

Integrating omics data to refine or make context-specific models is an active field of constraint-based modeling. Proteomics now cover over 95% of the Escherichia coli proteome by mass. Genome-scale models of Metabolism and macromolecular Expression (ME) compute proteome allocation linked to metabolism and fitness. Using proteomics data, we formulated allocation constraints for key proteome sectors in the ME model. The resulting calibrated model effectively computed the “generalist” (wild-type) E. coli proteome and phenotype across diverse growth environments. Across 15 growth conditions, prediction errors for growth rate and metabolic fluxes were 69% and 14% lower, respectively. The sector-constrained ME model thus represents a generalist ME model reflecting both growth rate maximization and “hedging” against uncertain environments and stresses, as indicated by significant enrichment of these sectors for the general stress response sigma factor σS. Finally, the sector constraints represent a general formalism for integrating omics data from any experimental condition into constraint-based ME models. The constraints can be fine-grained (individual proteins) or coarse-grained (functionally-related protein groups) as demonstrated here. This flexible formalism provides an accessible approach for narrowing the gap between the complexity captured by omics data and governing principles of proteome allocation described by systems-level models.
Synthesis of (3R)-acetoin and 2,3-butanediol isomers by metabolically engineered Lactococcus lactis
Authors: Kandasamy Vijayalakshmi , Liu Jianming , Dantoft Shruti Harnal , Solem Christian , Jensen Peter Ruhdal
Published: November 2016

The potential that lies in harnessing the chemical synthesis capabilities inherent in living organisms is immense. Here we demonstrate how the biosynthetic machinery of Lactococcus lactis, can be diverted to make (3R)-acetoin and the derived 2,3-butanediol isomers meso-(2,3)-butanediol (m-BDO) and (2R,3R)-butanediol (R-BDO). Efficient production of (3R)-acetoin was accomplished using a strain where the competing lactate, acetate and ethanol forming pathways had been blocked. By introducing different alcohol dehydrogenases into this strain, either EcBDH from Enterobacter cloacae or SadB from Achromobacter xylosooxidans, it was possible to achieve high-yield production of m-BDO or R-BDO respectively. To achieve biosustainable production of these chemicals from dairy waste, we transformed the above strains with the lactose plasmid pLP712. This enabled efficient production of (3R)-acetoin, m-BDO and R-BDO from processed whey waste, with titers of 27, 51, and 32 g/L respectively. The corresponding yields obtained were 0.42, 0.47 and 0.40 g/g lactose, which is 82%, 89%, and 76% of maximum theoretical yield respectively. These results clearly demonstrate that L. lactis is an excellent choice as a cell factory for transforming lactose containing dairy waste into value added chemicals.
Osteogenic and bactericidal surfaces from hydrothermal titania nanowires on titanium substrates
Authors: Tsimbouri P. M. , Fisher L. , Holloway N. , Sjostrom T. , Nobbs A. H. , Meek R. M. D , Su B. , Dalby M. J.
Published: November 2016

Nanotopographical cues on Ti have been shown to elicit different cell responses such as cell differentiation and selective growth. Bone remodelling is a constant process requiring specific cues for optimal bone growth and implant fixation. Moreover, biofilm formation and the resulting infection on surgical implants is a major issue. Our aim is to identify nanopatterns on Ti surfaces that would be optimal for both bone remodelling and for reducing risk of bacterial infection. Primary human osteoblast/osteoclast co-cultures were seeded onto Ti substrates with TiO2 nanowires grown under alkaline conditions at 240 °C for different times (2, 2.5 or 3 h). Cell growth and behaviour was assessed by scanning electron microscopy (SEM), immunofluorescence microscopy, histochemistry and quantitative RT-PCR methods. Bacterial colonisation of the nanowire surfaces was also assessed by confocal microscopy and SEM. From the three surfaces tested the 2 h nanowire surface supported osteoblast and to a lesser extent osteoclast growth and differentiation. At the same time bacterial viability was reduced. Hence the 2 h surface provided optimal bone remodeling in vitro conditions while reducing infection risk, making it a favourable candidate for future implant surfaces.
Low-voltage scanning electron microscopy study of lampbrush chromosomes and nuclear bodies in avian and amphibian oocytes
Authors: Kulikova Tatiana , Khodyuchenko Tatiana , Petrov Yuri , Krasikova Alla
Published: November 2016

Nucleus is a highly compartmentalized part of the cell where the key processes of genome functionality are realized through the formation of non-membranous nuclear domains. Physically nuclear domains appear as liquid droplets with different viscosity stably maintained throughout the interphase or during the long diplotene stage of meiosis. Since nuclear body surface represents boundary between two liquid phases, the ultrastructural surface topography of nuclear domains is of an outstanding interest. The aim of this study was to examine ultrathin surface topography of the amphibian and avian oocyte nuclear structures such as lampbrush chromosomes, nucleoli, histone-locus bodies, Cajal body-like bodies, and the interchromatin granule clusters via low-voltage scanning electron microscopy. Our results demonstrate that nuclear bodies with similar molecular composition may differ dramatically in the surface topography and vice versa, nuclear bodies that do not share common molecular components may possess similar topographical characteristics. We also have analyzed surface distribution of particular nuclear antigens (double stranded DNA, coilin and splicing snRNA) using indirect immunogold labeling with subsequent secondary electron detection of gold nanoparticles. We suggest that ultrastructural surface morphology reflects functional status of a nuclear body.
A Direct Mapping of Max k-SAT and High Order Parity Checks to a Chimera Graph
Authors: Chancellor N. , Zohren S. , Warburton P. A. , Benjamin S. C. , Roberts S.
Published: November 2016

We demonstrate a direct mapping of max k-SAT problems (and weighted max k-SAT) to a Chimera graph, which is the non-planar hardware graph of the devices built by D-Wave Systems Inc. We further show that this mapping can be used to map a similar class of maximum satisfiability problems where the clauses are replaced by parity checks over potentially large numbers of bits. The latter is of specific interest for applications in decoding for communication. We discuss an example in which the decoding of a turbo code, which has been demonstrated to perform near the Shannon limit, can be mapped to a Chimera graph. The weighted max k-SAT problem is the most general class of satisfiability problems, so our result effectively demonstrates how any satisfiability problem may be directly mapped to a Chimera graph. Our methods faithfully reproduce the low energy spectrum of the target problems, so therefore may also be used for maximum entropy inference.