bluuebunny/crossref_metadata_2025 huggingface dataset:
Second order fully discrete defect‐correction scheme for nonstationary conduction‐convection problem at high Reynolds number
Authors: Su Haiyan , Feng Xinlong , He Yinnian
Published: October 2016

This survey enfolds rigorous analysis of the defect‐correction finite element (FE) method for the time‐dependent conduction‐convection problem which based on the Crank‐Nicolson scheme. The method consists of two steps: solve a nonlinear problem with an added artificial viscosity term on a FE grid and correct the solutions on the same grid using a linearized defect‐correction technique. The stability and optimal error estimate of the fully discrete scheme are derived. As a consequence, the effectiveness of the method to deal with high Reynolds number is illustrated in several numerical experiments. © 2016 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 33: 681–703, 2017
Investigation on the buckling and postbuckling performance of aero stiffened composite panels under axial compression
Authors: Feng Yu , Zhang Haoyu , Tan Xiangfei , An Tao , He Yuting , Zheng Jie
Published: October 2016

Buckling and postbuckling performances of aero stiffened composite panels were studied in this article. The average failure load is 2.43 times larger than the average buckling load, which indicates the high postbuckling carrying capacity. The failure modes are complex, which contain the debonding of skin to stiffeners, breaking of stiffeners together with tearing and splitting of skin. A method to verify the buckling patterns of stiffened composite panels was proposed by the analysis based on strains. There are four half waves in each skin bay. However, the locations of convex and concave in each skin bay are different. The buckling patterns are local buckling of skin, which keep stable without global buckling occurring during compression. Buckling load was evaluated using the governing function and a stronger result was obtained. An engineering approach to estimate the failure load was proposed, which could predict the failure load accurately. At last, the FE analysis was conducted using nonlinear method by ABAQUS. The FE results are very consistent to the experimental ones. POLYM. COMPOS., 39:2547–2559, 2018. © 2016 Society of Plastics Engineers
Thermomechanical properties and bioactivity evaluation of silicone rubber composites
Authors: Vasilakos Sozon P. , Athanasoulia Ioanna‐Georgia , Tarantili Petroula A. , Kyriakidou Kyriaki , Papadopoulos Triantafyllos
Published: October 2016

The effect of incorporation of nanofillers (montmorillonite, silica, hydroxyapatite) and bioactive glass (BG) microparticles into a silicone elastomer matrix, on its thermomechanical properties and bioactivity was investigated. The obtained samples were characterized using differential scanning calorimetry and dynamic mechanical analysis, as well as by hardness, tensile, and tear testing, whereas their bioactivity was evaluated by immersion of specimens into simulated body fluid solution and by cell culture experiments (fibroblasts and osteoblasts). Montmorillonites and especially Cloisite 20A have been shown the most efficient reinforcement for improving mechanical properties of silicone rubber composites. On the other hand, BG and silica hybrids exhibited significant bioactive properties. POLYM. COMPOS., 39:2560–2570, 2018. © 2016 Society of Plastics Engineers
Synthesis and characterization of novel semiaromatic copolyamides bearing both polar hydroxyl and unsaturated allyl substituents
Authors: Wang Wenbin , Qi Xiang , Zhang Fei , Zhu Yingdan , Wan Xinhua
Published: October 2016

A series of novel semiaromatic (co)polyamides, poly(octylene terephthalamide)‐ran‐poly[octylene 2,5‐bis(allyloxy)terephthalamide] (APA8T‐x, x represents the molar fraction of allyloxy containing structure unit), were prepared via the interfacial polymerization of 1,8‐diaminooctane, terephthaloyl chloride, and 2,5‐bis(allyloxy)terephthaloyl chloride. The polymerization conditions were optimized in terms of the yields and the molecular weights of the resultant polymers. These polymers were converted to the target macromolecules, poly(octylene terephthalamide)‐ran‐poly[octylene (2,5‐dihydroxy‐3,6‐diallyl)terephthalamide] (CRPA8T‐x), through solid state Claisen rearrangement reaction, as characterized by 1H NMR and FT‐IR spectroscopies. While APA8T‐x was only soluble in very limited solvents, the solubility of CRPA8T‐x in polar solvents improved remarkably, especially for those with high counit content. Due to the polarity of hydroxyl group, CRPA8T‐x showed an improved hydrophilicity than APA8T‐x. The treatment of aramid fibers with CRPA8T‐x, as sizing agents, enhanced obviously their interfacial adhesion toward epoxy resin. The fibers sized with 0.5 wt% CRPA8T‐75 solution in the mixture of 1,1,2,2‐tetrachloroethane and phenol (40:60, w/w) exhibited a maximum increase of 60% in interfacial shear strength than the naked fibers. The easy preparation and the facility for the further modification through the dual functional substituents may greatly widen the application of semiaromatic polyamides. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 690–698
Cold atmospheric plasma treatment of melanoma and glioblastoma cancer cells
Authors: Vermeylen Stijn , De Waele Jorrit , Vanuytsel Steven , De Backer Joey , Van der Paal Jonas , Ramakers Marleen , Leyssens Karen , Marcq Elly , Van Audenaerde Jonas , L. J. Smits Evelien , Dewilde Sylvia , Bogaerts Annemie
Published: October 2016

In this paper, two types of melanoma and glioblastoma cancer cell lines are treated with cold atmospheric plasma to assess the effect of several parameters on the cell viability. The cell viability decreases with treatment duration and time until analysis in all cell lines with varying sensitivity. The majority of dead cells stains both AnnexinV (AnnV) and propidium iodide, indicating that the plasma‐treated non‐viable cells are mostly late apoptotic or necrotic. Genetic mutations might be involved in the response to plasma. Comparing the effects of two gas mixtures, as well as indirect plasma‐activated medium versus direct treatment, gives different results per cell line. In conclusion, this study confirms the potential of plasma for cancer therapy and emphasizes the influence of experimental parameters on therapeutic outcome.
Therapeutic laryngoscopy during exercise: A novel non‐surgical therapy for refractory EILO
Authors: Olin J. Tod , Deardorff Emily H. , Fan Elizabeth M. , Johnston Kristina L. , Keever Valerie L. , Moore Camille M. , Bender Bruce G.
Published: October 2016

Background

Exercise‐induced laryngeal obstruction (EILO) may affect as many as 6% of the adolescent population, with some patients experiencing symptoms refractory to conservative interventions.

Objectives

This report describes therapeutic laryngoscopy during exercise, a novel, non‐surgical intervention that harnesses real‐time laryngoscopy video as biofeedback to control laryngeal aperture during high‐intensity exercise. Additionally, we quantitate patient‐reported perceptions of procedure safety, tolerability, learning value, and effectiveness.

Methods

Clinical EILO patients with symptoms refractory to conventional respiratory retraining and other therapies were referred for the procedure which features laryngoscopy video as biofeedback during serial physician‐guided 1‐min exercise sprints. We quantify perceptions of procedure safety, tolerability, learning value, and effectiveness through questionnaires offered to all patients as well as observers of the procedure.

Results

Forty‐one patients and 37 parent observers were approached for feedback; 88% of patients and 95% of observers consented to participation. Patients and observers reported perceptions of safety and tolerability (81% and 86%, respectively), learning value (78% and 91%, respectively), and effectiveness (58% and 80%, respectively) with patient age predicting some responses. Seventy‐five percent of patients noted that “Since the procedure, my breathing during exercise has improved,” and 85% of this group noted that therapeutic laryngoscopy during exercise was “the most important therapy leading to my breathing improvement.” The procedure also provided insight into the psychological experience of patients, a domain not clinically apparent prior to the procedure.

Conclusions

Our data support further study of therapeutic laryngoscopy during exercise as a possible intervention for patients with refractory EILO. Pediatr Pulmonol. 2017;52:813–819. © 2016 Wiley Periodicals, Inc.
Implementation of cystic fibrosis clinical pathways improved physician adherence to care guidelines
Authors: Singh Sachinkumar B. , Shelton Annie U. , Greenberg Barbara , Starner Timothy D.
Published: October 2016

Introduction

There is significant variability in clinical outcomes, including growth and lung function, between the various cystic fibrosis (CF) centers. No specific or unique therapeutic practices have been identified to account for these differences. However, more uniform care within centers was associated with better outcomes. The objective of this study was to implement clinical pathways for diagnosis and treatment of nutritional failure and lung inflammation in order to achieve better health care provider adherence to center‐specific, agreed‐on practices.

Methods

Agreed‐on clinical pathway treatment plans for both nutrition and lower airway inflammation were implemented on January 1, 2010. The primary outcome measure was to evaluate if patients’ diagnoses and treatments were consistent with the agreed‐on clinical pathways.

Results

The proportion of clinic visits from baseline to 18 months post‐intervention where the provider completely followed nutrition clinical pathway increased from 57.72% to 79.49% (P = 0.049) and the proportion for lower airway inflammation clinical pathway increased from 65.85% to 86.32% (P = 0.035). The use of nutritional diagnosis and documentation of associated clinical pathway in the clinical plan increased from 16.26% to 61.54% and 56.10% to 94.87%, respectively. Similarly, diagnosis of lower airway inflammation and documentation related to their treatment plans increased from 1.63% to 43.59% and 30.08% to 87.18%, respectively.

Conclusion

Implementation of clinical pathways for nutrition and lower airway inflammation issues resulted in more uniform care of CF patients. Having objective criteria for diagnoses and agreed‐on treatment plans for each of those diagnoses allowed for monitoring and individual feedback. Increases in utilization of correct diagnoses and discussion of specific therapeutic interventions in the clinic notes were associated with increased adherence to clinical pathways. Pediatr Pulmonol. 2017;52:175–181. © 2016 Wiley Periodicals, Inc.
Systematic Quality Control Analysis of LINCS Data
Authors: Cheng L , Li L
Published: October 2016

The Library of Integrated Cellular Signatures (LINCS) project provides comprehensive transcriptome profiling of human cell lines before and after chemical and genetic perturbations. Its L1000 platform utilizes 978 landmark genes to infer the transcript levels of 14,292 genes computationally. Here we conducted the L1000 data quality control analysis by using MCF7, PC3, and A375 cell lines as representative examples. Before perturbations, a promising 80% correlation in transcriptome was observed between L1000‐ and Affymetrix HU133A‐platforms. After library‐based shRNA perturbations, a moderate 30% of differentially expressed genes overlapped between any two selected controls viral vectors using the L1000 platform. The mitogen‐activated protein kinase, vascular endothelial growth factor, and T‐cell receptor pathways were identified as the most significantly shared pathways between chemical and genetic perturbations in cancer cells. In conclusion, L1000 platform is reliable in assessing transcriptome before perturbation. Its response to perturbagens needs to be interpreted with caution. A quality control analysis pipeline of L1000 is recommended before addressing biological questions.
Crystal Structures and Hydrogen Bonding of Two Complexes containing the [Ammine‐chlorido‐ethylenediamine‐bis(pyridine)cobalt(III)]2+ Cation
Authors: Liebing Phil , Hilfert Liane , Lorenz Volker , Edelmann Frank T.
Published: October 2016

The crystal structures of two classical cobalt(III) complexes comprising the [CoCl(NH3)(en)(py)2]2+ cation were determined by single‐crystal X‐ray diffraction. Both complexes, dark red [CoCl(NH3)(en)(py)2]Cl2·H2O (1) and purple [CoCl(NH3)‐(en)(py)2][HgCl4]·1.125H2O (2), crystallize in the triclinic space group P1. In both compounds, the Co atom exhibits a typical octahedral coordination and the configuration index of the complex is OC‐6‐43. In the case of the chloride (1), the asymmetric unit comprises one formula unit, whereas there are two formula units in the case of the tetrachloridomercurate (2). Complex cations, anions, and crystal water molecules are interconnected by various N–H···N, N–H···Cl, N–H···O, O–H···Cl, and O–H···O bridge bonds. As a result, compound 1 features a two‐dimensional layer structure and compound 2 exists as a three‐dimensional network.
Impact of the Level of Anastomosis on Reflux Esophagitis Following Esophagectomy with Gastric Tube Reconstruction
Authors: Sakai Makoto , Sohda Makoto , Miyazaki Tatsuya , Yoshida Tomonori , Kumakura Yuji , Honjo Hiroaki , Hara Keigo , Yokobori Takehiko , Kuwano Hiroyuki
Published: October 2016

Background

Among patients who undergo gastric tube reconstruction after esophagectomy, it is generally accepted that the incidence of reflux esophagitis (RE) is significantly lower in patients with neck anastomosis than in those with intrathoracic anastomosis. However, the true impact of the level of anastomosis on RE currently remains unclear.

Methods

We examined 53 patients with thoracic esophageal cancer underwent radical esophagectomy with gastric tube reconstruction and neck anastomosis. The level of anastomosis was assessed by measuring the distance from the sternal notch to the stapled ring by computed tomography. The relative level of anastomosis was calculated by the distance from the sternal notch to the most caudal side of the stapled ring (mm)/height (cm).

Results

The relative level of anastomosis in 30 (56.6%) patients showed <0, which indicated that anastomosis in these patients was located at a lower level than the sternal notch. The mean relative level of anastomosis was significantly lower in patients with RE (grade A to D) than in those without RE (grade N) (−0.062 vs. −0.012 mm/cm, respectively; p = 0.043). RE was more severe with a lower relative level of anastomosis (p for trends = 0.044).

Conclusions

The level of anastomosis in patients with gastric tube reconstruction following esophagectomy was associated with the incidence of RE. The displacement of anastomosis into the thoracic cavity was detected in approximately half of the patients with neck anastomosis. RE was more severe with a lower level of anastomosis, even in patients with neck anastomosis.
Strategies for manipulation of oxygen utilization by the electron transfer chain in microbes for metabolic engineering purposes
Authors: Bennett George N , San Ka-Yiu
Published: October 2016

Microaerobic growth is of importance in ecological niches, pathogenic infections and industrial production of chemicals. The use of low levels of oxygen enables the cell to gain energy and grow more robustly in the presence of a carbon source that can be oxidized and provide electrons to the respiratory chain in the membrane. A considerable amount of information is available on the genes and proteins involved in respiratory growth and the regulation of genes involved in aerobic and anaerobic metabolism. The dependence of regulation on sensing systems that respond to reduced quinones (e.g. ArcB) or oxygen levels that affect labile redox components of transcription regulators (Fnr) are key in understanding the regulation. Manipulation of the amount of respiration can be difficult to control in dense cultures or inadequately mixed reactors leading to inhomogeneous cultures that may have lower than optimal performance. Efforts to control respiration through genetic means have been reported and address mutations affecting components of the electron transport chain. In a recent report completion for intermediates of the ubiquinone biosynthetic pathway was used to dial the level of respiration vs lactate formation in an aerobically grown E. coli culture.
Sant'Omobono: an interim status quaestionis
Authors: Diffendale Daniel P. , Brocato Paolo , Terrenato Nicola , Brock Andrea L.
Published: October 2016

The church of Sant’Omobono sits above one of the highest human occupation sequences in the city of Rome. Some 3.5 m of sediment lie between the earliest known Bronze Age occupation lens and the base of the foundations of the early 6th c. B.C. temple, a further 13 m above which lies the floor of the present church, reconstructed in A.D. 1482. The site was sacred to the goddesses Fortuna and Mater Matuta for more than a millennium, before one of their temples was converted into a church of San Salvatore, rebuilt many times and eventually rededicated to Saints Anthony and Omobono. The archaeological remains were discovered by chance in 1936, when the dense neighborhood surrounding the church was demolished to make way for new Fascist infrastructure. The site was spared from further construction, and excavations continued sporadically through the latter half of the 20th c. This work was carried out by a diverse cast of archaeologists employing an equally diverse range of methodologies and field practices, though none of this work has been fully published. Since 2009, the Sant’Omobono Project, a collaboration between the University of Michigan, the Università della Calabria, and the Sovrintendenza Capitolina of the Comune di Roma, has continued this research with the goal of understanding and publishing whatever possible from the earlier excavations and bringing updated methodologies to bear on the site. While preparations for comprehensive publication are ongoing, the present article summarizes the main occupation and construction phases at the site as understood after 6 years of work by the project.
The early development of concrete in the domestic architecture of pre-Roman Pompeii
Authors: Mogetta Marcello
Published: October 2016

Because of its exceptional state of preservation, Pompeii has traditionally been viewed as an ideal site at which to study the early development of Roman architecture. Scholars have looked to the Pompeian evidence in order to provide parallels for periods and classes of buildings that in Rome are less well documented archaeologically. The focus of recent debate has been on the Mid- to Late Republican transition, with an emphasis on building types whose introduction at Pompeii would demonstrate a direct cultural link with practice at Rome. The prevailing view is that both the town-planning and the architecture of Pompeii in the 3rd-2nd c. B.C. were strongly influenced by Roman models or prototypes. Similarly, there has been a tendency to refer to the Pompeian materials as the missing link for the high dating of early Roman concrete architecture in Rome, which would have been introduced around the same period. In a recent review of the evidence from Rome, I have argued for a later chronology, which, inevitably, prompts a reconsideration of the development and cultural significance of concrete construction at Pompeii.
Shipwreck cargoes in the western Mediterranean and the organization of Roman maritime trade
Authors: Rice Candace
Published: October 2016

Much has been written about the nature and scale of Roman maritime trade, yet there remains no detailed analysis of the range of shipwreck cargoes at our disposal and the information that they provide for the organizational aspects of maritime trade. Identifying the mechanisms through whih products were traded is one of the most challenging aspects of the study of Roman trade.
In ampitζatru Carthaginis: the Carthage amphitheatre and its uses
Authors: Rossiter Jeremy
Published: October 2016

The amphitheatre at Carthage lies on the W edge of the ancient city just south of the decumanus maximus as it heads inland (fig. 1). Modern investigation dates back to the late 19th c. when A.-L. Delattre spent several years (1894-96) excavating the building, but, apart from a handful of inscriptions and minor objects recovered, few details were ever published. In the decades following, parts of the amphitheatre were reconstructed but no further archaeological work was undertaken (fig. 2). It was not until the 1980s that a detailed study of the building was attempted, at which time not one but two important publications appeared, one by J.-Cl. Golvin, the other by D. L. Bomgardner. The building history is not known with much certainty, but Golvin and Bomgardner are generally in agreement on the following key points. It was originally built in the early 1st c. A.D. but was extensively rebuilt in the 2nd c., probably under the Antonines. At this time its capacity was nearly doubled and a new limestone façade added. A description of the façade by the 11th-c. Arab geographer al-Bakri mentions three levels of arcades embellished with engaged columns and with relief sculptures depicting ‘craftsmen, animals, and ships’.
Funerary practices and sacerdotal rank in pre-Roman northern and central Italy: new data for interpreting the ‘ritual shovel’
Authors: Sacchetti Federica
Published: October 2016

In Early Iron Age cultures (the Golasecca, Este and Villanovan/Etruscan of the Po valley in the 7th-4th c. B.C.), a characteristic metal object has often been linked to unspecified ritual practices of protohistoric Italic peoples, raising various archaeological, anthropological and religious questions. This object, a ‘ritual shovel’ (Italian: paletta rituale; German: Bronzepalette) was first described by G. Ghirardini, who published two examples, one from Padua and one in Rome's Pigorini Museum. In 1902, he drew up a catalogue of 13 pieces and attempted to establish the first chronological sequence. During the first half of the 19th c., various pieces were published, but no studies addressed the typological, chronological and functional questions relating to the ritual shovel until M. Zuffa focused on it, providing what is still the most recent catalogue and the only discussion (fig. 1).
Another eyewitness to the plague described by Cyprian, with notes on the “Persecution of Decius”
Authors: Harper Kyle
Published: October 2016

In JRA 28 (2015), I published a study of the sources for the pandemic mortality event that struck the Roman Empire during the years A.D. c.249-270. Although relatively neglected in recent historiography, this pandemic is surprisingly well attested both by contemporary witnesses and by later sources reflecting the earlier tradition. The study identified at least 6 contemporary testimonies and 6 other independent lines of transmission about the disease, disentangling some two dozen sources of information down through the Late Byzantine chronicles. The plague described by Cyprian, despite progressing against the backdrop of one of the most poorly documented phases of Roman history, has left behind a body of literary evidence that in sheer volume exceeds the testimony for the better-studied Antonine plague of the late 2nd c. Moreover, the evidence for the plague described by Cyprian is, collectively, quite compelling; the consistency of independent testimony adds credence to the claims of a major mortality event. My study claimed to have gathered the ancient sources “comprehensively and collectively”, but such claims are precarious and an electronic search of the Cetedoc Library of Christian Latin Texts has uncovered yet another (seventh) contemporary witness to the pandemic.
Social clustering in 5th-c. Constantinople: the evidence of the Notitia
Authors: Anderson Benjamin
Published: October 2016

Clustering of residents of similar social status, ethnic or religious identity, or geographical origin into distinct areas of a city is a “common, but by no means universal, attribute of urban neighborhoods”. Different cities within a single culture and era exhibit diversity in the occurrence and nature of clustering: “there is no such thing as a ‘typical’ pattern of clustering within, say, Medieval cities or Islamic cities”.

The existence and nature of clustering in Roman cities have rarely been the object of systematic study, and most contributions have focused on textual evidence for clustering in the city of Rome. A recent consideration of Rome under the Principate finds

no evidence for strong clustering along social lines. The evidence points rather to the reverse: social mixing, at all levels.

Similarly, a study of the neighborhoods of Augustan Rome observes that,

although areas of the city might develop reputations as more or less desirable, ancient Rome was not generally segregated by class. Apartment buildings for poorer residents existed alongside the houses of more affluent residents in almost every quarter of the city.
The status of Serena and the Stilicho diptych
Authors: Cameron Alan
Published: October 2016

One of the best known (and best preserved) of late-antique ivories is what is generally known as the Stilicho diptych, kept in the tesoro of the cathedral at Monza. It represents a military man with a spear and shield on one panel, and, on the other, a high-ranking woman holding a flower above the head of a small boy, not more than 10 years old; he stands between them wearing a chlamys and holding the codicils of office in his left hand (fig. 1). Ever since the basic article by C. Jullian more than 130 years ago, it has been generally accepted that the only candidates who fit this description are the western magister utriusque militiae Stilicho (d. 408), his wife Serena, the niece and (according to Claudian) adoptive daughter of Theodosius I, and their son Eucherius, appointed to the office of tribunus et notarius in (probably) 395/6.
E1A enhances cellular sensitivity to DNA-damage-induced apoptosis through PIDD-dependent caspase-2 activation
Authors: Radke Jay R , Siddiqui Zeba K , Figueroa Iris , Cook James L
Published: October 2016

Expression of the adenoviral protein, E1A, sensitizes mammalian cells to a wide variety of apoptosis-inducing agents through multiple cellular pathways. For example, E1A sensitizes cells to apoptosis induced by TNF-superfamily members by inhibiting NF-kappa B (NF-κB)-dependent gene expression. In contrast, E1A sensitization to nitric oxide, an inducer of the intrinsic apoptotic pathway, is not dependent upon repression of NF-κB-dependent transcription but rather is dependent upon caspase-2 activation. The latter observation suggested that E1A-induced enhancement of caspase-2 activation might be a critical factor in cellular sensitization to other intrinsic apoptosis pathway-inducing agents. Etoposide and gemcitabine are two DNA damaging agents that induce intrinsic apoptosis. Here we report that E1A-induced sensitization to both of these agents, like NO, is independent of NF-κB activation but dependent on caspase-2 activation. The results show that caspase-2 is a key mitochondrial-injuring caspase during etoposide and gemcitabine-induced apoptosis of E1A-positive cells, and that caspase-2 is required for induction of caspase-3 activity by both chemotherapeutic agents. Expression of PIDD was required for caspase-2 activation, mitochondrial injury and enhanced apoptotic cell death. Furthermore, E1A-enhanced sensitivity to injury-induced apoptosis required PIDD cleavage to PIDD-CC. These results define the PIDD/caspase-2 pathway as a key apical, mitochondrial-injuring mechanism in E1A-induced sensitivity of mammalian cells to chemotherapeutic agents.
Disposal of iron by a mutant form of lipocalin 2
Authors: Barasch Jonathan , Hollmen Maria , Deng Rong , Hod Eldad A. , Rupert Peter B. , Abergel Rebecca J. , Allred Benjamin E. , Xu Katherine , Darrah Shaun F. , Tekabe Yared , Perlstein Alan , Wax Rebecca , Bruck Efrat , Stauber Jacob , Corbin Kaitlyn A. , Buchen Charles , Slavkovich Vesna , Graziano Joseph , Spitalnik Steven L. , Bao Guanhu , Strong Roland K. , Qiu Andong
Published: October 2016

Iron overload damages many organs. Unfortunately, therapeutic iron chelators also have undesired toxicity and may deliver iron to microbes. Here we show that a mutant form (K3Cys) of endogenous lipocalin 2 (LCN2) is filtered by the kidney but can bypass sites of megalin-dependent recapture, resulting in urinary excretion. Because K3Cys maintains recognition of its cognate ligand, the iron siderophore enterochelin, this protein can capture and transport iron even in the acidic conditions of urine. Mutant LCN2 strips iron from transferrin and citrate, and delivers it into the urine. In addition, it removes iron from iron overloaded mice, including models of acquired (iron-dextran or stored red blood cells) and primary (Hfe−/−) iron overload. In each case, the mutants reduce redox activity typical of non-transferrin-bound iron. In summary, we present a non-toxic strategy for iron chelation and urinary elimination, based on manipulating an endogenous protein:siderophore:iron clearance pathway.
In situ single-atom array synthesis using dynamic holographic optical tweezers
Authors: Kim Hyosub , Lee Woojun , Lee Han-gyeol , Jo Hanlae , Song Yunheung , Ahn Jaewook
Published: October 2016

Establishing a reliable method to form scalable neutral-atom platforms is an essential cornerstone for quantum computation, quantum simulation and quantum many-body physics. Here we demonstrate a real-time transport of single atoms using holographic microtraps controlled by a liquid-crystal spatial light modulator. For this, an analytical design approach to flicker-free microtrap movement is devised and cold rubidium atoms are simultaneously rearranged with 2N motional degrees of freedom, representing unprecedented space controllability. We also accomplish an in situ feedback control for single-atom rearrangements with the high success rate of 99% for up to 10 μm translation. We hope this proof-of-principle demonstration of high-fidelity atom-array preparations will be useful for deterministic loading of N single atoms, especially on arbitrary lattice locations, and also for real-time qubit shuttling in high-dimensional quantum computing architectures.
Correction: Corrigendum: Cortical dynamics during cell motility are regulated by CRL3KLHL21 E3 ubiquitin ligase
Authors: Courtheoux Thibault , Enchev Radoslav I. , Lampert Fabienne , Gerez Juan , Beck Jochen , Picotti Paola , Sumara Izabela , Peter Matthias
Published: October 2016

Nature Communications 7: Article number: 12810 (2016); Published: 19 September 2016; Updated: 31 October 2016 References cited within the Supplementary Methods section of this Article were not identified in the Supplementary References section. The references are as follows: 44. Enchev, R. I., Schreiber, A.
The Cardamine hirsuta genome offers insight into the evolution of morphological diversity
Authors: Gan Xiangchao , Hay Angela , Kwantes Michiel , Haberer Georg , Hallab Asis , Ioio Raffaele Dello , Hofhuis Hugo , Pieper Bjorn , Cartolano Maria , Neumann Ulla , Nikolov Lachezar A. , Song Baoxing , Hajheidari Mohsen , Briskine Roman , Kougioumoutzi Evangelia , Vlad Daniela , Broholm Suvi , Hein Jotun , Meksem Khalid , Lightfoot David , Shimizu Kentaro K. , Shimizu-Inatsugi Rie , Imprialou Martha , Kudrna David , Wing Rod , Sato Shusei , Huijser Peter , Filatov Dmitry , Mayer Klaus F. X. , Mott Richard , Tsiantis Miltos
Published: October 2016

Finding causal relationships between genotypic and phenotypic variation is a key focus of evolutionary biology, human genetics and plant breeding. To identify genome-wide patterns underlying trait diversity, we assembled a high-quality reference genome of Cardamine hirsuta, a close relative of the model plant Arabidopsis thaliana. We combined comparative genome and transcriptome analyses with the experimental tools available in C. hirsuta to investigate gene function and phenotypic diversification. Our findings highlight the prevalent role of transcription factors and tandem gene duplications in morphological evolution. We identified a specific role for the transcriptional regulators PLETHORA5/7 in shaping leaf diversity and link tandem gene duplication with differential gene expression in the explosive seed pod of C. hirsuta. Our work highlights the value of comparative approaches in genetically tractable species to understand the genetic basis for evolutionary change.
Synthesis of Micelles Guided Magnetite (Fe3O4) Hollow Spheres and their application for AC Magnetic Field Responsive Drug Release
Authors: Mandal Goswami Madhuri
Published: October 2016

This paper reports on synthesis of hollow spheres of magnetite, guided by micelles and their application in drug release by the stimulus responsive technique. Here oleyelamine micelles are used as the core substance for the formation of magnetite nano hollow spheres (NHS). Diameter and shell thickness of NHS have been changed by changing concentration of the micelles. Mechanism of NHS formation has been established by investigating the aliquot collected at different time during the synthesis of NHS. It has been observed that oleyelamine as micelles play an important role to generate hollow-sphere particles of different diameter and thickness just by varying its amount. Structural analysis was done by XRD measurement and morphological measurements, SEM and TEM were performed to confirm the shape and size of the NHS. FTIR measurement support the formation of magnetite phase too. Frequency dependent AC magnetic measurements and AC magnetic field stimulated drug release event by these particles provide a direction of the promising application of these NHS for better cancer treatment in near future. Being hollow & porous in structure and magnetic in nature, such materials will also be useful in other applications such as in removal of toxic materials, magnetic separation etc.
Clinical analysis of HIV/AIDS patients with drug eruption in Yunnan, China
Authors: Li Yu-Ye , Jin Yong-Mei , He Li-Ping , Bai Jin-Song , Liu Jun , Yu Min , Chen Jian-Hua , Wen Jing , Kuang Yi-Qun
Published: October 2016

Drug eruption is the most common clinical presentation in patients with HIV/AIDS. The systemic clinical and risk factors associated with drug eruption remain unknown. A retrospective analysis in HIV/AIDS patients with drug eruption was carried out with demographic data, epidemiological data, clinical characteristics, laboratory data and follow-up data. The risk factors correlated with prognosis were assessed by case control analysis. A total of 134 out of 1817 HIV/AIDS patients (7.4%) presented drug eruptions. The major class of sensitizing drug was HAART drugs (47.7%), followed by antibiotics (47.0%). Nevirapine (39.6%) was the most common sensitizing drug in the HAART regimens. The patients received HAART or had allergic history were prone to develop drug eruption. The alanine aminotransferase, albumin, globulin, creatinine, blood urea nitrogen (BUN), lymphocytes, red blood cells (RBC) and eosinophils of the drug eruption patients were significantly different the control patients. The allergic history, opportunistic infection, viral load, CD4 cell count, high globulin and low albumin were the risk factors correlated with death in HIV/AIDS patients with drug eruption. It is proposed that patients with higher viral loads, higher globulin levels and lower white blood cells (WBC) should be given special attention for the prevention of complications and death.
Fluorescently labeled circular DNA molecules for DNA topology and topoisomerases
Authors: Gu Maxwell , Berrido Andrea , Gonzalez Walter G. , Miksovska Jaroslava , Chambers Jeremy W. , Leng Fenfei
Published: October 2016

DNA topology plays essential roles in several fundamental biological processes, such as DNA replication, recombination, and transcription. Typically agarose gel electrophoresis is employed to study DNA topology. Since gel electrophoresis is time-consuming and labor intensive, it is desirable to develop other methods, such as fluorescence-based methods, for such studies. In this paper we report the synthesis of a type of unique fluorescence-labeled DNA molecules that can be used to study DNA topology and topoisomerases by fluorescence resonance energy transfer (FRET). Specifically, we inserted an 82 nt. synthetic DNA oligomer FL905 carrying a 42 nt. AT sequence with fluorescein and dabcyl labels into a gapped DNA molecule to generate relaxed and supercoiled pAB1_FL905. Since the fluorescence intensity of pAB1_FL905 is dependent on its supercoiling status, pAB1_FL905 is a powerful tool to study DNA topology and topoisomerases by FRET. pAB1_FL905 can also be developed into rapid and efficient high-throughput screening assays to identify inhibitors that target various DNA topoisomerases.
Orexin signaling regulates both the hippocampal clock and the circadian oscillation of Alzheimer’s disease-risk genes
Authors: Ma Zhixiong , Jiang Weiliang , Zhang Eric Erquan
Published: October 2016

Alzheimer’s disease (AD) is a circadian clock-related disease. However, it is not very clear whether pre-symptomatic AD leads to circadian disruption or whether malfunction of circadian rhythms exerts influence on development of AD. Here, we report a functional clock that exists in the hippocampus. This oscillator both receives input signals and maintains the cycling of the hippocampalPer2gene. One of the potential inputs to the oscillator is orexin signaling, which can shorten the hippocampal clock period and thereby regulate the expression of clock-controlled-genes (CCGs). A 24-h time course qPCR analysis followed by a JTK_CYCLE algorithm analysis indicated that a number of AD-risk genes are potential CCGs in the hippocampus. Specifically, we found thatBace1andBace2, which are related to the production of the amyloid-beta peptide, are CCGs.BACE1is inhibited byE4BP4, a repressor of D-box genes, whileBACE2is activated by CLOCK:BMAL1. Finally, we observed alterations in the rhythmic expression patterns ofBace2andApoEin the hippocampus of agedAPP/PS1dE9mice. Our results therefore indicate that there is a circadian oscillator in the hippocampus whose oscillation could be regulated by orexins. Hence, orexin signaling regulates both the hippocampal clock and the circadian oscillation of AD-risk genes.
Targeting Non-classical Myelin Epitopes to Treat Experimental Autoimmune Encephalomyelitis
Authors: Wang Xiaohua , Zhang Jintao , Baylink David J. , Li Chih-Huang , Watts Douglas M. , Xu Yi , Qin Xuezhong , Walter Michael H. , Tang Xiaolei
Published: October 2016

Qa-1 epitopes, the peptides that bind to non-classical major histocompatibility complex Ib Qa-1 molecules and are recognized by Qa-1-restricted CD8+ regulatory T (Treg) cells, have been identified in pathogenic autoimmune cells that attack myelin sheath in experimental autoimmune encephalomyelitis (EAE, an animal model for multiple sclerosis [MS]). Additionally, immunization with such epitopes ameliorates the EAE. However, identification of such epitopes requires knowledge of the pathogenic autoimmune cells which are largely unknown in MS patients. Hence, we asked whether the CD8+ Treg cells could directly target the myelin sheath to ameliorate EAE. To address this question, we analyzed Qa-1 epitopes in myelin oligodendrocyte glycoprotein (MOG that is a protein in myelin sheath). Here, we report identification of a MOG-specific Qa-1 epitope. Immunization with this epitope suppressed ongoing EAE, which was abrogated by CD8+ T cell depletion. Additionally, the epitope immunization activated the epitope-specific CD8+ T cells which specifically accumulated in the CNS-draining cervical lymph nodes. Finally, CD8+ T cells primed by the epitope immunization transferred EAE suppression. Hence, this study reveals a novel regulatory mechanism mediated by the CD8+ Treg cells. We propose that immunization with myelin-specific HLA-E epitopes (human homologues of Qa-1 epitopes) is a promising therapy for MS.
High-resolution MALDI mass spectrometry imaging of gallotannins and monoterpene glucosides in the root of Paeonia lactiflora
Authors: Li Bin , Bhandari Dhaka Ram , Römpp Andreas , Spengler Bernhard
Published: October 2016

High-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) at 10 μm pixel size was performed to unravel the spatio-chemical distribution of major secondary metabolites in the root of Paeonia lactiflora. The spatial distributions of two major classes of bioactive components, gallotannins and monoterpene glucosides, were investigated and visualized at the cellular level in tissue sections of P. lactiflora roots. Accordingly, other primary and secondary metabolites were imaged, including amino acids, carbohydrates, lipids and monoterpenes, indicating the capability of untargeted localization of metabolites by using high-resolution MSI platform. The employed AP-SMALDI MSI system provides significant technological advancement in the visualization of individual molecular species at the cellular level. In contrast to previous histochemical studies of tannins using unspecific staining reagents, individual gallotannin species were accurately localized and unequivocally discriminated from other phenolic components in the root tissues. High-quality ion images were obtained, providing significant clues for understanding the biosynthetic pathway of gallotannins and monoterpene glucosides and possibly helping to decipher the role of tannins in xylem cells differentiation and in the defence mechanisms of plants, as well as to investigate the interrelationship between tannins and lignins.
Development and characterization of a microfluidic model of the tumour microenvironment
Authors: Ayuso Jose M. , Virumbrales-Muñoz María , Lacueva Alodia , Lanuza Pilar M. , Checa-Chavarria Elisa , Botella Pablo , Fernández Eduardo , Doblare Manuel , Allison Simon J. , Phillips Roger M. , Pardo Julián , Fernandez Luis J. , Ochoa Ignacio
Published: October 2016

The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live ‘window’ into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device’s potential to enable more physiological in vitro drug screening.
Lymphadenectomy and risk of reoperation or mortality shortly after surgery for oesophageal cancer
Authors: Lagergren Jesper , Mattsson Fredrik , Davies Andrew , Lindblad Mats , Lagergren Pernilla
Published: October 2016

The prognostic role of lymphadenectomy during surgery for oesophageal cancer is questioned. We aimed to test whether higher lymph node harvest increases the risk of early postoperative reoperation or mortality. A population-based cohort study including almost all patients who underwent resection for oesophageal cancer in Sweden in 1987–2010. Data were collected from medical records and well-established nationwide Swedish registries. The exposures were number of removed lymph nodes (primary) and number of node metastases (secondary). The main study outcome was reoperation/mortality within 30 days of primary surgery. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated using Poisson regression, adjusted for age, sex, co-morbidity, neoadjuvant therapy, tumour stage, tumour histology, surgeon volume, and calendar period. Among 1,820 participants, the risk of reoperation/mortality did not increase with greater lymph node harvest (RR = 0.98, 95%CI 0.96–1.00, discrete variable) or with greater number of removed metastatic nodes (RR = 1.00, 95% CI 0.95–1.05, discrete variable). Similarly, in stratified analyses within pre-defined categories of tumor stage, surgeon volume and calendar period, increased number of removed nodes or node metastases did not increase the risk of reoperation/mortality. Lymphadenectomy during oesophageal cancer surgery is a safe procedure in the short term perspective.
Prognostic significance of miR-1268a expression and its beneficial effects for post-operative adjuvant transarterial chemoembolization in hepatocellular carcinoma
Authors: Lu Yun-Long , Yao Jin-Guang , Huang Xiao-Ying , Wang Chao , Wu Xue-Min , Xia Qiang , Long Xi-Dai
Published: October 2016

Our recent investigation has shown that the variables of microRNA-1268a may involve in hepatocellular carcinoma (HCC) tumorigenesis. Here, we attempted to identify the prognostic significance of microRNA-1268a expression in tumor tissues by a retrospective analysis in 411 patients with HCC, and analyze its effects on post-operative adjuvant transarterial chemoembolization (TACE) improving HCC prognosis. All cases received tumor resection or tumor resection plus post-operative adjuvant TACE as an initial treatment. Logistical regression analysis exhibited that microRNA-1268a expression was significantly correlated with tumor stage, tumor grade, tumor size, and microvessel density. Cox regression analysis showed that microRNA-1268a expression was an independent prognostic factor for HCC, and TACE treatment had no effects on prognosis of HCC patients with high microRNA-1268a expression. More intriguingly, TACE improved the prognosis of HCC patients with low microRNA-1268a expression. Functionally, overexpression of microRNA-1268a inhibited while its inhibitor enhanced doxorubicin-induced the death of cancer cells. These results suggest that microRNA-1268a may be an independent prognostic factor for HCC patients, and that decreasing microRNA-1268a expression may be beneficial for post-operative adjuvant TACE treatment in HCC.