bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ALCOHOL (MINIMUM PRICING) (SCOTLAND) ACT 2012 AND THE COLLISION BETWEEN SINGLE-MARKET OBJECTIVES AND PUBLIC-INTEREST REQUIREMENTS
Authors: Albors-Llorens Albertina
Published: April 2017

THE recent and high-profile decisions of the Court of Justice (Case C-333/14, ECLI: EU:C:2015:845) and of the First Division of the Inner House of the Court of Session ([2016] CSIH 77) in The Scotch Whisky Association and Others v The Lord Advocate and The Advocate General for Scotland have shed further light both on the role of national courts in cases where Member States invoke the protection of public health to justify derogations from the TFEU provisions on the free movement of goods and on the application of the proportionality test. The model of free movement provided in the Treaty is not one that guarantees an entirely untrammelled freedom of trade across the EU or the automatic precedence of common-market objectives. While Article 34 TFEU provides for the removal of national obstacles of a non-fiscal nature, Article 36 TFEU allows Member States, in the absence of harmonisation, to argue a number of public-interest grounds to justify national measures that, in principle, contravene Article 34 TFEU. The protection of public health ranks very prominently in this list of interests. However, although it is for the Member States to decide the appropriate level of health protection that they wish to ensure (C-174/82, Sandoz [1983] E.C.R. 2445), the national action must be proportionate and national authorities must select the action that is the least restrictive of intra-Union trade (Case 40/82, Commission v UK [1984] E.C.R. 283). The outcome in The Scotch Whisky Association case has highlighted the difficulties involved in choosing among alternatives the least restrictive measure that would achieve the public-health objectives of the national legislation. Moreover, it has demonstrated clearly, in these difficult times for the EU, that EU law can be interpreted and applied to safeguard sensitive national policies.
SOME TEXTUAL PROBLEMS IN AELIUS DONATUS’ COMMENTARY ON TERENCE
Authors: Cioffi Carmela
Published: April 2017

In the first act of Terence'sAndria, we find a dialogue between the old man Simo and Sosia, the freedman, with the former explaining why he has decided to arrange a false wedding for his young son Pamphilus. He has, in fact, learned that his son, despite being betrothed, has had a relationship with another girl and that—quite a serious matter—the fiancée's father, Chremes, has heard about the clandestine affair. In verses 144–9 Simo reports on the not-altogether friendly meeting he has had with Chremes, who is furious about the complete disrespect that has been shown to his daughter; Simo's only defence is to attempt to deny the truth (146:ego illud sedulo negare factum).
INDOOR AND OUTDOOR: OBSERVATIONS ON THE ORIGINALS OF TERENCE'SANDRIAANDHECYRA
Authors: Victor Benjamin
Published: April 2017

Inquiry will be made here into a specific challenge facing writers offabulae palliatae, namely the interior scene, which they had not always the same means to display as did the poets of the νέα they adapted. One of them, Terence, will be seen to have reacted by eliminating the interior scenes that he found in his models.
CATULLUS 66.53 AND VIRGIL,ECLOGUES5.5
Authors: Larsen Kristoffer Maribo Engell
Published: April 2017

Modern editors of Catullus all agree on the text of line 53. The manuscripts also agree on the line, the only difference being R transmittingmutantibus, while O and G transmitnutantibus. Nevertheless, a few scholars have in the past questioned the reading ofnutantibus. As the lines quoted above illustrate, Catullus generally translates Callimachus’ poem closely. But neither of the words suggested in the manuscripts seems wholly to describe the rapid and vigorous movement of Callimachus’ κυκλώσας βαλιὰ πτερά, ‘having whirled its swift wings’. The reading ofnutantibusis somewhat supported by Apuleius’pinnarum nutantium(Met. 6.15.5). But there too the nodding, swaying and wavering sense ofnutaredoes not seem to illustrate the hurried and rapid action of Jupiter's eagle. Additionally, the wording of the passage is sufficiently disputed to make it possible thatnutantiumis not the correct reading.
THE PERSIAN ROYAL TENT AND CEREMONIAL OF ALEXANDER THE GREAT
Authors: Collins Andrew W.
Published: April 2017

From 330b.c. Alexander transformed his court by adopting a number of court personnel and practices from the Achaemenids. This included the adoption by the king of a mixed Persian and Macedonian royal costume,proskynēsis, Persian spear-bearers and certain Persian officers, such as the chiliarch and the chief usher (εἰσαγγελεύς). But Alexander also used an imposing tent and an audience style modelled on that of the Great King. It is my intention here to investigate the Persian-style tent of Alexander and the two court offices called the chiliarch and chief usher, associated with the king's new audience-style.
A crown group priapulid from the early Cambrian Guanshan Lagerstätte
Authors: HU SHI-XUE , ZHU MAO-YAN , ZHAO FANG-CHEN , STEINER MICHAEL
Published: April 2017

A well-preserved fossil priapulid worm,Xiaoheiqingellasp., is reported from the early Cambrian Guanshan Lagerstätte (Cambrian Series II, Stage 4) near Kunming City, Yunnan Province, SW China. The body of the animal consists of four sections: a swollen introvert, a constricted neck, a finely annulated trunk and a caudal appendage. The body configuration exhibits a close resemblance to that of the crown group priapulidXiaoheiqingella peculiarisfrom the early Cambrian Chengjiang Lagerstätte. The new discovery provides another striking example of crown group priapulids, representing the third occurrence of crown group fossil priapulids after the Chengjiang Lagerstätte (Cambrian Series II, Stage 3) and the Mazon Creek Lagerstätte (late Moscovian Stage, Pennsylvanian). The discovery also sheds new light on the early diversity and evolution of priapulid worms.
A LA-ICP-MS analysis of rare earth elements on phosphatic grains of the Ediacaran Doushantuo phosphorite at Weng'an, South China: implication for depositional conditions and diagenetic processes
Authors: ZHU BI , JIANG SHAO-YONG
Published: April 2017

The Ediacaran Doushantuo Formation at Weng'an, South China hosts well-preserved phosphatized microfossils known as the Weng'an biota. A laser ablation ICP-MS analysis of rare earth element (REE) characteristics of the fossil-bearing black phosphorite unit of the Doushantuo Formation at Weng'an was conducted, with the aim of unravelling the depositional conditions and diagenetic processes during formation of the phosphorites. Spherical phosphatized microfossils and phosphatic clasts were analysed, and the REE data display middle REE (MREE) -enriched shale-normalized REE patterns. The spherical phosphatized microfossils show an increase in total REE contents (∑REE) from core to rim. Negative correlations between ∑REE and the extent of MREE enrichment over the other REE (indicated by LaN/SmN, YbN/SmN) are observed for analysed spots within individual phosphatic grains, which may be due to complex diagenetic history of the phosphatic grains, with fluctuations in REE sources and chemical parameters in a high-energy shallow-water environment being additional factors. The LaN/YbNand LaN/SmNcharacteristics of the phosphatic grains suggest they were mostly influenced by early diagenetic alteration rather than late extensive recrystallization. The negative Ce anomalies in the samples suggest they formed under oxic-bottom-water conditions. Positive Eu anomalies are present in all samples, and are likely to reflect involvement of hydrothermal fluids rather than changes in redox conditions of porewater. Overall this study has major implications for phosphorites as important archives for the study of geochemical proxies, the Ediacaran period and also evolutionary changes.
English Baptists and the Struggle for Theological Authority, 1642–1646
Authors: BINGHAM MATTHEW C.
Published: April 2017

This article explores interactions between Baptist lay theologians and ordained clergy during the first English civil war. Despite their marginalised position outside the national Church, Baptists employed a variety of innovative techniques to coerce ordained ministers into debates which the latter would have preferred to avoid. Though Baptists during the period did not achieve intellectual parity with the members of the Westminster Assembly and others whom they sought to influence, their efforts contributed to an ongoing transition within the early modern English Atlantic whereby religious culture was made more participatory and theological authority democratised.
Transoral laser resection or radiotherapy? Patient choice in the treatment of early laryngeal cancer: a prospective observational cohort study
Authors: Zahoor T , Dawson R , Sen M , Makura Z
Published: April 2017

Objectives:

The choices made by patients offered treatment for early laryngeal cancer with radiotherapy or transoral laser resection were reviewed.

Methods:

A prospective review was conducted of all patients diagnosed and treated for early laryngeal carcinoma from December 2002 to September 2009 at the Leeds Teaching Hospitals NHS Trust. A total of 209 patients with tumour stage T1 or T2 laryngeal cancer were treated; each new patient suitable for radiotherapy or transoral laser resection was seen jointly by the clinical (radiation) oncologist and head and neck surgeon, and offered the choice of treatment.

Results:

Of the patients, 47.4 per cent were given a choice between radiotherapy and transoral laser resection; 51.2 per cent were advised to have radiotherapy, and there were no records for the remaining 1.4 per cent. From those given the choice, 59.6 per cent chose transoral laser resection (p < 0.02 (t-test)) and 35.4 per cent chose radiotherapy.

Conclusion:

When given the choice, a statistically significant majority of patients choose transoral laser resection rather than radiotherapy.
Cetacean stranding and diet analyses in the North Aegean Sea (Greece)
Authors: Milani C.B. , Vella A. , Vidoris P. , Christidis A. , Koutrakis E. , Frantzis A. , Miliou A. , Kallianiotis A.
Published: April 2017

Cetacean stranding reports in the North Aegean Sea were recorded since 1998 from Strimonikos Gulf in Chalkidiki up to Alexandroupoli on the Turkish border and in a few northern Aegean islands. On site, the specimens were examined to identify species, gender, approximate age and, when possible, cause for stranding. A total of 26 filled stomachs of five cetacean species collected since 2002 were analysed: bottlenose dolphinsTursiops truncatus(N = 8), common dolphinsDelphinus delphis(N = 8), harbour porpoisesPhocoena phocoena(N = 5), striped dolphinsStenella coeruleoalba(N = 4) and Risso's dolphinsGrampus griseus(N = 1). From the analysed stomachs it was found that the bottlenose dolphins fed mainly on snake blennyOphidion barbatum(34%), bogueBoops boops(22%) and round sardinellaSardinella aurita(13%); common dolphins on round sardinella (17%), picarelsSpicaraspp. (10%) and Cocco's lantern fishLobianchia gemellaris(9%); harbour porpoises on Gobidae (four-spotted gobyDeltentosteus quadrimaculatus41% and black gobyGobius niger37%) and round sardinella (7%); striped dolphins on Myctophydae (Madeira lantern fishCeratoscopelus maderensis51%), and on Pfeffer's enople squidAbraliopsis morisii(10%) and bogue (8%); and Risso's dolphin exclusively on Teuthidae (31%), the umbrella squidHistioteuthis bonellii(30%) and the reverse jewel squidH. reversa(14%). The present work represents the first attempt to investigate the diet up to species level for several cetaceans in Greek waters and for harbour porpoises stranded in the Mediterranean Sea.
Safety and efficacy of current alternatives in the topical treatment of cutaneous leishmaniasis: a systematic review
Authors: WOLF NASSIF PRISCILA , DE MELLO TATIANE FRANÇA PERLES , NAVASCONI TAÍSA ROCHA , MOTA CAMILA ALVES , DEMARCHI IZABEL GALHARDO , ARISTIDES SANDRA MARA ALESSI , LONARDONI MARIA VALDRINEZ CAMPANA , TEIXEIRA JORGE JUAREZ VIEIRA , SILVEIRA THAÍS GOMES VERZIGNASSI
Published: April 2017

Studies of topical treatments for leishmaniasis were systematically reviewed, to evaluate the therapeutic efficacy, safety and any adverse effects of these treatments. The papers identified in the databases PubMed and Web of Knowledge involved eight studies with a total of 1744 patients. The majority of trials was from Iran (4/8), covered a period of 8 years (2003–2011), and included patients 4–85 years of age. The most frequent Leishmania species in the studies were L. tropica (4/8) and L. major (2/8). The treatments administered were thermotherapy, paromomycin and combinations, CO2 laser, 5-aminolevulinic acid hydrochloride (10%) plus visible red light (633 nm) and cryotherapy. Six articles reported cure rates over 80·0%. Six studies reported on failure rates, three of them reporting rates lower than 10%. Four studies did not report relapses or recurrences, while the other studies reported low rates (1·8–6·3%). The most common adverse effects of the topical treatments were redness/erythema, pain, pruritus burning, oedema, vesicles and hyper- or hypopigmentation. The results provide strong evidence that the treatments topical evaluated showed high cure rates, safety and effectiveness, with low side-effects, relapse and recurrence rates, except for cryotherapy, which showed a moderate cure rate.
Simple dialkyl pyrazole-3,5-dicarboxylates show in vitro and in vivo activity against disease-causing trypanosomatids
Authors: REVIRIEGO FELIPE , OLMO FRANCISCO , NAVARRO PILAR , MARÍN CLOTILDE , RAMÍREZ-MACÍAS INMACULADA , GARCÍA-ESPAÑA ENRIQUE , ALBELDA MARÍA TERESA , GUTIÉRREZ-SÁNCHEZ RAMÓN , SÁNCHEZ-MORENO MANUEL , ARÁN VICENTE J.
Published: April 2017

The synthesis and antiprotozoal activity of some simple dialkyl pyrazole-3,5-dicarboxylates (compounds 2–6) and their sodium salts (pyrazolates) (compounds 7–9) against Trypanosoma cruzi, Leishmania infantum and Leishmania braziliensis are reported. In most cases the studied compounds showed, especially against the clinically significant amastigote forms, in vitro activities higher than those of the reference drugs (benznidazole for T. cruzi and glucantime for Leishmania spp.); furthermore, the low non-specific cytotoxicities against Vero cells and macrophages shown by these compounds led to good selectivity indexes, which are 8–72 times higher for T. cruzi amastigotes and 15–113 times higher for Leishmania spp. amastigotes than those of the respective reference drugs. The high efficiency of diethyl ester 3 and its sodium salt 8 against the mentioned protozoa was confirmed by further in vitro assays on infection rates and by an additional in vivo study in a murine model of acute and chronic Chagas disease. The inhibitory capacity of compounds 3 and 8 on the essential iron superoxide dismutase of the aforementioned parasites may be related to the observed anti-trypanosomatid activity. The low acute toxicity of compounds 3 and 8 in mice is also reported in this article.
The political economy of currency internationalisation: the case of the RMB
Authors: Germain Randall , Schwartz Herman Mark
Published: April 2017

The rise of China has sparked a debate about the economic and political consequences for the global economy of the internationalisation of the renminbi. We argue that the dominant focus of this literature – primarily the external conditions and requirements for a national currency to become an international currency – misspecifies the connections between the international and domestic requirements for currency internationalisation, as well as the potential to become the dominant international reserve currency. We correct this oversight by developing an integrated theoretical framework that highlights the domestic adjustment costs which a state must accommodate before its currency can carry the weight of internationalisation. These costs constitute a critical element of an international currency’s ‘political economy’, and they force states to negotiate contentious social trade-offs among competing domestic claims on finite public resources in a sustainable manner. Our analysis suggests that the likelihood of China being able to successfully negotiate the social costs associated with running a fully internationalised currency is currently very low, precisely because this will place unacceptable pressure on groups benefiting from the economic and political status quo. This further suggests that the American dollar will remain unchallenged as the global economy’s pre-eminent international currency for the foreseeable future.
Epidemics and aetiology of hand, foot and mouth disease in Xiamen, China, from 2008 to 2015
Authors: HE S. Z. , CHEN M. Y. , XU X. R. , YAN Q. , NIU J. J. , WU W. H. , SU X. S. , GE S. X. , ZHANG S. Y. , XIA N. S.
Published: April 2017

Over the past 8 years, human enteroviruses (HEVs) have caused 27 227 cases of hand, foot and mouth disease (HFMD) in Xiamen, including 99 severe cases and six deaths. We aimed to explore the molecular epidemiology of HFMD in Xiamen to inform the development of diagnostic assays, vaccines and other interventions. From January 2009 to September 2015, 5866 samples from sentinel hospitals were tested using nested reverse transcription PCR that targeted the HEV 5′ untranslated region and viral protein 1 region. Of these samples, 4290 were tested positive for HEV and the amplicons were sequenced and genotyped. Twenty-two genotypes were identified. Enterovirus 71 (EV71) and coxsackieviruses A16, A6 and A10 (CA16, CA6 and CA10) were the most common genotypes, and there were no changes in the predominant lineages of these genotypes. EV71 became the most predominant genotype every 2 years. From 2013, CA6 replaced CA16 as one of the two most common genotypes. The results demonstrate the vast diversity of HFMD pathogens, and that minor genotypes are able to replace major genotypes. We recommend carrying-out long-term monitoring of the full spectrum of HFMD pathogens, which could facilitate epidemic prediction and the development of diagnostic assays and vaccines.
Regional solar radiation is inversely correlated with incidence and severity of tuberculosis in Chile
Authors: BALCELLS M. E. , CERDA J. , CONCHA S. , HOYOS–BACHILOGLU R. , CAMARGO C. A. , MARTINEAU A. R. , BORZUTZKY A.
Published: April 2017

Vitamin D (VD) deficiency has been linked to increased incidence and morbidity of tuberculosis (TB). Chile has large variations in solar radiation (SR; a proxy of VD status) and high prevalence of VD deficiency in its southernmost regions with low SR. We investigated the correlation between regional SR and rates of TB incidence, admissions and deaths in Chile by reviewing national records on prospectively collected mandatory disease notifications, admissions and mortality between 2001 and 2011. Over the study period, 26 691 new TB notifications were registered. The TB incidence rate was 14·77 (95% confidence intervals (CIs) 14·60–14·95), admission rate was 12·12 (95% CI 11·96–12·28) and mortality rate was 1·61 (95% CI 1·55–1·67) per 100 000 population per year. Multivariable linear regressions adjusting for significant demographic TB risk factors in Chile (regional prevalence of HIV infection, rates of migration from TB-endemic countries and rates of imprisonment) revealed an independent and highly statistically significant inverse association between SR and TB incidence rate (β −1·05, 95% CI −1·73 to −0·36, P = 0·007), admission rate (β −1·58, 95% CI −2·23 to −0·93, P < 0·001), and mortality rate (β −0·15, 95% CI −0·23 to −0·07, P = 0·002). These findings support a potential pathogenic role of VD deficiency in TB incidence and severity.
High number of asymptomatic dogs as leptospiral carriers in an endemic area indicates a serious public health concern
Authors: SANT'ANNA R. , VIEIRA A. S. , GRAPIGLIA J. , LILENBAUM W.
Published: April 2017

Asymptomatic dogs can be potential hosts of leptospirosis. However, the extension of this phenomenon in endemic areas has not yet been clearly defined. This study is aimed at evaluating the role of asymptomatic dogs as carriers of Leptospira in an endemic area of Brazil. A total of 131 male dogs without apparent leptospirosis symptoms were included in the study based on clinical and hematologic exams. Serum and urine samples were collected for microscopic agglutination tests (MAT) and polymerase chain reactions (PCR) targeted the LipL32 gene, respectively. Forty-two dogs (32·1%) presented seroreactivity (titres ⩾100). The serogroup Icterohaemorrhagiae was predominant, representing 92·7% of the seropositive samples. Overall, leptospiral DNA was detected on 26 urine samples (19·8%). PCR positivity was more common (28·6%) on seropositive dogs than on seronegative (15·7%) ones. Nevertheless, MAT was not correlated to PCR (P > 0·05). Age was not associated with seroreactivity, but dogs older than 5 years of age had 4·07 more chances (odds ratio) of being carriers (PCR positive) than younger ones. Although the fact of knowing that asymptomatic dogs can act as leptospiral carriers is not new, the extension of this fact is impressive in an endemic region, and its role and impact on public health cannot be neglected.
Segregating bodily isomerism or heterotaxy: potential echocardiographic correlations of morphological findings
Authors: Tremblay Cornelia , Loomba Rohit S. , Frommelt Peter C. , Perrin Donald , Spicer Diane E. , Backer Carl , Anderson Robert H.
Published: April 2017

Background

Bodily isomerism, also referred to as heterotaxy, involves predominantly the thoracic organs, although other organs are usually abnormally positioned. Previously assessed on the basis of splenic anatomy, it is now understood that isomerism is better segregated on the basis of atrial appendage morphology. This allows for anticipation of associated findings. We aimed to assess the accuracy of segregation based on the morphology of the atrial appendages and other structures more easily identified by echocardiography.

Methods

We reviewed postmortem specimens of hearts from the archives at four institutions categorised as obtained from patients with “heterotaxy”. The cardiac structures were analysed using sequential segmental analysis. Non-cardiac structures were also examined if available. Statistical analyses were performed to compare differences in the settings of right as opposed to left isomerism.

Results

Specimens were available from 188 patients. Of these, 57 had left isomerism, and 131 had right isomerism. Atrial appendages were isomeric in all patients. A coronary sinus was found only in left isomerism, whereas a terminal crest, or a Eustachian valve, was found only in right isomerism. Interruption of the inferior caval vein was associated with left isomerism, whereas totally anomalous pulmonary venous connection was associated with right isomerism.

Conclusion

Isomerism is uniformly segregated on the basis of the morphology of the atrial appendages, itself defined by the extent of the pectinate muscles. Other features such as the presence of a coronary sinus and systemic venous return can further help with such segregation of isomerism.
Stunting among children under 3 years of age in Côte d’Ivoire: spatial and temporal variations between 1994 and 2011
Authors: Barankanira Emmanuel , Molinari Nicolas , Msellati Philippe , Laurent Christian , Bork Kirsten A
Published: April 2017

Objective

To investigate spatial heterogeneity of stunting prevalence among children in Côte d’Ivoire and examine changes in stunting between 1994 and 2011, to assess the impact of the 2002–2011 civil war that led to temporary partitioning of the country.

Design

Data from 1994, 1998 and 2011 Côte d’Ivoire Demographic and Health Surveys (DHS) were analysed using a geostatistical approach taking into account spatial autocorrelation. Stunting data were interpolated using ordinary kriging; spatial clusters with high and low stunting prevalence were identified using Kulldorff spatial scan statistics. Multilevel multivariable logistic regression was then carried out, with year of survey as the main independent variable and an interaction term for time by geographic zone (Abidjan, South, North).

Setting

Côte d’Ivoire, West Africa.

Subjects

Children aged 0–35 months included in three DHS (n6709).

Results

Overall stunting prevalence was 30·7, 28·7 and 27·8 % in 1994, 1998 and 2011, respectively (P=0·32). Clusters with high prevalence were found in 1994 (in the West region,P<0·001) and 1998 (in the West and North-West regions,P<0·01 andP=0·01, respectively), but not in 2011. Abidjan was included in a cluster with low prevalence in all surveys (P<0·05). Risk of stunting did not change between 1994 and 2011 at national level (adjusted OR; 95 % CI: 1·39; 0·72, 2·64), but decreased in the South (0·74; 0·58, 0·94) and increased from 1998 to 2011 in Abidjan (1·96; 1·06, 3·64).

Conclusions

In Côte d’Ivoire, significant changes in stunting prevalence were observed at the sub-national level between 1994 and 2011.
DNA damage-induced phosphatase Wip1 in regulation of hematopoiesis, immune system and inflammation
Authors: Uyanik B , Grigorash B B , Goloudina A R , Demidov O N
Published: April 2017

PP2C serine–threonine phosphatase, Wip1, is an important regulator of stress response. Wip1 controls a number of critical cellular functions: proliferation, cell cycle arrest, senescence and programmed cell death, apoptosis or autophagy. Ppm1d, the gene encoding Wip1 phosphatase, is expressed in hematopoietic progenitors, stem cells, neutrophils, macrophages B and T lymphocytes in bone marrow and peripheral blood. The Wip1−/− mice display immunodeficiency, abnormal lymphoid histopathology in thymus and spleen, defects in B- and T-cell differentiation, as well as susceptibility to viral infection. At the same time, Wip1 knockout mice exhibit pro-inflammatory phenotype in skin and intestine in the model of inflammatory bowel disease (IBD) with elevated levels of inflammation-promoting cytokines TNF-α, IL-6, IL-12, IL-17. Several Wip1 downstream targets can mediate Wip1 effects on hematopoietic system including, p53, ATM, p38MAPK kinase, NFkB, mTOR. Here, we summarized the current knowledge on the role of Wip1 in the differentiation of various hematopoietic lineages and how Wip1 deficiency affects the functions of immune cells.
On-surface synthesis of aligned functional nanoribbons monitored by scanning tunnelling microscopy and vibrational spectroscopy
Authors: Kalashnyk Nataliya , Mouhat Kawtar , Oh Jihun , Jung Jaehoon , Xie Yangchun , Salomon Eric , Angot Thierry , Dumur Frédéric , Gigmes Didier , Clair Sylvain
Published: April 2017

In the blooming field of on-surface synthesis, molecular building blocks are designed to self-assemble and covalently couple directly on a well-defined surface, thus allowing the exploration of unusual reaction pathways and the production of specific compounds in mild conditions. Here we report on the creation of functionalized organic nanoribbons on the Ag(110) surface. C–H bond activation and homo-coupling of the precursors is achieved upon thermal activation. The anisotropic substrate acts as an efficient template fostering the alignment of the nanoribbons, up to the full monolayer regime. The length of the nanoribbons can be sequentially increased by controlling the annealing temperature, from dimers to a maximum length of about 10 nm, limited by epitaxial stress. The different structures are characterized by room-temperature scanning tunnelling microscopy. Distinct signatures of the covalent coupling are measured with high-resolution electron energy loss spectroscopy, as supported by density functional theory calculations.
A bright triggered twin-photon source in the solid state
Authors: Heindel T. , Thoma A. , von Helversen M. , Schmidt M. , Schlehahn A. , Gschrey M. , Schnauber P. , Schulze J. -H. , Strittmatter A. , Beyer J. , Rodt S. , Carmele A. , Knorr A. , Reitzenstein S.
Published: April 2017

A non-classical light source emitting pairs of identical photons represents a versatile resource of interdisciplinary importance with applications in quantum optics and quantum biology. To date, photon twins have mostly been generated using parametric downconversion sources, relying on Poissonian number distributions, or atoms, exhibiting low emission rates. Here we propose and experimentally demonstrate the efficient, triggered generation of photon twins using the energy-degenerate biexciton–exciton radiative cascade of a single semiconductor quantum dot. Deterministically integrated within a microlens, this nanostructure emits highly correlated photon pairs, degenerate in energy and polarization, at a rate of up to (234±4) kHz. Furthermore, we verify a significant degree of photon indistinguishability and directly observe twin-photon emission by employing photon-number-resolving detectors, which enables the reconstruction of the emitted photon number distribution. Our work represents an important step towards the realization of efficient sources of twin-photon states on a fully scalable technology platform.
Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma
Authors: Verstraete Kenneth , Peelman Frank , Braun Harald , Lopez Juan , Van Rompaey Dries , Dansercoer Ann , Vandenberghe Isabel , Pauwels Kris , Tavernier Jan , Lambrecht Bart N. , Hammad Hamida , De Winter Hans , Beyaert Rudi , Lippens Guy , Savvides Savvas N.
Published: April 2017

The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) is pivotal to the pathophysiology of widespread allergic diseases mediated by type 2 helper T cell (Th2) responses, including asthma and atopic dermatitis. The emergence of human TSLP as a clinical target against asthma calls for maximally harnessing its therapeutic potential via structural and mechanistic considerations. Here we employ an integrative experimental approach focusing on productive and antagonized TSLP complexes and free cytokine. We reveal how cognate receptor TSLPR allosterically activates TSLP to potentiate the recruitment of the shared interleukin 7 receptor α-chain (IL-7Rα) by leveraging the flexibility, conformational heterogeneity and electrostatics of the cytokine. We further show that the monoclonal antibody Tezepelumab partly exploits these principles to neutralize TSLP activity. Finally, we introduce a fusion protein comprising a tandem of the TSLPR and IL-7Rα extracellular domains, which harnesses the mechanistic intricacies of the TSLP-driven receptor complex to manifest high antagonistic potency.
p53 targets TSPAN8 to prevent invasion in melanoma cells
Authors: Agaësse G , Barbollat-Boutrand L , El Kharbili M , Berthier-Vergnes O , Masse I
Published: April 2017

Cutaneous melanoma is a very deadly cancer because of its proclivity to metastasize. Despite the recent development of targeted and immune therapies, patient survival remains low. It is therefore crucial to enhance understanding of the molecular mechanisms underlying invasion. We previously identified tetraspanin 8 (TSPAN8) as an important modulator of melanoma invasiveness, and several of its transcriptional regulators, which affect TSPAN8 expression during melanoma progression toward an invasive stage. This study found that TSPAN8 promoter contains consensus-binding sites for p53 transcription factor. We demonstrated that p53 silencing was sufficient to turn on Tspan8 expression in non-invasive melanoma cells and that p53 acts as a direct transcriptional repressor of TSPAN8. We also showed that p53 modulated matrigel invasion in melanoma cells in a TSPAN8-dependent manner. In conclusion, this study reveals p53 as a negative regulator of Tspan8 expression. As TP53 gene is rarely mutated in melanoma, it was hitherto poorly studied but its role in apoptosis and growth suppression in melanoma is increasingly becoming clear. The study highlights the importance of p53 as a regulator of melanoma invasion and the concept that reactivating p53 could provide a strategy for modulating not only proliferative but also invasive capacity in melanoma treatment.
Komodo dragon-inspired synthetic peptide DRGN-1 promotes wound-healing of a mixed-biofilm infected wound
Authors: Chung Ezra M. C. , Dean Scott N. , Propst Crystal N. , Bishop Barney M. , van Hoek Monique L.
Published: April 2017

Cationic antimicrobial peptides are multifunctional molecules that have a high potential as therapeutic agents. We have identified a histone H1-derived peptide from the Komodo dragon (Varanus komodoensis), called VK25. Using this peptide as inspiration, we designed a synthetic peptide called DRGN-1. We evaluated the antimicrobial and anti-biofilm activity of both peptides against Pseudomonas aeruginosa and Staphylococcus aureus. DRGN-1, more than VK25, exhibited potent antimicrobial and anti-biofilm activity, and permeabilized bacterial membranes. Wound healing was significantly enhanced by DRGN-1 in both uninfected and mixed biofilm (Pseudomonas aeruginosa and Staphylococcus aureus)-infected murine wounds. In a scratch wound closure assay used to elucidate the wound healing mechanism, the peptide promoted the migration of HEKa keratinocyte cells, which was inhibited by mitomycin C (proliferation inhibitor) and AG1478 (epidermal growth factor receptor inhibitor). DRGN-1 also activated the EGFR-STAT1/3 pathway. Thus, DRGN-1 is a candidate for use as a topical wound treatment. Wound infections are a major concern; made increasingly complicated by the emerging, rapid spread of bacterial resistance. The novel synthetic peptide DRGN-1 (inspired by a peptide identified from Komodo dragon) exhibits pathogen-directed and host-directed activities in promoting the clearance and healing of polymicrobial (Pseudomonas aeruginosa & Staphylococcus aureus) biofilm infected wounds. The effectiveness of this peptide cannot be attributed solely to its ability to act upon the bacteria and disrupt the biofilm, but also reflects the peptide’s ability to promsote keratinocyte migration. When applied in a murine model, infected wounds treated with DRGN-1 healed significantly faster than did untreated wounds, or wounds treated with other peptides. The host-directed mechanism of action was determined to be via the EGFR-STAT1/3 pathway. The pathogen-directed mechanism of action was determined to be via anti-biofilm activity and antibacterial activity through membrane permeabilization. This novel peptide may have potential as a future therapeutic for treating infected wounds.
Scallop genome provides insights into evolution of bilaterian karyotype and development
Authors: Wang Shi , Zhang Jinbo , Jiao Wenqian , Li Ji , Xun Xiaogang , Sun Yan , Guo Ximing , Huan Pin , Dong Bo , Zhang Lingling , Hu Xiaoli , Sun Xiaoqing , Wang Jing , Zhao Chengtian , Wang Yangfan , Wang Dawei , Huang Xiaoting , Wang Ruijia , Lv Jia , Li Yuli , Zhang Zhifeng , Liu Baozhong , Lu Wei , Hui Yuanyuan , Liang Jun , Zhou Zunchun , Hou Rui , Li Xue , Liu Yunchao , Li Hengde , Ning Xianhui , Lin Yu , Zhao Liang , Xing Qiang , Dou Jinzhuang , Li Yangping , Mao Junxia , Guo Haobing , Dou Huaiqian , Li Tianqi , Mu Chuang , Jiang Wenkai , Fu Qiang , Fu Xiaoteng , Miao Yan , Liu Jian , Yu Qian , Li Ruojiao , Liao Huan , Li Xuan , Kong Yifan , Jiang Zhi , Chourrout Daniel , Li Ruiqiang , Bao Zhenmin
Published: April 2017

Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallopPatinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. ScallopHoxgene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancientPax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.
Microfluidic Electrochemical Impedance Spectroscopy of Carbon Composite Nanofluids
Authors: Jung Lee Hye , Bai Seoung-Jai , Seok Song Young
Published: April 2017

Understanding the internal structure of composite nanofluids is critical for controlling their properties and engineering advanced composite nanofluid systems for various applications. This goal can be made possible by precise analysis with the help of a systematic robust platform. Here, we demonstrate a microfluidic device that can control the orientation of carbon nanomaterials in a suspension by applying external fields and subsequently examine the electrochemical properties of the fluids at microscale. Composite ﻿nanofluids were prepared using carbon nanomaterials, and their rheological, thermal, electrical, and morphological characteristics were examined. The analysis revealed that microfluidic electrochemical impedance spectroscopy (EIS) in the device offered more reliable in-depth information regarding the change in the microstructure of carbon composite nanofluids than typical bulk measurements. Equivalent circuit modelling was performed based on the EIS results. Furthermore, the hydrodynamics and electrostatics of the microfluidic platform were numerically investigated. We anticipate that this microfluidic approach can serve as a new strategy for designing and analyzing composite nanofluids more efficiently.
Dual function of tropodithietic acid as antibiotic and signaling molecule in global gene regulation of the probiotic bacterium Phaeobacter inhibens
Authors: Beyersmann Paul G. , Tomasch Jürgen , Son Kwangmin , Stocker Roman , Göker Markus , Wagner-Döbler Irene , Simon Meinhard , Brinkhoff Thorsten
Published: April 2017

Antibiotics are typically regarded as microbial weapons, but whereas their function at concentrations lethal for bacteria is often well characterized, the role of antibiotics at much lower concentrations as possibly found under natural conditions remains poorly understood. By using whole-transcriptome analyses and phenotypic screenings of the marine bacterium Phaeobacter inhibens we found that the broad-spectrum antibiotic tropodithietic acid (TDA) causes the same regulatory effects in quorum sensing (QS) as the common signaling molecule N-acyl-homoserine lactone (AHL) at concentrations 100-fold lower than the minimal inhibitory concentration against bacteria. Our results show that TDA has a significant impact on the expression of ~10% of the total genes of P. inhibens, in the same manner as the AHL. Furthermore, TDA needs the AHL associated LuxR-type transcriptional regulator, just as the AHL molecule. Low concentrations of antibiotics can obviously have a strong influence on the global gene expression of the bacterium that produces it and drastically change the metabolism and behaviour of the bacterium. For P. inhibens this includes motility, biofilm formation and antibiotic production, all important for settlement on new host-associated surfaces. Our results demonstrate that bacteria can produce antibiotics not only to antagonise other bacteria, but also to mediate QS like endogenous AHL molecules.
Identification of IGF-1-enhanced cytokine expressions targeted by miR-181d in glioblastomas via an integrative miRNA/mRNA regulatory network analysis
Authors: Ho Kuo-Hao , Chen Peng-Hsu , Hsi Edward , Shih Chwen-Ming , Chang Wei-Chiao , Cheng Chia-Hsiung , Lin Cheng-Wei , Chen Ku-Chung
Published: April 2017

The insulin-like growth factor (IGF)-1 signaling is relevant in regulating cell growth and cytokine secretions by glioblastomas. MicroRNAs determine the cell fate in glioblastomas. However, relationships between IGF-1 signaling and miRNAs in glioblastoma pathogenesis are still unclear. Our aim was to validate the IGF-1-mediated mRNA/miRNA regulatory network in glioblastomas. Using in silico analyses of mRNA array and RNA sequencing data from The Cancer Genome Atlas (TCGA), we identified 32 core enrichment genes that were highly associated with IGF-1-promoted cytokine-cytokine receptor interactions. To investigate the IGF-1-downregulated miRNA signature, microarray-based approaches with IGF-1-treated U87-MG cells and array data in TCGA were used. Four miRNAs, including microRNA (miR)-9-5p, miR-9-3p, miR-181d, and miR-130b, exhibited an inverse correlation with IGF-1 levels. The miR-181d, that targeted the most IGF-1-related cytokine genes, was significantly reduced in IGF-1-treated glioma cells. Statistical models incorporating both high-IGF-1 and low-miR-181d statuses better predicted poor patient survival, and can be used as an independent prognostic factor in glioblastomas. The C-C chemokine receptor type 1 (CCR1) and interleukin (IL)-1b demonstrated inverse correlations with miR-181d levels and associations with patient survival. miR-181d significantly attenuated IGF-1-upregulated CCR1 and IL-1b gene expressions. These findings demonstrate a distinct role for IGF-1 signaling in glioma progression via miR-181d/cytokine networks.
Biochemical analysis of leishmanial and human GDP-Mannose Pyrophosphorylases and selection of inhibitors as new leads
Authors: Mao Wei , Daligaux Pierre , Lazar Noureddine , Ha-Duong Tâp , Cavé Christian , van Tilbeurgh Herman , Loiseau Philippe M. , Pomel Sébastien
Published: April 2017

Leishmaniases are an ensemble of diseases caused by the protozoan parasite of the genus Leishmania. Current antileishmanial treatments are limited and present main issues of toxicity and drug resistance emergence. Therefore, the generation of new inhibitors specifically directed against a leishmanial target is an attractive strategy to expand the chemotherapeutic arsenal. GDP-Mannose Pyrophosphorylase (GDP-MP) is a prominent therapeutic target involved in host-parasite recognition which has been described to be essential for parasite survival. In this work, we produced and purified GDP-MPs from L. mexicana (LmGDP-MP), L. donovani (LdGDP-MP), and human (hGDP-MP), and compared their enzymatic properties. From a rationale design of 100 potential inhibitors, four compounds were identified having a promising and specific inhibitory effect on parasite GDP-MP and antileishmanial activities, one of them exhibits a competitive inhibition on LdGDP-MP and belongs to the 2-substituted quinoline series.
Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats
Authors: Bedussi Beatrice , Naessens Daphne M. P. , de Vos Judith , Olde Engberink Rik , Wilhelmus Micha M. M. , Richard Edo , ten Hove Malyssa , vanBavel Ed , Bakker Erik N. T. P.
Published: April 2017

Hypertension is associated with cognitive decline and various forms of dementia, including Alzheimer’s disease. In animal models of hypertension, many of Alzheimer’s disease characteristics are recapitulated, including brain atrophy, cognitive decline, amyloid β accumulation and blood brain barrier dysfunction. Removal of amyloid β and other waste products depends in part on clearance via the brain interstitial fluid (ISF). Here we studied the impact of hypertension on ISF drainage, using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). At 8 months, high (500 kD) and low (3 kD) fluorescent molecular weight tracers released passively into the hippocampus showed a drastically enhanced spreading in SHR. Tracer spreading was inhomogeneous, with accumulation at ISF-CSF borders, around arteries, and towards the stratum lacunosum moleculare. These locations stained positively for the astrocyte marker GFAP, and aquaporin 4. Despite enhanced dispersion, clearance of tracers was not affected in SHR. In conclusion, these data indicate enhanced bulk flow of ISF in the hippocampus of hypertensive rats. ISF drains along astrocytes towards the cerebrospinal fluid compartment, which leads to sieving of high molecular weight solutes. Sieving may lead to a local increase in the concentration of waste products and potentially promotes the aggregation of amyloid β.
Assembly of Ruminococcus flavefaciens cellulosome revealed by structures of two cohesin-dockerin complexes
Authors: Bule Pedro , Alves Victor D. , Israeli-Ruimy Vered , Carvalho Ana L. , Ferreira Luís M. A. , Smith Steven P. , Gilbert Harry J. , Najmudin Shabir , Bayer Edward A. , Fontes Carlos M. G. A.
Published: April 2017

Abtract

Cellulosomes are sophisticated multi-enzymatic nanomachines produced by anaerobes to effectively deconstruct plant structural carbohydrates. Cellulosome assembly involves the binding of enzyme-borne dockerins (Doc) to repeated cohesin (Coh) modules located in a non-catalytic scaffoldin. Docs appended to cellulosomal enzymes generally present two similar Coh-binding interfaces supporting a dual-binding mode, which may confer increased positional adjustment of the different complex components. Ruminococcus flavefaciens’ cellulosome is assembled from a repertoire of 223 Doc-containing proteins classified into 6 groups. Recent studies revealed that Docs of groups 3 and 6 are recruited to the cellulosome via a single-binding mode mechanism with an adaptor scaffoldin. To investigate the extent to which the single-binding mode contributes to the assembly of R. flavefaciens cellulosome, the structures of two group 1 Docs bound to Cohs of primary (ScaA) and adaptor (ScaB) scaffoldins were solved. The data revealed that group 1 Docs display a conserved mechanism of Coh recognition involving a single-binding mode. Therefore, in contrast to all cellulosomes described to date, the assembly of R. flavefaciens cellulosome involves single but not dual-binding mode Docs. Thus, this work reveals a novel mechanism of cellulosome assembly and challenges the ubiquitous implication of the dual-binding mode in the acquisition of cellulosome flexibility.
Effective Hamiltonian for surface states of topological insulator nanotubes
Authors: Siu Zhuo Bin , Tan Seng Ghee , Jalil Mansoor B. A.
Published: April 2017

In this work we derive an effective Hamiltonian for the surface states of a hollow topological insulator (TI) nanotube with finite width walls. Unlike a solid TI cylinder, a TI nanotube possesses both an inner as well as outer surface on which the states localized at each surface are coupled together. The curvature along the circumference of the nanotube leads to a spatial variation of the spin orbit interaction field experienced by the charge carriers as well as an asymmetry between the inner and outer surfaces of the nanotube. Both of these features result in terms in the effective Hamiltonian for a TI nanotube absent in that of a flat TI thin film of the same thickness. We calculate the numerical values of the parameters for a Bi2Se3 nanotube as a function of the inner and outer radius, and show that the differing relative magnitudes between the parameters result in qualitatively differing behaviour for the eigenstates of tubes of different dimensions.
Floquet prethermalization and regimes of heating in a periodically driven, interacting quantum system
Authors: Weidinger Simon A. , Knap Michael
Published: April 2017

We study the regimes of heating in the periodically driven O(N)-model, which is a well established model for interacting quantum many-body systems. By computing the absorbed energy with a non-equilibrium Keldysh Green’s function approach, we establish three dynamical regimes: at short times a single-particle dominated regime, at intermediate times a stable Floquet prethermal regime in which the system ceases to absorb, and at parametrically late times a thermalizing regime. Our simulations suggest that in the thermalizing regime the absorbed energy grows algebraically in time with an exponent that approaches the universal value of 1/2, and is thus significantly slower than linear Joule heating. Our results demonstrate the parametric stability of prethermal states in a many-body system driven at frequencies that are comparable to its microscopic scales. This paves the way for realizing exotic quantum phases, such as time crystals or interacting topological phases, in the prethermal regime of interacting Floquet systems.