bluuebunny/crossref_metadata_2025 huggingface dataset:
Momentum-forbidden dark excitons in hBN-encapsulated monolayer MoS2
Authors: Uchiyama Yosuke , Kutana Alex , Watanabe Kenji , Taniguchi Takashi , Kojima Kana , Endo Takahiko , Miyata Yasumitsu , Shinohara Hisanori , Kitaura Ryo
Published: July 2019

Encapsulation by hexagonal boron nitride (hBN) has been widely used to address intrinsic properties of two-dimensional (2D) materials. The hBN encapsulation, however, can alter properties of 2D materials through interlayer orbital hybridization. In this paper, we present measurements of temperature dependence of photoluminescence intensity from monolayer MoS2 encapsulated by hBN flakes. The obtained temperature dependence shows an opposite trend to that of previously observed in a monolayer MoS2 on a SiO2 substrate. This is caused by the existence of stable momentum-forbidden dark excitons in the hBN-encapsulated MoS2. Ab-initio band-structure calculations have shown that orbital hybridization between MoS2 and hBN leads to upward shift of Γ-valley of MoS2, which results in lowering of energy of the momentum-forbidden dark excitons. This work shows an important implication that the hBN-encapsulated structures used to address intrinsic properties of two-dimensional crystals can alter basic properties of encapsulated materials.
The regulatory role of sulfated polysaccharides in facilitating rhBMP-2-induced osteogenesis
Authors: Chen Han , Yu Yuanman , Wang Chenmin , Wang Jing , Liu Changsheng
Published: July 2019

2-N,6-O-sulfated chitosan (26 SCS) could specifically bind to rhBMP-2 and protect it to promote bone regeneration.
Hydrothermal synthesis of natroalunite nanostructures and their F−-ion removal properties in water
Authors: Kim TongIl , Li Yang , Yun HakSung , Ho JinHyok , Jon Yung , O SeGwon , Kim ChangSok , Li Yang , Wang Jiao , Liu Xianhua
Published: July 2019

The formation and growth mechanism of alunite crystallites by ionic liquid-assisted hydrothermal process was investigated.
Enhancing single-molecule magnet behaviour through decorating terminal ligands in Dy2 compounds
Authors: Ma Xiufang , Chen Bingbing , Zhang Yi-Quan , Yang Jinhui , Shi Quan , Ma Yulong , Liu Xiangyu
Published: July 2019

The alternation of terminal substituents on ligands results in different dynamic magnetic behaviors in two Dy2 single-molecule magnets.
Food matrix and co-presence of turmeric compounds influence bioavailability of curcumin in healthy humans
Authors: Ahmed Nasef Noha , Loveday Simon M. , Golding Matt , Martins Ralph N. , Shah Tejal M. , Clarke Michael , Coad Jane , Moughan Paul J. , Garg Manohar L. , Singh Harjinder
Published: July 2019

Turmeric enhances curcumin bioavailability in healthy men.
Ceria/cobalt borate hybrids as efficient electrocatalysts for water oxidation under neutral conditions
Authors: Zhou Xuemei , Guo Sijia , Cai Qiran , Huang Shaoming
Published: July 2019

Oxygen evolution reaction (OER) catalysts are of importance for electrochemical water splitting and fuel generation.
Effect of linear side-chain length on the photovoltaic performance of benzodithiophene-alt-dicarboxylic ester terthiophene polymers
Authors: Ma Kangqiao , Zhang Tao , Wan Pan , Xu Bowei , Zhou Pengxin , An Cunbin
Published: July 2019

Two conjugated polymers with different side chains were synthesized to study their photovoltaic performances.
Application of magnetic Fe3O4nanoparticles as a reusable heterogeneous catalyst in the synthesis of β-lactams containing amino groups
Authors: Moslehi Aleme , Zarei Maaroof
Published: July 2019

The catalytic activity of magnetic Fe3O4nanoparticles to promote the reduction of β-lactams containing nitroaryl groups to β-lactams containing aminoaryl groups in ethanol was reported. This methodology is convenient and green.
TiO2doped polydimethylsiloxane (PDMS) andLuffa cylindricabased photocatalytic nanosponge to absorb and desorb oil in diatom solar panels
Authors: Khan Mohd Jahir , Singh Ramesh , Joshi Khashti Ballabh , Vinayak Vandana
Published: July 2019

Our previous report(s) demonstrated that piezoelectric disc fabricated diatom solar panels worked as micro resonating devices.
Deleterious effects of non-framework Al species on the catalytic performance of ZSM-5 crystals synthesized at low temperature
Authors: Qin Wei , Zhou Yunwen , Rimer Jeffrey D.
Published: July 2019

ZSM-5 synthesis at low temperature leads to a large percentage of non-framework octahedral and penta-coordinated aluminum species that negatively impact catalyst performance.
Water inversed helicity of nanostructures from ionic self-assembly of a chiral gelator and an achiral component
Authors: Liu Changxia , Yang Dong , Zhang Li , Liu Minghua
Published: July 2019

The ISA of a chiral gelator and an achiral component exhibited a left-handed helical nanostructure in ethanol. The formed helical nanostructures can be inverted by adding water to the ethanol solvent.
C2O and C3O in low-mass star-forming regions
Authors: Urso R. G. , Palumbo M. E. , Ceccarelli C. , Balucani N. , Bottinelli S. , Codella C. , Fontani F. , Leto P. , Trigilio C. , Vastel C. , Bachiller R. , Baratta G. A. , Buemi C. S. , Caux E. , Jaber Al-Edhari A. , Lefloch B. , López-Sepulcre A. , Umana G. , Testi L.
Published: July 2019

Context.C2O and C3O belong to the carbon chain oxides family. Both molecules have been detected in the gas phase towards several star-forming regions, and to explain the observed abundances, ion-molecule gas-phase reactions have been invoked. On the other hand, laboratory experiments have shown that carbon chain oxides are formed after energetic processing of CO-rich solid mixtures. Therefore, it has been proposed that they are formed in the solid phase in dense molecular clouds after cosmic ion irradiation of CO-rich icy grain mantles and released in the gas phase after their desorption.

Aims.In this work, we contribute to the understanding of the role of both gas-phase reactions and energetic processing in the formation of simple carbon chain oxides that have been searched for in various low-mass star-forming regions.

Methods.We present observations obtained with the Noto-32m and IRAM-30 m telescopes towards star-forming regions. We compare these with the results of a gas-phase model that simulates C2O and C3O formation and destruction, and laboratory experiments in which both molecules are produced after energetic processing (with 200 keV protons) of icy grain mantle analogues.

Results.New detections of both molecules towards L1544, L1498, and Elias 18 are reported. The adopted gas phase model is not able to reproduce the observed C2O/C3O ratios, while laboratory experiments show that the ion bombardment of CO-rich mixtures produces C2O/C3O ratios that agree with the observed values.

Conclusions.Based on the results obtained here, we conclude that the synthesis of both species is due to the energetic processing of CO-rich icy grain mantles. Their subsequent desorption because of non-thermal processes allows the detection in the gas-phase of young star-forming regions. In more evolved objects, the non-detection of both C2O and C3O is due to their fast destruction in the warm gas.
Laboratory rotational spectroscopy of isotopic acetone, CH313C(O)CH3and13CH3C(O)CH3, and astronomical search in Sagittarius B2(N2)
Authors: Ordu Matthias H. , Zingsheim Oliver , Belloche Arnaud , Lewen Frank , Garrod Robin T. , Menten Karl M. , Schlemmer Stephan , Müller Holger S. P.
Published: July 2019

Context.Spectral lines of minor isotopic species of molecules that are abundant in space may also be detectable. Their respective isotopic ratios may provide clues about the formation of these molecules. Emission lines of acetone in the hot molecular core Sagittarius B2(N2) are strong enough to warrant a search for its singly substituted13C isotopologs.

Aims.We want to study the rotational spectra of CH313C(O)CH3and13CH3C(O)CH3and search for them in Sagittarius B2(N2).

Methods.We investigated the laboratory rotational spectrum of isotopically enriched CH313C(O)CH3between 40 GHz and 910 GHz and of acetone between 36 GHz and 910 GHz in order to study13CH3C(O)CH3in natural isotopic composition. In addition, we searched for emission lines produced by these species in a molecular line survey of Sagittarius B2(N) carried out with the Atacama Large Millimeter/submillimeter Array (ALMA). Discrepancies between predictions of the main isotopic species and the ALMA spectrum prompted us to revisit the rotational spectrum of this isotopolog.

Results.We assigned 9711 new transitions of CH313C(O)CH3and 63 new transitions of13CH3C(O)CH3in the laboratory spectra. More than 1000 additional transitions were assigned for the main isotopic species. We modeled the ground state data of all three isotopologs satisfactorily with the ERHAM program. We find that models of the torsionally excited statesv12 = 1 andv17 = 1 of CH3C(O)CH3improve only marginally. No transitrrrion of CH313C(O)CH3is clearly detected toward the hot molecular core Sgr B2(N2). However, we report a tentative detection of13CH3C(O)CH3with a12C/13C isotopic ratio of 27 that is consistent with the ratio previously measured for alcohols in this source. Several dozens of transitions of both torsional states of the main isotopolog are detected as well.

Conclusion.Our predictions of CH313C(O)CH3and CH3C(O)CH3are reliable into the terahertz region. The spectrum of13CH3C(O)CH3should be revisited in the laboratory with an enriched sample. The torsionally excited statesv12 = 1 andv17 = 1 of CH3C(O)CH3were not reproduced satisfactorily in our models. Nevertheless, transitions pertaining to both states could be identified unambiguously in Sagittarius B2(N2).
Prävalenz von Komorbiditäten bei Lymphödemerkrankungen
Authors: Reißhauer Anett , Schuester Leon , Kling Annelies , Liebl Max Emanuel
Published: July 2019

Hintergrund Komorbiditäten sind Erkrankungen, die nebeneinander auftreten, entweder voneinander unabhängig, oder als Folgeerkrankung einer Indexerkrankung. Bekannte Ursachen oder Risikofaktoren für Lymphödeme (LÖ) sind u. a. maligne Erkrankungen und ihre Behandlung, Adipositas, chronisch-venöse Insuffizienz und das Lipödem. Bekannte Folgeerkrankungen sind u. a. Erysipele sowie Haut- und Nagelpilzerkrankungen. Ziel ist die Erhebung der Prävalenz von Komorbiditäten bei Lymphödem-Erkrankungen.

Methoden Retrospektive Analyse von 457 konsekutiven Fällen der Sprechstunde für Lymphödemerkrankungen der Hochschulambulanz einer Universitätsklinik hinsichtlich der Prävalenz von Komorbiditäten.

Ergebnisse n=391 Fälle kamen zur Auswertung, getrennt nach Ödemgenese, darunter n=51 primäre Lymphödeme (pL) (Verdacht und gesichert, davon 8 gesicherte syndromale Erkrankungen) und n=340 sekundäre Lymphödeme (sL). Das Geschlechterverhältnis in der Stichprobe war 9:1 (w:m). Während die pL-PatientInnen einen BMI vergleichbar der altersentsprechenden Referenzgruppe der Allgemeinbevölkerung aufweisen, zeigen PatientInnen mit sL einen durchschnittlichen BMI von 33,8 und einen Anteil von 64% adipöser Patientinnen (21% mit BMI über 40). Die Prävalenz rezidivierender Erysipele ist mit 7,8 bzw. 7,9% zwischen pL und sL vergleichbar häufig. Weitere Prävalenzen wie Diagnosen aus dem muskuloskeletalen Bereich (ICD-Kapitel XIII/„M“) zeigten sich in der Stichprobe in altersgerechter Verteilung. Eine besonders hohe Prävalenz zeigen in der Gruppe der sL Schilddrüsenerkrankungen (30%), dabei überwiegend die Schilddrüsenunterfunktion.

Diskussion Nur z. T. kann das Patientenalter und Geschlecht die Prävalenzen der Komorbiditäten erklären. Auffällig beim sekundären LÖ ist die Prävalenz der Adipositas, die als Kofaktor bei der Entstehung und als aggravierender Faktor bekannt ist. Von Interesse ist auch die vergleichbare Prävalenz von Erysipelen zwischen den primären und sekundären Lymphödemen. Offenbar spielt die Genese des LÖ für die Entstehung eines Erysipels keine Rolle. Bislang kaum beschrieben, aber höchst auffällig ist die hohe Prävalenz von Schilddrüsenerkrankungen, insbesondere der Hypothyreose, bei sekundären LÖ.
Stereotype – Maier-Kolumne
Authors: Maier Ulrike
Published: July 2019

Kennen Sie das auch? Kollegen in der Praxis mit besonders einprägsamen Eigenschaften, deren Handeln immer einem typischen Muster folgt? Klassische Stereotype gibt es wohl in jeder Physiotherapiepraxis. Besonders eindrückliche Typen stellt Ulrike Maier hier vor.
Seilzug to go – Funktionelles Training mit textilen Widerstandsbändern
Authors: Jenewein Olaf
Published: July 2019

Bei einem Dutzend Patienten auf der Trainingsfläche und nur zwei Seilzügen ist guter Rat oft teuer. Was folgt, sind lange Wartezeiten und ungeduldige Patienten. Es geht auch anders, weiß KGG-Instruktor Olaf Jenewein. Er bietet seinen Patienten mit den elastischen FLEXVIT-Bändern eine willkommene Alternative.
Meldepflicht beachten – Gastroenteritis
Authors: Baumgärtner Martina
Published: July 2019

Übelkeit, Durchfall, Erbrechen – wer an einem Magen-Darm-Infekt leidet, kennt Symptome wie diese. Die Erkrankung kommt meist schnell, und ist nach ein paar Tagen wieder abgeheilt. Sich daran anzustecken ist je nach Erreger auch noch Wochen später möglich. Auch die Meldepflicht ist vom Erreger abhängig. In manchen Fällen müssen sogar Physiotherapeuten erkrankte Patienten dem Gesundheitsamt melden.
Der schwierige Weg zum Frau-Sein
Authors: Saucke Elsbeth
Published: July 2019

Gynäkologische Störungen in der Pubertät lassen sich mit Homöopathie oft leicht behandeln. Die erfolgreiche Behandlung kann eine Pathologisierung mit entsprechender Dauermedikation verhindern. Ich möchte Ihnen 3 Fälle erfolgreicher Behandlung von Dysmenorrhö, Amenorrhö bzw. Körperwahrnehmungsstörung vorstellen. Die gebrauchten Arzneimittel waren Cyclamen, Pulsatilla, Natrium muriaticum, Calcium carbonicum.
Zwei gynäkologische Fälle
Authors: Schipflinger Guntmar , Zauner Bernhard
Published: July 2019

In den 2 dargestellten gynäkologischen Fällen wird die Mittelfindung mit dem Symptomenlexikon dargestellt. Diese Methode eignet sich auch für Beschwerden des weiblichen Unterleibs, obwohl zu Zeiten Hahnemanns relativ wenige Prüfsymptome dieses Körperbereichs bekannt waren.
Recurring Migraines as the Presenting Symptom of Pediatric Multiple Sclerosis in a Teenage Girl: A Case Report
Authors: Meiling James Bryan , Bui Priya Kaji
Published: July 2019

Multiple sclerosis (MS) is a chronic disease of the central nervous system that leads to a progressive breakdown of the myelin sheath by self-harming autoantibodies. Both MS and migraines have a predilection for women as opposed to men. In addition, both can come across as acute attacks on the body that negatively affect the ability of an individual to function. Are they associative concurrent afflictions or is one the primary causality of the other? This case report represents a teenage girl who presented to her pediatrician with recurrent migraines, which led to a diagnosis of pediatric MS.
Pharmacist integration into general practice in New Zealand
Authors: Haua Robert , Harrison Jeff , Aspden Trudi
Published: July 2019

ABSTRACT
IntroductionPharmacist integration into general practice is gaining momentum internationally, with benefits noted in reducing medication errors, improving chronic disease management and alleviating general practitioner workforce shortages. Little is known about how general practice pharmacists are working in New Zealand.
AimThis study characterised the current landscape of pharmacist integration into general practice in New Zealand.
MethodsAn online questionnaire was developed, piloted and distributed to all pharmacists in New Zealand.
ResultsThirty-six responses were analysed. Respondents were more likely to be female, have been pharmacists for at least 10 years and all but one held formal postgraduate clinical pharmacy qualifications. Seven pharmacists were working as pharmacist prescribers. Primary health organisations (PHOs) were the most common employer, with funding primarily derived from either PHOs or District Health Boards. Pharmacist integration into general practice appears to have progressed further in particular regions of New Zealand, with most respondents located in the North Island. Tasks performed by respondents included medication reviews, managing long-term conditions and medicines reconciliation. Increased job satisfaction compared with previous roles was reported by most respondents. Funding and a general lack of awareness about pharmacists’ professional scope were seen as barriers to further expansion of the role.
DiscussionThis study describes the characteristics of pharmacists currently working in general practices in New Zealand and provides insights into key requirements for the role. Understanding the way practice pharmacists are currently employed and funded can inform general practices considering employing pharmacists.
Neural Redundancy and Its Relation to Neural Reuse
Authors: Zerilli John
Published: July 2019

Evidence of the pervasiveness of neural reuse in the human brain has forced a revision of the standard conception of modularity in the cognitive sciences. One persistent line of argument against such revision, however, cites the evidence of cognitive dissociations. While this article takes the dissociations seriously, it contends that the traditional modular account is not the best explanation. The key to the puzzle is neural redundancy. The article offers both a philosophical analysis of the relation between reuse and redundancy as well as a plausible solution to the problem of dissociations.
Exascale supercomputer intiative launched
Authors: Gwynne Peter
Published: July 2019

The US Department of Energy (DOE) has announced plans to build the world’s first exascale supercomputer.
Upgrade to major European synchrotron gears up
Authors: Banks Michael
Published: July 2019

The first components have been installed in a major upgrade to the European Synchrotron Radiation Facility (ESRF) in Grenoble, France.
Technologies to study spatial genome organization: beyond 3C
Authors: Übelmesser Nadine , Papantonis Argyris
Published: July 2019

The way that chromatin is organized in three-dimensional nuclear space is now acknowledged as a factor critical for the major cell processes, like transcription, replication and cell division. Researchers have been armed with new molecular and imaging technologies to study this structure-to-function link of genomes, spearheaded by the introduction of the ‘chromosome conformation capture’ technology more than a decade ago. However, this technology is not without shortcomings, and novel variants and orthogonal approaches are being developed to overcome these. As a result, the field of nuclear organization is constantly fueled by methods of increasing resolution and/or throughput that strive to eliminate systematic biases and increase precision. In this review, we attempt to highlight the most recent advances in technology that promise to provide novel insights on how chromosomes fold and function.
Strategies to prevent cleavage of the linker region between ligand-binding repeats 4 and 5 of the LDL receptor
Authors: Strøm Thea Bismo , Bjune Katrine , Costa Luís Teixeira da , Leren Trond P
Published: July 2019

A main strategy for lowering plasma low-density lipoprotein (LDL) cholesterol levels is to increase the number of cell-surface LDL receptors (LDLRs). This can be achieved by increasing the synthesis or preventing the degradation of the LDLR. One mechanism by which an LDLR becomes non-functional is enzymatic cleavage within the 10 residue linker region between ligand-binding repeats 4 and 5. The cleaved LDLR has only three ligand-binding repeats and is unable to bind LDL. In this study, we have performed cell culture experiments to identify strategies to prevent this cleavage. As a part of these studies, we found that Asp193 within the linker region is critical for cleavage to occur. Moreover, both 14-mer synthetic peptides and antibodies directed against the linker region prevented cleavage. As a consequence, more functional LDLRs were observed on the cell surface. The observation that the cleaved LDLR was present in extracts from the human adrenal gland indicates that cleavage of the linker region takes place in vivo. Thus, preventing cleavage of the LDLR by pharmacological measures could represent a novel lipid-lowering strategy.
Cushing’s syndrome due to interaction between ritonavir or cobicistat and corticosteroids: a case–control study in the French Pharmacovigilance Database
Authors: Peyro-Saint-Paul Laure , Besnier Paul , Demessine Ludivine , Biour Michel , Hillaire-Buys Dominique , de Canecaude Claire , Fedrizzi Sophie , Parienti Jean-Jacques
Published: July 2019

Objectives

To explore the frequent interaction between antiretroviral-boosting agents and corticosteroids causing Cushing’s syndrome (CS) in the French Pharmacovigilance Database (FPVD).

Methods

We conducted a retrospective case–control study describing CS recorded in the FPVD between 1996 and 2018. Case was defined as CS occurring in people living with HIV (PLWH) and control was defined as CS in uninfected individuals. Drug–drug interaction (DDI) was defined as an interaction between corticosteroids and CYP3A4 inhibitors. Data concerning the DDI, corticosteroids involved, route of administration and seriousness of the CS were described.

Results

Among the 139 instances of CS identified, 34/35 cases (97%) had DDIs (31 with ritonavir and 3 with cobicistat) and 7/104 controls (7%) had DDIs (6 with itraconazole and 1 with verapamil). The main corticosteroid involved was inhaled fluticasone (28/35, 80%) among the cases and oral prednisone (38/104, 37%) among the controls. More CS cases (30/35, 86%) than CS controls (62/104, 60%) were serious (OR = 4.0, 95% CI = 1.4–14.4; P = 0.007).

Conclusions

Antiretroviral-boosting agents were responsible for one out of four iatrogenic CS cases in a French national database. Prescribers should be aware of the risk of potentially serious DDIs between antiretroviral-boosting agents and corticosteroids, including single-tablet regimens containing cobicistat.
Identifying phenological phases in strawberry using multiple change-point models
Authors: Labadie Marc , Denoyes Béatrice , Guédon Yann
Published: July 2019

Phenological phases are a cornerstone of phenology, the study of recurrent biological events over time. We introduce a new statistical modeling approach for identifying phases in phenological series.
The MAGIC project – II. Discovery of two new Galactic lithium-rich Cepheids
Authors: Kovtyukh V , Lemasle B , Kniazev A , Berdnikov L , Bono G , Usenko I , Grebel E K , Hajdu G , Pastukhova E
Published: July 2019

We report the discovery of two new lithium-rich Cepheids in the Milky Way (A(Li) ≈ 2.9 dex) among the targets of the MAGIC spectroscopic survey with the Southern African Large Telescope spectrographs. The 6707 Å Li feature is usually not detectable in the atmosphere of Cepheids. Only three Cepheids (two in the Milky Way and one in the Large Magellanic Cloud) had been reported so far with high lithium abundances. We examine the possibility that the Li-rich Cepheids are evolving towards the red giant branch, crossing the instability strip for the first time, as well as other possible scenarios. The two stars are mixed-mode Cepheids pulsating simultaneously in the first and in the second overtone modes. We briefly discuss the possible connection between their unusual chemical composition and their pulsational properties.
Three-dimensional dust mapping of 12 supernovae remnants in the Galactic anticentre
Authors: Yu Bin , Chen B Q , Jiang B W , Zijlstra A
Published: July 2019

We present three-dimensional (3D) dust mapping of 12 supernova remnants (SNRs) in the Galactic anticentre (Galactic longitude l between 150○ and 210○) based on a recent 3D interstellar extinction map. The dust distribution of the regions, which cover the full extents in the radio continuum for the individual SNRs, is discussed. Four SNRs show significant spatial coincidences between molecular clouds (MCs) revealed from the 3D extinction mapping and the corresponding radio features. The results confirm the interactions between these SNRs and their surrounding MCs. Based on these correlations, we provide new distance estimates of the four SNRs, G189.1+3.0 (IC443, $d=1729^{+116}_{-94} \rm \, pc$), G190.9–2.2 ($d=1036^{+17}_{-81} \rm \, pc$), G205.5+0.5 ($d=941^{+96}_{-94}$ or $1257^{+92}_{-101} \rm \, pc$), and G213.0–0.6 ($d=1146^{+79}_{-80} \rm \, pc$). In addition, we find indirect evidences of potential interactions between SNRs and MCs for three other SNRs. New distance constraints are also given for these three SNRs.
Multiband optical variability of 3C 279 on diverse time-scales
Authors: Agarwal Aditi , Cellone Sergio A , Andruchow Ileana , Mammana Luis , Singh Mridweeka , Anupama G C , Mihov B , Raj Ashish , Slavcheva-Mihova L , Özdönmez Aykut , Ege Ergün
Published: July 2019

We have monitored the flat spectrum radio quasar, 3C 279, in the optical B, V, R, and I passbands from 2018 February to 2018 July for 24 nights, with a total of 716 frames, to study flux, colour, and spectral variability on diverse time-scales. 3C 279 was observed using seven different telescopes: two in India, two in Argentina, two in Bulgaria, and one in Turkey to understand the nature of the source in optical regime. The source was found to be active during the whole monitoring period and displayed significant flux variations in B, V, R, and I passbands. Variability amplitudes on intraday basis varied from 5.20 to 17.9 per cent. A close inspection of variability patterns during our observation cycle reveals simultaneity among optical emissions from all passbands. During the complete monitoring period, progressive increase in the amplitude of variability with frequency was detected for our target. The amplitudes of variability in B, V, R, and I passbands have been estimated to be 177 per cent, 172 per cent, 171 per cent, and 158 per cent, respectively. Using the structure function technique, we found intraday time-scales ranging from ∼23 min to about 115 min. We also studied colour–magnitude relationship and found indications of mild bluer-when-brighter trend on shorter time-scales. Spectral indices ranged from 2.3 to 3.0 with no clear trend on long-term basis. We have also generated spectral energy distributions for 3C 279 in optical B, V, R, and I passbands for 17 nights. Finally, possible emission mechanisms causing variability in blazars are discussed briefly.
Trypanosoma brucei ribonuclease H2A is an essential R-loop processing enzyme whose loss causes DNA damage during transcription initiation and antigenic variation
Authors: Briggs Emma , Crouch Kathryn , Lemgruber Leandro , Hamilton Graham , Lapsley Craig , McCulloch Richard
Published: July 2019

Ribonucleotides represent a threat to DNA genome stability and transmission. Two types of Ribonuclease H (RNase H) excise ribonucleotides when they form part of the DNA strand, or hydrolyse RNA when it base-pairs with DNA in structures termed R-loops. Loss of either RNase H is lethal in mammals, whereas yeast survives the absence of both enzymes. RNase H1 loss is tolerated by the parasite Trypanosoma brucei but no work has examined the function of RNase H2. Here we show that loss of T. brucei RNase H2 (TbRH2A) leads to growth and cell cycle arrest that is concomitant with accumulation of nuclear damage at sites of RNA polymerase (Pol) II transcription initiation, revealing a novel and critical role for RNase H2. Differential gene expression analysis reveals limited overall changes in RNA levels for RNA Pol II genes after TbRH2A loss, but increased perturbation of nucleotide metabolic genes. Finally, we show that TbRH2A loss causes R-loop and DNA damage accumulation in telomeric RNA Pol I transcription sites, also leading to altered gene expression. Thus, we demonstrate separation of function between two nuclear T. brucei RNase H enzymes during RNA Pol II transcription, but overlap in function during RNA Pol I-mediated gene expression during host immune evasion.
Expanding Indications for Flow Diverters: Ruptured Aneurysms, Blister Aneurysms, and Dissecting Aneurysms
Authors: Kan Peter , Sweid Ahmad , Srivatsan Aditya , Jabbour Pascal
Published: July 2019

BACKGROUND

The safety and efficacy of flow diversion (FD) in the treatment of cerebral aneurysms have been reported by many studies. FD has enabled the treatment of complex aneurysms and aneurysms that were previously untreatable by conventional means. It has achieved high rates of obliteration with essentially no recanalization, and its indications have continued to expand, now including ruptured aneurysms, blister aneurysms, and dissecting aneurysms.

OBJECTIVE

To provide a review on the outcomes of studies covering the use of FD in the settings of ruptured, blister, and dissecting aneurysms. In addition, to discuss dual antiplatelet therapy (DAPT) used in preparation for FD deployment in these scenarios, including associated complications with DAPT use in the acute rupture setting.

METHODS

References for this topical review were identified by PubMed searches between January 2000 and January 2019. The search terms “aneurysm”, “flow diverter”, “stent”, “pipeline”, “ruptured”, “blister”, and “dissecting aneurysms” were used.

RESULTS

FD carries a higher complication rate in the acute rupture setting than for unruptured aneurysms. Patient selection is of paramount importance for achieving good functional and angiographic outcomes. DAPT still remains challenging, especially in ruptured aneurysms. Advancements in surface modification of flow diverters can reduce the risk of thromboembolism and perhaps lead to a safer antiplatelet regimen.

CONCLUSION

In summary, FD shows promise to be an effective treatment for ruptured, blister, and dissecting aneurysms.
Acute hepatitis C infection among adults with HIV in the Netherlands: a capture-recapture analysis
Authors: Boender Tamara Sonia , de Coul Eline Op , Arends Joop , Prins Maria , van der Valk Marc , van der Meer Jan T.M. , van Benthem Birgit , Reiss Peter , Smit Colette
Published: July 2019

Background

Reliable surveillance systems are essential to assess the national response to eliminating hepatitis C virus (HCV), in the context of the global strategy towards eliminating viral hepatitis.

Aim

We aimed to assess the completeness of the two national registries of acute HCV infection in people with HIV, and estimated the number of acute HCV infections among adults with HIV in the Netherlands.

Methods

For 2003-2016, cases of HCV infection and reinfection among adults with a positive or unknown HIV-serostatus were identified in two national registries: the ATHENA cohort, and the National Registry for Notifiable Diseases. For 2013-2016, cases were linked, and two-way capture-recapture analysis was carried out.

Results

During 2013-2016, there were an estimated 282 (95%CI: 264-301) acute HCV infections among adults with HIV. The addition of cases with an unknown HIV-serostatus increased the matches (from N=104 to N=129), and a subsequently increased the estimated total: 330 (95%CI: 309-351). Underreporting was estimated at 14-20%.

Conclusion

In 2013-2016, up to 330 cases of acute HCV infection were estimated to have occurred among adults with HIV. National surveillance of acute HCV can be improved by increased notification of infections. Surveillance data should ideally include both acute and chronic HCV infections, and be able to distinguish between acute and chronic infections, and initial and reinfections.

Classifications

The Netherlands; sexually transmitted infections; hepatitis C; HIV infection; Surveillance; epidemiology
HIV-associated sensory neuropathy continues to be a problem in individuals starting tenofovir-based antiretroviral treatment
Authors: Pillay Prinisha , Wadley Antonia L , Cherry Catherine L , Karstaedt Alan S , Kamerman Peter R
Published: July 2019

HIV-associated sensory neuropathy (HIV-SN) is a common and often painful neurological condition associated with HIV-infection and its treatment. However, data on the incidence of HIV-SN in neuropathy-free individuals initiating combination antiretroviral therapies (cART) that do not contain the neurotoxic agent stavudine are lacking. We investigated the six-month incidence of HIV-SN in ART naïve individuals initiating tenofovir (TDF)-based cART, and the clinical factors associated with the development of HIV-SN. 120 neuropathy-free and ART naïve individuals initiating cART at a single centre in Johannesburg, South Africa were enrolled. Participants were screened for HIV-SN at study enrolment and then approximately every two-months for a period of approximately six-months. Symptomatic HIV-SN was defined by the presence of at least one symptom (pain/burning, numbness, paraesthesias) and at least two clinical signs (reduced vibration sense, absent ankle reflexes or pin-prick hypoaesthesia). Asymptomatic HIV-SN required at least two clinical signs only. A total of 88% of the cohort completed three visits within the six-month period. Eleven individuals developed asymptomatic HIV-SN and nine developed symptomatic HIV-SN, giving a six-month cumulative incidence of neuropathy of 140 cases per 1000 patients (95% CI: 80 - 210) at an incidence rate of 0.37 (95% CI: 0.2 - 0.5) per person year. Increasing height and active tuberculosis (TB) disease were independently associated with the risk of developing HIV-SN (p < 0.05). We found that within the first six months of starting cART, incident SN persists in the post-stavudine era, but may be asymptomatic.
Power and pitfalls of computational methods for inferring clone phylogenies and mutation orders from bulk sequencing data
Authors: Miura Sayaka , Vu Tracy , Deng Jiamin , Buturla Tiffany , Choi Jiyeong , Kumar Sudhir
Published: July 2019

Background

Tumors harbor extensive genetic heterogeneity in the form of distinct clone genotypes that arise over time and across different tissues and regions of a cancer patient. Many computational methods produce clone phylogenies from population bulk sequencing data collected from multiple tumor samples. These clone phylogenies are used to infer mutation order and clone origin times during tumor progression, rendering the selection of the appropriate clonal deconvolution method quite critical. Surprisingly, absolute and relative accuracies of these methods in correctly inferring clone phylogenies have not been consistently assessed.

Methods

We evaluated the performance of seven computational methods in producing clone phylogenies for simulated datasets in which clones were sampled from multiple sectors of a primary tumor (multi-region) or primary and metastatic tumors in a patient (multi-site). We assessed the accuracy of tested methods metrics in determining the order of mutations and the branching pattern within the reconstructed clone phylogenies.

Results

The accuracy of the reconstructed mutation order varied extensively among methods (9% – 44% error). Methods also varied significantly in reconstructing the topologies of clone phylogenies, as 24% – 58% of the inferred clone groupings were incorrect. All the tested methods showed limited ability to identify ancestral clone sequences present in tumor samples correctly. The occurrence of multiple seeding events among tumor sites during metastatic tumor evolution hindered deconvolution of clones for all tested methods.

Conclusions

Overall, CloneFinder, MACHINA, and LICHeE showed the highest overall accuracy, but none of the methods performed well for all simulated datasets and conditions.
Plant respiration: controlled by photosynthesis or biomass?
Authors: Collalti Alessio , Tjoelker Mark G. , Hoch Günter , Mäkelä Annikki , Guidolotti Gabriele , Heskel Mary , Petit Giai , Ryan Michael G. , Battipaglia Giovanna , Prentice I. Colin
Published: July 2019

Two simplifying hypotheses have been proposed for whole-plant respiration. One links respiration to photosynthesis; the other to biomass. Using a first-principles carbon balance model with a prescribed live woody biomass turnover, applied at a forest research site where multidecadal measurements are available for comparison, we show that if turnover is fast the accumulation of respiring biomass is low and respiration depends primarily on photosynthesis; while if turnover is slow the accumulation of respiring biomass is high and respiration depends primarily on biomass. But the first scenario is inconsistent with evidence for substantial carryover of fixed carbon between years, while the second implies far too great an increase in respiration during stand development – leading to depleted carbohydrate reserves and an unrealistically high mortality risk. These two mutually incompatible hypotheses are thus both incorrect. Respiration isnotlinearly related either to photosynthesis or to biomass, but it is more strongly controlled by recent photosynthates (and reserve availability) than by total biomass.
Coevolution between life-history and metabolic rate depends on ontogenetic stage
Authors: Sowersby Will , Morozov Sergey , Eckerström-Liedholm Simon , Lehmann Philipp , Rowiński Piotr K. , Näslund Joacim , Gonzalez-Voyer Alejandro , Rogell Björn
Published: July 2019

Metabolic rate is considered to determine the energetic investment placed into life-history traits, regulating the speed of an organism’s life-cycle and forming the so called “pace-of-life”. However, how metabolic rate and life-history traits co-evolve remains unclear. For instance, the energetic demands of life-history traits, including the number of energy allocation trade-offs, is unlikely to remain constant over ontogeny. Therefore, the predicted coevolution between metabolic rate and life-history could be specific to particular ontogenetic stages, rather than a stable property of an organism. Here, we test the ontogenetic dependency of the coevolution between metabolic rate and the pace of life-history, under strictly standardized conditions using 30 species of killifish, which are either annual species adapted to ephemeral pools or non-annual species inhabiting more permanent waterbodies. Standard metabolic rates were estimated at three ontogenetic stages, together with relevant life-history traits, i.e. growth (juveniles), maturity (young adults), and reproductive rate (reproductive adults). Life-history traits largely followed predicted pace-of-life patterns, with overall faster/higher rates in annual species. The divergences in life-history traits across species tended to increase over ontogeny, being smallest during juvenile growth and largest in reproductive adults. However, associations between life-history strategy and metabolic rate followed a reversed pattern, being strongest in juveniles, but lowest in reproductive adults. Our results are concordant with the number of energetic trade-offs increasing over ontogeny, which results in a stronger covariation between physiology and life-history traits earlier in ontogeny.
Multiple cyanotoxin congeners produced by sub-dominant cyanobacterial taxa in riverine cyanobacterial and algal mats
Authors: Kelly Laura T. , Bouma-Gregson Keith , Puddick Jonathan , Fadness Rich , Ryan Ken G. , Davis Timothy W. , Wood Susanna A.
Published: July 2019

Benthic cyanobacterial proliferations in rivers are have been reported with increasing frequency worldwide. In the Eel and Russian rivers of California, more than a dozen dog deaths have been attributed to cyanotoxin toxicosis since 2000. Periphyton proliferations in these rivers comprise multiple cyanobacterial taxa capable of cyanotoxin production, hence there is uncertainty regarding which taxa are producing toxins. In this study, periphyton samples dominated by the cyanobacterial genera Anabaena spp. and Microcoleus spp. and the green alga Cladophora glomerata were collected from four sites in the Eel River catchment and one site in the Russian River. Samples were analysed for potential cyanotoxin producers using polymerase chain reaction (PCR) in concert with Sanger sequencing. Cyanotoxin concentrations were measured using liquid chromatography tandem-mass spectrometry, and anatoxin quota determined using droplet digital PCR. Sequencing indicated Microcoleus sp. and Nodularia sp. were the putative producers of anatoxins and nodularins, respectively, regardless of the dominant taxa in the mat. Anatoxin concentrations in the mat samples varied from 0.1 to 18.6 μg g−1 and were significantly different among sites (p < 0.01, Wilcoxon test); however, anatoxin quotas were less variable (< 5-fold). Dihydroanatoxin-a was generally the most abundant variant in samples comprising 38% to 71% of the total anatoxins measured. Mats dominated by the green alga C. glomerata contained both anatoxins and nodularin-R at concentrations similar to those of cyanobacteria-dominated mats. This highlights that even when cyanobacteria are not the dominant taxa in periphyton, these mats may still pose a serious health risk and indicates that more widespread monitoring of all mats in a river are necessary.
Pervasive introgression of MHC genes in newt hybrid zones
Authors: Dudek K. , Gaczorek T. S. , Zieliński P. , Babik W.
Published: July 2019

Variation in the vertebrate major histocompatibility complex (MHC) genes is crucial for fighting pathogen assault. Because new alleles confer a selective advantage, MHC should readily introgress between species, even under limited hybridization. Using replicated transects through two hybrid zones between strongly reproductively isolated newts, we demonstrated recent and ongoing MHC introgression. Its extent correlated with the age of contact. In the older zone, MHC similarity between species within transects exceeded that of between transects within species, implying pervasive introgression – a massive exchange of MHC genes, not limited to specific variants. In simulations, the observed pattern emerged under the combined action of balancing selection and hybridization, but not when these processes acted separately. Thus, massive introgression at advanced stages of divergence can introduce novel and restore previously lost MHC variation, boosting the adaptive potential of hybridizing taxa. In consequence, MHC genes may be the last to stop introgressing between incipient species.
A unique lower X-gate in TASK channels traps inhibitors within the vestibule
Authors: Rödström Karin E. J. , Kiper Aytuğ K. , Zhang Wei , Rinné Susanne , Pike Ashley C. W. , Goldstein Matthias , Conrad Linus , Delbeck Martina , Hahn Michael , Meier Heinrich , Platzk Magdalena , Quigley Andrew , Speedman David , Shrestha Leela , Mukhopadhyay Shubhashish M.M. , Burgess-Brown Nicola A. , Tucker Stephen J. , Mueller Thomas , Decher Niels , Carpenter Elisabeth P.
Published: July 2019

TASK channels are unusual members of the two-pore domain potassium (K2P) channel family, with unique and unexplained physiological and pharmacological characteristics. TASKs are found in neurons1,2, cardiomyocytes3–5 and vascular smooth muscle cells6 where they are involved in regulation of heart rate7, pulmonary artery tone6,8, sleep/wake cycles9 and responses to volatile anaesthetics9–12. K2P channels regulate the resting membrane potential, providing background K+ currents controlled by numerous physiological stimuli13,14. Unlike other K2P channels, TASK channels have the capacity to bind inhibitors with high affinity, exceptional selectivity and very slow compound washout rates. These characteristics make the TASK channels some of the the most easily druggable potassium channels, and indeed TASK-1 inhibitors are currently in clinical trials for obstructive sleep apnea (OSA) and atrial fibrillation (Afib)15 (The DOCTOS and SANDMAN Trials). Generally, potassium channels have an intramembrane vestibule with a selectivity filter above and a gate with four parallel helices below. However, K2P channels studied to date all lack a lower gate. Here we present the structure of TASK-1, revealing a unique lower gate created by interaction of the two crossed C-terminal M4 transmembrane helices at the vestibule entrance, which we designate as an ‟X-gate”. This structure is formed by six residues (V243LRFMT248) that are essential for responses to volatile anaesthetics11, neuro-transmitters16 and G-protein coupled receptors16. Interestingly, mutations within the X-gate and surrounding regions drastically affect both open probability and activation by anaesthetics. Structures of TASK-1 with two novel, high-affinity blockers, shows both inhibitors bound below the selectivity filter, trapped in the vestibule by the X-gate, thus explaining their exceptionally low wash-out rates. Thus, the presence of the X-gate in TASK channels explains many aspects of their unusual physiological and pharmacological behaviour, which is invaluable for future development and optimization of TASK modulators for treatment of heart, lung and sleep disorders.
Comparing the selective landscape of TLR7 and TLR8 across primates reveals unique sites under positive selection inAlouatta
Authors: Torosin Nicole S. , Argibay Hernan , Webster Timothy H. , Corneli Patrice Showers , Knapp Leslie A.
Published: July 2019

Among primates, susceptibility to yellow fever (YFV), a single-stranded (ss) RNA virus, ranges from complete resistance to high susceptibility. Howler monkeys (genusAlouatta) are the most susceptible to YFV. In order to identifyAlouatta-specific genetic factors that may be responsible for their susceptibility, we collected skin samples from howler monkey museum specimens of the speciesA. carayaandA. guariba clamitans. We compared the rate of nonsynonymous to synonymous (dN/dS) changes of Toll-like receptor (TLR) 7 and TLR8, the two genes responsible for detecting all ssRNA viruses, across the Primate order. Overall, we found that the TLR7 gene is under stronger purifying selection in howler monkeys compared to other New World and Old World primates, but TLR8 is under the same selective pressure. When we evaluateddN/dSat each codon, we found six codons under positive selection inAlouattaTLR8 and two codons under positive selection in TLR7. The changes in TLR7 are unique toA. guariba clamitansand are found in functionally important regions likely to affect detection of ssRNA viruses by TLR7/TLR8, as well as downstream signaling. These amino acid differences inA. guariba clamitansmay play a role in YFV susceptibility. These results have implications for identifying genetic factors affecting YFV susceptibility in primates.
Dysregulated interactions triggered by a neuropathy-causing mutation in the IPV motif of HSP27
Authors: Alderson T. Reid , Adriaenssens Elias , Asselbergh Bob , Pritišanac Iva , Gastall Heidi Y. , Wälti Marielle A. , Louis John M. , Timmerman Vincent , Baldwin Andrew J. , Benesch Justin L. P.
Published: July 2019

HSP27 (HSPB1) is a systemically expressed human small heat-shock protein that forms large, dynamic oligomers and functions in various aspects of cellular homeostasis. Mutations in HSP27 cause Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. A particularly severe form of the disease is triggered by the P182L mutation within the highly conserved IxI/V motif of HSP27. Here, we observed that the P182L variant of HSP27 lacks the ability to prevent the aggregation of client proteins and formed significantly larger oligomers both in vitro and in vivo. NMR spectroscopy revealed that the P182L IxI/V motif binds its α-crystallin domain with significantly lower association rate, and thus affinity, rendering the binding site more available for other interactors. We identified 22 IxI/V-containing proteins that are known to interact with HSP27 and could therefore bind with enhanced affinity to the P182L variant. We validated this hypothesis through co-immunoprecipitation experiments, revealing that the IxI/V motif-bearing co-chaperone BAG3 indeed binds with higher affinity to the P182L variant. Our results provide a mechanistic basis for the impact of the P182L mutation on HSP27, and highlight the general importance of the IxI/V motif and its role in protein-protein interaction networks.