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Borrelia burgdorferi sensu lato (Bbsl), the causative agent of Lyme disease, establishes an initial infection in the host’s skin following a tick bite, and then disseminates to distant organs, leading to multisystem manifestations. Tick-to-vertebrate host transmission requires that Bbsl survives during blood feeding. Complement is an important innate host defense in blood and interstitial fluid. Bbsl produces a polymorphic surface protein, CspA, that binds to a complement regulator, Factor H (FH) to block complement activation in vitro. However, the role that CspA plays in the Bbsl enzootic cycle remains unclear. In this study, we demonstrated that different CspA variants promote spirochete binding to FH to inactivate complement and promote serum resistance in a host-specific manner. Utilizing a tick-to-mouse transmission model, we observed that a cspA-knockout B. burgdorferi is eliminated from nymphal ticks in the first 24 hours of feeding and is unable to be transmitted to naïve mice. Conversely, ectopically producing CspA derived from B. burgdorferi or B. afzelii, but not B. garinii in a cspA-knockout strain restored spirochete survival in fed nymphs and tick-to-mouse transmission. Furthermore, a CspA point mutant, CspA-L246D that was defective in FH-binding, failed to survive in fed nymphs and at the inoculation site or bloodstream in mice. We also allowed those spirochete-infected nymphs to feed on C3-/- mice that lacked functional complement. The cspA-knockout B. burgdorferi or this mutant strain complemented with cspA variants or cspA-L246D was found at similar levels as wild type B. burgdorferi in the fed nymphs and mouse tissues. These novel findings suggest that the FH-binding activity of CspA protects spirochetes from complement-mediated killing in fed nymphal ticks, which ultimately allows Bbsl transmission to mammalian hosts.
Global investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science or by failing to investigate topics that benefit women and men equitably). Women across the world tend to be significantly underrepresented in research both as researchers and research participants, receive less research funding, and appear less frequently than men as authors on research publications. There is also some evidence that women are relatively disadvantaged as the beneficiaries of research, in terms of its health, societal and economic impacts. Historical gender biases may have created a path dependency that means that the research system and the impacts of research are biased towards male researchers and male beneficiaries, making it inherently difficult (though not impossible) to eliminate gender bias. In this commentary, we – a group of scholars and practitioners from Africa, America, Asia and Europe – argue that gender-sensitive research impact assessment could become a force for good in moving science policy and practice towards gender equity. Research impact assessment is the multidisciplinary field of scientific inquiry that examines the research process to maximise scientific, societal and economic returns on investment in research. It encompasses many theoretical and methodological approaches that can be used to investigate gender bias and recommend actions for change to maximise research impact. We offer a set of recommendations to research funders, research institutions and research evaluators who conduct impact assessment on how to include and strengthen analysis of gender equity in research impact assessment and issue a global call for action.
Bayessche Methoden zur Schätzung von Stammbäumen mit Verzweigungszeitpunkten aus molekularen Daten
(2009)
Ein großes Ziel der Evolutionsbiologie ist es, die Stammesgeschichte der Arten zu rekonstruieren. Historisch verwendeten Systematiker hierfür morphologische und anatomische Merkmale. Mit dem stetigen Zuwachs an verfügbaren Sequenzdaten werden heute verstärkt Methoden entwickelt und eingesetzt, welche die Rekonstruktion auf Basis von molekularen Daten ermöglichen. Im Fokus der aktuellen Forschung steht die Anwendung und Weiterentwicklung Bayesscher Methoden. Diese Methoden besitzen große Popularität, da sie in Verbindung mit Markov-Ketten-Monte-Carlo-Verfahren eingesetzt werden können, um einen Stammbaum zu vorgegebenen Spezies zu schätzen und dessen Variabilität zu bestimmen. Im Rahmen dieser Dissertation wurde die erweiterbare Software TreeTime entwickelt. TreeTime bietet Schnittstellen für die Einbindung von molekularen Evolutions- und Ratenänderungsmodellen und stellt neu entwickelte Methoden bereit, um Stammbäume mit Verzweigungszeitpunkten zu rekonstruieren. In TreeTime werden die molekularen Daten und die zeitlichen Informationen, wie z.B. Fossilfunde, in einem Bayes-Verfahren simultan berücksichtigt, um die Zeitpunkte der Artaufspaltungen genauer zu datieren. Für die Anwendung Bayesscher Methoden in der Rekonstruktion von Stammbäumen wird ein stochastisches Modell benötigt, das die Evolution der molekularen Sequenzen entlang den Kanten eines Stammbaums beschreibt. Der Mutationsprozess der Sequenzen wird durch ein molekulares Evolutionsmodell definiert. Die Verwendung der klassischen molekularen Evolutionsmodelle impliziert die Annahme einer konstanten Evolutionsgeschwindigkeit der Sequenzen im Stammbaum. Diese Annahme wird als Hypothese der molekularen Uhr bezeichnet und bildet die Grundlage zum Schätzen der Verzweigungszeiten des Stammbaums. Der Verzweigungszeitpunkt, an dem sich zwei Spezies im Stammbaum aufspalten, spiegelt sich in der Ähnlichkeit der zugehörigen molekularen Sequenzen. Je älter dieser Verzweigungszeitpunkt ist, desto größer ist die Anzahl der unterschiedlichen Positionen in den Sequenzen. Häufig ist jedoch die Annahme der molekularen Uhr verletzt, so dass in gewissen Teilbereichen eines Stammbaums eine erhöhte Evolutionsgeschwindigkeit nachweisbar ist. Falls die Verletzung konstanter Evolutionsgeschwindigkeiten nicht ausgeschlossen werden kann, sollten schwankende Mutationsraten in der Modellierung explizit berücksichtigt werden. Hierfür wurden verschiedene Ratenänderungsmodelle vorgeschlagen. Bisher sind nur wenige dieser Ratenänderungsmodelle in Softwarepaketen verfügbar und ihre Eigenschaften sind nicht ausreichend erforscht. Das Ziel dieser Arbeit ist die Entwicklung und Bereitstellung von Bayesschen Modellen und Methoden zum Schätzen von Stammbäumen mit Verzweigungszeitpunkten. Die Methoden sollten auch bei unterschiedlichen Evolutionsgeschwindigkeiten im Stammbaum anwendbar sein. Vorgestellt wird ein neues Ratenänderungsmodell, eine neue Möglichkeit der Angabe von flexiblen Beschränkungen für die Topologie des Stammbaums sowie die Nutzung dieser Beschränkungen für die zeitliche Kalibrierung. Das neue Raten Änderungsmodell sowie die topologischen und zeitlichen Beschränkungen werden in einen modularen Softwareentwurf eingebettet. Durch den erweiterbaren Entwurf können bestehende und zukünftige molekulare Evolutionsmodelle und Ratenänderungsmodelle in die Software eingebunden und verwendet werden. Die vorgestellten Modelle und Methoden werden gemäß dem Softwareentwurf in das neu entwickelte Programm TreeTime aufgenommen und effzient implementiert. Zusätzlich werden bereits vorhandene Modelle programmiert und eingebunden, die nicht in anderen Softwarepaketen verfügbar sind. Des Weiteren wird eine neue Methode entwickelt und angewendet, um die Passgenauigkeit eines Modells für die Apriori-Verteilung auf der Menge der Baumtopologien zu beurteilen. Diese Methode wird zur Auswahl geeigneter Modelle benutzt, indem eine Auswertung der beobachteten Baumtopologien der Datenbank TreeBASE durchgeführt wird. Anschließend wird die Software TreeTime in einer Simulationsstudie eingesetzt, um die Eigenschaften der implementierten Ratenänderungsmodelle zu vergleichen. Die Software wird für die Rekonstruktion des Stammbaums zu 38 Spezies aus der Familie der Eidechsen (Lacertidae) verwendet. Da die zugehörigen molekularen Daten von der Hypothese der molekularen Uhr abweichen, werden unterschiedliche Ratenänderungsmodelle bei der Rekonstruktion verwendet und abschließend bewertet. ........
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are commonly prescribed to treat acid-related disorders. Some direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have reduced efficacy in patients taking concomitant acid-reducing agents, including PPIs, due to interactions between drugs. We analyzed data from 9 multicenter, phase 2 and 3 trials to determine the efficacy and pharmacokinetics of an HCV therapeutic regimen comprising glecaprevir and pibrentasvir (glecaprevir/pibrentasvir) in patients taking concomitant acid-reducing agents.
METHODS: We analyzed data from 2369 patients infected with HCV genotypes 1-6 and compensated liver disease treated with an all-oral regimen of glecaprevir/pibrentasvir for 8-16 weeks. We compared efficacy and pharmacokinetics among patients receiving at least 1 dose of an acid-reducing agent (a PPI, an H2 blocker, or antacid). High-dose PPI was defined as daily dose greater than 20 mg omeprazole dose equivalent. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and to assess steady-state glecaprevir and pibrentasvir exposures in patients on acid-reducing agents.
RESULTS: Of the 401 patients (17%) who reported use of acid-reducing agents, 263 took PPIs (11%; 109 patients took a high-dose PPI and 154 patients took a low-dose PPI). Rates of SVR12 were 97.0% among patients who used acid-reducing agents and 97.5% among those not using acid-reducing agents (P = .6). An SVR12 was achieved in 96.3% taking a high-dose PPI and 97.4% taking a low-dose PPI, with no virologic failures in those receiving a high-dose PPI (P = .7). Glecaprevir, but not pibrentasvir, bioavailability was affected; its exposure decreased by 41% in patients taking a high-dose PPI.
CONCLUSIONS: In an analysis of data from 9 clinical trials, we observed a high rate of SVR12 (approximately 97%) among patients treated with glecaprevir/pibrentasvir for HCV infection-even among patients taking concomitant ARA or high-dose PPI. This was despite decreased glecaprevir exposures in patients when on high-dose PPIs. ClinicalTrials.gov numbers, NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02640482 (ENDURANCE-2), NCT02640157 (ENDURANCE-3), NCT02636595 (ENDURANCE-4), NCT02642432 (EXPEDITION-1), NCT02651194 (EXPEDITION-4), NCT02446717 (MAGELLAN-I).
Camellia sinensis is one of the major crops grown in Taiwan and has been widely cultivated around the island. Tea leaves are prone to various fungal infections, and leaf spot is considered one of the major diseases in Taiwan tea fields. As part of a survey on fungal species causing leaf spots on tea leaves in Taiwan, 19 fungal strains morphologically similar to the genus Diaporthe were collected. ITS (internal transcribed spacer), tef1-α (translation elongation factor 1-α), tub2 (beta-tubulin), and cal (calmodulin) gene regions were used to construct phylogenetic trees and determine the evolutionary relationships among the collected strains. In total, six Diaporthe species, including one new species, Diaporthe hsinchuensis, were identified as linked with leaf spot of C. sinensis in Taiwan based on both phenotypic characters and phylogeny. These species were further characterized in terms of their pathogenicity, temperature, and pH requirements under laboratory conditions. Diaporthe tulliensis, D. passiflorae, and D. perseae were isolated from C. sinensis for the first time. Furthermore, pathogenicity tests revealed that, with wound inoculation, only D. hongkongensis was pathogenic on tea leaves. This investigation delivers the first assessment of Diaporthe taxa related to leaf spots on tea in Taiwan.
Pathogens possess the ability to adapt and survive in some host species but not in others–an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.
Heart valve disease is a major clinical problem worldwide. Cardiac valve development and homeostasis need to be precisely controlled. Hippo signaling is essential for organ development and tissue homeostasis, while its role in valve formation and morphology maintenance remains unknown. VGLL4 is a transcription cofactor in vertebrates and we found it was mainly expressed in valve interstitial cells at the post-EMT stage and was maintained till the adult stage. Tissue specific knockout of VGLL4 in different cell lineages revealed that only loss of VGLL4 in endothelial cell lineage led to valve malformation with expanded expression of YAP targets. We further semi-knockout YAP in VGLL4 ablated hearts, and found hyper proliferation of arterial valve interstitial cells was significantly constrained. These findings suggest that VGLL4 is important for valve development and manipulation of Hippo components would be a potential therapy for preventing the progression of congenital valve disease.
Strong electron correlations can give rise to extraordinary properties of metals with renormalized Landau quasiparticles. Near a quantum critical point, these quasiparticles can be destroyed and non-Fermi liquid behavior ensues. YbRh2Si2 is a prototypical correlated metal exhibiting the formation of quasiparticle and Kondo lattice coherence, as well as quasiparticle destruction at a field-induced quantum critical point. Here we show how, upon lowering the temperature, Kondo lattice coherence develops at zero field and finally gives way to non-Fermi liquid electronic excitations. By measuring the single-particle excitations through scanning tunneling spectroscopy, we find the Kondo lattice peak displays a non-trivial temperature dependence with a strong increase around 3.3 K. At 0.3 K and with applied magnetic field, the width of this peak is minimized in the quantum critical regime. Our results demonstrate that the lattice Kondo correlations have to be sufficiently developed before quantum criticality can set in.
Efficient derivation of extraembryonic endoderm stem cell lines from mouse postimplantation embryos
(2016)
Various types of stem cell lines have been derived from preimplantation or postimplantation mouse embryos: embryonic stem cell lines, epiblast stem cell lines, and trophoblast stem cell lines. It is not known if extraembryonic endoderm stem (XEN) cell lines can be derived from postimplantation mouse embryos. Here, we report the derivation of 77 XEN cell lines from 85 postimplantation embryos at embryonic day E5.5 or E6.5, in parallel to the derivation of 41 XEN lines from 69 preimplantation embryos at the blastocyst stage. We attain a success rate of 100% of XEN cell line derivation with our E5.5 whole-embryo and E6.5 disaggregated-embryo methods. Immunofluorescence and NanoString gene expression analyses indicate that the XEN cell lines that we derived from postimplantation embryos (post-XEN) are very similar to the XEN cell lines that we derived from preimplantation embryos (pre-XEN) using a conventional method. After injection into blastocysts, post-XEN cells contribute to extraembryonic endoderm in chimeras at E6.5 and E7.5.
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the US and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H (FH). To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds FH to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because FH-binding cloaks potentially protective epitopes. We modified CspZ by conjugating to virus-like particles (VLP-CspZ) and eliminating FH binding (modified VLP-CspZ) to increase immunogenicity. We observed greater bactericidal antibody titers in mice vaccinated with modified VLP-CspZ: A serum dilution of 1:395 (modified VLP-CspZ) vs 1:143 (VLP-CspZ) yielded 50% borreliacidal activity. Immunizing mice with modified VLP-CspZ cleared spirochete infection, as did passive transfer of elicited antibodies. This work developed a novel Lyme disease vaccine candidate by conjugating CspZ to VLP and eliminating FH-binding ability. Such a strategy of conjugating an antigen to a VLP and eliminating binding to the target ligand can serve as a general model for developing vaccines against other bacterial infectious agents.
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Background. Intervertebral disc degeneration (IDD) at the cervicothoracic junction of spine is clinically relevant, however, little attention had been paid. T2 mapping and magnetic transfer ratio (MTR) are useful magnetic resonance imaging (MRI) techniques to quantitatively evaluate IDD, revealing the biochemical changes within the intervertebral disc. To compare T2 mapping with MTR imaging regarding their accuracy to quantitatively diagnose intervertebral disc degeneration at the cervicothoracic junction, influences of anatomical level, gender, age, and Pfrrmann grade of T2 relaxation time values and MTR values were evaluated.
Methods. Sixty-seven patients with neck and upper back pain were included and examined with both T2 mapping andMTR imaging. Te Pfrrmann grade, T2 relaxation time values, and MTR value of each disc between C7 and T3 were measured. Diferences were investigated among diferent segmental levels, genders, age ranges, and Pfrrmann grades. Te diagnostic accuracy of both MRI techniques was compared using the receiver operating characteristic (ROC) curves.
Results. No signifcant diference was detected comparing T2 relaxation time values or MTR values among diferent anatomical levels, genders, and segmental levels. And we generally found that T2 relaxation time values decreased, while MTR value increased with increasing age. Importantly, we demonstrated the signifcant correlation between either T2 relaxation time values or MTR value and Pfrrmann grade.
Conclusion. We proved the better accuracy of T2 mapping over MTR imaging to quantitatively evaluate the intervertebral disc degeneration of the cervicothoracic junction.
Conventional treatments for mood disorders primarily focus on reducing negative affect, but little on enhancing positive affect. Loving-kindness meditation (LKM) is a traditional meditation practice directly oriented toward enhancing unconditional and positive emotional states of kindness towards oneself and others. We report here two independent and uncontrolled studies carried out at different centers, one in Boston, USA (n = 10), and one in Frankfurt, Germany (n = 8), to examine the potential therapeutic utility of a brief LKM group intervention for symptoms of dysthymia and depression. Results at both centers suggest that LKM was associated with large-sized effects on self-reported symptoms of depression (d = 3.33 and 1.90), negative affect (d = 1.98 and 0.92), and positive affect (d = 1.63 and 0.94). Large effects were also found for clinician-reported changes in depression, rumination and specific positive emotions, and moderate effects for changes in adaptive emotion regulation strategies. The qualitative data analyses provide additional support for the potential clinical utility of the intervention. This proof-of-concept evaluation of LKM as a clinical strategy warrants further investigation.
Background: While the efficacy of cognitive therapy (CT) has been well established for social anxiety disorder (SAD) in several randomized controlled trials, there are still large differences between trials with respect to effect sizes. The present study investigates the question of whether enhanced training and the use of behavioral experiments (BEs) increases the efficacy of traditional CT, based on verbal methods of cognitive restructuring. Methods/design: A mixed within/between conditions design will be applied, with therapists and patients being randomly allocated to one of two conditions: (1) training of CT plus BEs, (2) training of CT “as usual”. Sixty patients with the primary diagnosis of SAD will be recruited and treated in the outpatient clinic of the Department of Psychology, University of Frankfurt. To ensure adherence to therapist protocols, all therapists will be trained and supervised by the project coordinators. In addition, videotaped treatment sessions will be independently evaluated to guarantee both adherence to protocols and the quality of the intervention. Treatment effects will be assessed by independent SAD symptom ratings using the Liebowitz Social Anxiety Scale as the primary outcome measure and self-report measures as secondary outcome measures. Discussion: The present cognitive behavioral therapy (CBT) trial will be the first to clarify the contribution of BEs to the efficacy of CT in a randomized controlled design. Study results are relevant to clinical training and implementation of evidence-based treatments. Trial registration: German Clinical Trials Register International Clinical Trials Registry Platform (ICTRP) identifier: DRKS00014349. Trial status: recruiting.
The planthopper genus Arcofaciella Fennah, 1956 (Hemiptera: Fulgoromorpha: Delphacidae) is reviewed. Four species are recognized, of which A. obflexa Guo & Liang, 2005 and A. verrucosa Fennah, 1956 are redescribed, and one new species, A. indiana sp. nov., is described. Habitus photos for adults and illustrations of male genitalia (excluding A. penangensis (Muir, 1919)) are given. A key for identifying the species of Arcofaciella is also provided.
The planthopper genus Augilina Melichar, 1914, is recorded in China for the first time. Two new species of the genus Augilina, A. tetraina Chen & Gong sp. nov. and A. triaina Chen & Gong sp. nov., are described and illustrated from South China. The genus now has a total of four described species. New generic characteristics are proposed and photographs of the new species are provided. A checklist and a key to the species of Augilina are also included.
The Taiwan cobra (Naja naja atra) chymotrypsin inhibitor (NACI) consists of 57 amino acids and is related to other Kunitz-type inhibitors such as bovine pancreatic trypsin inhibitor (BPTI) and Bungarus fasciatus fraction IX (BF9), another chymotrypsin inhibitor. Here we present the solution structure of NACI. We determined the NMR structure of NACI with a root-mean-square deviation of 0.37 Å for the backbone atoms and 0.73 Å for the heavy atoms on the basis of 1,075 upper distance limits derived from NOE peaks measured in its NOESY spectra. To investigate the structural characteristics of NACI, we compared the three-dimensional structure of NACI with BPTI and BF9. The structure of the NACI protein comprises one 310-helix, one α-helix and one double-stranded antiparallel β-sheet, which is comparable with the secondary structures in BPTI and BF9. The RMSD value between the mean structures is 1.09 Å between NACI and BPTI and 1.27 Å between NACI and BF9. In addition to similar secondary and tertiary structure, NACI might possess similar types of protein conformational fluctuations as reported in BPTI, such as Cys14–Cys38 disulfide bond isomerization, based on line broadening of resonances from residues which are mainly confined to a region around the Cys14–Cys38 disulfide bond.
Three new species of the bamboo-feeding genus Bambusiphaga Huang & Ding, 1979, B. parvula sp. nov., B. angulosa sp. nov., and B. nigrigena sp. nov., are described and illustrated from China. A key to species of the genus is provided. Habitus photos for adults and illustrations of male genitalia are also given.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt(s_NN)=130 GeV using the STAR TPC at RHIC. The elliptic flow signal, v_2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Two new species, Russula pseudopunicea C.L.Hou, G.Q.Cheng & H.Zhou sp. nov. and R. wulingshanensis C.L.Hou, G.Q.Cheng & H.Zhou sp. nov., from Yanshan mountains in North China are described herein based on morphological and phylogenetic analyses of nrITS, and nrLSU-rpb2-mtSSU gene regions. Morphologically, R. pseudopunicea sp. nov. is characterised by a reddish brown, light brown to brownish orange pileus with a greyish yellow margin, subglobose to broadly ellipsoid basidiospores with warts forming a partial reticulum and pleurocystidia turning grey to purplish red in sulfovanillin. Russula wulingshanensis sp. nov. is characterised by a purple pinkish pileus with a grey-white to grey-purple margin, subglobose to broadly ellipsoid basidiospores with isolated warts, and pileocystidia turning black in sulfovanillin. Phylogenetic and morphological analyses resolved the two species in Russula subg. Heterophyllidia. Russula pseudopunicea sp. nov. and R. wulingshanensis sp. nov. were placed in the lineages of subsect. Virescentinae and subsect. Griseinae, respectively.
The emerging relapsing fever spirochete Borrelia (B.) miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD). More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a plasmin(ogen) receptor that enables B. miyamotoi to interact with the serine protease plasmin(ogen). Recombinant CbiA was able to bind plasminogen in a dose-dependent fashion. Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was inhibited by the lysine analog tranexamic acid as well as increasing ionic strength. Of relevance, plasminogen bound to CbiA can be converted by urokinase-type plasminogen activator (uPa) to active plasmin which cleaved both, the chromogenic substrate S-2251 and its physiologic substrate fibrinogen. Concerning the involvement of specific amino acids in the interaction with plasminogen, lysine residues located at the C-terminus are frequently involved in the binding as reported for various other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine residues located within the C-terminal domain were substituted with alanine to generate single, double, triple, and quadruple point mutants. However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the C-terminus might be involved in the interaction.
The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi–Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.
Virus-infected cells are eliminated by cytotoxic T lymphocytes, which recognize viral epitopes displayed on major histocompatibility complex class I molecules at the cell surface. Herpesviruses have evolved sophisticated strategies to escape this immune surveillance. During the lytic phase of EBV infection, the viral factor BNLF2a interferes with antigen processing by preventing peptide loading of major histocompatibility complex class I molecules. Here we reveal details of the inhibition mechanism of this EBV protein. We demonstrate that BNLF2a acts as a tail-anchored protein, exploiting the mammalian Asna-1/WRB (Get3/Get1) machinery for posttranslational insertion into the endoplasmic reticulum membrane, where it subsequently blocks antigen translocation by the transporter associated with antigen processing (TAP). BNLF2a binds directly to the core TAP complex arresting the ATP-binding cassette transporter in a transport-incompetent conformation. The inhibition mechanism of EBV BNLF2a is distinct and mutually exclusive of other viral TAP inhibitors.
This paper provides new geochemical data focusing on valuable elements in the coal, parting, and floor samples in the No. 5 coal seam of the Taiyuan Formation from the Wujiawan mine, Datong coalfield, northern China. The minerals mainly consist of kaolinite, calcite, and pyrite, as well as trace amounts of quartz and illite. The No. 5 coal is enriched in Li, Ga, high field strength elements (HFSEs), and rare earth elements and yttrium (REY) when compared with world hard coals. Of particular interest is the high average concentration of Li (67.66 μg/g), which is around seven times higher than the value for world hard coals. Lithium, Ga, and HFSEs have strong inorganic affinities, whereas REY have organic affinities. The main carrier of Li, Ga, and HFSEs is aluminosilicate minerals, while REY appear to occur with organophosphorus. These HFSEs are enriched, both in the parting and in the adjacent coal samples. This suggests that these elements are likely to leach out during the diagenetic process. The distribution patterns of REY, along with the ratio of Al2O3/TiO2 and the figure of Zr/TiO2 vs. Nb/Y are suggestive of their derivation from felsic parent material. In the northern and eastern part of the Datong coalfield, there are several regions where the Li content is higher than the mineable grade, in particular in the northern Datong coalfield where there is a mine with an Li content of 294.6 μg/g. This is significantly higher than the mineable grade. Therefore, there is a potential for financially viable recovery of Li in these coals of the Datong coalfield.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
Borrelia miyamotoi, a relapsing fever spirochete transmitted by Ixodid ticks causes B. miyamotoi disease (BMD). To evade the human host´s immune response, relapsing fever borreliae, including B. miyamotoi, produce distinct variable major proteins. Here, we investigated Vsp1, Vlp15/16, and Vlp18 all of which are currently being evaluated as antigens for the serodiagnosis of BMD. Comparative analyses identified Vlp15/16 but not Vsp1 and Vlp18 as a plasminogen-interacting protein of B. miyamotoi. Furthermore, Vlp15/16 bound plasminogen in a dose-dependent fashion with high affinity. Binding of plasminogen to Vlp15/16 was significantly inhibited by the lysine analog tranexamic acid suggesting that the protein–protein interaction is mediated by lysine residues. By contrast, ionic strength did not have an effect on binding of plasminogen to Vlp15/16. Of relevance, plasminogen bound to the borrelial protein cleaved the chromogenic substrate S-2251 upon conversion by urokinase-type plasminogen activator (uPa), demonstrating it retained its physiological activity. Interestingly, further analyses revealed a complement inhibitory activity of Vlp15/16 and Vlp18 on the alternative pathway by a Factor H-independent mechanism. More importantly, both borrelial proteins protect serum sensitive Borrelia garinii cells from complement-mediated lysis suggesting multiple roles of these two variable major proteins in immune evasion of B. miyamotoi.
Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.
There is evidence that endothelial nitric-oxide synthase (eNOS) is regulated by reciprocal dephosphorylation of Thr497 and phosphorylation of Ser1179. To examine the interrelationship between these sites, cells were transfected with wild-type (WT), T497A, T497D, S1179D, and T497A/S1179D eNOS and activity, NO release and eNOS localization were assessed. Although eNOS T497A, S1179D and T497A/S1179D eNOS had greater enzymatic activity than did WT eNOS in lysates, basal production of NO from cells was markedly reduced in cells transfected with T497A and T497A/S1179D eNOS but augmented in cells transfected with S1179D eNOS. Stimulating cells with ATP or ionophore normalized the loss of function seen with T497A and T497A/S1179D eNOS to levels observed with WT and S1179D eNOS, respectively. Despite these functional differences, the localization of eNOS mutants were similar to WT. Because both T497A and T497A/S1179D eNOS exhibited higher enzyme activity but reduced production of NO, we examined whether these mutations were “uncoupling” NO synthesis. T497A and T497A/S1179D eNOS generated 2-3 times more superoxide anion than WT eNOS, and both basal and stimulated interactions of T497A/S1179D eNOS with hsp90 were reduced in co-immunoprecipitation experiments. Thus, the phosphorylation/dephosphorylation of Thr497 may be an intrinsic switch mechanism that determines whether eNOS generates NO versus superoxide in cells.
The results from the STAR Collaboration on directed flow (v1), elliptic flow (v2), and the fourth harmonic (v4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrt[sNN]=200GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a blast-wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v2, scaling with the number of constituent quarks and parton coalescence are discussed. For v4, scaling with v22 and quark coalescence are discussed.
This paper deals with the brachypterous Meconematini, including three new genera, Acosmetides gen. nov., Neocyrtopsides gen. nov. and Macrocosmetura gen. nov. Five new species are described: Acosmetides peltates gen. et sp. nov., Acosmetides dilobosa gen. et sp. nov., Acosmetides platycerca gen. et sp. nov., Neocyrtopsides bispina gen. et sp. nov. and Macrocosmetura truncata gen. et sp. nov. Two new combinations are proposed: Acosmetides trigentis (Wang, Bian & Shi, 2016) gen. et comb. nov. and Neocyrtopsides platycata (Shi & Zheng, 1994) gen. et comb. nov.
Serial quantification of BCR–ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR–ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 106, 1.08±0.11 × 105, 1.03±0.10 × 104, 1.02±0.09 × 103, 1.04±0.10 × 102 and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR–ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR–ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).
The p300/CBP‐associated factor (PCAF) and related GCN5 bromodomain‐containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine‐based L‐45 (dubbed L‐Moses) as the first potent, selective, and cell‐active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)‐(−)‐norephedrine furnished L‐45 in enantiopure form. L‐45 was shown to disrupt PCAF‐Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co‐crystal structure of L‐45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L‐45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell‐permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use.
We present a systematic analysis of two-pion interferometry in Au+Au collisions at sqrt[sNN]=200GeV using the STAR detector at Relativistic Heavy Ion Collider. We extract the Hanbury-Brown and Twiss radii and study their multiplicity, transverse momentum, and azimuthal angle dependence. The Gaussianness of the correlation function is studied. Estimates of the geometrical and dynamical structure of the freeze-out source are extracted by fits with blast-wave parametrizations. The expansion of the source and its relation with the initial energy density distribution is studied.
We present three-particle mixed-harmonic correlations 〈cos(mφa + nφb − (m + n)φc )〉 for harmonics m, n = 1 − 3 for charged particles in √sN N = 200 GeV Au+Au collisions at RHIC. These measurements provide information on the three-dimensional structure of the initial collision zone and are important for constraining models of a subsequent low-viscosity quark–gluon plasma expansion phase. We investigate correlations between the first, second and third harmonics predicted as a consequence of fluctuations in the initial state. The dependence of the correlations on the pseudorapidity separation between particles show hints of a breaking of longitudinal invariance. We compare our results to a number of state-of-the art hydrodynamic calculations with different initial states and temperature dependent viscosities. These measurements provide important steps towards constraining the temperature dependent viscosity and longitudinal structure of the initial state at RHIC.
Fluctuations of conserved quantities such as baryon number, charge, and strangeness are sensitive to the correlation length of the hot and dense matter created in relativistic heavy-ion collisions and can be used to search for the QCD critical point. We report the first measurements of the moments of net-kaon multiplicity distributions in Au+Au collisions at √sNN = 7.7, 11.5, 14.5, 19.6, 27, 39, 62.4, and 200 GeV. The collision centrality and energy dependence of the mean (M), variance (σ 2), skewness (S), and kurtosis (κ) for net-kaon multiplicity distributions as well as the ratio σ 2/M and the products Sσ and κσ 2 are presented. Comparisons are made with Poisson and negative binomial baseline calculations as well as with UrQMD, a transport model (UrQMD) that does not include effects from the QCD critical point. Within current uncertainties, the net-kaon cumulant ratios appear to be monotonic as a function of collision energy.
New measurements of directed flow for charged hadrons, characterized by the Fourier coefficient v1, are presented for transverse momenta pT, and centrality intervals in Au+Au collisions recorded by the STAR experiment for the center-of-mass energy range √sN N = 7.7–200 GeV. The measurements underscore the importance of momentum conservation, and the characteristic dependencies on √sN N , centrality and pT are consistent with the expectations of geometric fluctuations generated in the initial stages of the collision, acting in concert with a hydrodynamic-like expansion. The centrality and pT dependencies of veven 1 , as well as an observed similarity between its excitation function and that for v3, could serve as constraints for initial-state models. The veven 1 excitation function could also provide an important supplement to the flow measurements employed for precision extraction of the temperature dependence of the specific shear viscosity.
A collection of 1149 otoliths of the Ypresian and Ypresian–Lutetian transition (early Eocene) from 18 sites across five states in the eastern and southern regions of the USA was analyzed. In total, 33 otolith-based taxa are documented, of which 27 are identified at the species level. Nine of these are introduced as new species: “Conger” biaculeatus sp. nov., Bauzaia gibbosa sp. nov., Ampheristus brevicaudatus sp. nov., Symmetrosulcus virginicus sp. nov., Neobythites longesulcatus sp. nov., “Neobythites” pamunkeyensis sp. nov., “Neobythites” stringeri sp. nov., Waitakia dorsogibbosa sp. nov., and “Haemulon” ypresiensis sp. nov. The assemblages are distinct when compared to their younger Eocene counterparts in America. This distinction is primarily characterized by the high proportion of the newly introduced species or exclusive Ypresian species. Additionally, we highlight the presence of 10 amphi-Atlantic species originally described in European deposits. Significantly, the composition of the otolith collection supports the interpretation of a shallow-water environment for the sampled sites during the Ypresian. This ecological setting appears to persist into the subsequent middle and late Eocene within the same geographic region.
Four new species of the genus Catonidia Uhler, 1896, C. triangula sp. nov., C. saccata sp. nov., C. trilobata sp. nov. and C. uncinata sp. nov. from China (Fujian, Guizhou, Yunnan and Hainan provinces), are described and illustrated, giving the genus 14 species in total. A checklist and key to all known species of Catonidia are provided, as well as a map of their geographic distributions.
Background: Pythium ultimum (P. ultimum) is a ubiquitous oomycete plant pathogen responsible for a variety of diseases on a broad range of crop and ornamental species. Results: The P. ultimum genome (42.8 Mb) encodes 15,290 genes and has extensive sequence similarity and synteny with related Phytophthora species, including the potato blight pathogen Phytophthora infestans. Whole transcriptome sequencing revealed expression of 86% of genes, with detectable differential expression of suites of genes under abiotic stress and in the presence of a host. The predicted proteome includes a large repertoire of proteins involved in plant pathogen interactions although surprisingly, the P. ultimum genome does not encode any classical RXLR effectors and relatively few Crinkler genes in comparison to related phytopathogenic oomycetes. A lower number of enzymes involved in carbohydrate metabolism were present compared to Phytophthora species, with the notable absence of cutinases, suggesting a significant difference in virulence mechanisms between P. ultimum and more host specific oomycete species. Although we observed a high degree of orthology with Phytophthora genomes, there were novel features of the P. ultimum proteome including an expansion of genes involved in proteolysis and genes unique to Pythium. We identified a small gene family of cadherins, proteins involved in cell adhesion, the first report in a genome outside the metazoans. Conclusions: Access to the P. ultimum genome has revealed not only core pathogenic mechanisms within the oomycetes but also lineage specific genes associated with the alternative virulence and lifestyles found within the pythiaceous lineages compared to the Peronosporaceae.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
We present a measurement of inclusive J /ψ production at mid-rapidity (|y| < 1) in p+p collisions at a center-of-mass energy of √s = 200 GeV with the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The differential production cross section for J /ψ as a function of transverse momentum (p T ) for 0 < p T < 14 GeV/c and the total cross section are reported and compared to calculations from the color evaporation model and the non-relativistic Quantum Chromodynamics model. The dependence of J /ψ relative yields in three p T intervals on charged-particle multiplicity at mid-rapidity is measured for the first time in p+p collisions at √s = 200 GeV and compared with that measured at √s = 7 TeV, PYTHIA8 and EPOS3 Monte Carlo generators, and the Percolation model prediction.
The fossil otoliths of the southern USA have been known for more than 130 years and are among the richest assemblages worldwide. However, previous studies are often scattered and with outdated systematic scheme. A collection of over 25000 otoliths ranging in age from the Lutetian to the Priabonian from 47 sites in five states in the eastern and southern USA is analysed here. Combined with the earlier described material, at least 101 otolith-based taxa are documented, of which 83 are identified at species level. Fourteen of these are introduced as new species: Elopothrissus bernardlemorti sp. nov., “Muraenesox” barrytownensis sp. nov., Pseudophichthys texanus sp. nov., Paraconger wechesensis sp. nov., Neoopisthopterus weltoni sp. nov., “aff. Glyptophidium” stringeri sp. nov., Symmetrosulcus dockeryi sp. nov., Mene garviei sp. nov., “Citharus” varians sp. nov., Waitakia beelzebub sp. nov., Astroscopus compactus sp. nov., Parascombrops yanceyi sp. nov., Anisotremus rambo sp. nov., and Pagellus pamunkeyensis sp. nov. The assemblages are distinct fom contemporary European faunas by the complete lack of mesopelagic fish otoliths, and by the presence of sciaenids. Dominant taxa in the American Eocene are the Ophidiidae, Sciaenidae, Lactariidae, and Congridae. They indicate shallow-water environments for all the sampled sites. The notable abundance of those taxa suggests that they could have a higher turnover rate, and provided fundamental nutrition in the local Paleogene marine ecosystem. Further analyses of the species in the stratigraphic succession revealed that a faunal turnover between the Claiborne and Jackson seas was evident in teleosts, and it might be more widespread in other marine organisms in the region.
Tortonian teleost otoliths from northern Italy: taxonomic synthesis and stratigraphic significance
(2017)
The Tortonian fish otoliths of northern Italy have been studied for more than a century and represent one of the best known otolith-based teleost faunas in the Miocene of the Mediterranean Basin. Yet with the growing knowledge on Recent otoliths, an updated taxonomic overview of this fauna is needed. Moreover, new material from hemipelagic Tortonian marls sampled at nine localities is described herein, revealing 109 taxa of which 88 are recognised at species level. Four of these are new: Coryphaenoides biobtusus sp. nov., “Merluccius” rattazzii sp. nov., Neobythites auriculatus sp. nov. and Lesueurigobius stironensis sp. nov. The compilation of previously studied and newly acquired material revealed a total of 118 nominal Tortonian species. At generic level, the fauna is characterised by many modern forms; more than 90% can be assigned to present day genera. At species level, however, more than half of the represented taxa are extinct. Based on the fossil otolith record, the Tortonian fauna of the Mediterranean is most similar to that of the Langhian (Badenian) of the Central Paratethys by sharing many extinct Miocene species, but it is also very close to that of the Pliocene Mediterranean, by sharing many modern Atlantic-Mediterranean forms. The Tortonian fauna is further characterised by many species that are apparently confined to the upper Miocene, resulting in a unique combination of its taxonomic composition.
Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs; however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64–1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to “contemporary NOACs”. The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding; however, more randomized controlled trials are warranted.
We present the first measurement of the proton–Ω correlation function in heavy-ion collisions for the central (0–40%) and peripheral (40–80%) Au + Au collisions at √sNN = 200 GeV by the STAR experiment at the Relativistic Heavy-Ion Collider (RHIC). Predictions for the ratio of peripheral collisions to central collisions for the proton–Ω correlation function are sensitive to the presence of a nucleon– bound state. These predictions are based on the proton– interaction extracted from (2 + 1)-flavor lattice QCD calculations at the physical point. The measured ratio of the proton–Ω correlation function between the peripheral (small system) and central (large system) collisions is less than unity for relative momentum smaller than 40 MeV/c. Comparison of our measured correlation ratio with theoretical calculation slightly favors a proton– bound system with a binding energy of ∼ 27 MeV.
Quark interactions with topological gluon configurations can induce chirality imbalance and local parity violation in quantum chromodynamics. This can lead to electric charge separation along the strong magnetic field in relativistic heavy-ion collisions – the chiral magnetic effect (CME). We report measurements by the STAR collaboration of a CME-sensitive observable in p + Au and d + Au collisions at 200 GeV, where the CME is not expected, using charge-dependent pair correlations relative to a third particle. We observe strong charge-dependent correlations similar to those measured in heavy-ion collisions. This bears important implications for the interpretation of the heavy-ion data.
We report the direct virtual photon invariant yields in the transverse momentum ranges 1 < pT < 3 GeV/c and 5 < pT < 10 GeV/c at mid-rapidity derived from the dielectron invariant mass continuum region 0.10 < Mee < 0.28 GeV/c2 for 0–80% minimum-bias Au+Au collisions at √sN N = 200 GeV. A clear excess in the invariant yield compared to the nuclear overlap function T A A scaled p + p reference is observed in the pT range 1 < pT < 3 GeV/c. For pT > 6 GeV/c the production follows T A A scaling. Model calculations with contributions from thermal radiation and initial hard parton scattering are consistent ithin uncertainties with the direct virtual photon invariant yield.
The polarization of Λ and Λ¯ hyperons along the beam direction has been measured relative to the second and third harmonic event planes in isobar Ru+Ru and Zr+Zr collisions at √sNN = 200 GeV. This is the first experimental evidence of the hyperon polarization by the triangular flow originating from the initial density fluctuations. The amplitudes of the sine modulation for the second and third harmonic results are comparable in magnitude, increase from central to peripheral collisions, and show a mild pT dependence. The azimuthal angle dependence of the polarization follows the vorticity pattern expected due to elliptic and triangular anisotropic flow, and qualitatively disagree with most hydrodynamic model calculations based on thermal vorticity and shear induced contributions. The model results based on one of existing implementations of the shear contribution lead to a correct azimuthal angle dependence, but predict centrality and pT dependence that still disagree with experimental measurements. Thus, our results provide stringent constraints on the thermal vorticity and shear-induced contributions to hyperon polarization. Comparison to previous measurements at RHIC and the LHC for the second-order harmonic results shows little dependence on the collision system size and collision energy.
The inclusive J/ψ transverse momentum spectra and nuclear modification factors are reported at midrapidity (|y| < 1.0) in Au+Au collisions at √sN N = 39, 62.4 and 200 GeV taken by the STAR experiment. A suppression of J/ψ production, with respect to the production in p + p scaled by the number of binary nucleon–nucleon collisions, is observed in central Au+Au collisions at these three energies. No significant energy dependence of nuclear modification factors is found within uncertainties. The measured nuclear modification factors can be described by model calculations that take into account both suppression of direct J/ψ production due to the color screening effect and J/ψ regeneration from recombination of uncorrelated charm–anticharm quark pairs.
The transversity distribution, which describes transversely polarized quarks in transversely polarized nucleons, is a fundamental component of the spin structure of the nucleon, and is only loosely constrained by global fits to existing semi-inclusive deep inelastic scattering (SIDIS) data. In transversely polarized p↑+p collisions it can be accessed using transverse polarization dependent fragmentation functions which give rise to azimuthal correlations between the polarization of the struck parton and the final state scalar mesons.This letter reports on spin dependent di-hadron correlations measured by the STAR experiment. The new dataset corresponds to 25 pb−1 integrated luminosity of p↑+p collisions at s=500 GeV, an increase of more than a factor of ten compared to our previous measurement at s=200 GeV. Non-zero asymmetries sensitive to transversity are observed at a Q2 of several hundred GeV and are found to be consistent with the former measurement and a model calculation. We expect that these data will enable an extraction of transversity with comparable precision to current SIDIS datasets but at much higher momentum transfers where subleading effects are suppressed.
We present the first measurements of charge-dependent correlations on angular difference variables η1 − η2 (pseudorapidity) and φ1 − φ2 (azimuth) for primary charged hadrons with transverse momentum 0.15 <= pt <= 2 GeV/c and |η| <= 1.3 from Au–Au collisions at √sNN = 130 GeV. We observe correlation structures not predicted by theory but consistent with evolution of hadron emission geometry with increasing centrality from one-dimensional fragmentation of color strings along the beam direction to an at least two-dimensional hadronization geometry along the beam and azimuth directions of a hadron-opaque bulk medium.
J/ψ suppression has long been considered a sensitive signature of the formation of the Quark-Gluon Plasma (QGP) in relativistic heavy-ion collisions. In this letter, we present the first measurement of inclusive J/ψ production at mid-rapidity through the dimuon decay channel in Au+Au collisions at √sNN = 200 GeV with the STAR experiment. These measurements became possible after the installation of the Muon Telescope Detector was completed in 2014. The J/ψ yields are measured in a wide transverse momentum (pT) range of 0.15 GeV/c to 12 GeV/c from central to peripheral collisions. They extend the kinematic reach of previous measurements at RHIC with improved precision. In the 0-10% most central collisions, the J/ψ yield is suppressed by a factor of approximately 3 for pT > 5 GeV/c relative to that in p + p collisions scaled by the number of binary nucleon-nucleon collisions. The J/ψ nuclear modification factor displays little dependence on pT in all centrality bins. Model calculations can qualitatively describe the data, providing further evidence for the color-screening effect experienced by J/ψ mesons in the QGP.
Fungi belonging to the Rhytismatales (Ascomycota) are parasites or endophytes of plants, some are saprophytes. Their fruiting bodies are localized in different organs of the host plants belonging to many different families of gymnosperms and angiosperms. Many species of Rhytismatales are known on species of Pinaceae, Ericaceae, and Poaceae. These fungi usually have ascomata that are more or less embedded in host tissue and open by longitudinal or radial splits. They have a more or less carbonized covering stroma, thin-walled, iodine negative asci, and ascospores usually covered by gelatinous sheaths.
In the present study, two lists of species of Rhytismatales in China are presented. One is based on literature and includes 103 species in 15 genera. The second one contains the names of the species in the present study, 57 species in 20 genera based on 90 specimens I collected in the Yunnan and Anhui province in China during July to August in 2001. 31 species in the second list are new species or new records for China, so we presently know 134 species in 22 genera of Rhytismatales for China. 28 new species of Rhytismatales are proposed, 21 species from the Yunnan province and seven from the Anhui province. Among them, three new species are proposed in three new genera, Nematococcomyces, New Genus 1, and New Genus 2, respectively. The 28 new species are Cerion sp., Coccomyces spp. 1-2, Colpoma spp. 1-2, Hypoderma spp. 1-6, Lirula sp., Lophodermella sp., Lophodermium spp. 1-5, Nematococcomyces rhododendri C.-L. Hou, M. Piepenbr. & Oberw., Neococcomyces sp., New Genus 1 sp., New Genus 2 sp., Rhytisma spp. 1-2, Soleella sp., Terriera spp. 1-2, and Therrya sp. The genus Davisomycella is proposed as a synonym of Lophodermella based on observations of the morphology, ecology, and the infected organ. The four genera Cerion, Naemacyclus, Terriera, and Therrya, and three species, Hypoderma rubi, Lophodermium uncinatum, and Naemacyclus pinastri, are reported for the first time for China. All the new taxa, the newly recorded ones, as well as six species which had not been illustrated in detail before, are carefully described and illustrated by line drawings in the present study.
The results show that species of Rhytismatales are highly diverse especially in the natural vegetation in high mountainous areas in China. Most species of Rhytismatales are conspicuously host specific. The diversity of Rhytismatales is closely related to that of the preferred hosts, which are members of Pinaceae, Ericaceae, and Cupressaceae. Based on the detailed morphological observations, the significance of different morphological characteristics for a natural classification of Rhytismatales is discussed. Genera are traditionally defined by character states of a few characteristics, namely the opening patterns of ascomata, the depth of ascomata in the host tissue, and asci and ascospore shape. Data from collections in the field, detailed morphological investigation, and molecular data show, however, that the ecology, the infected organ, the host relationship, and many other characteristics have to be combined to circumscribe natural groups.
The discussion of the systematic significance of morphological characteristics is complemented by molecular data. In the present study, partial nuclear large subunit rDNA sequences of 52 specimens representing 38 species are used to analyse phylogenetic relationships for members of Rhytismatales.
Most species of Rhytismatales are placed in a monophyletic group corresponding to the Rhytismatales in the Maximum Parsimony analysis. The delimitation of the Rhytismatales from the Helotiales is, however, difficult. Cyclaneusma minus should be transferred from the Rhytismatales to the Helotiales, and Cudonia circinans and Spathularia flavida from the Helotiales to the Rhytismatales. These tranfers have previously been proposed based on SSU rDNA analysis by other authors. New Genus 1 sp. has morphological characteristics typical for species of Rhytismatales. In the LSU rDNA analysis, however, it is more closely related to Helotiales rather than toRhytismatales. Therefore New Genus 1 sp. is placed in the Helotiales.
Tryblidiopsis pinastri is morphologically intermediate between members of Rhytismataceae and Cudoniaceae. LSU rDNA sequences in the present study show that T. pinastri is more closely related to species of Cudoniaceae. Therefore, this species is removed from the Rhytismataceae to the Cudoniaceae. The delimitation of further families could not be resolved in the present analysis.
Though many new morphological, ecological, and molecular phylogenetic findings are contributed for the first time, the systematic conclusions at generic, family, and order level can only be fragmentary in the present study. With more collections and more molecular data of the worldwide 450 known and many more unknown species of Rhytismatales at hand, a natural system combining morphological and molecular analysis can be elaborated.
We report a measurement of the observed cross sections of e+ e− → J/ψX based on 3.21 fb − 1 of data accumulated at energies from 3.645 to 3.891 GeV with the BESIII detector operated at the BEPCII collider. In analysis of the cross sections, we measured the decay branching fractions of B(ψ(3686) → J/ψX) = (64.4 ± 0.6 ± 1.6)% and B(ψ(3770) → J/ψX) = (0.5 ± 0.2 ± 0.1)% for the first time. The energy-dependent line shape of these cross sections cannot be well described by two Breit-Wigner (BW) amplitudes of the expected decays ψ (3686) → J/ψX and ψ(3770) → J/ψX. Instead, it can be better described with one more BW amplitude of the decay R(3760)→ J/ψX. Under this assumption, we extracted the R (3760) mass M R (3760 ) = 3766.2 ± 3.8 ± 0.4 MeV/c2, total width Γ tot R ( 3760 ) = 22.2 ± 5.9 ± 1.4 MeV, and product of leptonic width and decay branching fraction
ΓeeR(3760) B[R(3760) → J/ψX] = (79.4 ± 85.5 ± 11.7) eV. The significance of the R(3760) is 5.3σ. The first uncertainties of these measured quantities are from fits to the cross sections and second systematic.
We measure the inclusive semielectronic decay branching fraction of the D+s meson. A double-tag technique is applied to e+e− annihilation data collected by the BESIII experiment at the BEPCII collider, operating in the center-of-mass energy range 4.178–4.230 GeV. We select positrons fromD+s→Xe+νe with momenta greater than 200 MeV/c and determine the laboratory momentum spectrum, accounting for the effects of detector efficiency and resolution. The total positron yield and semielectronic branching fraction are determined by extrapolating this spectrum below the momentum cutoff. We measure the D+s semielectronic branching fraction to be(6.30±0.13(stat.)±0.09(syst.)±0.04(ext.))%, showing no evidence for unobserved exclusive semielectronic modes. We combine this result with external data taken from literature to determine the ratio of the D+s and D0 semielectronic widths, Γ(D+s→Xe+νe)Γ(D0→Xe+νe)=0.790±0.016(stat.)±0.011(syst.)±0.016(ext.). Our results are consistent with and more precise than previous measurements.
Using data samples collected with the BESIII detector operating at the BEPCII storage ring at center-of-mass energies from 4.178 to 4.600 GeV, we study the process eþe− → π0Xð3872Þγ and search for Zcð4020Þ0 → Xð3872Þγ. We find no significant signal and set upper limits on σðeþe− → π0Xð3872ÞγÞ · BðXð3872Þ → πþπ−J=ψÞ and σðeþe− → π0Zcð4020Þ0Þ · BðZcð4020Þ0 → Xð3872ÞγÞ · BðXð3872Þ → πþπ−J=ψÞ for each energy point at 90% confidence level, which is of the order of several tenths pb.
By analyzing the large-angle Bhabha scattering events e+e− → (γ)e+e− and diphoton events e+e− → (γ)γγ for the data sets collected at center-of-mass (c.m.) energies between 2.2324 and 4.5900 GeV (131 energy points in total) with the upgraded Beijing Spectrometer (BESIII) at the Beijing Electron-Positron Collider (BEPCII), the integrated luminosities have been measured at the different c.m. energies, individually. The results are important inputs for the R value and J/ψ resonance parameter measurements.
The Born cross sections and effective form factors for process 𝑒+𝑒−→Ξ−¯Ξ+ are measured at eight center-of-mass energies between 2.644 and 3.080 GeV, using a total integrated luminosity of 363.9 pb−1 𝑒+𝑒− collision data collected with the BESIII detector at BEPCII. After performing a fit to the Born cross section of 𝑒+𝑒−→Ξ−¯Ξ+, no significant threshold effect is observed.
Relative fractions and phases of the intermediate decays are determined. With the detection efficiency estimated by the results of the amplitude analysis, the branching fraction of Dþ s → K−Kþπþπ0 decay is measured to be ð5.42 0.10stat 0.17systÞ%.
The process e+e−→ϕη is studied at 22 center-of-mass energy points (√s) between 2.00 and 3.08 GeV using 715 pb−1 of data collected with the BESIII detector. The measured Born cross section of e+e−→ϕη is found to be consistent with BABAR measurements, but with improved precision. A resonant structure around 2.175 GeV is observed with a significance of 6.9σ with mass (2163.5±6.2±3.0) MeV/c2 and width (31.1+21.1−11.6±1.1) MeV, where the first uncertainties are statistical and the second are systematic.
By analyzing 6.32 fb − 1 of e+ e− annihilation data collected at the center-of-mass energies between 4.178 and 4.226 GeV with the BESIII detector, we determine the branching fraction of the leptonic decay D + s → τ + ντ, with τ+ → π + π0¯ντ, to be B D + s → τ + ν τ = (5.29 ± 0.25 stat ± 0.20 syst) %. We estimate the product of the Cabibbo-Kobayashi-Maskawa matrix element |Vcs|and the D + s decay constant f D + s to be f D + s|Vcs| = (244.8 ± 5.8 stat ± 4.8syst) MeV, using the known values of the τ + and D + s masses as well as the D + s lifetime, together with our branching fraction measurement. Combining the value of |Vcs| obtained from a global fit in the standard model and f D + s from lattice quantum chromodynamics, we obtain f D + s = (251.6 ± 5.9 stat ± 4.9syst) MeV and |Vcs| = 0.980 ± 0.023 stat ± 0.019 syst. Using the branching fraction of B D + s → μ + νμ = (5.35±0.21)×10−3, we obtain the ratio of the branching fractions B D + s → τ + ντ/B D +s → μ+νμ = 9.89±0.71, which is consistent with the standard model prediction of lepton flavor universality.
Using 10.1 × 109 J/ψ events produced by the Beijing Electron Positron Collider (BEPCII) at a center-of-mass energy √s = 3.097 GeV and collected with the BESIII detector, we present a search for the rare semi-leptonic decay J/ψ → D−e+νe + c.c. No excess of signal above background is observed, and an upper limit on the branching fraction ℬ(J/ψ → D−e+νe + c. c.) < 7.1 × 10−8 is obtained at 90% confidence level. This is an improvement of more than two orders of magnitude over the previous best limit.
Using a data sample of e+e− collision data corresponding to an integrated luminosity of 2.93 fb−1 collected with the BESIII detector at a center-of-mass energy of s=3.773GeV, we search for the singly Cabibbo-suppressed decays D0→π0π0π0, π0π0η, π0ηη and ηηη using the double tag method. The absolute branching fractions are measured to be B(D0→π0π0π0)=(2.0±0.4±0.3)×10−4, B(D0→π0π0η)=(3.8±1.1±0.7)×10−4 and B(D0→π0ηη)=(7.3±1.6±1.5)×10−4 with the statistical significances of 4.8σ, 3.8σ and 5.5σ, respectively, where the first uncertainties are statistical and the second ones systematic. No significant signal of D0→ηηη is found, and the upper limit on its decay branching fraction is set to be B(D0→ηηη)<1.3×10−4 at the 90% confidence level.
Though immensely successful, the standard model of particle physics does not offer any explanation as to why our Universe contains so much more matter than antimatter. A key to a dynamically generated matter–antimatter asymmetry is the existence of processes that violate the combined charge conjugation and parity (CP) symmetry1. As such, precision tests of CP symmetry may be used to search for physics beyond the standard model. However, hadrons decay through an interplay of strong and weak processes, quantified in terms of relative phases between the amplitudes. Although previous experiments constructed CP observables that depend on both strong and weak phases, we present an approach where sequential two-body decays of entangled multi-strange baryon–antibaryon pairs provide a separation between these phases. Our method, exploiting spin entanglement between the double-strange Ξ− baryon and its antiparticle2 Ξ¯+
, has enabled a direct determination of the weak-phase difference, (ξP − ξS) = (1.2 ± 3.4 ± 0.8) × 10−2 rad. Furthermore, three independent CP observables can be constructed from our measured parameters. The precision in the estimated parameters for a given data sample size is several orders of magnitude greater than achieved with previous methods3. Finally, we provide an independent measurement of the recently debated Λ decay parameter αΛ (refs. 4,5). The ΛΛ¯
asymmetry is in agreement with and compatible in precision to the most precise previous measurement.
Based on an e+e− collision data sample corresponding to an integrated luminosity of 2.93 fb−1 collected with the BESIII detector at √s=3.773 GeV, the first amplitude analysis of the singly Cabibbo-suppressed decay D+→K+K0Sπ0 is performed. From the amplitude analysis, the K∗(892)+K0S component is found to be dominant with a fraction of (57.1±2.6±4.2)%, where the first uncertainty is statistical and the second systematic. In combination with the absolute branching fraction B(D+→K+K0Sπ0) measured by BESIII, we obtain B(D+→K∗(892)+K0S)=(8.69±0.40±0.64±0.51)×10−3, where the third uncertainty is due to the branching fraction B(D+→K+K0Sπ0). The precision of this result is significantly improved compared to the previous measurement. This result also differs from most of theoretical predictions by about 4σ, which may help to improve the understanding of the dynamics behind.
By using 6.32 fb−1 of data collected with the BESIII detector at center-of-mass energies between 4.178 and 4.226 GeV, we perform an amplitude analysis of the decay D+s ! K0S + 0 and determine the relative fractions and phase differences of different intermediate processes, which include K0S (770)+, K0S (1450)+, K (892)0 +, K (892)+ 0, and K (1410)0 +. With the detection efficiency based on the amplitude analysis results, the absolute branching fraction is measured to be B(D+s ! K0S + 0) = (5.43 ± 0.30stat ± 0.15syst) × 10−3.
Using 2.93 fb−1 of 𝑒+𝑒− collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector, we report the first measurements of the absolute branching fractions of 14 hadronic 𝐷0(+) decays to exclusive final states with an 𝜂, e.g., 𝐷0→𝐾−𝜋+𝜂, 𝐾0𝑆𝜋0𝜂, 𝐾+𝐾−𝜂, 𝐾0𝑆𝐾0𝑆𝜂, 𝐾−𝜋+𝜋0𝜂, 𝐾0𝑆𝜋+𝜋−𝜂, 𝐾0𝑆𝜋0𝜋0𝜂, and 𝜋+𝜋−𝜋0𝜂; 𝐷+→𝐾0𝑆𝜋+𝜂, 𝐾0𝑆𝐾+𝜂, 𝐾−𝜋+𝜋+𝜂, 𝐾0𝑆𝜋+𝜋0𝜂, 𝜋+𝜋+𝜋−𝜂, and 𝜋+𝜋0𝜋0𝜂. Among these decays, the 𝐷0→𝐾−𝜋+𝜂 and 𝐷+→𝐾0 𝑆𝜋+𝜂 decays have the largest branching fractions, which are ℬ(𝐷0→𝐾−𝜋+𝜂) = (1.853±0.025stat±0.031syst)% and ℬ(𝐷+→𝐾0𝑆𝜋+𝜂) = (1.309±0.037stat±0.031syst)%, respectively. The charge-parity asymmetries for the six decays with highest event yields are determined, and no statistically significant charge-parity violation is found.
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
The genus Parandes Muir, 1925 (Cixiinae, Andini) is recorded from China for the first time with two new species, Parandes circinatus Wang & Chen sp. nov. and Parandes fuscus Wang & Chen sp. nov. Color images for the adults of the two new species and line drawings for the genitalia are provided. A key is presented to separate all species within the genus.
While the liver, specifically hepatocytes, are widely accepted as the main source of hepatitis C virus (HCV) production, the role of the liver/hepatocytes in clearance of circulating HCV remains unknown. Frequent HCV kinetic data were recorded and mathematically modeled from five liver transplant patients throughout the anhepatic (absence of liver) phase and for 4 hr post-reperfusion. During the anhepatic phase, HCV remained at pre-anhepatic levels (n = 3) or declined (n = 2) with t1/2~1 hr. Immediately post-reperfusion, virus declined in a biphasic manner in four patients consisting of a rapid decline (t1/2 = 5 min) followed by a slower decline (t1/2 = 67 min). Consistent with the majority of patients in the anhepatic phase, when we monitored HCV clearance at 37°C from culture medium in the absence/presence of chronically infected hepatoma cells that were inhibited from secreting HCV, the HCV t1/2 in cell culture was longer in the absence of chronically HCV-infected cells. The results suggest that the liver plays a major role in the clearance of circulating HCV and that hepatocytes may be involved.
While the liver, specifically hepatocytes, are widely accepted as the main source for hepatitis C virus (HCV) production, the role of the liver/hepatocytes in the clearance of circulating HCV remains largely unknown. Here we evaluated the function of the liver/hepatocytes in clearing virus from the circulation by investigating viral clearance during liver transplantation and from culture medium in vitro. Frequent HCV kinetic data during liver transplantation were recorded from 5 individuals throughout the anhepatic (AH) phase and for 4 hours after reperfusion (RP), along with recordings of fluid balances. Using mathematical modeling, the serum viral clearance rate, c, was estimated. Analogously, we monitored the clearance rate of HCV at 37°C from culture medium in vitro in the absence and presence of chronically infected Huh7 human hepatoma cells. During the AH phase, in 3 transplant cases viral levels remained at pre-AH levels, while in the other 2 cases HCV declined (half-life, t1/2~1h). Immediately post-RP, virus declined in a biphasic manner in Cases 1-4 consisting of an extremely rapid (median t1/2=5min) decline followed by a slower decline (HCV t1/2=67min). In Case 5, HCV remained at the same level post-RP as at the end of AH. Declines in virus level were not explained by adjusting for dilution from IV fluid and blood products. Consistent with what was observed in the majority of patients in the anhepatic phase, the t1/2 of HCV in cell culture was much longer in the absence of chronically HCV-infected Huh7 cells. Therefore, kinetic and modeling results from both in vivo liver transplantation cases and in vitro cell culture studies suggest that the liver plays a major role in clearing HCV from the circulation.
A new planthopper genus, Aodingus Chen & Li gen. nov. and three new species (A. hainanensis Chen & Li gen. et sp. nov., A. obscurus Chen & Li gen. et sp. nov. and A. cuongi Chen & Li gen. et sp. nov.) are described from China and Vietnam. The new genus is superficially similar to Procidelphax Bartlett, 2009 in general appearance in that the body is strongly dorsoventrally flattened. Distinctive features of the new taxon include broadly compressed body with vertex broad, apical margin broadly rounded, middle part concave, median and submedian carinae absent, frons broad and large, wider at base than at apex, forewing broad and long, aedeagus tubular, curved ventrally. A diagnosis for all species, illustrations and an identification key of new genus are provided. A key to the Chinese genera of Tropidocephalini is also provided.
In this short note, we investigate simultaneous recovery inverse problems for semilinear elliptic equations with partial data. The main technique is based on higher order linearization and monotonicity approaches. With these methods at hand, we can determine the diffusion, cavity and coefficients simultaneously by knowing the corresponding localized Dirichlet-Neumann operators.
The integrated luminosities of the data samples collected in the BESIII experiment in 2016--2017 at center-of-mass energies between 4.19 and 4.28 GeV are measured with a precision better than 1% by analyzing large-angle Bhabha scattering events. The integrated luminosities of the old data sets collected in 2010--2014 are updated by considering correction related to the detector performance, offsettting the effect of newly discovered readout errors in the electromagnetic calorimeter that happen haphazardly.
The elliptic (v2) and triangular (v3) azimuthal anisotropy coefficients in central 3He+Au, d+Au, and p+Au collisions at sNN−−−√ = 200 GeV are measured as a function of transverse momentum (pT) at mid-rapidity (|η|<0.9), via the azimuthal angular correlation between two particles both at |η|<0.9. While the v2(pT) values depend on the colliding systems, the v3(pT) values are system-independent within the uncertainties, suggesting an influence on eccentricity from sub-nucleonic fluctuations in these small-sized systems. These results also provide stringent constraints for the hydrodynamic modeling of these systems.
A decisive experimental test of the Chiral Magnetic Effect (CME) is considered one of the major scientific goals at the Relativistic Heavy-Ion Collider (RHIC) towards understanding the nontrivial topological fluctuations of the Quantum Chromodynamics vacuum. In heavy-ion collisions, the CME is expected to result in a charge separation phenomenon across the reaction plane, whose strength could be strongly energy dependent. The previous CME searches have been focused on top RHIC energy collisions. In this Letter, we present a low energy search for the CME in Au+Au collisions at sNN−−−√=27 GeV. We measure elliptic flow scaled charge-dependent correlators relative to the event planes that are defined at both mid-rapidity |η|<1.0 and at forward rapidity 2.1<|η|<5.1. We compare the results based on the directed flow plane (Ψ1) at forward rapidity and the elliptic flow plane (Ψ2) at both central and forward rapidity. The CME scenario is expected to result in a larger correlation relative to Ψ1 than to Ψ2, while a flow driven background scenario would lead to a consistent result for both event planes. In 10-50\% centrality, results using three different event planes are found to be consistent within experimental uncertainties, suggesting a flow driven background scenario dominating the measurement. We obtain an upper limit on the deviation from a flow driven background scenario at the 95\% confidence level. This work opens up a possible road map towards future CME search with the high statistics data from the RHIC Beam Energy Scan Phase-II.
A decisive experimental test of the Chiral Magnetic Effect (CME) is considered one of the major scientific goals at the Relativistic Heavy-Ion Collider (RHIC) towards understanding the nontrivial topological fluctuations of the Quantum Chromodynamics vacuum. In heavy-ion collisions, the CME is expected to result in a charge separation phenomenon across the reaction plane, whose strength could be strongly energy dependent. The previous CME searches have been focused on top RHIC energy collisions. In this Letter, we present a low energy search for the CME in Au+Au collisions at sNN−−−√=27 GeV. We measure elliptic flow scaled charge-dependent correlators relative to the event planes that are defined at both mid-rapidity |η|<1.0 and at forward rapidity 2.1<|η|<5.1. We compare the results based on the directed flow plane (Ψ1) at forward rapidity and the elliptic flow plane (Ψ2) at both central and forward rapidity. The CME scenario is expected to result in a larger correlation relative to Ψ1 than to Ψ2, while a flow driven background scenario would lead to a consistent result for both event planes. In 10-50\% centrality, results using three different event planes are found to be consistent within experimental uncertainties, suggesting a flow driven background scenario dominating the measurement. We obtain an upper limit on the deviation from a flow driven background scenario at the 95\% confidence level. This work opens up a possible road map towards future CME search with the high statistics data from the RHIC Beam Energy Scan Phase-II.
In relativistic heavy-ion collisions, a global spin polarization, PH, of Λ and Λ¯ hyperons along the direction of the system angular momentum was discovered and measured across a broad range of collision energies and demonstrated a trend of increasing PH with decreasing sNN−−−√. A splitting between Λ and Λ¯ polarization may be possible due to their different magnetic moments in a late-stage magnetic field sustained by the quark-gluon plasma which is formed in the collision. The results presented in this study find no significant splitting at the collision energies of sNN−−−√=19.6 and 27 GeV in the RHIC Beam Energy Scan Phase II using the STAR detector, with an upper limit of PΛ¯−PΛ<0.24% and PΛ¯−PΛ<0.35%, respectively, at a 95% confidence level. We derive an upper limit on the naïve extraction of the late-stage magnetic field of B<9.4⋅1012 T and B<1.4⋅1013 T at sNN−−−√=19.6 and 27 GeV, respectively, although more thorough derivations are needed. Differential measurements of PH were performed with respect to collision centrality, transverse momentum, and rapidity. With our current acceptance of |y|<1 and uncertainties, we observe no dependence on transverse momentum and rapidity in this analysis. These results challenge multiple existing model calculations following a variety of different assumptions which have each predicted a strong dependence on rapidity in this collision-energy range.
In relativistic heavy-ion collisions, a global spin polarization, PH, of Λ and Λ¯ hyperons along the direction of the system angular momentum was discovered and measured across a broad range of collision energies and demonstrated a trend of increasing PH with decreasing sNN−−−√. A splitting between Λ and Λ¯ polarization may be possible due to their different magnetic moments in a late-stage magnetic field sustained by the quark-gluon plasma which is formed in the collision. The results presented in this study find no significant splitting at the collision energies of sNN−−−√=19.6 and 27 GeV in the RHIC Beam Energy Scan Phase II using the STAR detector, with an upper limit of PΛ¯−PΛ<0.24% and PΛ¯−PΛ<0.35%, respectively, at a 95% confidence level. We derive an upper limit on the naïve extraction of the late-stage magnetic field of B<9.4⋅1012 T and B<1.4⋅1013 T at sNN−−−√=19.6 and 27 GeV, respectively, although more thorough derivations are needed. Differential measurements of PH were performed with respect to collision centrality, transverse momentum, and rapidity. With our current acceptance of |y|<1 and uncertainties, we observe no dependence on transverse momentum and rapidity in this analysis. These results challenge multiple existing model calculations following a variety of different assumptions which have each predicted a strong dependence on rapidity in this collision-energy range.
In relativistic heavy-ion collisions, a global spin polarization, PH, of Λ and Λ¯ hyperons along the direction of the system angular momentum was discovered and measured across a broad range of collision energies and demonstrated a trend of increasing PH with decreasing sNN−−−√. A splitting between Λ and Λ¯ polarization may be possible due to their different magnetic moments in a late-stage magnetic field sustained by the quark-gluon plasma which is formed in the collision. The results presented in this study find no significant splitting at the collision energies of sNN−−−√=19.6 and 27 GeV in the RHIC Beam Energy Scan Phase II using the STAR detector, with an upper limit of PΛ¯−PΛ<0.24% and PΛ¯−PΛ<0.35%, respectively, at a 95% confidence level. We derive an upper limit on the naïve extraction of the late-stage magnetic field of B<9.4⋅1012 T and B<1.4⋅1013 T at sNN−−−√=19.6 and 27 GeV, respectively, although more thorough derivations are needed. Differential measurements of PH were performed with respect to collision centrality, transverse momentum, and rapidity. With our current acceptance of |y|<1 and uncertainties, we observe no dependence on transverse momentum and rapidity in this analysis. These results challenge multiple existing model calculations following a variety of different assumptions which have each predicted a strong dependence on rapidity in this collision-energy range.
A decisive experimental test of the Chiral Magnetic Effect (CME) is considered one of the major scientific goals at the Relativistic Heavy-Ion Collider (RHIC) towards understanding the nontrivial topological fluctuations of the Quantum Chromodynamics vacuum. In heavy-ion collisions, the CME is expected to result in a charge separation phenomenon across the reaction plane, whose strength could be strongly energy dependent. The previous CME searches have been focused on top RHIC energy collisions. In this Letter, we present a low energy search for the CME in Au+Au collisions at sNN−−−√=27 GeV. We measure elliptic flow scaled charge-dependent correlators relative to the event planes that are defined at both mid-rapidity |η|<1.0 and at forward rapidity 2.1<|η|<5.1. We compare the results based on the directed flow plane (Ψ1) at forward rapidity and the elliptic flow plane (Ψ2) at both central and forward rapidity. The CME scenario is expected to result in a larger correlation relative to Ψ1 than to Ψ2, while a flow driven background scenario would lead to a consistent result for both event planes. In 10-50\% centrality, results using three different event planes are found to be consistent within experimental uncertainties, suggesting a flow driven background scenario dominating the measurement. We obtain an upper limit on the deviation from a flow driven background scenario at the 95\% confidence level. This work opens up a possible road map towards future CME search with the high statistics data from the RHIC Beam Energy Scan Phase-II.
We report the beam energy and collision centrality dependence of fifth and sixth order cumulants (C5, C6) and factorial cumulants (κ5, κ6) of net-proton and proton distributions, from sNN−−−−√=3−200 GeV Au+Au collisions at RHIC. The net-proton cumulant ratios generally follow the hierarchy expected from QCD thermodynamics, except for the case of collisions at sNN−−−−√ = 3 GeV. C6/C2 for 0-40\% centrality collisions is increasingly negative with decreasing sNN−−−−√, while it is positive for the lowest sNN−−−−√ studied. These observed negative signs are consistent with QCD calculations (at baryon chemical potential, μB≤ 110 MeV) that include a crossover quark-hadron transition. In addition, for sNN−−−−√≥ 11.5 GeV, the measured proton κn, within uncertainties, does not support the two-component shape of proton distributions that would be expected from a first-order phase transition. Taken in combination, the hyper-order proton number fluctuations suggest that the structure of QCD matter at high baryon density, μB∼750 MeV (sNN−−−−√ = 3 GeV) is starkly different from those at vanishing μB∼20MeV (sNN−−−−√ = 200 GeV and higher).
We report on measurements of sequential Υ suppression in Au+Au collisions at sNN−−−√ = 200 GeV with the STAR detector at the Relativistic Heavy Ion Collider (RHIC) through both the dielectron and dimuon decay channels. In the 0-60% centrality class, the nuclear modification factors (RAA), which quantify the level of yield suppression in heavy-ion collisions compared to p+p collisions, for Υ(1S) and Υ(2S) are 0.40±0.03 (stat.)±0.03 (sys.)±0.09 (norm.) and 0.26±0.08 (stat.)±0.02 (sys.)±0.06 (norm.), respectively, while the upper limit of the Υ(3S) RAA is 0.17 at a 95% confidence level. This provides experimental evidence that the Υ(3S) is significantly more suppressed than the Υ(1S) at RHIC. The level of suppression for Υ(1S) is comparable to that observed at the much higher collision energy at the Large Hadron Collider. These results point to the creation of a medium at RHIC whose temperature is sufficiently high to strongly suppress excited Υ states.
The decays of χc2→K+K−π0, KSK±π∓ and π+π−π0 are studied with the ψ(3686) data samples collected with the Beijing Spectrometer (BESIII). For the first time, the branching fractions of χc2→K∗K¯¯¯¯¯, χc2→a±2(1320)π∓/a02(1320)π0 and χc2→ρ(770)±π∓ are measured. Here K∗K¯¯¯¯¯ denotes both K∗±K∓ and K∗0K¯¯¯¯¯0+c.c., and K∗ denotes the resonances K∗(892), K∗2(1430) and K∗3(1780). The observations indicate a strong violation of the helicity selection rule in χc2 decays into vector and pseudoscalar meson pairs. The measured branching fractions of χc2→K∗(892)K¯¯¯¯¯ are more than 10 times larger than the upper limit of χc2→ρ(770)±π∓, which is so far the first direct observation of a significant U-spin symmetry breaking effect in charmonium decays.
Using a sample of about 1010 𝐽/𝜓 events collected at a center-of-mass energy √𝑠=3.097 GeV with the BESIII detector, the electromagnetic Dalitz decays 𝐽/𝜓→𝑒+𝑒−𝜋+𝜋−𝜂′, with 𝜂′→𝛾𝜋+𝜋− and 𝜂′→𝜋+𝜋−𝜂, have been studied. The decay 𝐽/𝜓→𝑒+𝑒−𝑋(1835) is observed with a significance of 15𝜎, and also an 𝑒+𝑒− invariant-mass dependent transition form factor of 𝐽/𝜓→𝑒+𝑒−𝑋(1835) is presented for the first time. The intermediate states 𝑋(2120) and 𝑋(2370) are also observed in the 𝜋+𝜋−𝜂′ invariant-mass spectrum with significances of 5.3𝜎 and 7.3𝜎. The corresponding product branching fractions for 𝐽/𝜓→𝑒+𝑒−𝑋, 𝑋→𝜋+𝜋−𝜂′ [𝑋=𝑋(1835), 𝑋(2120), and 𝑋(2370)] are reported.
Using a data sample of 4.481×108 𝜓(3686) events collected with the BESIII detector, we report the first observation of the four-lepton-decays 𝐽/𝜓→𝑒+𝑒−𝑒+𝑒− and 𝐽/𝜓→𝑒+𝑒−𝜇+𝜇− utilizing the process 𝜓(3686)→𝜋+𝜋−𝐽/𝜓. The branching fractions are determined to be [5.48±0.31(stat)±0.45(syst)]×10−5 and [3.53±0.22(stat)±0.13(syst)]×10−5, respectively. The results are consistent with theoretical predictions. No significant signal is observed for 𝐽/𝜓→𝜇+𝜇−𝜇+𝜇−, and an upper limit on the branching fraction is set at 1.6×10−6 at the 90% confidence level. A 𝐶𝑃 asymmetry observable is constructed for the first two channels, which is measured to be (−0.012±0.054±0.010) and (0.062±0.059±0.006), respectively. No evidence for 𝐶𝑃 violation is observed in this process.
Using 2.93 fb−1 of 𝑒+𝑒− collision data taken at a center-of-mass energy of 3.773 GeV by the BESIII detector at the BEPCII, we measure the branching fractions of the singly Cabibbo-suppressed decays 𝐷→𝜔𝜋𝜋 to be ℬ(𝐷0→𝜔𝜋+𝜋−)=(1.33±0.16±0.12)×10−3 and ℬ(𝐷+→𝜔𝜋+𝜋0)=(3.87±0.83±0.25)×10−3, where the first uncertainties are statistical and the second ones systematic. The statistical significances are 12.9𝜎 and 7.7𝜎, respectively. The precision of ℬ(𝐷0→𝜔𝜋+𝜋−) is improved by a factor of 2.1 over prior measurements, and ℬ(𝐷+→𝜔𝜋+𝜋0) is measured for the first time. No significant signal for 𝐷0→𝜔𝜋0𝜋0 is observed, and the upper limit on the branching fraction is ℬ(𝐷0→𝜔𝜋0𝜋0)<1.10×10−3 at the 90% confidence level. The branching fractions of 𝐷→𝜂𝜋𝜋 are also measured and consistent with existing results.
The decays D → K−π+π+π− and D → K−π+π 0 are studied in a sample of quantum-correlated DD¯ pairs produced through the process e+e− → ψ(3770) → DD¯, exploiting a data set collected by the BESIII experiment that corresponds to an integrated luminosity of 2.93 fb−1 . Here D indicates a quantum superposition of a D0 and a D¯ 0 meson. By reconstructing one neutral charm meson in a signal decay, and the other in the same or a different final state, observables are measured that contain information on the coherence factors and average strong-phase differences of each of the signal modes. These parameters are critical inputs in the measurement of the angle γ of the Unitarity Triangle in B− → DK− decays at the LHCb and Belle II experiments. The coherence factors are determined to be RK3π = 0.52+0.12−0.10 and RKππ0 = 0.78 ± 0.04, with values for the average strong-phase differences that are δ K3π D = (167+31−19)◦ and δKππ0D = (196+14−15◦ , where the uncertainties include both statistical and systematic contributions. The analysis is re-performed in four bins of the phase-space of the D → K−π+π+π− to yield results that will allow for a more sensitive measurement of γ with this mode, to which the BESIII inputs will contribute an uncertainty of around 6◦.
We report new measurements of the branching fraction ℬ(𝐷+𝑠→ℓ+𝜈), where ℓ+ is either 𝜇+ or 𝜏+(→𝜋+¯𝜈𝜏), based on 6.32 fb−1 of electron-positron annihilation data collected by the BESIII experiment at six center-of-mass energy points between 4.178 and 4.226 GeV. Simultaneously floating the 𝐷+𝑠→𝜇+𝜈𝜇 and 𝐷+𝑠→𝜏+𝜈𝜏 components yields ℬ(𝐷+𝑠→𝜏+𝜈𝜏)=(5.21±0.25±0.17)×10−2, ℬ(𝐷+𝑠→𝜇+𝜈𝜇)=(5.35±0.13±0.16)×10−3, and the ratio of decay widths 𝑅=Γ(𝐷+𝑠→𝜏+𝜈𝜏)Γ(𝐷+𝑠→𝜇+𝜈𝜇)=9.73+0.61−0.58±0.36, where the first uncertainties are statistical and the second systematic. No evidence of 𝐶𝑃 asymmetry is observed in the decay rates 𝐷±𝑠→𝜇±𝜈𝜇 and 𝐷±𝑠→𝜏±𝜈𝜏: 𝐴𝐶𝑃(𝜇±𝜈)=(−1.2±2.5±1.0)% and 𝐴𝐶𝑃(𝜏±𝜈)=(+2.9±4.8±1.0)%. Constraining our measurement to the Standard Model expectation of lepton universality (𝑅=9.75), we find the more precise results ℬ(𝐷+𝑠→𝜏+𝜈𝜏)=(5.22±0.10±0.14)×10−2 and 𝐴𝐶𝑃(𝜏±𝜈𝜏)=(−0.1±1.9±1.0)%. Combining our results with inputs external to our analysis, we determine the 𝑐→¯𝑠 quark mixing matrix element, 𝐷+𝑠 decay constant, and ratio of the decay constants to be |𝑉𝑐𝑠|=0.973±0.009±0.014, 𝑓𝐷+𝑠=249.9±2.4±3.5 MeV, and 𝑓𝐷+𝑠/𝑓𝐷+=1.232±0.035, respectively.
Using 2.93 fb−1 of e+e− collision data taken with the BESIII detector at a center-of-mass energy of 3.773 GeV, the observation of the D0→K1(1270)−e+νe semileptonic decay is presented. The statistical significance of the decay D0→K1(1270)−e+νe is greater than 10σ. The branching fraction of D0→K1(1270)−e+νe is measured to be (1.09±0.13+0.09−0.13±0.12)×10−3. Here, the first uncertainty is statistical, the second is systematic, and the third originates from the assumed branching fraction of K1(1270)−→K−π+π−.
Using 2.93 fb−1 of e+e− collision data taken with the BESIII detector at a center-of-mass energy of 3.773 GeV, the observation of the D0→K1(1270)−e+νe semileptonic decay is presented. The statistical significance of the decay D0→K1(1270)−e+νe is greater than 10σ. The branching fraction of D0→K1(1270)−e+νe is measured to be (1.09±0.13+0.09−0.16±0.12)×10−3. Here, the first uncertainty is statistical, the second is systematic, and the third originates from the assumed branching fraction of K1(1270)−→K−π+π−. The fraction of longitudinal polarization in D0→K1(1270)−e+νe is determined for the first time to be 0.50±0.19stat±0.08syst.
Using 6.32 fb−1 of 𝑒+𝑒− collision data collected by the BESIII detector at the center-of-mass energies between 4.178 and 4.226 GeV, an amplitude analysis of the 𝐷+𝑠→𝐾0𝑆𝐾−𝜋+𝜋+ decays is performed for the first time to determine the intermediate-resonant contributions. The dominant component is the 𝐷+𝑠→𝐾*(892)+¯𝐾*(892)0 decay with a fraction of (40.6±2.9stat±4.9sys)%. Our results of the amplitude analysis are used to obtain a more precise measurement of the branching fraction of the 𝐷+𝑠→𝐾0𝑆𝐾−𝜋+𝜋+ decay, which is determined to be (1.46±0.05stat±0.05sys)%.
he Born cross sections for the process 𝑒+𝑒−→𝜂′𝜋+𝜋− at different center-of-mass energies between 2.00 and 3.08 GeV are reported with improved precision from an analysis of data samples collected with the BESIII detector operating at the BEPCII storage ring. An obvious structure is observed in the Born cross section line shape. Fit as a Breit-Wigner resonance, it has a statistical significance of 6.3𝜎 and a mass and width of 𝑀=(2111±43±25) MeV/𝑐2 and Γ=(135±34±30) MeV, where the uncertainties are statistical and systematic, respectively. These measured resonance parameters agree with the measurements of BABAR in 𝑒+𝑒−→𝜂′𝜋+𝜋− and BESIII in 𝑒+𝑒−→𝜔𝜋0 within two standard deviations.
Using e+e− collision data at ten center-of-mass energies between 2.644 and 3.080 GeV collected with the BESIII detector at BEPCII and corresponding to an integrated luminosity of about 500 pb−1, we measure the cross sections and effective form factors for the process e+e−→Ξ0Ξ¯0 utilizing a single-tag method. A fit to the cross section of e+e−→Ξ0Ξ¯0 with a pQCD-driven power function is performed, from which no significant resonance or threshold enhancement is observed. In addition, the ratio of cross sections for the processes e+e−→Ξ−Ξ¯+ and Ξ0Ξ¯0 is calculated using recent BESIII measurement and is found to be compatible with expectation from isospin symmetry.
Using 2.93 fb−1 of e+e− collision data collected with the BESIII detector at a center-of-mass energy of 3.773 GeV, we measure the absolute branching fractions of the decays D0→K−e+νe and D+→K¯0e+νe to be (3.567±0.031stat±0.025syst)% and (8.68±0.14stat±0.16syst)%, respectively. Starting with the process e+e−→DD¯, a new reconstruction method is employed to select events that contain candidates for both D→K¯e+νe and D¯→Ke−ν¯e decays. The branching fractions reported in this work are consistent within uncertainties with previous BESIII measurements that selected events containing D→K¯e+νe and hadronic D¯ decays. Combining our results with the lifetimes of the D0 and D+ mesons and the previous BESIII measurements leads to a ratio of the two decay partial widths of Γ¯D0→K−e+νeΓ¯D+→K¯0e+νe=1.039±0.021. This ratio supports isospin symmetry in the D0→K−e+νe and D+→K¯0e+νe decays within 1.9σ.