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We report the first measurements of absolute branching fractions for the W -exchange-only processes + c → 0K + and + c → (1530)0K + with the double-tag technique, by analyzing an e+e− collision data sample, that corresponds to an integrated luminosity of 567 pb−1 collected at a center-of-mass energy of 4.6 GeV by the BESIII detector. The branching fractions are measured to be B(+c → 0K +) = (5.90 ± 0.86 ± 0.39) × 10−3 and B(+c → (1530)0K +) = (5.02 ± 0.99 ± 0.31) × 10−3, where the first uncertainties are statistical and the second systematic. Our results are more precise than the previous relative measurements.
With a notional amount outstanding of more than USD 500 trillion, the market for OTC derivatives is of vital importance for global financial stability. A growing proportion of these contracts are cleared via central counterparties (CCPs), which means that CCPs are gaining in importance as critical financial market infrastructures. At the same time, there is growing concern that a new „too big to fail" problem could arise, as the CCP industry is highly concentrated due to economies of scale. From a European perspective, it should be noted that the clearing of euro-denominated OTC derivatives mainly takes place in London, hence outside the EU in the foreseeable future. For some time there has been a controversial discussion as to whether this can remain the case post Brexit. CCPs, which clear a significant proportion of euro OTC derivatives and are systemically relevant from an EU perspective, should be subject to direct supervision by EU authorities and should be established in the EU. This would represent an important building block for a future Capital Markets Union in Europe, as regulatory or supervisory arbitrage in favour of systemically important third-country CCPs could be prevented. In addition, if a systemically relevant CCP handling a considerable portion of the euro OTC derivatives business were to run into serious difficulties, this may impact ECB monetary policy. This applies both to demand for central bank money and to the transmission of monetary policy measures, which can be significantly impaired, particularly in the event that the repo market or payment systems are disrupted. It is therefore essential for the ECB to be closely involved in the supervision of CCPs. Against this background, the draft amendment of EMIR (European Market Infrastructure Regulation) presented on 13 June 2017 is a step in the right direction. In addition, there is an urgent need to introduce a recovery and resolution mechanism for CCPs in the EU to complement the existing single resolution mechanism (SRM) for banks in the eurozone. Only then can the diverse interdependencies between banks and CCPs be adequately taken into account in the recovery and resolution programmes required in a financial crisis.
he process e+e−→pK0Sn¯K−+c.c. and its intermediate processes are studied for the first time, using data samples collected with the BESIII detector at BEPCII at center-of-mass energies of 3.773, 4.008, 4.226, 4.258, 4.358, 4.416, and 4.600 GeV, with a total integrated luminosity of 7.4 fb−1. The Born cross section of e+e−→pK0Sn¯K−+c.c. is measured at each center-of-mass energy, but no significant resonant structure in the measured cross-section line shape between 3.773 and 4.600 GeV is observed. No evident structure is detected in the pK−, nK0S, pK0S, nK+, pn¯, or K0SK− invariant mass distributions except for Λ(1520). The Born cross sections of e+e−→Λ(1520)n¯K0S+c.c. and e+e−→Λ(1520)p¯K++c.c. are measured, and the 90\% confidence level upper limits on the Born cross sections of e+e−→Λ(1520)Λ¯(1520) are determined at the seven center-of-mass energies.
An amplitude analysis of the 𝐾𝑆𝐾𝑆 system produced in radiative 𝐽/𝜓 decays is performed using the (1310.6±7.0)×106 𝐽/𝜓 decays collected by the BESIII detector. Two approaches are presented. A mass-dependent analysis is performed by parametrizing the 𝐾𝑆𝐾𝑆 invariant mass spectrum as a sum of Breit-Wigner line shapes. Additionally, a mass-independent analysis is performed to extract a piecewise function that describes the dynamics of the 𝐾𝑆𝐾𝑆 system while making minimal assumptions about the properties and number of poles in the amplitude. The dominant amplitudes in the mass-dependent analysis include the 𝑓0(1710), 𝑓0(2200), and 𝑓′2(1525). The mass-independent results, which are made available as input for further studies, are consistent with those of the mass-dependent analysis and are useful for a systematic study of hadronic interactions. The branching fraction of radiative 𝐽/𝜓 decays to 𝐾𝑆𝐾𝑆 is measured to be (8.1±0.4)×10−4, where the uncertainty is systematic and the statistical uncertainty is negligible.
Background: Alternative splicing is a key mechanism in eukaryotic cells to increase the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied both across human tissues and in genetically diverse individuals. This has identified disease-relevant splicing events, as well as associations between splicing and genomic variations, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue and its determinants remain poorly understood.
Results: We applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results shows that splicing rates in single cells can be accurately predicted based on sequence composition and other genomic features. We also identified a moderate but significant contribution from DNA methylation to splicing variation across cells. By combining sequence information and DNA methylation, we derived an accurate model (AUC=0.85) for predicting different splicing modes of individual cassette exons. These explain conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.
Conclusions: Our study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated component of DNA methylation variation on splicing.
Background: Alternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied across human tissues and in genetically diverse populations. This has identified disease-relevant splicing events, as well as associations between splicing and genomic variations, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue or cell type and its determinants remain poorly understood.
Results: We applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results shows that variation in single-cell splicing can be accurately predicted based on local sequence composition and genomic features. We observe moderate but consistent contributions from local DNA methylation profiles to splicing variation across cells. A combined model that is built based on sequence as well as DNA methylation information accurately predicts different splicing modes of individual cassette exons (AUC=0.85). These categories include the conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.
Conclusions: Our study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated link between DNA methylation variation and splicing.
Background: Alternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied across human tissues and in genetically diverse populations. This has identified disease-relevant splicing events, as well as associations between splicing and genomic features, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue or cell type and its determinants remains poorly understood.
Results: We applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results show that variation in single-cell splicing can be accurately predicted based on local sequence composition and genomic features. We observe moderate but consistent contributions from local DNA methylation profiles to splicing variation across cells. A combined model that is built based on genomic features as well as DNA methylation information accurately predicts different splicing modes of individual cassette exons. These categories include the conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.
Conclusions: Our study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated link between DNA methylation variation and splicing.
Eugen Helmlé, 1927–2000
(2018)
Eugen Helmlé (1927–2000) war einer der verwegensten und besessensten Übersetzer seiner Zunft, der an die 150 Bücher übersetzt hat und in ganz besonderer Weise Georges Perec verbunden war, dem herausragenden französischen Autor des 1960 gegründeten Oulipo-Kreises, der gemeinsam mit seinem Übersetzer Helmlé neue formale Wege der Literaturproduktion beschritt.
Using an 𝑒+𝑒− collision data sample of 2.93 fb−1 collected at a center-of-mass energy of 3.773 GeV by the BESIII detector at BEPCII, we report the observation of 𝐷0→𝑎0(980)−𝑒+𝜈𝑒 and evidence for 𝐷+→𝑎0(980)0𝑒+𝜈𝑒 with significances of 6.4𝜎 and 2.9𝜎, respectively. The absolute branching fractions are determined to be ℬ(𝐷0→𝑎0(980)−𝑒+𝜈𝑒)×ℬ(𝑎0(980)−→𝜂𝜋−) = [1.33+0.33−0.29(stat)±0.09(syst)]×10−4 and ℬ(𝐷+→𝑎0(980)0𝑒+𝜈𝑒)×ℬ(𝑎0(980)0→𝜂𝜋0)=[1.66+0.81
−0.66(stat)±0.11(syst)]×10−4. This is the first time the 𝑎0(980) meson has been measured in a 𝐷0 semileptonic decay, which would open one more interesting page in the investigation of the nature of the puzzling 𝑎0(980) states.
Using a data sample of 448.1×106 𝜓(3686) events collected with the BESIII detector operating at the BEPCII, we perform search for the hadronic transition ℎ𝑐→𝜋+𝜋−𝐽/𝜓 via 𝜓(3686)→𝜋0ℎ𝑐. No signals of the transition are observed, and the upper limit on the product branching fraction ℬ(𝜓(3686)→𝜋0ℎ𝑐)ℬ(ℎ𝑐→𝜋+𝜋−𝐽/𝜓) at the 90% confidence level (C.L.) is determined to be 2.0×10−6. This is the most stringent upper limit to date.
The decay 𝐽/𝜓→𝛾𝛾𝜙 is studied using a sample of 1.31×109 𝐽/𝜓 events collected with the BESIII detector. Two structures around 1475 MeV/𝑐2 and 1835 MeV/𝑐2 are observed in the 𝛾𝜙 invariant mass spectrum for the first time. With a fit on the 𝛾𝜙 invariant mass, which takes into account the interference between the two structures, and a simple analysis of the angular distribution, the structure around 1475 MeV/𝑐2 is found to favor an assignment as the 𝜂(1475) and the mass and width for the structure around 1835 MeV/𝑐2 are consistent with the 𝑋(1835). The statistical significances of the two structures are 13.5𝜎 and 6.3𝜎, respectively. The results indicate that both 𝜂(1475) and 𝑋(1835) contain a sizeable 𝑠¯𝑠 component.
Using a low background data sample of 9.7×105 𝐽/𝜓→𝛾𝜂′, 𝜂′→𝛾𝜋+𝜋− events, which are 2 orders of magnitude larger than those from the previous experiments, recorded with the BESIII detector at BEPCII, the decay dynamics of 𝜂′→𝛾𝜋+𝜋− are studied with both model-dependent and model-independent approaches. The contributions of 𝜔 and the 𝜌(770)−𝜔 interference are observed for the first time in the decays 𝜂′→𝛾𝜋+𝜋− in both approaches. Additionally, a contribution from the box anomaly or the 𝜌(1450) resonance is required in the model-dependent approach, while the process specific part of the decay amplitude is determined in the model-independent approach.
Using a sample of 4.48×108 ψ(3686) events collected with the BESIII detector at the BEPCII collider, we study the two-photon decays of the pseudoscalar mesons π0, η, η′, η(1405), η(1475), η(1760), and X(1835) in J/ψ radiative decays using ψ(3686)→π+π−J/ψ events. The π0, η and η′ mesons are clearly observed in the two-photon mass spectra, and the branching fractions are determined to be B(J/ψ→γπ0→3γ)=(3.57±0.12±0.16)×10−5, B(J/ψ→γη→3γ)=(4.42±0.04±0.18)×10−4, and B(J/ψ→γη′→3γ)=(1.26±0.02±0.05)×10−4, where the first errors are statistical and the second systematic. No clear signal for η(1405), η(1475), η(1760) or X(1835) is observed in the two-photon mass spectra, and upper limits at the 90% confidence level on the product branching fractions are obtained.
Based on an 𝑒+𝑒− collision data sample corresponding to an integrated luminosity of 567 pb−1 taken at the center-of-mass energy of √𝑠=4.6 GeV with the BESIII detector, we measure the absolute branching fraction of the inclusive decay Λ+𝑐→Λ+𝑋 to be ℬ(Λ+𝑐→Λ+𝑋)=(38.2+2.8−2.2±0.9)% using the double-tag method, where 𝑋 refers to any possible final state particles. In addition, we search for direct 𝐶𝑃 violation in the charge asymmetry of this inclusive decay for the first time, and obtain 𝒜𝐶𝑃≡[ℬ(Λ+𝑐→Λ+𝑋)−ℬ(¯Λ−𝑐 → ¯Λ+𝑋)]/[ℬ(Λ+𝑐→Λ+𝑋)+ℬ(¯Λ−𝑐 → ¯Λ+𝑋)]=(2.1+7.0−6.6±1.6)%, a statistically limited result with no evidence of 𝐶𝑃 violation.
We report new measurements of the cross sections for the production of Dbar D final states at the ψ(3770) resonance. Our data sample consists of an integrated luminosity of 2.93 fb−1 of e+e− annihilation data produced by the BEPCII collider and collected and analyzed with the BESIII detector. We exclusively reconstruct three D0 and six D+ hadronic decay modes and use the ratio of the yield of fully reconstructed Dbar D events ("double tags") to the yield of all reconstructed D or bar D mesons ("single tags") to determine the number of D0bar D0 and D+D− events, benefiting from the cancellation of many systematic uncertainties. Combining these yields with an independent determination of the integrated luminosity of the data sample, we find the cross sections to be σ(e+e− → D0bar D0) nb and σ(e+e− → D+D−) = (2.830 ± 0.011 ± 0.026) nb, where the uncertainties are statistical and systematic, respectively.
Using a data sample of 𝑒+𝑒− collisions corresponding to an integrated luminosity of 567 pb−1 collected at a center-of-mass energy of √𝑠=4.6 GeV with the BESIII detector, we measure the absolute branching fraction of the inclusive semileptonic Λ+𝑐 decay with a double-tag method. We obtain ℬ(Λ+𝑐→𝑋𝑒+𝜈𝑒)=(3.95±0.34±0.09)%, where the first uncertainty is statistical and the second systematic. Using the known Λ+𝑐 lifetime and the charge-averaged semileptonic decay width of nonstrange charmed mesons (𝐷0 and 𝐷+), we obtain the ratio of the inclusive semileptonic decay widths Γ(Λ+𝑐→𝑋𝑒+𝜈𝑒)/¯Γ(𝐷→𝑋𝑒+𝜈𝑒)=1.26±0.12.
Using a data sample of 448.1 × 106 ψ(3686) events collected with the BESIII detector at the BEPCII collider, we report the first observation of the electromagnetic Dalitz decay ψ(3686) → η e+e−, with significances of 7.0σ and 6.3σ when reconstructing the η meson via its decay modes η → γπ+π− and η → π+π−η (η → γγ ), respectively. The weighted average branching fraction is determined to be B(ψ(3686) → η e+e−) = (1.90 ± 0.25 ± 0.11) × 10−6, where the first uncertainty is statistical and the second systematic.
b̄b̄ud tetraquark resonances in the Born-Oppenheimer approximation using lattice QCD potentials
(2018)
We study tetraquark resonances using lattice QCD potentials for a pair of static antiquarks b¯b¯ in the presence of two light quarks ud. The system is treated in the Born-Oppenheimer approximation and we use the emergent wave method. We focus on the isospin I=0 channel, but consider different orbital angular momenta l of the heavy antiquarks b¯b¯. We extract the phase shifts and search for S and T matrix poles on the second Riemann sheet. For orbital angular momentum l=1 we find a tetraquark resonance with quantum numbers I(JP)=0(1−), resonance mass m=10576+4−4MeV and decay width Γ=112+90−103MeV, which can decay into two B mesons.
Background: Dialectical behaviour therapy for posttraumatic stress disorder (DBT-PTSD), which is tailored to treat adults with PTSD and co-occurring emotion regulation difficulties, has already demonstrated its efficacy, acceptance and safety in an inpatient treatment setting. It combines elements of DBT with trauma-focused cognitive behavioural interventions.
Objective: To investigate the feasibility, acceptance and safety of DBT-PTSD in an outpatient treatment setting by therapists who were novice to the treatment, we treated 21 female patients suffering from PTSD following childhood sexual abuse (CSA) plus difficulties in emotion regulation in an uncontrolled clinical trial.
Method: The Clinician Administered PTSD Symptom Scale (CAPS), the Davidson Trauma Scale (DTS), the Borderline Section of the International Personality Disorder Examination (IPDE) and the Borderline Symptom List (BSL-23) were used as primary outcomes. For secondary outcomes, depression and dissociation were assessed. Assessments were administered at pretreatment, post-treatment and six-week follow-up.
Results: Improvement was significant for PTSD as well as for borderline personality symptomatology, with large pretreatment to follow-up effect sizes for completers based on the CAPS (Cohens d = 1.30), DTS (d = 1.50), IPDE (d = 1.60) and BSL-23 (d = 1.20).
Conclusion: The outcome suggests that outpatient DBT-PTSD can safely be used to reduce PTSD symptoms and comorbid psychopathology in adults who have experienced CSA.
Telemonitoring devices can be used to screen consumer characteristics and mitigate information asymmetries that lead to adverse selection in insurance markets. Nevertheless, some consumers value their privacy and dislike sharing private information with insurers. In a secondbest efficient Miyazaki-Wilson-Spence (MWS) framework, we allow consumers to reveal their risk type for an individual subjective cost and show analytically how this affects insurance market equilibria as well as social welfare. We find that information disclosure can substitute deductibles for consumers whose transparency aversion is sufficiently low. This can lead to a Pareto improvement of social welfare. Yet, if all consumers are offered cross-subsidizing contracts, the introduction of a screening contract decreases or even eliminates cross-subsidies. Given the prior existence of a cross-subsidizing MWS equilibrium, utility is shifted from individuals who do not reveal their private information to those who choose to reveal. Our analysis informs the discussion on consumer protection in the context of digitalization. It shows that new technologies challenge cross-subsidization in insurance markets, and it stresses the negative externalities that digitalization has on consumers who are unwilling to take part in this
development
Weiträumige Kontaktnetzwerke sorgen für Verbreitung und Transfer von Wissen und Gütern sowie von kulturellen Werten. Der Transport von Lasten und Menschen kann als einer der wichtigsten Eckpfeiler solcher Austauschsysteme gesehen werden. Daher dürften die Suche nach Transportmöglichkeiten und die Entwicklung geeigneter Vehikel in der menschlichen Gedankenwelt seit jeher fest verankert sein. Die hier vorliegenden Beiträge basieren auf den Vorträgen der Tagung „Transporte, Transportwege und Transportstrukturen“ der Arbeitsgemeinschaft Bronzezeit und des Sonderforschungsbereiches 1070 RessourcenKulturen. Sie fassen im archäologischen Befund der Bronzezeit vorhandene Evidenzen zu Transportwegen und -fahrzeugen sowie Aussagen zu Infrastruktur nicht nur zusammen, sondern ergänzen diese um zahlreiche wissenswerte Aspekte. Was können diese Befunde über die Transportvehikel und ihre Bedeutung aussagen? Welche Eigenschaften wiesen diese auf? Handelt es sich bei den Fundstücken um abgenutzte oder mutwillig zerstörte Fahrzeuge bzw. Teile von solchen? Welche Implikationen auf technologischer und sozialer Ebene lassen sich mit den Befunden verbinden? Wie muss man sich die bronzezeitliche Infrastruktur in unterschiedlichen Regionen vorstellen? Inwiefern bildeten Verkehrswege und Austausch eine Ressource? Der detaillierten Beantwortung dieser Fragen ist dieser Band gewidmet, woraus eine übergreifende Zusammenschau von Funden, Befunden und Theorien entstanden ist.
We prove the existence of an equilibrium in competitive markets with adverse selection in the sense of Miyazaki (1977), Wilson (1977), and Spence (1978) when the distribution of unobservable risk types is continuous. Our proof leverages the finite-type proof in Spence (1978) and a limiting argument akin to Hellwig (2007)’s study of optimal taxation.
Attention-deficit/hyperactivity disorder (ADHD) is highly heritable and the most common neurodevelopmental disorder in childhood. In recent decades, it has been appreciated that in a substantial number of cases the disorder does not remit in puberty, but persists into adulthood. Both in childhood and adulthood, ADHD is characterised by substantial comorbidity including substance use, depression, anxiety, and accidents. However, course and symptoms of the disorder and the comorbidities may fluctuate and change over time, and even age of onset in childhood has recently been questioned. Available evidence to date is poor and largely inconsistent with regard to the predictors of persistence versus remittance. Likewise, the development of comorbid disorders cannot be foreseen early on, hampering preventive measures. These facts call for a lifespan perspective on ADHD from childhood to old age. In this selective review, we summarise current knowledge of the long-term course of ADHD, with an emphasis on clinical symptom and cognitive trajectories, treatment effects over the lifespan, and the development of comorbidities. Also, we summarise current knowledge and important unresolved issues on biological factors underlying different ADHD trajectories. We conclude that a severe lack of knowledge on lifespan aspects in ADHD still exists for nearly every aspect reviewed. We encourage large-scale research efforts to overcome those knowledge gaps through appropriately granular longitudinal studies.
Through the lens of market participants' objective to minimize counterparty risk, we provide an explanation for the reluctance to clear derivative trades in the absence of a central clearing obligation. We develop a comprehensive understanding of the benefits and potential pitfalls with respect to a single market participant's counterparty risk exposure when moving from a bilateral to a clearing architecture for derivative markets. Previous studies suggest that central clearing is beneficial for single market participants in the presence of a sufficiently large number of clearing members. We show that three elements can render central clearing harmful for a market participant's counterparty risk exposure regardless of the number of its counterparties: 1) correlation across and within derivative classes (i.e., systematic risk), 2) collateralization of derivative claims, and 3) loss sharing among clearing members. Our results have substantial implications for the design of derivatives markets, and highlight that recent central clearing reforms might not incentivize market participants to clear derivatives.
Prenatal and postnatal experiences associated with epigenetic changes in the adult mouse brain
(2018)
To analyze the influences of early-life history on the brain epigenome, the offspring of mouse dams kept in an enriched or standard environment were exposed postnatally to enriched, standard, or adverse conditions. The methylation patterns of 7 candidate genes (9 loci) involved in developmental programming of stress vulnerability/resilience and psychiatric disease were analyzed in 6 brain regions of adult male and female mice. Exposure to an enriched prenatal environment was associated with widespread epigenetic changes (all of small effect size), affecting 29 of 324 (9%) gene/region-specific methylation patterns. The effects of either adverse or enriched postnatal conditions were tested separately in the two prenatal cohorts. Significant changes were observed in 2 of 324 (0.6%) loci in offspring of dams in a standard environment and 6 of 324 (1.9%) loci in animals that were exposed prenatally to an enriched environment. Prenatal life experiences appear to have a bigger effect on the adult brain epigenome than postnatal experiences. Positive prenatal life experiences may increase epigenetic plasticity of the brain later in life. All observed between-group differences were sex-specific, consistent with largely different developmental trajectories of the male and female brain. Multiple changes of small effect size are consistent with a multifactorial model of developmental programming of adult behavior and disease susceptibility.
The enzyme acetyl-CoA carboxylase (ACC) plays a crucial role in fatty acid metabolism. In recent years, ACC has been recognized as a promising drug target for treating different diseases. However, the role of ACC in vascular endothelial cells (ECs) has been neglected so far. To characterize the role of ACC, we used the ACC inhibitor, soraphen A, as a chemical tool, and also a gene silencing approach. We found that ACC1 was the predominant isoform in human umbilical vein ECs as well as in human microvascular ECs and that soraphen A reduced the levels of malonyl-CoA. We revealed that ACC inhibition shifted the lipid composition of EC membranes. Accordingly, membrane fluidity, filopodia formation, and migratory capacity were reduced. The antimigratory action of soraphen A depended on an increase in the cellular proportion of PUFAs and, most importantly, on a decreased level of phosphatidylglycerol. Our study provides a causal link between ACC, membrane lipid composition, and cell migration in ECs. Soraphen A represents a useful chemical tool to investigate the role of fatty acid metabolism in ECs and ACC inhibition offers a new and valuable therapeutic perspective for the treatment of EC migration-related diseases.
Pseudomonas aeruginosa is a human pathogen that causes health-care associated blood stream infections (BSI). Although P. aeruginosa BSI are associated with high mortality rates, the clinical relevance of pathogen-derived prognostic biomarker to identify patients at risk for unfavorable outcome remains largely unexplored. We found novel pathogen-derived prognostic biomarker candidates by applying a multi-omics approach on a multicenter sepsis patient cohort. Multi-level Cox regression was used to investigate the relation between patient characteristics and pathogen features (2298 accessory genes, 1078 core protein levels, 107 parsimony-informative variations in reported virulence factors) with 30-day mortality. Our analysis revealed that presence of the helP gene encoding a putative DEAD-box helicase was independently associated with a fatal outcome (hazard ratio 2.01, p = 0.05). helP is located within a region related to the pathogenicity island PAPI-1 in close proximity to a pil gene cluster, which has been associated with horizontal gene transfer. Besides helP, elevated protein levels of the bacterial flagellum protein FliL (hazard ratio 3.44, p < 0.001) and of a bacterioferritin-like protein (hazard ratio 1.74, p = 0.003) increased the risk of death, while high protein levels of a putative aminotransferase were associated with an improved outcome (hazard ratio 0.12, p < 0.001). The prognostic potential of biomarker candidates and clinical factors was confirmed with different machine learning approaches using training and hold-out datasets. The helP genotype appeared the most attractive biomarker for clinical risk stratification due to its relevant predictive power and ease of detection.
Rhythmic neural spiking and attentional sampling arising from cortical receptive field interactions
(2018)
Summary: Growing evidence suggests that distributed spatial attention may invoke theta (3-9 Hz) rhythmic sampling processes. The neuronal basis of such attentional sampling is however not fully understood. Here we show using array recordings in visual cortical area V4 of two awake macaques that presenting separate visual stimuli to the excitatory center and suppressive surround of neuronal receptive fields elicits rhythmic multi-unit activity (MUA) at 3-6 Hz. This neuronal rhythm did not depend on small fixational eye movements. In the context of a distributed spatial attention task, during which the monkeys detected a spatially and temporally uncertain target, reaction times (RT) exhibited similar rhythmic fluctuations. RTs were fast or slow depending on the target occurrence during high or low MUA, resulting in rhythmic MUA-RT cross-correlations at at theta frequencies. These findings suggest that theta-rhythmic neuronal activity arises from competitive receptive field interactions and that this rhythm may subserve attentional sampling.
Highlights:
* Center-surround interactions induce theta-rhythmic MUA of visual cortex neurons
* The MUA rhythm does not depend on small fixational eye movements
* Reaction time fluctuations lock to the neuronal rhythm under distributed attention
From August to November 2017, Madagascar endured an outbreak of plague. A total of 2417 cases of plague were confirmed, causing a death toll of 209. Public health intervention efforts were introduced and successfully stopped the epidemic at the end of November. The plague, however, is endemic in the region and occurs annually, posing the risk of future outbreaks. To understand the plague transmission, we collected real-time data from official reports, described the outbreak's characteristics, and estimated transmission parameters using statistical and mathematical models. The pneumonic plague epidemic curve exhibited multiple peaks, coinciding with sporadic introductions of new bubonic cases. Optimal climate conditions for rat flea to flourish were observed during the epidemic. Estimate of the plague basic reproduction number during the large wave of the epidemic was high, ranging from 5 to 7 depending on model assumptions. The incubation and infection periods for bubonic and pneumonic plague were 4.3 and 3.4 days and 3.8 and 2.9 days, respectively. Parameter estimation suggested that even with a small fraction of the population exposed to infected rat fleas (1/10,000) and a small probability of transition from a bubonic case to a secondary pneumonic case (3%), the high human-to-human transmission rate can still generate a large outbreak. Controlling rodent and fleas can prevent new index cases, but managing human-to-human transmission is key to prevent large-scale outbreaks.
The interaction of trimethyl(methylcyclopentadienyl)platinum(IV) ((C5H4CH3)Pt(CH3)3) molecules on fully and partially hydroxylated SiO2 surfaces, as well as the dynamics of this interaction were investigated using density functional theory (DFT) and finite temperature DFT-based molecular dynamics simulations. Fully and partially hydroxylated surfaces represent substrates before and after electron beam treatment and this study examines the role of electron beam pretreatment on the substrates in the initial stages of precursor dissociation and formation of Pt deposits. Our simulations show that on fully hydroxylated surfaces or untreated surfaces, the precursor molecules remain inactivated while we observe fragmentation of (C5H4CH3)Pt(CH3)3 on partially hydroxylated surfaces. The behavior of precursor molecules on the partially hydroxylated surfaces has been found to depend on the initial orientation of the molecule and the distribution of surface active sites. Based on the observations from the simulations and available experiments, we discuss possible dissociation channels of the precursor.
Meta Forkel, 1765–1853
(2018)
Sophie Margarethe ("Meta") Dorothea Liebeskind, als Mitarbeiterin in der "Übersetzungsfabrik" Georg Forsters besser bekannt unter dem Namen ihres ersten Mannes, Forkel, gehört mit über 20, zum Teil mehrbändigen übersetzten Werken zu den produktivsten Übersetzerinnen ihrer Zeit. Ihre beachtliche Leistung als Übersetzerin wird noch deutlicher, wenn man sich vor Augen hält, dass ihre Übersetzungen bis auf wenige Ausnahmen in dem vergleichsweise kurzen Zeitraum zwischen 1788 und 1799 entstanden sind.
Measurement of the inclusive J/ψ polarization at forward rapidity in pp collisions at √s = 8 TeV
(2018)
We report on the measurement of the inclusive J/ψ polarization parameters in pp collisions at a center of mass energy s√=8 TeV with the ALICE detector at the LHC. The analysis is based on a data sample corresponding to an integrated luminosity of 1.23 pb−1. J/ψ resonances are reconstructed in their di-muon decay channel in the rapidity interval 2.5<y<4.0 and over the transverse-momentum interval 2<pT<15 GeV/c. The three polarization parameters (λθ, λφ, λθφ) are measured as a function of pT both in the helicity and Collins-Soper reference frames. The measured J/ψ polarization parameters are found to be compatible with zero within uncertainties, contrary to expectations from all available predictions. The results are compared with the measurement in pp collisions at s√=7 TeV.
ϕ meson measurements provide insight into strangeness production, which is one of the key observables for the hot medium formed in high-energy heavy-ion collisions. ALICE measured ϕ production through its decay in muon pairs in Pb-Pb collisions at sNN−−−√ = 2.76 TeV in the intermediate transverse momentum range 2<pT<5 GeV/c and in the rapidity interval 2.5<y<4. The ϕ yield was measured as a function of the transverse momentum and collision centrality. The nuclear modification factor was obtained as a function of the average number of participating nucleons. Results were compared with the ones obtained via the kaon decay channel in the same pT range at midrapidity. The values of the nuclear modification factor in the two rapidity regions are in agreement within uncertainties.
The elliptic (v2), triangular (v3), and quadrangular (v4) flow coefficients of π±, K±, p+p¯¯¯, Λ+Λ¯¯¯¯, K0S, and the ϕ-meson are measured in Pb-Pb collisions at sNN−−−√=5.02 TeV. Results obtained with the scalar product method are reported for the rapidity range |y|< 0.5 as a function of transverse momentum, pT, at different collision centrality intervals between 0-70%, including ultra-central (0-1%) collisions for π±, K±, and p+p¯¯¯. For pT<3 GeV/c, the flow coefficients exhibit a particle mass dependence. At intermediate transverse momenta (3<pT<~8-10 GeV/c), particles show an approximate grouping according to their type (i.e., mesons and baryons). The ϕ-meson v2, which tests both particle mass dependence and type scaling, follows p+p¯¯¯ v2 at low pT and π± v2 at intermediate pT. The evolution of the shape of vn(pT) as a function of centrality and harmonic number n is studied for the various particle species. Flow coefficients of π±, K±, and p+p¯¯¯ for pT<3 GeV/c are compared to iEBE-VISHNU and MUSIC hydrodynamical calculations coupled to a hadronic cascade model (UrQMD). The iEBE-VISHNU calculations describe the results fairly well for pT<2.5 GeV/c, while MUSIC calculations reproduce the measurements for pT<1 GeV/c. A comparison to vn coefficients measured in Pb-Pb collisions at sNN−−−√ = 2.76 TeV is also provided.
Measurements of anisotropic flow coefficients with two- and multi-particle cumulants for inclusive charged particles in Pb-Pb collisions at sNN−−−√=5.02 and 2.76 TeV are reported in the pseudorapidity range |η|<0.8 and transverse momentum 0.2<pT<50 GeV/c. The full data sample collected by the ALICE detector in 2015 (2010), corresponding to an integrated luminosity of 12.7 (2.0) μb−1 in the centrality range 0-80%, is analysed. Flow coefficients up to the sixth flow harmonic (v6) are reported and a detailed comparison among results at the two energies is carried out. The pT dependence of anisotropic flow coefficients and its evolution with respect to centrality and harmonic number n are investigated. An approximate power-law scaling of the form vn(pT)∼pn/3T is observed for all flow harmonics at low pT (0.2<pT<3 GeV/c). At the same time, the ratios vn/vn/mm are observed to be essentially independent of pT for most centralities up to about pT=10 GeV/c. Analysing the differences among higher-order cumulants of elliptic flow (v2), which have different sensitivities to flow fluctuations, a measurement of the standardised skewness of the event-by-event v2 distribution P(v2) is reported and constraints on its higher moments are provided. The Elliptic Power distribution is used to parametrise P(v2), extracting its parameters from fits to cumulants. The measurements are compared to different model predictions in order to discriminate among initial-state models and to constrain the temperature dependence of the shear viscosity to entropy-density ratio.
Der Beitrag beschäftigt sich mit der Typologie und Chronologie einer besonders vielfältigen und bisher schlecht fassbaren Gruppe unter den metallenen Wagenbeschlägen der Urnenfelder- und Hallstattzeit in Südost-, Mittel- und Westeuropa, den Tüllen und Kappen. Neben einem Gesamtüberblick über das entsprechende Fundmaterial werden einzelne Typen detailliert beschrieben, abgebildet und in ihren wechselseitigen Bezügen diskutiert. Deutlich lassen sich auch bei dieser Objektgruppe die engen typologischen Verbindungen zwischen den urnenfelder- und hallstattzeitlichen Wagenbeschlägen darstellen. Die quantitativ wie qualitativ sehr viel bessere Überlieferung der hallstattzeitlichen Wagen legt es nahe, die urnenfelderzeitliche Wagenentwicklung vor allem in der Rückschau zu betrachten. Insbesondere was den einstigen Anbringungsort der metallenen Beschläge am Wagen angeht, ist das Studium gut dokumentierter in situ-Befunde hallstattzeitlicher Wagengräber sehr hilfreich. Hinsichtlich der Tüllen und Kappen sind vielfältige Möglichkeiten der Anbringung festzustellen, die praktisch alle Teile des Wagens von den Achsen über die Zugvorrichtung und den Langbaum bis zum Wagenkasten betreffen. Eine interessante Möglichkeit ist zudem die Deutung einiger schmaler Tüllen als Griffenden von Treibstacheln, deren Existenz bereits in der Bronzezeit verschiedentlich belegbar ist...
Relevance of the natural HDAC inhibitor sulforaphane as a chemopreventive agent in urologic tumors
(2018)
Due to an increased understanding of molecular biology and the genomics of cancer, new and potent agents have been approved by the Food and Drug Administration (FDA) to fight this disease. However, all of these drugs cause severe side effects and resistance inevitably develops, re-activating tumor growth and dissemination. For this reason, patients turn to natural compounds as alternative or complementary treatment options, since it has been found that natural plant products may block, inhibit, or reverse cancer development. The present review focusses on the role of the natural compound sulforaphane (SFN) as an anti-tumor agent in urologic cancer. SFN is a natural compound found in cruciferous vegetables from the Brassicaceae family such as broccoli, cauliflower and cabbage. Several epidemiologic and clinical studies have documented chemopreventive properties of SFN, making it an interesting candidate for additive cancer treatment. SFN shows remarkable anti-tumor effects in vitro and in vivo without exerting toxicity. The review summarizes the current understanding of SFN and provides insights into its molecular mode of action with particular emphasis on epigenetic tumor control.
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.
A measurement of the production of prompt Λ+c baryons in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC is reported. The Λ+c and Λ¯¯¯¯−c were reconstructed at midrapidity (|y|<0.5) via the hadronic decay channel Λ+c→pK0S (and charge conjugate) in the transverse momentum and centrality intervals 6<pT<12 GeV/c and 0-80%. The Λ+c/D0 ratio, which is sensitive to the charm quark hadronisation mechanisms in the medium, is measured and found to be larger than the ratio measured in minimum-bias pp collisions at s√=7 TeV and in p-Pb collisions at sNN−−−√=5.02 TeV. In particular, the values in p-Pb and Pb-Pb collisions differ by about two standard deviations of the combined statistical and systematic uncertainties. The Λ+c/D0 ratio is also compared with model calculations including different implementations of charm quark hadronisation. The measured ratio is reproduced by models implementing a pure coalescence scenario, while adding a fragmentation contribution leads to an underestimation. The Λ+c nuclear modification factor, RAA, is also presented. The measured values of the RAA of Λ+c, Ds and non-strange D mesons are compatible within the combined statistical and systematic uncertainties. They show, however, a hint of a hierarchy (RD0AA<RDsAA<RΛ+cAA), conceivable with a contribution of recombination mechanisms to charm hadron formation in the medium.
Charged-particle pseudorapidity density at mid-rapidity in p–Pb collisions at √sNN = 8.16 TeV
(2018)
The pseudorapidity density of charged particles, dNch/dη, in p-Pb collisions has been measured at a centre-of-mass energy per nucleon-nucleon pair of sNN−−−√ = 8.16 TeV at mid-pseudorapidity for non-single-diffractive events. The results cover 3.6 units of pseudorapidity, |η|<1.8. The dNch/dη value is 19.1±0.7 at |η|<0.5. This quantity divided by ⟨Npart⟩/2, is 4.73±0.20, which is 9.5% higher than the corresponding value for p-Pb collisions at sNN−−−√ = 5.02 TeV. Measurements are compared with models based on different mechanisms for particle production. All models agree within uncertainties with data in the Pb-going side, while HIJING overestimates, showing a symmetric behaviour, and EPOS underestimates the p-going side of the dNch/dη distribution. Saturation-based models reproduce the distributions well for η>−1.3. The dNch/dη is also measured for different centrality estimators, based both on the charged-particle multiplicity and on the energy deposited in the Zero-Degree Calorimeters. A study of the implications of the large multiplicity fluctuations due to the small number of participants for systems like p-Pb in the centrality calculation for multiplicity-based estimators is discussed, demonstrating the advantages of determining the centrality with energy deposited near beam rapidity.
We present the first measurements of femtoscopic correlations between the K0S and K± particles in pp collisions at s√=7 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding solely via the a0(980) resonance. The extracted kaon source radius and correlation strength parameters for K0SK− are found to be equal within the experimental uncertainties to those for K0SK+. Results of the present study are compared with those from identical-kaon femtoscopic studies also performed with pp collisions at s√=7 TeV by ALICE and with a K0SK± measurement in Pb-Pb collisions at sNN−−−√=2.76 TeV. Combined with the Pb-Pb results, our pp analysis is found to be compatible with the interpretation of the a0(980) having a tetraquark structure instead of that of a diquark.
The first measurement of dielectron (e+e−) production in central (0−10%) Pb-Pb collisions at sNN−−−√ = 2.76 TeV at the LHC is presented. The dielectron invariant-mass spectrum is compared to the expected contributions from hadron decays in the invariant-mass range 0<mee<3.5 GeV/c2. The ratio of data and the cocktail of hadronic contributions without vacuum ρ0 is measured in the invariant-mass range 0.15<mee<0.7 GeV/c2, where an excess of dielectrons is observed in other experiments, and its value is 1.40±0.28 (stat.)±0.08 (syst.)±0.27 (cocktail). The dielectron spectrum measured in the invariant mass range 0<mee<1 GeV/c2 is consistent with the predictions from two theoretical model calculations that include thermal dielectron production from both partonic and hadronic phases with in-medium broadened ρ0 meson. The fraction of direct virtual photons over inclusive virtual photons is extracted for dielectron pairs with invariant mass 0.1<mee<0.3 GeV/c2, and in the transverse-momentum intervals 1<pT,ee<2 GeV/c and 2<pT,ee<4 GeV/c. The measured fraction of virtual direct photons is consistent with the measurement of real direct photons by ALICE and with the expectations from previous dielectron measurements at RHIC within the experimental uncertainties.
The production yield of the Λ(1520) baryon resonance is measured at mid-rapidity in Pb-Pb collisions at sNN−−−√ = 2.76 TeV with the ALICE detector at the LHC. The measurement is performed in the Λ(1520)→pK− (and charge conjugate) hadronic decay channel as a function of the transverse momentum (pT) and collision centrality. The pT-integrated production rate of Λ(1520) relative to Λ in central collisions is suppressed by about a factor of 2 with respect to peripheral collisions. This is the first observation of the suppression of a baryonic resonance at LHC and the first evidence of Λ(1520) suppression in heavy-ion collisions. The measured Λ(1520)/Λ ratio in central collisions is smaller than the value predicted by the statistical hadronisation model calculations. The shape of the measured pT distribution and the centrality dependence of the suppression are reproduced by the EPOS3 Monte Carlo event generator. The measurement adds further support to the formation of a dense hadronic phase in the final stages of the evolution of the fireball created in heavy-ion collisions, lasting long enough to cause a significant reduction in the observable yield of short-lived resonances.
We report the differential charged jet cross section and jet fragmentation distributions measured with the ALICE detector in proton-proton collisions at a centre-of-mass energy s√= 7 TeV. Jets with pseudo-rapidity |η|<0.5 are reconstructed from charged particles using the anti-kT jet finding algorithm with a resolution parameter R = 0.4. The jet cross section is measured in the transverse momentum interval 5 ≤pchjetT< 100 GeV/c. Jet fragmentation is studied measuring the scaled transverse momentum spectra of the charged constituents of jets in four intervals of jet transverse momentum between 5 GeV/c and 30 GeV/c. The measurements are compared to calculations from the PYTHIA model as well as next-to-leading order perturbative QCD calculations with POWHEG + PYTHIA8. The charged jet cross section is described by POWHEG for the entire measured range of pchjetT. For pchjetT > 40 GeV/c, the PYTHIA calculations also agree with the measured charged jet cross section. PYTHIA6 simulations describe the fragmentation distributions to 15%. Larger discrepancies are observed for PYTHIA8.
Comprehensive results on the production of unidentified charged particles, π±, K±, K0S, K*(892)0, p, p¯¯¯, ϕ(1020), Λ, Λ¯¯¯¯, Ξ−, Ξ¯¯¯¯+, Ω− and Ω¯¯¯¯+ hadrons in proton-proton (pp) collisions at s√ = 7 TeV at midrapidity (|y|<0.5) as a function of charged-particle multiplicity density are presented. In order to avoid auto-correlation biases, the actual transverse momentum (pT) spectra of the particles under study and the event activity are measured in different rapidity windows. In the highest multiplicity class, the charged-particle density reaches about 3.5 times the value measured in inelastic collisions. While the yield of protons normalized to pions remains approximately constant as a function of multiplicity, the corresponding ratios of strange hadrons to pions show a significant enhancement that increases with increasing strangeness content. Furthermore, all identified particle to pion ratios are shown to depend solely on charged-particle multiplicity density, regardless of system type and collision energy. The evolution of the spectral shapes with multiplicity and hadron mass shows patterns that are similar to those observed in p-Pb and Pb-Pb collisions at LHC energies. The obtained pT distributions and yields are compared to expectations from QCD-based pp event generators as well as to predictions from thermal and hydrodynamic models. These comparisons indicate that traces of a collective, equilibrated system are already present in high-multiplicity pp collisions.
The transverse structure of jets was studied via jet fragmentation transverse momentum (jT) distributions, obtained using two-particle correlations in proton-proton and proton-lead collisions, measured with the ALICE experiment at the LHC. The highest transverse momentum particle in each event is used as the trigger particle and the region 3<pTt<15 GeV/c is explored in this study. The measured distributions show a clear narrow Gaussian component and a wide non-Gaussian one. Based on Pythia simulations, the narrow component can be related to non-perturbative hadronization and the wide component to quantum chromodynamical splitting. The width of the narrow component shows a weak dependence on the transverse momentum of the trigger particle, in agreement with the expectation of universality of the hadronization process. On the other hand, the width of the wide component shows a rising trend suggesting increased branching for higher transverse momentum. The results obtained in pp collisions at s√ = 7 TeV and in p-Pb collisions at sNN−−−√ = 5.02 TeV are compatible within uncertainties and hence no significant cold nuclear matter effects are observed. The results are compared to previous measurements from CCOR and PHENIX as well as to Pythia 8 and Herwig 7 simulations.
At the Large Hadron Collider at CERN in Geneva, Switzerland, atomic nuclei are collided at ultra-relativistic energies. Many final-state particles are produced in each collision and their properties are measured by the ALICE detector. The detector signals induced by the produced particles are digitized leading to data rates that are in excess of 48 GB/s. The ALICE High Level Trigger (HLT) system pioneered the use of FPGA- and GPU-based algorithms to reconstruct charged-particle trajectories and reduce the data size in real time. The results of the reconstruction of the collision events, available online, are used for high level data quality and detector-performance monitoring and real-time time-dependent detector calibration. The online data compression techniques developed and used in the ALICE HLT have more than quadrupled the amount of data that can be stored for offline event processing.
Medium modification of the shape of small-radius jets in central Pb–Pb collisions at √sNN = 2.76 TeV
(2018)
We present the measurement of a new set of jet shape observables for track-based jets in central Pb-Pb collisions at sNN−−−√=2.76 TeV. The set of jet shapes includes the first radial moment or angularity, g; the momentum dispersion, pTD; and the difference between the leading and sub-leading constituent track transverse momentum, LeSub. These observables provide complementary information on the jet fragmentation and can constrain different aspects of the theoretical description of jet-medium interactions. The jet shapes were measured for a small resolution parameter R=0.2 and were fully corrected to particle level. The observed jet shape modifications indicate that in-medium fragmentation is harder and more collimated than vacuum fragmentation as obtained by PYTHIA calculations, which were validated with the measurements of the jet shapes in proton-proton collisions at s√=7 TeV. The comparison of the measured distributions to templates for quark and gluon-initiated jets indicates that in-medium fragmentation resembles that of quark jets in vacuum. We further argue that the observed modifications are not consistent with a totally coherent energy loss picture where the jet loses energy as a single colour charge, suggesting that the medium resolves the jet structure at the angular scales probed by our measurements (R=0.2). Furthermore, we observe that small-R jets can help to isolate purely energy loss effects from other effects that contribute to the modifications of the jet shower in medium such as the correlated background or medium response.