644 research outputs found
Reducing the weak lensing noise for the gravitational wave Hubble diagram using the non-Gaussianity of the magnification distribution
Gravitational wave sources are a promising cosmological standard candle
because their intrinsic luminosities are determined by fundamental physics (and
are insensitive to dust extinction). They are, however, affected by weak
lensing magnification due to the gravitational lensing from structures along
the line of sight. This lensing is a source of uncertainty in the distance
determination, even in the limit of perfect standard candle measurements. It is
commonly believed that the uncertainty in the distance to an ensemble of
gravitational wave sources is limited by the standard deviation of the lensing
magnification distribution divided by the square root of the number of sources.
Here we show that by exploiting the non-Gaussian nature of the lensing
magnification distribution, we can improve this distance determination,
typically by a factor of 2--3; we provide a fitting formula for the effective
distance accuracy as a function of redshift for sources where the lensing noise
dominates.Comment: matches PRD accepted version (expanded description of the
cosmological parameter space + minor changes
Exploiting Single-Cell Tools in Gene and Cell Therapy.
Single-cell molecular tools have been developed at an incredible pace over the last five years as sequencing costs continue to drop and numerous molecular assays have been coupled to sequencing readouts. This rapid period of technological development has facilitated the delineation of individual molecular characteristics including the genome, transcriptome, epigenome, and proteome of individual cells, leading to an unprecedented resolution of the molecular networks governing complex biological systems. The immense power of single-cell molecular screens has been particularly highlighted through work in systems where cellular heterogeneity is a key feature, such as stem cell biology, immunology, and tumor cell biology. Single-cell-omics technologies have already contributed to the identification of novel disease biomarkers, cellular subsets, therapeutic targets and diagnostics, many of which would have been undetectable by bulk sequencing approaches. More recently, efforts to integrate single-cell multi-omics with single cell functional output and/or physical location have been challenging but have led to substantial advances. Perhaps most excitingly, there are emerging opportunities to reach beyond the description of static cellular states with recent advances in modulation of cells through CRISPR technology, in particular with the development of base editors which greatly raises the prospect of cell and gene therapies. In this review, we provide a brief overview of emerging single-cell technologies and discuss current developments in integrating single-cell molecular screens and performing single-cell multi-omics for clinical applications. We also discuss how single-cell molecular assays can be usefully combined with functional data to unpick the mechanism of cellular decision-making. Finally, we reflect upon the introduction of spatial transcriptomics and proteomics, its complementary role with single-cell RNA sequencing (scRNA-seq) and potential application in cellular and gene therapy
The Janthinobacterium sp. HH01 genome encodes a homologue of the V. cholerae CqsA and L. pneumophila LqsA autoinducer synthases
Janthinobacteria commonly form biofilms on eukaryotic hosts and are known to synthesize antibacterial and antifungal compounds. Janthinobacterium sp. HH01 was recently isolated from an aquatic environment and its genome sequence was established. The genome consists of a single chromosome and reveals a size of 7.10 Mb, being the largest janthinobacterial genome so far known. Approximately 80% of the 5,980 coding sequences (CDSs) present in the HH01 genome could be assigned putative functions. The genome encodes a wealth of secretory functions and several large clusters for polyketide biosynthesis. HH01 also encodes a remarkable number of proteins involved in resistance to drugs or heavy metals. Interestingly, the genome of HH01 apparently lacks the N-acylhomoserine lactone (AHL)-dependent signaling system and the AI-2-dependent quorum sensing regulatory circuit. Instead it encodes a homologue of the Legionella- and Vibrio-like autoinducer (lqsA/cqsA) synthase gene which we designated jqsA. The jqsA gene is linked to a cognate sensor kinase (jqsS) which is flanked by the response regulator jqsR. Here we show that a jqsA deletion has strong impact on the violacein biosynthesis in Janthinobacterium sp. HH01 and that a jqsA deletion mutant can be functionally complemented with the V. cholerae cqsA and the L. pneumophila lqsA genes
Pan-chromatic observations of the remarkable nova LMC 2012
We present the results of an intensive multiwavelength campaign on nova LMC
2012. This nova evolved very rapidly in all observed wavelengths. The time to
fall two magnitudes in the V band was only 2 days. In X-rays the super soft
phase began 135 days after discovery and ended around day 50 after
discovery. During the super soft phase, the \Swift/XRT and \Chandra\ spectra
were consistent with the underlying white dwarf being very hot, 1 MK,
and luminous, 10 erg s. The UV, optical, and near-IR
photometry showed a periodic variation after the initial and rapid fading had
ended. Timing analysis revealed a consistent 19.240.03 hr period in all
UV, optical, and near-IR bands with amplitudes of 0.3 magnitudes which
we associate with the orbital period of the central binary. No periods were
detected in the corresponding X-ray data sets. A moderately high inclination
system, = 6010^{\arcdeg}, was inferred from the early optical
emission lines. The {\it HST}/STIS UV spectra were highly unusual with only the
\ion{N}{5} (1240\AA) line present and superposed on a blue continuum. The lack
of emission lines and the observed UV and optical continua from four epochs can
be fit with a low mass ejection event, 10 M, from a hot
and massive white dwarf near the Chandrasekhar limit. The white dwarf, in turn,
significantly illuminated its subgiant companion which provided the bulk of the
observed UV/optical continuum emission at the later dates. The inferred extreme
white dwarf characteristics and low mass ejection event favor nova LMC 2012
being a recurrent nova of the U Sco subclass.Comment: 18 figures, 6 tables (one online only containing all the photometry
Die Digitale Bibliothek der Akademie der Wissenschaften zu Göttingen
Die Akademie der Wissenschaften zu Göttingen (AdWG) und die niedersächsische Staats- und Universitätsbibliothek Göttingen (SUB) haben ihre bestehende Kooperation zum Webportal der AdWG intensiviert, das einen Überblick über die Aktivitäten der Göttinger Akademie und umfangreiche Information zu den zahlreichen Langzeitvorhaben bietet und die digitalen Publikationen präsentiert. Zentraler Bestandteil des Webportals ist die Digitale Bibliothek der AdWG, für die im Rahmen der Kooperation neue Präsentationsformen für die Forschungsdaten aus den Akademie-Vorhaben konzipiert und entwickelt wurden. Ein Beispiel für die Umsetzung neuer Präsentationsformen im Portal ist das Edfu-Projekt, dessen Ziel eine Gesamtübersetzung aller Inschriften des Tempels von Edfu in Oberägypten ist. Hinzugezogen werden dazu alle internen, greifbaren, in den Schriften enthaltenen Parallelen, auf die online über das Webportal zugegriffen werden kann. Zerstörte Bereiche lassen sich dadurch oftmals ebenso ergänzen, wie zunächst unverständliche Textpassagen mit Sinn versehen werden können. Nicht nur die bereits vorübersetzten Texte sind auf diese Weise abrufbar, sondern darüber hinaus zahlreiche zusätzliche Materialien, wie z.B. das Fotoarchiv mit seinen mehr als 20.000 Bildern. Die Vernetzung all dieser Daten schafft einen für die Wissenschaft ungewöhnlich tiefen Einblick in die Planung und Konzeption eines altägyptischen Tempels, seiner religiösen Hintergründe und historischen Zusammenhänge.The Göttingen Academy of Sciences and Humanities (AdWG) and the Göttingen State and University Library (SUB) have intensified their existing cooperation on the web portal of the AdWG. The portal provides an overview of the activities of the Göttingen Academy as well as extensive information on its numerous long-term projects. It also presents the academy’s digital publications. A crucial part of the web portal is the Digital Library of the AdWG. Within the framework of the cooperation, new forms of presentation for the research data from the Academy projects have been conceptualized and developed. An example of the implementation of such a new form of presentation is the Edfu project. The goal of this project is an exhaustive translation of all inscriptions from the temple of Edfu in Upper Egypt. For this, all internal text parallels, which are accessible on the internet platform, are taken into account. This helps to reconstruct damaged inscriptions and recover the meaning of texts which seem incomprehensible at first. Not only the pre-translated texts are accessible online, but also the digital photo archive which covers more than 20.000 images. Bringing all this data into one network offers unusually deep insights into the planning and conceptualization of an ancient Egyptian temple, its religious background und historical context
Distinguishing Social from Nonsocial Navigation in Moving Animal Groups
Many animals, such as migrating shoals of fish, navigate in groups. Knowing the mechanisms involved in animal navigation is important when it comes to explaining navigation accuracy, dispersal patterns, population and evolutionary dynamics, and consequently, the design of conservation strategies. When navigating toward a common target, animals could interact socially by sharing available information directly or indirectly, or each individual could navigate by itself and aggregations may not disperse because all animals are moving toward the same target. Here we present an analysis technique that uses individual movement trajectories to determine the extent to which individuals in navigating groups interact socially, given knowledge of their target. The basic idea of our approach is that the movement directions of individuals arise from a combination of responses to the environment and to other individuals. We estimate the relative importance of these responses, distinguishing between social and nonsocial interactions. We develop and test our method, using simulated groups, and we demonstrate its applicability to empirical data in a case study on groups of guppies moving toward shelter in a tank. Our approach is generic and can be extended to different scenarios of animal group movement. © 2012 by The University of Chicago
Deoxyfluorination using CuF2 : enabled by a Lewis base activating group strategy
We thank the University of St Andrews for PhD studentships (D.E.S and S.C.), GlaxoSmithKline and the University of Glasgow for financial support.Deoxyfluorination is a primary method for the formation of C–F bonds. Bespoke reagents are commonly used due to issues associated with the low reactivity of metal fluorides. Here, we report the development of a simple strategy for deoxyfluorination using first‐row transition metal fluorides that overcomes these limitations. Using CuF2 as an exemplar, activation of an O ‐alkylisourea adduct formed in situ allows effective nucleophilic fluoride transfer to a range of primary and secondary alcohols. Spectroscopic investigations have been used to probe the origin of the enhanced reactivity of CuF2 . The utility of the process towards enabling 18F‐radiolabeling is also presented.PostprintPeer reviewe
EXCHANGE-2: investigating the efficacy of add-on plasma exchange as an adjunctive strategy against septic shock—a study protocol for a randomized, prospective, multicenter, open-label, controlled, parallel-group trial
Background
Sepsis is as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. The mortality of sepsis and particular of septic shock is very high. Treatment mostly focuses on infection control but a specific intervention that targets the underlying pathological host response is lacking to the present time.
The investigators hypothesize that early therapeutic plasma exchange (TPE) will dampen the maladaptive host response by removing injurious mediators thereby limiting organ dysfunction and improving survival in patients with septic shock. Although small prospective studies demonstrated rapid hemodynamic stabilization under TPE, no adequately powered randomized clinical trial has investigated hard outcomes.
Methods
This is a randomized, prospective, multicenter, open-label, controlled, parallel-group interventional trial to test the adjunctive effect of TPE in patients with early septic shock. Patients with a refractory (defined as norepinephrine (NE) ≥ 0.4 μg/kg/min ≥ 30 min OR NE 0.3 μg/kg/min + vasopressin) and early (shock onset < 24 h) septic shock will be included. The intervention is a standard TPE with donor fresh frozen plasma (1.2 × individual plasma volume) performed within 6 h after randomization and will be compared to a standard of care (SOC) control arm. The primary endpoint is 28 days mortality for which the power analysis revealed a group size of 137 / arm (n = 274) to demonstrate a benefit of 15%. The key secondary objective will be to compare the extent of organ failure indicated by mean SOFA over the first 7 days as well as organ support-free days until day 28 following randomization. Besides numerous biological secondary, safety endpoints such as incidence of bleeding, allergic reactions, transfusion associated lung injury, severe thrombocytopenia, and other severe adverse events will be assessed during the first 7 days. For exploratory scientific analyses, biomaterial will be acquired longitudinally and multiple predefined scientific subprojects are planned. This study is an investigator-initiated trial supported by the German Research Foundation (DFG, DA 1209/7–1), in which 26 different centers in Germany, Switzerland, and Austria will participate over a duration of 33 months.
Discussion
This trial has substantial clinical relevance as it evaluates a promising adjunctive treatment option in refractory septic shock patients suffering from an extraordinary high mortality. A positive trial result could change the current standard of care for this septic subgroup. The results of this study will be disseminated through presentations at international congresses, workshops, and peer-reviewed publications.
Trial registration
ClinicalTrials.gov NCT05726825, Registered on 14 February 2023
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