256 research outputs found
Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer
To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naΓ―ve, and Eastern Oncology Cooperative Group 0β2. The first cohort received SPI-77 at 100βmgβmβ2, the second 200βmgβmβ2 and the final cohort 260βmgβmβ2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200βmgβmβ2 dose level for an overall response rate of 4.5% (7.1% at β©Ύ200βmgβmβ2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC
The angular-momentum flux in the solar wind observed during Solar Orbiter's first orbit
Aims: We present the first measurements of the angular-momentum flux in the solar wind recorded by the Solar Orbiter spacecraft.
Our aim is to validate these measurements to support future studies of the Sunβs angular-momentum loss.
Methods: We combined 60-min averages of the proton bulk moments and the magnetic field measured by the Solar Wind Analyser
(SWA) and the magnetometer (MAG) onboard Solar Orbiter. We calculated the angular-momentum flux per solid-angle element using
data from the first orbit of the missionβs cruise phase in 2020. We separated the contributions from protons and from magnetic stresses
to the total angular-momentum flux.
Results: The angular-momentum flux varies significantly over time. The particle contribution typically dominates over the magneticfield contribution during our measurement interval. The total angular-momentum flux shows the largest variation and is typically anticorrelated with the radial solar-wind speed. We identify a compression region, potentially associated with a co-rotating interaction
region or a coronal mass ejection, which leads to a significant localised increase in the angular-momentum flux, albeit without a
significant increase in the angular momentum per unit mass. We repeated our analysis using the density estimate from the Radio and
Plasma Waves (RPW) instrument. Using this independent method, we find a decrease in the peaks of positive angular-momentum
flux, but otherwise, our results remain consistent.
Conclusions: Our results largely agree with previous measurements of the solar windβs angular-momentum flux in terms of amplitude,
variability, and dependence on radial solar-wind bulk speed. Our analysis highlights the potential for more detailed future studies of
the solar windβs angular momentum and its other large-scale properties with data from Solar Orbiter. We emphasise the need for
studying the radial evolution and latitudinal dependence of the angular-momentum flux in combination with data from Parker Solar
Probe and other assets at heliocentric distances of 1 au and beyond
Recommended from our members
A Search for MeV to TeV Neutrinos from Fast Radio Bursts with IceCube
We present two searches for IceCube neutrino events coincident with 28 fast radio bursts (FRBs) and 1 repeating FRB. The first improves on a previous IceCube analysis - searching for spatial and temporal correlation of events with FRBs at energies greater than roughly 50 GeV - by increasing the effective area by an order of magnitude. The second is a search for temporal correlation of MeV neutrino events with FRBs. No significant correlation is found in either search; therefore, we set upper limits on the time-integrated neutrino flux emitted by FRBs for a range of emission timescales less than one day. These are the first limits on FRB neutrino emission at the MeV scale, and the limits set at higher energies are an order-of-magnitude improvement over those set by any neutrino telescope
Recommended from our members
Efficient propagation of systematic uncertainties from calibration to analysis with the SnowStorm method in IceCube
Efficient treatment of systematic uncertainties that depend on a large number of nuisance parameters is a persistent difficulty in particle physics and astrophysics experiments. Where low-level effects are not amenable to simple parameterization or re-weighting, analyses often rely on discrete simulation sets to quantify the effects of nuisance parameters on key analysis observables. Such methods may become computationally untenable for analyses requiring high statistics Monte Carlo with a large number of nuisance degrees of freedom, especially in cases where these degrees of freedom parameterize the shape of a continuous distribution. In this paper we present a method for treating systematic uncertainties in a computationally efficient and comprehensive manner using a single simulation set with multiple and continuously varied nuisance parameters. This method is demonstrated for the case of the depth-dependent effective dust distribution within the IceCube Neutrino Telescope
Recommended from our members
Search for sources of astrophysical neutrinos using seven years of icecube cascade events
Low-background searches for astrophysical neutrino sources anywhere in the sky can be performed using cascade events induced by neutrinos of all flavors interacting in IceCube with energies as low as βΌ1 TeV. Previously we showed that, even with just two years of data, the resulting sensitivity to sources in the southern sky is competitive with IceCube and ANTARES analyses using muon tracks induced by charge current muon neutrino interactions - especially if the neutrino emission follows a soft energy spectrum or originates from an extended angular region. Here, we extend that work by adding five more years of data, significantly improving the cascade angular resolution, and including tests for point-like or diffuse Galactic emission to which this data set is particularly well suited. For many of the signal candidates considered, this analysis is the most sensitive of any experiment to date. No significant clustering was observed, and thus many of the resulting constraints are the most stringent to date. In this paper we will describe the improvements introduced in this analysis and discuss our results in the context of other recent work in neutrino astronomy
Recommended from our members
Design and performance of the first IceAct demonstrator at the South Pole
In this paper we describe the first results of IceAct, a compact imaging air-Cherenkov telescope operating in coincidence with the IceCube Neutrino Observatory (IceCube) at the geographic South Pole. An array of IceAct telescopes (referred to as the IceAct project) is under consideration as part of the IceCube-Gen2 extension to IceCube. Surface detectors in general will be a powerful tool in IceCube-Gen2 for distinguishing astrophysical neutrinos from the dominant backgrounds of cosmic-ray induced atmospheric muons and neutrinos: the IceTop array is already in place as part of IceCube, but has a high energy threshold. Although the duty cycle will be lower for the IceAct telescopes than the present IceTop tanks, the IceAct telescopes may prove to be more effective at lowering the detection threshold for air showers. Additionally, small imaging air-Cherenkov telescopes in combination with IceTop, the deep IceCube detector or other future detector systems might improve measurements of the composition of the cosmic ray energy spectrum. In this paper we present measurements of a first 7-pixel imaging air Cherenkov telescope demonstrator, proving the capability of this technology to measure air showers at the South Pole in coincidence with IceTop and the deep IceCube detector
The contribution of alpha particles to the solar wind angular momentum flux in the inner heliosphere
This is the final version. Available from EDP Sciences via the DOI in this recordContext. An accurate assessment of the Sunβs angular momentum (AM) loss rate is an independent constraint for models that describe the rotation
evolution of Sun-like stars.
Aims. In-situ measurements of the solar wind taken by Parker Solar Probe (PSP), at radial distances of βΌ 28β55R , are used to constrain the solar
wind AM-loss rate. For the first time with PSP, this includes a measurement of the alpha particle contribution.
Methods. The mechanical AM flux in the solar wind protons (core and beam), and alpha particles, is determined as well as the transport of AM
through stresses in the interplanetary magnetic field. The solar wind AM flux is averaged over three hour increments, so that our findings more
accurately represent the bulk flow.
Results. During the third and fourth perihelion passes of PSP, the alpha particles contain around a fifth of the mechanical AM flux in the solar
wind (the rest is carried by the protons). The proton beam is found to contain βΌ 10β50% of the proton AM flux. The sign of the alpha particle AM
flux is observed to correlate with the proton core. The slow wind has a positive AM flux (removing AM from the Sun as expected), and the fast
wind has a negative AM flux. As with previous works, the differential velocity between the alpha particles and the proton core tends to be aligned
with the interplanetary magnetic field.
Conclusions. In future, by utilising the trends in the alpha-proton differential velocity, it may be possible to estimate the alpha particle contribution
when only measurements of the proton core are available. Based on the observations from this work, the alpha particles contribute an additional
10 β 20% to estimates of the solar wind AM-loss rate which consider only the proton and magnetic field contributions. Additionally, the AM flux
of the proton beam can be just as significant as the alpha particles, and so should not be neglected in future studies.European Union Horizon 202
DroID: the Drosophila Interactions Database, a comprehensive resource for annotated gene and protein interactions
<p>Abstract</p> <p>Background</p> <p>Charting the interactions among genes and among their protein products is essential for understanding biological systems. A flood of interaction data is emerging from high throughput technologies, computational approaches, and literature mining methods. Quick and efficient access to this data has become a critical issue for biologists. Several excellent multi-organism databases for gene and protein interactions are available, yet most of these have understandable difficulty maintaining comprehensive information for any one organism. No single database, for example, includes all available interactions, integrated gene expression data, and comprehensive and searchable gene information for the important model organism, <it>Drosophila melanogaster</it>.</p> <p>Description</p> <p>DroID, the <it>Drosophila </it>Interactions Database, is a comprehensive interactions database designed specifically for <it>Drosophila</it>. DroID houses published physical protein interactions, genetic interactions, and computationally predicted interactions, including interologs based on data for other model organisms and humans. All interactions are annotated with original experimental data and source information. DroID can be searched and filtered based on interaction information or a comprehensive set of gene attributes from Flybase. DroID also contains gene expression and expression correlation data that can be searched and used to filter datasets, for example, to focus a study on sub-networks of co-expressed genes. To address the inherent noise in interaction data, DroID employs an updatable confidence scoring system that assigns a score to each physical interaction based on the likelihood that it represents a biologically significant link.</p> <p>Conclusion</p> <p>DroID is the most comprehensive interactions database available for <it>Drosophila</it>. To facilitate downstream analyses, interactions are annotated with original experimental information, gene expression data, and confidence scores. All data in DroID are freely available and can be searched, explored, and downloaded through three different interfaces, including a text based web site, a Java applet with dynamic graphing capabilities (IM Browser), and a Cytoscape plug-in. DroID is available at <url>http://www.droidb.org</url>.</p
Pleiotropic Effects of Deubiquitinating Enzyme Ubp5 on Growth and Pathogenesis of Cryptococcus neoformans
Ubiquitination is a reversible protein modification that influences various cellular processes in eukaryotic cells. Deubiquitinating enzymes remove ubiquitin, maintain ubiquitin homeostasis and regulate protein degradation via the ubiquitination pathway. Cryptococcus neoformans is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily in the immunocompromised population. In order to understand the possible influence deubiquitinases have on growth and virulence of the model pathogenic yeast Cryptococcus neoformans, we generated deletion mutants of seven putative deubiquitinase genes. Compared to other deubiquitinating enzyme mutants, a ubp5Ξ mutant exhibited severely attenuated virulence and many distinct phenotypes, including decreased capsule formation, hypomelanization, defective sporulation, and elevated sensitivity to several external stressors (such as high temperature, oxidative and nitrosative stresses, high salts, and antifungal agents). Ubp5 is likely the major deubiquitinating enzyme for stress responses in C. neoformans, which further delineates the evolutionary divergence of Cryptococcus from the model yeast S. cerevisiae, and provides an important paradigm for understanding the potential role of deubiquitination in virulence by other pathogenic fungi. Other putative deubiquitinase mutants (doa4Ξ and ubp13Ξ) share some phenotypes with the ubp5Ξ mutant, illustrating functional overlap among deubiquitinating enzymes in C. neoformans. Therefore, deubiquitinating enzymes (especially Ubp5) are essential for the virulence composite of C. neoformans and provide an additional yeast survival and propagation advantage in the host
- β¦