1,930 research outputs found
Stalking influenza by vaccination with pre-fusion headless HA mini-stem.
Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity
Improved performance of the LHCb Outer Tracker in LHC Run 2
The LHCb Outer Tracker is a gaseous detector covering an area of with 12 double layers of straw tubes. The performance of the detector is
presented based on data of the LHC Run 2 running period from 2015 and 2016.
Occupancies and operational experience for data collected in , pPb and
PbPb collisions are described. An updated study of the ageing effects is
presented showing no signs of gain deterioration or other radiation damage
effects. In addition several improvements with respect to LHC Run 1 data taking
are introduced. A novel real-time calibration of the time-alignment of the
detector and the alignment of the single monolayers composing detector modules
are presented, improving the drift-time and position resolution of the detector
by 20\%. Finally, a potential use of the improved resolution for the timing of
charged tracks is described, showing the possibility to identify low-momentum
hadrons with their time-of-flight.Comment: 29 pages, 20 figures, minor changes to match the published versio
A detailed description of the phenotypic spectrum of North Sea Progressive Myoclonus Epilepsy in a large cohort of seventeen patients
Introduction: In 2011, a homozygous mutation in GOSR2 (c.430G > T; p. Gly144Trp) was reported as a novel cause of Progressive Myoclonus Epilepsy (PME) with early-onset ataxia. Interestingly, the ancestors of patients originate from countries bound to the North Sea, hence the condition was termed North Sea PME (NSPME). Until now, only 20 patients have been reported in literature. Here, we provide a detailed description of clinical and neurophysiological data of seventeen patients. Methods: We collected clinical and neurophysiological data from the medical records of seventeen NSPME patients (5–46 years). In addition, we conducted an interview focused on factors influencing myoclonus severity. Results: The core clinical features of NSPME are early-onset ataxia, myoclonus and seizures, with additionally areflexia and scoliosis. Factors such as fever, illness, heat, emotions, stress, noise and light (flashes) all exacerbated myoclonic jerks. Epilepsy severity ranged from the absence of or incidental clinical seizures to frequent daily seizures and status epilepticus. Some patients made use of a wheelchair during their first decade, whereas others still walked independently during their third decade. Neurophysiological features suggesting neuromuscular involvement in NSPME were variable, with findings ranging from indicative of sensory neuronopathy and anterior horn cell involvement to an isolated absent H-reflex. Conclusion: Although the sequence of symptoms is rather homogeneous, the severity of symptoms and rate of progression varied considerably among individual patients. Common triggers for myoclonus can be identified and myoclonus is difficult to treat; to what extent neuromuscular involvement contributes to the phenotype remains
ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies:a propensity-matched analysis
BACKGROUND: Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. METHODS: We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. RESULTS: 296 ABOi were compared to 1184 center and propensity matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group and PRA). Patient survival was better compared to deceased donor (hazard ratio (HR) for death of HR 0.69 [0.49-0.96], and not-significantly different from ABOc living donor recipients (HR 1.28 [0.90-1.81]). Rate of graft failure was higher compared to ABOc living donor transplantation (HR 2.63 [1.72-4.01]). Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab treated recipients (p <0.001). CONCLUSIONS: ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared to matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy
Nature and mental health: An ecosystem service perspective
This is the final version. Available on open access from American Association for the Advancement of Science via the DOI in this recordData and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.A growing body of empirical evidence is revealing the value of nature experience for mental health. With rapid urbanization and declines in human contact with nature globally, crucial decisions must be made about how to preserve and enhance opportunities for nature experience. Here, we first provide points of consensus across the natural, social, and health sciences on the impacts of nature experience on cognitive functioning, emotional well-being, and other dimensions of mental health. We then show how ecosystem service assessments can be expanded to include mental health, and provide a heuristic, conceptual model for doing so.Doug Walker Endowed ProfessorshipCraig McKibben and Sarah MernerJohn MillerMarianne and Marcus Wallenberg FoundationWinslow FoundationGeorge Rudolf Fellowship FundVictoria and David Rogers FundMr. & Mrs. Dean A. McGee Fun
The ANTARES Optical Beacon System
ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It
consists of a three dimensional array of photomultiplier tubes that can detect
the Cherenkov light induced by charged particles produced in the interactions
of neutrinos with the surrounding medium. High angular resolution can be
achieved, in particular when a muon is produced, provided that the Cherenkov
photons are detected with sufficient timing precision. Considerations of the
intrinsic time uncertainties stemming from the transit time spread in the
photomultiplier tubes and the mechanism of transmission of light in sea water
lead to the conclusion that a relative time accuracy of the order of 0.5 ns is
desirable. Accordingly, different time calibration systems have been developed
for the ANTARES telescope. In this article, a system based on Optical Beacons,
a set of external and well-controlled pulsed light sources located throughout
the detector, is described. This calibration system takes into account the
optical properties of sea water, which is used as the detection volume of the
ANTARES telescope. The design, tests, construction and first results of the two
types of beacons, LED and laser-based, are presented.Comment: 21 pages, 18 figures, submitted to Nucl. Instr. and Meth. Phys. Res.
The Iron−Sulfur Clusters 2 and Ubisemiquinone Radicals of NADH:Ubiquinone Oxidoreductase Are Involved in Energy Coupling in Submitochondrial Particles
Pathways through care of severely mentally ill individuals experiencing multiple public crisis events: a qualitative description
Observation of two new baryon resonances
Two structures are observed close to the kinematic threshold in the mass spectrum in a sample of proton-proton collision data, corresponding
to an integrated luminosity of 3.0 fb recorded by the LHCb experiment.
In the quark model, two baryonic resonances with quark content are
expected in this mass region: the spin-parity and
states, denoted and .
Interpreting the structures as these resonances, we measure the mass
differences and the width of the heavier state to be
MeV,
MeV,
MeV, where the first and second
uncertainties are statistical and systematic, respectively. The width of the
lighter state is consistent with zero, and we place an upper limit of
MeV at 95% confidence level. Relative
production rates of these states are also reported.Comment: 17 pages, 2 figure
Observation of associated production of a boson with a meson in the~forward region
A search for associated production of a boson with an open charm meson is
presented using a data sample, corresponding to an integrated luminosity of
of proton--proton collisions at a centre-of-mass energy
of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for
associated production of a boson with a meson and four candidate
events for a boson with a meson are observed with a combined
significance of 5.1standard deviations. The production cross-sections in the
forward region are measured to be where the first uncertainty is statistical and the
second systematic.Comment: 18 pages, 2 figure
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