159 research outputs found
Cytoplasmic dynein/dynactin drives kinetochore protein transport to the spindle poles and has a role in mitotic spindle checkpoint inactivation
We discovered that many proteins located in the kinetochore outer domain, but not the inner core, are depleted from kinetochores and accumulate at spindle poles when ATP production is suppressed in PtK1 cells, and that microtubule depolymerization inhibits this process. These proteins include the microtubule motors CENP-E and cytoplasmic dynein, and proteins involved with the mitotic spindle checkpoint, Mad2, Bub1R, and the 3F3/2 phosphoantigen. Depletion of these components did not disrupt kinetochore outer domain structure or alter metaphase kinetochore microtubule number. Inhibition of dynein/dynactin activity by microinjection in prometaphase with purified p50 “dynamitin” protein or concentrated 70.1 anti-dynein antibody blocked outer domain protein transport to the spindle poles, prevented Mad2 depletion from kinetochores despite normal kinetochore microtubule numbers, reduced metaphase kinetochore tension by 40%, and induced a mitotic block at metaphase. Dynein/dynactin inhibition did not block chromosome congression to the spindle equator in prometaphase, or segregation to the poles in anaphase when the spindle checkpoint was inactivated by microinjection with Mad2 antibodies. Thus, a major function of dynein/dynactin in mitosis is in a kinetochore disassembly pathway that contributes to inactivation of the spindle checkpoint
Towards a Nonequilibrium Quantum Field Theory Approach to Electroweak Baryogenesis
We propose a general method to compute -violating observables from
extensions of the standard model in the context of electroweak baryogenesis. It
is alternative to the one recently developed by Huet and Nelson and relies on a
nonequilibrium quantum field theory approach. The method is valid for all
shapes and sizes of the bubble wall expanding in the thermal bath during a
first-order electroweak phase transition. The quantum physics of -violation
and its suppression coming from the incoherent nature of thermal processes are
also made explicit.Comment: 19 pages, 1 figure available upon e-mail reques
Upscaling miscanthus production in the United Kingdom: the benefits, challenges, and trade‐offs
The UK sixth carbon budget has recommended domestic biomass supply should increase to meet growing demand, planting a minimum of 30,000 hectares of perennial energy crops a year by 2035, with a view to establishing 700,000 hectares by 2050 to meet the requirements of the balanced net zero pathway. Miscanthus is a key biomass crop to scale up domestic biomass production in the United Kingdom. A cohesive land management strategy, based on robust evidence, will be required to ensure upscaling of miscanthus cultivation maximizes the environmental and economic benefits and minimizes undesirable consequences. This review examines research into available land areas, environmental impacts, barriers to uptake, and the challenges, benefits, and trade-offs required to upscale miscanthus production on arable land and grassland in the United Kingdom. Expansion of perennial biomass crops has been considered best restricted to marginal land, less suited to food production. The review identifies a trade-off between avoiding competition with food production and a risk of encroaching on areas containing high-biodiversity or high-carbon stocks, such as semi-natural grasslands. If areas of land suitable for food production are needed to produce the biomass required for emission reduction, the review indicates there are multiple strategies for miscanthus to complement long-term food security rather than compete with it. On arable land, a miscanthus rotation with a cycle length of 10–20 years can be employed as fallow period for fields experiencing yield decline, soil fatigue, or persistent weed problems. On improved grassland areas, miscanthus presents an option for diversification, flood mitigation, and water quality improvement. Strategies need to be developed to integrate miscanthus into farming systems in a way that is profitable, sensitive to local demand, climate, and geography, and complements rather than competes with food production by increasing overall farm profitability and resilience
Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy
First published: 16 February 2022Objective: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real-world practice, in a broad population of infants with spinal muscular atrophy (SMA). Methods: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described. Results: 21 children were treated (age range, 0.65–24 months; body weight range, 2.5–12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment-related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57–274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge. Interpretation: This study provides real-world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks.Arlene M. D’Silva, Sandra Holland, Didu Kariyawasam, Karen Herbert, Peter Barclay, Anita Cairns, Suzanna C. MacLennan, Monique M. Ryan, Hugo Sampaio, Nicholas Smith, Ian R. Woodcock, Eppie M. Yiu, Ian E. Alexander and Michelle A. Farra
Nuclear transparency from quasielastic A(e,e'p) reactions uo to Q^2=8.1 (GeV/c)^2
The quasielastic (e,ep) reaction was studied on targets of
deuterium, carbon, and iron up to a value of momentum transfer of 8.1
(GeV/c). A nuclear transparency was determined by comparing the data to
calculations in the Plane-Wave Impulse Approximation. The dependence of the
nuclear transparency on and the mass number was investigated in a
search for the onset of the Color Transparency phenomenon. We find no evidence
for the onset of Color Transparency within our range of . A fit to the
world's nuclear transparency data reflects the energy dependence of the free
proton-nucleon cross section.Comment: 11 pages, 6 figure
Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum
We report a first measurement for ultra-high energy cosmic rays of the
correlation between the depth of shower maximum and the signal in the water
Cherenkov stations of air-showers registered simultaneously by the fluorescence
and the surface detectors of the Pierre Auger Observatory. Such a correlation
measurement is a unique feature of a hybrid air-shower observatory with
sensitivity to both the electromagnetic and muonic components. It allows an
accurate determination of the spread of primary masses in the cosmic-ray flux.
Up till now, constraints on the spread of primary masses have been dominated by
systematic uncertainties. The present correlation measurement is not affected
by systematics in the measurement of the depth of shower maximum or the signal
in the water Cherenkov stations. The analysis relies on general characteristics
of air showers and is thus robust also with respect to uncertainties in
hadronic event generators. The observed correlation in the energy range around
the `ankle' at differs significantly from
expectations for pure primary cosmic-ray compositions. A light composition made
up of proton and helium only is equally inconsistent with observations. The
data are explained well by a mixed composition including nuclei with mass . Scenarios such as the proton dip model, with almost pure compositions, are
thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray
flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report
Numbe
Probing exotic phenomena at the interface of nuclear and particle physics with the electric dipole moments of diamagnetic atoms: A unique window to hadronic and semi-leptonic CP violation
The current status of electric dipole moments of diamagnetic atoms which
involves the synergy between atomic experiments and three different theoretical
areas -- particle, nuclear and atomic is reviewed. Various models of particle
physics that predict CP violation, which is necessary for the existence of such
electric dipole moments, are presented. These include the standard model of
particle physics and various extensions of it. Effective hadron level combined
charge conjugation (C) and parity (P) symmetry violating interactions are
derived taking into consideration different ways in which a nucleon interacts
with other nucleons as well as with electrons. Nuclear structure calculations
of the CP-odd nuclear Schiff moment are discussed using the shell model and
other theoretical approaches. Results of the calculations of atomic electric
dipole moments due to the interaction of the nuclear Schiff moment with the
electrons and the P and time-reversal (T) symmetry violating
tensor-pseudotensor electron-nucleus are elucidated using different
relativistic many-body theories. The principles of the measurement of the
electric dipole moments of diamagnetic atoms are outlined. Upper limits for the
nuclear Schiff moment and tensor-pseudotensor coupling constant are obtained
combining the results of atomic experiments and relativistic many-body
theories. The coefficients for the different sources of CP violation have been
estimated at the elementary particle level for all the diamagnetic atoms of
current experimental interest and their implications for physics beyond the
standard model is discussed. Possible improvements of the current results of
the measurements as well as quantum chromodynamics, nuclear and atomic
calculations are suggested.Comment: 46 pages, 19 tables and 16 figures. A review article accepted for
EPJ
Atmospheric effects on extensive air showers observed with the Surface Detector of the Pierre Auger Observatory
Atmospheric parameters, such as pressure (P), temperature (T) and density,
affect the development of extensive air showers initiated by energetic cosmic
rays. We have studied the impact of atmospheric variations on extensive air
showers by means of the surface detector of the Pierre Auger Observatory. The
rate of events shows a ~10% seasonal modulation and ~2% diurnal one. We find
that the observed behaviour is explained by a model including the effects
associated with the variations of pressure and density. The former affects the
longitudinal development of air showers while the latter influences the Moliere
radius and hence the lateral distribution of the shower particles. The model is
validated with full simulations of extensive air showers using atmospheric
profiles measured at the site of the Pierre Auger Observatory.Comment: 24 pages, 9 figures, accepted for publication in Astroparticle
Physic
Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter
Data collected by the Pierre Auger Observatory through 31 August 2007 showed
evidence for anisotropy in the arrival directions of cosmic rays above the
Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{eV}. The
anisotropy was measured by the fraction of arrival directions that are less
than from the position of an active galactic nucleus within 75 Mpc
(using the V\'eron-Cetty and V\'eron catalog). An updated
measurement of this fraction is reported here using the arrival directions of
cosmic rays recorded above the same energy threshold through 31 December 2009.
The number of arrival directions has increased from 27 to 69, allowing a more
precise measurement. The correlating fraction is , compared
with expected for isotropic cosmic rays. This is down from the early
estimate of . The enlarged set of arrival directions is
examined also in relation to other populations of nearby extragalactic objects:
galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in
hard X-rays by the Swift Burst Alert Telescope. A celestial region around the
position of the radiogalaxy Cen A has the largest excess of arrival directions
relative to isotropic expectations. The 2-point autocorrelation function is
shown for the enlarged set of arrival directions and compared to the isotropic
expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201
The exposure of the hybrid detector of the Pierre Auger Observatory
The Pierre Auger Observatory is a detector for ultra-high energy cosmic rays.
It consists of a surface array to measure secondary particles at ground level
and a fluorescence detector to measure the development of air showers in the
atmosphere above the array. The "hybrid" detection mode combines the
information from the two subsystems. We describe the determination of the
hybrid exposure for events observed by the fluorescence telescopes in
coincidence with at least one water-Cherenkov detector of the surface array. A
detailed knowledge of the time dependence of the detection operations is
crucial for an accurate evaluation of the exposure. We discuss the relevance of
monitoring data collected during operations, such as the status of the
fluorescence detector, background light and atmospheric conditions, that are
used in both simulation and reconstruction.Comment: Paper accepted by Astroparticle Physic
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