922 research outputs found
Cyclic nucleotide in oocyte In vitro maturation in Assisted Reproductive Technology
In vitro maturation (IVM) is a promising assisted reproductive technology (ART) for human infertility treatment. However, when cumulus oocyte complexes (COCs) are removed from their follicular environment when manipulated in vitro, it can lead to a decrease of intra-oocyte cyclic adenosine 3’, 5’-monophosphare (cAMP) causing spontaneous nuclear maturation and an asynchrony with the oocytes’ cytoplasmic maturation, resulting in poor embryo developmental outcomes. Nuclear and cytoplasmic synchrony is important during oocyte maturation within antral follicles.It is maintained partially by the actions of c-type natriuretic peptide (CNP) binding with natriuretic peptide receptor 2 (NPR2), supporting high cAMP levels thus holding the oocyte in meiotic arrest. Addition of CNP to pre-IVM media has the capacity of maintaining cAMP levels and thus improve synchrony. Moreover, in women with advanced maternal age, successful IVM of aging oocytes faces significant challenges due to the morphological and cellular changes. Inhibiting initiation of nuclear maturation by cAMP modulator, CNP during pre-IVM period and thus improve oocyte developmental competence regardless of oocyte age
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Antileukemic Activity of Nuclear Export Inhibitors that Spare Normal Hematopoietic Cells
Drugs that target the chief mediator of nuclear export, chromosome region maintenance 1 protein (CRM1) have potential as therapeutics for leukemia, but existing CRM1 inhibitors show variable potencies and a broad range of cytotoxic effects. Here, we report the structural analysis and antileukemic activity of a new generation of small-molecule inhibitors of CRM1. Designated selective inhibitors of nuclear export (SINE), these compounds were developed using molecular modeling to screen a small virtual library of compounds against the nuclear export signal (NES) groove of CRM1. The 2.2-Å crystal structure of the CRM1-Ran-RanBP1 complex bound to KPT-251, a representative molecule of this class of inhibitors, shows that the drug occupies part of the groove in CRM1 that is usually occupied by the NES, but penetrates much deeper into the groove and blocks CRM1-directed protein export. SINE inhibitors exhibit potent antileukemic activity, inducing apoptosis at nanomolar concentrations in a panel of 14 human acute myeloid leukemia (AML) cell lines representing different molecular subtypes of the disease. When administered orally to immunodeficient mice engrafted with human AML cells, KPT-251 had potent antileukemic activity with negligible toxicity to normal hematopoietic cells. Thus, KPT-SINE CRM1 antagonists represent a novel class of drugs that warrant further testing in AML patients
Cluster randomised controlled trial to assess a tailored intervention to reduce antibiotic prescribing in rural China:study protocol
INTRODUCTION: Up to 80% of patients with respiratory tract infections (RTI) attending healthcare facilities in rural areas of China are prescribed antibiotics, many of which are unnecessary. Since 2009, China has implemented several policies to try to reduce inappropriate antibiotic use; however, antibiotic prescribing remains high in rural health facilities. METHODS AND ANALYSIS: A cluster randomised controlled trial will be carried out to estimate the effectiveness and cost effectiveness of a complex intervention in reducing antibiotic prescribing at township health centres in Anhui Province, China. 40 Township health centres will be randomised at a 1:1 ratio to the intervention or usual care arms. In the intervention group, practitioners will receive an intervention comprising: (1) training to support appropriate antibiotic prescribing for RTI, (2) a computer-based treatment decision support system, (3) virtual peer support, (4) a leaflet for patients and (5) a letter of commitment to optimise antibiotic use to display in their clinic. The primary outcome is the percentage of antibiotics (intravenous and oral) prescribed for RTI patients. Secondary outcomes include patient symptom severity and duration, recovery status, satisfaction, antibiotic consumption. A full economic evaluation will be conducted within the trial period. Costs and savings for both clinics and patients will be considered and quality of life will be measured by EuroQoL (EQ-5D-5L). A qualitative process evaluation will explore practitioner and patient views and experiences of trial processes, intervention fidelity and acceptability, and barriers and facilitators to implementation. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Biomedical Research Ethics Committee of Anhui Medical University (Ref: 20180259); the study has undergone due diligence checks and is registered at the University of Bristol (Ref: 2020-3137). Research findings will be disseminated to stakeholders through conferences and peer-reviewed journals in China, the UK and internationally. TRIAL REGISTRATION NUMBER: ISRCTN30652037
Observation of charge asymmetry dependence of pion elliptic flow and the possible chiral magnetic wave in heavy-ion collisions
We present measurements of and elliptic flow, , at
midrapidity in Au+Au collisions at 200, 62.4, 39, 27,
19.6, 11.5 and 7.7 GeV, as a function of event-by-event charge asymmetry,
, based on data from the STAR experiment at RHIC. We find that
() elliptic flow linearly increases (decreases) with charge asymmetry
for most centrality bins at and higher.
At , the slope of the difference of
between and as a function of exhibits a
centrality dependence, which is qualitatively similar to calculations that
incorporate a chiral magnetic wave effect. Similar centrality dependence is
also observed at lower energies.Comment: 6 pages, 4 figure
Azimuthal anisotropy in U+U and Au+Au collisions at RHIC
Collisions between prolate uranium nuclei are used to study how particle
production and azimuthal anisotropies depend on initial geometry in heavy-ion
collisions. We report the two- and four-particle cumulants, and
, for charged hadrons from U+U collisions at =
193 GeV and Au+Au collisions at = 200 GeV. Nearly fully
overlapping collisions are selected based on the amount of energy deposited by
spectators in the STAR Zero Degree Calorimeters (ZDCs). Within this sample, the
observed dependence of on multiplicity demonstrates that ZDC
information combined with multiplicity can preferentially select different
overlap configurations in U+U collisions. An initial-state model with gluon
saturation describes the slope of as a function of multiplicity in
central collisions better than one based on Glauber with a two-component
multiplicity model.Comment: Final paper version accepted for publication in Phys. Rev. Lett. New
version includes comparisons to a constituent quark glauber mode
Energy dependence of acceptance-corrected dielectron excess mass spectrum at mid-rapidity in Au+Au collisions at and 200 GeV
The acceptance-corrected dielectron excess mass spectra, where the known
hadronic sources have been subtracted from the inclusive dielectron mass
spectra, are reported for the first time at mid-rapidity in
minimum-bias Au+Au collisions at = 19.6 and 200 GeV. The excess
mass spectra are consistently described by a model calculation with a broadened
spectral function for GeV/. The integrated
dielectron excess yield at = 19.6 GeV for
GeV/, normalized to the charged particle multiplicity at mid-rapidity, has
a value similar to that in In+In collisions at = 17.3 GeV. For
= 200 GeV, the normalized excess yield in central collisions is
higher than that at = 17.3 GeV and increases from peripheral to
central collisions. These measurements indicate that the lifetime of the hot,
dense medium created in central Au+Au collisions at = 200 GeV
is longer than those in peripheral collisions and at lower energies.Comment: 9 pages, 6 figure
Centrality and transverse momentum dependence of elliptic flow of multi-strange hadrons and meson in Au+Au collisions at = 200 GeV
We present high precision measurements of elliptic flow near midrapidity
() for multi-strange hadrons and meson as a function of
centrality and transverse momentum in Au+Au collisions at center of mass energy
200 GeV. We observe that the transverse momentum dependence of
and is similar to that of and , respectively,
which may indicate that the heavier strange quark flows as strongly as the
lighter up and down quarks. This observation constitutes a clear piece of
evidence for the development of partonic collectivity in heavy-ion collisions
at the top RHIC energy. Number of constituent quark scaling is found to hold
within statistical uncertainty for both 0-30 and 30-80 collision
centrality. There is an indication of the breakdown of previously observed mass
ordering between and proton at low transverse momentum in the
0-30 centrality range, possibly indicating late hadronic interactions
affecting the proton .Comment: 7 pages and 4 figures, Accepted for publication in Physical Review
Letter
Observation of Transverse Spin-Dependent Azimuthal Correlations of Charged Pion Pairs in at GeV
We report the observation of transverse polarization-dependent azimuthal
correlations in charged pion pair production with the STAR experiment in
collisions at RHIC. These correlations directly probe quark
transversity distributions. We measure signals in excess of five standard
deviations at high transverse momenta, at high pseudorapidities eta>0.5, and
for pair masses around the mass of the rho-meson. This is the first direct
transversity measurement in p+p collisions. Comparing the results to data from
lepton-nucleon scattering will test the universality of these spin-dependent
quantities.Comment: 11 pages, 5 figures, 15 tables. Submitted to PR
Long-range pseudorapidity dihadron correlations in +Au collisions at GeV
Dihadron angular correlations in +Au collisions at
GeV are reported as a function of the measured zero-degree calorimeter neutral
energy and the forward charged hadron multiplicity in the Au-beam direction. A
finite correlated yield is observed at large relative pseudorapidity
() on the near side (i.e. relative azimuth ). This
correlated yield as a function of appears to scale with the
dominant, primarily jet-related, away-side () yield. The
Fourier coefficients of the correlation, , have a strong dependence. In addition, it is
found that is approximately inversely proportional to the mid-rapidity
event multiplicity, while is independent of it with similar magnitude
in the forward (-going) and backward (Au-going) directions.Comment: 8 pages, 4 figure
Isolation of Flow and Nonflow Correlations by Two- and Four-Particle Cumulant Measurements of Azimuthal Harmonics in 200 GeV Au+Au Collisions
A data-driven method was applied to measurements of Au+Au collisions at
200 GeV made with the STAR detector at RHIC to isolate
pseudorapidity distance -dependent and -independent
correlations by using two- and four-particle azimuthal cumulant measurements.
We identified a component of the correlation that is -independent,
which is likely dominated by anisotropic flow and flow fluctuations. It was
also found to be independent of within the measured range of
pseudorapidity . The relative flow fluctuation was found to be for particles of transverse momentum
less than GeV/. The -dependent part may be attributed to
nonflow correlations, and is found to be relative to the
flow of the measured second harmonic cumulant at
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