252 research outputs found
A Comparative Transcriptome and Proteome Analysis in Rat Models Reveals Effects of Aging and Diabetes on Expression of Neuronal Genes
SummaryBackgroundTo understand neuronal molecular changes in senile diabetes we established a rat senile diabetes model and analyzed transcriptome and proteome changes.MethodsWistar rats were fed a high sugar, high fat diet for 16 months to induce diabetes. Non-diabetic aged rats and young rats were used as controls. Transcript and protein levels in the liver were then analyzed by microarray and antibody arrays, respectively.ResultsNeuronal genes that were differentially expressed between senile diabetic rats, non-diabetic aged rats, and young rats were distributed across 12 pathways and 23 Gene Ontology (GO) clusters. Among them, 2267 genes were aging-related, 1230 genes were diabetes-associated, and 9 proteins might be associated with neurological disorders.ConclusionIn this study, we investigated transcriptome and proteome changes in animal models, analyzed the impact of aging and diabetes on neuronal molecules, and confirmed the correlations. Our study provides support for further studies on mechanisms of neuronal diseases
Probing Primordial Gravitational Waves: Ali CMB Polarization Telescope
In this paper, we will give a general introduction to the project of Ali CMB
Polarization Telescope (AliCPT), which is a Sino-US joint project led by the
Institute of High Energy Physics (IHEP) and has involved many different
institutes in China. It is the first ground-based Cosmic Microwave Background
(CMB) polarization experiment in China and an integral part of China's
Gravitational Waves Program. The main scientific goal of AliCPT project is to
probe the primordial gravitational waves (PGWs) originated from the very early
Universe.
The AliCPT project includes two stages. The first stage referred to as
AliCPT-1, is to build a telescope in the Ali region of Tibet with an altitude
of 5,250 meters. Once completed, it will be the worldwide highest ground-based
CMB observatory and open a new window for probing PGWs in northern hemisphere.
AliCPT-1 telescope is designed to have about 7,000 TES detectors at 90GHz and
150GHz. The second stage is to have a more sensitive telescope (AliCPT-2) with
the number of detectors more than 20,000.
Our simulations show that AliCPT will improve the current constraint on the
tensor-to-scalar ratio by one order of magnitude with 3 years' observation.
Besides the PGWs, the AliCPT will also enable a precise measurement on the CMB
rotation angle and provide a precise test on the CPT symmetry. We show 3 years'
observation will improve the current limit by two order of magnitude.Comment: 11 pages, 7 figures, 2 table
Multiplet patterns due to co-existing intermolecular dipolar and intramolecular scalar couplings in liquid nuclear magnetic resonance
When both intermolecular dipolar couplings (D couplings) and intramolecular scalar couplings (J couplings) exist in a highly polarized multiple-spin liquid, some forbidden nuclear magnetic resonance signals originating from intermolecular multiple-quantum coherences may become observable. Moreover, their multiplet patterns are quite different from what are observed in a multiple-spin system with J couplings only. In this paper, these forbidden resonance peaks and unique multiplet patterns are studied theoretically and experimentally. For comparison and verification, an I2S3 + X spin system is chosen as an example to present five types of signal patterns from the interactions of D and J couplings with either selective or non-selective radio-frequency pulse sequences for double-quantum coherences. The multiplet pattern rules for a more general IpSq + X-k (p;q k = 1, 2, 3....) spin system are derived as well. It is demonstrated that some unusual multiplet amplitude patterns such as (1:0:-1) may "magnify" J splittings, allowing more accurate measurement of J coupling in the case of small J coupling constants and/or in inhomogeneous fields. It is shown that the theoretical predictions, computer simulations, and experimental observations are all in agreement with one another very well
A phase 1 dose-escalation study of the poly(ADP-ribose) polymerase inhibitor senaparib in Australian patients with advanced solid tumors
Background: Senaparib is a novel, selective poly(ADP-ribose) polymerase-1/2 inhibitor with strong antitumor activity in preclinical studies. This first-in-human, phase 1, dose-escalation study examined the safety and preliminary efficacy of senaparib in patients with advanced solid tumors. Methods: Patients with advanced solid tumors were enrolled from three centers in Australia, using a conventional 3 + 3 design. Dose-escalation cohorts continued until the maximum tolerated dose or a recommended phase 2 dose was determined. Patients received one dose of oral senaparib and, if no dose-limiting toxicity occurred within 7 days, they received senaparib once daily in 3-week cycles. The primary end points were safety and tolerability. Results: Thirty-nine patients were enrolled at 10 dose levels ranging from 2 to 150 mg. No dose-limiting toxicities were observed in any cohort. Most treatment-emergent adverse events were grade 1–2 (91%). Seven patients (17.9%) reported hematologic treatment-emergent adverse events. Treatment-related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib-related bone marrow failure. Pharmacokinetic analysis indicated that senaparib the accumulation index was 1.06–1.67, and absorption saturation was 80–150 mg daily. In 22 patients with evaluable disease, the overall response rate was 13.6%, and the disease control rate was 81.8%. The overall response rate was 33.3% for the BRCA mutation-positive subgroup and 6.3% for the nonmutated subgroup. Conclusions: Senaparib was well tolerated in Australian patients with advanced solid tumors, with encouraging signals of antitumor activity. The recommended phase 2 dose for senaparib was determined to be 100 mg daily. ClinicalTrials.gov ID: NCT03507543
Search for Quasi-Periodical Oscillations in Precursors of Short and Long Gamma Ray Bursts
The precursors of short and long Gamma Ray Bursts (SGRBs and LGRBs) can serve
as probes of their progenitors, as well as shedding light on the physical
processes of mergers or core-collapse supernovae. Some models predict the
possible existence of Quasi-Periodically Oscillations (QPO) in the precursors
of SGRBs. Although many previous studies have performed QPO search in the main
emission of SGRBs and LGRBs, so far there was no systematic QPO search in their
precursors. In this work, we perform a detailed QPO search in the precursors of
SGRBs and LGRBs detected by Fermi/GBM from 2008 to 2019 using the power density
spectrum (PDS) in frequency domain and Gaussian processes (GP) in time domain.
We do not find any convinced QPO signal with significance above 3 ,
possibly due to the low fluxes of precursors. Finally, the PDS continuum
properties of both the precursors and main emissions are also studied for the
first time, and no significant difference is found in the distributions of the
PDS slope for precursors and main emissions in both SGRBs and LGRBs.Comment: submitte
The Minimum Variation Timescales of X-ray bursts from SGR J1935+2154
The minimum variation timescale (MVT) of soft gamma-ray repeaters can be an
important probe to estimate the emission region in pulsar-like models, as well
as the Lorentz factor and radius of the possible relativistic jet in gamma-ray
burst (GRB)-like models, thus revealing their progenitors and physical
mechanisms. In this work, we systematically study the MVTs of hundreds of X-ray
bursts (XRBs) from SGR J1935+2154 observed by {\it Insight}-HXMT, GECAM and
Fermi/GBM from July 2014 to Jan 2022 through the Bayesian Block algorithm. We
find that the MVTs peak at 2 ms, corresponding to a light travel time
size of about 600 km, which supports the magnetospheric origin in pulsar-like
models. The shock radius and the Lorentz factor of the jet are also constrained
in GRB-like models. Interestingly, the MVT of the XRB associated with FRB
200428 is 70 ms, which is longer than that of most bursts and implies
its special radiation mechanism. Besides, the median of MVTs is 7 ms, shorter
than the median MVTs of 40 ms and 480 ms for short GRBs or long GRBs,
respectively. However, the MVT is independent of duration, similar to GRBs.
Finally, we investigate the energy dependence of MVT and suggest that there is
a marginal evidence for a power-law relationship like GRBs but the rate of
variation is at least about an order of magnitude smaller. These features may
provide an approach to identify bursts with a magnetar origin.Comment: accepted for publication in ApJ
Childhood Sexual Abuse and the Development of Recurrent Major Depression in Chinese Women
Background
Our prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set? Method
Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression. Results
We confirmed earlier results by replicating prior analyses in 3,950 new recurrent MD cases. There were no significant differences between the two data sets. Any form of CSA was significantly associated with recurrent MD (OR 4.06, 95% confidence interval (CI) [3.19–5.24]). This association strengthened with increasing CSA severity: non-genital (OR 2.21, 95% CI 1.58–3.15), genital (OR 5.24, 95% CI 3.52–8.15) and intercourse (OR 10.65, 95% CI 5.56–23.71). Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes. Recurrent MD patients those with CSA had an increased risk for dysthymia (OR 1.60, 95%CI 1.11–2.27) and phobia (OR 1.41, 95%CI 1.09–1.80). Any form of CSA was significantly associated with suicidal ideation or attempt (OR 1.50, 95% CI 1.20–1.89) and feelings of worthlessness or guilt (OR 1.41, 95% CI 1.02–2.02). Intercourse (OR 3.47, 95%CI 1.66–8.22), use of force and threats (OR 1.95, 95%CI 1.05–3.82) and how strongly the victims were affected at the time (OR 1.39, 95%CI 1.20–1.64) were significantly associated with recurrent MD
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