A simulation study on the measurement of D0-D0bar mixing parameter y at BES-III

We established a method on measuring the \dzdzb mixing parameter $y$ for BESIII experiment at the BEPCII $e^+e^-$ collider. In this method, the doubly tagged $\psi(3770) \to D^0 \overline{D^0}$ events, with one $D$ decays to CP-eigenstates and the other $D$ decays semileptonically, are used to reconstruct the signals. Since this analysis requires good $e/\pi$ separation, a likelihood approach, which combines the $dE/dx$, time of flight and the electromagnetic shower detectors information, is used for particle identification. We estimate the sensitivity of the measurement of $y$ to be 0.007 based on a $20fb^{-1}$ fully simulated MC sample.Comment: 6 pages, 7 figure

Safety and Efficacy of Low-Dose Tirofiban Combined With Intravenous Thrombolysis and Mechanical Thrombectomy in Acute Ischemic Stroke: A Matched-Control Analysis From a Nationwide Registry

Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p > 0.05). Similar results were obtained after propensity score matching.Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy

Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway

Tumor cell migration is a critical step in cancer metastasis. Over-activated Notch pathway can promote the migration of cancer cells, especially in the breast cancer. However, the underlying mechanism of non-canonical Notch signaling in modulating the migration has not yet been clearly characterized. Here we demonstrated that DAPT, a gamma secretase inhibitor, inhibited protrusion formation and cell motility, and then reduced the migration of triple-negative breast cancer cells, through increasing the activity of Cdc42 by non-canonical Notch pathway. Phosphorylation of AKT on S473 was surprisingly increased when Notch signaling was inhibited by DAPT. Inhibition of PI3K and AKT by LY294002 and MK2206, respectively, or knockdown of AKT expression by siRNA blocked DAPT-induced activation of Cdc42. Moreover, immunofluorescence staining further showed that DAPT treatment reduced the formation of lamellipodia and induced actin cytoskeleton remodeling. Taken together, these results indicated that DAPT inhibited Notch signaling and consequently activated PI3K/AKT/Cdc42 signaling by non-canonical pathway, facilitated the formation of filopodia and inhibited the assembly of lamellipodia, and finally resulted in the decrease of migration activity of breast cancer cells

Ground calibration of Gamma-Ray Detectors of GECAM-C

As a new member of GECAM mission, GECAM-C (also named High Energy Burst Searcher, HEBS) was launched onboard the SATech-01 satellite on July 27th, 2022, which is capable to monitor gamma-ray transients from $\sim$ 6 keV to 6 MeV. As the main detector, there are 12 gamma-ray detectors (GRDs) equipped for GECAM-C. In order to verify the GECAM-C GRD detector performance and to validate the Monte Carlo simulations of detector response, comprehensive on-ground calibration experiments have been performed using X-ray beam and radioactive sources, including Energy-Channel relation, energy resolution, detection efficiency, SiPM voltage-gain relation and the non-uniformity of positional response. In this paper, the detailed calibration campaigns and data analysis results for GECAM-C GRDs are presented, demonstrating the excellent performance of GECAM-C GRD detectors.Comment: third versio

Observation of GRB 221009A early afterglow in X/γ\gamma-ray energy band

The early afterglow of a Gamma-ray burst (GRB) can provide critical information on the jet and progenitor of the GRB. The extreme brightness of GRB 221009A allows us to probe its early afterglow in unprecedented detail. In this letter, we report comprehensive observation results of the early afterglow of GRB 221009A (from $T_0$+660 s to $T_0$+1860 s, where $T_0$ is the \textit{Insight}-HXMT/HE trigger time) in X/$\gamma$-ray energy band (from 20 keV to 20 MeV) by \textit{Insight}-HXMT/HE, GECAM-C and \textit{Fermi}/GBM. We find that the spectrum of the early afterglow in 20 keV-20 MeV could be well described by a cutoff power-law with an extra power-law which dominates the low and high energy bands respectively. The cutoff power-law $E_{\rm peak}$ is $\sim$ 30 keV and the power-law photon index is $\sim$ 1.8 throughout the early afterglow phase. By fitting the light curves in different energy bands, we find that a significant achromatic break (from keV to TeV) is required at $T_0$ + 1246$^{+27}_{-26}$ s (i.e. 1021 s since the afterglow starting time $T_{\rm AG}$=$T_0$+225 s), providing compelling evidence of a jet break. Interestingly, both the pre-break and post-break decay slopes vary with energy, and these two slopes become closer in the lower energy band, making the break less identifiable. Intriguingly, the spectrum of the early afterglow experienced a slight hardening before the break and a softening after the break. These results provide new insights into the understanding of this remarkable GRB.Comment: Accepted for publication in ApJ Letters on 19-Jan-2024, 11 pages, 7 figures and 2 table

Calibration of the Timing Performance of GECAM-C

As a new member of the Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) after GECAM-A and GECAM-B, GECAM-C (originally called HEBS), which was launched on board the SATech-01 satellite on July 27, 2022, aims to monitor and localize X-ray and gamma-ray transients from $\sim$ 6 keV to 6 MeV. GECAM-C utilizes a similar design to GECAM but operates in a more complex orbital environment. In this work, we utilize the secondary particles simultaneously produced by the cosmic-ray events on orbit and recorded by multiple detectors, to calibrate the relative timing accuracy between all detectors of GECAM-C. We find the result is 0.1 $\mu \rm s$, which is the highest time resolution among all GRB detectors ever flown and very helpful in timing analyses such as minimum variable timescale and spectral lags, as well as in time delay localization. Besides, we calibrate the absolute time accuracy using the one-year Crab pulsar data observed by GECAM-C and Fermi/GBM, as well as GECAM-C and GECAM-B. The results are $2.02\pm 2.26\ \mu \rm s$ and $5.82\pm 3.59\ \mu \rm s$, respectively. Finally, we investigate the spectral lag between the different energy bands of Crab pulsar observed by GECAM and GBM, which is $\sim -0.2\ {\rm \mu s\ keV^{-1}}$.Comment: submitte

Hepcidin Is Involved in Iron Regulation in the Ischemic Brain

Oxidative stress plays an important role in neuronal injuries caused by cerebral ischemia. It is well established that free iron increases significantly during ischemia and is responsible for oxidative damage in the brain. However, the mechanism of this ischemia-induced increase in iron is not completely understood. In this report, the middle cerebral artery occlusion (MCAO) rat model was performed and the mechanism of iron accumulation in cerebral ischemia-reperfusion was studied. The expression of L-ferritin was significantly increased in the cerebral cortex, hippocampus, and striatum on the ischemic side, whereas H-ferritin was reduced in the striatum and increased in the cerebral cortex and hippocampus. The expression level of the iron-export protein ferroportin1 (FPN1) significantly decreased, while the expression of transferrin receptor 1 (TfR1) was increased. In order to elucidate the mechanisms of FPN1 regulation, we studied the expression of the key regulator of FPN1, hepcidin. We observed that the hepcidin level was significantly elevated in the ischemic side of the brain. Knockdown hepcidin repressed the increasing of L-ferritin and decreasing of FPN1 invoked by ischemia-reperfusion. The results indicate that hepcidin is an important contributor to iron overload in cerebral ischemia. Furthermore, our results demonstrated that the levels of hypoxia-inducible factor-1α (HIF-1α) were significantly higher in the cerebral cortex, hippocampus and striatum on the ischemic side; therefore, the HIF-1α-mediated TfR1 expression may be another contributor to the iron overload in the ischemia-reperfusion brain

Nonstandard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants