Abstract
The image-charge detection provides a new direct method for the detection of the Rydberg transition of electrons trapped on the surface of liquid helium. The interest in this method is ...motivated by the possibility to accomplish the spin state readout for a single trapped electron, thus opening a new pathway towards using electron spins on liquid helium for quantum computing. Here, we report on the image-charge detection of the Rydberg transition in a many-electron system confined in an array of 20
μ
m wide and 4
μ
m deep channels filled with superfluid helium. Such detection is made possible because of a significant enhancement of the image-charge signal due to close proximity of trapped electrons to the electrodes embedded in the microchannel structure. The transition frequency of electrons in the range of 400–500 GHz is highly controllable by the dc bias voltages applied to the device and is in a good agreement with our calculations. This work demonstrates that microchannel structures provide a suitable platform for electron manipulation and their quantum state detection, with a feasibility of scaling the detection method to a single electron.
A limitation of spatial transcriptomics technologies is that individual measurements may contain contributions from multiple cells, hindering the discovery of cell-type-specific spatial patterns of ...localization and expression. Here, we develop robust cell type decomposition (RCTD), a computational method that leverages cell type profiles learned from single-cell RNA-seq to decompose cell type mixtures while correcting for differences across sequencing technologies. We demonstrate the ability of RCTD to detect mixtures and identify cell types on simulated datasets. Furthermore, RCTD accurately reproduces known cell type and subtype localization patterns in Slide-seq and Visium datasets of the mouse brain. Finally, we show how RCTD's recovery of cell type localization enables the discovery of genes within a cell type whose expression depends on spatial environment. Spatial mapping of cell types with RCTD enables the spatial components of cellular identity to be defined, uncovering new principles of cellular organization in biological tissue. RCTD is publicly available as an open-source R package at https://github.com/dmcable/RCTD .
Summary
Abaloparatide (ABL) is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture. ...However, real-world data regarding its long-term safety and tolerability in large sample population are incomplete. We evaluated abaloparatide-associated safety signals by data mining of the FDA pharmacovigilance database.
Introduction
We investigated 33,480(0.14%) ABL-related adverse events (AEs) through data mining of Food and Drug Administration Adverse Event Reporting System (FAERS) retrospectively.
Methods
Reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed to quantify the signals of ABL-related AEs from 2017Quarter2 to 2022.Serious and non-serious cases were compared by Mann-Whitney
U
test or Chi-squared (
χ
2
) test.
Results
We collected 8,470,497 reports from the FAERS database, including 11,487 reports defined ABL as the primary suspected (PS) drug. Additionally, 36.16% of the reports were submitted by healthcare professionals (
n
=4154), compared to 62.26% reported by consumers (
n
=7140). A total 99 signals simultaneously conforming to four algorithms were detected, among which, 35 signals were identified as unexpected signals. Such as growing pains (
n
=13), waist circumference increased (
n
=21), sensory disturbance (
n
=103), tinnitus (
n
=65), visual acuity reduced (
n
=54), blood alkaline phosphatase increased (
n
=61), and hair growth abnormal (
n
=13). Patient age (
p
< 0.001) might be associated with an increased risk of AEs severity. The most common timeframe for AE occurrence was 0–7 days.
Conclusion
Our study provided a deeper and broader understanding of abaloparatide’s safety profiles, which would help healthcare professionals to mitigate the risk of AEs in clinical practice, a low number of unexpected AEs supporting ongoing additional pharmacovigilance.
A critical, long‐standing problem in substorm research is identification of the sequence of events leading to substorm auroral onset. Based on event and statistical analysis of THEMIS all‐sky imager ...data, we show that there is a distinct and repeatable sequence of events leading to onset, the sequence having similarities to and important differences from previous ideas. The sequence is initiated by a poleward boundary intensification (PBI) and followed by a north‐south (N‐S) arc moving equatorward toward the onset latitude. Because of the linkage of fast magnetotail flows to PBIs and to N‐S auroras, the results indicate that onset is preceded by enhanced earthward plasma flows associated with enhanced reconnection near the pre‐existing open‐closed field line boundary. The flows carry new plasma from the open field line region to the plasma sheet. The auroral observations indicate that Earthward‐transport of the new plasma leads to a near‐Earth instability and auroral breakup ∼5.5 min after PBI formation. Our observations also indicate the importance of region 2 magnetosphere‐ionosphere electrodynamic coupling, which may play an important role in the motion of pre‐onset auroral forms and determining the local times of onsets. Furthermore, we find motion of the pre‐onset auroral forms around the Harang reversal and along the growth phase arc, reflecting a well‐developed region 2 current system within the duskside convection cell, and also a high probability of diffuse‐appearing aurora occurrence near the onset latitude, indicating high plasma pressure along these inner plasma sheet field lines, which would drive large region 2 currents.
Understanding the toxicity of nanomaterials is essential for the safe and sustainable development of new applications. This is particularly true for a nanomaterial as widely used as graphene oxide ...(GO), which is utilized as films for electronics, membranes for filtration, drug carriers and more. Despite this, the current literature presents conflicting results on the overall toxicity of GO. Here, the cytotoxicity of three sizes of commercially available GO was investigated on six cell lines, as values of NOAEL/LOAEL. The effectiveness of four viability assays was also evaluated. The overall toxicity of GO greatly varied between cell lines; the suspension cells showed a greater response to the GO treatment compared to the adherent cell lines. Time dependent cytotoxicity was also cell line dependent, with only one cell line demonstrating obvious dependence. The six cell lines were also tested to evaluate their response to varying GO flake sizes: the suspension/phagocytic cells showed little variation in viability, while a difference was observed for the adherent/non-phagocytic cell lines. By systematically studying the effect of dose, GO size and treatment time for the six cell lines by using commercially available GO samples, we eliminate many of the variables which may result in the conflicting reports on the cytotoxicity of GO in the literature.
Vehicular emissions are the major sources of a number of air pollutants including nonmethane hydrocarbons (NMHCs) in urban area. The emission composition and emission factors of NMHCs from vehicles ...are currently lacking in Hong Kong. In this study, speciation and emission factors of NMHCs emitted from gasoline-fuelled private cars and liquefied petroleum gas (LPG)-fuelled taxis at different driving speeds were constructed using a chassis dynamometer. Large variations in the contributions of individual NMHC species to total emission were observed for different private cars at different driving speeds. The variations of individual NMHC emissions were relatively smaller for taxis due to their relatively homogeneous year of manufacture and mileages. Incomplete combustion products like ethane, ethene and propene were the major component of both types of vehicles, while unburned fuel component was also abundant in the exhausts of private cars and taxis (i.e.
i-pentane and toluene for private car, and propane and butanes for taxi). Emission factors of major NMHCs emitted from private cars and taxis were estimated. High emission factors of ethane,
n-butane,
i/
n-pentanes, methylpentanes, trimethylpentanes, ethene, propene,
i-butene, benzene, toluene and xylenes were found for private cars, whereas propane and
i/
n-butanes had the highest values for taxis. By evaluating the effect of vehicular emissions on the ozone formation potential (OFP), it was found that the contributions of olefinic and aromatic hydrocarbons to OFP were higher than that from paraffinic hydrocarbons for private car, whereas the contributions of propane and
i/
n-butanes were the highest for taxis. The total OFP value was higher at lower speeds (≤50 km h
−1) for private cars while a minimum value at driving speed of 100 km h
−1 was found for taxis. At the steady driving speeds, the total contribution of NMHCs emitted from LPG-fuelled taxis to the OFP was much lower than that from gasoline-fuelled private cars. However, at idling state, the contribution of NMHCs from LPG-fuelled vehicles to OFP was comparable to that from gasoline-fuelled vehicles. The findings obtained in this study can be used to mitigate the air pollution caused by vehicles in highly dense urban areas.
► The emission composition and emission factors of NMHCs from vehicles currently lack in Hong Kong. ► High emission factors of alkanes, benzene and toluene were found for private cars. ► Propane and
i/
n-butanes had the highest values for taxis. ► Aromatics and C3–C4 alkanes were the largest contributor to OFP for cars, and taxis, respectively. ► The findings are helpful to mitigate air pollution caused by vehicles in highly dense urban areas.
We present the first high resolution global MHD with coupled inner magnetosphere simulation results of an observed theta aurora event. We use the Space Weather Modeling Framework in the Geospace ...configuration, which produces accurate field aligned current closure in the ionosphere that is integral to theta aurora formation. At the location of the observed theta aurora, the simulation produces a narrow channel of Joule heating along both open and closed field lines, and between a pair of oppositely directed field‐aligned current sheets in the ionosphere. We demonstrate that this Joule heating pattern that we identify as theta aurora maps to a reconnection region at the magnetotail flanks as well as in the distant magnetotail. The theta aurora maps to a cross‐tail current disruption and field‐aligned current source region in a highly twisted magnetotail.
Plain Language Summary
The light of the aurora observed in the Earth's atmosphere is a signature of magnetic processes in outer space. The Sun produces hot magnetized plasma that blows through the solar system like a wind. The Earth's magnetic field shields us from the harmful impacts of the Sun's magnetized plasma wind. The interaction between the Earth's magnetic field and the Sun's plasma wind causes the ring of auroral light we see in the polar regions. Sometimes the ring of auroral light grows a bar of auroral light across its center (over the Earth's magnetic poles), transforming the ring into a structure like the Greek letter theta. We call this the theta aurora. It is unknown what physical processes in the Earth's magnetic field create the theta aurora. In this study we show the first realistic simulation that uses solar wind driver conditions of an observed theta aurora event, and demonstrate that we can successfully produce the theta aurora structure in the simulation. We find that the theta aurora's center bar of auroral light comes from multiple regions in the vast Earth's magnetotail. This new result helps us better understand the dynamics of the Earth's space environment and better protect ourselves against the Sun's hazardous plasma wind effects.
Key Points
We show first global MHD simulation event study that successfully produces a Joule heating signature that we identify as theta aurora
Simulation associates transpolar arc signatures with reconnection at the magnetospheric flank and in the distant magnetotail
The transpolar arc maps to a cross‐tail current disruption and field‐aligned current source region in a highly twisted magnetotail
We present Chandra observations of 23 galaxy groups and low-mass galaxy clusters at 0.03 < z < 0.15 with a median temperature of
${\sim }2{{\rm keV}}$
. The sample is a statistically complete ...flux-limited subset of the 400 deg2 survey. We investigated the scaling relation between X-ray luminosity (L) and temperature (T), taking selection biases fully into account. The logarithmic slope of the bolometric L–T relation was found to be 3.29 ± 0.33, consistent with values typically found for samples of more massive clusters. In combination with other recent studies of the L–T relation, we show that there is no evidence for the slope, normalization, or scatter of the L–T relation of galaxy groups being different than that of massive clusters. The exception to this is that in the special case of the most relaxed systems, the slope of the core-excised L–T relation appears to steepen from the self-similar value found for massive clusters to a steeper slope for the lower mass sample studied here. Thanks to our rigorous treatment of selection biases, these measurements provide a robust reference against which to compare predictions of models of the impact of feedback on the X-ray properties of galaxy groups.
The prognosis for pancreatic cancer is extremely poor. To improve the prognosis of pancreatic cancer, it is urgently needed to improve early detection to advance treatment. And basically, it is also ...necessary to emphasise basic research to find novel therapies. By promoting the disease-centered multidisciplinary team model, researchers should achieve high-quality closed-loop process management of the entire life cycle which consists of prevention, screening, diagnosis, treatment, rehabilitation,and follow-up, with the objective of establishing a standard clinical process to improve the outcome in essence. This article summarized the progress of pancreatic cancer at different stages of the whole cycle management recently and shared the experience of pancreatic cancer treatment from the author's team in the past ten years.
Recent studies indicate that persistent pain after tissue or nerve injury is accompanied by an enhanced net descending facilitatory drive that contributes to an amplification and spread of pain. ...Although 5-HT-containing neurons in the rostral ventromedial medulla (RVM) provide the major descending serotonergic projection to the spinal cord, it is not clear whether the neurotransmitter 5-HT itself released from RVM-spinal neurons contributes to descending pain modulation. In the present study, we determined the role of the descending 5-HT in rat nocifensive behaviors after persistent pain by selectively depleting functional phenotypes of 5-HT in RVM neurons with regional shRNA interference (RNAi) of tryptophan hydroxylase-2 (Tph-2), the rate-limiting enzyme in the synthesis of neuronal 5-HT. Compared to negative control shRNA, Tph-2 shRNA induced significantly prolonged downregulation of Tph-2 in the RVM and 5-HT in spinal dorsal horn. The 5-HT-depleted rats showed normal pain sensitivity in responses to acute noxious stimulation. However, the same RNAi treatment attenuated formalin-induced spontaneous nocifensive responses and tissue or nerve injury-induced allodynia and hyperalgesia. Furthermore, in control shRNA-treated animals, intra-RVM microinjection of brain-derived neurotrophic factor produced a reversible hyperalgesia, which was completely prevented by Tph-2 RNAi pretreatment. Descending inhibition induced by intra-RVM electrical stimulation, but not microinjection of the mu- or kappa-opioid receptor agonists in control shRNA-treated animals was eliminated in 5-HT-depleted rats. These results indicate that the descending 5-HT from the RVM is an important contributor to pain facilitation during the development of persistent pain, and may not mediate opioid-induced descending inhibition in acute pain.
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