Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved ...by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization
. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
Here, we present the first cosmological parameter constraints using measurements of type Ia supernovae (SNe Ia) from the Dark Energy Survey Supernova Program (DES-SN). The analysis uses a subsample ...of 207 spectroscopically confirmed SNe Ia from the first three years of DES-SN, combined with a low-redshift sample of 122 SNe from the literature. Our "DES-SN3YR" result from these 329 SNe Ia is based on a series of companion analyses and improvements covering SN Ia discovery, spectroscopic selection, photometry, calibration, distance bias corrections, and evaluation of systematic uncertainties. For a flat ΛCDM model we find a matter density ${{\rm{\Omega }}}_{{\rm{m}}}=0.331\pm 0.038$. For a flat wCDM model, and combining our SN Ia constraints with those from the cosmic microwave background (CMB), we find a dark energy equation of state $w=-0.978\pm 0.059$, and ${{\rm{\Omega }}}_{{\rm{m}}}=0.321\pm 0.018$. For a flat w 0 w a CDM model, and combining probes from SN Ia, CMB and baryon acoustic oscillations, we find ${w}_{0}=-0.885\pm 0.114$ and ${w}_{a}=-0.387\,\pm \,0.430$. These results are in agreement with a cosmological constant and with previous constraints using SNe Ia (Pantheon, JLA).
Broad-line type Ic SN 2020bvc Izzo, L.; Auchettl, K.; Hjorth, J. ...
Astronomy and astrophysics (Berlin),
07/2020, Letnik:
639
Journal Article
Recenzirano
Long-duration gamma-ray bursts (GRBs) are almost unequivocally associated with very energetic, broad-line supernovae of Type Ic-BL. While the gamma-ray emission is emitted in narrow jets, the SN ...emits radiation isotropically. Therefore, it has been hypothesized that some SN Ic-BL not associated with GRBs arise from events with inner engines such as off-axis GRBs or choked jets. Here we present observations of the nearby (
d
= 120 Mpc) SN 2020bvc (ASAS-SN 20bs) that support this scenario.
Swift
-UVOT observations reveal an early decline (up to two days after explosion), while optical spectra classify it as a SN Ic-BL with very high expansion velocities (≈70 000 km s
−1
), similar to that found for the jet-cocoon emission in SN 2017iuk associated with GRB 171205A. Moreover, the
Swift
X-Ray Telescope and CXO X-ray Observatory detected X-ray emission only three days after the SN and decaying onward, which can be ascribed to an afterglow component. Cocoon and X-ray emission are both signatures of jet-powered GRBs. In the case of SN 2020bvc, we find that the jet is off axis (by ≈23 degrees), as also indicated by the lack of early (≈1 day) X-ray emission, which explains why no coincident GRB was detected promptly or in archival data. These observations suggest that SN 2020bvc is the first orphan GRB detected through its associated SN emission.
New designs for compact reconfigurable antennas are introduced for mobile communication devices. The uniqueness of the antenna designs are that they allow various groups of their operating frequency ...bands to be selected electronically. In particular, each group of frequency bands, or mode, can be made to serve several different communication systems simultaneously. These systems may include various combinations of GSM, DCS, PCS, UMTS, Bluetooth, and wireless local-area network (LAN). Therefore, by electronically selecting different antenna modes, a variety of communication systems can be conveniently served by only one antenna. One advantage is that through the different operational modes, the total antenna volume can be reused, and therefore the overall antenna can be made compact. In these designs, the selection of the different modes is achieved by either i) switching different feeding locations of the antenna (switched feed) or ii) switching or breaking of the antenna's connection to the ground (switched ground). This paper demonstrates these two designs. For the first design of switched feed, it can support GSM, DCS, PCS, and UMTS. In the second design, the antenna makes use of a switched-ground technique, which can cover GSM, DCS, PCS, UMTS, Bluetooth, and 2.4 GHz wireless LAN. The designs are investigated when ideal switches and also various realistic active switches based on PIN diodes, GaAs field effect transistor, and MEMs configurations. The designs are verified through both numerical simulations and measurement of an experimental prototype. The results confirm good performance of the two multiband reconfigurable antenna designs.
The impact of estrogen receptor (ER) was examined for expression and activity of cytochrome P4501B1 (CYP1B1) and cytochrome P4501A1 (CYP1A1) in two pairs of ER+/ER– human breast epithelial cell lines ...derived from single lineages, and representing earlier (T47D) or later (MDA-MB-231) stages of tumorigenesis. Acute loss of ER was evaluated using the anti-estrogen ICI 182,780 (ICI). In all lines, CYP1B1 was expressed constitutively and was induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), whereas CYP1A1 was expressed only following induction. Expression of each CYP (with or without TCDD) was greater in T47D cells than MDA cells. The ER impacted expression of these genes in opposite directions. The ER– phenotype was associated with less TCDD-induced CYP1A1 expression, but greater basal and induced CYP1B1 expression. A 48 h treatment of ER+ cells with ICI did not revert the P450 expression pattern to that of ER– cells. Based on activities of recombinant enzyme and expression levels, differences in 7,2-dimethylbenz aanthracene (DMBA) metabolism between the cell lines were consistent with differences in CYP1A1 and CYP1B1 expression. In T47D lines, basal microsomal DMBA metabolism was primarily due to CYP1B1, based on regioselective metabolite distribution and inhibition by anti-CYP1B1 antibodies (>80%). Metabolism in TCDD-induced microsomes was mostly due to CYP1A1 and was inhibited by anti-CYP1A1 antibody (>50%). TCDD-induced MDA+ cells demonstrated CYP1A1 activity, whereas TCDD-induced MDA– cells displayed CYP1B1 activity. Aryl hydrocarbon receptor (AhR) levels, but not AhR nuclear translocator protein (ARNT) levels were highly dependent on cell type; AhR was high and ER-independent in MDA, and low and ER-linked in T47D. AhR levels were insensitive to ICI. ER does not directly modulate the expression of CYP1A1, CYP1B1 or AhR. Indeed, factors that have replaced ER in growth regulation during clonal selection predominate in this regulation. Characteristics unique to each cell line, including ER status, determine CYP1A1 and CYP1B1 expression.
We report on our study of the supernova (SN) 2022xxf based on observations obtained during the first four months of its evolution. The light curves (LCs) display two humps of similar maximum ...brightness separated by 75 days, unprecedented for a broad-lined (BL) Type Ic supernova (SN IcBL). SN 2022xxf is the most nearby SN IcBL to date (in NGC 3705,
z
= 0.0037, at a distance of about 20 Mpc). Optical and near-infrared photometry and spectroscopy were used to identify the energy source powering the LC. Nearly 50 epochs of high signal-to-noise ratio spectroscopy were obtained within 130 days, comprising an unparalleled dataset for a SN IcBL, and one of the best-sampled SN datasets to date. The global spectral appearance and evolution of SN 2022xxf points to typical SN Ic/IcBL, with broad features (up to ~14 000 km s
−1
) and a gradual transition from the photospheric to the nebular phase. However, narrow emission lines (corresponding to ~ 1000–2500 km s
−1
) are present in the spectra from the time of the second rise, suggesting slower-moving circumstellar material (CSM). These lines are subtle, in comparison to the typical strong narrow lines of CSM-interacting SNe, for example, Type IIn, Ibn, and Icn, but some are readily noticeable at late times, such as in Mg I
λ
5170 and O I
λ
5577. Unusually, the near-infrared spectra show narrow line peaks in a number of features formed by ions of O and Mg. We infer the presence of CSM that is free of H and He. We propose that the radiative energy from the ejecta-CSM interaction is a plausible explanation for the second LC hump. This interaction scenario is supported by the color evolution, which progresses to blue as the light curve evolves along the second hump, and by the slow second rise and subsequent rapid LC drop. SN 2022xxf may be related to an emerging number of CSM-interacting SNe Ic, which show slow, peculiar LCs, blue colors, and subtle CSM interaction lines. The progenitor stars of these SNe likely experienced an episode of mass loss consisting of H/He-free material shortly prior to explosion.
CYP1B1 and CYP1A1 expression and metabolism of 7,12-dimethylbenz(a)anthracene (DMBA) have been characterized in early-passage human mammary epithelial cells (HMECs) isolated from reduction ...mammoplasty tissue of seven individual donors. The level of constitutive microsomal CYP1B1 protein expression was donor dependent (<0.01-1.4 pmol/mg microsomal protein). CYP1B1 expression was substantially induced by exposure of the cells to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to levels ranging from 2.3 to 16.6 pmol/mg among the seven donors. Extremely low, reproducible levels of constitutive CYP1A1 expression were detectable in three donors (0.03-0.16 pmol/mg microsomal protein). TCDD inductions were larger for CYP1A1, as compared to CYP1B1, demonstrating substantial variability in the induced levels among the donors (0.8-16.5 pmol/mg). Northern and reverse transcriptase PCR analyses corroborate the donor-dependent differences in protein expression, whereby CYP1B1 mRNA (5.2 kb) was constitutively expressed and was highly induced by TCDD (33-fold). The contributions of CYP1B1 and CYP1A1 to the metabolism of DMBA were analyzed using recombinant human CYP1B1 and CYP1A1, as references, in conjunction with antibody-specific inhibition analyses (anti-CYP1B1 and anti-CYP1A1). Constitutive microsomal activity exhibited a profile of regioselective DMBA metabolism that was characteristic of human CYP1B1 (increased proportions of 5,6- and 10,11-DMBA-dihydrodiols), which was inhibited by anti-CYP1B1 (84%) but not by anti-CYP1A1. TCDD-induced HMEC microsomal DMBA metabolism generated the 8,9-dihydrodiol of DMBA as the predominant metabolite, with a regioselectivity similar to that of recombinant human CYP1A1, which was subsequently inhibited by anti-CYP1A1 (79%). A CYP1B1 contribution was indicated by the regioselectivity of residual metabolism and by anti-CYP1B1 inhibition (25%). DMBA metabolism analyses of one of three donors expressing measurable basal expression of CYP1A1 confirmed DMBA metabolism levels equivalent to that from CYP1B1. The HMECs of all donors expressed similar, very high levels of the aryl hydrocarbon receptor and the aryl hydrocarbon nuclear translocator protein, suggesting that aryl hydrocarbon receptor and aryl hydrocarbon nuclear translocator protein expression are not responsible for differences in cytochrome P450 expression. This study indicates that CYP1B1 is an important activator of polycyclic aromatic hydrocarbons in the mammary gland when environmental chemical exposures minimally induce CYP1A1. Additionally, certain individuals express low levels of basal CYP1A1 in HMECs, representing a potential risk factor of mammary carcinogenesis through enhanced polycyclic aromatic hydrocarbon bioactivation.
After endoscopic treatment to control bleeding of peptic ulcers, bleeding recurs in 15 to 20 percent of patients. In a prospective, randomized study, we compared endoscopic retreatment with surgery ...after initial endoscopy. Over a 40-month period, 1169 of 3473 adults who were admitted to our hospital with bleeding peptic ulcers underwent endoscopy to reestablish hemostasis. Of 100 patients with recurrent bleeding, 7 patients with cancer and 1 patient with cardiac arrest were excluded from the study; 48 patients were randomly assigned to undergo immediate endoscopic retreatment and 44 were assigned to undergo surgery. The type of operation used was left to the surgeon. Bleeding was considered to have recurred in the event of any one of the following: vomiting of fresh blood, hypotension and melena, or a requirement for more than four units of blood in the 72-hour period after endoscopic treatment.
Of the 48 patients who were assigned to endoscopic retreatment, 35 had long-term control of bleeding. Thirteen underwent salvage surgery, 11 because retreatment failed and 2 because of perforations resulting from thermocoagulation. Five patients in the endoscopy group died within 30 days, as compared with eight patients in the surgery group (P=0.37). Seven patients in the endoscopy group (including 6 who underwent salvage surgery) had complications, as compared with 16 in the surgery group (P=0.03). The duration of hospitalization, the need for hospitalization in the intensive care unit and the resultant duration of that stay, and the number of blood transfusions were similar in the two groups. In multivariate analysis, hypotension at randomization (P=0.01) and an ulcer size of at least 2 cm (P=0.03) were independent factors predictive of the failure of endoscopic retreatment.
In patients with peptic ulcers and recurrent bleeding after initial endoscopic control of bleeding, endoscopic retreatment reduces the need for surgery without increasing the risk of death and is associated with fewer complications than is surgery.
BACKGROUND: In order to reduce maternal mortality in South Africa (SA), it is important to understand the process of obstetric care, identify weaknesses within the system, and implement interventions ...for improving care. OBJECTIVE: To determine the spectrum of maternal morbidity and mortality in the Pretoria Academic Complex (PAC), SA. METHODS: A descriptive population-based study that included all women delivering in the PAC. The World Health Organization definition,criteria and indicators of near miss and maternal death were used to identify women with severe complications in pregnancy. RESULTS: Between 1 August 2013 and 31 July 2014, there were 26 614 deliveries in the PAC. The institutional maternal mortality ratio was71.4/100 000 live births. The HIV infection rate was 19.9%, and 2.7% of women had unknown HIV status. Of the women, 1 120 (4.2%) developed potentially life-threatening conditions and 136 (0.5%) life-threatening conditions. The mortality index was 14.0% overall, 30.0% for non-pregnancy-related infections, 2.0% for obstetric haemorrhage and 13.6% for hypertension. Of the women with life-threatening conditions, 39.3% were referred from the primary level of care. Vascular, uterine and coagulation dysfunctions were the most frequent organ dysfunctions in women with life-threatening conditions. The perinatal mortality rate was 26.9/1 000 births overall, 23.1/1 000 for women with non-life-threatening conditions, and 198.0/1 000 for women with life-threatening conditions. CONCLUSION: About one in 20 pregnant women in the PAC had a potentially life-threatening condition; 39.3% of women presented to a primary level facility as an acute emergency and had to be transferred for tertiary care. All healthcare professionals involved in maternity care must have knowledge and skills that equip them to manage obstetric emergencies. Review of the basic antenatal care protocol may be necessary.
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