ABSTRACT
We present 849 new bursts from FRB 20121102A detected with the 305-m Arecibo Telescope. Observations were conducted as part of our regular campaign to monitor activity and evolution of burst ...properties. The 10 reported observations were carried out between 1150 and $1730\, {\rm MHz}$ and fall in the active period around 2018 November. All bursts were dedispersed at the same dispersion measure and are consistent with a single value of $(562.4 \pm 0.1)\, {\rm pc\, cm^{-3}}$. The rate varies between 0 bursts and 218 ± 16 bursts per hour, the highest rate observed to date. The times between consecutive bursts show a bimodal distribution. We find that a Poisson process with varying rate best describes arrival times with separations ${\gt}{0.1\, {\rm s}}$. Clustering on time-scales of $22\, {\rm ms}$ reflects a characteristic time-scale of the source and possibly the emission mechanism. We analyse the spectro-temporal structure of the bursts by fitting 2D Gaussians with a temporal drift to each sub-burst in the dynamic spectra. We find a linear relationship between the sub-burst’s drift and its duration. At the same time, the drifts are consistent with coming from the sad-trombone effect. This has not been predicted by current models. The energy distribution shows an excess of high-energy bursts and is insufficiently modelled by a single power law even within single observations. We find long-term changes in the energy distribution, the average spectrum, and the sad-trombone drift, compared to earlier and later published observations. Despite the large burst rate, we find no strict short-term periodicity.
ABSTRACT We report the discovery of two long-term intermittent radio pulsars in the ongoing Pulsar Arecibo L-Band Feed Array survey. Following discovery with the Arecibo Telescope, extended ...observations of these pulsars over several years at Jodrell Bank Observatory have revealed the details of their rotation and radiation properties. PSRs J1910+0517 and J1929+1357 show long-term extreme bimodal intermittency, switching between active (ON) and inactive (OFF) emission states and indicating the presence of a large, hitherto unrecognized underlying population of such objects. For PSR J1929+1357, the initial duty cycle was fON = 0.008, but two years later, this changed quite abruptly to fON = 0.16. This is the first time that a significant evolution in the activity of an intermittent pulsar has been seen, and we show that the spin-down rate of the pulsar is proportional to the activity. The spin-down rate of PSR J1929+1357 is increased by a factor of 1.8 when it is in active mode, similar to the increase seen in the other three known long-term intermittent pulsars. These discoveries increase the number of known pulsars displaying long-term intermittency to five. These five objects display a remarkably narrow range of spin-down power ( ) and accelerating potential above their polar caps. If confirmed by further discoveries, this trend might be important for understanding the physical mechanisms that cause intermittency.
The factors necessary to maintain organ-specific progenitor cells are poorly understood and yet of extreme clinical importance. Here, we identify the transcription factor SOX9 as the first specific ...marker and maintenance factor of multipotential progenitors during pancreas organogenesis. In the developing pancreas, SOX9 expression is restricted to a mitotically active, Notch-responsive subset of PDX1⁺ pluripotent progenitors and is absent from committed endocrine precursors or differentiated cells. Similar to Notch mutations, organ-specific Sox9 inactivation in mice causes severe pancreatic hypoplasia resulting from depletion of the progenitor cell pool. We show that Sox9 maintains pancreatic progenitors by stimulating their proliferation, survival, and persistence in an undifferentiated state. Our finding that SOX9 regulates the Notch-effector HES1 suggests a Notch-dependent mechanism and establishes a possible genetic link between SOX factors and Notch. These findings will be of major significance for the development of in vitro protocols for cell replacement therapies.
FRB 121102, the only repeating fast radio burst (FRB) known to date, was discovered at 1.4 GHz and shortly after the discovery of its repeating nature, detected up to 2.4 GHz. Here, we present three ...bursts detected with the 100 m Effelsberg radio telescope at 4.85 GHz. All three bursts exhibited frequency structure on broad and narrow frequency scales. Using an autocorrelation function analysis, we measured a characteristic bandwidth of the small-scale structure of 6.4 1.6 MHz, which is consistent with the diffractive scintillation bandwidth for this line of sight through the Galactic interstellar medium (ISM) predicted by the NE2001 model. These were the only detections in a campaign totaling 22 hr in 10 observing epochs spanning five months. The observed burst detection rate within this observation was inconsistent with a Poisson process with a constant average occurrence rate; three bursts arrived in the final 0.3 hr of a 2 hr observation on 2016 August 20. We therefore observed a change in the rate of detectable bursts during this observation, and we argue that boosting by diffractive interstellar scintillations may have played a role in the detectability. Understanding whether changes in the detection rate of bursts from FRB 121102 observed at other radio frequencies and epochs are also a product of propagation effects, such as scintillation boosting by the Galactic ISM or plasma lensing in the host galaxy, or an intrinsic property of the burst emission will require further observations.
The generation of pancreas, liver, and intestine from a common pool of progenitors in the foregut endoderm requires the establishment of organ boundaries. How dorsal foregut progenitors activate ...pancreatic genes and evade the intestinal lineage choice remains unclear. Here, we identify Pdx1 and Sox9 as cooperative inducers of a gene regulatory network that distinguishes the pancreatic from the intestinal lineage. Genetic studies demonstrate dual and cooperative functions for Pdx1 and Sox9 in pancreatic lineage induction and repression of the intestinal lineage choice. Pdx1 and Sox9 bind to regulatory sequences near pancreatic and intestinal differentiation genes and jointly regulate their expression, revealing direct cooperative roles for Pdx1 and Sox9 in gene activation and repression. Our study identifies Pdx1 and Sox9 as important regulators of a transcription factor network that initiates pancreatic fate and sheds light on the gene regulatory circuitry that governs the development of distinct organs from multi-lineage-competent foregut progenitors.
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•Genetic studies show Pdx1 and Sox9 cooperatively specify the pancreatic lineage•Pdx1+Sox9 co-occupy regulatory sequences of pancreatic and intestinal genes•Pdx1+Sox9 cooperatively repress intestinal cell fate determinants such as Cdx2•Pdx1+Sox9 are necessary and sufficient to repress the intestinal fate choice
Shih et al. identify a positive cross-regulatory Pdx1-Sox9 loop that promotes expression of the pancreas-specific factors Ptf1a and Nkx6.1 while repressing intestinal cell fate determinants, including Cdx2, favoring adoption of a pancreatic fate.
Foramen of Winslow hernia (FWH) is an extremely rare entity accounting for up to 8% of internal hernias and 0.08% of all hernias. Only 150 cases of FWH have been described in the literature to date ...with a peak incidence between the third and sixth decades of life. Three main mechanisms seem to be implicated in the FWH pathogenesis: (a) excessive viscera mobility, (b) abnormal enlargement of the foramen of Winslow, and (c) changes in the intra-abdominal pressure. The presence of an abnormally long bowel, enlargement of the right liver lobe or cholecystectomy, a “wandering cecum,” and defects of the gastrohepatic ligaments are some reported predisposing factors. Timely diagnosis through computed tomography facilitates the appropriate treatment before complications are evident. Although open repair has been mostly utilized, recently laparoscopic approach seems to gain ground due to the encouraging preliminary results. To date, the debate continues as to whether prophylactic measures to prevent recurrence of the FWH need to be undertaken: closure of the foramen, fixation of the highly mobilized viscera, or both.
Transient receptor potential melastatin (TRPM)3 is a calcium-permeable ion channel activated by the neurosteroid pregnenolone sulfate and positively coupled to insulin secretion in beta cells. ...Although vascular TRPM3 mRNA has been reported, there is no knowledge of TRPM3 protein or its regulation and function in the cardiovascular system.
To determine the relevance and regulation of TRPM3 in vascular biology.
TRPM3 expression was detected at mRNA and protein levels in contractile and proliferating vascular smooth muscle cells. Calcium entry evoked by pregnenolone sulfate or sphingosine was suppressed by TRPM3 blocking antibody or knock-down of TRPM3 by RNA interference. Low-level constitutive TRPM3 activity was also detected. In proliferating cells, channel activity was coupled negatively to interleukin-6 secretion via a calcium-dependent mechanism. In freshly isolated aorta, TRPM3 positively modulated contractile responses independently of L-type calcium channels. Concentrations of pregnenolone sulfate required to evoke responses were higher than the known plasma concentrations of the steroids, leading to a screen for other stimulators. beta-Cyclodextrin was one of few stimulators of TRPM3, revealing the channels to be partially suppressed by endogenous cholesterol, the precursor of pregnenolone. Elevation of cholesterol further suppressed channel activity and loading with cholesterol to generate foam cells precluded observation of TRPM3 activity.
The data suggest functional relevance of TRPM3 in contractile and proliferating phenotypes of vascular smooth muscle cells, significance of constitutive channel activity, regulation by cholesterol, and potential value of pregnenolone sulfate in therapeutic vascular modulation.
Although dihydropyridines are widely used for the treatment of vasospasm, their effectiveness is questionable, suggesting that other voltage-dependent calcium channels (VDCCs) contribute to control ...of cerebrovascular tone. This study therefore investigated the role of dihydropyridine-insensitive VDCCs in cerebrovascular function. Using quantitative PCR and immunohistochemistry, we found mRNA and protein for L-type (CaV1.2) and T-type (CaV3.1 and CaV3.2) channels in adult rat basilar and middle cerebral arteries and their branches. Immunoelectron microscopy revealed both L- and T-type channels in smooth muscle cell (SMC) membranes. Using patch clamp electrophysiology, we found that a high-voltage-activated calcium current, showing T-type channel kinetics and insensitivity to nifedipine and nimodipine, comprised ∼20% of current in SMCs of the main arteries and ∼45% of current in SMCs from branches. Both components were abolished by the T-type antagonists mibefradil, NNC 55-0396, and efonidipine. Although nifedipine completely blocked vasoconstriction in pressurized basilar arteries, a nifedipine-insensitive constriction was found in branches and this increased in magnitude as vessel size decreased. We conclude that a heterogeneous population of VDCCs contributes to cerebrovascular function, with dihydropyridine-insensitive channels having a larger role in smaller vessels. Sensitivity of these currents to nonselective T-type channel antagonists suggests that these drugs may provide a more effective treatment for therapy-refractory cerebrovascular constriction.
We present evidence for chaotic dynamics within the spin-down rates of 17 pulsars originally presented by Lyne et al. Using techniques that allow us to resample the original measurements without ...losing structural information, we have searched for evidence of a strange attractor in the time series of frequency derivatives for each of the 17 pulsars. We demonstrate the effectiveness of our methods by applying them to a component of the Lorenz and Rössler attractors that were sampled with similar cadence to the pulsar time series. Our measurements of correlation dimension and Lyapunov exponent show that the underlying behaviour appears to be driven by a strange attractor with approximately three governing non-linear differential equations. This is particularly apparent in the case of PSR B1828−11 where a correlation dimension of 2.06 ± 0.03 and a Lyapunov exponent of (4.0 ± 0.3) × 10−4 inverse days were measured. These results provide an additional diagnostic for testing future models of this behaviour.
Candidate circulating disease response biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin-Reed-Sternberg (HRS) cells or nonmalignant tumor-infiltrating cells. HRS cells are ...sparse within the diseased node, whereas benign CD163(+) M2 tissue-associated macrophages (TAM) are prominent. CD163(+) cells within the malignant node may be prognostic, but there is no data on serum CD163 (sCD163). The HRS-specific serum protein sTARC shows promise as a disease response biomarker. Tumor-specific and tumor-infiltrating circulating biomarkers have not been compared previously.
We prospectively measured sCD163 and sTARC in 221 samples from 47 patients with Hodgkin lymphoma and 21 healthy participants. Blood was taken at five fixed time-points prior, during, and after first-line therapy. Results were compared with radiological assessment and plasma Epstein-Barr virus DNA (EBV-DNA). Potential sources of circulating CD163 were investigated, along with immunosuppressive properties of CD163.
Pretherapy, both sCD163 and sTARC were markedly elevated compared with healthy and complete remission samples. sCD163 better reflected tumor burden during therapy, whereas sTARC had greater value upon completion of therapy. sCD163 correlated with plasma EBV-DNA, and associated with B symptoms, stage, and lymphopenia. Circulating CD163(+) monocytes were elevated in patients, indicating that sCD163 are likely derived from circulating and intratumoral cells. Depletion of cHL CD163(+) monocytes markedly enhanced T-cell proliferation, implicating monocytes and/or TAMs as potential novel targets for immunotherapeutic manipulation.
The combination of circulating tumor-infiltrate (sCD163) and tumor-specific (sTARC) proteins is more informative than either marker alone as disease response biomarkers in early and advanced disease during first-line therapy for cHL.
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