Explore the vast range of titles available.

Fast radio bursts (FRBs) are millisecond-duration radio transients 1 , 2 of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres 3 – 5 or relativistic shocks far from the central energy source 6 – 8 . Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters 9 , 10 or variable polarization angles in some other apparently one-off events 11 , 12 . Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks. Polarization observations of the fast radio burst FRB 180301 with the FAST radio telescope show diverse polarization angle swings, consistent with a magnetospheric origin of the emission.

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts 1 – 3 . Recent observations of a Galactic FRB 4 – 8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref.  9 ). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit ( au ; Earth–Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy 10 – 12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova. Analysis of a set of 1,863 bursts from the repeating source FRB 20201124A provides evidence of a complicated magnetized site within about an astronomical unit from the source in a barred galaxy.

Most cancer cells exhibit increased glycolysis and use this metabolic pathway for generation of ATP as a main source of their energy supply. This phenomenon is known as the Warburg effect and is considered as one of the most fundamental metabolic alterations during malignant transformation. In recent years, there are significant progresses in our understanding of the underlying mechanisms and the potential therapeutic implications. Biochemical and molecular studies suggest several possible mechanisms by which this metabolic alteration may evolve during cancer development. These mechanisms include mitochondrial defects and malfunction, adaptation to hypoxic tumor microenvironment, oncogenic signaling, and abnormal expression of metabolic enzymes. Importantly, the increased dependence of cancer cells on glycolytic pathway for ATP generation provides a biochemical basis for the design of therapeutic strategies to preferentially kill cancer cells by pharmacological inhibition of glycolysis. Several small molecules have emerged that exhibit promising anticancer activity in vitro and in vivo , as single agent or in combination with other therapeutic modalities. The glycolytic inhibitors are particularly effective against cancer cells with mitochondrial defects or under hypoxic conditions, which are frequently associated with cellular resistance to conventional anticancer drugs and radiation therapy. Because increased aerobic glycolysis is commonly seen in a wide spectrum of human cancers and hypoxia is present in most tumor microenvironment, development of novel glycolytic inhibitors as a new class of anticancer agents is likely to have broad therapeutic applications.

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances 1 – 3 . It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources 4 – 13 , but no convincing evidence has been collected so far 14 . Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts 15 . One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare 18 – 21 . Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB–SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst. An 8-hour radio observational campaign of the Galactic magnetar SGR 1935+2154, assisted by multi-wavelength data, indicates that associations between fast radio bursts and soft γ-ray bursts are rare.

Deterministic creation of multiple ferroelectric states with intermediate values of polarization remains challenging due to the inherent bi-stability of ferroelectric switching. Here we show the ability to select any desired intermediate polarization value via control of the switching pathway in (111)-oriented PbZr 0.2 Ti 0.8 O 3 films. Such switching phenomena are driven by kinetic control of the volume fraction of two geometrically different domain structures which are generated by two distinct switching pathways: one direct, bipolar-like switching and another multi-step switching process with the formation of a thermodynamically-stable intermediate twinning structure. Such control of switching pathways is enabled by the competition between elastic and electrostatic energies which favors different types of ferroelastic switching that can occur. Overall, our work demonstrates an alternative approach that transcends the inherent bi-stability of ferroelectrics to create non-volatile, deterministic, and repeatedly obtainable multi-state polarization without compromising other important properties, and holds promise for non-volatile multi-state functional applications. The use of ferroeletric materials for multi-state device applications is still challenging. Here, the authors present a mechanism to stabilize non-volatile polarization states by populating volume fractions of two domain structures in PbZr 0.2 Ti 0.8 O 3 via kinetic control of switching pathways.

X-ray bursts are among the brightest stellar objects frequently observed in the sky by space-based telescopes. A type-I X-ray burst is understood as a violent thermonuclear explosion on the surface of a neutron star, accreting matter from a companion star in a binary system. The bursts are powered by a nuclear reaction sequence known as the rapid proton capture process (rp process), which involves hundreds of exotic neutron-deficient nuclides. At so-called waiting-point nuclides, the process stalls until a slower β+ decay enables a bypass. One of the handful of rp process waiting-point nuclides is 64Ge, which plays a decisive role in matter flow and therefore the produced X-ray flux. Here we report precision measurements of the masses of 63Ge, 64,65As and 66,67Se—the relevant nuclear masses around the waiting-point 64Ge—and use them as inputs for X-ray burst model calculations. We obtain the X-ray burst light curve to constrain the neutron-star compactness, and suggest that the distance to the X-ray burster GS 1826–24 needs to be increased by about 6.5% to match astronomical observations. The nucleosynthesis results affect the thermal structure of accreting neutron stars, which will subsequently modify the calculations of associated observables.Rapid proton capture nucleosynthesis stalls at waiting-point nuclides, including 64Ge. Precision mass measurements in the vicinity of this nuclide influence state-of-the-art calculations of X-ray bursts from accreting neutron stars.

HERV-K (human endogenous retrovirus type K) type 1-encoded Np9 is a tumor-specific biomarker, but its oncogenic role and targets in human leukemia remain elusive. We first identified Np9 as a potent viral oncogene in human leukemia. Silencing of Np9 inhibited the growth of myeloid and lymphoblastic leukemic cells, whereas expression of Np9 significantly promoted the growth of leukemia cells in vitro and in vivo . Np9 not only activated ERK, AKT and Notch1 pathways but also upregulated β-catenin essential for survival of leukemia stem cells. In human leukemia, Np9 protein level in leukemia patients was substantially higher than that in normal donors (56% vs 4.5%). Moreover, Np9 protein level was correlated with the number of leukemia stem/progenitor cells but not detected in normal CD34 + hematopoietic stem cells. In addition, Np9-positive samples highly expressed leukemia-specific pol-env polyprotein, env and transmembrane proteins as well as viral particles. Thus, the viral oncogene Np9 is a critical molecular switch of multiple signaling pathways regulating the growth of leukemia stem/progenitor cells. These findings open a new perspective to understand the etiology of human common leukemia and provide a novel target for treating leukemia.

Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity. Inhibition of glycolysis preferentially causes severe ATP depletion and massive cell death in FLT3/ITD leukemia cells. Glycolytic inhibitors significantly enhances the cytotoxicity induced by FLT3 tyrosine kinase inhibitor sorafenib. Importantly, such combination provides substantial therapeutic benefit in a murine model bearing FLT3/ITD leukemia. Our study suggests that FLT3/ITD mutation promotes Warburg effect, and such metabolic alteration can be exploited to develop effective therapeutic strategy for treatment of AML with FLT3/ITD mutation via metabolic intervention.

Polo family kinase 4 (Plk4) is required for mitotic progression, and is haploinsufficient for tumor suppression and timely hepatocyte polarization in regenerating liver. At the same time, recent evidence suggests that Plk4 expression may have a role in clinical cancer progression, although the mechanisms are not clear. Here we identify a gene expression pattern predictive of reduced motility in Plk4 +/− murine embryonic fibroblasts (MEFs) and validate this prediction with functional assays of cell spreading, migration and invasion. Increased Plk4 expression enhances cell spreading in Plk4 +/− MEFs and migration in human embryonic kidney 293T cells, and increases invasion by DLD-1 colon cancer cells. Plk4 depletion impairs invasion of wild-type MEFs and suppresses invasion by MDA-MB231 breast cancer cells. Cytoskeletal reorganization and development of polarity are impaired in Plk4-deficient cells that have been stimulated to migrate. Endogenous Plk4 phosphorylated at the autophosphorylation site S305 localizes to the protrusions of motile cells, coincident with the RhoA GEF Ect2, GTP-bound RhoA and the RhoA effector mDia. Taken together, our findings reveal an unexpected activity of Plk4 that promotes cell migration and may underlie an association between increased Plk4 expression, cancer progression and death from metastasis in solid tumor patients.

Abstract Introduction/Objective Why doesn't a patient show up for their appointment? Is it associated with the required travel distance? Urine drug testing clinics often observe patients' scheduled visit absenteeism and record the behavior on their profiles; these records were used to answer the question and explore other potential explanations. Methods/Case Report With a well-developed electronic health data system, a retrospective study was performed on a large data set collected across the US with more than half a million patient encounters to verify if our theories matched the statistical results. In addition, since the dataset was collected between January 2019 and December 2021, it has nearly a year of quarantine; thus, pandemic status was also analyzed as one variable. Patient demographic information (gender, race, and age), claimed drug use, participating programs, scheduling method, assigned risk of relapse, and collection site were included in the study too. Results (if a Case Study enter NA) For all required travel distance ranges, 40% of patients had unexplained absence on the record, and the frequency of missed appointments increased significantly (p < 0.001) by geographic distance from a clinic, including long distance (>20 miles) and walking distance (between 0-2 miles). Automated scheduling methods also demonstrated higher rates of missed appointments than manually scheduled visits. All demographic differences provide significant (p <= 0.001) but minimal effects on missed appointments. The overall rate of missing test appointments during the pandemic was higher and returned to pre-pandemic levels in 2021. Factor analysis of mixed data was used to give a clean and easy interpretation of the data set. Conclusion The required travel distance had an interesting impact on patient absenteeism rate; it increases the rate for both long and short walking distances. This study provides an empirical basis for healthcare providers to personalize service plans when scheduling patients’ visits.