ABSTRACT
We propose a compact binary model with an eccentric orbit to explain periodically active fast radio burst (FRB) sources, where the system consists of a neutron star (NS) with strong dipolar ...magnetic fields and a magnetic white dwarf (WD). In our model, the WD fills its Roche lobe at periastron, and mass transfer occurs from the WD to the NS around this point. The accreted material may be fragmented into a number of parts, which arrive at the NS at different times. The fragmented magnetized material may trigger magnetic reconnection near the NS surface. The electrons can be accelerated to an ultrarelativistic speed, and therefore the curvature radiation of the electrons can account for the burst activity. In this scenario, the duty cycle of burst activity is related to the orbital period of the binary. We show that such a model may work for duty cycles roughly from 10 min to 2 d. For the recently reported 16.35-d periodicity of FRB 180916.J0158 + 65, our model does not naturally explain such a long duty cycle, since an extremely high eccentricity (e > 0.95) is required.
Cholesteric liquid crystals (CLCs) exhibit selective reflection that can be tuned owing to the dynamic control of inherent self‐organized helical superstructures. Although phototunable reflection is ...reported, these systems hitherto suffer from a limitation in that the tuning range is restricted to one narrow period and the optically addressed images have to sacrifice one color in the visible spectrum to serve as the background, resulting from the insufficient variation in helical twisting power of existing photoresponsive chiral switches that are all bistable. Here, delicate patterns of three primary red, green, and blue (RGB) colors with a black background are presented, which is realized based on piecewise reflection tuning of the CLC induced by a newly designed photoresponsive tristable chiral switch. Three stable configurations of the chiral switch endow the CLC with two continuous and adjacent tuning periods of the reflection, covering not only entire visible spectrum, but also one more wide period within near‐infrared region. Therefore, the concept of piecewise tuning in CLC system demonstrates a new strategy for phototunable RGB and black reflective display.
A photoresponsive tristable chiral switch is constructed by incorporating two different azobenzenes into one chiral structure. Three stable configurations of the chiral switch endow the cholesteric liquid crystals with two tuning periods of the reflection, including the period in the visible spectrum and one more period within the near‐infrared region, which provides piecewise phototuning of self‐organized helical superstructures.
It is a long-standing challenge to achieve efficient and highly selective aerobic oxidation of methylarenes to benzaldehydes, owing to overoxidation problem stemming from the oxidizability of ...benzaldehyde far higher than the toluene under usual aerobic conditions. Herein we report a bio-inspired iron-catalyzed polymethylhydrosiloxane-promoted aerobic oxidation of methylarenes to benzaldehydes with high yields and selectivities. Notably, this method can tolerate oxidation-labile and reactive boronic acid group, which is normally required to be transformed immediately after its introduction, and represents a significant advance in the area of the chemistry of organoboronic acids, including the ability to incorporate both aldehyde and ketone functionalities into unprotected arylboronic acids, a class that can be difficult to access by current means. The robustness of this protocol is demonstrated on the late-stage oxidation of complex bioactive molecules, including dehydroabietic acid, Gemfibrozil, Tocopherol nicotinate, a complex polyol structure, and structurally complex arylboronic acids.
The p53 tumor suppressor protein has well-established roles in monitoring various types of stress signals by activating specific transcriptional targets that control cell cycle arrest and apoptosis, ...although some activities are also mediated in a transcription-independent manner. Here, we review the recent advances in our understanding of the wide spectrum of post-translational modifications that act as epigenetic-like codes for modulating specific functions of p53 in vivo and how deregulation of these modifications might contribute to tumorigenesis. We also discuss future research priorities to further understand p53 post-translational modifications and the interpretation of genetic data in appreciation of the increasing evidence that p53 regulates cellular metabolism, autophagy and many unconventional tumor suppressor activities.
Aberrant blood vessel functioning and systemic circulation are key causes for vascular disorders; cardiovascular, cerebrovascular, renal artery stenosis, and peripheral artery diseases. ...Epidemiological and basic science evidence supported genetic reasons, compounded by obesity, hypercholesterolemia, hypertension, diabetes, and smoking as risk factors. This is an umbrella review of risk factors and therapies in vascular disorders, exploring systematic reviews and meta‐analyses studies in PubMed, Cochrane, Embase, and Central published in January 2000–May 2018. We made qualitative eligibility gradation of the articles based on inclusion criteria, and independently extracted descriptive and methodologic data to compile their outcomes. We considered 95% confidence interval and the between‐study heterogeneity, designated by I
2. Overall, we extracted 217 studies of impressive quality and at low risk of bias, including 124, 30, 23, 32, and 8, respectively, for the search terms “cardiovascular,” “renal,” “cerebral,” and “limb ischemia” each in combination with “risk factors” and “therapeutics.” Our search on genome‐wide analyses revealed genes associated with HDL‐cholesterol, matrix metalloproteases, angiogenesis, notch3, renin‐angiotensin, apolipoprotein E, insulin, and cytokine levels as critical participants in the pathogenesis of vascular diseases. Hypertension and endothelial growth factor‐linked polymorphisms were found to contribute to vascular damage. The studies reinforced that lifestyle and dietary patterns influenced susceptibility of circulatory system diseases. Additionally, endovascular medicines, surgical vascularization, angioplasty, and renal artery stenting appeared as major therapeutic approaches in vascular patients. Altogether, our review offers up‐to‐date information on pathophysiology of vascular diseases and provides insight into existing research, clinical management and clinical gaps in the field.
This is an umbrella review of risk factors and therapies in vascular disorders, exploring systematic reviews and meta‐analyses studies in PubMed, Cochrane, Embase and Central published in January 2000–May 2018. Overall, we extracted 217 studies of impressive quality and at low risk of bias, including 124, 30, 23, 32, and 8 respectively for the search terms “cardiovascular,” “renal,” “cerebral,” and “limb ischemia” each in combination with “risk factors” and “therapeutics.” Our review offers up‐to‐date information on pathophysiology of vascular diseases and provides insight into existing research, clinical management and clinical gaps in the field.
This paper presents a 28-nm system-on-chip (SoC) for Internet of things (IoT) applications with a programmable accelerator design that implements a powerful fully connected deep neural network (DNN) ...classifier. To reach the required low energy consumption, we exploit the key properties of neural network algorithms: parallelism, data reuse, small/sparse data, and noise tolerance. We map the algorithm to a very large scale integration (VLSI) architecture based around an single-instruction, multiple-data data path with hardware support to exploit data sparsity by completely eliding unnecessary computation and data movement. This approach exploits sparsity, without compromising the parallel computation. We also exploit the inherent algorithmic noise-tolerance of neural networks, by introducing circuit-level timing violation detection to allow worst case voltage guard-bands to be minimized. The resulting intermittent timing violations may result in logic errors, which conventionally need to be corrected. However, in lieu of explicit error correction, we cope with this by accentuating the noise tolerance of neural networks. The measured test chip achieves high classification accuracy (98.36% for the MNIST test set), while tolerating aggregate timing violation rates > 10 −1 . The accelerator achieves a minimum energy of 0.36 <inline-formula> <tex-math notation="LaTeX">\mu \text{J} </tex-math></inline-formula>/inference at 667 MHz; maximum throughput at 1.2 GHz and 0.57 <inline-formula> <tex-math notation="LaTeX">\mu \text{J} </tex-math></inline-formula>/inference; or a 10% margined operating point at 1 GHz and 0.58 <inline-formula> <tex-math notation="LaTeX">\mu \text{J} </tex-math></inline-formula>/inference.
We study the prospects of searching for black hole (BH) binary systems with a stellar-mass BH and a non-compact visible companion, by utilizing the spectroscopic data of the Large Sky Area ...Multi-object Fiber Spectroscopic Telescope (LAMOST). We simulate the Galactic BH binary population and determine its optical visibility by considering the stellar synthetic population model and the distributions of binary orbital parameters. By convolving the visibility of BH binaries with the LAMOST detection sensitivity, we predict that 400 candidate BH binaries can be found by the low-resolution, non-time-domain survey, and ∼50-350 candidates by the LAMOST ongoing medium-resolution, time-domain spectroscopic survey. Most of the candidates are short-period (0.2-2 days) binaries with M-, K-, G-, or F-type companions, in which ∼47% have a mass function (the lower limit of the BH mass) larger than 3 M . By complementing the LAMOST spectroscopic data with other photometric/spectroscopic surveys or follow-up observations, these candidates could be confirmed. Therefore, by exploring the LAMOST data, we can enlarge the sample of dynamically confirmed BH binaries significantly, which can improve our understanding of the mass distribution of BHs and the stellar evolution model.
The last 40 years have witnessed how p53 rose from a viral binding protein to a central factor in both stress responses and tumor suppression. The exquisite regulation of p53 functions is of vital ...importance for cell fate decisions. Among the multiple layers of mechanisms controlling p53 function, posttranslational modifications (PTMs) represent an efficient and precise way. Major p53 PTMs include phosphorylation, ubiquitination, acetylation, and methylation. Meanwhile, other PTMs like sumoylation, neddylation, O-GlcNAcylation, adenosine diphosphate (ADP)-ribosylation, hydroxylation, and β-hydroxybutyrylation are also shown to play various roles in p53 regulation. By independent action or interaction, PTMs affect p53 stability, conformation, localization, and binding partners. Deregulation of the PTM-related pathway is among the major causes of p53-associated developmental disorders or diseases, especially in cancers. This review focuses on the roles of different p53 modification types and shows how these modifications are orchestrated to produce various outcomes by modulating p53 activities or targeted to treat different diseases caused by p53 dysregulation.
Neutrino-dominated accretion flows (NDAFs) around rotating stellar-mass black holes (BHs) are plausible candidates for the central engines of gamma-ray bursts (GRBs). NDAFs are hyperaccretion disks ...with accretion rates in the range of around 0.001–10 M⊙s−1, which have high density and temperature and therefore are extremely optically thick and geometrically slim or even thick. We review the theoretical progresses in studying the properties of NDAFs as well as their applications to the GRB phenomenology. The topics include: the steady radial and vertical structure of NDAFs and the implications for calculating neutrino luminosity and annihilation luminosity, jet power due to neutrino-antineutrino annihilation and Blandford–Znajek mechanism and their dependences on parameters such as BH mass, spin, and accretion rate, time evolution of NDAFs, effect of magnetic fields, applications of NDAF theories to the GRB phenomenology such as lightcurve variability, extended emission, X-ray flares, kilonovae, etc., as well as probing NDAFs using multi-messenger signals such as MeV neutrinos and gravitational waves.
Heart disease is the leading cause of death worldwide. A key pathogenic factor in the development of lethal heart failure is loss of terminally differentiated cardiomyocytes. However, mechanisms of ...cardiomyocyte death remain unclear. Here, we discovered and demonstrated that ferroptosis, a programmed iron-dependent cell death, as a mechanism in murine models of doxorubicin (DOX)- and ischemia/reperfusion (I/R)-induced cardiomyopathy. In canonical apoptosis and/or necroptosis-defective Ripk3−/−, Mlkl−/−, or Fadd−/−Mlkl−/− mice, DOX-treated cardiomyocytes showed features of typical ferroptotic cell death. Consistently, compared with dexrazoxane, the only FDA-approved drug for treating DOX-induced cardiotoxicity, inhibition of ferroptosis by ferrostatin-1 significantly reduced DOX cardiomyopathy. RNA-sequencing results revealed that heme oxygenase-1 (Hmox1) was significantly up-regulated in DOX-treated murine hearts. Administering DOX to mice induced cardiomyopathy with a rapid, systemic accumulation of nonheme iron via heme degradation by Nrf2-mediated upregulation of Hmox1, which effect was abolished in Nrf2-deficent mice. Conversely, zinc protoporphyrin IX, an Hmox1 antagonist, protected the DOX-treated mice, suggesting free iron released on heme degradation is necessary and sufficient to induce cardiac injury. Given that ferroptosis is driven by damage to lipid membranes, we further investigated and found that excess free iron accumulated inmitochondria and caused lipid peroxidation on its membrane. Mitochondria-targeted antioxidant MitoTEMPO significantly rescued DOX cardiomyopathy, supporting oxidative damage of mitochondria as a major mechanism in ferroptosis-induced heart damage. Importantly, ferrostatin-1 and iron chelation also ameliorated heart failure induced by both acute and chronic I/R in mice. These findings highlight that targeting ferroptosis serves as a cardioprotective strategy for cardiomyopathy prevention.
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