ABSTRACT
The High Energy (HE) X-ray telescope on board the Hard X-ray Modulation Telescope (Insight-HXMT) can serve as a wide field of view (FOV) gamma-ray monitor with high time resolution (μs) and ...large effective area (up to thousands cm2). We developed a pipeline to search for gamma-ray bursts (GRBs), using the traditional signal-to-noise ratio (SNR) method for blind search and the coherent search method for targeted search. By taking into account the location and spectrum of the burst and the detector response, the targeted coherent search is more powerful to unveil weak and sub-threshold bursts, especially those in temporal coincidence with gravitational wave (GW) events. Based on the original method in literature, we further improved the coherent search to filter out false triggers caused by spikes in light curves, which are commonly seen in gamma-ray instruments (e.g. Fermi/GBM, POLAR). We show that our improved targeted coherent search method could eliminate almost all false triggers caused by spikes. Based on the first two years of Insight-HXMT/HE data, our targeted search recovered 40 GRBs, which were detected by either Swift/BAT or Fermi/GBM but too weak to be found in our blind search. With this coherent search pipeline, the GRB detection sensitivity of Insight-HXMT/HE is increased to about 1.5E-08 erg cm−2 (200 keV–3 MeV). We also used this targeted coherent method to search Insight-HXMT/HE data for electromagnetic counterparts of LIGO-Virgo GW events (including O2 and O3a runs). However, we did not find any significant burst associated with GW events.
Prion diseases are transmissible fatal neurodegenerative disorders spreading between humans and other mammals. The pathogenic agent, prion, is a protease‐resistant, β‐sheet‐rich protein aggregate, ...converted from a membrane protein called PrPC. PrPSc is the misfolded form of PrPC and undergoes self‐propagation to form the infectious amyloids. Since the key hallmark of prion disease is amyloid formation, identifying and studying which segments are involved in the amyloid core can provide molecular details about prion diseases. It has been known that the prion protein could also form non‐infectious fibrils in the presence of denaturants. In this study, we employed a combination of site‐directed nitroxide spin‐labeling, fibril seeding, and electron spin resonance (ESR) spectroscopy to identify the structure of the in vitro‐prepared full‐length mouse prion fibrils. It is shown that in the in vitro amyloidogenesis, the formation of the amyloid core is linked to an α‐to‐β structural transformation involving the segment 160‐224, which contains strand 2, helix 2, and helix 3. This method is particularly suitable for examining the hetero‐seeded amyloid fibril structure, as the unlabeled seeds are invisible by ESR spectroscopy. It can be applied to study the structures of different strains of infectious prions or other amyloid fibrils in the future.
Presently, interesting research related to induced pluripotent stem cells (iPSCs) is emerging. However, the development of new therapies and techniques for treatment of refractory diseases is still ...required in dermatology. We are exploring novel methods to provide stem cell therapy and elucidate research mechanisms underlying troublesome diseases by reprogramming iPSCs from the fibroblasts of keloid lesions from patients in vitro.
Here, we identified the expression of fibroblastic genes in the fibroblast derived from diseased individuals. Corresponding iPSCs were then produced by transfecting patient fibroblasts with non-modified RNA cocktails, expressing OCT4, SOX2, KLF4, cMYC, NANOG, and LIN28 reprogramming factors. The pluripotency of these patient-derived iPSCs was identified by immunocytochemistry, real-time quantitative polymerase chain reaction, and teratoma formation in vivo in non-obese diabetic/severe combined immunodeficiency mice.
All iPSCs derived from patients significantly expressed the pluripotent transcription factors and could be expanded in vitro. Furthermore, induction of terminal differentiation in long-term culture and the capability of forming embryonic bodies to differentiate into all 3 germ layers in vivo were confirmed in immune-deficient mice.
Fibroblasts from a keloid patient were successfully reprogrammed to iPSCs in vitro. This reprogramming may provide a basis for the production of individualized modified artificial skin to prevent rejections after xenogeneic skin transplantation and trauma through autologous skin transplantation. These cells can also offer a new platform for research on mechanisms underlying skin diseases and personal medical applications.
•JSDK-iPSCs were reprogrammed from keloid patients' lesional dermal fibroblasts.•JSDK-iPSCs were pluripotent both in vivo and in vitro.•This reprogramming is a basis for building disease models.•The use of NM-RNA for reprogramming was found to be more efficient than other methods.
Topological Weyl semimetal (TWS), a new state of quantum matter, has sparked enormous research interest recently. Possessing unique Weyl fermions in the bulk and Fermi arcs on the surface, TWSs offer ...a rare platform for realizing many exotic physical phenomena. TWSs can be classified into type-I that respect Lorentz symmetry and type-II that do not. Here, we directly visualize the electronic structure of MoTe
, a recently proposed type-II TWS. Using angle-resolved photoemission spectroscopy (ARPES), we unravel the unique surface Fermi arcs, in good agreement with our ab initio calculations that have nontrivial topological nature. Our work not only leads to new understandings of the unusual properties discovered in this family of compounds, but also allows for the further exploration of exotic properties and practical applications of type-II TWSs, as well as the interplay between superconductivity (MoTe
was discovered to be superconducting recently) and their topological order.
Background: Intracranial hemorrhage (ICH) is the second leading cause of mortality in patients with acute myeloid leukemia (AML). However, the prognostic factors for ICH in AML patients are still ...under investigation. Patients and methods: A total of 841 AML patients admitted to the Department of Internal Medicine from January 1995 to December 2007 were enrolled in this study. Results: There were 51 patients with ICH, median age of 51 (range 17–86), including 12 patients diagnosed as acute promyelocytic leukemia. Forty-three patients were refractory/relapsed status. ICH was localized in the supratentorium (44 cases), basal ganglion (9), cerebellum (5), and brainstem (4). Twenty-one patients had multiple sites. Thirty-eight patients had intraparenchymal hemorrhage, 16 subarachnoid hemorrhage (SAH), 10 subdural hemorrhage, and one epidural hemorrhage (EDH). Hemorrhage ruptured into the ventricles in 13 patients. Thirty-four patients (67%) died of ICH within 30 days of diagnosis. Multivariate analysis revealed four independent prognostic factors, prolonged prothrombin time international normalized ratio >1.5 (P < 0.001), brainstem hemorrhage (P = 0.001), SAH (P = 0.017), and EDH (P = 0.014). Other clinico-laboratory data had no impact on 30-day survival. Conclusions: ICH has high morbidity and mortality in AML. Early detection and aggressive correction coagulopathy may prevent the catastrophic event. Prompt image study for locations and types of ICH can predict outcomes.
Infectious diseases are closely related to cancer. Human cytomegalovirus (HCMV) has been implicated in the promotion of tumour growth, and is present in the tumour specimens of colorectal cancer ...(CRC). This study aimed to investigate whether tumoral presence of HCMV is associated with a different clinical outcome in elderly patients with CRC. We analysed archived tumour specimens from 95 CRC patients aged ≥65 years. HCMV was detected by PCR. Clinical, pathological, disease-free and overall survival data were compared between patients with HCMV-positive and HCMV-negative tumours. A quantitative RT-PCR array was used to evaluate the expression levels of cytokines genes of T-helper subpopulations in tumours. In the Kaplan–Meier analysis of the 81 patients who underwent curative surgery, 39 patients with HCMV-positive tumours had a lower disease-free survival rate (p 0.024). For patients with stage II or stage III tumours, tumoral HCMV status correlated with disease-free survival more closely than the traditional histopathological staging methods. In a multivariate Cox proportional hazard model, tumoral presence of HCMV independently predicted tumour recurrence in 5 years (hazard ratio 4.42; 95% CI 1.54–12.69, p 0.006). The qRT-PCR analysis of ten stage II tumours showed that the gene expression levels of interleukin-17—the signature cytokine of T-helper 17 cells—and its receptor, interleukin-17 receptor C, were higher in the five HCMV-positive tumours. Our results suggest that the presence of HCMV in CRC is associated with poorer outcome in elderly patients. How the virus interacts with the tumour microenvironment should be further investigated.
Two-mode interferometers lay the foundations for quantum metrology. Instead of exploring quantum entanglement in the two-mode interferometers, a single bosonic mode also promises a measurement ...precision beyond the shot-noise limit (SNL) by taking advantage of the infinite-dimensional Hilbert space of Fock states. Here, we demonstrate a single-mode phase estimation that approaches the Heisenberg limit (HL) unconditionally. Due to the strong dispersive nonlinearity and long coherence time of a microwave cavity, quantum states of the form Formula: see text can be generated, manipulated and detected with high fidelities, leading to an experimental phase estimation precision scaling as ∼N
. A 9.1 dB enhancement of the precision over the SNL at N = 12 is achieved, which is only 1.7 dB away from the HL. Our experimental architecture is hardware efficient and can be combined with quantum error correction techniques to fight against decoherence, and thus promises quantum-enhanced sensing in practical applications.
AIMS: To investigate the medium‐pressure (MP) and low‐pressure (LP) Ultraviolet (UV) susceptibility and the repair potential of Enterococcus faecalis (DSM 20478) after UV treatment. METHODS AND ...RESULTS: A range of UV doses from 4 to 19 mJ cm⁻² was selected in this study. Photoreactivation and dark repair performance were investigated under fluorescent light or in the dark respectively. The inactivation and repair performance of UV disinfection under a range of salinities (0, 1%, 3%) and temperature (4 and 25°C) were compared. Results indicated that MP UV exposure resulted in higher inactivation efficiency against Ent. faecalis than LP UV exposure. For repair potential, LP UV resulted in a greater level of light repair than MP UV. Effect of salinity on the inactivation and repair of Ent. faecalis was correlated with UV sources, whereas low temperature generally adversely affected the inactivation efficiency and final repair levels after both MP and LP UV exposure. CONCLUSIONS: Both salinity and temperature demonstrated to play an important role in the inactivation and repair capability when UV light was used to treat ballast water. SIGNIFICANCE AND IMPACT OF THE STUDY: Considering that UV‐treated ballast water is exposed or discharged to marine water environment in many countries with various temperature and salinity conditions, results of this study provide significant implications for the management of public health associated with ballast water treatment and discharge.
Fibrils of the hamster prion peptide (sHaPrP, sequence 108–144) were prepared in an acidic solution, and their structure was solved by cryogenic electron microscopy with a resolution of 2.23 Å based ...on the gold-standard Fourier shell correlation (FSC) curve. The fibril has a novel architecture that has never been found in other amyloid fibrils. Each fibril is assembled by four protofilaments (PFs) and has an ordered water channel in the center. Each protofilament contains three β-strands (125–130, 133–135, and 138–141) arranged in an “R”-shaped construct. The structural data indicate that these three β-strand segments are the most amyloidogenic region of the prion peptide/protein and might be the site of nucleation during fibrillization under conditions without denaturants.