The phase contrast imaging of surface steps in reflection electron microscopy is analysed.It is shown that the typical images are seriously affected by incoherence effects and that this arises, not from the strong inelastic scattering which is often present, but from the effective angular spread in the illumination which is frequently determined by the width of the Bragg reflection.
Interleukin-1 receptor-associated kinases (IRAKs) are key components in the signal transduction pathways utilized by interleukin-1 receptor (IL-1R), interleukin-18 receptor (IL-18R), and Toll-like receptors (TLRs). Out of four members in the mammalian IRAK family, IRAK-4 is considered to be the “master IRAK”, the only family member indispensable for IL-1R/TLR signaling. In humans, mutations resulting in IRAK-4 deficiency have been linked to susceptibility to bacterial infections, especially recurrent pyogenic bacterial infections. Furthermore, knock-in experiments by several groups have clearly demonstrated that IRAK-4 requires its kinase activity for its function. Given the critical role of IRAK-4 in inflammatory processes, modulation of IRAK-4 kinase activity presents an attractive therapeutic approach for the treatment of immune and inflammatory diseases. The recent success in the determination of the 3-dimensional structure of the IRAK-4 kinase domain in complex with inhibitors has facilitated the understanding of the mechanistic role of IRAK-4 in immunity and inflammation as well as the development of specific IRAK-4 kinase inhibitors. In this article, we review the biological function of IRAK-4, the structural characteristics of the kinase domain, and the development of small molecule inhibitors targeting the kinase activity. We also review the key pharmacophores required for several classes of inhibitors as well as important features for optimal protein/inhibitor interactions. Lastly, we summarize how these insights can be translated into strategies to develop potent IRAK-4 inhibitors with desired properties as new anti-inflammatory therapeutic agents. Keywords: Interleukin-1 receptor-associated kinase (IRAK), IRAK-4 inhibitors, kinase inhibitors, binding mode, X-ray crystal structure
Abstract With the rapid development of Internet of Things (IoT) technology, sensors have become the most important nodes for information exchange in the IoT. However, ensuring stable power supply and network communication of a plethora of distributed sensing nodes has become the key technical bottleneck that restricts the development of marine IoT. Herein, a self‐adaptive gyroscope‐structured hybrid triboelectric‐electromagnetic nanogenerator (SAG‐HTENG) is designed for omnidirectional wave energy harvesting. Through seamlessly integrating an electromagnetic generator (EMG) and triboelectric nanogenerator (TENG) modules into one device, the wave energy conversion efficiency can be significantly enhanced. Furthermore, through incorporating ferromagnetic electrode, remarkable peak power density of 29.92 W m −3 Hz −1 of the TENG module and 402.08 W m −3 Hz −1 of the EMG module can be achieved, respectively. Meanwhile, the TENG module exhibited superior working stability and applicability for harvesting low‐frequency wave energy in a water tank field test compared to the EMG module. Leveraging the IoT platform, a self‐powered real‐time ocean currents monitoring buoy system (OCMBS) is constructed of determining the wave direction and current type. This work offers a novel energy solution for the distributed sensing nodes toward future smart marine IoT.
An experimental technique for performing electron holography using a non-FEG, non-biprism transmission electron microscope (TEM) has been introduced by Ru et al. A double stacked specimens, one being a single crystal foil and the other the specimen, are loaded in the normal specimen position in TEM. The single crystal, which is placed onto the specimen, is responsible to produce two beams that are equivalent to two virtual coherent sources illuminating the specimen beneath, thus, permitting electron holography of the specimen. In this paper, the imaging theory of this technique is described. Procedures are introduced for digitally reconstructing the holograms.
Abstract Background To investigate distributions of cervical lesions and factors associated with the severity of the cervical lesions in high-risk HPV (hr-HPV) positive women with atypical squamous cells of undetermined significance (ASC-US) cytology. Methods Clinical information of 250,000 women who underwent HPV and cytological test was collected from January 2012 to January 2019. The association between the severity of the cervical lesions and hr-HPV genotypes, hr-HPV viral load, and ages, were analyzed in hr-HPV-positive/ASC-US women. Results 3459 hr-HPV-positive/ASC-US women were enrolled in this study. Overall, 43.51% of women with ASC-US had normal histological results, 34.35% had high-grade squamous intraepithelial lesion (HSIL), and 1.30% had cervical cancer. The rate of HSIL or worse (HSIL+) in women with single HPV16 infection (63.09%) was the highest, followed by HPV33 (57.50%), HPV51 (36.11%), HPV58 (36.11%), HPV52 (28.28%), HPV18(26.37%), HPV66 (19.35%), HPV39 (18.92%), HPV53 (15.00%), and HPV56 (8.51%). Detection rate of HSIL + in low, intermediate and high viral-load groups were 15.87% (n = 30), 34.91% (n = 74) and 40.68% (n = 214) (Cochran-Armitage Trend test χ 2 = 35.03, P < 0.0001). Compared with the 51-60-year-old group (21.65%), the women in ≤ 30 (40.52%), 31–40 (39.67%), and 41–50 (34.22%) year-old groups had significantly higher risk of HSIL+. The women in ≤ 51–60 (2.68%) and > 60 (3.41%) year-old groups were at increased risk for cervical cancer, compared with the ≤ 30-year-old group (0.61%). Conclusions ASC-US women with HPV 16/18/33/51/52/58 single infection and multiple infections, as well as high HPV viral loads, have high risk of HSIL+.
