The HGF/MET signaling pathway is critical in mediating a wide range of normal physiological functions including embryological development, wound healing, and tissue regeneration. Aberrant activation ...of the pathway has frequently been found in human cancers via protein overexpression, mutation, gene amplification, and also paracrine or autocrine up-regulation. In addition, the activation of HGF/MET signaling confers resistance to the effects of cancer treatments. Therefore, inhibition of the HGF/MET signaling pathway has great potential for therapeutic intervention in cancer. Currently, there are three approaches toward modulating HGF/MET signaling in human clinical studies of cancer: anti-HGF monoclonal antibodies, MET monoclonal antibodies, and small molecule MET inhibitors. Preliminary clinical benefit from inhibition of HGF or MET has been reported. This Perspective will provide an overview of the HGF/MET signaling pathway in cancer and then will review the development of small molecule MET inhibitors and their progress in clinical applications.
This paper is concerned with the dynamics of large bubbles subject to various strengths of buoyancy effects, which are associated with applications for underwater explosion. The bubble is produced by ...electric discharge in a low-pressure tank to enhance the buoyancy effects. Experiments are carried out for a bubble in an infinite field, below a free surface and above a rigid boundary. The effects of buoyancy are reflected by the dimensionless parameter
${\it\delta}=\sqrt{{\it\rho}gR_{m}/(p_{amb}-p_{v})}$
, where
$R_{m}$
,
$p_{amb}$
,
$p_{v}$
,
${\it\rho}$
and
$g$
are the maximum bubble radius, ambient pressure, saturated vapour pressure, density of water and the acceleration of gravity respectively. A systematic study of buoyancy effects is carried out for a wide range of
${\it\delta}$
from 0.034 to 0.95. A series of new phenomena and new features is observed. The bubbles recorded are transparent, and thus we are able to display and study the jet formation, development and impact on the opposite bubble surface as well as the subsequent collapsing and rebounding of the ring bubble. Qualitative analyses are carried out for the bubble migration, jet velocity and jet initiation time, etc. for different values of
${\it\delta}$
. When a bubble oscillates below a free surface or above a rigid boundary, the Bjerknes force due to the free surface (or rigid boundary) and the buoyancy are in opposite directions. Three situations are studied for each of the two configurations: (i) the Bjerknes force being dominant, (ii) the buoyancy force being dominant and (iii) the two forces being approximately balanced. For case (iii), we further consider two subcases, where both the balanced Bjerknes and buoyancy forces are weak or strong. When the Bjerknes and buoyancy forces are approximately balanced over the pulsation, some representative bubble behaviours are observed: the bubble near free surface is found to split into two parts jetting away from each other for small
${\it\delta}$
, or involutes from both top and bottom for large
${\it\delta}$
. A bubble above a rigid wall is found to be subject to contraction from the lateral part leading to bubble splitting. New criteria are established based on experimental results for neutral collapses where there is no dominant jetting along one direction, which correlate well with the criteria of Blake et al. (J. Fluid Mech., vol. 170, 1986, pp. 479–497; J. Fluid Mech., vol. 181, 1987, pp. 197–212) but agree better with the experimental and computational results.
With the development of antitumor therapies, different treatment methods including monotherapy and combined therapy have achieved clinical efficacy in advanced epidermal growth factor receptor (EGFR) ...mutant non-small cell lung cancer (NSCLC) patients. Exon 19 deletion (ex19del) and exon 21 L858R mutation are common sensitive subtypes of EGFR mutation. However, potential distinct mechanisms are found from several dimensions including molecular structures, biological behaviors, concomitant mutations, resistance mechanisms and tumor mutation burdens. More evidence indicates the prognostic difference of EGFR subgroups. This review focused on the progress of potential distinct mechanisms and outcomes in clinical trials of advanced NSCLC patients with ex19del or exon 21 L858R mutation.
Circular RNAs (circRNAs) represent a class of non-coding RNAs that are widely expressed in mammals. However, it is largely unknown about the function of human circRNAs and the roles of circRNAs in ...human oral squamous cell carcinomas (OSCC). Here we performed a comprehensive study of circRNAs in human OSCC using circRNA and mRNA microarrays, and identified many circRNAs that are differentially expressed between OSCC tissue and paired non-cancerous matched tissue. We further found a circRNA termed circRNA_100290 that served as a critical regulator in OSCC development. We discovered that circRNA_100290 was upregulated and co-expressed with CDK6 in OSCC tissue. Knockdown of circRNA_100290 decreased expression of CDK6 and inhibited proliferation of OSCC cell lines in vitro and in vivo. Via luciferase reporter assays, circRNA_100290 was observed to directly bind to miR-29 family members. Further EGFP/RFP reporter assays showed that CDK6 was the direct target of miR-29b. Taken together, we conclude that circRNA_100290 may function as a competing endogenous RNA to regulate CDK6 expression through sponging up miR-29b family members. Taken together, it indicates that circRNAs may exert regulatory functions in OSCC and may be a potential target for OSCC therapy.
Broadband Ground-Plane Cloak Liu, R; Ji, C; Mock, J.J ...
Science (American Association for the Advancement of Science),
01/2009, Letnik:
323, Številka:
5912
Journal Article
Recenzirano
The possibility of cloaking an object from detection by electromagnetic waves has recently become a topic of considerable interest. The design of a cloak uses transformation optics, in which a ...conformal coordinate transformation is applied to Maxwell's equations to obtain a spatially distributed set of constitutive parameters that define the cloak. Here, we present an experimental realization of a cloak design that conceals a perturbation on a flat conducting plane, under which an object can be hidden. To match the complex spatial distribution of the required constitutive parameters, we constructed a metamaterial consisting of thousands of elements, the geometry of each element determined by an automated design process. The ground-plane cloak can be realized with the use of nonresonant metamaterial elements, resulting in a structure having a broad operational bandwidth (covering the range of 13 to 16 gigahertz in our experiment) and exhibiting extremely low loss. Our experimental results indicate that this type of cloak should scale well toward optical wavelengths.
To evaluate a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and compare it with RT-PCR.
...We designed primers specific to the orf1ab and S genes of SARS-CoV-2. Total viral RNA was extracted using the QIAamp Viral RNA Mini Kit. We optimized the RT-LAMP assay, and evaluated it for its sensitivity and specificity of detection using real-time turbidity monitoring and visual observation.
The primer sets orf1ab-4 and S-123 amplified the genes in the shortest times, the mean (±SD) times were 18 ± 1.32 min and 20 ± 1.80 min, respectively, and 63°C was the optimum reaction temperature. The sensitivities were 2 × 101 copies and 2 × 102 copies per reaction with primer sets orf1ab-4 and S-123, respectively. This assay showed no cross-reactivity with 60 other respiratory pathogens. To describe the availability of this method in clinical diagnosis, we collected 130 specimens from patients with clinically suspected SARS-CoV-2 infection. Among them, 58 were confirmed to be positive and 72 were negative by RT-LAMP. The sensitivity was 100% (95% CI 92.3%–100%), specificity 100% (95% CI 93.7%–100%). This assay detected SARS-CoV-2 in a mean (±SD) time of 26.28 ± 4.48 min and the results can be identified with visual observation.
These results demonstrate that we developed a rapid, simple, specific and sensitive RT-LAMP assay for SARS-CoV-2 detection among clinical samples. It will be a powerful tool for SARS-CoV-2 identification, and for monitoring suspected patients, close contacts and high-risk groups.
Oedometer tests starting from a very small effective vertical stress of 0·5 kPa were performed on three reconstituted clays with different liquid limits. The soils were prepared at various initial ...water contents, ranging from 0·7 to 2·0 times their corresponding liquid limits. It is observed that the e–log Formula: see text compression curves show an inverse ‘S' shape due to suction pressure resisting deformation, similar to that of soft natural clays caused by consolidation yield stress. The suction pressure Formula: see text of the reconstituted clays can be correlated with the ratio of initial void ratio to void ratio at liquid limit e 0 /e L . The suction pressure curve defined by a unique relationship between suction pressure Formula: see text and the normalised void ratio at suction pressure e s /e L is also proposed to distinguish between the pre-suction and the post-suction states. In addition, Burland's concept of the intrinsic compression line is adopted for correlating the compression curves of various reconstituted clays at high initial water contents. It has been found that the void index is a powerful parameter for normalising the compression curves in the post-suction state. Nevertheless, it seems that Burland's intrinsic compression line slightly underestimates the void index at the low stresses considered in this study. An extended intrinsic compression line is then derived in order to better fit the data for stresses lower than 25 kPa.
Quantum entanglement involving coherent superpositions of macroscopically distinct states is among the most striking features of quantum theory, but its realization is challenging because such states ...are extremely fragile. Using a programmable quantum simulator based on neutral atom arrays with interactions mediated by Rydberg states, we demonstrate the creation of "Schrödinger cat" states of the Greenberger-Horne-Zeilinger (GHZ) type with up to 20 qubits. Our approach is based on engineering the energy spectrum and using optimal control of the many-body system. We further demonstrate entanglement manipulation by using GHZ states to distribute entanglement to distant sites in the array, establishing important ingredients for quantum information processing and quantum metrology.
PDF
