A novel microRNA (miRNA) quantification method has been developed using one-step rolling circle-quantitative PCR (RC-qPCR) analysis. Vent (exo-) DNA polymerase is firstly utilized to combine a ...rolling circle amplification (RCA) and qPCR in one step with high sensitivity and specificity in our RC-qPCR assay. Before performing the RC-qPCR, a padlock probe is ligated only when it is perfectly hybridized with miRNA. This ligation-based miRNA assay is highly specific for mature miRNAs, discriminating among related miRNAs that differ by as little as one nucleotide. It exhibits a dynamic range of seven orders of magnitude with a detection limit of 500 aM, and could be also used for the quantification of other small RNA molecules such as short interfering RNAs (siRNAs).
A novel microRNA quantification method has been developed using Rolling Circle-quantitative PCR (RC-qPCR) analysis. This RC-qPCR combines rolling circle amplification (RCA) and qPCR in one step with high sensitivity and specificity based on Vent (exo-) DNA polymerase. The former two enzymes for RCA and qPCR are replaced by Vent (exo-) DNA polymerase, which make detection more simple and time-saving. We expect our rapid, facile, and reliable PCR method will be a promising candidate for detection of miRNA in biomedical applications. Display omitted
•Rolling circle amplification (RCA) and qPCR are combined in one step and one tube by using Vent (exo-) DNA polymerase.•MiRNA could function as a trigger to initiate the RCA in the presence of DNA polymerase.•This RC-qPCR afforded a highly selective and sensitive detection for miRNA with minimized reagents and working steps.•Our rapid, facile, and reliable PCR method would be a promising candidate for detection of miRNA in biomedical applications.
Most circular RNAs are produced from the back-splicing of exons of precursor mRNAs. Recent technological advances have in part overcome problems with their circular conformation and sequence overlap ...with linear cognate mRNAs, allowing a better understanding of their cellular roles. Depending on their localization and specific interactions with DNA, RNA, and proteins, circular RNAs can modulate transcription and splicing, regulate stability and translation of cytoplasmic mRNAs, interfere with signaling pathways, and serve as templates for translation in different biological and pathophysiological contexts. Emerging applications of RNA circles to interfere with cellular processes, modulate immune responses, and direct translation into proteins shed new light on biomedical research. In this review, we discuss approaches used in circular RNA studies and the current understanding of their regulatory roles and potential applications.
Circular RNAs are an exciting emerging class of RNA species, but their closed-loop structures and sequence similarity to linear RNAs have presented challenges in characterizing their unique roles. Liu and Chen review the growing toolbox to characterize circular RNA, the resulting emerging understanding of their biological roles, and how circular RNA are being utilized for biomedical applications.
Abstract Blood flow in the circle of Willis (CoW) is modelled using the 1-D equations of pressure and flow wave propagation in compliant vessels. The model starts at the left ventricle and includes ...the largest arteries that supply the CoW. Based on published physiological data, it is able to capture the main features of pulse wave propagation along the aorta, at the brachiocephalic bifurcation and throughout the cerebral arteries. The collateral ability of the complete CoW and its most frequent anatomical variations is studied in normal conditions and after occlusion of a carotid or vertebral artery (VA). Our results suggest that the system does not require collateral pathways through the communicating arteries to adequately perfuse the brain of normal subjects. The communicating arteries become important in cases of missing or occluded vessels, the anterior communicating artery (ACoA) being a more critical collateral pathway than the posterior communicating arteries (PCoAs) if an internal carotid artery (ICA) is occluded. Occlusions of the VAs proved to be far less critical than occlusions of the ICAs. The worst scenario in terms of reduction in the mean cerebral outflows is a CoW without the first segment of an anterior cerebral artery combined with an occlusion of the contralateral ICA. Furthermore, in patients without any severe occlusion of a carotid or VA, the direction of flow measured at the communicating arteries corresponds to the side of the CoW with an absent or occluded artery. Finally, we study the effect of partial occlusions of the communicating arteries on the cerebral flows, which again confirms that the ACoA is a more important collateral pathway than the PCoAs if an ICA is occluded.
We provide, for any
r
∈
(
0
,
1
)
, lower and upper bounds on the maximal density of a packing in the Euclidean plane of discs of radius 1 and r. The lower bounds are mostly folk, but the upper ...bounds improve the best previously known ones for any
r
∈
0.11
,
0.74
. For many values of r, this gives a fairly good idea of the exact maximum density. In particular, we get new intervals for r which does not allow any packing more dense that the hexagonal packing of equal discs.
Vertebrobasilar dolichoectasia is a rare cerebrovascular disease characterized by obvious extension, dilation and tortuosity of vertebrobasilar artery, and its pathophysiological mechanism is not ...clear. This study focused on local hemodynamic changes in basilar arteries with typical vertebrobasilar dolichoectasia, together with unbalanced vertebral arteries and abnormal structures of the circle of Willis, through multi-scale modeling.
Three-dimensional models of 3 types of vertebrobasilar arteries were constructed from magnetic resonance images. The first type has no vertebrobasilar dolichoectasia, the second type has vertebrobasilar dolichoectasia and balanced vertebral arteries, and the third type has vertebrobasilar dolichoectasia and unbalanced vertebral arteries. A lumped parameter model of the circle of Willis was established and coupled to these three-dimensional models.
The results showed that unbalanced bilateral vertebral arteries, especially single vertebral artery deletion mutation, might associate with higher wall shear stress on anterior wall of basilar artery in patients with vertebrobasilar dolichoectasia. And unbalanced bilateral vertebral arteries would increase the blood pressure in basilar artery. Meanwhile, missing communicating arteries in the circle of Willis, especially bilateral posterior communicating arteries absences, would significantly increase blood pressure in basilar artery. The unilateral absence of posterior communicating arteries would increase differences in blood flow between the left and right posterior cerebral arteries.
This study provided a multi-scale modeling method and some preliminary results for helping understand the role of hemodynamics in occurrence and development of vertebrobasilar dolichoectasia.
•A multi-scale model of vertebral arteries, basilar artery and circle of Willis was built.•Unbalanced vertebral arteries increase wall shear stress at certain side of basilar artery.•Missing of posterior communicating arteries markedly increases blood pressure in basilar artery.
A family of spherical caps of the 2-dimensional unit sphere
S
2
is called a totally separable packing in short, a TS-packing if any two spherical caps can be separated by a great circle which is ...disjoint from the interior of each spherical cap in the packing. The separable Tammes problem asks for the largest density of given number of congruent spherical caps forming a TS-packing in
S
2
. We solve this problem up to eight spherical caps and upper bound the density of any TS-packing of congruent spherical caps in terms of their angular radius. Based on this, we show that the centered separable kissing number of unit balls in Euclidean 3-space is 8. Furthermore, we prove bounds for the maximum of the smallest inradius of the cells of the tilings generated by
n
>
1
great circles in
S
2
. Next, we prove dual bounds for TS-coverings of
S
2
by congruent spherical caps. Here a covering of
S
2
by spherical caps is called a totally separable covering in short, a TS-covering if there exists a tiling generated by finitely many great circles of
S
2
such that the cells of the tiling are covered by pairwise distinct spherical caps of the covering. Finally, we extend some of our bounds on TS-coverings to spherical spaces of dimension
>
2
.
30 Years of space–time covariance functions Porcu, Emilio; Furrer, Reinhard; Nychka, Douglas
Wiley interdisciplinary reviews. Computational statistics,
March/April 2021, Letnik:
13, Številka:
2
Journal Article
Recenzirano
Odprti dostop
In this article, we provide a comprehensive review of space–time covariance functions. As for the spatial domain, we focus on either the d‐dimensional Euclidean space or on the unit d‐dimensional ...sphere. We start by providing background information about (spatial) covariance functions and their properties along with different types of covariance functions. While we focus primarily on Gaussian processes, many of the results are independent of the underlying distribution, as the covariance only depends on second‐moment relationships. We discuss properties of space–time covariance functions along with the relevant results associated with spectral representations. Special attention is given to the Gneiting class of covariance functions, which has been especially popular in space–time geostatistical modeling. We then discuss some techniques that are useful for constructing new classes of space–time covariance functions. Separate treatment is reserved for spectral models, as well as to what are termed models with special features. We also discuss the problem of estimation of parametric classes of space–time covariance functions. An outlook concludes the paper.
This article is categorized under:
Statistical and Graphical Methods of Data Analysis > Analysis of High Dimensional Data
Statistical Learning and Exploratory Methods of the Data Sciences > Modeling Methods
Statistical and Graphical Methods of Data Analysis > Multivariate Analysis
A separable covariance function (left) and a space‐time covariance function with dynamical compact support.
Little is known about vascular smooth muscle cell (SMC) phenotypic modulation in the cerebral circulation or pathogenesis of intracranial aneurysms. Tumor necrosis factor-alpha (TNF-α) has been ...associated with aneurysms, but potential mechanisms are unclear. Cultured rat cerebral SMCs overexpressing myocardin induced expression of key SMC contractile genes (SM-α-actin, SM-22α, smooth muscle myosin heavy chain), while dominant-negative cells suppressed expression. Tumor necrosis factor-alpha treatment inhibited this contractile phenotype and induced pro-inflammatory/matrix-remodeling genes (monocyte chemoattractant protein-1, matrix metalloproteinase-3, matrix metalloproteinase-9, vascular cell adhesion molecule-1, interleukin-1 beta). Tumor necrosis factor-alpha increased expression of KLF4, a known regulator of SMC differentiation. Kruppel-like transcription factor 4 (KLF4) small interfering RNA abrogated TNF-α activation of inflammatory genes and suppression of contractile genes. These mechanisms were confirmed in vivo after exposure of rat carotid arteries to TNF-α and early on in a model of cerebral aneurysm formation. Treatment with the synthesized TNF-α inhibitor 3,6-dithiothalidomide reversed pathologic vessel wall alterations after induced hypertension and hemodynamic stress. Chromatin immunoprecipitation assays in vivo and in vitro demonstrated that TNF-α promotes epigenetic changes through KLF4-dependent alterations in promoter regions of myocardin, SMCs, and inflammatory genes. In conclusion, TNF-α induces phenotypic modulation of cerebral SMCs through myocardin and KLF4-regulated pathways. These results demonstrate a novel role for TNF-α in promoting a pro-inflammatory/matrix-remodeling phenotype, which has important implications for the mechanisms behind intracranial aneurysm formation.
Background and Purpose: The circle of Willis (COW) is a circulatory anastomosis located at the base of the brain. Little is known about the association between covert vascular brain injury and COW ...configurations in the general population. We explored this relationship in a community-based Chinese sample. Methods: A total of 1,055 patients (mean age, 54.8 ± 8.9 years; 36.0% men) without intracranial arterial stenosis were included in the analysis. Magnetic resonance imaging was performed to evaluate the presence of imaging markers of covert vascular brain injury, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces, and brain atrophy. Magnetic resonance angiography was used to classify the COW configurations according to the completeness, symmetry, and presence of the fetal posterior cerebral artery (FTP). The association between vascular lesions and variations in COW was analyzed. Results: Among the 1,055 patients, 104 (9.9%) had a complete COW. Completeness correlated with age (p = 0.001). Incomplete COW was positively associated with WMH severity (OR = 2.071; 95% CI, 1.004–4.270) and CMB presence (OR = 1.542; 95% CI, 1.012–2.348), independent of age and sex. The presence of FTP was associated with lacunes (OR = 1.878; 95% CI, 1.069–3.298), more severe WMHs (OR = 1.739; 95% CI, 1.064–2.842), and less severe enlarged perivascular spaces (OR = 0.562; 95% CI, 0.346–0.915). Conclusions: COW configuration was significantly related to various covert vascular brain injuries.
Large‐scale ionospheric gradients associated with the solar terminator can deflect high frequency (HF) radio waves to off‐great circle paths during the morning and evening, negatively impacting ...technologies reliant on HF radio wave propagation. For example, geolocation algorithms used by scientific and military over‐the‐horizon radars (OTHRs) generally assume on‐great circle propagation, and thus lateral deviations from the great‐circle path can lead to positioning errors. In this study, radio wave propagation is simulated via 3D numerical ray traces though an empirical, high‐latitude model ionosphere initialized for a variety of times of the day and year to explore and quantify high‐latitude off‐great circle propagation associated with the solar terminator. Analysis of these simulations show large scale east‐west ionospheric gradients due to the solar terminator can cause lateral deviations in north‐directed propagation paths exceeding 20° at sunrise and sunset depending on radio wave frequency, though the largest portion of received signal power tends to experience maximum deflections of 5°. An exploration of the dependence of propagation direction on deflection shows that propagation paths parallel to the solar terminator tend to experience the largest deflections. Since the solar terminator at high latitudes is at an angle with respect to north in the winter and summer, propagation paths oriented west or east of north can experience larger deflections than north oriented paths at sunrise and sunset during these times of year. Impacts of these diurnal deflections on the operation of OTHR and scientific radar are discussed, as well as possible strategies for mitigating them.
Plain Language Summary
High frequency (HF) radio waves are able to travel long distances by bouncing between the ionosphere (an upper layer of the Earth's atmosphere) and the ground. HF radio waves transmitted north can have their paths deflected east or west by changes in the ionosphere that happen at sunrise and sunset. In this paper, simulations of radio waves are used to explore how large these deflections can be and how they change over the course of the day and year. It is found that north pointing radio signals at certain frequencies can be deflected by more than 20° at sunrise and sunset. These simulations are also used to explore how radio waves transmitted in different directions are deflected at sunrise and sunset. It is found that radio waves transmitted along the dividing line between day and night tend to experience the largest deflections. The Earth is tilted with respect to its rotation, meaning this dividing line is not always aligned with North. The deviation from north is largest in the winter and summer. This means that radio waves transmitted west or east of north at these times of year can experience larger deflections than northward transmissions.
Key Points
The lateral deflection of high frequency radio waves caused by the solar terminator is investigated with ray tracing simulations
North‐south propagation paths can experience significant (>20°) deflections in the morning and evening
East‐west paths can also see significant deflections at high latitudes, at times when the solar terminator is also oriented east‐west
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