Ratiometric Detection of microRNA Using Hybridization Chain Reaction and Fluorogenic Silver Nanoclusters

miRNA (miR)-155 is a potential biomarker for breast cancers. We aimed at developing a nanosensor for miR-155 detection by integrating hybridization chain reaction (HCR) and silver nanoclusters (AgNCs). HCR serves as an enzyme-free and isothermal amplification method, whereas AgNCs provide a built-in fluorogenic detection probe that could simplify the downstream analysis. The two components were integrated by adding a nucleation sequence of AgNCs to the hairpin of HCR. The working principle was based on the influence of microenvironment towards the hosted AgNCs, whereby unfolding of hairpin upon HCR has manipulated the distance between the hosted AgNCs and cytosine-rich toehold region of hairpin. As such, the dominant emission of AgNCs changed from red to yellow in the absence and presence of miR-155, enabling a ratiometric measurement of miR with high sensitivity. The limit of detection (LOD) of our HCR-AgNCs nanosensor is 1.13 fM in buffered solution. We have also tested the assay in diluted serum samples, with comparable LOD of 1.58 fM obtained. This shows the great promise of our HCR-AgNCs nanosensor for clinical application.     

On the orthogonality of natural modes of vibration

The natural modes of a discrete linear system are orthogonal with respect to the mass and stiffness matrices in a generalized sense. However, these modes are usually not orthogonal to each other in the ordinary sense. The purpose of this paper is to document a number of conditions under which the modes are also orthogonal in an ordinary fashion.     

A Characterisation of Posets that Are nearly Antichains

We present a characterisation of posets of size n with linear discrepancy n − 2. These are the posets that are “furthest” from a linear order without being an antichain. This revised version was published online in September 2006 with corrections to the Cover Date.     

Invariant ideals of twisted crossed products

We will prove a result concerning the inclusion of non-trivial invariant ideals inside non-trivial ideals of a twisted crossed product. We will also give results concerning the primeness and simplicity of crossed products of twisted actions of locally compact groups on -algebras. Received: 25 January 2002; in final form: 22 May 2002/Published online: 2 December 2002 This work is partially supported by Hong Kong RGC Direct Grant.     

Perspectives on Advanced Mathematical Thinking

This article sets the stage for the following 3 articles. It opens with a brief history of attempts to characterize advanced mathematical thinking, beginning with the deliberations of the Advanced Mathematical Thinking Working Group of the International Group for the Psychology of Mathematics Education. It then locates the articles within 4 recurring themes: (a) the distinction between identifying kinds of thinking that might be regarded as advanced at any grade level, and taking as advanced any thinking about mathematical topics considered advanced; (b) the utility of characterizing such thinking for integrating the entire curriculum; (c) general tests, or criteria, for identifying advanced mathematical thinking; and (d) an emphasis on advancing mathematical practices. Finally, it points out some commonalities and differences among the 3 following articles.     

Discrete global descent method for discrete global optimization and nonlinear integer programming

A novel method, entitled the discrete global descent method, is developed in this paper to solve discrete global optimization problems and nonlinear integer programming problems. This method moves from one discrete minimizer of the objective function f to another better one at each iteration with the help of an auxiliary function, entitled the discrete global descent function. The discrete global descent function guarantees that its discrete minimizers coincide with the better discrete minimizers of f under some standard assumptions. This property also ensures that a better discrete minimizer of f can be found by some classical local search methods. Numerical experiments on several test problems with up to 100 integer variables and up to 1.38 × 10¹⁰⁴ feasible points have demonstrated the applicability and efficiency of the proposed method.     

Large Scale Linear Programs and Heuristics for the Design of Survivable Telecommunication Networks

We consider the problem of providing a minimum cost multi-service network subject to one link failure scenarios. We assume our network is fully meshed and demand is satisfied by using direct or two hop-paths. We provide a large scale linear programming formulation and propose and test two effective heuristics.     

Some aerodynamic and acoustic characteristicsof acute laryngitis

The purpose of the present study was to describe the effects ofacute laryngitis on some aerodynamic, acoustic, and perceptual measures. Eleven subjects with diagnosed acute laryngitis due to upper respiratory infection were recorded during a laryngitic episode and 1 week to 10 days after amelioration of the laryngitic condition. Fundamental frequency values, collapsed across the five vowels, were significantly reduced in the laryngitic compared with the normal speaking condition. The decrease in fundamental frequency associated with acute laryngitis suggests an increase in the mass of the vocal folds. In addition, aerodynamic values differed significantly for the laryngitic condition compared with the normal speaking condition, suggesting the presence of laryngeal hypofunction. Perceptual data indicated that speakers in the laryngitic condition were judged to have a hoarse voice when compared with the normal speaking condition.     

Rational approximation of vertical segments

In many applications, observations are prone to imprecise measurements. When constructing a model based on such data, an approximation rather than an interpolation approach is needed. Very often a least squares approximation is used. Here we follow a different approach. A natural way for dealing with uncertainty in the data is by means of an uncertainty interval. We assume that the uncertainty in the independent variables is negligible and that for each observation an uncertainty interval can be given which contains the (unknown) exact value. To approximate such data we look for functions which intersect all uncertainty intervals. In the past this problem has been studied for polynomials, or more generally for functions which are linear in the unknown coefficients. Here we study the problem for a particular class of functions which are nonlinear in the unknown coefficients, namely rational functions. We show how to reduce the problem to a quadratic programming problem with a strictly convex objective function, yielding a unique rational function which intersects all uncertainty intervals and satisfies some additional properties. Compared to rational least squares approximation which reduces to a nonlinear optimization problem where the objective function may have many local minima, this makes the new approach attractive.