AURKA mRNA expression is an independent predictor of poor prognosis in patients with non-small cell lung cancer

Deregulation of mitotic spindle genes has been reported to contribute to the development and progression of malignant tumours. The aim of the present study was to explore the association between the expression profiles of Aurora kinases (AURKA, AURKB and AURKC), cytoskeleton-associated protein 5 (CKAP5), discs large-associated protein 5 (DLGAP5), kinesin-like protein 11 (KIF11), microtubule nucleation factor (TPX2), monopolar spindle 1 kinase (TTK), and β-tubulins (TUBB) and (TUBB3) genes and clinicopathological characteristics in human non-small cell lung carcinoma (NSCLC). Reverse transcription-quantitative polymerase chain reaction-based RNA gene expression profiles of 132 NSCLC and 44 adjacent wild-type tissues were generated, and Cox's proportional hazard regression was used to examine associations. With the exception of AURKC, all genes exhibited increased expression in NSCLC tissues. Of the 10 genes examined, only AURKA was significantly associated with prognosis in NSCLC. Multivariate Cox's regression analysis demonstrated that AURKA mRNA expression [hazard ratio (HR), 1.81; 95% confidence interval (CI), 1.16-2.84; P=0.009], age (HR, 1.03; 95% CI, 1.00-1.06; P=0.020), pathological tumour stage 2 (HR, 2.43; 95% CI, 1.16-5.10; P=0.019) and involvement of distal nodes (pathological node stage 2) (HR, 3.14; 95% CI, 1.24-7.99; P=0.016) were independent predictors of poor prognosis in patients with NSCLC. Poor prognosis of patients with increased AURKA expression suggests that those patients may benefit from surrogate therapy with AURKA inhibitors

Structured squaring down and zero assignment

The problem of zero assignment by squaring down is considered for a system of p-inputs, n-outputs and n-states (m > p), where not all outputs are free variables for design. We consider the case where a k-subset of outputs is preserved in the new output set, and the rest are recombined to produce a total new set of p-outputs. New invariants for the problem are introduced which include a new class of fixed zeros and the methodology of the global linearization, developed originally for the output feedback pole assignment problem, is applied to this restricted form of the squaring down problem. It is shown that the problem can be solved generically if (p − k)(m − p) > δ*, where k (k < p) is the number of fixed outputs and δ* is a system and compensation scheme invariant, which is defined as the restricted Forney degree

Symbols of One-Loop Integrals From Mixed Tate Motives

We use a result on mixed Tate motives due to Goncharov (arXiv:alg-geom/9601021) to show that the symbol of an arbitrary one-loop 2m-gon integral in 2m dimensions may be read off directly from its Feynman parameterization. The algorithm proceeds via recursion in m seeded by the well-known box integrals in four dimensions. As a simple application of this method we write down the symbol of a three-mass hexagon integral in six dimensions.Comment: 13 pages, v2: minor typos correcte

Collinear and Soft Limits of Multi-Loop Integrands in N=4 Yang-Mills

It has been argued in arXiv:1112.6432 that the planar four-point integrand in N=4 super Yang-Mills theory is uniquely determined by dual conformal invariance together with the absence of a double pole in the integrand of the logarithm in the limit as a loop integration variable becomes collinear with an external momentum. In this paper we reformulate this condition in a simple way in terms of the amplitude itself, rather than its logarithm, and verify that it holds for two- and three-loop MHV integrands for n>4. We investigate the extent to which this collinear constraint and a constraint on the soft behavior of integrands can be used to determine integrands. We find an interesting complementarity whereby the soft constraint becomes stronger while the collinear constraint becomes weaker at larger n. For certain reasonable choices of basis at two and three loops the two constraints in unison appear strong enough to determine MHV integrands uniquely for all n.Comment: 27 pages, 14 figures; v2: very minor change

R^4 counterterm and E7(7) symmetry in maximal supergravity

The coefficient of a potential R^4 counterterm in N=8 supergravity has been shown previously to vanish in an explicit three-loop calculation. The R^4 term respects N=8 supersymmetry; hence this result poses the question of whether another symmetry could be responsible for the cancellation of the three-loop divergence. In this article we investigate possible restrictions from the coset symmetry E7(7)/SU(8), exploring the limits as a single scalar becomes soft, as well as a double-soft scalar limit relation derived recently by Arkani-Hamed et al. We implement these relations for the matrix elements of the R^4 term that occurs in the low-energy expansion of closed-string tree-level amplitudes. We find that the matrix elements of R^4 that we investigated all obey the double-soft scalar limit relation, including certain non-maximally-helicity-violating six-point amplitudes. However, the single-soft limit does not vanish for this latter set of amplitudes, which suggests that the E7(7) symmetry is broken by the R^4 term.Comment: 33 pages, typos corrected, published versio

Double quantum dot with integrated charge sensor based on Ge/Si heterostructure nanowires

Coupled electron spins in semiconductor double quantum dots hold promise as the basis for solid-state qubits. To date, most experiments have used III-V materials, in which coherence is limited by hyperfine interactions. Ge/Si heterostructure nanowires seem ideally suited to overcome this limitation: the predominance of spin-zero nuclei suppresses the hyperfine interaction and chemical synthesis creates a clean and defect-free system with highly controllable properties. Here we present a top gate-defined double quantum dot based on Ge/Si heterostructure nanowires with fully tunable coupling between the dots and to the leads. We also demonstrate a novel approach to charge sensing in a one-dimensional nanostructure by capacitively coupling the double dot to a single dot on an adjacent nanowire. The double quantum dot and integrated charge sensor serve as an essential building block required to form a solid-state spin qubit free of nuclear spin.Comment: Related work at http://marcuslab.harvard.edu and http://cmliris.harvard.ed

Distance Optimization and the Extremal Variety of the Grassmann Variety

The approximation of a multivector by a decomposable one is a distance-optimization problem between the multivector and the Grassmann variety of lines in a projective space. When the multivector diverges from the Grassmann variety, then the approximate solution sought is the worst possible. In this paper, it is shown that the worst solution of this problem is achieved, when the eigenvalues of the matrix representation of a related two-vector are all equal. Then, all these pathological points form a projective variety. We derive the equation describing this projective variety, as well as its maximum distance from the corresponding Grassmann variety. Several geometric and algebraic properties of this extremal variety are examined, providing a new aspect for the Grassmann varieties and the respective projective spaces

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Thermal phases of D1-branes on a circle from lattice super Yang-Mills

We report on the results of numerical simulations of 1+1 dimensional SU(N) Yang-Mills theory with maximal supersymmetry at finite temperature and compactified on a circle. For large N this system is thought to provide a dual description of the decoupling limit of N coincident D1-branes on a circle. It has been proposed that at large N there is a phase transition at strong coupling related to the Gregory-Laflamme (GL) phase transition in the holographic gravity dual. In a high temperature limit there was argued to be a deconfinement transition associated to the spatial Polyakov loop, and it has been proposed that this is the continuation of the strong coupling GL transition. Investigating the theory on the lattice for SU(3) and SU(4) and studying the time and space Polyakov loops we find evidence supporting this. In particular at strong coupling we see the transition has the parametric dependence on coupling predicted by gravity. We estimate the GL phase transition temperature from the lattice data which, interestingly, is not yet known directly in the gravity dual. Fine tuning in the lattice theory is avoided by the use of a lattice action with exact supersymmetry.Comment: 21 pages, 8 figures. v2: References added, two figures were modified for clarity. v3: Normalisation of lattice coupling corrected by factor of two resulting in change of estimate for c_cri

A simple approach to counterterms in N=8 supergravity

We present a simple systematic method to study candidate counterterms in N=8 supergravity. Complicated details of the counterterm operators are avoided because we work with the on-shell matrix elements they produce. All n-point matrix elements of an independent SUSY invariant operator of the form D^{2k} R^n +... must be local and satisfy SUSY Ward identities. These are strong constraints, and we test directly whether or not matrix elements with these properties can be constructed. If not, then the operator does not have a supersymmetrization, and it is excluded as a potential counterterm. For n>4, we find that R^n, D^2 R^n, D^4 R^n, and D^6 R^n are excluded as counterterms of MHV amplitudes, while only R^n and D^2 R^n are excluded at the NMHV level. As a consequence, for loop order L<7, there are no independent D^{2k}R^n counterterms with n>4. If an operator is not ruled out, our method constructs an explicit superamplitude for its matrix elements. This is done for the 7-loop D^4 R^6 operator at the NMHV level and in other cases. We also initiate the study of counterterms without leading pure-graviton matrix elements, which can occur beyond the MHV level. The landscape of excluded/allowed candidate counterterms is summarized in a colorful chart.Comment: 25 pages, 1 figure, published versio