Novel polyamide amidine anthraquinone platinum(II) complexes: cytotoxicity, cellular accumulation, and fluorescence distributions in 2D and 3D cell culture models

1- and 1,5-Aminoalkylamine substituted anthraquinones (AAQs, 1C3 and 1,5C3) were peptide coupled to 1-, 2-, and 3-pyrrole lexitropsins to generate compounds that incorporated both DNA minor groove and intercalating moieties. The corresponding platinum(II) amidine complexes were synthesized through a synthetically facile amine-to-platinum mediated nitrile 'Click' reaction. The precursors as well as the corresponding platinum(II) complexes were biologically evaluated in 2D monolayer cells and 3D tumour cell models. Despite having cellular accumulation levels that were up to five-fold lower than that of cisplatin, the platinum complexes had cytotoxicities that were only three-fold lower. Accumulation was lowest for the complexes with two or three pyrrole groups, but the latter was the most active of the complexes exceeding the activity of cisplatin in the MDA-MB-231 cell line. All compounds showed moderate to good penetration into spheroids of DLD-1 cells with the distributions being consistent with active uptake of the pyrrole containing complexes in regions of the spheroids starved of nutrients

Unsupervised Deformable Image Registration Using Cycle-Consistent CNN

Medical image registration is one of the key processing steps for biomedical image analysis such as cancer diagnosis. Recently, deep learning based supervised and unsupervised image registration methods have been extensively studied due to its excellent performance in spite of ultra-fast computational time compared to the classical approaches. In this paper, we present a novel unsupervised medical image registration method that trains deep neural network for deformable registration of 3D volumes using a cycle-consistency. Thanks to the cycle consistency, the proposed deep neural networks can take diverse pair of image data with severe deformation for accurate registration. Experimental results using multiphase liver CT images demonstrate that our method provides very precise 3D image registration within a few seconds, resulting in more accurate cancer size estimation.Comment: accepted for MICCAI 201

Perceptual grouping ability in Williams syndrome: Evidence for deviant patterns of performance

Williams syndrome (WS) is a rare genetic disorder. At a cognitive level, this population display poor visuo-spatial cognition when compared to verbal ability. Within the visuo-spatial domain, it is now accepted that individuals with WS are able to perceive both local and global aspects of an image, albeit at a low level. The present study examines the manner in which local elements are grouped into a global whole in WS. Fifteen individuals with WS and 15 typically developing controls, matched for non-verbal ability, were presented with a matrix of local elements and asked whether these elements were perceptually grouped horizontally or vertically. The WS group were at the same level as the control group when grouping by luminance, closure, and alignment. However, their ability to group by shape, orientation and proximity was significantly poorer than controls. This unusual profile of grouping abilities in WS suggests that these individuals do not form a global percept in a typical manner

Automated analysis of digital fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration using confocal scanning laser ophthalmoscopy (cSLO)

BACKGROUND: Fundus autofluorescence (AF) imaging using confocal scanning laser ophthalmoscopy (cSLO) provides an accurate delineation of areas of geographic atrophy (GA). Automated computer-assisted methods for detecting and removing interfering vessels are needed to support the GA quantification process in longitudinal studies and in reading centres. METHODS: A test tool was implemented that uses region-growing techniques to segment GA areas. An algorithm for illuminating shadows can be used to process low-quality images. Agreement between observers and between three different methods was evaluated by two independent readers in a pilot study. Agreement and objectivity were assessed using the Bland-Altman approach. RESULTS: The new method (C) identifies vascular structures that interfere with the delineation of GA. Results are comparable to those of two commonly used procedures (A, B), with a mean difference between C and A of -0.67 mm(2 )(95% CI [-0.99, -0.36]), between B and A of -0.81 mm(2), (95% CI [-1.08, -0.53]), and between C and B of 0.15 mm(2 )(95% CI [-0.12, 0.41]). Objectivity of a method is quantified by the mean difference between observers: A 0.30 mm(2 )(95% CI [0.02, 0.57]), B -0.11 mm(2 )(95% CI [-0.28, 0.10]), and C 0.12 mm(2 )(95% CI [0.02, 0.22]). CONCLUSION: The novel procedure is comparable with regard to objectivity and inter-reader agreement to established methods of quantifying GA. It considerably speeds up the lengthy measurement process in AF with well defined GA zones

Universal scaling relation in high-temperature superconductors

Scaling laws express a systematic and universal simplicity among complex systems in nature. For example, such laws are of enormous significance in biology. Scaling relations are also important in the physical sciences. The seminal 1986 discovery of high transition-temperature (high-T_c) superconductivity in cuprate materials has sparked an intensive investigation of these and related complex oxides, yet the mechanism for superconductivity is still not agreed upon. In addition, no universal scaling law involving such fundamental properties as T_c and the superfluid density \rho_s, a quantity indicative of the number of charge carriers in the superconducting state, has been discovered. Here we demonstrate that the scaling relation \rho_s \propto \sigma_{dc} T_c, where the conductivity \sigma_{dc} characterizes the unidirectional, constant flow of electric charge carriers just above T_c, universally holds for a wide variety of materials and doping levels. This surprising unifying observation is likely to have important consequences for theories of high-T_c superconductivity.Comment: 11 pages, 2 figures, 2 table

Quantum interference and Klein tunneling in graphene heterojunctions

The observation of quantum conductance oscillations in mesoscopic systems has traditionally required the confinement of the carriers to a phase space of reduced dimensionality. While electron optics such as lensing and focusing have been demonstrated experimentally, building a collimated electron interferometer in two unconfined dimensions has remained a challenge due to the difficulty of creating electrostatic barriers that are sharp on the order of the electron wavelength. Here, we report the observation of conductance oscillations in extremely narrow graphene heterostructures where a resonant cavity is formed between two electrostatically created bipolar junctions. Analysis of the oscillations confirms that p-n junctions have a collimating effect on ballistically transmitted carriers. The phase shift observed in the conductance fringes at low magnetic fields is a signature of the perfect transmission of carriers normally incident on the junctions and thus constitutes a direct experimental observation of ``Klein Tunneling.''Comment: 13 pages and 6 figures including supplementary information. The paper has been modified in light of new theoretical results available at arXiv:0808.048

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

Spin torque resonant vortex core expulsion for an efficient radio-frequency detection scheme

Spin-polarised radio-frequency currents, whose frequency is equal to that of the gyrotropic mode, will cause an excitation of the core of a magnetic vortex confined in a magnetic tunnel junction. When the excitation radius of the vortex core is greater than that of the junction radius, vortex core expulsion is observed, leading to a large change in resistance, as the layer enters a predominantly uniform magnetisation state. Unlike the conventional spin-torque diode effect, this highly tunable resonant effect will generate a voltage which does not decrease as a function of rf power, and has the potential to form the basis of a new generation of tunable nanoscale radio-frequency detectors

Construction et classification de certaines solutions algébriques des systèmes de Garnier

22 pagesInternational audienceIn this paper, we classify all (complete) non elementary algebraic solutions of Garnier systems that can be constructed by Kitaev's method: they are deduced from isomonodromic deformations defined by pulling back a given fuchsian equation E by a family of ramified covers. We first introduce orbifold structures associated to a fuchsian equation. This allow to get a refined version of Riemann-Hurwitz formula and then to promtly deduce that E is hypergeometric. Then, we can bound exponents and degree of the pull-back maps and further list all possible ramification cases. This generalizes a result due to C. Doran for the Painleve VI case. We explicitely construct one of these solutions