Superconducting nanowire photon number resolving detector at telecom wavelength

The optical-to-electrical conversion, which is the basis of optical detectors, can be linear or nonlinear. When high sensitivities are needed single-photon detectors (SPDs) are used, which operate in a strongly nonlinear mode, their response being independent of the photon number. Nevertheless, photon-number resolving (PNR) detectors are needed, particularly in quantum optics, where n-photon states are routinely produced. In quantum communication, the PNR functionality is key to many protocols for establishing, swapping and measuring entanglement, and can be used to detect photon-number-splitting attacks. A linear detector with single-photon sensitivity can also be used for measuring a temporal waveform at extremely low light levels, e.g. in long-distance optical communications, fluorescence spectroscopy, optical time-domain reflectometry. We demonstrate here a PNR detector based on parallel superconducting nanowires and capable of counting up to 4 photons at telecommunication wavelengths, with ultralow dark count rate and high counting frequency

Effect of promoter architecture on the cell-to-cell variability in gene expression

According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect noise in gene expression in a systematic rather than case-by-case fashion. In this article, we make such a systematic investigation, based on a simple microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcription product from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte

Laser written waveguide photonic quantum circuits

We report photonic quantum circuits created using an ultrafast laser processing technique that is rapid, requires no lithographic mask and can be used to create three-dimensional networks of waveguide devices. We have characterized directional couplers--the key functional elements of photonic quantum circuits--and found that they perform as well as lithographically produced waveguide devices. We further demonstrate high-performance interferometers and an important multi-photon quantum interference phenomenon for the first time in integrated optics. This direct-write approach will enable the rapid development of sophisticated quantum optical circuits and their scaling into three-dimensions.Comment: 4 pages, 4 figures. Submitted to Optics Express 04/04/2009, accepted for publication 30/06/0

Nucleosomes in gene regulation: theoretical approaches

This work reviews current theoretical approaches of biophysics and bioinformatics for the description of nucleosome arrangements in chromatin and transcription factor binding to nucleosomal organized DNA. The role of nucleosomes in gene regulation is discussed from molecular-mechanistic and biological point of view. In addition to classical problems of this field, actual questions of epigenetic regulation are discussed. The authors selected for discussion what seem to be the most interesting concepts and hypotheses. Mathematical approaches are described in a simplified language to attract attention to the most important directions of this field

Lethal privacy: Quantifying life years lost if the right to informational self-determination guides genetic screening for Lynch syndrome.

Genetic relatives of hereditary colorectal cancer patients with Lynch syndrome (LS) are at risk of cancer. Testing both colorectal cancer patients and relatives of mutation carriers for LS allows targeted prevention. However, this could mean disclosing sensitive health data to family members. In light of potential trade-offs between cost-effectiveness and patient privacy, this study investigates the implications of increasing test uptake in Germany.Out of 22 screening strategies for LS, the non-dominated and current German strategies were assessed from the perspective of the statutory health insurance. Life years gained by increased prevention were estimated with Markov models. The effects and implications of different test uptake rates in index patients and their relatives were investigated by scenario analysis.Privacy limitations could yield health gains of up to 2500 undiscounted life years for first-degree relatives of index patients and substantially improve cost-effectiveness. However, this approach may contradict the right to informational self-determination.This study demonstrates the effect higher LS test uptakes could have on the lives and rights of colorectal cancer patients and their relatives. It shows potential conflicts between the efficient use of health care resources on the one hand and reasonable consideration of patient autonomy on the other

Flow profile near a wall measured by double-focus fluorescence cross-correlation

We present an experimental approach to flow profiling within femtoliter sample volumes, which allows the high-precision measurements at the solid interface. The method is based on the spatial cross-correlation of the fluorescence response from labeled tracer particles (latex nanospheres or single dye molecules). Two excitation volumes, separated by a few micrometers, are created by two laser foci under a confocal microscope. The velocity of tracer particles is measured in a channel about 100 μm wide within a typical accuracy of 0.1%, and the positions of the walls are estimated independently of any hydrodynamic data. The underlying theory for the optical method is given for an arbitrary velocity profile, explicitly presenting the numerical convolutions necessary for a quantitative analysis. It is illustrated by using the Poiseuille flow of a Newtonian liquid with slip as an example. Our analysis yields a large apparent fluid velocity at the wall, which is mostly due to the impact of the colloidal (electrostatic) forces. This colloidal lift is crucially important in accelerating the transport processes of molecules and nanoparticles in microfluidic devices

Nucleosome disassembly intermediates characterized by single-molecule FRET

The nucleosome has a central role in the compaction of genomic DNA and the control of DNA accessibility for transcription and replication. To help understanding the mechanism of nucleosome opening and closing in these processes, we studied the disassembly of mononucleosomes by quantitative single-molecule FRET with high spatial resolution, using the SELEX-generated “Widom 601” positioning sequence labeled with donor and acceptor fluorophores. Reversible dissociation was induced by increasing NaCl concentration. At least 3 species with different FRET were identified and assigned to structures: (i) the most stable high-FRET species corresponding to the intact nucleosome, (ii) a less stable mid-FRET species that we attribute to a first intermediate with a partially unwrapped DNA and less histones, and (iii) a low-FRET species characterized by a very broad FRET distribution, representing highly unwrapped structures and free DNA formed at the expense of the other 2 species. Selective FCS analysis indicates that even in the low-FRET state, some histones are still bound to the DNA. The interdye distance of 54.0 Å measured for the high-FRET species corresponds to a compact conformation close to the known crystallographic structure. The coexistence and interconversion of these species is first demonstrated under non-invasive conditions. A geometric model of the DNA unwinding predicts the presence of the observed FRET species. The different structures of these species in the disassembly pathway map the energy landscape indicating major barriers for 10-bp and minor ones for 5-bp DNA unwinding steps