An integrated chemical biology approach provides insight into cdk2 functional redundancy and inhibitor sensitivity

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Highlights? Demonstration that Cdk2 is rate-limiting for DNA replication due to insufficient Cdk1 activity ? A simple bioinformatic approach to design inhibitor resistant mutations in kinases ? Demonstration of distinct binding modes and selectivity of Cdk inhibitors ? Identification of kinetic and structural mechanisms of inhibitor resistance     

A Rigorous Proof of the Landau-Peierls Formula and much more

We present a rigorous mathematical treatment of the zero-field orbital magnetic susceptibility of a non-interacting Bloch electron gas, at fixed temperature and density, for both metals and semiconductors/insulators. In particular, we obtain the Landau-Peierls formula in the low temperature and density limit as conjectured by Kjeldaas and Kohn (Phys Rev 105:806–813, 1957).     

Sensitivity kernel for surface scattering in a waveguide

Using the Born approximation, a linearized sensitivity kernel is derived to describe the relationship between a local change at the free surface and its effect on the acoustic propagation in the water column. The structure of the surface scattering kernel is investigated numerically and experimentally for the case of a waveguide at the ultrasonic scale. To better demonstrate the sensitivity of the multipath propagation to the introduction of a localized perturbation at the air-water interface, the kernel is formulated both in terms of point-to-point and beam-to-beam representations. Agreement between theory and experiment suggests applications to sensitivity analysis of the wavefield for sea surface perturbations.     

Enhancing the emergence rate of coherent wavefronts from ocean ambient noise correlations using spatio-temporal filters

Extracting coherent wavefronts between passive receivers using cross-correlations of ambient noise (CAN) provides a means for monitoring the seismoacoustic environment without using active sources. However, using cross-correlations between single receivers can require a long recording time in order to extract stable coherent arrivals from CAN. This becomes an issue if the propagation medium fluctuates significantly during the recording period. To address this issue, this article presents a general spatio-temporal filtering procedure to enhance the emergence rate for coherent wavefronts extracted from time-averaged ambient noise correlations between two spatially separated arrays. The robustness of this array-based CAN technique is investigated using ambient shipping noise recorded over 24?h in the frequency band [250-850 Hz] on two vertical line arrays deployed 143?m apart in shallow water (depth 20?m). Experimental results confirm that the array-based CAN technique can significantly reduce the recording duration (e.g., from 22?h to 30?min) required for extracting coherent wavefronts of sufficient amplitude (e.g., 20?dB over residual temporal fluctations) when compared to conventional CAN implementations between single pairs of hydrophones. These improvements of the CAN technique could benefit the development of noise-based ocean monitoring applications such as passive acoustic tomography.     

Sobolev Periodic Solutions of Nonlinear Wave Equations in Higher Spatial Dimensions

We prove the existence of Cantor families of periodic solutions for nonlinear wave equations in higher spatial dimensions with periodic boundary conditions. We study both forced and autonomous PDEs. In the latter case our theorems generalize previous results of Bourgain to more general nonlinearities of class C ^k and assuming weaker non-resonance conditions. Our solutions have Sobolev regularity both in time and space. The proofs are based on a differentiable Nash–Moser iteration scheme, where it is sufficient to get estimates of interpolation-type for the inverse linearized operators. Our approach works also in presence of very large “clusters of small divisors”.     

Flow-induced polymer degradation probed by a high throughput microfluidic set-up

A complex fluid submitted to strong flows can endure irreversible changes in its structure. This is the case for long chain polymer additives that are commonly used as viscosity enhancers in industry, notably for oil recovery. These polymers break in solution when submitted to high deformation rates, eventually causing a serious viscosity loss. This problem of practical importance is though difficult to handle from a fundamental point of view given its complexity. We introduce here a new tool, based on microfluidic technology, for the screening of the degradation of solutions in the model situation of the flow through a constriction. We integrate two functions in a single set-up, a micro-fabricated constriction and an on-chip viscosimeter. This tool enables us to probe rapidly the viscosity loss imparted by flowing through the constriction at a given flow rate. Thanks to microfluidics, the sample preparation and measurement time are significantly lower than those implied by classical measurement protocols (reduction by up to two orders of magnitude). In addition, confinement provides control of the flow in terms of inertia. To illustrate the potential of this approach in a screening perspective, we use this tool to study the degradation of a series of semi-dilute aqueous solutions of PEO of varying molecular weights and concentrations. For each solution we identify a threshold flow rate for polymer degradation. The corresponding critical deformation rate decreases with molecular weight and concentration, as expected (the mass dependence is in line with previous reports and theories for dilute solutions). In addition we characterize the viscosity loss for larger deformation rates and find that, despite the polydispersity of our solutions, the observations for the various solutions can be roughly recast on a master curve by renormalization of the imposed deformation rates according to a law $M_w^{?1.7\pm 03}{c}^{?0.7\pm 03}$.     

Labelling and binding of poly-( -lysine) to functionalised gold surfaces. Combined FT-IRRAS and XPS characterisation

We compare herein the interfacial reactivity of self-assembled monolayers (SAMs) of 11-mercaptoundecanoic acid (MUA), 1-undecanethiol (UDT) and 11-mercaptoundecanol (MUD) on gold surfaces towards aqueous solutions of poly-( -lysine) (PL). Liquid-phase labelling of PL with the alkyne dicobalt hexacarbonyl cluster 1 combined with analysis of the substrates by Fourier transform infrared reflection–absorption spectroscopy (FT-IRRAS) and X-ray photoelectron spectroscopy (XPS) revealed that irreversible binding of PL occurred in all cases. However, the mechanism of binding involved differed markedly from one monolayer to the other. The main mode of interaction of PL to MUA SAM was of electrostatic nature between the terminal carboxylate of MUA and the ammonium groups of PL. For a similar number of bound thiolate molecules, the UDT adsorbed layer was found less continuous than the MUA one, allowing a higher fraction of PL to directly bind to the gold surface. As for MUD, very little thiolate molecules were adsorbed, leaving bare gold surface areas for non specific adsorption of PL.