Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

Defocusing image to pattern contact holes using attenuated phase shift masks

The patterning of contact holes by selecting out-of-focus image plane (defocus) using attenuated phase shift masks (APSM) has been studied. Defocus is found to enhance the image modulation at low partial coherence for contact holes with negative local average of mask function. Semi-dense holes up to 130 nm in 8% APSM have been printed by 0.5 μm defocus at a partial coherence of 0.31 using KrF scanner with highest numerical aperture of 0.68. However, these holes were closed with in-focus imaging. Defocus is also found to be beneficial for patterning the pitches that have extensive side lobes with in-focus imaging.     

Adaptive motion control using neural network approximations

In this paper, we present a new adaptive technique for tracking control of mechanical systems in the presence of friction and periodic disturbances. Radial Basis Functions (RBFs) are used to compensate for the effects of nonlinearly occurring parameters in the friction and periodic disturbance model. Theoretical analysis, such as stability and transient performance, is provided. Furthermore, the performance of the adaptive RBF controller and its non-adaptive counterpart are compared.     

Acoustic Properties of Amorphous Solids at Very Low Temperatures: The Quest for Interacting Tunneling States

We discuss the strain dependence of the acoustic properties of amorphous metals in both normal and superconducting states, in the temperature range 0.1 mK<T<1 K. A crossover is found when the strain energy is of the order of the effective interaction energy between tunneling systems at the corresponding temperature. Our results provide clear evidence for the interaction between tunneling systems, whose energy is in quantitative agreement with theoretical expectations, and reveal that without the knowledge of the corresponding strain dependences, the measured temperature dependences below ～50 mK of the acoustic properties of disordered solids are rather meaningless.     

Determination of the uranium enrichment with the NaIGEM code

The traditional method used to non-destructively determine the uranium enrichment with an NaI detector is based on the “enrichment meter principle” (Progress report LA-4605-MS, Los Alamos National Laboratory, NNM, 1970, p. 19), which involves measuring the intensity of the 186 keV line of ²³⁵U by selecting two regions of interest for the peak and the background. This type of method suffers from several limitations, the most limiting of which are the impossibility to make wall thickness correction or to take the inference of foreign radioisotopes into account. The NaIGEM software (A guide for using NaIGEM code, version 1.5 for DOS and Windows, 2001; Nucl. Instr. and Meth. A 458 (2001) 196) was developed to overcome these limitations by calculating the 186 keV line intensity with a fitting procedure. The code was tested in different measurement conditions on the wide variety of certified samples, in particular, on reprocessed uranium and on depleted material with thick steel filters interposed between the source and the detector. The results are presented to illustrate the performance and limitations of the tested version (A guide for using NaIGEM code, version 1.5 for DOS and Windows, 2001). The general performance is good except in the case of low-enriched uranium in thick containers.     

Topology preservation of template-based 6-subiteration reduction operations

Generally, a reduction operation (e.g., thinning and shrinking) on 3D binary images can be represented as a set of reduction templates where every object voxel of the image satisfying any template is turned to a background voxel. Generally, it is rather difficult, error-prone and time-consuming for verifying the topological soundness of a 3D parallel reduction operation. This paper proposes sufficient conditions of time complexity O(n) for verifying the topological soundness of 3D parallel 6-subiteration reduction operations of n templates where such a kind of 3D reduction operations is performed alternatively from the six orthogonal directions to turn object voxels to background voxels. By such sufficient conditions, the topology soundness of a 3D 6-subiteration parallel reduction operation can be verified by checking each and every of its templates.     

Control of discrete time nonlinear systems with a time-varying structure

In this paper, we present a control methodology for a class of discrete time nonlinear systems that depend on a possibly exogenous scheduling variable. This class of systems consists of an interpolation of nonlinear dynamic equations in strict feedback form, and it may represent systems with a time-varying nonlinear structure. Moreover, this class of systems is able to represent some cases of gain scheduling control, Takagi-Sugeno fuzzy systems, as well as input-output realizations of nonlinear systems which are approximated via localized linearizations. We present two control theorems, one using what we call a “global” approach (akin to traditional backstepping), and a “local” approach, our main result, where backstepping is again used but the control law is an interpolation of local control terms. An aircraft wing rock regulation problem with varying angle of attack is used to illustrate and compare the two approaches.     

Stability robustness of networked control systems with respect to packet loss

This paper is concerned with stability analysis of discrete-time networked control systems over a communication channel subject to packet loss whose behavior is modeled by an i.i.d Bernoulli process with a packet dropping probability bounded by a constant. A necessary and sufficient condition for stability is obtained. A packet dropping margin is introduced as a measure of stability robustness of a system against packet dropping, and a formula for it is derived. A design method is proposed for achieving a large margin subject to a constraint that the system has a set of prescribed nominal closed-loop poles.     

Decentralized adaptive coordinated control of multiple robot arms without using a force sensor

This paper presents a distributed adaptive coordinated control method for multiple robot arms grasping a common object. The cases of rigid contact and rolling contact are analyzed. In the proposed controller, the dynamic parameters of both object and robot arms are estimated adaptively. The desired motions of the robot arms are generated by an estimated object reference model. The control method requires only the measurements of the positions and velocities of the object and robot arms, but not the measurements of forces and moments at contact points. The asymptotic convergence of trajectory is proven by the Lyapunov-like Lemma. Experiments involving two robot arms handling a common object are shown.