A mutational analysis of receptor binding sites of interleukin-1{beta}:differences in binding of human interleukin-1{beta} muteins to human and mouse receptors

The 3-D crystal structure of interleukin-1ß(IL-1ß)has been used to define its receptor binding surface by mutationalanalysis. The surface of IL-1ß was probed by site-directedmutagenesis. A total of 27 different IL-1ß muteinswere constructed, purified and analyzed. Receptor binding measurementson mouse and human cell lines were performed to identify receptoraffinities. IL-1ß muteins with modified receptor affinitywere evaluated for structural integrity by CD spectroscopy orX-ray crystallography. Changes in six surface loops, as wellas in the C- and N-termini, yielded muteins with lower bindingaffinities. Two muteins with intact binding affinities showed10- to 100-fold reduced biological activity. The surface regioninvolved in receptor binding constitutes a discontinuous areaof 1000 Å2 formed by discontinuous polypeptide chain stretches.Based on these results, a subdivision into two distinct localareas is proposed. Differences in receptor binding affinitiesfor human and mouse receptors have been observed for some muteins,but not for wild-type IL-1ß. This is the first timea difference in binding affinity of IL-1ß muteinsto human and mouse receptors has been demonstrated     

Theory of asymmetric organocatalysis of Aldol and related reactions: rationalizations and predictions

Computational studies have led to models to understand some classic and contemporary asymmetric reactions involving organocatalysts. The Hajos-Parrish-Eder-Sauer-Wiechert reaction and intermolecular aldol reactions as well as Mannich reactions and oxyaminations catalyzed by proline and other amino acids, and Diels-Alder reactions catalyzed by MacMillan's chiral amine organocatalysts have been studied with density functional theory. Quantitative predictions for several new catalysts and reactions are provided.     

Flux pinning effect of cubic equiaxed morphology and its Ti stabilizing in Nb<Subscript>3</Subscript>Sn superconductors

Two sets of internal-Sn Nb3Sn superconducting strands were fabricated through RRP method, one with 2 wt% of Ti alloyed in Sn core and the other just pure Sn. Four reaction temperatures of 650℃, 675℃, 700℃ and 725℃ and 128 h duration were applied for A15 phase formation heat treatment after Cu-Sn alloying procedure of 210℃/50 h + 340℃/25 h. For the heat-treated coil samples, transport non-Cu JC was examined through standard 4-probe technique and phase microstructure was observed by means of Field Emission Sc...     

Preparation and properties of raney nickel electrodes on Ni-Zn base for H2 and O2 evolution from alkaline solutions Part I: electrodeposition of Ni-Zn alloys from chloride solutions

Experimental results for the electrodeposition of Ni-Zn alloys from chloride solutions, with addition of H₃BO₃ and without other additives, in a laboratory cell with a perforated nickel sheet cathode and with recirculating electrolyte are presented. The dependence of the zinc content in the alloy on the following operating conditions was investigated: cathodic current density, 1.0–20.0 A dm^–2; temperature, 35–65°C; pH 1.5–5.5; total molarity,M _tot=M _Ni ²⁺ +M _Zn ²⁺ =1.1–2.8 M; and, molar ratio,P=M _Ni ²⁺ /M _Zn ²⁺ =1.0–15. Depending on the operating conditions the Zn content in the alloy varied over the range 22–88 mol%. In separate experiments galvanostatic polarization curves were measured in the direction of increasing and then decreasing cathodic current density in the range 0.1–20.0 A dm^–2 with all other operating conditions as used for electroplating experiments. In all cases significant hysteresis effects were observed. It was found that the current efficiency for the electrodeposition of Ni-Zn alloys from chloride solutions as a function of the zinc content in the alloy showed a sharp minimum of about 55% atX _Zn=55 mol % irrespective of other operating conditions.     

Runout effects in milling: Surface finish, surface location error, and stability

This paper investigates the effect of milling cutter teeth runout on surface topography, surface location error, and stability in end milling. Runout remains an important issue in machining because commercially-available cutter bodies often exhibit significant variation in the teeth/insert radial locations; therefore, the chip load on the individual cutting teeth varies periodically. This varying chip load influences the machining process and can lead to premature failure of the cutting edges. The effect of runout on cutting force and surface finish for proportional and non-proportional tooth spacing is isolated here by completing experiments on a precision milling machine with 0.1 μm positioning repeatability and 0.02 μm spindle error motion. Experimental tests are completed with different amounts of radial runout and the results are compared with a comprehensive time-domain simulation. After verification, the simulation is used to explore the relationships between runout, surface finish, stability, and surface location error. A new instability that occurs when harmonics of the runout frequency coincide with the dominant system natural frequency is identified.     

Siamese multi-layer perceptrons for dimensionality reduction and face identification

This paper presents a framework using siamese Multi-layer Perceptrons (MLP) for supervised dimensionality reduction and face identification. Compared with the classical MLP that trains on fully labeled data, the siamese MLP learns on side information only, i.e., how similar of data examples are to each other. In this study, we compare it with the classical MLP on the problem of face identification. Experimental results on the Extended Yale B database demonstrate that the siamese MLP training with side information achieves comparable classification performance with the classical MLP training on fully labeled data. Besides, while the classical MLP fixes the dimension of the output space, the siamese MLP allows flexible output dimension, hence we also apply the siamese MLP for visualization of the dimensionality reduction to the 2-d and 3-d spaces.     

Exact Sampling of a Linear Interval Predictor

Recent advances in the design of interval observers have made it possible to ensure the non‐divergence of the computed state bounds from the stability of LTI systems under bounded inputs, with no need for additional monotony assumptions. Time‐varying changes of coordinates can be used to that purpose. Most of the related works result in either continuous‐time or discrete‐time interval dynamics. This paper proposes a constructive algorithm to compute the exact sampled response of a linear interval predictor under bounded inputs, gives a stability equivalence result and discusses the design of interval observers. The exact sampling requires held input bounds but the uncertain input itself needs not to be held. A numerical example exhibiting an oscillatory behavior illustrates the main results.     

In-focus electron microscopy of frozen-hydrated biological samples with a Boersch phase plate

We report the implementation of an electrostatic Einzel lens (Boersch) phase plate in a prototype transmission electron microscope dedicated to aberration-corrected cryo-EM. The combination of phase plate, C_s corrector and Diffraction Magnification Unit (DMU) as a new electron-optical element ensures minimal information loss due to obstruction by the phase plate and enables in-focus phase contrast imaging of large macromolecular assemblies. As no defocussing is necessary and the spherical aberration is corrected, maximal, non-oscillating phase contrast transfer can be achieved up to the information limit of the instrument. A microchip produced by a scalable micro-fabrication process has 10 phase plates, which are positioned in a conjugate, magnified diffraction plane generated by the DMU. Phase plates remained fully functional for weeks or months. The large distance between phase plate and the cryo sample permits the use of an effective anti-contaminator, resulting in ice contamination rates of <0.6 nm/h at the specimen. Maximal in-focus phase contrast was obtained by applying voltages between 80 and 700 mV to the phase plate electrode. The phase plate allows for in-focus imaging of biological objects with a signal-to-noise of 5-10 at a resolution of 2-3 nm, as demonstrated for frozen-hydrated virus particles and purple membrane at liquid-nitrogen temperature.     

Fast online graph clustering via Erd?s-Rényi mixture

In the context of graph clustering, we consider the problem of simultaneously estimating both the partition of the graph nodes and the parameters of an underlying mixture of affiliation networks. In numerous applications the rapid increase of data size over time makes classical clustering algorithms too slow because of the high computational cost. In such situations online clustering algorithms are an efficient alternative to classical batch algorithms. We present an original online algorithm for graph clustering based on a Erd?s-Rényi graph mixture. The relevance of the algorithm is illustrated, using both simulated and real data sets. The real data set is a network extracted from the French political blogosphere and presents an interesting community organization.