Structure-based design of supercharged, highly thermoresistant antibodies

Mutation of surface residues to charged amino acids increases resistance to aggregation and can enable reversible unfolding. We have developed a protocol using the Rosetta computational design package that "supercharges" proteins while considering the energetic implications of each mutation. Using?a homology model, a single-chain variable fragment antibody was designed that has a markedly enhanced resistance to thermal inactivation and displays an unanticipated ≈30-fold improvement in affinity. Such supercharged antibodies should prove useful for assays in resource-limited settings and for developing reagents with improved shelf lives.     

Quantifying intermittency in the open drivebelt billiard

A "drivebelt" stadium billiard with boundary consisting of circular arcs of differing radius connected by their common tangents shares many properties with the conventional "straight" stadium, including hyperbolicity and mixing, as well as intermittency due to marginally unstable periodic orbits (MUPOs). Interestingly, the roles of the straight and curved sides are reversed. Here, we discuss intermittent properties of the chaotic trajectories from the point of view of escape through a hole in the billiard, giving the exact leading order coefficient lim(t→∞)tP(t) of the survival probability P(t) which is algebraic for fixed hole size. However, in the natural scaling limit of small hole size inversely proportional to time, the decay remains exponential. The big distinction between the straight and drivebelt stadia is that in the drivebelt case, there are multiple families of MUPOs leading to qualitatively new effects. A further difference is that most marginal periodic orbits in this system are oblique to the boundary, thus permitting applications that utilise total internal reflection such as microlasers.     

Three-dimensional biomolecule patterning

A new method is demonstrated, where three-dimensional protein structures are made by employing multi-photon polymerization and photobiotin photolysis. The technique enables the construction of arbitrary two- and three-dimensional shapes with submicron resolution. The integrity of the immobilized biotin is confirmed by derivatization with fluorescently labeled streptavidin. Fluorescence microscopy is used in order to visualize the distribution of fluorescent streptavidin on the 3D structure.     

Photochemical effects in the UV laser ablation of polymers: Implications for laser restoration of painted artworks

0 ∝t^1/2. The best results are expected for a circular top-hat beam shape. Received: 15 January 1999 / Accepted: 18 January 1999     

Toward Hybrid Materials: Group Transfer Polymerization of 3‐(Trimethoxysilyl)propyl Methacrylate

In this study, the group transfer polymerization (GTP) of the functional monomer 3‐(trimethoxysilyl)propyl methacrylate (TMSPMA) is reported to produce polymers of different architectures and topologies. TMSPMA is successfully polymerized and copoly­merized with GTP to produce well‐defined (co)polymers that can be used to fabricate functional hybrid materials like hydrogels and films.

     

On the compact open and finest splitting topologies

In [M.H. Escardo, J. Lawson, A. Simpson, Comparing cartesian closed categories of (core) compactly generated spaces, Topology Appl. 143 (2004) 105-145] it is shown that in the set C(Nω,N) of all continuous maps of Nω into N, where N is an infinitely countable discrete topological space, the compact-open topology is not the finest splitting topology. Since Nω is consonant (see [S. Dolecki, G.H. Greco, A. Lechicki, When do the upper Kuratowski topology (homeomorphically, Scott topology) and the co-compact topology coincide? Trans. Amer. Math. Soc. 347 (1995) 2869-2884]) the Isbell topology on C(Nω,N) also is not the finest splitting topology. This result is generalized in the present paper proving that it is true also for spaces having the so-called Specific Extension Property. The following spaces have the Specific Extension Property: (a) infinitely countable free unions of non-empty spaces, (b) non-compact Lindelöf zero-dimensional spaces, and (c) metric locally convex linear spaces. In particular, we prove that on the set of all real-valued functions on the (separable infinite dimensional) Hilbert space the compact-open topology does not coincide with the finest splitting topology.