Content-dependent chunking for differential compression,the local maximum approach

When a file is to be transmitted from a sender to a recipient and when the latter already has a file somewhat similar to it, remote differential compression seeks to determine the similarities interactively so as to transmit only the part of the new file not already in the recipient's old file. Content-dependent chunking means that the sender and recipient chop their files into chunks, with the cutpoints determined by some internal features of the files, so that when segments of the two files agree (possibly in different locations within the files) the cutpoints in such segments tend to be in corresponding locations, and so the chunks agree. By exchanging hash values of the chunks, the sender and recipient can determine which chunks of the new file are absent from the old one and thus need to be transmitted.We propose two new algorithms for content-dependent chunking, and we compare their behavior, on random files, with each other and with previously used algorithms. One of our algorithms, the local maximum chunking method, has been implemented and found to work better in practice than previously used algorithms.Theoretical comparisons between the various algorithms can be based on several criteria, most of which seek to formalize the idea that chunks should be neither too small (so that hashing and sending hash values become inefficient) nor too large (so that agreements of entire chunks become unlikely). We propose a new criterion, called the slack of a chunking method, which seeks to measure how much of an interval of agreement between two files is wasted because it lies in chunks that don't agree.Finally, we show how to efficiently find the cutpoints for local maximum chunking.     

Using Computer Algebra techniques for the specification,verification and synthesis of recursive programs

We describe an innovative method for proving total correctness of tail recursive programs having a specific structure, namely programs in which an auxiliary tail recursive function is driven by a main nonrecursive function, and only the specification of the main function is provided. The specification of the auxiliary function is obtained almost fully automatically by solving coupled linear recursive sequences with constant coefficients. The process is carried out by means of CA (Computer Algebra) and AC (Algorithmic Combinatorics) and is implemented in the Theorema system (using Mathematica). We demonstrate this method on an example involving polynomial expressions. Furthermore, we develop a method for synthesis of recursive programs for computing polynomial expressions of a fixed degree by means of “cheap” operations, e.g., additions, subtractions and multiplications. For a given polynomial expression, we define its recursive program in a schemewise manner. The correctness of the synthesized programs follows from the general correctness of the synthesis method, which is proven once for all, using the verification method presented in the first part of this paper.     

Proteomic analysis of human osteoprogenitor response to disordered nanotopography

Previous studies have shown that microgroove-initiated contact guidance can induce bone formation in osteoprogenitor cells (OPGs) and produce changes in the cell proteome. For proteomic analysis, differential in-gel electrophoresis (DIGE) can be used as a powerful diagnostic method to provide comparable data between the proteomic profiles of cells cultured in different conditions. This study focuses on the response of OPGs to a novel nanoscale pit topography with osteoinductive properties compared with planar controls. Disordered near-square nanopits with 120 nm diameter and 100 nm depth with an average 300 nm centre-to-centre spacing (300 nm spaced pits in square pattern, but with ±50 nm disorder) were fabricated on 1×1 cm² polycaprolactone sheets. Human OPGs were seeded onto the test materials. DIGE analysis revealed changes in the expression of a number of distinct proteins, including upregulation of actin isoforms, beta-galectin1, vimentin and procollagen-proline, 2-oxoglutarate 4-dioxygenase and prolyl 4-hydroxylase. Downregulation of enolase, caldesmon, zyxin, GRASP55, Hsp70 (BiP/GRP78), RNH1, cathepsin D and Hsp27 was also observed. The differences in cell morphology and mineralization are also reported using histochemical techniques.     

Learning from directed evolution: Further lessons from theoretical investigations into cooperative mutations in lipase enantioselectivity

An earlier experimental study, which involved the directed evolution of enantioselective lipase variants from Pseudomonas aeruginosa as catalysts in the hydrolytic kinetic resolution of 2-methyl-decanoic acid p-nitrophenyl ester, provided a mutant with six mutations. Consequently, the selectivity factor was found to increase from E = 1.1 for the wild-type to E = 51 for the best mutant. Only one of the amino acid exchanges in this mutant was found to occur next to the binding pocket, the other mutations being remote. Our previous theoretical analysis with molecular-dynamics simulations helped to unveil the source of enhanced enantioselectivity: a relay mechanism that involves two of the six mutations was shown to induce strong cooperativity. In this investigation, single, double, and triple mutants were constructed and tested as enantioselective catalysts. This study supports our original postulate regarding the relay mechanism, offers further mechanistic insight into the role of individual mutations, and provides mutants that display even higher enantioselectivity (E of up to 64).     

Complex Permeability of Ferrites as Intrinsic and Extrinsic Properties

CIP （complex initial permeability） spectra of PF （polycrystalline ferrite） are studied both as intrinsic and extrinsic properties. In the former case, main steps of modeling, based on effects coming from polycrystal grain sizes distribution and defects, are described. The obtained relations work well in practice for PF with more or less normal MS （microstructure） and no size effects. Besides, fundamental connection between parameters of CIP and MS is found. Another case--PF with possible size effects （MnZn-ferrites） are studied experimentally for different sizes of cores, unveiling the dependence of phenomena on： dimensions of cross-section, number of turns, width of nonmagnetic gap.     

Synthesis and preliminary biological evaluation of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives as group I selective metabotropic glutamate receptor ligands

The first series of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives, (2R)- and (2S)-(2',2'-dichloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (10) and (11), and 2-(2'-chloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (12) were synthesized and evaluated as mGluR ligands. Compounds 11 and 12 were shown to be competitive group I mGluR antagonists. These results are also discussed in light of docking studies with both the active (closed) and inactive (open) conformations of mGluR1.     

Engineering Pyrrolysyl-tRNA Synthetase for the Incorporation of Non-Canonical Amino Acids with Smaller Side Chains

Site-specific incorporation of non-canonical amino acids (ncAAs) into proteins has emerged as a universal tool for systems bioengineering at the interface of chemistry, biology, and technology. The diversification of the repertoire of the genetic code has been achieved for amino acids with long and/or bulky side chains equipped with various bioorthogonal tags and useful spectral probes. Although ncAAs with relatively small side chains and similar properties are of great interest to biophysics, cell biology, and biomaterial science, they can rarely be incorporated into proteins. To address this gap, we report the engineering of PylRS variants capable of incorporating an entire library of aliphatic “small-tag” ncAAs. In particular, we performed mutational studies of a specific PylRS, designed to incorporate the shortest non-bulky ncAA (S-allyl-l-cysteine) possible to date and based on this knowledge incorporated aliphatic ncAA derivatives. In this way, we have not only increased the number of translationally active “small-tag” ncAAs, but also determined key residues responsible for maintaining orthogonality, while engineering the PylRS for these interesting substrates. Based on the known plasticity of PylRS toward different substrates, our approach further expands the reassignment capacities of this enzyme toward aliphatic amino acids with smaller side chains endowed with valuable functionalities.