Padé approximations to the logarithm II: Identities, recurrences, and symbolic computation

Combinatorial identities that were needed in [25] are proved, mostly with C. Schneider’s computer algebra package Sigma. The form of the Padé approximation of the logarithm of arbitrary order is stated as a conjecture. 2000 Mathematics Subject Classification Primary—41A21, 05A19, 33F10 Supported by NRF-grant 2047226. Supported by NRF-grant 2053748. Supported by the Austrian Academy of Sciences, by the John Knopfmacher Research Centre for Applicable Analysis and Number Theory, and by the SFB-grant F1305 and the grant P16613-N12 of the Austrian FWF. Supported by NRF-grant 2053756.     

The pros and cons of apoptosis assays for use in the study of cells, tissues, and organs.

Programmed cell death or apoptosis occurs in many tissues during normal development and in the normal homeostasis of adult tissues. Apoptosis also plays a significant role in abnormal development and disease. Increased interest in apoptosis and cell death in general has resulted in the development of new techniques and the revival of old ones. Each assay has its advantages and disadvantages that can render it appropriate and useful for one application, but inappropriate or difficult to use in another. Understanding the strengths and limitations of the assays would allow investigators to select the best methods for their needs.     

Vault ribonucleoprotein particles and the central mass of the nuclear pore complex

Nuclear pore complexes (NPCs) are macromolecular pores that span the nuclear envelope and undergo conformational changes in response to changes in cisternal calcium levels. Depletion of cisternal calcium leads to the appearance of a mass within the pore. The identity and role of this central mass remain unknown, although some studies suggest they are vault complexes. Vault complexes are 13 MDa ribonucleoproteins found in the cytoplasm and recently in the nuclei of some species, suggesting that they associate with NPCs to cross the nuclear envelope. Using Förster resonance energy transfer (FRET) measurements between labeled vaults and NPCs, we find significant energy transfer suggesting that vaults and NPCs are closely associated at the nuclear envelope. This is supported by high‐resolution electron microscopy measurements revealing significant spatial correlations between gold‐labeled vaults and NPCs. As the location of the central mass in the NPC is dependent on cisternal calcium levels, FRET signals under conditions of varying cisternal calcium were also measured and shown to undergo significant changes. Together, these findings suggest that the central mass observed in NPCs may be, at least in part, due to the presence of vaults in the pore. Possible roles in cyto‐nuclear trafficking are discussed.     

Design of new imidazole derivatives with anti-HCMV activity: QSAR modeling,synthesis and biological testing

Journal of Computer-Aided Molecular Design - The problem of designing new antiviral drugs against Human Cytomegalovirus (HCMV) was addressed using the Online Chemical Modeling Environment (OCHEM)....     

Versatile site-specific conjugation of small molecules to siRNA using click chemistry

We have previously demonstrated that conjugation of small molecule ligands to small interfering RNAs (siRNAs) and anti-microRNAs results in functional siRNAs and antagomirs in vivo. Here we report on the development of an efficient chemical strategy to make oligoribonucleotide-ligand conjugates using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) or click reaction. Three click reaction approaches were evaluated for their feasibility and suitability for high-throughput synthesis: the CuAAC reaction at the monomer level prior to oligonucleotide synthesis, the solution-phase postsynthetic "click conjugation", and the "click conjugation" on an immobilized and completely protected alkyne-oligonucleotide scaffold. Nucleosides bearing 5'-alkyne moieties were used for conjugation to the 5'-end of the oligonucleotide. Previously described 2'- and 3'-O-propargylated nucleosides were prepared to introduce the alkyne moiety to the 3' and 5' termini and to the internal positions of the scaffold. Azido-functionalized ligands bearing lipophilic long chain alkyls, cholesterol, oligoamine, and carbohydrate were utilized to study the effect of physicochemical characteristics of the incoming azide on click conjugation to the alkyne-oligonucleotide scaffold in solution and on immobilized solid support. We found that microwave-assisted click conjugation of azido-functionalized ligands to a fully protected solid-support bound alkyne-oligonucleotide prior to deprotection was the most efficient "click conjugation" strategy for site-specific, high-throughput oligonucleotide conjugate synthesis tested. The siRNA conjugates synthesized using this approach effectively silenced expression of a luciferase gene in a stably transformed HeLa cell line.     

Biophysical characterization of DNA binding from single molecule force measurements

Single molecule force spectroscopy is a powerful method that uses the mechanical properties of DNA to explore DNA interactions. Here we describe how DNA stretching experiments quantitatively characterize the DNA binding of small molecules and proteins. Small molecules exhibit diverse DNA binding modes, including binding into the major and minor grooves and intercalation between base pairs of double-stranded DNA (dsDNA). Histones bind and package dsDNA, while other nuclear proteins such as high mobility group proteins bind to the backbone and bend dsDNA. Single-stranded DNA (ssDNA) binding proteins slide along dsDNA to locate and stabilize ssDNA during replication. Other proteins exhibit binding to both dsDNA and ssDNA. Nucleic acid chaperone proteins can switch rapidly between dsDNA and ssDNA binding modes, while DNA polymerases bind both forms of DNA with high affinity at distinct binding sites at the replication fork. Single molecule force measurements quantitatively characterize these DNA binding mechanisms, elucidating small molecule interactions and protein function.     

Reservoir Computing with Delayed Input for Fast and Easy Optimisation

Reservoir computing is a machine learning method that solves tasks using the response of a dynamical system to a certain input. As the training scheme only involves optimising the weights of the responses of the dynamical system, this method is particularly suited for hardware implementation. Furthermore, the inherent memory of dynamical systems which are suitable for use as reservoirs mean that this method has the potential to perform well on time series prediction tasks, as well as other tasks with time dependence. However, reservoir computing still requires extensive task-dependent parameter optimisation in order to achieve good performance. We demonstrate that by including a time-delayed version of the input for various time series prediction tasks, good performance can be achieved with an unoptimised reservoir. Furthermore, we show that by including the appropriate time-delayed input, one unaltered reservoir can perform well on six different time series prediction tasks at a very low computational expense. Our approach is of particular relevance to hardware implemented reservoirs, as one does not necessarily have access to pertinent optimisation parameters in physical systems but the inclusion of an additional input is generally possible.