Supramolecular copolymers: structure and composition revealed by theoretical modeling

Supramolecular copolymers, non-covalent analogues of synthetic copolymers, constitute a new and promising class of polymers. In contrast to their covalent counterparts, the details of their mechanism of formation, as well as the factors determining their composition and length, are still poorly understood. Here, the supramolecular copolymerization between two slightly structurally different benzene-1,3,5-tricarboxamide (BTA) monomers functionalized with either oligodimethylsiloxane (oDMSi) or alkyl side chains is unraveled by combining experimental and theoretical approaches. By applying the “sergeant-and-soldiers” approach using circular dichroism (CD) experiments, we are able to obtain detailed insights into the structure and composition of these supramolecular copolymers. Moreover, we observe an unexpected chiral induction upon mixing two independently CD-silent solutions of the achiral (soldier) and chiral (sergeant) monomers. We find that the subtle differences in the chemical structure of the two monomers impact their homopolymerization mechanism: whereas alkyl-BTAs cooperatively self-assemble, oDMSi-BTAs self-assemble in an isodesmic manner. The effect of these mechanistic differences in the supramolecular copolymerization process is investigated as a function of the composition of the two monomers and explicitly rationalized by mathematical modeling. The results show that, at low fractions of oDMSi-BTA sergeants (25 mol%), the isodesmic assembly of the increasing amounts of sergeant becomes more dominant, and different species start to coexist in the copolymerization process. The analysis of the experimental data with a newly developed theoretical model allows us to quantify the thermodynamic parameters, the distribution of different species, and the compositions and stack lengths of the formed supramolecular copolymers existing at various feed ratios of the two monomers.This work was financially supported by The Netherlands Organization for Scientific Research (NWO-TOP PUNT Grant 10018944) and the Dutch Ministry of Education, Culture and Science (Gravity Program 024.001.035)

Hemichannel-Mediated and pH-Based Feedback from Horizontal Cells to Cones in the Vertebrate Retina

Background: Recent studies designed to identify the mechanism by which retinal horizontal cells communicate with cones have implicated two processes. According to one account, horizontal cell hyperpolarization induces an increase in pH withinthe synaptic cleft that activates the calcium current (Ca2+-current) in cones, enhancing transmitter release. An alternative account suggests that horizontal cell hyperpolarization increases the Ca2+-current to promote transmitter release through ahemichannel-mediated ephaptic mechanism.Methodology/Principal Findings: To distinguish between these mechanisms, we interfered with the pH regulating systems in the retina and studied the effects on the feedback responses of cones and horizontal cells. We found that the pH buffers HEPES and Tris partially inhibit feedback responses in cones and horizontal cells and lead to intracellular acidification ofneurons. Application of 25 mM acetate, which does not change the extracellular pH buffer capacity, does lead to both intracellular acidification and inhibition of feedback. Because intracellular acidification is known to inhibit hemichannels, the key experiment used to test the pH hypothesis, i.e. increasing the extracellular pH buffer capacity, does not discriminatebetween a pH-based feedback system and a hemichannel-mediated feedback system. To test the pH hypothesis in a manner independent of artificial pH-buffer systems, we studied the effect of interfering with the endogenous pH buffer, the bicarbonate/carbonic anhydrase system. Inhibition of carbonic anhydrase allowed for large changes in pH in the synapticcleft of bipolar cell terminals and cone terminals, but the predicted enhancement of the cone feedback responses, according to the pH-hypothesis, was not observed. These experiments thus failed to support a proton mediated feedback mechanism. The alternative hypothesis, the hemichannel-mediated ephaptic feedback mechanism, was therefore studied experimentally, and its feasibility was buttressed by means of a quantitative computer model of the cone/horizontal cellsynapse.Conclusion: We conclude that the data presented in this paper offers further support for physiologically relevant ephaptic interactions in the retina

Press reslease from the Premier and Tourism Minister, Mr Dunstan: New amenity block for Moonta Bay Caravan Park

Getting rid of the tubes: An assessment of the retention of functionalized multi-walled carbon nanotubes (MWNTs) in the organs of mice was carried out using single photon emission computed tomography and quantitative scintigraphy (see scheme). Increasing the degree of functionalization on MWNTs enhanced renal clearance, while lower functionalization promoted reticuloendethelial system accumulation

Synaptic Transmission from Horizontal Cells to Cones Is Impaired by Loss of Connexin Hemichannels

In the vertebrate retina, horizontal cells generate the inhibitory surround of bipolar cells, an essential step in contrast enhancement. For the last decades, the mechanism involved in this inhibitory synaptic pathway has been a major controversy in retinal research. One hypothesis suggests that connexin hemichannels mediate this negative feedback signal; another suggests that feedback is mediated by protons. Mutant zebrafish were generated that lack connexin 55.5 hemichannels in horizontal cells. Whole cell voltage clamp recordings were made from isolated horizontal cells and cones in flat mount retinas. Light-induced feedback from horizontal cells to cones was reduced in mutants. A reduction of feedback was also found when horizontal cells were pharmacologically hyperpolarized but was absent when they were pharmacologically depolarized. Hemichannel currents in isolated horizontal cells showed a similar behavior. The hyperpolarization-induced hemichannel current was strongly reduced in the mutants while the depolarization-induced hemichannel current was not. Intracellular recordings were made from horizontal cells. Consistent with impaired feedback in the mutant, spectral opponent responses in horizontal cells were diminished in these animals. A behavioral assay revealed a lower contrast-sensitivity, illustrating the role of the horizontal cell to cone feedback pathway in contrast enhancement. Model simulations showed that the observed modifications of feedback can be accounted for by an ephaptic mechanism. A model for feedback, in which the number of connexin hemichannels is reduced to about 40%, fully predicts the specific asymmetric modification of feedback. To our knowledge, this is the first successful genetic interference in the feedback pathway from horizontal cells to cones. It provides direct evidence for an unconventional role of connexin hemichannels in the inhibitory synapse between horizontal cells and cones. This is an important step in resolving a long-standing debate about the unusual form of (ephaptic) synaptic transmission between horizontal cells and cones in the vertebrate retina

On the knowledge of students and professors at Eindhoven UNiversity of Technology

Using methods from statistical learning theory we compute the Vapnik-Chervonenkis dimension of full professors and students of the Eindhoven University of Technology. The results are surprising and disappointing. Furthermore, it is shown that during their study the students must have learned things on which professors have no knowledge at all. This leads to the mathematical proof of the existence of an additional group of teaching personal at the university

Infinite hierarchies of t‐independent and t‐dependent conserved functionals of the Federbush model

The construction of four infinite hierarchies of t-independent and t-dependent conserved functionals for the Federbush model is given. A formal proof of the existence of these infinite hierarchies is given in Appendix B