The Sweetness Barrier

The Sweetness Barrier is a collection of eight short stories representative of the impact the food industry has had on North America. Unlike other popular Canadian food writing, which focuses on the jovial and humorous aspects of food culture, this collection details the ways in which we, consumers and producers of food, have been eating, growing, buying, and distributing irresponsibly. While food may aid in emotional, mental and physical recovery, this thesis highlights the ways it also wreaks havoc, ravishes and destroys us. The convictions behind this work originate in Samuel de Champlain\u27s Order of Good Cheer and in the idea that we are healed when we eat and celebrate together, and are explored further by illustrating how Western society has become increasingly atomized as consequence of our collective, albeit perhaps unconscious, refusal to eat together at the dinner table

Nonlinear hopping transport in ring systems and open channels

We study the nonlinear hopping transport in one-dimensional rings and open channels. Analytical results are derived for the stationary current response to a constant bias without assuming any specific coupling to the external fields. It is shown that anomalous large effective jump lengths, as observed in recent experiments by taking the ratio of the third order nonlinear and the linear conductivity, can occur already in ordered systems. Rectification effects due to site energy disorder in ring systems are expected to become irrelevant for large system sizes. In open channels in contrast, rectification effects occur already for disorder in the jump barriers and do not vanish in the thermodynamic limit. Numerical solutions for a sinusoidal bias show that the ring system provides a good description for the transport behavior in the open channel for intermediate and high frequencies. For low frequencies temporal variations in the mean particle number have to be taken into account in the open channel, which cannot be captured in the more simple ring model.Comment: 25 pages, 7 figure

Investing in Emerging and Frontier Economies: How Blended Finance can make the most of public funding

Combating climate change and achieving the SDGs require vast investment in sustainable projects in developing countries, but the world is falling short.A crucial reason is that a rich source of funds is not being fully tapped into: the private sector, which is eager to significantly increase its sustainable investments, but is constrained by avoidable obstacles.Private investors face an unattractive risk-return nexus; they lack easy access to crucial information: e.g. which projects the public sector is planning that they could take part in, and what they entail.Exposure to the risks of investing in less mature markets, with insufficient insurance available, deters them as well.In this report, the Investor Leadership Network (ILN), whose members manage over USD 9 trillion of investments, offers solutions.It calls for better collaboration between public and private sectors to make blended finance (public/private investment partnerships) a driving force in this area.Compiled with the support of The Rockefeller Foundation, the report calls for a sea change in how multilateral development banks (MDBs), governments, foundations, and other public institutions see private-sector involvement

Model Channel Ion Currents in NaCl - SPC/E Solution with Applied-Field Molecular Dynamics

Using periodic boundary conditions and a constant applied field, we have simulated current flow through an 8.125 Angstrom internal diameter, rigid, atomistic channel with polar walls in a rigid membrane using explicit ions and SPC/E water. Channel and bath currents were computed from ten 10-ns trajectories for each of 10 different conditions of concentration and applied voltage. An electric field was applied uniformly throughout the system to all mobile atoms. On average, the resultant net electric field falls primarily across the membrane channel, as expected for two conductive baths separated by a membrane capacitance. The channel is rarely occupied by more than one ion. Current-voltage relations are concentration-dependent and superlinear at high concentrations.Comment: Accepted for publication in Biophysical Journa

Free energy barrier for melittin reorientation from a membrane-bound state to a transmembrane state

An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight into understanding peptide and lipid properties that influence the existence of the free energy barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free energy barrier is reduced when the P/L ratio increased. In addition, we study the cooperative effect; specifically we investigate if the barrier is smaller for a second melittin reorientation, given that another neighboring melittin was already in the transmembrane state. We observe that indeed the barrier of the PMF curve is reduced in this case, thus confirming the presence of a cooperative effect

Cooperative Transition between Open and Closed Conformations in Potassium Channels

Potassium (K+) ion channels switch between open and closed conformations. The nature of this important transition was revealed by comparing the X-ray crystal structures of the MthK channel from Methanobacterium thermoautotrophicum, obtained in its open conformation, and the KcsA channel from Streptomyces lividans, obtained in its closed conformation. We analyzed the dynamic characteristics and energetics of these homotetrameric structures in order to study the role of the intersubunit cooperativity in this transition. For this, elastic models and in silico alanine-scanning mutagenesis were used, respectively. Reassuringly, the calculations manifested motion from the open (closed) towards the closed (open) conformation. The calculations also revealed a network of dynamically and energetically coupled residues. Interestingly, the network suggests coupling between the selectivity filter and the gate, which are located at the two ends of the channel pore. Coupling between these two regions was not observed in calculations that were conducted with the monomer, which emphasizes the importance of the intersubunit interactions within the tetrameric structure for the cooperative gating behavior of the channel

Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels

Comparison of the crystal structures of the KcsA and MthK potassium channels suggests that the process of opening a K+ channel involves pivoted bending of the inner pore-lining helices at a highly conserved glycine residue. This bending motion is proposed to splay the transmembrane domains outwards to widen the gate at the “helix-bundle crossing”. However, in the inwardly rectifying (Kir) potassium channel family, the role of this “hinge” residue in the second transmembrane domain (TM2) and that of another putative glycine gating hinge at the base of TM2 remain controversial. We investigated the role of these two positions in heteromeric Kir4.1/Kir5.1 channels, which are unique amongst Kir channels in that both subunits lack a conserved glycine at the upper hinge position. Contrary to the effect seen in other channels, increasing the potential flexibility of TM2 by glycine substitutions at the upper hinge position decreases channel opening. Furthermore, the contribution of the Kir4.1 subunit to this process is dominant compared to Kir5.1, demonstrating a non-equivalent contribution of these two subunits to the gating process. A homology model of heteromeric Kir4.1/Kir5.1 shows that these upper “hinge” residues are in close contact with the base of the pore α-helix that supports the selectivity filter. Our results also indicate that the highly conserved glycine at the “lower” gating hinge position is required for tight packing of the TM2 helices at the helix-bundle crossing, rather than acting as a hinge residue

On Conduction in a Bacterial Sodium Channel

Voltage-gated Na+-channels are transmembrane proteins that are responsible for the fast depolarizing phase of the action potential in nerve and muscular cells. Selective permeability of Na+ over Ca2+ or K+ ions is essential for the biological function of Na+-channels. After the emergence of the first high-resolution structure of a Na+-channel, an anionic coordination site was proposed to confer Na+ selectivity through partial dehydration of Na+ via its direct interaction with conserved glutamate side chains. By combining molecular dynamics simulations and free-energy calculations, a low-energy permeation pathway for Na+ ion translocation through the selectivity filter of the recently determined crystal structure of a prokaryotic sodium channel from Arcobacter butzleri is characterised. The picture that emerges is that of a pore preferentially occupied by two ions, which can switch between different configurations by crossing low free-energy barriers. In contrast to K+-channels, the movements of the ions appear to be weakly coupled in Na+-channels. When the free-energy maps for Na+ and K+ ions are compared, a selective site is characterised in the narrowest region of the filter, where a hydrated Na+ ion, and not a hydrated K+ ion, is energetically stable