Voltage-sensitive potassium ion channels are essential for life, but the molecular basis of their ion conduction is not well understood. In particular, the impact of ion concentration on ion conduction has not been fully studied. We performed several micro-second molecular dynamics simulations of the pore domain of the Kv1.2 potassium channel in KCl solution at four different ion concentrations, and scrutinized each of the conduction events, based on graphical representations of the simulation trajectories. As a result, we observed that the conduction mechanism switched with different ion concentrations: at high ion concentrations, potassium conduction occurred by Hodgkin and Keynes' knock-on mechanism, where the association of an incoming ion with the channel is tightly coupled with the dissociation of an outgoing ion, in a one-step manner. On the other hand, at low ion concentrations, ions mainly permeated by a two-step association/dissociation mechanism, in which the association and dissociation of ions were not coupled, and occurred in two distinct steps. We also found that this switch was triggered by the facilitated association of an ion from the intracellular side within the channel pore and by the delayed dissociation of the outermost ion, as the ion concentration increased.
Copyright: © 2013 Kasahara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was funded by the "HD-Physiology" Grant-in-Aid for Scientific Research on Innovative Areas (22136005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Ion channels play essential roles in establishing accurate communications across plasma membranes. In particular, potassium (K+) ion channels are the most ubiquitously distributed proteins throughout the living world, conducting K+ ions with extreme selectivity, as compared to sodium ions –. In higher eukaryotes such as mammals, the K+ current through these channels is finely regulated, on the bases of the K+ gradient across the plasma membrane (∼5 mM and ∼100 mM outside and inside the cell, respectively) and the membrane voltage, and thus plays crucial roles in neuronal activities and the electrical conduction system of the heart. Illuminating the nature of this family of proteins is critically important to understand the molecular basis of living organisms.
The crystal structures of the ion channels have provided variable information to understand the molecular mechanisms of K+ conduction –. The ion conduction pore, which is formed by the interface of a homo-tetramer, can be roughly divided into two parts: the central cavity and the selectivity filter (SF). The SF, a quite narrow pore consisting of four residues (Thr-Val-Gly-Tyr) in each monomer, is the main player in the discrimination of K+ ions from other ions , . From the crystal structures, the ion-binding sites in the SF were also identified, and it is considered to conduct K+ ions in a stepwise, single-file manner , .
To describe the dynamics of the K+ conduction processes by the SF, two possible different models have been proposed. In the one-step, "knock-on" model by Hodgkin and Keynes , K+ conductions are considered to occur by repeating a single step, where an incoming ion from the intracellular side enters the SF and the outermost ion in the SF is pushed out at the same time. On the other hand, in the two-step association/dissociation model (A/D model) by Nelson , , conductions are considered to occur in a two-step manner, called the association step and the dissociation step, where the dissociation of the ion at the outermost site is followed by the subsequent association of a new ion from the intracellular side. These mechanisms are difficult to observe directly by experimental techniques, and thus it has been hard to discriminate the models.
One of the powerful ways to gain insight into biological phenomena at the molecular level is the molecular dynamics (MD) approach, which can calculate the time courses of molecular systems, based on Newtonian mechanics. This method has been extensively applied to analyze the dynamics of ion conductions –, but this approach is quite computationally demanding, because long simulation times are required for statistically relevant discussions of ion conductions.
One important milestone of MD approaches to ion conductions was presented by Jensen et al. . They achieved microsecond-scale MD simulations with a voltage sensitive K+ channel from rat brain (Kv1.2), by using specialized hardware for MD simulations . Their simulations revealed that K+ conductions by the Kv1.2 channel pore follow Hodgkin and Keynes's knock-on model, but their simulations were performed with a 600 mM KCl solution, where the ion conductance is considered to be saturated . Their simulations were mainly focused on the voltage sensitivity of the ion channels, and thus their strategy to observe as many ion conductions as possible is quite reasonable. However, the extremely high ion concentration may cause some differences in the dynamic behaviors at the atomistic scale from lower ion concentration, e.g., physiological ion concentration .
In this study, we focused on the ion concentration effects on ion conduction, and presented distinct observations of K+ conductions by the same Kv1.2 channel as in Jensen's simulation. In our simulations, we used four systems with different ion concentrations, from 150 mM to 600 mM, with intervals of 150 mM. We performed long-term 3.0 µs MD simulations in total (1.0 µs for the 150 mM and 600 mM conditions, and 0.5 µs for the intermediate (300 mM and 450 mM) conditions). In addition, we analyzed the mechanisms of ion conduction from the trajectories by using an "ion-binding state graph", where a set of binding positions of the K+ ions in the pore is treated as a node, and transitions among the states are treated as edges. As a result, we found that the ion conduction behavior gradually changes from the two-step A/D model at lower concentrations to the knock-on model at higher concentrations.
We successfully observed repeating ion conduction events in the systems consisting of a homo-tetrameric pore domain of the Kv1.2 channel protein (which includes S5, S6, and the S4–S5 linker helices, obtained from PDB-ID: 2r9r), a POPE membrane, and KCl solution. We used four different concentrations of KCl: 150 mM, 300 mM, 450 mM, and 600 mM (Fig. 1; the numbers of waters and ions in each system are shown in Table S1), and each simulation time was 1.0 µs, 0.5 µs, 0.5 µs, and 1.0 µs, respectively. The system at the highest ion concentration (600 mM) was quite similar to that investigated by Jensen et al. . During the simulations, the temperature and pressure were maintained at 310 K and 1.0 bar, respectively.
Figure 1. The simulation system at the 600 mM ion concentration.
The system is composed of a homotetrameric Kv1.2 channel with paddle chimera (PDB-ID: 2r9r; shown as cyan ribbons), a POPE membrane (shown as gray sticks), and a KCl solution (waters, potassium ions, and chloride ions are depicted as red dots, green balls, and cyan balls, respectively). The electric field was applied toward the extracellular side (shown as the arrow labeled 'E').
In these simulations, an electric field was applied to the entire system to as 920 mV of the membrane voltage, calculated by the following equation: V = ELz (V denotes the voltage, E denotes the electric field, and Lz denotes the length of simulation box along z-axis). This condition is roughly consistent with the previous simulation by Jensen et al. referred as 123 mV of the membrane voltage in their paper , because they calculated the membrane voltage by the equation: V = EΔz (Δz is the length of the SF). It should be noted that the membrane potential which a channel experiences under the electric field is equal to the potential drop not over the SF but over the entire system as demonstrated by Roux and colleagues by using the Poisson-Boltzmann equation  and all-atom MD simulations . These theoretical studies are now widely accepted and Jensen et al. have changed the way to calculate the membrane voltage in their recent work .
In our simulations, 30, 31, 27, and 71 K+ ions permeated through the pore, at the four ion concentrations in ascending order, which were equivalent to 4.8 pA, 9.9 pA, 8.7 pA and 11 pA, respectively. The order of magnitude and the ratio of these values roughly agree with the experimental results with a Shaker channel, reported by Heginbotham and MacKinnon , and are comparable to the previous simulation by Jensen et al. . There was an increasing trend in conductance with ion concentration, except for the lower conductance at 450 mM than that at 300 mM. This can be interpreted as trivial differences in the initial coordinates of each atom, which can produce such an exceptional outcome. Thus, even the long sampling over submicro-second may still be insufficient to estimate quantitatively the correct conductance, although the behaviors of the systems are qualitatively consistent.
As an example of some ion conduction events, a part of trajectory including some ion conduction processes at 150 mM ion concentration is shown in Movie S1 and Fig. S1.
To describe the ion conduction events through the channel pore schematically, we followed the definition of K+ binding sites based on carboxyl groups of the SF, as described by Jensen et al. . With this definition, the pore has four internal ion binding sites, named S1–4, and three additional peripheral sites, called S0, S5, and the central cavity, denoted as S6 (Fig. 2A).
Figure 2. Trajectories of K+ ions.
(A) The structure of the selectivity filter consisting of four residues (Thr-Val-Gly-Tyr) is shown with an additional Gly residue, to clarify the binding sites. Green, red, and white balls represent potassium, oxygen, and hydrogen atoms, respectively. (B, D) Trajectories of each K+ ion in the pore along the simulation time, for the simulations at 150 mM and 600 mM. The color of each line corresponds to the ID of each K+ ion. The pore axis is defined as the line between the centers of the four backbone carbonyl oxygen atoms of Thr-374 and those of Tyr-377. (C, E) Densities of K+ ion position (green line) and water molecule positions (blue line) at 150 mM (C) and at 600 mM (E) K+ ion concentrations.
Firstly, the occupancy of the ion-binding sites was analyzed from the density maps of the ion locations along the pore axis. The results revealed the use of distinct sets of ion binding sites between the low and high ion concentrations (Fig. 2C and E). The density distribution at the highest ion concentration (600 mM; Fig. 2E) clearly shows that the conducted K+ ions bound exclusively to S0, S2, and S4, and the waters bound exclusively to the intervening sites: i.e., S1 and S3. Note that water molecules did not always intervene the K+ ions; ratios of the number of conducted water molecules over those of K+ ions were 0.83, 0.84, 0.67, and 0.79, at the four ion concentrations in the ascending order, respectively. This result roughly agreed with an experiment reported by Ando et al. . In the case of the lowest ion concentration (150 mM), the K+ ions were also retained in S1 and S3, in addition to the three sites used at the high ion concentration (Fig. 2C). This result qualitatively agreed with the electron density map around the selectivity filter of a KcsA channel at a 200 mM ion concentration, presented by Morais-Cabral et al. . Furthermore, the peaks at S1 for K+ ions and waters overlapped well, which means that the K+ ions and waters can use the same binding sites, in contrast to the case of conduction at the high ion concentration. At the 300 mM and 450 mM concentrations, the systems show intermediate properties between 150 mM and 600 mM (Fig. S2). From these observations, we concluded that the binding sites usage gradually changes with the increasing ion concentration of the solution, which implies that changes in the ion concentration can cause differences in the ion conduction mechanisms.
We then monitored the number of K+ ions bound to the pore in each of the ion concentrations. At higher ion concentrations, larger number of ions were kept in the pore (Fig. S3). At 600 mM, the pore almost always retained three or four ions, because ions were continuously supplied from the intracellular fluid. In contrast, at 150 mM, the pore had only two ions during about half of the simulation time. This indicates that the release of the third ion from the pore in the three ion states occurred rapidly than the provision of a new ion at the lower ion concentrations.
The results described above imply that K+ ions are conducted in different manners between the high and low ion concentrations. To clarify the difference, the ion conduction processes were analyzed, using a graphical representation of the ion-binding states of the pore (Fig. 3 and Fig. S4, S5, and S6). The graph is referred to as "ion-binding state graph", and its definition is described below.
Figure 3. Ion-binding state graph.
The ion-binding state graph for the simulation at 150 mM ion concentration. A node and an edge indicate the state of the binding ions in the pore, and the transition between two states, respectively. The size and color of each node mean log existence probability of the state during the simulation. The red edges mean that a new K+ ion is entering from the intracellular side, and the blue ones indicate that an ion in S0 is exiting to the extracellular side. The nodes are classified into the four groups: II, IIIr, IIIe, and IV, for the following discussion. The two major ways to conduct K+ are shown as cyan and pink bold arrows (see the main text for details). The graph was drawn with Cytoscape 2.8 .
The ion-binding state graphs were drawn according to the following steps: (i) the seven binding sites, S0–6, were identified by the pore axis coordinates (the thresholds of each site are shown as dashed lines in Fig. 2A; see Text S1 for details), (ii) the ion-binding states of the pore were defined based on the combinations of the binding sites containing ions; for example, when K+ ions bound to S0, S2, and S4, this state was denoted as "K∶0∶2∶4", (iii) the ion-binding state in each snapshot was recorded, and a graph was drawn from the information about the frequencies of each state and that of the transitions between pairs of states. Here, a node means an ion-binding state, and a directed edge means a transition from one state to another. In addition, color and size of a node show the log existence probability of each state (more stable states are shown as brighter and larger). Each ion-binding state graph summarizes all of the ion-binding states and transitions observed during each simulation. Note that, in contrast to the schematic diagrams previously used –, we explicitly considered the peripheral binding sites (denoted as S0, S5, and S6), in addition to the sites in the SF. We confirmed that the systems stationary behaved during the simulations, by comparing the existence probabilities of each ion-biding state between the first and last half of the simulation time (Fig. S7).
Figure 3 represents an ion-binding state graph for the 1.0 µs simulation at the 150 mM ion concentration. In this simulation, 42 states and 211 edges were identified. To interpret the ion-binding state graph, we will focus on two important events: the dissociation of the K+ ion in S0 to the extracellular side (blue arrows), and the association of a new K+ ion from the intracellular side (red arrows). K+ ion conductions occurred with repeating alternate transitions between these dissociation and association events.
For the following discussion, the ion-binding states are classified into four groups, II, IIIr, IIIe, and IV, indicating the two-ion states, the three-ion states grouped with the "resting state", the three-ion states as the "entrance" to the resting states (the meaning of it will be described later), and the four-ion states, respectively. According to this classification, Fig. 3 can be simplified as Fig. 4A, and it emphasizes the two significant events, i.e., the association and the dissociation of an ion. The system at the IIIe state can easily transit to IIIr (many bold arrows from IIIe to IIIr, as shown in Fig. 3). Therefore, we can see the two types of cyclic pathways in this graph: (a) IIIr, II, IIIe, IIIr, and (b) IIIr, IV, IIIe, IIIr, shown in the order of the passed groups. This result indicated that the conduction of K+ ions can occur in one of two ways; that is, (a) via the two-ion states, and (b) via the four-ion states.
Figure 4. Simplified ion-binding state graphs.
A simplified version of the ion-binding state graph shown in Fig. 3, according to the four groups of ion-binding states: II, IIIr, IIIe, and IV. Nodes labeled as II, IIIr, IIIe, and IV are correspond to the sets of ion-binding sites shown in the Fig. 3. (A) 150 mM. (B) 600 mM.
We also analyzed the time courses of the system on the graphs. In the simulation, the system began with the state K∶0∶2∶4. In following time steps, the system repeatedly moved to one of the successive nodes along an edge, or stayed at the same node, like a man on a Monopoly game board, and thus the trajectory of the system can be described as a path on the ion-binding state graph. Here, the trajectory was first divided into several short paths, corresponding to each conduction event. We then identified major ways to conduct K+ ions, by classifying each short path.
In the entire trajectory of the simulation at 150 mM, there were two stable states, K∶0∶2∶4 and K∶1∶3, with lifetimes of 38.4% and 22.2% of the simulation time, respectively, as consistent with previous simulations . The state K∶0∶2∶4 can be regarded as the "resting state". In the simulation, the system repeatedly made round trips, departing from the resting state and return to the same state. The time course of the simulation can be regarded as a set of round trips, or cyclic paths on the graph. In the simulations at the other ion concentrations, similar cyclic transition events were observed, with the resting state (or K∶0∶2∶4) existence probabilities of 57.0%, 74.2%, and 70.0%, at 300 mM, 450 mM and 600 mM KCl, respectively. Thus, these trajectories may be compared in terms of the variations in the cyclic paths on the ion-binding state graphs, due to the changes in the ion concentration.
There were 38 cyclic paths in the 1.0 µs simulation at the 150 mM ion concentration, which corresponded to 31 K+ ions passing through the pore from the intracellular side to the extracellular side (the inconsistency of these two values was due to some paths without ion conductions). On the other hand, there were 86 cycles with 71 K+ ion conductions in the simulation at 600 mM. Here, these 38 and 86 cyclic paths were compared and classified by hierarchical clustering, in order to discuss the underlying mechanisms of ion conduction at each ion concentration. Each path was represented as a sequence of characters, each of which corresponding to a state (for example, the one-letter code of the resting state, or K∶0∶2∶4, was assigned as 'E'. See Fig. 3 for the other states). The 124 paths were converted into 124 sequences, and an all-against-all sequence alignment was performed by using the dynamic programming. The hierarchical clustering revealed two major clusters and some minor ones (Fig. S8; the clustering for all ion concentrations is shown in Fig. S9).
As an example of the first cluster, the typical path "EB310HFE" in Fig. 5A represents that (i) the system starts from the resting state ('E' or K∶0∶2∶4), (ii) the K+ ions at S2 and S4 move to the next sites ('B' or K∶0∶1∶3), (iii) the ion at S0 goes out to the extracellular side ('3' or K∶1∶3), (iv) the ions at S3 proceed to the next sites ('1' or K∶1∶2), (v) the S1 ion moves to S0 ('0' or K∶0∶2), (vi) a new K+ comes in from the extracellular side ('H' or K∶0∶2∶6), (vii) the new K+ ion moves to the next site by one ('F' or K∶0∶2∶5), and (viii) the system returns to the resting state ('E' or K∶0∶2∶4). This process can be considered to follow the A/D model, where the outermost K+ ion is released first (K∶1∶3), and then the system returns to the most stable state (K∶0∶2∶4) by receiving a new ion from the intracellular side.
Figure 5. Schematic diagrams of ion conduction cycles and passage times of state transitions.
Examples of schematic diagrams of ion conduction paths in each of the two major ways: via the two-ion states (A), and via the four-ion states (B). Each character shown means each ion-binding state, as shown in Fig. 3.
In a similar way, the typical case of the other cluster was "EkidKIGE" (Fig. 5B), which can be interpreted as (i) the system starts from the resting state (K∶0∶2∶4), (ii) a new K+ comes in ('k' or K∶0∶2∶4∶6), (iii) the incoming ion goes up, and pushes the existing ones ('i' or K∶0∶2∶4∶5), (iv) the pushed ions push the neighboring K+ ions successively ('d' or K∶0∶1∶3∶5), (v) the outermost ion is pushed out ('K' or K∶1∶3∶5), (vi) the K+ in the innermost site pushes the upper K+ ion ('I' or K∶1∶3∶4 and 'G' or K∶1∶2∶4), and finally, (vii) the system returns to the resting state ('E' or K∶0∶2∶4). This path corresponds to the knock-on mechanism.
In short, these two major clusters correspond to the two ways described in the previous subsection: the way via the two-ion states, and that via the four-ion states. The classification of the conduction events confirmed that they were based on the two mechanisms, in which the former way via the two-ion states corresponds to the A/D model, and the other way, via the four-ion states, corresponds to Hodgkin and Keynes' knock-on model.
There were two major ion conduction paths at the lowest ion concentration as described above. Here, we examined effects of the ion concentration to the ion conduction mechanism. At the 150 mM ion concentration, the ratio of the cyclic paths via the four-ion states (knock-on mechanism) over those via the two-ion states (A/D mechanism) was 0.48 (10/21), which indicates that the A/D mechanism was preferred twice as much as the knock-on mechanism. This ratio gradually raised with increasing ion concentrations, as 0.67, 3.5, and 5.8, at 300 mM, 450 mM, and 600 mM, respectively (Table S2). In other words, an increase in the ion concentration switches the ion conduction mechanism from the A/D mechanism to the knock-on mechanism.
This alteration of the ion conduction mechanism may be interpreted from changes in the stability of each state. In the ion-binding state graphs (Fig. 3, S4, S5, and S6), the color and area of each node reflects log existence probability of each state (Fig. 3), which corresponds to the stability of a node. The simplified graphs for the simulations at 150 mM and 600 mM (Fig. 4A and 4B, respectively) clearly show that an increase in the ion concentration destabilizes two-ion states (II). When the pore in states II receives a K+ ion from the intracellular side, the state changed to IIIe and A/D conduction is occurred. Alternatively, if the pore is in states IIIr when a K+ ion comes, the state transits to IV and a K+ ion is conducted in the knock-on mechanism. Thus, the changing in the balance of the stabilities of states II and IIIr causes the alteration of the conduction mechanism.
The stabilities of states II, IIIr, IIIe, and IV will be determined by the balance between associations and dissociations of K+ ions, where frequent associations of K+ ions will lead the pore to the states with higher number of ions (IV), and vice versa. We analyzed times spent for each association and dissociation event (for example, in the conduction process shown in Fig. 5A, the time for the transitions from the first 'E' to '3' was measured as a dissociation event, and that from '3' to 'H' was an association event). As a result, the increase in ion concentration from 150 mM to 600 mM significantly accelerated the associations, and hinders the dissociations of ions (Fig. 6). These results indicate that the high ion concentration facilitated attacks of ions from the solution to the pore, and delayed releases of bound ions. Details of the transition times of each state are shown in Fig. S10 and discussed in the Text S1.
Figure 6. Times for ion association and dissociation events.
Boxplots of times for the association (A) and dissociation (B) events, in the simulations at 150 mM (cyan) and 600 mM (black). Both of the events showed significant differences between the two ion concentrations; the P-values of Wilcoxon tests were 2.6e-5 (A) and 4.7e-3 (B). The increase in ion concentration facilitated the ion association, and delayed the ion dissociation.
Some behaviors other than the two conduction mechanisms described above were also observed. Interestingly, after releasing the K+ ion in S0 from the three-ion state, another K+ ion occasionally entered from the extracellular side and bound to S0; i.e., the system transited the following path, IIIr-II-IIIr. Our simulation showed that such back-running events frequently occurred during the outward conductions. For the resting state, i.e., K∶0∶2∶4, a considerable part of its lifetime was with a back-ran K+ ion; the ratio of lifetime with a back-ran K+ ion over the entire lifetime of K∶0∶2∶4 were 64.3%, 45.2%, 26.1%, and 45.5%, for each ion concentration in ascending order. There was no clear trend between ion concentrations and back-ran K+ lifetimes. Because the back-running event can occur when a K+ ion attacks the pore in the two-ion states from the extracellular side, the two factors may be crucial for the occurrence of the back-running: the stability of two-ion states (denoted as II in Fig. 4), and the frequency of the attack of K+ ions. As an increase in ion concentration decreases the former and increases the latter, it is reasonable the fact that there was no clear trend in the ratio with the ion concentration.
The other minor ways were combinations of various events (see Table S2).
Here, we will summarize the ion concentration-dependent ion conduction mechanism of a Kv1.2 channel. In the channel, the pore can bind two, three, or four ions in its seven binding sites, simultaneously. Basically, the pore adopts the most stable three-ion state, which is K+ ions in S0, S2, and S4. From this state, one of two types of events will occur: (a) one way pops the K+ ion from S0, and (b) the alternative one is the entrance of a new K+ ion from the intracellular side. In the former way (a), as the K+ ion in S0 is relatively unstable, it will eventually be released to the extracellular side (the transition from IIIr to II in Fig. 4). Then, the remaining two K+ ions move to S1 and S3, and the sub-stable two-ion state is adopted. Subsequently, the pore waits for a third ion, from either the intra- or extracellular side. When a K+ ion enters from the intracellular side, the state of the pore rapidly transits to the resting state (from IIIe to IIIr). This conduction event via the sub-stable two-ion state (K∶1∶3) corresponds to the A/D model. Alternatively, when a K+ ion enters from the extracellular side, the pore returns to the resting state (from II to IIIr). When we assume the actual situation (not the MD system with the periodic boundary condition), this event does not change the membrane potential (one K+ ion is released to the extracellular side, and another one comes from the same side). The latter event in the resting state (b) will occur if a K+ ion enters from the intracellular side before the dissociation of the K+ ion in S0 (this transition means from IIIr to IV). The pore assumes an unstable four-ion state, and the outermost K+ ion will be rapidly released to the extracellular side (from IV to IIIe). Subsequently, the pore smoothly returns to the resting state (K∶0∶2∶4; from IIIe to IIIr). This event corresponds to the knock-on conduction mechanism.
The preference for these events depends on the ion concentration. The barrier to the dissociation of the outermost K+ ion and that to the association of a new K+ ion from the intracellular side depend on the ion concentration (Fig. 6). An increase in the ion concentration facilitates the associations, and delays the dissociations. At the lowest ion concentration (150 mM), conductions by the A/D model were dominant (two-fold preferred over that by the knock-on model). In contrast, the knock-on model was six-fold preferred over the A/D model at the highest ion concentration (600 mM), in which ion conductance is saturated. The results of the simulations at the intermediate ion concentrations (300 mM and 450 mM) showed that the preference in the conduction mechanisms gradually changed with the increasing ion concentration. Our simulation revealed that the dependency of ion conductance on the ion concentrations is not only due to differences in the frequency of chances for attacking to the pore by ion diffusion but also by distinct conduction mechanisms.
Simulation systems, consisting of the pore domain of the Kv1.2/Kv2.1 paddle chimera (PDB-ID: 2r9r ), a POPE bilayer, and a KCl solution were built with the Maestro and Desmond software . The simulations for the four systems at 150 mM, 300 mM, 450 mM, and 600 mM ion concentrations were subsequently performed by GROMACS 4.5.3 , using Charmm27 forcefield  with CMAP correction . TIP3P model was applied for water molecules. For potassium and chloride ions, the standard Charmm27 parameters were applied without any correction. An electric field was applied to imitate 920 mV of membrane potential to agree with Jensen's study , and the particle mesh Ewald method was applied for the long-range electrostatic potential. The bonds to hydrogen atoms were constrained by the LINCS algorithm . The temperature of the systems was controlled at 310K by the Nosé-Hoover thermostat algorithm , , and the pressure was maintained at 1 bar by the Parrinello-Rahman method , . For more details, see the Text S1.
Numbers of water molecules and ions in each system. Actual numbers of water molecules and ions consisting of each system are shown.
Summary of deduction events observed during the four simulations. Summary of the cyclic paths based on node group II, IIIr, IIIe, and IV, defined in the manuscript. The values indicate the number of observations for each type of cyclic paths.
A movie for ion conduction processes described in Fig. S1.
Snapshots of some ion conduction events at 150 mM of ion concentration. Snapshots of the structure around the SF along the time course from 251,000 ps (panel A) to 290,680 ps (panel H) in the simulation under 150 mM of ion concentration. The trajectory including these snapshots is also shown as a movie, Movie S1. Sticks show the structure of SF residues; two of the four subunits are hidden for clarity. Balls shown in red and white indicate oxygen and hydrogen atoms; those in blue, orange, and purple are potassium ions. The strings started by "K:", for example "K∶0∶2∶4" in the panel (A), indicate ion-binding states of the SF (see subsection "Graphical analysis of the ion-binding states" in Results/Discussion).
Trajectories of K+ from the simulations at 300 mM and 450 mM ion concentrations. See Fig. 2 in the main text.
Ratio of the lifetimes of states with two, three, and four K+. The ratio of the lifetimes of two-, three-, and four-states are shown as 'II', 'III', and 'IV', respectively.
Ion-binding state graphs at 300 mM ion concentration. The size and color of each node reflects the lifetime of each state in the simulation, and the width of each edge indicates the transition probability between the two nodes. A red edge means a new coming from the intracellular side, and a blue one means the release of the ion in the outermost site to the extracellular side. See also the legend of Fig. 3 in the main text.
Ion-binding state graphs at 450 mM ion concentration. See the legend of Fig. 3 in the main text.
Ion-binding state graphs at 600 mM ion concentration. See the legend of Fig. 3 in the main text.
Lifetime of each state in the first and last half of a simulation. Horizontal and vertical axes are the log lifetimes of each state during the first and last half of the simulation, respectively. Each point corresponds to each ion-binding state, as shown in Fig. 3. The high PCC, stands for Pearson correlation coefficient, showed high stationarity of these simulations at the 150 mM (A) and 600 mM (B).
Cluster analysis of all of the cyclic paths in 150 mM and 600 mM. Each sequence represents a cyclic path on the graph that begins at K∶0∶2∶4 and ends at the same state. A character was assigned to each state, and is shown as an orange character in each node, in which the first and last 'E' mean that the K∶0∶2∶4 state in the sequences was omitted. The sequences with the cyan arrow or marked with cyan asterisks are the conduction paths with the A/D model, and those with the pink arrow or pink asterisks are the path with the knock-on model. The sequences with orange asterisks represent other exceptional conduction events (see Table S2).
All of the cyclic paths in the four simulations. (A) Hierarchical clustering of the cyclic paths in the ion-binding state graphs for all four simulations. In addition to 38 sequences from the simulation at 150 mM (cyan) and 86 from that at 600 mM (black), 37 and 34 sequences from the simulations at 300 mM (green) and 450 mM (purple), respectively, were added. (B) Tables of the cyclic paths, ordered along the time course in each simulation. The color of the column "path in group" indicates the category of events: pink, cyan, and green mean a conduction by the knock-on, that by the A/D, and go and back-running events, respectively. The paths (a) and (b) corresponds the paths shown in Fig. 5A and B, respectively.
Passage times of state transitions. Boxplots displaying the time of each transition event between groups of the ion-binding states, in simulations at 150 mM (cyan) and 600 mM (black). Significant differences between the two ion concentrations were marked as ** and * (the P-value of Wilcoxon test ≤0.001 and ≤0.05, respectively). A) Transitions with association of an ion: from IIIr to IV, and from II to IIIe. B) Transitions with dissociation of an ion: from IIIr to II, and from IV to IIIe. C) the transition from IIIe to IIIr. The P-values were 3.6e-1 (A, left), 1.1e-4 (A, right), 8.2e-3 (B, left), 3.9e-2 (B, right), 9.9e-1 (C).
The super-computing resource was provided by the Human Genome Center (Univ. of Tokyo).
Conceived and designed the experiments: K. Kinoshita MS. Performed the experiments: K. Kasahara. Analyzed the data: K. Kasahara. Wrote the paper: K. Kinoshita MS K. Kasahara.
1. Miller C (2000) An overview of the potassium channel family. Genome Biol 1: REVIEWS0004.
2. MacKinnon R (2003) Potassium channels. FEBS Letters 555: 62–65 .
3. Wulff H, Castle NA, Pardo LA (2009) Voltage-gated potassium channels as therapeutic targets. 1–20 .
4. Alam A, Jiang Y (2011) Perspectives on: Ion selectivity: Structural studies of ion selectivity in tetrameric cation channels. The Journal of General Physiology 137: 397–403 .
5. Doyle DA (1998) The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity. Science 280: 69–77 .
6. Zhou Y, Morais-Cabral JH, Kaufman A, MacKinnon R (2001) Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution. Nature 414: 43–48 .
7. Long SB (2005) Voltage Sensor of Kv1.2: Structural Basis of Electromechanical Coupling. Science 309: 903–908 .
8. Long SB, Tao X, Campbell EB, MacKinnon R (2007) Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment. Nature 450: 376–382 .
9. Ye S, Li Y, Jiang Y (2010) Novel insights into K+ selectivity from high-resolution structures of an open K+ channel pore. Nature Publishing Group 17: 1019–1023 .
10. Chakrapani S, Cordero-Morales JF, Jogini V, Pan AC, Cortes DM, et al. (2010) On the structural basis of modal gating behavior in K+ channels. Nature Publishing Group 18: 67–74 .
11. Lu Z, Klem AM, Ramu Y (2001) Ion conduction pore is conserved among potassium channels. Nature 413: 809–813 .
12. Heginbotham L, Abramson T, MacKinnon R (1992) A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels. Science 258: 1152–1155.
13. Hille B, Schwarz W (1978) Potassium channels as multi-ion single-file pores. J Gen Physiol 72: 409–442.
14. Hodgkin AL, Keynes RD (1955) The potassium permeability of a giant nerve fibre. The Journal of Physiology 128: 61–88.
15. Nelson PH (2003) A permeation theory for single-file ion channels: Concerted-association/dissociation. J Chem Phys 119: 6981 .
16. Nelson PH (2011) A permeation theory for single-file ion channels: One- and two-step models. J Chem Phys 134: 165102 .
17. Bernèche S, Roux B (2001) Energetics of ion conduction through the K+ channel. Nature 414: 73–77 .
18. Miloshevsky G (2004) Permeation in ion channels: the interplay of structure and theory. Trends in Neurosciences 27: 308–314 .
19. Khalili-Araghi F, Tajkhorshid E, Schulten K (2006) Dynamics of K+ ion conduction through Kv1.2. Biophysical Journal 91: L72–L74 .
20. Kraszewski S, Boiteux CL, Langner M, Ramseyer C (2007) Insight into the origins of the barrier-less knock-on conduction in the KcsA channel: molecular dynamics simulations and ab initio calculations. Phys Chem Chem Phys 9: 1219 .
21. Jensen MO, Borhani DW, Lindorff-Larsen K, Maragakis P, Jogini V, et al. (2010) Principles of conduction and hydrophobic gating in K+ channels. Proceedings of the National Academy of Sciences 107: 5833–5838 .
22. Kim I, Allen TW (2011) On the selective ion binding hypothesis for potassium channels. Proceedings of the National Academy of Sciences 108: 17963–17968 .
23. Shaw DE, Deneroff MM, Dror RO, Kuskin JS, Larson RH, et al. (2007) Anton, a special-purpose machine for molecular dynamics simulation. ACM SIGARCH Computer Architecture News 35: 1–12.
24. Heginbotham L, MacKinnon R (1993) Conduction properties of the cloned Shaker K+ channel. Biophysical Journal 65: 2089–2096 .
25. Iwamoto M, Oiki S (2011) Counting Ion and Water Molecules in a Streaming File through the Open-Filter Structure of the K Channel. Journal of Neuroscience 31: 12180–12188 .
26. Roux B (2008) The Membrane Potential and its Representation by a Constant Electric Field in Computer Simulations. Biophysical Journal 95: 4205–4216 .
27. Gumbart J, Khalili-Araghi F, Sotomayor M, Roux B (2012) Constant electric field simulations of the membrane potential illustrated with simple systems. Biochimica et Biophysica Acta (BBA) - Biomembranes 1818: 294–302 .
28. Jensen MO, Jogini V, Borhani DW, Leffler AE, Dror RO, et al. (2012) Mechanism of Voltage Gating in Potassium Channels. Science Signaling 336: 229 .
29. Ando H (2005) Coupled K+-Water Flux through the HERG Potassium Channel Measured by an Osmotic Pulse Method. The Journal of General Physiology 126: 529–538 .
30. Morais-Cabral JH, Zhou Y, MacKinnon R (2001) Energetic optimization of ion conduction rate by the K+ selectivity filter. Nature 414: 37–42 .
31. qvist JA, Luzhkov V (2000) Ion permeation mechanism of the potassium channel. Nature 404: 881–884 .
32. Oiki S, Iwamoto M, Sumikama T (2011) Cycle Flux Algebra for Ion and Water Flux through the KcsA Channel Single-File Pore Links Microscopic Trajectories and Macroscopic Observables. PLoS ONE 6: e16578 .
33. Bowers K, Chow E, Xu H, Dror R, Eastwood M, et al.. (2006) Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters IEEE. pp. 43–43. doi:https://doi.org/10.1109/SC.2006.54.
34. Hess B, Kutzner C, van der Spoel D, Lindahl E (2008) GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. J Chem Theory Comput 4: 435–447 .
35. MacKerell AD Jr, Bashford D, Bellott M, Dunbrack RL Jr, Evanseck J, et al. (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. The Journal of Physical Chemistry B 102: 3586–3616.
36. MacKerell AD, Feig M, Brooks CL (2004) Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J Comput Chem 25: 1400–1415 .
37. Hess B, Bekker H, Berendsen HJC, Fraaije JGEM (1997) LINCS: a linear constraint solver for molecular simulations. J Comput Chem 18: 1463–1472.
38. Nosé S (1984) A molecular dynamics method for simulations in the canonical ensemble. Molecular Physics 52: 255–268 .
39. Hoover W (1985) Canonical dynamics: Equilibrium phase-space distributions. Phys Rev, A 31: 1695–1697.
40. Parrinello M (1981) Polymorphic transitions in single crystals: A new molecular dynamics method. J Appl Phys 52: 7182 .
41. Nosé S, Klein ML (1983) Constant pressure molecular dynamics for molecular systems. Molecular Physics 50: 1055–1076 .
42. Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T (2011) Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27: 431–432 .
Is the Subject Area "Potassium" applicable to this article?


text:
Soumbeyla Diakité (* 25. August 1984 in Djicoroni-Para, Bamako) ist ein malischer Fußballspieler.

Karriere

Verein
Diakité begann seine Karriere mit Stade Malien und gehört seit seinem 15. Lebensjahr zum Malien Premiére Division team.

International
Diakité nahm für sein Heimatland an der Junioren-Fußballweltmeisterschaft 2003 in den Vereinigten Arabischen Emiraten teil und spielte die Olympischen Sommerspiele 2004. 2011 nahm er an den African Nations Championship in Sudan teil.

Einzelnachweise

Teilnehmer der Olympischen Sommerspiele 2004
Olympiateilnehmer (Mali)
Fußballnationaltorhüter (Mali)
Malier
Geboren 1984
Person (Bamako)
Mann

redpajama_set_name: RedPajamaWikipedia


text:
Bukowiński Państwowy Uniwersytet Medyczny (ukr.: Буковинський державний медичний університет) – ukraińska uczelnia wyższa.

Poprzednikiem uczelni był Instytut Przemysłowo-Medyczny (Київський виробничо-медичний інститут), utworzony w 1931 roku w Kijowie. W 1936 roku został on przemianowany na II Kijowski Państwowy Instytut Medyczny (2-й Київський державний медичний інститут). W czasie II wojny światowej Instytut został ewakuowany do Charkowa i tymczasowo funkcjonował razem z I Kijowskim Instytutem Medycznym. W 1944 roku, ze względu na zniszczenia wojenne Kijowa podjęto decyzję o przeniesieniu Instytutu do Czerniowców, które miały lepiej zachowaną infrastrukturę, która pozwalała na szybsze wznowienie działalności uczelni. Uczelnia zmieniła wówczas nazwę na Czerniowiecki Państwowy Instytut Medyczny (Чернівецький державний медичний інститут). W 1997 przemianowano ją na Bukowińską Państwową Akademię Medyczną (Буковинська державна медична академія), a w 2005 nadano status uniwersytetu i obecną nazwę.

W ramach uczelni funkcjonują następujące jednostki:
 Koledż Pielęgniarstwa i Farmacji
 Wydział Medyczny I (dla obywateli Ukrainy)
 Wydział Medyczny II (dla obywateli Ukrainy i cudzoziemców)
 Wydział Medyczny III (studia podyplomowe)

Przypisy

Oświata w Czerniowcach
Uczelnie medyczne na Ukrainie
Hasła utworzone w ramach Tygodni Tematycznych 2019
Architektura w obwodzie czerniowieckim


You can find me on Twitter. There is a link at the bottom of the page.
I have some Pinterest boards of boats I really want to build and think are beautiful. You can look at those if you like.
I will also be working on some Youtube videos and vlogs in the future so look out for those!
If you want to email me then there is also this nifty little form on the right for your perusal.


Connecting more people via the Internet is accompanied by the creation of greater gender inequality. Women face general challenges, such as affordability of devices and connectivity, as well as specific ones, such as cultural issues. Some measures to mitigate the gender gap were discussed, such as reducing prices, removing taxes on low-cost devices, and tailoring capacity building to the needs of women.
The moderator started the session by providing an overview of the 'After Access' project, which conducted a survey and case studies in 20 countries from the Global South.
Ms Alison Gillwald, Executive-Director of Research ICT Africa (RIA), explained the selection of countries and methodology of the After Access survey. The project goes beyond big data and supply-side data to develop a model based on demand-side data. Gillwad presented some of the findings of the research.
Ms Aileen Agüero, Institute for Peruvian Studies, commented on other findings, focusing on Latin America. She mentioned that even when women have online access, other challenges remain, such as continuing stereotypes. In addition, cross-cutting gaps, such as the urban-rural divide and gender gaps in regard to online money usage remain. In regard to the later, private sector initiatives, such as M-Pesa in Kenya, and public policies, such as introduced in Paraguay, can facilitate women's access to online money.
Ms Helaini Galapaya, Board Member at Global Partnership for Sustainable Development Data, commented on the results of the 'After Access' survey in Asia and the barriers to gender equality. The affordability of mobile phones is still a significant issue. While these devices are cheap, they are increasingly less affordable among the parts of society with less income. In addition, a lack of skills in the proper use of these devices or to meaningfully use the Internet, sustains the gender gap. Certain regions also face specific challenges, such as the lack of a reliable electrical infrastructure to charge mobile phones.
According to Gillwald, a digital paradox is emerging: the success in connecting more people is accompanied by the creation of greater inequality, that is, a gap between those who are barely online and those who are skillful in using the Internet. While the quantitative data of the 'After Access' survey is nationally representative, the limitations of the data collected also stand out. One of the limitations is the difficulty in understanding the interrelated nature of inequality. Combining different sets of data allows richer conclusions, such as that poor urban women access the Internet more than rural men. This helps to understand the problems and prioritise strategies to mitigate them. Some short-term strategies include reducing prices and getting rid of taxes on low-cost devices.
Ms Muge Haseki, University of Pennsylvania, presented some results and case studies from the project 'One world connected'. One result from the project is that some barriers confront all people, such as financial constraints and access to infrastructure. However, women face some unique challenges, such as Internet access that is controlled by husbands or mothers-in-law. She provided the example of a project that built telecenters that aggravated the gender divide, because women could not attend alone. It is important to adapt projects to the specific needs of women, such as to communicate with other women and to obtain information related to motherhood and health. Digital training programs need to provide a mixture of basic literacy skills and to address these needs.
Ms Claire Sibthorpe, Head of GSMA Connected Women, highlighted barriers related to the cost of devices and connectivity, and socio-cultural issues. She mentioned that GSMA conducts an annual study looking at the gender gap related to Internet use, based on operators' data, qualitative research, and household surveys. According to data, people in low income countries are 26 percent less likely to access the internet; women are 30 percent less likely to use mobile money. Affordability and ownership of devices and connectivity are important, but even if women earn their own income, they are usually not the decision-makers in purchases. Access to technology is only one side of the coin: agency and self-determination are also important.
The questions from the audience were related to the role of states and international organisations, and to difficulties in gathering and improving research indicators, specially concerning LGBT communities.


text:
Cooking Challenge 101
Previous Prev Why Check Your A1C
MAIN MENU Real Health Summer 2015
Next Takin' Hits
Diabetes dishes that are healthy for everyone
June 2, 2015 • By Jeanette L. Pinnace
Click here to read a digital edition of this article.
When Leticia Moreinos Schwartz committed to being a spokesperson for a health education campaign called "Desafiando La Diabetes," to educate Latinos about type 2 diabetes, she relished the opportunity to also transform traditional recipes into more diabetes--friendly dishes.
Pharmaceutical company Merck sought out the Brazilian chef, teacher, food stylist and cookbook author who specializes in Latin cuisine for the campaign. Merck wanted Moreinos Schwartz because of her culinary expertise and passionate commitment to educating Latinos about managing type 2 diabetes.
Type 2 diabetes is the most common form of diabetes. The illness causes blood sugar levels to rise because the body is unable to properly use insulin, a hormone that regulates the amount of glucose in the blood.
After struggling with the disease for many years, Moreinos Schwartz's grandfather died of a stroke, one of many serious complications type 2 diabetes can cause. "I was probably 15 or 16 at the time," she recalls. "I noticed that my grandmother wasn't completely educated about how to treat diabetes and how to help my grandfather control his A1C number. Also, she didn't know what types of foods she should prepare for him and the family."
The A1C number is derived from a test that measures the average amount of glucose, or sugar, in your blood for the previous two to three months. Guidelines for the American Diabetes Association suggest many people with diabetes should have an A1C number of less than 7 to help reduce the risk of complications, such as heart disease and stroke. (Remember, everyone is different, and a higher or lower A1C goal may be appropriate for some people.) However, nearly half of people with diabetes don't have an A1C number that's below 7.
Better management of Moreinos Schwartz's grandfather's A1C number might have added years to his life. Instead, his death dealt the family a blow. They were shaken and saddened not only by his passing, but also because "we started to realize that maybe this could have been avoided if we had more information about the disease and a better comprehension of it," she says. "That's when we started to really pay a lot of attention to our lifestyle and to exercise a lot more; our minds became very conscious about healthy living."
As in many families, food plays an important role in the social dynamics of Moreinos Schwartz's family. But when her grandfather died, they looked harder at their food choices. "We were eating traditional Latin foods, and all of a sudden we had to modify," she says. "I was always into the food, and I thought I would have to stop eating meals with ingredients that are really iconic to us in Brazil—the same ingredients we share with the rest of South America. But I knew I'd have to modify my diet in order to take good care of my health."
Diet modification is also the solution the Centers for Disease Control and Prevention (CDC) offers to address statistics showing that diabetes disproportionately affects African Americans and Latinos. When Merck requested Moreinos Schwartz's support on its campaign, she was eager to help educate others about the importance of understanding how high blood sugar levels can eventually lead to serious long-term health problems. Also, being a chef, Moreinos Schwartz was excited to take on the culinary challenge of creating dishes that are not only healthy and nutritious for those living with diabetes, but also tasty and enjoyable recipes for the whole family.
Experts have long stressed that diabetes doesn't mean you must deprive yourself of all your favorite foods. Many flavorful substitutions can be made to excite the taste buds and satisfy your appetite. In Moreinos Schwartz's cooking classes, she stresses how to season food properly. "When you know how to season and you use salt and pepper and herbs and spices from the very beginning, you don't need that much extra salt to flavor the food, which is huge," she says.
Moreinos Schwartz also uses chicken stock to add flavor to food, bypassing the butter, cream, cheese or any of "those things that aren't really good for you," she says. She encourages folks to make their chicken stock at home or buy some of the low-sodium brands, which are healthier.
Indeed, learning what to eat and making healthful choices can make you feel better. But not only that: Modifying your diet can help you lose weight and lower your risk of some of the scarier complications caused by diabetes, such as heart disease, stroke, kidney problems, blindness and amputation. "Knowledge is power. Learning how the foods you eat affect your health and well-being gives you the power to become healthy, live longer, and feel better every single day," says Joel Fuhrman, MD, author of the best-selling book The End of Diabetes.
"When you eat a diet rich in healthy, natural foods from the earth, you give your body the nutrients it needs to heal and protect itself," he continues. Fuhrman also believes that type 2 diabetes is a disorder triggered by not making the proper food choices that could help extend our lives and prevent many of the diseases that we face.
But there's more to controlling and managing diabetes besides choosing healthier foods and changing the way they're prepared. "We can't emphasize enough the importance of people talking about nutrition, knowing their A1C number and developing a personalized plan with their doctor," Moreinos Schwartz stresses.
What's more, a diabetes-friendly diet isn't only a good idea for those living with the disease. Experts at the Mayo Clinic believe a healthy eating plan that is rich in nutrients found in fruits, vegetables and whole grains, which is automatically low in fat and calories, is the most nutritious diet for almost anyone.
"Choose recipes that are good for the whole family," Moreinos Schwartz suggests. "Make it a family affair. When the family is involved, this tends to lead to a more successful outcome for a family member with diabetes."
But what about dessert? Sweet treats at the end of a meal are also a traditional part of many families' dining experience. Moreinos Schwartz agrees, but she stresses that for those with diabetes, allowing themselves sweets is part of a discussion to be had with their doctor. "It's more appropriate that each person develop a plan with their doctor to control diabetes, and that will include the consumption of sweets," she advises.
Still, the chef does agree that sweet treats can also be modified and made more diabetes-friendly, even rich and creamy Latin desserts such as arroz con leche. "This is another traditional Latin dish that we have adapted with a lot less sugar," she shares. "When we give a tasting of that, people go crazy."
If you want to see for yourself, check out Moreinos Schwartz's recipe for this crowd-pleaser in the sidebar on this page. This sweet treat is one of Moreinos Schwartz's diabetes-friendly recipes that she created to be generally lower in sodium, carbohydrates, saturated fat, trans fat and cholesterol, and higher in fiber than its traditional counterpart.
But portion control is also part of the equation. "We try to encourage people to eat a lot less," she cautions. That means enjoying just a tablespoon or two of the creamy creation instead of scarfing down a whole bowl.
Says Moreinos Schwartz, "Again, I think a successful way for someone with diabetes to go about including sweets in a meal plan is to really talk to their doctor."
#blood sugar
#type 2 diabetes
What Do You Prefer? Meals High in Fat, Protein or Carbohydrates?
A Blood Sugar Test Also Predicts Memory Problems
Harlem-born Rapper Biz Markie Dead At 57
Alzheimer's Disease and African Americans: What You Need to Know

redpajama_set_name: RedPajamaCommonCrawl


Lexmark P Inkjet Printer Lexmark. This website is using cookies. Solvusoft's close relationship with Microsoft as a Gold Certified Partner enables us to provide best-in-class software solutions that are optimized for performance on Windows operating systems. To achieve a Gold competency level, Solvusoft goes through extensive independent analysis that looks for, amongst other qualities, a high level of software expertise, a successful customer service track record, and top-tier customer value. However, I ignored this, removed the CD and attempted to print a test page. Furthermore, installing the wrong Lexmark drivers can make these problems even worse. You can follow the question or vote as helpful, but you cannot reply to this thread.
Power off your device. Note that this is a USB printer Windows 8 – Fix Printer Problems http: This page contains information about installing the latest Lexmark Z driver downloads using the Lexmark Driver Update Tool.
If a language seried is given, select serles language. Hi, This is what I had to do for a X in Win 8. It is a software utility that will find the right driver for you – automatically.
AngieBJ Replied on November 11, Maintaining updated Lexmark Z software prevents crashes and maximizes hardware and system performance. Mac OS X To achieve a Gold competency level, Solvusoft goes through seris independent analysis that looks for, amongst other qualities, a high level of software expertise, a successful customer service track record, and top-tier customer value.
My Lexmark series printer worked fine until my computer updated to Windows 8. Lexmark windows 8. This website is using cookies.
Visit our Driver Support Page for lxmark step-by-step videos. Lexmark Drivers Printer Drivers. They add hundreds of new drivers to our site every day. News Blog Facebook Twitter Newsletter. Hi, Windows Compatibility Center http: I unchecked a "Shared" on the first window. This site in other languages x.
After a computer restart, Ldxmark used the installation CD that came with the printer to reinstall the printer. Download the latest Lexmark Z Series driver for your computer's operating system.
Lexmark Z drivers are tiny programs that enable your Inkjet Printer hardware to communicate with your operating system software. Lexmark Z Series Drivers Download.
Since then, it has worked with no problems! You are downloading trial software. This esries will download and update the correct Lexmark Z driver versions automatically, protecting you against installing the wrong Z drivers.
Browse the list below to find the driver that meets your lexark. Using outdated or corrupt Lexmark Z drivers can cause system errors, crashes, and cause your computer or hardware to fail.
Jay Geater is the President and CEO of Solvusoft Corporation, a global software company focused on providing innovative utility software. Furthermore, installing the wrong Lexmark drivers can make these problems even worse.
Hook Printer back up when Prompted.


"Here we are trying to create the principles of democracy in Iraq. Every speech we give in that country is about democracy. And we're breaking all the first principles of democracy when we're doing it," said a senior Pentagon official who opposes the practice of planting stories in the Iraqi media."
Um, I think the real concern is if they are paying to have false stories planted in the press.
What's the problem with true stories?
Coolblue, are you serious? What's the problem with the government paying the press to run (true) pro-government pieces? No problem as long as it's clear that the pieces are advertisements, which is what they are. If the pieces are run as news stories and the government paid for them, then the press loses all usefulness and is merely a shill for the government. This idea is fundamental to democracy. Maybe I misunderstood your question.
It's easily possible to lie by telling the truth. You can just tell the papers that instead of the latest scandal, they should print an article about how the Wonderful Leader just presided over the opening of a new bridge.
I think it's time we started really striking at the root of the problem: Representative government is not good enough. It does get closer to being democratic as people have more accurate information and more choices in elections, but it never really gets very close at all. There is still a great degree to which the public can be misled. We need to start thinking about how to make governments that are truly accountable and transparent.
"Though the articles are basically factual, they present only one side of events and omit information that might reflect poorly on the U.S. or Iraqi governments, officials said."
First, I must point out that this is not a government controlled media as it is, say, in Syria, Iran, or Egypt. What that means is that the US point of view is not the only one out there.
Certainly the US view is competing at the very least with al Qaida propaganda, most of which is untrue.
Secondly, I would argue that the US military is working with willing Iraqi newspapers in an effort to combat the terrorist in the sphere of public perception as well as on the battlefield.
To the extent that ordinary Iraqis have faith in their government, faith in US intentions, and most importantly faith that the Terrorists are not on their side, is precisely the extent to which ordinary Iraqis will be willing to give intelligence against the murderers and thugs looking to defeat self-sustaining democratic institutions in Iraq.
To me, that's a good thing.
I would also point out that during World War II, the US government paid Hollywood to create blatently patriotic propaganda.
mungojelly wrote: "I think it's time we started really striking at the root of the problem: Representative government is not good enough. It does get closer to being democratic as people have more accurate information and more choices in elections, but it never really gets very close at all. There is still a great degree to which the public can be misled. We need to start thinking about how to make governments that are truly accountable and transparent."
I'll just lob a couple grenades into the debate for fun, and mayhaps will come by with something more substantive later.
The military's top commanders, including Gen. Peter Pace, the chairman of the joint chiefs of staff, did not know about the Lincoln Group contract until Wednesday, when it was first described by The Los Angeles Times, said a senior military official who was not authorized to speak publicly.
Pentagon officials said General Pace and other top officials were disturbed by the reported details of the propaganda campaign and demanded explanations from senior officers in Iraq, the official said.
Once we understand how necessary it is for propaganda to be adjusted to the broad mass, the following rule results: It is a mistake to make propaganda many-sided, like scientific instruction, for instance.
What is Truth? Is it unchanging law? We both have truths: are mine the same as yours?
Um, are you arguing that everything is true? Are you arguing that there are no lies?
Are you saying that I shouldn't worry about if what is written in a newspaper is true or not because it's "true" to someone?
I don't believe this is a practical philosophy.
But my main point is that what the LA Times is reporting is not, to my mind, an abuse of public trust. On the other hand, this is.
I think it *is* an abuse of public trust. I think it's sneaky and underhanded. I think it reflects poorly on the American government, mainly because the message it sends is that the only way we can get positive news coverage is by paying for it.
Ultimately, I doubt that it helps achieve its desired end, which is to help us secure peace in Iraq.
But I expect we'll have to agree to disagree.
No, I'm quoting Pontius Pilate from Jesus Christ Superstar.


text:
Ornithine Transcarbamylase Deficiency
Home » Ornithine Transcarbamylase Deficiency
Follow this disease
What is ornithine transcarbamylase deficiency?
Ornithine transcarbamylase deficiency is a genetic disorder that is characterized by an accumulation of ammonia in the blood. When ammonia levels are too high, it becomes toxic and especially impacts the nervous system, along with the liver.
There are multiple forms of this condition which are defined by the age of onset. The neonatal-onset form is very severe and occurs early in life, whereas the late-onset form does not appear until adolescence or adulthood and is less severe.
What are the symptoms of ornithine transcarbamylase deficiency?
In the neonatal-onset form, symptoms appear soon after birth. The first effects include vomiting, refusal to eat, poor sucking, irritability, and lethargy. Respiratory abnormalities, seizures, an enlarged liver, and poor muscle tone soon follow. Without immediate treatment, children could slip into a coma, develop cerebral palsy, experience developmental delays, and develop intellectual disabilities. Treatment is extremely important, as this condition can be fatal without it.
Symptoms of the late-onset form of ornithine transcarbamylase deficiency occur in episodes, often brought on by another illness. Symptoms during an episode include vomiting, irritability, lethargy, self-mutilation (such as biting), confusion, hyperactivity, and ataxia. During an episode, treatment is just as necessary as in the neonatal-onset form. Without it, there could be fatalities.
What causes ornithine transcarbamylase deficiency?
A mutated OTC gene is responsible for this condition, and it is responsible for the ornithine transcarbamylase enzyme. This enzyme is necessary for the urea cycle, and when it is mutated, the cycle cannot run smoothly, resulting in an accumulation of ammonia.
It is an X-linked disorder, so it impacts males more often than females. If females do have this condition, it is often less severe.
How is ornithine transcarbamylase deficiency diagnosed?
A diagnosis is made after noticing the characteristic symptoms. To confirm a diagnosis, doctors will perform blood tests, biopsies, and genetic testing.
What are the treatments for ornithine transcarbamylase deficiency?
A team of specialists are often needed to best treat this condition. The goal of treatment is to reduce levels of ammonia in the blood and lower levels during an episode. Hospitalization may be necessary during an episode, too. Long-term treatment consists of dietary restrictions and alternative pathways therapy. The drugs Buphenyl, Ravicti, and Ammonul have been approved for ornithine transcarbamylase deficiency as well.
Monitoring of the blood is heavily suggested to ensure that ammonia levels do not get too high. While a liver transplant can cure this condition, it is a very risky procedure and can cause complications.
Symptomatic treatment is also used, such as occupational, language, speech, and physical therapy.
Where can I find out more about ornithine transcarbamylase deficiency?
Ornithine Transcarbamylase Deficiency Articles
New Data Available for GSD1a, OTC Deficiency, and Wilson Disease Studies
Jessica Lynn	January 19, 2021
ARCT-810 Dosing Begun in Phase 1b Trial for OTC Deficiency
Jessica Lynn	December 15, 2020
Rare Classroom: Ornithine Transcarbamylase Deficiency
James Moore	October 26, 2020
An Ornithine Transcarbamylase Deficiency Treatment Has Been Approved for Clinical Trials
Kendall Mason	April 16, 2020
Gene Therapy: The New Frontier for Cancer
Rose Duesterwald	February 13, 2020
New Updates From Translate Bio in Drug Development for Cystic Fibrosis and OTC Deficiency
James Moore	January 8, 2019


Swedish Dota 2 esports team Alliance has signed a new equipment partnership with US gaming accessories brand Razer.
Under the two-year deal, Razer will supply peripherals such as mice, keyboards and headsets to the team. Alliance will also take part in testing and development of new Razer products.
Previously, Razer partnered with Alliance when the team was founded in 2013 – the same year it won The International for Dota 2.
Other Alliance sponsors currently include drinks brand Monster Energy, gambling platform GG.Bet, streaming service Twitch and esports market research brand Newzoo.
Razer also has partnerships with Alliance rivals such as SK Telecom T1, the Seoul Dynasty, 100 Thieves, Immortals, SK Gaming, Gen.G, Tribe Gaming, Team Vitality and Williams esports.
Founded in 2005 and dual-headquartered in San Francisco and Singapore, Razer has 15 offices worldwide and is listed on the Hong Kong Stock Exchange.


HUNTSVILLE, Ala. (WAAY) – City officials announced Monday that the old Holiday Inn site in downtown Huntsville will be redeveloped into a $70 million site with a hotel, offices, restaurants and apartments.
The city awarded the development to CRS Big Spring, which is made up of Central Realty Holdings in Greeneville, S.C., RCP Companies in Huntsville and Strand Development Company in Myrtle Beach.
City officials said the development will include a hotel, 28,000 square feet of space for offices, restaurants and retail shops, 200 residential units and a parking deck.
The old Holiday Inn building is scheduled to be torn down starting in November. Construction on the new development would begin by April 2015 with a projected finish date in summer 2016.


Moisture present in roof tiles speeds up the heat transfer from inside the building through the roof to outside. However, RSL@Renotec roof coating has unique properties helping to create dry roof tiles, slowing down heat movement, therefore helping to keep fuel bills and energy consumption down.
By slowing down heat transfer RSL@Renotec roof coating will drop a building's U-Value, reducing the amount of energy required to heat the building reducing energy bills in the process. The application of RSL@Renotec will create a dry roof tile and slow down heat transfer from inside to out.
RSL@Renotec roof coating is an easy 2 coat application which will prevent water ingress and create a beading effect on the roof tile. Water will run off the surface and will not be absorbed.
The latest thermally efficient German technology allows the damp in the roof tile to escape, allowing more efficient heating/cooling of the building.
RSL@ Renotec is an easy 2 coat application which will prevent water ingress and create a beading effect on the roof tile. Water will run off the surface and will not be absorbed.
RSL@Renotec achieves a long lifespan of over 20 years due to its chemical bond to the roof tile, creating a hydrophobic surface. This resists any moisture trying to pass through the coating.


High speed, high voltage mini servo for 500 class helicopters, cars and airplanes.
This high end mini servo offers lightening fast speeds, plenty of torque and it is 100% high voltage compatible. Ideal for 500 class helicopters, such as the Goblin 500, T-Rex 500, GAUI NX4 or X4 and more. Suitable for airplanes and cars also! Now available in a pack of 3!


This is the coolest ride ever!! DO NOT visit Islands of Adventure without going on this! You WILL NOT be disappointed! I love coasters...my mom hates them....and we both LOVED this ride! You just cant explain how awesome this ride is...you need to experience it!
This ride is so great. It is even better than most coasters are. I hope more of these are made soon. IT RULES!!!!!
This ride was AWESOME! I really liked the effects and the special things that happened during it. I liked the water spray parts and the "falling 25 stories" part which both were definitely a plus. The reason why its 9 not 10 was because some of the effects werent going and some were different "I rode this two times and the second time, the first water part didnt spray at all"
overall, I think it did great though!
A truly awesome ride. Quite possibly the best virtual ride anywhere. The 3-d affects are mind boggling. The heat, cold, and fire affects were awesome as well. Last but not least, the drop off the building was done so well that I actually thought I was falling off a building in New York! A very good ride with a detailed queue worth at least 1 ride anytime your at Islands of Adventure.
This is a great ride,I go on it every trip to IOA. Ive been on it so many times that I have practically memorized the whole attraction. The only reason this ride gets a 9 is because the queue is always an hour or more and some of the effects dont always work.
AMAZING!! In my opinion, it is the best of all dark rides. I got my brother, who hates rollercoasters, to go on it. It is really the only ride I go on with him. This and the Hulk are the best at Islands of Adventure.
Fun Fun Fun Fun!!!! I cant explain it, it must be ridden to be believed! Fun Fun FUN FUN!!! Skip Disneydump and go to Universal!!
The only thing like it in the entire world. It is the unique combination of thrill ride and 4-D movie that make this the best dark ride in America. The entire experience is awesome, the movie is great, the theming is awesome, the first time I rode it I was speachless when I came off. I still dont know how they do some of the things they do on this ride. I mean the feeling of freefalling is awesome, especially since you are barely moving. I just cant say enough about this ride.
The best 3-D ride in the U.S.! Go Universal IOA!!!That was soooo cool when it looked like you are dropping, and the buildings look as if you are falling! and how the mivies in front of you are perfectly placed to look soooo real! I can see how this ride might displease 6 5" people (see the ground, not good) but overall this is so cool! I remeber when I got off, I was in shock at what I had just experienced. But when I got out of my trance, I was like, "That was SOOOOOOOO AWESOME!!!" 1,000,000 OUT OF 10!!!
The shining gem of a boring and small park. This was really awesome and fun! I would even go so far as to say the possible future of rides to come. Be prepared, though, it will make you a little queezy if you dont go in expecting it. Its a 3-D ride that makes you really feel like youre flying and falling. Can freak you out and make ya a little sick if you dont expect it. But, heck! Ride it anyway! Its too awesome not to.


There have been reports that Carlos Boozer would consider playing in China if an NBA contract didn't come around.
It's almost the end of August and Boozer is still a free agent. So is he going to head West from Los Angeles?
Nope. Not according to Adrian Wojnarowski of Yahoo Sports.
Boozer has a place in the NBA, but that role is shrinking.
He can help a team on offense — he averaged 11.8 points while shooting 49.9 percent, and grabbing 6.8 rebounds a game last season for the Lakers. His PER of 16.8 is above the league average. He has value as a scoring big off the bench who can run the pick-and-pop.
But his defense is a mess, and that scares teams off. While it's always trendy to say, "NBA players don't play defense" that usually comes from people who don't know the game or don't follow the NBA closely. Defense in the league is still up and down, but it's improved over even a decade ago. (Go watch some regular season games from the '80s and tell me about defensive effort.) Boozer hurts teams on that end.
That said, Boozer is making the right play here. Some team will go into training camp and either suffer an injury to a big man, or realize the guys they have aren't as good as they thought, and Boozer's phone will ring. He's flawed but a solid NBA veteran you can bring in and know what you will get. The man can still put up points.
If he's patient, his time will come. And apparently he'd rather be patient than play in China.


The Usos put their SmackDown Tag Team Championship on the line in a Fatal 4-Way match at WrestleMania 35 against The Bar, Ricochet & Aleister Black and Shinsuke Nakamura & Rusev.
Very good match. The Usos retained after hitting the double splash and pin on Sheamus.


text:
Ring worn by Margaret Thatcher on day she became first female PM up for auction
The ring Margaret Thatcher wore the day she became Prime Minister and a bracelet worn while meeting Nelson Mandela are among items going up for auction next month.
Auction house Christie's is holding an online sale of some personal items to mark the 40th anniversary of her election as the UK's first female Prime Minister.
The auction will comprise 170 lots with items from Mrs Thatcher's time in office, as well as personal possessions, clothes, handbags and her "uniform" jewellery – pieces that appear in many photographs of her at the height of her career.
Christie's has estimated that pieces will sell from between £100 to £15,000.
Margaret Thatcher's 18-carat gold and amethyst ring (Christie's)
The 18-carat gold and amethyst ring, worn on the day she became Prime Minister, is expected to sell for between £1,200 and £1,800.
The ring, which she was photographed wearing arriving at 10 Downing Street on May 4 1979, is understood to have been one of her favourites as it was chosen by her children.
Another piece of her uniform jewellery going under the hammer is a hardstone-mounted gold bracelet with colourful cabochon gemstones, which has an estimated sale price of £2,000 to £3,000.
Nelson Mandela meeting Margaret Thatcher in 1990 (Mike Stephens/PA)
A gift from her husband Denis, it was worn by Mrs Thatcher during her meeting with Mandela at 10 Downing Street in 1990.
A sapphire, diamond and cultured pearl necklace is estimated to sell for between £600 and £800, and two evening suits – one of which was the blue outfit worn at a dinner to celebrate the Queen's Golden Jubilee in 2002 – are expected to go for between £1,000 and £1,500.
Other items include a diamond-set gilt Cartier pen in its box, Mrs Thatcher's House of Commons desk blotter and one of her signature handbags by Asprey with a lizard exterior.
The auction will be the third by Christie's of Mrs Thatcher's belongings, after previous sales in 2015 saw her items sell for a total of £4.5 million.
A hardstone-mounted gold bracelet of vari-shaped cabochons (Christie's)
Adrian Hume-Sayer, director and specialist of private collections, said: "The market's response to the historic sales in 2015 – both the online sale and the traditional live auction – was remarkable, with the overall result for The Mrs Thatcher Collection Part I and II far exceeding pre-sale expectations.
"Clients from all over the world seized the opportunity to acquire items which gave insights into the life of Britain's first female Prime Minister, who was a political giant on the world stage.
"In May 2019, Christie's third and final sale in this trilogy of auctions coincides with the 40th anniversary of Mrs Thatcher's historic election, offering collectors, admirers and enthusiasts with one last chance to bid for a memento of 'The Iron Lady'."
Mrs Thatcher, Part III, an online sale, will be open for bidding between May 2 – May 9. The sale is available to view online now.


We realize that sometimes patients need to contact us with a concern or general question. It might be something that you've read or seen online that you'd like to ask us about, or a query regarding the cost of your treatment.
You can e-mail one of the principal dentists using the link below. They will receive your e-mail with a priority alert try and will try to get back to you within 48 hours.


text:
(11754) Herbig (2560 P-L) – planetoida z pasa głównego asteroid okrążająca Słońce w ciągu 4,9 lat w średniej odległości 2,88 j.a. Odkryta 24 września 1960 roku.

Zobacz też
 lista planetoid 11001–12000
 lista planetoid

Linki zewnętrzne

Planetoidy pasa głównego
Nazwane planetoidy
Obiekty astronomiczne odkryte w 1960


The Switch has become a hotbed for ports of arcade games, but Sega seems to be going above and beyond for their next arcade port.
Sega revealed new details for their Sega Ages port of Virtua Racing yesterday, and it's a bit crazy. The Switch version of the game will support online multiplayer for two players, as well as an absolutely bonkers local multiplayer mode supporting split-screen gameplay for up to eight players.
Sega Ages: Virtua Racing launches in Japan in Spring of this year (Autumn for us down under), but there's currently no word as to when we'll see the game in the West. However, given the amount of Ages games still to come, and the seemingly increasing delay between the Japanese and Western releases of these games, we wager it'll probably be a while.
Suicune, Pikachu and Gardevoir join the Pokkén Tournament!


I have an idea for a medical appliance that I do not believe is currently on the market. I have no engineering background and have no idea where to start to get this idea evaluated, mocked up, and potentially marketed.
I can give you the perspective of a medical device inventor with almost 40 years in the medical device industry.
First, you need to come up with a sufficiently vague description of your invention so that you can talk about it without losing key patent rights here or abroad. For a "ball-park" quick estimate of the viability of this idea, you can follow these steps.
You need to see if the idea is for a "must-have" or "nice-to-have" product. If it's the former, talk to several potential customers about what the product does, how it would help the patient, why it's better than existing products, how much the potential customer would be willing to pay for the device, whether there are similar products already cleared for marketing by the FDA, whether the use of those other products in a medical procedure has been assigned a CPT (Common Procedural Terminology) code by the AMA (American Medical Association), how long it will take to perform this procedure, whether insurance companies (called third-party payers, and including Medicare) will pay (reimburse) the healthcare provider for performing the procedure and how much the reimbursement is in, say, Manhattan, NY (one of the highest reimbursed regions in the US.) You may have to guess at the manufacturing cost of a device you have not designed yet, but if there is a similar device on the market and it's not too complex, you could guess that cost as less than 20% of the selling price.
If your idea is for a single-use disposable device, you will need to calculate if its delivered cost is significantly less than the "technical component," or TC, of the reimbursement amount. Finally you will need to calculate if use of your disposable device is worth the doctor's time, especially if you are going to try to influence them to use a procedure involving your device instead of another procedure using a competitor's existing device; you calculate the "return on time" (R.O.T.) by dividing the professional component (PC) of the reimbursement by the time to do the procedure. If you are likely to achieve at least as good a clinical result as existing equipment but with a higher R.O.T. then doctors are more likely to use your invention.
If your idea is for capital equipment that the doctor buys, then you need to calculate how many times a week that equipment will be used, how much the total reimbursements (TC + PC) will be per week and calculate how many weeks it will take the doctor to break even. Many doctors in private practice are happy to break even in a year. You will still need to calculate the R.O.T. for your device versus the competition (where now you use both components of the reimbursement in the calculation) and show the doctor an advantage.
Again, this is a very rough estimate, given that your product idea is not a costed-out design. But if the quick analyses above indicate that you will have an advantage over your competition and that you can generate enough revenue to support a company (or other options), it will be worth taking the next step and consulting a patent agent or attorney to protect your idea, and the folks that can turn the idea into a product.
Of course, Jerry didn't have much information to base his answer on, but he offers a lot of great insights for entrepreneurs considering the feasibility of a medical device venture.


text:
maandag, 03 juni 2019 / Published in Nieuws (Internationaal)
French Retail Chain Carrefour Registers Sales Boost Following Blockchain Integration
French retail giant Carrefour has seen an increase in sales after the implementation of a blockchain-based tracking system.
French retail giant Carrefour has seen an increase in sales after the implementation of a blockchain-based tracking system, Reuters reported on June 3.
Carrefour's blockchain tracking system enables customers to track the supply chain of 20 items, including meat, milk, and fruit from farms to stores, thus avoiding products with genetically modified organisms, antibiotics, and pesticides. This year, the company reportedly plans to add 100 more products, including non-food lines, to the system.
Emmanuel Delerm, Carrefour's blockchain project manager, told Reuters that "the pomelo sold faster than the year before due to blockchain. We had a positive impact on the chicken versus the non-blockchain chicken."
The company also revealed that the tracking system was most widely used in China, followed by Italy and France. "Millennials are buying less but buying better products for their health, for the planet," Delerm said.
Carrefour initially began working on the tracking system in collaboration with IBM by joining IBM's blockchain-based food tracking network dubbed Food Trust last year along with other supermarket chains and retail companies like Nestle SA, Dole Food Co., McCormick and Co., McLane Co., Tyson Foods Inc., and Unilever NV, among others.
In mid-April, Carrefour and Switzerland-based food giant Nestlé partnered with IBM to use the latter's blockchain technology to track the supply chain of Mousline, a well-known brand of instant mashed potatoes. The system lets consumers check the varieties of potato used, the dates and places of manufacture, information on quality control, and places and dates of storage.
Recently, Big Four audit firm EY revealed that it is now providing its proprietary blockchain solution for a major new platform that helps consumers across Asia determine the quality, provenance and authenticity of imported European wines.
Weiss Ratings Now Favors BTC Out of 122 Cryptocurrencies
Crypto Mining Could Bring Russia $1B in Taxes, Report Suggests
Blockchain-Driven Real Estate Platform Closes Seed Funding Round Backed by Morgan Creek


Family Fun Night is TOMORROW and we are ready!!
PTP Dessert Table - volunteers please bring 2 dozen treats anytime tomorrow to the school. If you place in the teacher's lounge during the day please mark "Family Fun Night". If you bring after school or into the evening please take directly into the cafeteria. If possible please individually wrap items in shrink wrap or plastic baggies. We have extra supplies and volunteers if needed at the school that can help wrap items.
Set Up Volunteers - if you are able to help set up before Family Fun Night please come to the school at anytime between 3:30 - 5:30pm and we can assign you a job when you get to the school.
Event Volunteers: please arrive by 5:15pm if you are on the early shift so we can get organized. If anyone has any middle school or high schoolers that would like to help with the food area please let me know!
Childcare - if you are utilizing the free childcare at the rec center, please drop them off directly at the rec. There will be a sign in/sign out sheet for parents.
Event Pictures - if anyone has a digital camera and is interested in taking event pictures throughout the school please let me know!
T-Shirts - if you ordered a Mouse & The Motorcycle shirt please wear it to school and/or the event tomorrow evening. If you didn't order a shirt please feel free to wear a Falcons pride shirt!
If anyone has any questions please do not hesitate to ask! My cell number is 712-371-9681 if you need to reach me tomorrow.
Thank you to everyone for all of your hard work with our One Book, One School Event - this is going to be MOUSE-TASTIC! GO FALCONS!


text:
Home Sports Kumarasinghe looks back on stellar year for Thomian cricket
Kumarasinghe looks back on stellar year for Thomian cricket
By Amindha de Alwis
The 2018-19 season has been one like no other for Thomian cricket. Led by Captain Sithara Hapuhinna, S. Thomas' College emerged champions in the Singer U-19 Division One Limited-overs tournament, won the Royal-Thomian Big Match encounter after a lapse of 12 years and reached the finals of the U-19 Two-day Championship. To cap it all off, the team also made two successful tours to Australia and England in December and June respectively.
In an exclusive interview with the 'Daily Mirror', Head Coach Dinesh Kumarasinghe who retired at the end of the season, remarked that this was one of the most successful cricketing seasons in Thomian history. Indeed, reaching the finals of both major U-19 tournaments as well as winning the Big Match is a feat unparalleled by any Thomian side.
Kumarasinghe stressed that the heights achieved by the side was the culmination of a lot of hard work. "We start three months before the season and we have a special physical training programme with a trainer. We also play a series of practice matches, so by September we are ready for the season," he said. He also stated that the team is trained at a level akin to club standards which helps them play with a professional mindset that aids consistent performance.
Standout Performers
Leading the way with the bat was skipper Sithara Hapuhinna who amassed 1049 runs over the course of the 2-day tournament. Shalin de Mel too had a prolific season with 899 runs next to his name. Ravindu de Silva and Umayanga Suwaris made headlines in the semi-final of the 2-day tournament, putting on a triple century partnership against Nalanda College with de Silva notching up a double century (213).
In the bowling department, former captain Dellon Peiris (78 wickets) and Sri Lanka U-19 National Kalana Perera were the wreckers-in-chief. Left arm seamer, Perera in particular, had a fine season, picking up 90 wickets in the Two-day tournament -an achievement that is no mean feat for a fast bowler on Sri Lankan wickets. He starred in this year's Royal-Thomian Big Match with six wickets in the first innings, as well as an important 62 runs with the bat. The six wicket haul brought him his third 5-fer in the Royal-Thomian which is a record in the series.
Kumarasinghe referred to Perera as someone who could go far in his cricketing career. "Kalana Perera is a potential national player. At the moment he is in South Africa with the emerging team. He has a good future ahead of him but he needs to be managed properly. At College we handled him carefully and limited him to short sharp spells because with the conditions in this country, if you give such bowlers 10-12 overs in a row, they get injuries," he said.
Limited overs championship
S. Thomas' College clinched the U-19 Limited Overs title with a 12 run victory over Richmond College, Galle in the final held on the 9th of April. Yohan Perera's 124 runs and three important wickets by Shannon Fernando made the difference in what was a closely fought tussle. This was in fact the third occasion that S. Thomas' College had won the 50-over championship under Kumarasinghe with the other 2 championships having been won during his first stint as Thomian coach from 1988-2003.
The Thomian outfit came within touching distance of the Two-day Championship, but was beaten to the trophy by St. Joseph's College in the final.
Tours to Australia and England
During the mid-season break in December, the team travelled to Adelaide, Australia to participate in the Chappell Brothers Challenge Trophy. The team was able to win the trophy and Kalana Perera was adjudged the 'best bowler of the tournament'.
In addition, as a reward for their performance during the season, the team recently made a tour to England and participated in seven matches with local teams. Two of the games were washed out, but the Thomians put up an impressive display to win four of the remaining matches while losing just the one game; and that too in the final over.
The tour of England marked the second occasion that a Thomian side coached by Kumarasinghe had made a tour to the country. He had previously been at the helm when the Royal-Thomian winning side skippered by Nilanka Peiris, made a visit to the country to play seven minor counties in 1997.
Developing the structure of Thomian cricket
When Kumarasinghe commenced his second stint as Thomian coach in 2013, on an invitation by then Warden, Prof. Indra De Soysa and the cricket advisory committee, his long term plan was to develop the junior structure in the school. "So I started an academy and we now have more than 200 boys involved in it. The academy is for kids below 11 years of age and at the end of the year we have a cricket carnival where we pick the cream and train them," Kumarasinghe said. He added that the boys who miss out on selection to the development squadsalso continue to receive training since there may be late developers among them.
Outside the schoolboy level, S. Thomas' College recently started the Old Thomians Cricket Club to encourage players who have left school to continue playing the game. "A lot of Thomians don't continue playing cricket after leaving school. They give up. So when we have our own club, they have incentive to continue because we have all the facilities. When we entered for the Division Three tournament, we won the Championship in our first year and we were promoted to division two. Then in Division Two we won the Western Province Championship," he said.
Kumarasinghe who retired from his position as Head Coach at the end of the season, was appreciative of the support rendered to him bythe Warden Rev. Marc Billimoria, the Sub-Warden Asanka Perera, the cricket advisory committee and old boys around the world for helping him develop cricket in the school.
Upcoming 2019/20 season
S. Thomas' will enter the upcoming season having lost eight (8) of their senior players from the last season. Sri Lanka U-19 representative Ravindu de Silva who impressed with 85 runs in the final match of the recent Youth ODI series against Pakistan U-19s will be the one to watch in what will be his final season at school and Shalin de Mel, Umayanga Suwaris, Thevin Eriyagama and Maneesha Rupasinghe will be among the other players expected to lead the team forward.


project plan template communication microsoft team excel 9 templates word format download.
project com plan template luxury change free templates it management communication pdf templa.
project communication plan example non profit crisis template picture excel ppt mergers and acquisitions templates.
communication plan e for project management change and example a social media strategy communications template doc comm.
free communication plan template project example doc simple examples templates lab.
project communication plan template communications word free client pmbok sample.
template sample project communication plan 9 in communications strategy microsoft team excel free commu.
project com plan template excel internal exceptional download event large communication doc management succe.
project communication plan your organization template example pdf.
gallery of project communication plan template lovely document brochure templates professional fold bi doc pro.
sample pr plan template communications strategy project communication example doc templates free.
project communication plan template best of initiation pmbok elegant c.
project communication plan template free download girls guide management pmbok.
communication and visibility plan template program project excel example.
free communication plan template project management example pdf simple examples templates lab.
communications plan example project communication template doc planning management.
simple project management plan template excel communication download communications sample free planning matrix doc strategic co.
project communication plan template word sample management simple format neat example of church planning via f excel schedule communic.
communication management plan template project sample doc program excel comm.
project communication plan template management large example doc communications.
project com plan template excel new communication free modern master.
the project communication plan template ppt.
project communication plan template flow chart large management example flowchart what is.
the project communication plan template pdf.
project team communication plan word format free download template 9 templates.
project com plan template elegant management communication excel man.
university communication plan template strategic communications planning a free example page project manageme.
communications strategy template awesome risk management google search project communication plan example pdf 7 m.
communication plan template project example pdf samples of templates word.
data management strategy template vendor checklist project strategic plan example planning form communication team excel the.
internal communications plan template example project communication management free.


Is there a safe way to move a Time Machine backup on an external USB hard drive to a Time Capsule?
Yes, it's straightforward to do it, even though it would take quite sometime to complete depending on the size of your current backups. Follow the detailed procedure at Copy Local backups to be used on a NETWORK.
Here's a summary of what's required and the steps.
The backups go into a sparsebundle on a Time Capsule. So you need to create that sparsebundle on the Time Capsule, mount it in Finder and then copy over everything from your USB drive into the mounted volume.
Configure Time Machine to back up to the Time Capsule and start a backup. This will make it create the sparsebundle.
Cancel the backup once the copying starts (as seen in the progress window).
Delete the Backups.backupdb folder inside this volume (you'll be replacing it with the backup you already have).
Open your current Time Machine backup USB drive in Finder and copy the Backups.backupdb folder from it to the Time Machine Backups partition (mounted from the Time Capsule).
Enter your administrator password and accept the prompts (this may happen a couple of times).
Not the answer you're looking for? Browse other questions tagged time-machine time-capsule .
How to migrate several usb Time Machine backups to a Time Capsule?
Any ideas why my Airport Extreme identifies itself as a Time Capsule in Time Machine?
Can I backup a Time Capsule to a HDD drive connected to its USB port?