A vocal valve for connection to a tracheostoma comprises a filter (16) for moisture and heat exchange at breathing through the vocal valve, and a housing (15) receiving the filter and having a first opening at one side of the filter to be connected to the tracheostoma, and at least one second opening at the opposite side of the filter, which communicates with the surroundings. A manually operated valve element (15′) for blocking the air passage through the filter is constructed to close said first opening at manual operation thereof.
Voltage-gated ion channels play fundamental roles in neural excitability, they are for instance responsible for every single heart beat in our bodies, and dysfunctional channels cause disease that can be even lethal. Understanding how the voltage sensor of these channels function is critical for drug design of compounds targeting neuronal excitability.. The opening and closing of the pore in voltage-gated potassium (Kv) channels is caused by the arginine-rich S4 helix of the voltage sensor domain (VSD) moving in response to an external potential. In fact, VSDs are remarkably efficient at turning membrane potential into conformational changes, which likely makes them the smallest existing biological engines. Exactly how this is accomplished is not yet fully known and an area of hot debate, especially due to the lack of structures of the resting and intermediate states along the activation pathway. In this thesis I study how the VSD activation works and show how toxic compounds modulate channel ...
Ion channel conductance can be influenced by electrostatic effects originating from fixed surface charges that are remote from the selectivity filter. To explore whether surface charges contribute to the conductance properties of Kir2.1 channels, unitary conductance was measured in cell-attached recordings of Chinese hamster ovary (CHO) cells transfected with Kir2.1 channels over a range of K + activities (4.6-293.5 mM) using single-channel measurements as well as nonstationary fluctuation analysis for low K + activities. K + ion concentrations were shown to equilibrate across the cell membrane in our studies using the voltage-sensitive dye DiBAC 4 (5). The dependence of γ on the K + activity (a K ) was fit well by a modified Langmuir binding isotherm, with a nonzero intercept as a K approaches 0 mM, suggesting electrostatic surface charge effects. Following the addition of 100 mM N-methyl-D-glucamine (NMG + ), a nonpermeant, nonblocking cation or following pretreatment with 50 mM ...
In this study, we found that mutation E219R shifts Q-V relationship leftwards by 126 mV at 0 Ca2+ compared with WT and changes slope factor from 50 to 38 mV, indicating an increase of gating charge (Fig. 1A,B). In addition to the direct effects on voltage sensor movements, the mutation also shifts G-V relationship rightwards at 0 Ca2+ and increases Ca2+ sensitivity (Fig. 1C-F), which are the results of an electrostatic interaction between E219R and E321/E324 (Figs. 2 and 3) that alters the coupling among the activation gate, voltage sensor, and Ca2+ binding (Fig. 4; Table 2).. Ion channels often contain distinct structural domains for sensing physiological stimuli and the pore-activation gate. The coupling among these domains during channel activation is an important molecular process that has not been fully understood. One basic question is as follows: what kind of changes in the properties of channel function would indicate a change of coupling? It has been elegantly shown that, in ...
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Na Channel Has a quick onset and quickly turns off: inactivating channel. K is the opposite with slow onset and slow turn off: noninactivating channel. This difference is caused by differences in the two proteins. The Na channel has two gates: the activation gate and the inactivation gate. The activation gate is sensitive to the potential. When the activation gate is closed the inactivation gate is closed. When the inside of the cell is depolarized, the activation gate quickly opens. The inactivation gate, composed of negative proteins, slowly is repelled by the positive change in the intracellular environment, so it closes the channel by find its way into the pore of the channel.. K Channel. Has a single gate activated by the membrane potential, so it will stay open all the time the membrane has a certain potential. Na and K Conductances Nas conductance is characterized by a rapid onset and a rapid offset. Ks conductance is characterized by a slow onset and a slow offset. Membrane potential ...
A device for the uniform dosing of an amount of faeces onto reagent paper for the detection of a component material in the faeces. The device comprises test paper and a template disposed thereover having a given thickness and comprising at least one set of two superposed openings of any desired shape. Each set of openings includes a first opening and a second opening disposed between the first opening and the test paper and having a larger area than and encompassing the area of the first opening.
A coordinate measuring system having a quick disconnect is disclosed. The coordinate measuring system includes a multijointed arm having a first end and a plurality of transfer housings for generating signals indicating the position of the first end. A first locking device is mountable to a second end of the arm. The first locking device has a first surface which is removably received within a first opening in a housing. The housing is mountable to a support and includes a second opening for communicating with the first opening. A second locking device having a second surface is movably received within the second opening from an unlocked position to a locked position and constitutes a cam which rotates to engage the first locking device. The second surface engages the first surface in the locked position to prevent the first locking member from being removed from the first opening. The first and second surfaces are not engaged in the unlocked position so that the first locking member can be removed from
A method and system are disclosed for enabling point-to-point and multicast communication in a multiple access network using three types of communication channels, namely, one or more upstream payload channels, one or more upstream control channels and one or more downstream channels. Each channel illustratively is divided into slots or mini-slots. Each upstream payload channel is assigned for carrying upstream directed payload bitstreams from stations to a central controller. The central controller has an independent receiver for each upstream channel for simultaneous reception of control and payload bitstreams. Each station has at least one frequency agile programmable transmitter for sequential transmission of control and payload bitstreams or separate upstream control and payload channel transmitters, respectively, for simultaneous transmission of control and payload bitstreams. Each upstream control channel is assigned for carrying upstream directed control bitstreams, such as reservation request
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The above discussion suggests that the inner vestibule would be large enough for sugars to enter. On this basis, the presence of sugars in the vestibule would be expected to interfere with the passage of K+ from the intracellular bulk solution through the vestibule to the selectivity filter. Our data support this conclusion. For sucrose ≤1 M, glycerol and glucose ≤2 M, and for voltages ≤200 mV, diffusion-limited currents were not observed, yet sugars still reduced the unitary currents (Figs. 1 and 2). Because the diffusion of K+ from the bulk solution into the vestibule was not rate limiting for these experiments, then these observations suggest that sugars are entering the vestibule and slowing the transit of K+ through the vestibule to the selectivity filter.. Sugars within the vestibule would reduce the effective area available for diffusion through the vestibule. An empirical model that assumed that the fractional reduction of outward current was proportional to the fractional volume ...
CiteSeerX - Scientific articles matching the query: Side Channel Analysis of Practical Pairing Implementations: Which Path Is More Secure?
Archaeal TRIC family homologue of 205 aas and 7 TMSs. In animals, Ca2+ release from the sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER) is crucial for muscle contraction, cell growth, apoptosis, learning and memory. The eukaryotic TRIC channels are cation channels balancing the SR and ER membrane potentials, and are implicated in Ca2+ signaling and homeostasis. Kasuya et al. 2016 presented crystal structures of two prokaryotic TRIC channels in the closed state and conducted structure-based functional analyses of these channels. Each trimer subunit consists of seven TMSs with two inverted 3 TMS repeats (Silverio and Saier 2011). The electrophysiological, biochemical and biophysical analyses revealed that TRIC channels possess an ion-conducting pore within each subunit, and that trimer formation contributes to the stability of the protein. The symmetrically related TMS2 and TMS5 helices are kinked at conserved glycine clusters, and these kinks are important for channel activity. The ...
To describe the [K+]ext and voltage dependence of Po at depolarized voltages, we developed a series of kinetic schemes in which both K+ binding and hyperpolarization are coupled to relative energetic stabilization of the open-conductive state over the open-inactivated state. Rate constants and voltage dependences for transitions among conductive and inactivated states in the schemes were constrained by two-dimensional distributions of adjacent open and closed dwell-times obtained over a range of [K+]ext and voltage for each channel (Rothberg and Magleby, 1998, 1999, 2000). Schemes were ranked statistically after applying a penalty for increasing the number of free parameters in a scheme, according to Eq. 6.. We took the approach of fitting the simplest scheme, with one open-conductive (O) and one open-inactivated (I) state, and then adding additional states (O or I) until a further addition yielded no significant improvement in the maximum likelihood value for the scheme. For each scheme, we ...
A balloon dilation catheter comprising a tubular member having a proximal end and a distal end. An inflatable balloon is disposed at the distal end of the tubular member. A first lumen is disposed in the tubular member and in is communication with an interior of the inflatable balloon. A second lumen is disposed in the tubular member for receiving a guidewire substantially along a portion of its length. The second lumen has a first opening in the proximal region of the tubular member and a second opening at the distal region of the tubular member. A first slit is disposed longitudinally in the tubular member and extends along at least a portion of the tubular member, the first slit comprising a first pair of longitudinal edges in a side by side relationship. The tubular member is constructed of a resilient material such that, as the guidewire is separated from the second lumen, the longitudinal edges are biassed open from a first position to a second position having a gap greater than or equal a
A modular fluid heating apparatus may be assembled from a plurality of modular heating components. Each modular heating component includes a first molded section defining a first opening therethrough and a second molded section defining a second opening therethrough. The molded sections are mated and define an enclosed area between the molded sections. The first and second openings are aligned to form a fluid tight passage through the modular heating component. A resistance heating element is secured between the first and second molded sections in the enclosed area. The resistance heating element includes a supporting substrate having a first surface thereon and an electrical resistance heating material fastened to the first surface of the supporting substrate. The resistance heating material forms a predetermined circuit path having a pair of terminal end portions fixed to a pair of electrical connectors. The modular heating components are sealably mated to define a fluid collection area between
A high-speed race awaits guests this summer when Wet ‘n Wild Orlando opens Florida’s tallest and fastest water-based racing attraction of its kind.
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Solidarités International (SI) is a French humanitarian organisation operating for over 35 years who is committed to providing aid in the event of
Hi all, posting a book here: My Windows 7 Ultimate 64 bit does not seem to open any 32 bit programs. When I try to open a 32 bit program, it shows up in the task manager for a few seconds (e.g. firefox.exe x32), then disappears after a few seconds. I can open Internet Explorer 64 bit fine, run it with no programs, but the 32 bit version doesnt work. I also cant access many of the Windows control panel settings, such as Uninstall Programs. I can open the Control Panel folder, but
Four years ago, James Larrimore didnt give a second thought to putting on a pair of pants or taking a shower. Then came the mulching machine accident in which he lost his left arm.Since then, Mr.
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My pool builder opened our pool about a month ago. As the pool was built late last summer, its the first opening weve had. Pool builder says he typically adds sequestriant when he opens his pools. Well when he came out last month, he didnt have the sequestriant with him and said he would drop it by the house. I figured it couldnt hurt to add it when I received it. Cut to today, where I have everything fairly well dialed in (I have a SWG): FC 5 pH 7.6 TA 80 Calcium 240 CYA 40 (still
Introducing myself -- an old newbie. Bought a house 2 years ago with an inground pool. Never owned or managed a pool before. First year, first opening, what a mess, too many trees near the uncovered pool. lots of vacuuming, scooping, bleach, backwashing, etc. Finally got into a routine, about 4 gallons a week. Then got the Del Ozonator, then the FloatTron, down to one gallon a week. Installed a new timer for the pump so that it didnt run 24/7, and had a leak (pool light) fixed. Next
Each α subunit - hence also Nav1.7 - is composed of four homologous domains (DI-DIV), with each domain consisting of six transmembrane segments (S1-S6), with S4 acting as a voltage-sensor and S5 and S6 lining the pore [815]. Structural modellings approach of Nav1.7 have identified an aromatic residue within the cytoplasm-proximal portion of each of the pore-lining S6 helices that were predicted to form a hydrophobic ring at the cytoplasmic end of the pore that stabilizes the channels pre-open state. This element is predicted to raise the energy barrier for the movement of S6, which is necessary to open the channels pore, thus stabilizing the closed or pre-open state of the channel [1419][1420]. ...
Network Forgetting a new co-workers name is a common problem, but admitting it openly is a surprisingly welcomed solution, and it can open the door to positive rapport. Eric Cai writes more from his experience.. ...
Sigma-Aldrichs Cell Signaling & Neuroscience Voltage-Gated Ion Channels. The majority of ion channels fall into two broad categories: voltage-gated ion channels (VGIC) and ligand-gated ion channels (LGIC). Members of the VGIC superfamily are usually closed at the resting potential of the cell.
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TY - JOUR. T1 - Hypoxia modulates nitric oxide-induced regulation of NMDA receptor currents and neuronal cell death. AU - Gbadegesin, Muyiwa. AU - Vicini, Stefano. AU - Hewett, Sandra. AU - Wink, David A.. AU - Espey, Michael. AU - Pluta, Ryszard M.. AU - Colton, Carol A.. PY - 1999. Y1 - 1999. N2 - Nitric oxide (NO) released from a new chemical class of donors enhances N-methyl-D-aspartate (NMDA) channel activity. Using whole cell and single- channel patch-clamp techniques, we have shown that (Z)-1-[N(3-ammoniopropyl)- N-(n-propyl)amino]-NO (PAPA-NO) and diethylamine NO, commonly termed NONOates, potentiate the glutamate-mediated response of recombinant rat NMDA receptors(NR1/NR2A) expressed in HEK-293 cells. The overall effect is an increase in both peak and steady-state whole cell currents induced by glutamate. Single-channel studies demonstrate a significant increase in open probability but no change in the mean single-channel open time or mean channel conductance. Reduction in oxygen levels ...
Experiments are often performed to study the behaviour of a single ion channel in response to a perturbation produced by a step change (jump) in a variable that influences its equilibrium position, for example a voltage jump or jump in agonist concentration. It is also common to apply a rectangular pulse (consisting of an on jump followed by an off jump); for example brief concentration pulses are used to mimic synaptic transmission.. Assuming a general Markov mechanism for channel dynamics, we obtain theoretical probability distributions of observable characteristics that describe the non-stationary behaviour of single ion channels which are subject to a jump, or to a pulse of finite duration. These characteristics are such things as open times, shut times, first latency, burst length and length of activation. We concentrate particularly on jumps to or from a zero level of agonist, which necessitates some modification to the usual arguments to cope with having some absorbing sets of states. ...
Changes of the electrical charges across the surface cell membrane are absolutely necessary to maintain cellular homeostasis in physiological as well as in pathological conditions. The opening of ion channels alter the charge distribution across the surface membrane as they allow the diffusion of ions such as K+, Ca++, Cl−, Na+. Traditionally, voltage-gated ion channels (VGIC) are known to play fundamental roles in controlling rapid bioelectrical signaling including action potential and/or contraction. However, several investigations have revealed that these classes of proteins can also contribute significantly to cell mitotic biochemical signaling, cell cycle progression, as well as cell volume regulation. All these functions are critically important for cancer cell proliferation. Interestingly, a variety of distinct VGICs are expressed in different cancer cell types, including metastasis but not in the tissues from which these tumors were generated. Given the increasing evidence suggesting ...
Concentration-dependent biphasic effects of drugs on ion channel activity have been reported in a variety of preparations, usually with stimulatory effects seen at low concentrations followed by increasingly dominant inhibition at higher levels. Such behaviour is often interpreted as evidence for the existence of separate modulatory drug binding sites. We demonstrate in this paper that it is possible for biphasic effects to be produced in an allosteric model of a ligand-activated ion channel, where diffusion-limited binding of the modulatory drug is restricted to either a stimulatory or an inhibitory site (but not both) because of steric overlap. The possibility of such an interaction mechanism should be kept in mind when interpreting experimental data if stoichiometric evidence from complementary techniques suggests that only one drug molecule is bound per receptor/ion channel complex.. ...
A system that stores a color management transform, typically using a grid table, where one or more of the input channels represents parameters used to control the reproduction of the conventional color image channels. The invention augments the existing grid-table based transform structure with additional channels to control the operation of the color models involved. These additional channels are not the conventional calorimetric or colorant image channels such as red, green, and blue, but are to control other aspects of the color transformation, such as exposure level or saturation. The augmentation also includes identification information that identifies the type of control (exposure, grey component replacement, etc.) the extra channels provide.
The gating of voltage-gated ion channels is controlled by the arginine-rich S4 helix of the voltage-sensor domain moving in response to an external potential. Recent studies have suggested that S4 moves in three to four steps to open the conducting pore, thus visiting several intermediate conformations during gating. However, the exact conformational changes are not known in detail. For instance, it has been suggested that there is a local rotation in the helix corresponding to short segments of a 3(10)-helix moving along S4 during opening and closing. Here, we have explored the energetics of the transition between the fully open state (based on the X-ray structure) and the first intermediate state towards channel closing (C-1), modeled from experimental constraints. We show that conformations within 3 angstrom of the X-ray structure are obtained in simulations starting from the C-1 model, and directly observe the previously suggested sliding 3(10)-helix region in S4. Through systematic free ...
Correlations between the voltage-gated ion channels shal (A-C), CbNav (D-F), and shaker (G-I) and soma size, actin, and tubulin expression. Points represe
Voltage-gated potassium (KV) channels open in response to membrane depolarization and are present in many cell types. In excitable cells, KV channels serve as the primary mechanism of repolarization of action potentials, whereas in nonexcitable cells, KV channels control the cell resting potential. Given the role of KV channels, it is not surprising that they regulate many fundamental physiological processes and are therefore considered important therapeutic targets for treatment of autoimmune, metabolic, neurological, and cardiovascular disorders, as well as cancer (Wulff et al., 2009). Despite these facts, there has been limited success in the clinical development of therapeutic agents that target KV channels. One reason for this is that many of the small molecules identified to date lack true molecular selectivity across members of the KV and other ion channel families, which could significantly compromise their therapeutic index. The lack of ion channel selectivity seems to be due to binding ...
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Some characteristic features of band structures, like the band degeneracy at high symmetry points or the existence of energy gaps, usually reflect the symmetry of the crystal or, more precisely, the symmetry of the wave vector group at the relevant points of the Brillouin zone. In this paper, we will illustrate this property by considering two-dimensional (2D)-hexagonal lattices characterized by a possible two-fold degenerate band at the K points with a linear dispersion (Dirac points). By combining scanning tunneling spectroscopy and angle-resolved photoemission, we study the electronic properties of a similar system: the Ag/Cu(111) interface reconstruction characterized by a hexagonal superlattice, and we show that the gap opening at the K points of the Brillouin zone of the reconstructed cell is due to the symmetry breaking of the wave vector group.
Voltage-dependent ion channels are gated by voltage sensors that show a switchlike response to voltage differences across the membrane. Tao et al. used mutagenesis, electrophysiology, and x-ray crystallography to gain insight into the molecular basis of this response in voltage-dependent potassium channels. An occluded site was identified that catalyzes translation of positive charges across the membrane. The closed channel appears to be associated with a distribution of conformations, depending on the degree of hyperpolarization of the membrane, whereas the open channel appears to be associated with a specific conformation. Thus, the transition of the ion channel from open to closed occurs over a very small voltage difference.. X. Tao, A. Lee, W. Limapichat, D. A. Dougherty, R. MacKinnon, A gating charge transfer center in voltage sensors. Science 328, 67-73 (2010). [Abstract] [Full Text] ...
101年公務人員特種考試關務人員考試、101年公務人員特種考試 移民行政人員考試及101年國軍上校以上軍官轉任公務人員考試試題 代號:11130 等 別: 三等關務人員考試 類(科)別: 藥事 科 目: 藥理學與藥物化學 一、請說明下列各專有名詞之異同處。(20 分) (一) Antagonist & Inverse agonist (二) Pharmacodynamic & Pharmacokinetic (三) Ligand-gated channels & Voltage-gated channels (四) Ionotropic receptors & Metabotropic receptors (五) Tachyphylaxis & Supersensitivity ...
TY - JOUR. T1 - Voltage-Dependent Inactivation of MscS Occurs Independently of the Positively Charged Residues in the Transmembrane Domain. AU - Nomura, Takeshi. AU - Sokabe, Masahiro. AU - Yoshimura, Kenjiro. PY - 2016. Y1 - 2016. N2 - MscS (mechanosensitive channel of small conductance) is ubiquitously found among bacteria and plays a major role in avoiding cell lysis upon rapid osmotic downshock. The gating of MscS is modulated by voltage, but little is known about how MscS senses membrane potential. Three arginine residues (Arg-46, Arg-54, and Arg-74) in the transmembrane (TM) domain are possible to respond to voltage judging from the MscS structure. To examine whether these residues are involved in the voltage dependence of MscS, we neutralized the charge of each residue by substituting with asparagine (R46N, R54N, and R74N). Mechanical threshold for the opening of the expressed wild-type MscS and asparagine mutants did not change with voltage in the range from -40 to +100 mV. By contrast, ...
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NMDARs retained in circulating RBCs remain functional and keep responding to stimulation with glutamate, HCA, or NMDA as well as to the inhibition by MK-801 (Figs. 3-6). Calcium transport through the receptor is electrogenic, putting NMDARs in line with other calcium-transporting ion channels (Fig. 4). The number of such ion channels in RBC is rather limited and their molecular identity often remains unknown (28). Among the TRP channels, only TRPC6 is described in RBC (17). Furthermore, there is biochemical and functional evidence for a CaV2.1 channel (1, 71). There are numerous electrophysiological reports of Ca2+-permeable channels that can be grouped in two categories: nonselective voltage activated cation channels (NSVAC; e.g., Refs. 4, 29) and receptor-mediated channels (e.g., Refs. 13, 25). Although the I-V curve for NSVAC in whole cell conductance mode (55) differs from that shown in Fig. 4D, NMDARs and NSVACs have one common property. Both channels share the hysteresis of whole cell ...
... and Cobalt 10 are offered as a base console with 5000 control channels and 4,096 outputs (8 universes of DMX512A). A single control channel may control only intensity (dimmers) or it may control a DMX-controlled device (moving light, LED, media server, etc ...
Adenoviral i-eag domains restored slow deactivation in hiPSC-CMs.Representative tail currents recorded from hiPSC-CMs infected by: A, WT hERG1a.Ad; B, hERG1a(R5
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
Business Overview from 10-K filing for Icagen, Inc.:. We are a biopharmaceutical company focused on the discovery, development and commercialization of novel orally-administered small molecule drugs that modulate ion channel targets. Ions are charged particles, such as sodium, potassium, calcium and chloride. Ion channels are protein structures found in virtually every cell of the human body. Ion channels span the cell membrane and regulate the flow of ions into and out of cells. There are currently over 35 drugs marketed by third parties for multiple indications that modulate ion channels according to data from IMS Health. We believe this demonstrates that ion channels are attractive drug targets. Utilizing our proprietary know-how and integrated scientific and drug development capabilities, we have identified multiple drug candidates that modulate ion channels. ...
An apparatus for establishing a re-usable, recurring, mechanical connection to an organ within a patient is provided. A body fluid cartridge exchange platform device includes a hollow cartridge platform housing with a first end having an opening. The platform housing can additionally have a second end with a second opening. The first opening and the second opening facilitate insertion of an exchange cartridge insert that sealably engages the housing. The first opening and the second opening additionally facilitate removal of the exchange cartridge insert. The exchange cartridge insert can facilitate a flow path between a first leg and a second leg of the platform housing, and can facilitate a flow path between the platform housing and an external location for medical procedure or drug delivery purposes.
A pressure swing sorption system comprises first and second sorbing chambers each including first and second openings defining a gas flow path between them, a sorbent bed disposed in the gas flow path and having a sorption inlet region near the first opening, and a heater positioned near the sorption inlet region of the sorbent bed. A valve arrangement interconnects an intake, an exhaust, and the first openings of the first and second sorbing chambers and also interconnects an outlet and the second openings of the first and second sorbing chambers. A connecting apparatus connects an energy source external to the first and second sorbing chambers to the heaters of the first and second sorbing chambers. A controller coupled to the valve arrangement and the connecting apparatus simultaneously directs gas from the first sorbing chamber to the outlet and directs a portion of the outlet gas through the second sorbing chamber to the exhaust. The controller also provides energy from the energy source to the
Structural model of hERG channels. (a) Key elements of hERG channel topology illustrated using the X-ray structure of KvAP. Two of the four subunits comprising the tetrameric channel are shown. (b) Model of the pore portion of hERG channel. The P-S6 fragment is shown for a dimer. Aromatic residues Phe656 and Tyr652 are critical for hERG block by most known small molecule ligands. Polar residues Thr623 and Ser624 modulate the binding potency for a number of reported hERG blockers ...