This study investigates changes to channel morphology along Chilliwack River in southwest British Columbia, and relates these changes to the transport of bed material. The channel was mapped using a stereoplotter from a sequence of historical aerial photography between 1952 and 1991. Maps for selected years were overlaid, then analyzed with a GIS. Erosion and deposition volumes of bed material were determined by multiplying measured planimetric changes by the varying depth of bed material along the river. A sediment budget framework was used to estimate bed material transport rates from these net changes in stored sediment volumes. The transport rate of bed material for Chilliwack River is estimated as 55,000±10,000 m3/yr for the period 1983 to 1991. Instability along lower channel reaches has increased over the 40 year period of study due to an increase in both the magnitude and frequency of large floods. As a consequence, channel width, bank erosion rates and the volume of sediment transported past Vedder Crossing became increasingly large. Between 1952 and 1975, Chilliwack River was in a transient state of equilibrium as the channel continued to recover from a sequence of large floods in previous decades. Large floods in 1975 and 1980 caused significant bank erosion along lower reaches, which increased the amount of sediment available for transport. Extreme floods in 1989 and 1990 caused further erosion, and in fact, were large enough to alter the pre-flood channel regime. However, in the absence of further large floods, the channel should recover from these events in 10 to 20 years. Significant morphologic change on Chilliwack River occurs roughly once every 5 years, when peak flows exceed 500 m3/s. These floods are sufficient to erode channel banks, where the dominant supply of mobile bed material is stored. Aggradation occurs in the short term as more sediment is introduced to the active channel zone than can be removed by subsequent smaller flows. However, as flows as small as 250 m3/s (which occur several times per year, on average) are capable of mobilizing bed material, there is net degradation over the longer term. As the length between survey dates used in this study averaged 10 years, some information on bed material transport between dates is lost. Nonetheless, this study has demonstrated that considerable information on historic channel change can be obtained form aerial photographs. / Arts, Faculty of / Geography, Department of / Graduate

<p></p><p>The<b> </b>L-type VGCC subtypes, including subtypes Ca_v1.1-1.4, have been shown to play critical roles in various cellular activities, including muscle contraction, hormone secretion, and neurotransmitter release. Recent research indicates the potential involvement of Ca_v1.3 in various neurological and psychiatric disorders, such as the early onset of Parkinson’s disease and substance abuse disorders. Non-selective L-VGCC subtype blockers such as dihydropyridines (DHPs) are used to treat hypertension and angina because they potently inhibit Ca_v1.2, but no selective Ca_v1.3 inhibitors have been developed yet. We resolved the molecular determinants to differentiate Ca_v1.2 and Ca_v1.3 in response to DHP nifedipine. Nifedipine IC₅₀ for Ca_v1.2 and Ca_v1.3 are 22nM and 289nM determined by whole-cell patch-clamp. We identified two significant amino acids, Ca_v1.3/M1030 to Ca_v1.2/V1036 in the transmembrane IIIS5 and Ca_v1.3/S1100 Ca_v1.2/A1106 in the extracellular IIIS-3P loop, to differentiate the subtype affinity to nifedipine. </p> <p>We found that the Ca_v1.3/II-III loop fused to eGFP decreased glucose-activated action potential (GSAP) frequency by ~80% in the pancreatic β-cell. We introduced several synthetic peptides, and peptide P3-1 from C-terminal induced a -16mV shift in V_1/2 inactivation with an EC₅₀ of 231nM. P3-1 contains a protein kinase G (PKG) phosphorylation site (RRISE) required for PKG inhibition of Ca_v1.3 current but not conserved in Ca_v1.2. We found that the shift in V_1/2 inactivation induced by co-expression of Ca_v1.3 with the Ca_v1.3/II-III loop/GFP requires the presence of a Ca_vβ subunit, and Ca_vβ₃ also exhibits selectivity over other β subunits. Significantly, P3-1 shifts the Ca_v1.2 inactivation to a more positive voltage when co-expressed with either Ca_vβ_2aor Ca_vβ₃, demonstrating the ability of P3-1 to differentiate Ca_v1.2 and Ca_v1.3 in a Ca_vβ-dependent manner.</p> <p><b> </b>Failure of pancreatic β-cells to secrete enough insulin to maintain glucose homeostasis is a hallmark of Type 2 diabetes. However, the consequences of the dysregulation of the endoplasmic reticulum (ER) Ca²⁺ channel ryanodine receptor-2 (RyR2) in pancreatic β-cells are not fully understood. Therefore, we characterized the electrical activity in INS-1 in which RyR2 has been deleted via CRISPR/Cas9 gene editing. We observed a decreased level of IP₃ receptor binding protein (IRBIT) in RyR2^KO INS-1 cells and generated IRBIT^KO INS-1 cells. VGCC current density in RyR2^KO doubled compared to controls and was also elevated in IRBIT^KOcompared to control cells. All HVA Ca²⁺ channels were upregulated, determined by fractional current blocked by nifedipine. We also found that GSAP frequency is doubled by RyR2 deletion due to failure to activate apamin sensitive SK (small conductance calcium-activated potassium) channels. </p><br><p></p>

We look at some inventory models for dual channel retailers who fulfill demands from both channels from the same pool of stock. Since the arrival of the internet, companies, particularly retailers, have been trying to figure out how best to take advantage of this new channel. This became acute for retailers when Amazon.com became the pre-dominant bookseller overcoming rivals like Barnes and Noble and Borders who had been operating for several decades. Firms in other categories were worried that a web only retailer like Amazon.com could end up dominating their sectors as well. To respond to such threats, existing retailers like Tesco and Lands End began offering their products through a web-site which became their web channel. To improve efficiency and to take advantage of specific characteristics of this channel, firms had to modify the operations of their existing channels. In this thesis, we look at retailers who took advantage of the web channel to better their operations for the entire firm. / Thesis / Doctor of Business Administration (DBA)

Acid-sensing ion channels (ASICs) are trimeric, sodium-selective proton-gated ion channels. Having ligands as small as protons presents a challenge when studying the structure-function relationships of pH-dependent gating. Knowing where protons must bind to evoke a pH-dependent conformational change related to gating would provide one with insights into the molecular mechanisms underlying pH-dependent function in ASICs. We use molecular dynamics (MD) simulations that allow us to model explicit protons and directly examine the effects of changing protonation states on ASIC1 dynamics. We first combine the use of unbiased MD simulations with pKₐ prediction on the three functional states of cASIC1 to identify the effects of protonation state changes on interactions between ionizable residues in the acidic pocket (ACP), a region rich in acidic residues in the protein that plays a role in pH-sensing. We interpret the importance of E98, a buried residue in the ACP with a highly shifted pKₐ value, as well as the positively charged R191, also in the ACP, which has a flexible side chain and can interact with multiple negatively charged side chains, and the role of these residues in the pH-dependent collapse of the ACP. Additionally, we identify a hydrogen-bond network in the palm domain that consists of the Q277 side chain that interacts with the E80 side chain and L414 backbone carbonyl. This network contributes to a stable desensitized state and is stabilized by an E80-/E412H/E417H protonation configuration. Next, targeted MD was combined with pKₐ prediction to simulate the full transition pathways and to link protonation states with the molecular mechanisms involved in conformational changes. Our results suggest four residues, E98, E314, H328, and E374, that may be important in pH-sensing and gating, and that require further functional investigation in the context of activation and desensitization. This research exemplifies how MD is a useful tool in studying how protonation directly affects the structural dynamics of a protein and how it can complement existing functional studies and be used to suggest future experimental investigations.

No description available.

A fresh perspective on covert channels is presented in this work. A new class, air-gap covert channels, is defined as an unintentional communication channel established between systems that are physically and electronically isolated from one another. A specific class of air-gap covert channel is studied in depth, out-of-band covert channels (OOB-CCs), which are defined as policy-breaking communication channels established between isolated, physically unmodified systems. It is shown that OOB-CCs can be categorized by the physical channel that they communicate over: acoustic, light, seismic, magnetic, thermal, and radio-frequency, and the hardware that is required at the transmitter and receiver to make covert communication possible. In general, OOB-CCs are not as high-bandwidth as conventional radio-frequency channels; however, they are capable of leaking sensitive information that requires low data rates to communicate (e.g., text, recorded audio, cryptographic key material). The ability for malware to communicate information using a specific type of OOB-CC, the covert-acoustic channel, is also analyzed. It is empirically demonstrated that using physically unmodified, commodity systems (e.g., laptops, desktops, and mobile devices), covert-acoustic channels can be used to communicate at data rates of hundreds of bits per second, without being detected by humans in the environment, and data rates of thousands of bits per second when nobody is around to hear the communication. Defence mechanisms to counter covert-acoustic channels are also proposed and evaluated, and, as a result, best practices for the designers of secure systems and secure facilities are presented. Additionally, the covertness of OOB-CCs, i.e., the amount of data that can be leaked before the channel is detected, is also determined for classical communication channels as well as for covert-acoustic channels.

Attempts were made to determine the pore properties, such as permeability, rectification and voltage-dependent block, of the putative TRPV4-TRPC1 channel. We demonstrated that this putative TRPV4-TRPC1 heterotetrameric channels displays distinct property different (although not drastically different) from TRPV4 homotetrameric channel with regard to I-V relation, kinetics of cation current, cations permeability and rectification properties. Together, the data from FRET and functional studies both suggest that heterologous expression of TRPV4 and TRPC1 can produce functional TRPV4-TRPC1 heterotetrameric channel. / Hemodynamic blood flow is one of most important physiological factors that control vascular tone. Flow shear stress acts on the endothelium to stimulate the release of vasodilators such as nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factors, causing endothelium-dependent vascular relaxation. In many cases, a key early signal in this flow-induced vascular dilation is Ca2+ influx in endothelial cells in response to flow. There is intense interest in searching for the molecular identity of the channels that mediate flow-induced Ca2+ influx. The present study aimed at identifying an interaction of TRPV4 with TRPC1, and investigating functional role of such a complex in flow-induced Ca2+ influx / In functional study, flow elicited a [Ca2+]i rise in TRPV4-expressing HEK cells. Co-expression of TRPC1 with TRPV4 markedly prolonged this [Ca2+]i transient, and it also enabled this [Ca2+]i transient to be negatively modulated by protein kinase G (PKG). Furthermore, this [Ca2+]i rise was inhibited by an anti-TRPC1 blocking antibody T1E3 and a dominant negative construct TRPC1Delta567-793. Physical interaction of TRPV4 with TRPC1 and functional role of such a complex were also found in the primary cultured rat mesenteric artery endothelial cells (MAECs) and human umbilical vein endothelial cells (HUVECs). A TRPC 1-specific siRNA was used to knock-down TRPC1 protein levels in HUVECs. Interestingly, this siRNA not only reduced the magnitude of flow-induced [Ca2+]i rise, but also accelerated the decay of flow-induced [Ca2+]i transient. Pressure myograph was used to investigate the functional role of such a complex in flow-induced vascular dilation. T1E3 also decreased flow-induced vascular dilation. Thogether, the data from endothelial cells are consistent with those in overexpressed HEK cells, supporting the notion that TRPC 1 interacts with TRPV4 to prolong the flow-induced[Ca2+]i transient, and that TRPV4-TRPC1 complex plays an important role in flow-induced vascular dilation. / In summary, my study demonstrated that TRPV4 is capable of assembling with TRPC1 to form a functional TRPV4-TRPC1 heteromeric channel. TRPV4-TRPC1 heteromeric channel can rapidly translocate to the plasma membrane after Ca 2+ depletion in intracellular stores. This TRPV4-TRPC1 heteromeric channel plays an important role in flow-induced endothelial Ca2+ influx and its associated vascular relaxation. / Ion channels are delivered to the plasma membrane via vesicle trafficking. Thus the vesicle trafficking is a key mechanism to control the amount of TRP channel proteins in the plasma membrane, where they perform their function. TRP channels in vivo are often composed of heteromeric subunits. However, up to the present, there is lack of knowledge on trafficking of heteromeric TRP channels via vesicular translocation. In the present study, we examined the effect of Ca2+ store depletion on the translocation of TRPV4-TRPC1 heteromeric channels to the plasma membrane. Experiments using total internal fluorescence reflection microscopy (TIRFM) and biotin surface labeling showed that depletion of intracellular Ca2+ stores triggered a rapid translocation of TRPV4-TRPC1 channel proteins into the plasma membrane. Fluorescent Ca2+ measurement and patch clamp studies demonstrated that store Ca2+ depletion augmented several TRPV4-TRPC1 complex-related functions, which include store-operated Ca2+ influx and cation current as well as 4alpha-PDD-stimulated Ca2+ influx and cation current. The translocation required stromal interacting molecule 1 (STIM1). Furthermore, TRPV4-TRPC1 complex is more favorably translocated to the plasma membrane than TRPC1 or TRPV4 homomers. Similar mechanisms were identified in native endothelial cells, where the TRPV4-TRPC I complex is a key component mediating flow-induced Ca2+ influx and subsequent vascular relaxation. / With the use of fluorescence resonance energy transfer (FRET), co-immunoprecipitation and subcellular colocalization methods, it was found that TRPC1 interacts physically with TRPV4 to form a heteromeric channel complex. In addition, our experimental results indicate that C-terminal and N-terminal domains of both channels are required for their interaction. / Ma, Xin. / Adviser: Yao Xiaodiang. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 109-121). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

This paper offers a comprehensive and integrative overview of all empirical data available from the open literature on the in-tunnel radiowave-communication channel's power loss characteristics, as a function of the tunnel's cross-sectional shape, cross-sectional size, longitudinal shape, wall materials, presence or absence of vehicular/human traffic, and presence/absence of branches. These data were originally presented in about 50 papers in various journals, conferences, and books.

This paper offers a comprehensive and integrative overview of all empirical data available from the open literature on the in-tunnel radiowave-communication channel's power loss characteristics, as a function of the tunnel's cross-sectional shape, cross-sectional size, longitudinal shape, wall materials, presence or absence of vehicular/human traffic, and presence/absence of branches. These data were originally presented in about 50 papers in various journals, conferences, and books.

Ma, Yan. / "Ca" in the title is subscript. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 143-166). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.