A common mechanism of defective channel trafficking underlying DFNA2 hearing loss result in different cell surface expression levels of KCNQ4 mutants

KCNQ4 mutations underlie DFNA2, a subtype of autosomal dominant hearing loss. We had previously identified the pore-region p.G296S mutation that impaired channel activity in two manners: it greatly reduced surface expression and abolished channel function. Moreover, G296S mutant exerted a strong dominant-negative effect on potassium currents by reducing the channel expression at the cell surface representing the first study to identify a trafficking-dependent dominant mechanism for the loss of KCNQ4 channel function in DFNA2. Here, we have investigated the pathogenic mechanism associated with all the described KCNQ4 mutations (F182L, W242X, E260K, D262V, L274H, W276S, L281S, G285C, G285S and G321S) that are located in different domains of the channel protein. F182L mutant showed a wild type-like cell-surface distribution in transiently transfected NIH3T3 fibroblasts and the recorded currents in Xenopus oocytes resembled those of the wild-type. The remaining KCNQ4 mutants abolished potassium currents, but displayed distinct levels of defective cell-surface expression in NIH3T3 as quantified by flow citometry. Co-localization studies revealed these mutants were retained in the ER, unless W242X, which showed a clear co-localization with Golgi apparatus. Interestingly, this mutation results in a truncated KCNQ4 protein at the S5 transmembrane domain, before the pore region, that escapes the protein quality control in the ER but does not reach the cell surface at normal levels. Currently we are investigating the trafficking behaviour and electrophysiological properties of several KCNQ4 truncated proteins artificially generated in order to identify specific motifs involved in channel retention/exportation. Altogether, our results indicate that a defect in KCNQ4 trafficking is the common mechanism underlying DFNA2

Profiling the temperature distribution in AlGaN/GaN HEMTs with nanocrystalline diamond heat spreading layers

Reduced performance in Gallium Nitride (GaN) based high electron mobility transistors (HEMTs) as a result of self-heating has been well-documented. A new approach, termed “diamond-before-gate" is shown to improve the thermal budget of the deposition process and enables large area diamond without degrading the gate metal NCD capped devices had a 20% lower channel temperature at equivalent power dissipation.

Secure optical networks based on quantum key distribution and weakly trusted repeaters

Abstract—In this paper we explore how recent technologies can improve the security of optical networks. In particular, we study how to use quantum key distribution(QKD) in common optical network infrastructures and propose a method to overcome its distance limitations. QKD is the first technology offering information theoretic secretkey distribution that relies only on the fundamental principles of quantum physics. Point-to-point QKDdevices have reached a mature industrial state; however, these devices are severely limited in distance, since signals at the quantum level (e.g., single photons) are highly affected by the losses in the communication channel and intermediate devices. To overcome this limitation, intermediate nodes (i.e., repeaters) are used. Both quantum-regime and trusted, classical repeaters have been proposed in the QKD literature, but only the latter can be implemented in practice. As a novelty, we propose here a new QKD network model based on the use of not fully trusted intermediate nodes, referred to as weakly trusted repeaters. This approach forces the attacker to simultaneously break several paths to get access to the exchanged key, thus improving significantly the security of the network. We formalize the model using network codes and provide real scenarios that allow users to exchange secure keys over metropolitan optical networks using only passive components. Moreover, the theoretical framework allows one to extend these scenarios not only to accommodate more complex trust constraints, but also to consider robustness and resiliency constraints on the network.

Entanglement Distribution in Quantum Metropolitan Optical Networks

The ability to generate entangled photon-pairs over a broad wavelength range opens the door to the simultaneous distribution of entanglement to multiple users of a network using a single source and wavelength-division multiplexing technologies. Here we show the design of a metropolitan optical network made of tree-type access networks where entangled photon-pairs are distributed to any pair of users, independently of their location. The resulting network improves the reach, number of users and capabilities of existing proposals. Moreover, it is made up of typical commercial components and uses the existing infrastructure, which allows for moderate deployment costs. Finally, we develop a channel plan and a network design that allow direct optical communications, quantum and classical, between any pair of users. Therefore, multiple quantum information technologies can make use of this network.

Entanglement distribution in optical networks

The ability to generate entangled photon pairs over a broad wavelength range opens the door to the simultaneous distribution of entanglement to multiple users in a network by using centralized sources and flexible wavelength-division multiplexing schemes. Here, we show the design of a metropolitan optical network consisting of tree-type access networks, whereby entangled photon pairs are distributed to any pair of users, independent of their location. The network is constructed employing commercial off-the-shelf components and uses the existing infrastructure, which allows for moderate deployment costs. We further develop a channel plan and a network-architecture design to provide a direct optical path between any pair of users; thus, allowing classical and one-way quantum communication, as well as entanglement distribution. This allows the simultaneous operation of multiple quantum information technologies. Finally, we present a more flexible backbone architecture that pushes away the load limitations of the original network design by extending its reach, number of users and capabilities.

Information reconciliation for Quantum Key Distribution

Secret-key agreement, a well-known problem in cryptography, allows two parties holding correlated sequences to agree on a secret key communicating over a public channel. It is usually divided into three different procedures: advantage distillation, information reconciliation and privacy amplification. The efficiency of each one of these procedures is needed if a positive key rate is to be attained from the legitimate parties? correlated sequences. Quantum key distribution (QKD) allows the two parties to obtain correlated sequences, provided that they have access to an authenticated channel. The new generation of QKD devices is able to work at higher speeds and in noisier or more absorbing environments. This exposes the weaknesses of current information reconciliation protocols, a key component to their performance. Here we present a new protocol based in low-density parity-check (LDPC) codes that presents the advantages of low interactivity, rate adaptability and high efficiency,characteristics that make it highly suitable for next generation QKD devices.

Influence of gravity on heavy particle statistics in turbulent channel and pipe flow at matched Kàrmàn number

In this work, we use large eddy simulations (LES) and Lagrangian tracking to study the influence of gravity on particle statistics in a fully developed turbulent upward/downward flow in a vertical channel and pipe at matched Kàrmàn number. Only drag and gravity are considered in the equation of motion for solid particles, which are assumed to have no influence on the flow field. Particle interactions with the wall are fully elastic. Our findings obtained from the particle statistics confirm that: (i) the gravity seems to modify both the quantitative and qualitative behavior of the particle distribution and statistics of the particle velocity in wall normal direction; (ii) however, only the quantitative behavior of velocity particle in streamwise direction and the root mean square of velocity components is modified; (iii) the statistics of fluid and particles coincide very well near the wall in channel and pipe flow with equal Kàrmàn number; (iv) pipe curvature seems to have quantitative and qualitative influence on the particle velocity and on the particle concentration in wall normal direction.

Information reconciliation methods in secret key distribution

We consider in this thesis the problem of information reconciliation in the context of secret key distillation between two legitimate parties. In some scenarios of interest this problem can be advantageously solved with low density parity check (LDPC) codes optimized for the binary symmetric channel. In particular, we demonstrate that our method leads to a significant efficiency improvement, with respect to earlier interactive reconciliation methods. We propose a protocol based on LDPC codes that can be adapted to changes in the communication channel extending the original source. The efficiency of our protocol is only limited by the quality of the code and, while transmitting more information than needed to reconcile Alice’s and Bob’s sequences, it does not reveal any more information on the original source than an ad-hoc code would have revealed.---ABSTRACT---En esta tesis estudiamos el problema de la reconciliación de información en el contexto de la destilación de secreto entre dos partes. En algunos escenarios de interés, códigos de baja densidad de ecuaciones de paridad (LDPC) adaptados al canal binario simétrico ofrecen una buena solución al problema estudiado. Demostramos que nuestro método mejora significativamente la eficiencia de la reconciliación. Proponemos un protocolo basado en códigos LDPC que puede ser adaptado a cambios en el canal de comunicaciones mediante una extensión de la fuente original. La eficiencia de nuestro protocolo está limitada exclusivamente por el código utilizado y no revela información adicional sobre la fuente original que la que un código con la tasa de información adaptada habría revelado.

Patch-clamp and amperometric recordings from norepinephrine transporters: Channel activity and voltage-dependent uptake

Transporters for the biogenic amines dopamine, norepinephrine, epinephrine and serotonin are largely responsible for transmitter inactivation after release. They also serve as high-affinity targets for a number of clinically relevant psychoactive agents, including antidepressants, cocaine, and amphetamines. Despite their prominent role in neurotransmitter inactivation and drug responses, we lack a clear understanding of the permeation pathway or regulation mechanisms at the single transporter level. The resolution of radiotracer-based flux techniques limits the opportunities to dissect these problems. Here we combine patch-clamp recording techniques with microamperometry to record the transporter-mediated flux of norepinephrine across isolated membrane patches. These data reveal voltage-dependent norepinephrine flux that correlates temporally with antidepressant-sensitive transporter currents in the same patch. Furthermore, we resolve unitary flux events linked with bursts of transporter channel openings. These findings indicate that norepinephrine transporters are capable of transporting neurotransmitter across the membrane in discrete shots containing hundreds of molecules. Amperometry is used widely to study neurotransmitter distribution and kinetics in the nervous system and to detect transmitter release during vesicular exocytosis. Of interest regarding the present application is the use of amperometry on inside-out patches with synchronous recording of flux and current. Thus, our results further demonstrate a powerful method to assess transporter function and regulation.

Apical sorting of a voltage- and Ca2+-activated K+ channel α-subunit in Madin-Darby canine kidney cells is independent of N-glycosylation

The voltage- and Ca2+-activated K+ (KV,Ca) channel is expressed in a variety of polarized epithelial cells seemingly displaying a tissue-dependent apical-to-basolateral regionalization, as revealed by electrophysiology. Using domain-specific biotinylation and immunofluorescence we show that the human channel KV,Ca α-subunit (human Slowpoke channel, hSlo) is predominantly found in the apical plasma membrane domain of permanently transfected Madin-Darby canine kidney cells. Both the wild-type and a mutant hSlo protein lacking its only potential N-glycosylation site were efficiently transported to the cell surface and concentrated in the apical domain even when they were overexpressed to levels 200- to 300-fold higher than the density of intrinsic Slo channels. Furthermore, tunicamycin treatment did not prevent apical segregation of hSlo, indicating that endogenous glycosylated proteins (e.g., KV,Ca β-subunits) were not required. hSlo seems to display properties for lipid-raft targeting, as judged by its buoyant distribution in sucrose gradients after extraction with either detergent or sodium carbonate. The evidence indicates that the hSlo protein possesses intrinsic information for transport to the apical cell surface through a mechanism that may involve association with lipid rafts and that is independent of glycosylation of the channel itself or an associated protein. Thus, this particular polytopic model protein shows that glycosylation-independent apical pathways exist for endogenous membrane proteins in Madin-Darby canine kidney cells.

A procedure for computation of the total river sand discharge and detailed distribution bed to surface /

"November 1968."

The role of semantic context and attentional resource distribution in semantic comprehension in Swedish pre-schoolers

Research on semantic processing focused mainly on isolated units in language, which does not reflect the complexity of language. In order to understand how semantic information is processed in a wider context, the first goal of this thesis was to determine whether Swedish pre-school children are able to comprehend semantic context and if that context is semantically built up over time. The second goal was to investigate how the brain distributes attentional resources by means of brain activation amplitude and processing type. Swedish preschool children were tested in a dichotic listening task with longer children’s narratives. The development of event-related potential N400 component and its amplitude were used to investigate both goals. The decrease of the N400 in the attended and unattended channel indicated semantic comprehension and that semantic context was built up over time. The attended stimulus received more resources, processed the stimuli in more of a top-down manner and displayed prominent N400 amplitude in contrast to the unattended stimulus. The N400 and the late positivity were more complex than expected since endings of utterances longer than nine words were not accounted for. More research on wider linguistic context is needed in order to understand how the human brain comprehends natural language. 

Vasa Creek Channel Conditions and Slope Stability, Bellevue, Washington

The focus of this report is is the channel conditions at Vasa Creek, Bellevue, Washington, with regard to kokanee habitat and slope stability. This required a geomorphic and geologic assessment of the stream and riparian corridor along Vasa Creek. I focused my efforts in a 720m study-reach just south of I-90 in which City of Bellevue had no information. My assessment is divided into 3 categories: channel morphology, geology, and landslide hazards. I described the channel morphology by determining the gradient of the channel, longitudinal and cross-channel geometries, grain size distribution, embeddedness observations, type of channel reaches present, and the locations of significant in-channel woody-debris, landslides, scarps, landslide debris, and erosional features. This was done by conducting a longitudinal survey, 7 cross-channel surveys, pebble counts, and visual observations with the aid of a GPS device for mapping. I completed my geological assessment using both field observations and borehole data provided by GeoMapNW. Borehole data provided logs of the subsurface material at specific locations. In the field, I interpreted local geology using material in the channel as well as exposures in the adjacent slope. I completed the landslide hazard assessment using GIS methods supplemented by field observations. GIS methods included the use of aerial LiDAR to discern slope values and locations of features. Features of interest include the locations of scarps, landslides, landslide debris, and erosional features which were observed in the field. I classified 4 slope classes using ArcMap10 along with the locations of previously mapped landslides, scarps, and landslide debris. I describe the risk of slope failure according to the Washington Administration Code definition of critical areas (WAC 365-190-120 6a-i). My results are presented in the form of a map suite containing a channel morphology map, geology map, and landslide hazard map. The channel is a free-formed alluvial plane-bed reach with infrequent step-pools with riffles associated with landslide debris that chokes the channel. Overall I found that there is not the potential for kokanee habitat due flashy behavior (sudden high flow events), landslide inundation, and a lack of favorable conditions within the channel. The updated geologic map displays advance outwash deposits and alluvium present within the study-reach, as opposed to exposures of the Blakeley Formation along with other corrections from borehole data interpretations. The landslide hazard map shows that there are areas at high risk for slope failure along the channel that should be looked into further.

The role of large woody debris and riparian forest in channel avulsion in the Carbon River, Mount Rainier National Park, Washington

A specific type of natural log jam in the upper alluvial reach of the Carbon River was found to influence secondary channel avulsion, causing flooding hazards to the adjacent Carbon River Road in the northwest quadrant of Mount Rainier National Park, Washington. The fence-like natural log jam was characterized by large woody debris buttressed horizontally against standing riparian trees (i.e. ìfence railsî and ìfence postî). The objectives of this report are two-fold. First, physical characteristics and spatial distribution were documented to determine the geomorphic controls on the fence-like log jams. Second, the function and timing of the natural log jam in relation to channel avulsion was determined to provide insight into flooding hazards along the Carbon River Road. The fence-like log jams are most abundant in the upper reaches of the Carbon River between 3.0 and 5.5 kilometers from the Carbon Glacier terminus, where longitudinal gradient significantly decreases from about 0.06 to 0.03. Sediment impoundment can occur directly upstream of the fence-like log jam, creating vertical bed elevation difference as high as 1.32 meters, and can form during low magnitude, high frequency flood event (3.5-year recurrence interval). In some locations, headcuts and widening of secondary channel were observed directly to the side of the log jams, suggesting its role in facilitating secondary channel avulsions. Areas along the Carbon River Road more prone to damages from avulsion hazards were identified by coupling locations of the log jams and Relative Water Surface Elevation map created using the 1-meter 2012 Light Detection and Ranging Digital Elevation Map. Ultimately, the results of this report may provide insight to flooding hazards along the Carbon River Road from log jam-facilitated channel avulsion.

No-switching quantum key distribution using broadband modulated coherent light

We realize an end-to-end no-switching quantum key distribution protocol using continuous-wave coherent light. We encode weak broadband Gaussian modulations onto the amplitude and phase quadratures of light beams. Our no-switching protocol achieves high secret key rate via a post-selection protocol that utilizes both quadrature information simultaneously. We establish a secret key rate of 25 Mbits/s for a lossless channel and 1 kbit/s for 90% channel loss, per 17 MHz of detected bandwidth, assuming individual Gaussian eavesdropping attacks. Since our scheme is truly broadband, it can potentially deliver orders of magnitude higher key rates by extending the encoding bandwidth with higher-end telecommunication technology.