Sediment dynamics in the subaquatic channel of the Rhone delta (Lake Geneva, France/Switzerland)

bstract With its smaller size, well-known boundary conditions, and the availability of detailed bathymetric data, Lake Geneva’s subaquatic canyon in the Rhone Delta is an excellent analogue to understand sedimentary pro- cesses in deep-water submarine channels. A multidisciplinary research effort was undertaken to unravel the sediment dynamics in the active canyon. This approach included innovative coring using the Russian MIR sub- mersibles, in situ geotechnical tests, and geophysical, sedimentological, geochemical and radiometric analysis techniques. The canyon floor/levee complex is character- ized by a classic turbiditic system with frequent spillover events. Sedimentary evolution in the active canyon is controlled by a complex interplay between erosion and sedimentation processes. In situ profiling of sediment strength in the upper layer was tested using a dynamic penetrometer and suggests that erosion is the governing mechanism in the proximal canyon floor while sedimen- tation dominates in the levee structure. Sedimentation rates progressively decrease down-channel along the levee structure, with accumulation exceeding 2.6 cm/year in the proximal levee. A decrease in the frequency of turbidites upwards along the canyon wall suggests a progressive confinement of the flow through time. The multi-proxy methodology has also enabled a qualitative slope-stability assessment in the levee structure. The rapid sediment loading, slope undercutting and over-steepening, and increased pore pressure due to high methane concentrations hint at a potential instability of the proximal levees. Fur- thermore, discrete sandy intervals show very high methane concentrations and low shear strength and thus could cor- respond to potentially weak layers prone to scarp failures.

Impact of dams, dam removal and dam-related river engineering structures on sediment connectivity and channel morphology of the Fugnitz and the Kaja Rivers

In terms of changing flow and sediment regimes of rivers, dams are often regarded as the most dominant form of human impact on fluvial systems. Dams can decrease the flux of water and sediments leading to channel changes such as upstream aggradation and downstream degradation. The opposite effects occur when dams are removed. Channel degradation often requires further intervention in terms of river bed and bank protection works. The situation evolves more complex in river systems that are impacted by a series of dams due to feedback processes between the different system compartments. A number of studies have recently investigated geomorphic systems using connectivity approaches to improve the understanding of geomorphic system response to change. This paper presents a case study investigating the impact of dam construction, dam removal and dam-related river bed and bank protection measures on the sediment connectivity and channel morphology of the Fugnitz and the Kaja Rivers using a combination of DEM analyses, field surveys and landscape evolution modelling. For both river systems the results revealed low sediment connectivity accompanied by a fine river bed sediment facies in river sections upstream of active dams and of removed dams with protection measures. Contrarily, high sediment connectivity which was accompanied by a coarse river bed sediment facies was observed in river sections either located downstream of active dams or of removed dams with upstream protection. In terms of channel changes, significant channel degradation was examined at locations downstream of active dams and of removed dams. Channel bed and bank protection measures prevent erosion and channel slope recovery after dam removal. Landscape evolution modeling revealed a complex geomorphic response to dam construction and dam removal as sediment output rates and therefore geomorphic processes have been shown to act in a non-linear manner. These insights are deemed to have major implications for river management and conservation, as quality and state of riverine habitats are determined by channel morphology and river bed sediment composition.

Comparison of stab wound probing versus radiological stab wound channel depiction with contrast medium

BACKGROUND Instillation of contrast medium into stab wounds has shown promising results regarding visibility and assessment of general stab direction with computed tomography. However, the accuracy of this method--and, incidentally also probing of stab wounds--has to our knowledge not previously been examined. Also the effect of bluntness of different stabbing objects on the examination of stab wounds was not considered before this study. METHODS Using a pocket-knife, a steak-knife, and a Phillips screwdriver, nine stab wounds each were inflicted to three pork haunches. The depths of the stab wounds were determined by probing and multislice computed tomography (MSCT) after instillation of a contrast medium (CM) and then compared to those observed by dissection, our internal "gold standard". RESULTS In stab wounds inflicted by knives, MSCT-CM and probing provided results which differed by roughly 10-11% from the dissection results. In screwdriver stabs MSCT-CM showed a deviation of almost 30%, probing over 33%. DISCUSSION MSCT-CM is a possible alternative to layer-by-layer dissection in autopsy cases of knife stab wounds. Probing, although obsolete in post-mortem examinations, is sufficiently accurate in determining the length of a stab wound of a living person. In cases of stab wounds with blunt objects such as screwdrivers, neither MSCT-CM nor probing proved to be sufficiently accurate. CONCLUSION MSCT-CM is a possible alternative to layer-by-layer dissection in autopsy cases of knife stab wounds. Probing, although obsolete in post-mortem examinations, is sufficiently accurate in determining the length of a stab wound of a living person. In cases of stab wounds with blunt objects such as screwdrivers, neither MSCT-CM nor probing proved to be sufficiently accurate.

Multi-channel search for squarks and gluinos in sqrts=7 TeV pp collisions with the ATLAS detector

A search for supersymmetric particles in final states with zero, one, and two leptons, with and without jets identified as originating from b-quarks, in 4.7 fb(-1) of root s = 7 TeV pp collisions produced by the Large Hadron Collider and recorded by the ATLAS detector is presented. The search uses a set of variables carrying information on the event kinematics transverse and parallel to the beam line that are sensitive to several topologies expected in supersymmetry. Mutually exclusive final states are defined, allowing a combination of all channels to increase the search sensitivity. No deviation from the Standard Model expectation is observed. Upper limits at 95 % confidence level on visible cross-sections for the production of new particles are extracted. Results are interpreted in the context of the constrained minimal supersymmetric extension to the Standard Model and in supersymmetry-inspired models with diverse, high-multiplicity final states.

Measurement of the ttbar production cross section in the tau+jets channel using the ATLAS detector

A measurement of the top quark pair production cross section in the final state with a hadronically decaying tau lepton and jets is presented. The analysis is based on proton-proton collision data recorded by the ATLAS experiment at the LHC, with a centre-of-mass energy of 7 TeV. The data sample corresponds to an integrated luminosity of 1.67 fb(-1). The cross section is measured to be sigma(t (t) over bar) = 194 +/- 18 (stat.) +/- 46 (syst.) pb and is in agreement with other measurements and with the Standard Model prediction.

Search for a light charged Higgs boson in the decay channel H⁺ o c ars in t art events using collisions at sqrts = 7 TeV with the ATLAS detector

A search for a charged Higgs boson (H+) in t (t) over bar decays is presented, where one of the top quarks decays via t -> H(+)b, followed by H+ -> two jets (c (s) over bar). The other top quark decays to Wb, where the W boson then decays into a lepton (e/mu) and a neutrino. The data were recorded in pp collisions at root s = 7 TeV by the ATLAS detector at the LHC in 2011, and correspond to an integrated luminosity of 4.7 fb(-1). With no observation of a signal, 95 % confidence level (CL) upper limits are set on the decay branching ratio of top quarks to charged Higgs bosons varying between 5 % and 1 % for H+ masses between 90 GeV and 150 GeV, assuming B(H+ -> c (s) over bar) = 100 %.

A novel open channel blocker of GABA-A receptors

GABA-A receptors are chloride ion channels composed of five subunits, mediating fast synaptic and tonic inhibition in the mammalian brain. 19 different subunit isoforms have been identified, with the major receptor type in mammalian adult brain consisting of α1, β2, and γ2 subunits. GABA-A receptors are the target of numerous sedating and anxiolytic drugs such as benzodiazepines. The currently known endogenous ligands are GABA, neurosteroids and the endocannabinoid 2- arachidonoyl glycerol (2-AG). The pharmacological properties of this chloride ion channel strictly depend on receptor subunit composition and arrangement. GABA-A receptors bind and are inhibited by epileptogenic agents such as picrotoxin, and cyclodiene insecticides such as dieldrin. We screened aromatic monovalent anions with five-fold symmetry for inhibition of GABA-A receptors. One of the anions, PCCPinhibited currents elicited by GABA with comparable potency as picrotoxin. This inhibition showed all characteristics of an open channel block. The GABA-A receptor ion channel is lined by residues from the M2 membrane-spanning segment. To identify important residues of the pore involved in the interaction with the blocking molecules PCCP-, a mutation scan was performed in combination with subsequent analysis of the expressed mutant proteins using electrophysiological techniques. In a second project we characterised a light-switchable modulator of GABA-A receptors based on propofol. It was my responsibility to investigate the switching kinetics in patch clamp experiments. After its discovery in 1980, propofol has become the most widely used intravenous general anaesthetic. It is commonly accepted that the anaesthesia induced by this unusually lipophilic drug mostly results from potentiation of GABA induced currents. While GABA-A receptors respond to a variety of ligands, they are normally not sensitive towards light. This light sensitivity could be indirectly achieved by using modulators that can be optically switched between an active and an inactive form. We tested an azobenzene derivative of propofol where an aryldiazene unit is directly coupled to the pharmacophore. This molecule was termed azopropofol (AP2). The effect of AP2 on Cl- currents was investigated with electrophysiological techniques using α1β2γ2 GABA-A receptors expressed in Xenopus oocytes and HEK-cells. In the third project we wanted to investigate the functional role of GABA-A receptors in the liver, and their possible involvement in cell proliferation. GABA-A receptors are also found in a wide range of peripheral tissues, including parts of the peripheral nervous system and non-neural tissues such as smooth muscle, the female reproductive system, liver and several cancer tissues. However their precise function in non neuronal or cancerous cells is still unknown. For this purpose we investigated expression, localization and function of the hepatocytes GABA-A receptors in model cell lines and healthy and cancerous hepatocytes.

A pentasymmetric open channel blocker for Cys-loop receptor channels.

γ-Aminobutyric acid type A receptors (GABAA receptors) are chloride ion channels composed of five subunits, mediating fast synaptic and tonic inhibition in the mammalian brain. These receptors show near five-fold symmetry that is most pronounced in the second trans-membrane domain M2 lining the Cl- ion channel. To take advantage of this inherent symmetry, we screened a variety of aromatic anions with matched symmetry and found an inhibitor, pentacyanocyclopentdienyl anion (PCCP-) that exhibited all characteristics of an open channel blocker. Inhibition was strongly dependent on the membrane potential. Through mutagenesis and covalent modification, we identified the region α1V256-α1T261 in the rat recombinant GABAA receptor to be important for PCCP- action. Introduction of positive charges into M2 increased the affinity for PCCP- while PCCP- prevented the access of a positively charged molecule into M2. Interestingly, other anion selective cys-loop receptors were also inhibited by PCCP-, among them the Drosophila RDL GABAA receptor carrying an insecticide resistance mutation, suggesting that PCCP- could serve as an insecticide.

PDZ domain-binding motif regulates cardiomyocyte compartment-specific NaV1.5 channel expression and function

BACKGROUND Sodium channel NaV1.5 underlies cardiac excitability and conduction. The last 3 residues of NaV1.5 (Ser-Ile-Val) constitute a PDZ domain-binding motif that interacts with PDZ proteins such as syntrophins and SAP97 at different locations within the cardiomyocyte, thus defining distinct pools of NaV1.5 multiprotein complexes. Here, we explored the in vivo and clinical impact of this motif through characterization of mutant mice and genetic screening of patients. METHODS AND RESULTS To investigate in vivo the regulatory role of this motif, we generated knock-in mice lacking the SIV domain (ΔSIV). ΔSIV mice displayed reduced NaV1.5 expression and sodium current (INa), specifically at the lateral myocyte membrane, whereas NaV1.5 expression and INa at the intercalated disks were unaffected. Optical mapping of ΔSIV hearts revealed that ventricular conduction velocity was preferentially decreased in the transversal direction to myocardial fiber orientation, leading to increased anisotropy of ventricular conduction. Internalization of wild-type and ΔSIV channels was unchanged in HEK293 cells. However, the proteasome inhibitor MG132 rescued ΔSIV INa, suggesting that the SIV motif is important for regulation of NaV1.5 degradation. A missense mutation within the SIV motif (p.V2016M) was identified in a patient with Brugada syndrome. The mutation decreased NaV1.5 cell surface expression and INa when expressed in HEK293 cells. CONCLUSIONS Our results demonstrate the in vivo significance of the PDZ domain-binding motif in the correct expression of NaV1.5 at the lateral cardiomyocyte membrane and underline the functional role of lateral NaV1.5 in ventricular conduction. Furthermore, we reveal a clinical relevance of the SIV motif in cardiac disease.

p.L1612P, a Novel Voltage-gated Sodium Channel Nav1.7 Mutation Inducing a Cold Sensitive Paroxysmal Extreme Pain Disorder

BACKGROUND Mutations in the SCN9A gene cause chronic pain and pain insensitivity syndromes. We aimed to study clinical, genetic, and electrophysiological features of paroxysmal extreme pain disorder (PEPD) caused by a novel SCN9A mutation. METHODS Description of a 4-generation family suffering from PEPD with clinical, genetic and electrophysiological studies including patch clamp experiments assessing response to drug and temperature. RESULTS The family was clinically comparable to those reported previously with the exception of a favorable effect of cold exposure and a lack of drug efficacy including with carbamazepine, a proposed treatment for PEPD. A novel p.L1612P mutation in the Nav1.7 voltage-gated sodium channel was found in the four affected family members tested. Electrophysiologically the mutation substantially depolarized the steady-state inactivation curve (V1/2 from -61.8 ± 4.5 mV to -30.9 ± 2.2 mV, n = 4 and 7, P < 0.001), significantly increased ramp current (from 1.8% to 3.4%, n = 10 and 12) and shortened recovery from inactivation (from 7.2 ± 5.6 ms to 2.2 ± 1.5 ms, n = 11 and 10). However, there was no persistent current. Cold exposure reduced peak current and prolonged recovery from inactivation in wild-type and mutated channels. Amitriptyline only slightly corrected the steady-state inactivation shift of the mutated channel, which is consistent with the lack of clinical benefit. CONCLUSIONS The novel p.L1612P Nav1.7 mutation expands the PEPD spectrum with a unique combination of clinical symptoms and electrophysiological properties. Symptoms are partially responsive to temperature but not to drug therapy. In vitro trials of sodium channel blockers or temperature dependence might help predict treatment efficacy in PEPD.

Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance

Aldosterone promotes electrogenic sodium reabsorption through the amiloride-sensitive epithelial sodium channel (ENaC). Here, we investigated the importance of ENaC and its positive regulator channel-activating protease 1 (CAP1/Prss8) in colon. Mice lacking the αENaC subunit in colonic superficial cells (Scnn1a(KO)) were viable, without fetal or perinatal lethality. Control mice fed a regular or low-salt diet had a significantly higher amiloride-sensitive rectal potential difference (∆PDamil) than control mice fed a high-salt diet. In Scnn1a(KO) mice, however, this salt restriction-induced increase in ∆PDamil did not occur, and the circadian rhythm of ∆PDamil was blunted. Plasma and urinary sodium and potassium did not change with regular or high-salt diets or potassium loading in control or Scnn1a(KO) mice. However, Scnn1a(KO) mice fed a low-salt diet lost significant amounts of sodium in their feces and exhibited high plasma aldosterone and increased urinary sodium retention. Mice lacking the CAP1/Prss8 in colonic superficial cells (Prss8(KO)) were viable, without fetal or perinatal lethality. Compared with controls, Prss8(KO) mice fed regular or low-salt diets exhibited significantly reduced ∆PDamil in the afternoon, but the circadian rhythm was maintained. Prss8(KO) mice fed a low-salt diet also exhibited sodium loss through feces and higher plasma aldosterone levels. Thus, we identified CAP1/Prss8 as an in vivo regulator of ENaC in colon. We conclude that, under salt restriction, activation of the renin-angiotensin-aldosterone system in the kidney compensated for the absence of ENaC in colonic surface epithelium, leading to colon-specific pseudohypoaldosteronism type 1 with mineralocorticoid resistance without evidence of impaired potassium balance.

Anamorphic pixels for multi-channel superresolution

Superresolution from plenoptic cameras or camera arrays is usually treated similarly to superresolution from video streams. However, the transformation between the low-resolution views can be determined precisely from camera geometry and parallax. Furthermore, as each low-resolution image originates from a unique physical camera, its sampling properties can also be unique. We exploit this option with a custom design of either the optics or the sensor pixels. This design makes sure that the sampling matrix of the complete system is always well-formed, enabling robust and high-resolution image reconstruction. We show that simply changing the pixel aspect ratio from square to anamorphic is sufficient to achieve that goal, as long as each camera has a unique aspect ratio. We support this claim with theoretical analysis and image reconstruction of real images. We derive the optimal aspect ratios for sets of 2 or 4 cameras. Finally, we verify our solution with a camera system using an anamorphic lens.

Measurement of Higgs boson production in the diphoton decay channel in pp collisions at center-of-mass energies of 7 and 8 TeV with the ATLAS detector

A measurement of the production processes of the recently discovered Higgs boson is performed in the two-photon final state using 4.5  fb −1 of proton-proton collisions data at s √ =7  TeV and 20.3  fb −1 at s √ =8  TeV collected by the ATLAS detector at the Large Hadron Collider. The number of observed Higgs boson decays to diphotons divided by the corresponding Standard Model prediction, called the signal strength, is found to be μ=1.17±0.27 at the value of the Higgs boson mass measured by ATLAS, m H =125.4  GeV . The analysis is optimized to measure the signal strengths for individual Higgs boson production processes at this value of m H . They are found to be μ ggF =1.32±0.38 , μ VBF =0.8±0.7 , μ WH =1.0±1.6 , μ ZH =0.1 +3.7 −0.1 , and μ tt ¯ H =1.6 +2.7 −1.8 , for Higgs boson production through gluon fusion, vector-boson fusion, and in association with a W or Z boson or a top-quark pair, respectively. Compared with the previously published ATLAS analysis, the results reported here also benefit from a new energy calibration procedure for photons and the subsequent reduction of the systematic uncertainty on the diphoton mass resolution. No significant deviations from the predictions of the Standard Model are found.