Testing of subgrid scale (SGS) models for large-eddy simulation (LES) of turbulent channel flow

Sub-grid scale (SGS) models are required in order to model the influence of the unresolved small scales on the resolved scales in large-eddy simulations (LES), the flow at the smallest scales of turbulence. In the following work two SGS models are presented and deeply analyzed in terms of accuracy through several LESs with different spatial resolutions, i.e. grid spacings. The first part of this thesis focuses on the basic theory of turbulence, the governing equations of fluid dynamics and their adaptation to LES. Furthermore, two important SGS models are presented: one is the Dynamic eddy-viscosity model (DEVM), developed by \cite{germano1991dynamic}, while the other is the Explicit Algebraic SGS model (EASSM), by \cite{marstorp2009explicit}. In addition, some details about the implementation of the EASSM in a Pseudo-Spectral Navier-Stokes code \cite{chevalier2007simson} are presented. The performance of the two aforementioned models will be investigated in the following chapters, by means of LES of a channel flow, with friction Reynolds numbers $Re_\tau=590$ up to $Re_\tau=5200$, with relatively coarse resolutions. Data from each simulation will be compared to baseline DNS data. Results have shown that, in contrast to the DEVM, the EASSM has promising potentials for flow predictions at high friction Reynolds numbers: the higher the friction Reynolds number is the better the EASSM will behave and the worse the performances of the DEVM will be. The better performance of the EASSM is contributed to the ability to capture flow anisotropy at the small scales through a correct formulation for the SGS stresses. Moreover, a considerable reduction in the required computational resources can be achieved using the EASSM compared to DEVM. Therefore, the EASSM combines accuracy and computational efficiency, implying that it has a clear potential for industrial CFD usage.

Measurement of tt ̄production cross section at 13 TeV in the fully-hadronic channel with CMS

Lo scopo di questa tesi è la misura di sezione d’urto di produzione di coppie top-antitop nel canale adronico. Per la misura sono stati utilizzati i dati raccolti dall’esperimento CMS in collisioni protone-protone ad LHC, con un’energia nel centro di massa pari a 13 TeV. Il campione di dati utilizzato corrisponde ad una luminosità integrata di 2.474 f b^ −1 . L’analisi dati inizia selezionando gli eventi che soddisfano determinate condizioni (e.g. trigger, tagli cinematici, sei o più jet, almeno 2 jet provenienti dall’adronizzazione di due quark bottom) con lo scopo di incrementare la purezza del segnale scartando il più possibile gli eventi di fondo. A seguire, viene ricostruita la massa del quark top usando un fit cinematico. Sulle distribuzioni di tale massa si basa la stima degli eventi di fondo e di segnale. Infine, attraverso un fit di verosimiglianza, si ottiene il valore della sezione d’urto: σ t t ̄ = 893 ± 57 (stat) ± 104 (syst) pb. Questo risultato è in buon accordo con il valore teorico di 832 pb e con altre misure di CMS effettuate in canali differenti.

The floating mass transducer at the round window: direct transmission or bone conduction?

The round window placement of a floating mass transducer (FMT) is a new approach for coupling an implantable hearing system to the cochlea. We evaluated the vibration transfer to the cochlear fluids of an FMT placed at the round window (rwFMT) with special attention to the role of bone conduction. A posterior tympanotomy was performed on eleven ears of seven human whole head specimens. Several rwFMT setups were examined using laser Doppler vibrometry measurements at the stapes and the promontory. In three ears, the vibrations of a bone anchored hearing aid (BAHA) and an FMT fixed to the promontory (pFMT) were compared to explore the role of bone conduction. Vibration transmission to the measuring point at the stapes was best when the rwFMT was perpendicularly placed in the round window and underlayed with connective tissue. Fixation of the rwFMT to the round window exhibited significantly lower vibration transmission. Although measurable, bone conduction from the pFMT was much lower than that of the BAHA. Our results suggest that the rwFMT does not act as a small bone anchored hearing aid, but instead, acts as a direct vibratory stimulator of the round window membrane.

Radiological stab wound channel depiction with instillation of contrast medium

The radiological depiction of stab wounds in soft-tissues using multislice computed tomography is difficult and the hereby obtained images often lack contrast. To overcome these shortcomings we tried a new method. We gently instilled the contrast medium Lipiodol((R)) Ultra-fluide into five experimentally induced stab wounds on a pork haunch. Subsequent MSCT reconstructions of the wounds delivered clear, for medical laymen easily appreciable images regarding the stab direction and the stab depth. We believe that this easy and rapid technique can be useful in the examination of stab wounds in living and dead victims of sharp trauma.

Improvement of non-paraneoplastic voltage-gated potassium channel antibody-associated limbic encephalitis without immunosuppressive therapy

We describe a 61-year-old patient with clinical evidence of limbic encephalitis who improved with anticonvulsant treatment only, that is, without the use of immunosuppressive agents. Three years following occurrence of anosmia, increasing memory deficits, and emotional disturbances, he presented with new-onset temporal lobe epilepsy, with antibodies binding to neuronal voltage-gated potassium channels and bitemporal hypometabolism on FDG-PET scan; the MRI scan was normal. This is most likely a case of spontaneous remission, illustrating that immunosuppressive therapy might be suspended in milder courses of limbic encephalitis. It remains open whether treatment with anticonvulsant drugs played an additional beneficiary role through the direct suppression of seizures or, additionally, through indirect immunomodulatory side effects.

Incidence and predictors of atrioventricular conduction impairment after transcatheter aortic valve implantation

Atrioventricular (AV) conduction impairment is well described after surgical aortic valve replacement, but little is known in patients undergoing transcatheter aortic valve implantation (TAVI). We assessed AV conduction and need for a permanent pacemaker in patients undergoing TAVI with the Medtronic CoreValve Revalving System (MCRS) or the Edwards Sapien Valve (ESV). Sixty-seven patients without pre-existing permanent pacemaker were included in the study. Forty-one patients (61%) and 26 patients (39%) underwent successful TAVI with the MCRS and ESV, respectively. Complete AV block occurred in 15 patients (22%), second-degree AV block in 4 (6%), and new left bundle branch block in 15 (22%), respectively. A permanent pacemaker was implanted in 23 patients (34%). Overall PR interval and QRS width increased significantly after the procedure (p <0.001 for the 2 comparisons). Implantation of the MCRS compared to the ESV resulted in a trend toward a higher rate of new left bundle branch block and complete AV block (29% vs 12%, p = 0.09 for the 2 comparisons). During follow-up, complete AV block resolved in 64% of patients. In multivariable regression analysis pre-existing right bundle branch block was the only independent predictor of complete AV block after TAVI (relative risk 7.3, 95% confidence interval 2.4 to 22.2). In conclusion, TAVI is associated with impairment of AV conduction in a considerable portion of patients, patients with pre-existing right bundle branch block are at increased risk of complete AV block, and complete AV block resolves over time in most patients.

Heavy metal cations permeate the TRPV6 epithelial cation channel

TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This calcium-selective channel is highly expressed in the duodenum and the placenta, being responsible for calcium absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to calcium but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as zinc and cadmium. We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells, and that this difference almost disappeared in nominally calcium-free solution. Live cell imaging experiments with Fura-2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability for Ca(2+), Ba(2+), Sr(2+), Mn(2+), Zn(2+), Cd(2+), and interestingly also for La(3+) and Gd(3+). These results were confirmed using the patch clamp technique. (45)Ca uptake experiments showed that cadmium, lanthanum and gadolinium were also highly efficient inhibitors of TRPV6-mediated calcium influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in calcium transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications.

Chemical inhibitors of the calcium entry channel TRPV6

Calcium entry channels in the plasma membrane are thought to play a major role in maintaining cellular Ca(2+) levels, crucial for growth and survival of normal and cancer cells. The calcium-selective channel TRPV6 is expressed in prostate, breast, and other cancer cells. Its expression coincides with cancer progression, suggesting that it drives cancer cell growth. However, no specific inhibitors for TRPV6 have been identified thus far.

Nerve excitability studies characterize Kv1.1 fast potassium channel dysfunction in patients with episodic ataxia type 1

Episodic ataxia type 1 is a neuronal channelopathy caused by mutations in the KCNA1 gene encoding the fast K(+) channel subunit K(v)1.1. Episodic ataxia type 1 presents with brief episodes of cerebellar dysfunction and persistent neuromyotonia and is associated with an increased incidence of epilepsy. In myelinated peripheral nerve, K(v)1.1 is highly expressed in the juxtaparanodal axon, where potassium channels limit the depolarizing afterpotential and the effects of depolarizing currents. Axonal excitability studies were performed on patients with genetically confirmed episodic ataxia type 1 to characterize the effects of K(v)1.1 dysfunction on motor axons in vivo. The median nerve was stimulated at the wrist and compound muscle action potentials were recorded from abductor pollicis brevis. Threshold tracking techniques were used to record strength-duration time constant, threshold electrotonus, current/threshold relationship and the recovery cycle. Recordings from 20 patients from eight kindreds with different KCNA1 point mutations were compared with those from 30 normal controls. All 20 patients had a history of episodic ataxia and 19 had neuromyotonia. All patients had similar, distinctive abnormalities: superexcitability was on average 100% higher in the patients than in controls (P < 0.00001) and, in threshold electrotonus, the increase in excitability due to a depolarizing current (20% of threshold) was 31% higher (P < 0.00001). Using these two parameters, the patients with episodic ataxia type 1 and controls could be clearly separated into two non-overlapping groups. Differences between the different KCNA1 mutations were not statistically significant. Studies of nerve excitability can identify K(v)1.1 dysfunction in patients with episodic ataxia type 1. The simple 15 min test may be useful in diagnosis, since it can differentiate patients with episodic ataxia type 1 from normal controls with high sensitivity and specificity.

In vivo assessment of HCN channel current (I(h)) in human motor axons

The "Trond" protocol of nerve excitability tests has been used widely to assess axonal function in peripheral nerve. In this study, the routine Trond protocol was expanded to refine assessment of cAMP-dependent, hyperpolarization-activated current (I(h)) activity. I(h) activity is generated by hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels in response to hyperpolarization. It limits activity-dependent hyperpolarization, contributes to neuronal automaticity, and is implicated in chronic pain states. Published data regarding I(h) activity in motor nerve are scant. We used additional strong, prolonged hyperpolarizing conditioning stimuli in the threshold electrotonus component of the Trond protocol to demonstrate the time-course of activation of I(h) in motor axons. Fifteen healthy volunteers were tested on four occasions during 1 week. I(h) action was revealed in the threshold electrotonus by the limiting and often reversal, after about 100 ms, of the threshold increase caused by strong hyperpolarizing currents. Statistical analysis by repeated-measures analysis of variance enabled confidence limits to be established for variation between subjects and within subjects. The results demonstrate that, of all the excitability parameters, those dependent on I(h) were the most characteristic of an individual, because variance between subjects was more than four times the variance within subjects. This study demonstrates a reliable method for in vivo assessment of I(h,) and also serves to document the normal variability in nerve excitability properties within subjects.