Dynamics of zonal flow-like structures in the edge of the TJ-II stellarator

The dynamics of fluctuating electric field structures in the edge of the TJ-II stellarator, that display zonal flow-like traits, is studied. These structures have been shown to be global and affect particle transport dynamically [J.A. Alonso et al., Nucl. Fus. 52 063010 (2012)]. In this article we discuss possible drive (Reynolds stress) and damping (Neoclassical viscosity, geodesic transfer) mechanisms for the associated ExB velocity. We show that: (a) while the observed turbulence-driven forces can provide the necessary perpendicular acceleration, a causal relation could not be firmly established, possibly because of the locality of the Reynolds stress measurements, (b) the calculated neoclassical viscosity and damping times are comparable to the observed zonal flow relaxation times, and (c) although an accompanying density modulation is observed to be associated to the zonal flow, it is not consistent with the excitation of pressure side-bands, like those present in geodesic acoustic oscillations, caused by the compression of the ExB flow field

Whole body vibration compared to conventional physiotherapy in patients with gonarthrosis: a protocol for a randomized, controlled study

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is the most common degenerative arthropathy. Load-bearing joints such as knee and hip are more often affected than spine or hands. The prevalence of gonarthrosis is generally higher than that of coxarthrosis.</p> <p>Because no cure for OA exists, the main emphasis of therapy is analgesic treatment through either mobility or medication. Non-pharmacologic treatment is the first step, followed by the addition of analgesic medication, and ultimately by surgery.</p> <p>The goal of non-pharmacologic and non-invasive therapy is to improve neuromuscular function, which in turn both prevents formation of and delays progression of OA. A modification of conventional physiotherapy, whole body vibration has been successfully employed for several years. Since its introduction, this therapy is in wide use at our facility not only for gonarthrosis, but also coxarthrosis and other diseases leading to muscular imbalance.</p> <p>Methods/Design</p> <p>This study is a randomized, therapy-controlled trial in a primary care setting at a university hospital. Patients presenting to our outpatient clinic with initial symptoms of gonarthrosis will be assessed against inclusion and exclusion criteria. After patient consent, 6 weeks of treatment will ensue. During the six weeks of treatment, patients will receive one of two treatments, conventional physiotherapy or whole-body-vibration exercises of one hour three times a week. Follow-up examinations will be performed immediately after treatment and after another 6 and 20 weeks, for a total study duration of 6 months. 20 patients will be included in each therapy group.</p> <p>Outcome measurements will include objective analysis of motion and ambulation as well as examinations of balance and isokinetic force. The Western Ontario and McMaster Universities Arthritis Index and SF-12 scores, the patients' overall status, and clinical examinations of the affected joint will be carried out.</p> <p>Discussion</p> <p>As new physiotherapy techniques develop for the treatment of OA, it is important to investigate the effectiveness of competing strategies. With this study, not only patient-based scores, but also objective assessments will be used to quantify patient-derived benefits of therapy.</p> <p>Trial registration</p> <p>Deutsches Register Klinischer Studien (DRKS) DRKS00000415</p> <p>Clinicaltrials.gov NCT01037972</p> <p>EudraCT 2009-017617-29</p

Characterization of the hyperpolarization-activated, highly-selective proton channel HCNL1 found in the sperm of the zebrafish "Danio rerio"

Zebrafish are external fertilizers and release their gametes into the surrounding water. Yet, the freshwater environment with its low osmolarity poses a challenge for the gametes. Given these unique ion conditions, it seems likely that zebrafish sperm have evolved specialized ion channels that are adapted to the freshwater environment. However, very little is known about the sperm of freshwater fish. Another field that is still poorly understood is that of proton channels. Proton channels are exceptional among ion channels. Since protons differ substantially from other ions in their properties, their permeation pathways are very different from those of other ion channels. Proton channels select protons against other ions that are up to a million-fold more abundant, and only a few have been identified so far. In my PhD thesis, I characterized a novel proton channel that belongs to the HCN channel family and is found in zebrafish sperm (drHCNL1). Despite its overall similarity to classical HCN channels that conduct K+ and Na+, drHCNL1 is exquisitely selective for protons. Activated by hyperpolarization, it conducts protons into the cytosol under physiological conditions, whereas the only other known voltage-gated proton channel, Hv1, is activated by depolarization and expels protons from the cell. Remarkably, protons permeate through drHCNL1’s voltage-sensing domain, whereas the “classical” pore domain is non-functional. Crucial for this proton permeation pathway is a methionine residue, which interrupts the series of regularly spaced arginine residues in the S4 voltage sensor. DrHCNL1 forms a tetramer and thus contains four proton pores. In contrast to classical HCN channels, drHCNL1 is not modulated by cyclic nucleotides. Another ion channel in zebrafish sperm previously identified, drCNGK, is also insensitive to cyclic nucleotides and, instead, is controlled by intracellular pH. My results suggest that both channels are functionally related, and that protons rather than cyclic nucleotides serve as cellular messengers in zebrafish sperm. The primary function of HCN channels is to depolarize the cell after hyperpolarization. In freshwater that is extremely low in Na+, a channel conducting Na+ would hyperpolarize sperm even further. Through small modifications in two key functional domains, drHCNL1 has been transformed to a proton-selective channel and thus evolutionarily adapted to the freshwater environment so that the sperm’s ability to depolarize is conserved.Zebrafische pflanzen sich durch externe Befruchtung fort und geben hierzu ihre Gameten in das umgebende Wasser ab. Die Süßwasserumgebung mit ihrer geringen Osmolarität stellt jedoch eine besondere Herausforderung für die Gameten dar. Angesichts dieser einzigartigen Ionenbedingungen scheint es wahrscheinlich, dass die Spermien des Zebrafisches spezialisierte Ionenkanäle entwickelt haben, die an die Süßwasserumgebung angepasst sind. Über die Spermien von Süßwasserfischen ist jedoch sehr wenig bekannt. Ein weiteres Feld, das noch wenig verstanden ist, ist das der Protonenkanäle. Protonenkanäle sind unter den Ionenkanälen eine Besonderheit. Da sich Protonen in ihren Eigenschaften wesentlich von anderen Ionen unterscheiden, erfolgt ihre Permeation auf eine ganz andere Art und Weise als die von anderen Ionen. Protonenkanäle selektieren für Protonen gegen andere Ionen, die bis zu einer Million Mal häufiger vorkommen, und nur wenige wurden bisher identifiziert. In meiner Doktorarbeit habe ich einen neuartigen Protonenkanal charakterisiert, der zur Familie der HCN-Kanäle gehört, und in den Spermien von Zebrafischen (drHCNL1) vorkommt. Trotz seiner prinzipiellen Ähnlichkeit mit klassischen HCN-Kanälen, die K+ und Na+ leiten, ist drHCNL1 ein äußerst selektiver Protonenkanal. Durch Hyperpolarisation aktiviert, leitet es Protonen in das Zytosol. Damit ist er das genaue Gegenteil des bisher einzigen anderen bekannten spannungsgesteuerten Protonenkanals Hv1, der durch Depolarisation aktiviert wird und die Protonen aus der Zelle ausstößt. Bemerkenswert ist, dass die Protonen durch die Spannungssensordomäne von drHCNL1 geleitet werden, während die Porendomäne nicht funktionsfähig ist. Entscheidend für diesen Protonen-Permeationsweg ist ein Methionin-Rest, der die Sequenz der regelmäßig angeordneten Arginin-Reste im S4-Spannungssensor unterbricht. DrHCNL1 bildet ein Tetramer und enthält somit vier Protonenporen. Im Gegensatz zu den klassischen HCN-Kanälen wird drHCNL1 nicht durch zyklische Nukleotide angesteuert. Ein weiterer, zuvor von Sylvia Fechner identifizierter Ionenkanal im Zebrafischsperma, drCNGK, ist ebenfalls unempfindlich gegenüber zyklischen Nukleotiden und wird stattdessen durch den intrazellulären pH-Wert gesteuert. Meine Ergebnisse deuten darauf hin, dass beide Kanäle eine enge funktionelle Beziehung haben und dass Protonen statt zyklischer Nukleotide als zelluläre Botenstoffe in Zebrafischspermien dienen. Eine Hauptfunktion der HCN-Kanäle ist die Depolarisation der Zelle nach der Hyperpolarisation. In Süßwasser, das einen extrem niedrigem Na+-Gehalt hat, würde ein Na+-leitender Kanal die Spermien nur weiter hyperpolarisieren. Durch kleine Modifikationen in zwei wichtigen funktionellen Domänen hat sich drHCNL1 in einen selektiven Protonenkanal verwandelt und damit evolutionär an die Süßwasserumgebung angepasst, so dass die Fähigkeit der Spermien zur Depolarisation erhalten bleibt

Spatial Working Memory Under Differential and Nondifferential Outcomes I: Effects of Nicotine

Previous studies have demonstrated the potential for nicotine to enhance cognitive ability including learning, attention, and memory in both animal and human models. The effects of 62 nicotine were examined while subjects performed a discrimination task under delayed conditions. Subjects were trained under nondifferential outcomes (NDO), or differential outcomes (DO) procedures. While subjects that were trained under (DO) did exhibit performance gains across delays indicative of the differential outcomes effect (DOE), no evidence of significant performance gain as a function of nicotine exposure were found under either condition. We are currently engaged in a follow-up study using a wider range of doses in which we investigate the effects of ethanol, scopolamine, MK-801, and dextromethorphan