Mechanical vibration in “double-wound” magnetic field exposure coils

It has been suggested that “double-wound” (bifilar) exposure coils are capable of producing a sham environment in which hum and vibration will be “similar” to the field-exposed condition. We found by direct measurements in a bifilar coil system that vibration amplitude in sham and exposed conditions differed by a factor of 50 when our test system was driven at B = 10 mT. We also found that the normal laboratory environment can include vibrations of an intensity similar to that produced by the exposure system, although not necessarily of similar spectral distribution. © 1996 Wiley-Liss, Inc.     

NKG2D discriminates diverse ligands through selectively mechano‐regulated ligand conformational changes

Stimulatory immune receptor NKG2D binds diverse ligands to elicit differential anti‐tumor and anti‐virus immune responses. Two conflicting degeneracy recognition models based on static crystal structures and in‐solution binding affinities have been considered for almost two decades. Whether and how NKG2D recognizes and discriminates diverse ligands still remain unclear. Using live‐cell‐based single‐molecule biomechanical assay, we characterized the in situ binding kinetics of NKG2D interacting with different ligands in the absence or presence of mechanical force. We found that mechanical force application selectively prolonged NKG2D interaction lifetimes with the ligands MICA and MICB, but not with ULBPs, and that force‐strengthened binding is much more pronounced for MICA than for other ligands. We also integrated steered molecular dynamics simulations and mutagenesis to reveal force‐induced rotational conformational changes of MICA, involving formation of additional hydrogen bonds on its binding interface with NKG2D, impeding MICA dissociation under force. We further provided a kinetic triggering model to reveal that force‐dependent affinity determines NKG2D ligand discrimination and its downstream NK cell activation. Together, our results demonstrate that NKG2D has a discrimination power to recognize different ligands, which depends on selective mechanical force‐induced ligand conformational changes.     

Wie V?gel ihr Auge schützen: Zur Arbeitsteilung von Oberlid, Unterlid und Nickhaut

Zusammenfassung Vögel schließen ihre Augen im Schlaf in einer für die großen Taxa typischen Weise. Entweder geht das Unterlid hoch wie bei der Mehrzahl der Arten, oder das Oberlid bewegt sich abwärts (Psittaciformes, Trochili), oder aber beide Lider schließen die Lidspalte (Strigiformes, Caprimulgi). Solche Kenntnis fehlt von den meisten Ordnungen, oder die Handbücher geben falsche oder widersprüchliche Information. Neben dem tonischen, schlafbegleitenden Augenschluss bewegen Vögel im Wachzustand eines oder beide Lider phasisch und meist schnell. Dieser häufige Lidschlag ist durch ein anderes Bewegungsmuster und durch eine andere Funktion gekennzeichnet. Photodokumente und genaue Beobachtungen führen erstmals zu einer funktionellen Deutung, der zufolge der Lidschlag das Auge mechanisch schützt. Droht dem Auge von vorn oder von oben eine potentielle Schädigung, so schließt das Oberlid bei Tauben, Eulen und Singvögeln, im Sprühwasser gleichzeitig auch das Unterlid (Cinclus). Der unabweisbarste Beleg stammt aus dem Vergleich des Aufpickens dorniger, sperriger Beuteinsekten mit Oberlidschluss gegenüber dem Aufnehmen harmloser Beeren ohne jede Lidbewegung (Gallicolumba). Weiter ist die Antwort des Oberlids, anders als beim Unterlid, öfter seitengerecht reizorientiert, so dass die Bewegung einseitig sein kann. Zudem kann der Schluss des Oberlids auch bei stationärem (Feind-)reiz seitenweise alternieren (Otus). Ausnahmsweise tritt eine adaptive Asymmetrie auch während kurzer Zeiten der Augenöffnung zum Spähen nach Feinden im Schlaf auf, und zwar hier beim Unterlid der bedrohten Seite (Anas).Eine neue Funktion wird auch dem Schlag der Nickhaut (Membrana nictitans) zugeschrieben. Traditionell als die Cornea reinhaltendes Organ gesehen, dient auch sie dem mechanischen Schutz des Auges. Auch sie kann seitenrichtig reizorientiert schlagen, doch ist hierüber wenig bekannt. Dieselben Reize, die den Lidschlag auslösen, können bei anderen Arten die Nickhaut schlagen lassen. Ihre Schlagrate ist schwierig zu messen, da viele Schläge (nur?) mit denen des Oberlides zusammenfallen und so verborgen bleiben (Otus). Diese Synchronie ist mit keiner der bisher vorgeschlagenen Funktionen erklärbar, ebenso wenig wie die verborgenen Schläge bei tonischem Augenschluss (Passer).Die Annahme einer Ausschaltung störender Sinnesinformation, z.B. während rascher Kopfbewegungen, durch die Nickhaut lässt sich aus vier Gründen verwerfen. Die Zunahme der Schlagrate während des Feindalarms (Ficedula) bleibt funktionell unerklärt.In einer bei Vögeln einzigartigen Weise schützt der Samtkleiber (Sitta azurea) sein Auge durch Zusammenziehen des nackten Augenrings (Lidblende), wenn er rücklings an der Unterseite von Ästen nahrungssuchend einem ständigen Regen von losgelösten Rindenteilchen u. ä. ausgesetzt ist.Sekundär haben sich die Bewegungen eines oder beider Lider oder aber der Nickhaut zu optischen Signalen entwickelt, und zwar durch kontrastierende Feder- oder Nickhautfärbung. Die betreffenden blitzschnell aufleuchtenden Signale sind an den Paarpartner (Cinclus, Corvidae,Cepphus), an mögliche Feinde (Anas) oder an bisher unbekannte Empfänger gesichtet (Ficedula).

---

On how birds protect their eyes: division of labour between the upper lid, lower lid and the nictitating membrane

Summary Birds close their eyes during sleep in various taxon-specific ways. Either the lower lid moves up as in the majority of species including the Anseres, Accipitres, Falconiformes, Galli, Charadrioidea, Columbiformes, and Oscines; or the upper lid moves down (Psittaciformes, Trochili), or both lids close the eye as in Strigiformes and Caprimulgi. Such information is absent for most orders, or the handbooks provide wrong or conflicting information. Beside the tonic, sleep-related eye closure, birds move one or both lids in a phasic, usually swift mode when awake. These frequent lid movements are typified by their different co-ordination and function. Photographic and observational evidence strongly suggests mechanical protection of the eye as a novel function (where this had not been proposed previously). When an impact from any object is imminent from in front of or above the head, the upper lid shuts in pigeons, owls and oscines, and with water splashing, the lower lid as well (Cinclus). The most convincing evidence for mechanical protection comes from the deployment of the upper lid during the picking up of spiny insect prey as compared to easy-to-swallow berries, when both lids stay at rest (Gallicolumba).Further, the response of the upper lid is more stimulus-oriented so that both upper lids move asymmetrically. But there is also a unilateral, alternating winking of the upper lids when causative (predator) stimuli remain stationary. This never occurs with the lower lids (Otus). As an exception, an adaptive asymmetry occurs during brief phases of unilateral scanning interrupting sleep, designed to detect approaching predators. This scanning involves the lower lid (Anas).A new function is also attributed to the beating of the nictitating membrane (Membrana nictitans). Traditionally viewed as a cleaning device it also serves to protect the eye from mechanical impact, and it also can be tuned to the side from where danger is threatening, though by and large there is a dearth of information from avian taxa. The non-visually elicited action of the membrane seems always to be bilateral (Falco, Harpia). The very stimuli eliciting the blinking of a lid can, in different species, trigger the beat of the membrane, and can cause it to move tonically (Falco). The membrane beats at a rate difficult to measure since many of its beats coincide with the blinking of the upper lid and thus remain hidden (Otus). This coincidence is difficult to account for by any function discussed so far, as are the many hidden beats during tonic eye closure with the lids (Passer).The hypothesis according to which the action of the membrane is filtering out undesirable retinal stimulation during e.g. rapid head movements is dismissed on four different grounds. The increase of the membrane activity during predator alarm (Ficedula) is functionally unaccounted for.In a fashion unique among birds, the Blue Nuthatch (Sitta azurea) protects its eyes by contracting the naked skin surrounding the eye, thereby minimizing the exposure of the cornea; during foraging along the underside of branches, a continual rain of bark particles and debris jeopardizes unimpeded vision.Secondarily, one or both lids or the nictitating membrane have taken on the function of optic signals by virtue of contrasting feather colour or coloration. The phasic (flashing) signal movements involved are directed at the pair mate (Cinclus, Corvidae,Cepphus), predators (Anas) or at unknown parties (Ficedula).

Dies ist Veröffentlichung Nr. 29 des Philippine Endemic Species Conservation Project der Zoologischen Gesellschaft Frankfurt.     

Monitoring clinical trials with multiple arms

In order to benefit from the substantial overhead expenses of a large group sequential clinical trial, the simultaneous investigation of several competing treatments becomes more popular. If at some interim analysis any treatment arm reveals itself to be inferior to any other treatment under investigation, this inferior arm may be or may even need to be dropped for ethical and/or economic reasons. Recently proposed methods for monitoring and analysis of group sequential clinical trials with multiple treatment arms are compared and discussed. The main focus of the article is on the application and extension of (adaptive) closed testing procedures in the group sequential setting that strongly control the familywise error rate. A numerical example is given for illustration.     

Expression of pattern in plants: combining molecular and calculus-based biophysical paradigms

Pattern formation in plant meristems occurs across a broad scale. At the topographical level (large scale), tissue folding in the meristem is responsible for the initiation of new organs in specific phyllotactic patterns and also determines organ shape. At the cellular level (small scale), oriented cell division and microtubule-based cellulose reinforcement control cell pattern and growth direction. I argue here that structural specification at each scale is highly efficient if the pertinent gene activity is manifested in two complementary biophysical categories. At large scale, one category is the tendency of the formative tissue to fold with a certain spatial periodicity determined by its material properties (e.g., bending stiffness from cellulose content). This latent tendency is formalized in a differential equation for physical buckling. The second category at this scale comprises boundary conditions that specify how the latent tendency is manifested as topography: whether tissue humps occur as whorls or Fibonacci spirals. This versatile combinatorial format accounts for the relative stability of alternative organ patterning as well as alternative organ shaping (e.g., stamens vs. carpels). It also accounts for the structural shifts seen in normal development and after mutation or chemical/physical intervention. At small scale, the latent differential activity is the tendency for groups of dividing cells to co-align their cytoskeletons. The curvature of the surface opposes this tendency. The least curved part of a new primordium is its quasicylindrical midportion. There, by aligning microtubules and cellulose coherently around the organ, a new growth direction is set. Thus large-scale buckling produces curvature variation, which, in turn, affects the localization and orientation of the cytoskeleton. This scheme for the coherent production of diverse geometrical features, involving calculus at two structural levels, is supported by complex organogenetic responses to simple physical intervention. Also, many morphological alternatives, wild type vs. mutant, reflect single changes in parameters in this differential-integral format.     

Thermal effects in stretching of Go-like models of titin and secondary structures

The effect of temperature on mechanical unfolding of proteins is studied using a Go-like model with a realistic contact map and Lennard-Jones contact interactions. The behavior of the I27 domain of titin and its serial repeats is contrasted to that of simple secondary structures. In all cases, thermal fluctuations accelerate the unraveling process, decreasing the unfolding force nearly linearly at low temperatures. However, differences in bonding geometry lead to different sensitivity to temperature and different changes in the unfolding pattern. Due to its special native-state geometry, titin is much more thermally and elastically stable than the secondary structures. At low temperatures, serial repeats of titin show a parallel unfolding of all domains to an intermediate state, followed by serial unfolding of the domains. At high temperatures, all domains unfold simultaneously, and the unfolding distance decreases monotonically with the contact order, that is, the sequence distance between the amino acids that form the native contact.