Theory of a Probe in a Strong Magnetic Field. AT(30-1)-1238-MATT 599

A kinetic approach is used to develop a theory of electrostatic probes in a fully ionized plasma in the presence of a magnetic field. A consistent asymptotic expansion is obtained assuming that the electron Larmor radius is small compared to the radius of the probe. The order of magnitude of neglected terms is given. It is found that the electric potential within the tube of force defined by the cross section of the probe decays non-mono tonic ally from the probe; this bump disappears at a certain probe voltage and the theory is valid up to this voltage. The transition region, which extends beyond plasma potential, is not exponential. The possible saturation of the electron current is discussed. Restricted numerical results are given; they seem to be useful for weaker magnetic fields down to the zero-field limit. Extensions of the theory a r e considered.

Emissive Langmuir Probes in the Strong Emission Regime for the Determination of the Plasma Properties

The determination of the plasma potential Vpl of unmagnetized plasmas by using the floating potential of emissive Langmuir probes operated in the strong emission regime is investigated. The experiments evidence that, for most cases, the electron thermionic emission is orders of magnitude larger than the plasma thermal electron current. The temperature-dependent floating potentials of negatively biased Vpmenor queVpl emissive probes are in agreement with the predictions of a simple phenomenological model that considers, in addition to the plasma electrons, an ad-ditional electron group that contributes to the probe current. The latter would be constituted by a fraction of the repelled electron thermionic current, which might return back to the probe with a different energy spectrum. Its origin would be a plasma potential well formed in the plasma sheath around the probe, acting as a virtual cathode or by collisions and electron thermalization pro-cesses. These results suggest that, for probe bias voltages close to the plasma potential Vp?Vpl, two electron populations coexist, i.e., the electrons from the plasma with temperatureTeand a large group of returned thermionic electrons. These results question the theoretical possibility of measuring the electron temperature by using emissive probes biased to potentials Vp about lower equal than ?Vpl.

Thin as a rail, strong as a rock

Satellite de-orbiting and re-entry is essential to halting the continuous increase in orbital space debris. The BETS project, which ends this month, is making waves with a new tether solution that is faster and more resistant to damage than any other existing technology.

Lateral Dynamic Models for High-Speed Railway Bridges and Vehicles

The analysis of the running safety of railway vehicles on viaducts subject to strong lateral actions such as cross winds requires coupled nonlinear vehicle-bridge interaction models, capable to study extreme events. In this paper original models developed by the authors are described, based on finite elements for the structure, multibody and finite element models for the vehicle, and specially developed interaction elements for the interface between wheel and rail. The models have been implemented within ABAQUS and have full nonlinear capabilities for the structure, the vehicle and the contact interface. An application is developed for the Ulla Viaduct, a 105 m tall arch in the Spanish high-speed railway network. The dynamic analyses allow obtaining critical wind curves, which define the running safety conditions for a given train in terms of speed of circulation and wind speed

Estudio de la respuesta dinámica transversal de viaductos altos de líneas de ferrocarril de alta velocidad bajo la acción de cargas de uso

Es conocido que las dimensiones de los puentes de ferrocarril han ido cambiando debido a las estrictas condiciones de trazado impuestas en las líneas de alta velocidad. Además, la creciente preocupación de la sociedad por cuidar y proteger el medio ambiente, reflejado en la correspondiente normativa, ha generado nuevos condicionantes en el diseño de estas infraestructuras. En concreto, se ha limitado el movimiento de grandes volúmenes de terreno particularmente en los espacios protegidos. Por estas razones, hoy en día se proyectan y construyen puentes de ferrocarril más altos y más largos en todo el mundo. En España se han construido varios viaductos de pilas altas para líneas de alta velocidad. Ejemplos de estas infraestructuras son el Viaducto O’Eixo y el Viaducto de Barbantiño, situados en la línea de alta velocidad Madrid-Galicia, Estos viaductos altos se caracterizan por tener una mayor flexibilidad lateral y una frecuencia fundamental de oscilación baja, de hasta 0.2 Hz. La respuesta dinámica de este tipo de estructura puede aumentar como consecuencia de la aproximación entre la frecuencias propias de la misma y las de excitación debidas al paso del tren y a la acción del viento. Por lo tanto, estas estructuras pueden presentar problemas a la hora de cumplir con las limitaciones impuestas en las normas de diseño de puentes de ferrocarril, y otras, para garantizar la seguridad del tráfico y el confort de los viajeros. La respuesta dinámica lateral de viaductos de pilas altas no ha sido suficientemente estudiada en la literatura científica. Se pueden intuir varios de los motivos para explicar esta carencia. El primero es la relativamente reciente aparición de este tipo de viaductos asociados al desarrollo de la alta velocidad. Por otro lado, se hace necesario, para estudiar este tema, construir nuevos modelos numéricos adecuados para el estudio de la interacción dinámica lateral del puente y del tren. La interacción entre el puente y un tren viajando sobre él es un problema dinámico no lineal, dependiente del tiempo y de acoplamiento entre los dos subsistemas que intervienen (vehículo y puente). Los dos subsistemas, que pueden ser modelados como estructuras elásticas, interaccionan el uno con el otro a través de las fuerzas de contacto, que tiene una marcada naturaleza no lineal por el rozamiento entre rueda y carril, y por la geometría de los perfiles de estos dos elementos en contacto. En esta tesis, se desarrolla la formulación completa de un modelo no lineal de interacción tren-vía-puente-viento que reproduce adecuadamente las fuerzas laterales de contacto rueda-carril, fuerzas que van a tener una gran influencia en los índices de seguridad del tráfico. Este modelo se ha validado a partir de casos resueltos en la literatura científica, y de medidas experimentales tomadas en eventos dinámicos ocurridos en los viaductos de Arroyo de Valle y Arroyo de las Piedras. Puentes altos que han estado monitorizados en servicio durante dos años. En los estudios realizados en este trabajo, se cuantifican, empleando el modelo construido, los niveles de seguridad del tráfico y de confort de los pasajeros de trenes ligeros de alta velocidad, como el tren articulado AVE S-100, que viajan sobre viaductos altos sometidos, o no, a fuertes vientos laterales racheados. Finalmente, se ha obtenido el grado de mejora de la seguridad del tráfico y del confort de los viajeros, cuando se emplean pantallas anti-viento en el tablero y amortiguadores de masa sintonizados en la cabeza de las pilas de un viaducto alto. Resultando, el uso simultaneo de estos dos dispositivos (pantallas y amortiguadores de masa), en puentes altos de líneas de alta velocidad, una opción a considerar en la construcción de estas estructuras para elevar significativamente el nivel de servicio de las mismas. It is known that dimensions of railway bridges have been changing due to the strict high-speed lines layout parameters. Moreover, the growing concern of society to take care of and protect the environment, reflected in the corresponding regulations, has created new environment requirements for the design of these infrastructures. Particularly, the mentioned regulations do not allow designers to move far from terrain to build these railway lines. Due to all these reasons, longer and higher railway bridges are being designed and built around the world. In Spain, several high pier railway viaducts have been built for high speed lines. Barbantiño Viaduct and Eixo Viaduct, belonging to the Madrid-Galicia high speed line, are examples of this kind of structures. These high viaducts have great lateral flexibility and a low fundamental vibration frequency of down to 0.2 Hz. The dynamic response of high speed railway bridges may increase because of the approximation between the natural viaduct frequencies and the excitation ones due to the train travel and the wind action. Therefore, this bridge response could not satisfy the serviceability limits states, for traffic safety and for passenger comfort, considered by the design standards of high speed bridges. It is difficult to find papers in the scientific literature about the lateral response of high-speed trains travel over long viaducts with high piers. Several reasons could explain this issue. On one hand, the construction of this kind of viaduct is relatively recent and it is associated to the development of the high speed railway. On the other hand, in order to study the dynamic lateral interaction between the train and the high bridge, it is necessary to build new numerical and complex models. The interaction between the bridge-track subsystem and the vehicle subsystem travelling over the bridge is a coupling, nonlinear and time dependent problem. Both subsystems, train and bridge, which can be modelled as elastic structures, interact each other through the contact forces. These forces have a strong nonlinear nature due to the friction and the geometry of rail and wheel profiles. In this thesis, the full formulation of a train-track-bridge-wind nonlinear interaction model is developed. This model can reproduce properly the lateral contact wheel-rail forces, which have a great influence on traffic safety indices. The validation of the model built has been reached through interaction solved cases found in the scientific literature and experimental measures taken in dynamic events which happened at Arroyo de las Piedras and Arroyo del Valle Viaducts. These high bridges have been controlled during two years of service by means of structural health monitoring. In the studies carried out for this thesis, the levels of traffic safety and passenger comfort are quantified using the interaction model built, in the cases of high speed and light trains, as AVE S-100, travelling over high pier bridges and with or without lateral turbulent winds acting. Finally, the improvement rate of the traffic safety and passenger comfort has been obtained, when wind barriers are used at the bridge deck and tuned mass dampers are installed at the pier heads of a high viaduct. The installation of both devices, wind barriers and tuned mass damper, at the same time, turned out to be a good option to be considered in the design of high pier railway viaducts, to improve significantly the serviceability level of this kind of structures.

Strong Connectivity in Directed Hypergraphs and its Application to the Atomic Decomposition of Ontologies

Los hipergrafos dirigidos se han empleado en problemas relacionados con lógica proposicional, bases de datos relacionales, linguística computacional y aprendizaje automático. Los hipergrafos dirigidos han sido también utilizados como alternativa a los grafos (bipartitos) dirigidos para facilitar el estudio de las interacciones entre componentes de sistemas complejos que no pueden ser fácilmente modelados usando exclusivamente relaciones binarias. En este contexto, este tipo de representación es conocida como hiper-redes. Un hipergrafo dirigido es una generalización de un grafo dirigido especialmente adecuado para la representación de relaciones de muchos a muchos. Mientras que una arista en un grafo dirigido define una relación entre dos de sus nodos, una hiperarista en un hipergrafo dirigido define una relación entre dos conjuntos de sus nodos. La conexión fuerte es una relación de equivalencia que divide el conjunto de nodos de un hipergrafo dirigido en particiones y cada partición define una clase de equivalencia conocida como componente fuertemente conexo. El estudio de los componentes fuertemente conexos de un hipergrafo dirigido puede ayudar a conseguir una mejor comprensión de la estructura de este tipo de hipergrafos cuando su tamaño es considerable. En el caso de grafo dirigidos, existen algoritmos muy eficientes para el cálculo de los componentes fuertemente conexos en grafos de gran tamaño. Gracias a estos algoritmos, se ha podido averiguar que la estructura de la WWW tiene forma de “pajarita”, donde más del 70% del los nodos están distribuidos en tres grandes conjuntos y uno de ellos es un componente fuertemente conexo. Este tipo de estructura ha sido también observada en redes complejas en otras áreas como la biología. Estudios de naturaleza similar no han podido ser realizados en hipergrafos dirigidos porque no existe algoritmos capaces de calcular los componentes fuertemente conexos de este tipo de hipergrafos. En esta tesis doctoral, hemos investigado como calcular los componentes fuertemente conexos de un hipergrafo dirigido. En concreto, hemos desarrollado dos algoritmos para este problema y hemos determinado que son correctos y cuál es su complejidad computacional. Ambos algoritmos han sido evaluados empíricamente para comparar sus tiempos de ejecución. Para la evaluación, hemos producido una selección de hipergrafos dirigidos generados de forma aleatoria inspirados en modelos muy conocidos de grafos aleatorios como Erdos-Renyi, Newman-Watts-Strogatz and Barabasi-Albert. Varias optimizaciones para ambos algoritmos han sido implementadas y analizadas en la tesis. En concreto, colapsar los componentes fuertemente conexos del grafo dirigido que se puede construir eliminando ciertas hiperaristas complejas del hipergrafo dirigido original, mejora notablemente los tiempos de ejecucion de los algoritmos para varios de los hipergrafos utilizados en la evaluación. Aparte de los ejemplos de aplicación mencionados anteriormente, los hipergrafos dirigidos han sido también empleados en el área de representación de conocimiento. En concreto, este tipo de hipergrafos se han usado para el cálculo de módulos de ontologías. Una ontología puede ser definida como un conjunto de axiomas que especifican formalmente un conjunto de símbolos y sus relaciones, mientras que un modulo puede ser entendido como un subconjunto de axiomas de la ontología que recoge todo el conocimiento que almacena la ontología sobre un conjunto especifico de símbolos y sus relaciones. En la tesis nos hemos centrado solamente en módulos que han sido calculados usando la técnica de localidad sintáctica. Debido a que las ontologías pueden ser muy grandes, el cálculo de módulos puede facilitar las tareas de re-utilización y mantenimiento de dichas ontologías. Sin embargo, analizar todos los posibles módulos de una ontología es, en general, muy costoso porque el numero de módulos crece de forma exponencial con respecto al número de símbolos y de axiomas de la ontología. Afortunadamente, los axiomas de una ontología pueden ser divididos en particiones conocidas como átomos. Cada átomo representa un conjunto máximo de axiomas que siempre aparecen juntos en un modulo. La decomposición atómica de una ontología es definida como un grafo dirigido de tal forma que cada nodo del grafo corresponde con un átomo y cada arista define una dependencia entre una pareja de átomos. En esta tesis introducimos el concepto de“axiom dependency hypergraph” que generaliza el concepto de descomposición atómica de una ontología. Un modulo en una ontología correspondería con un componente conexo en este tipo de hipergrafos y un átomo de una ontología con un componente fuertemente conexo. Hemos adaptado la implementación de nuestros algoritmos para que funcionen también con axiom dependency hypergraphs y poder de esa forma calcular los átomos de una ontología. Para demostrar la viabilidad de esta idea, hemos incorporado nuestros algoritmos en una aplicación que hemos desarrollado para la extracción de módulos y la descomposición atómica de ontologías. A la aplicación la hemos llamado HyS y hemos estudiado sus tiempos de ejecución usando una selección de ontologías muy conocidas del área biomédica, la mayoría disponibles en el portal de Internet NCBO. Los resultados de la evaluación muestran que los tiempos de ejecución de HyS son mucho mejores que las aplicaciones más rápidas conocidas. ABSTRACT Directed hypergraphs are an intuitive modelling formalism that have been used in problems related to propositional logic, relational databases, computational linguistic and machine learning. Directed hypergraphs are also presented as an alternative to directed (bipartite) graphs to facilitate the study of the interactions between components of complex systems that cannot naturally be modelled as binary relations. In this context, they are known as hyper-networks. A directed hypergraph is a generalization of a directed graph suitable for representing many-to-many relationships. While an edge in a directed graph defines a relation between two nodes of the graph, a hyperedge in a directed hypergraph defines a relation between two sets of nodes. Strong-connectivity is an equivalence relation that induces a partition of the set of nodes of a directed hypergraph into strongly-connected components. These components can be collapsed into single nodes. As result, the size of the original hypergraph can significantly be reduced if the strongly-connected components have many nodes. This approach might contribute to better understand how the nodes of a hypergraph are connected, in particular when the hypergraphs are large. In the case of directed graphs, there are efficient algorithms that can be used to compute the strongly-connected components of large graphs. For instance, it has been shown that the macroscopic structure of the World Wide Web can be represented as a “bow-tie” diagram where more than 70% of the nodes are distributed into three large sets and one of these sets is a large strongly-connected component. This particular structure has been also observed in complex networks in other fields such as, e.g., biology. Similar studies cannot be conducted in a directed hypergraph because there does not exist any algorithm for computing the strongly-connected components of the hypergraph. In this thesis, we investigate ways to compute the strongly-connected components of directed hypergraphs. We present two new algorithms and we show their correctness and computational complexity. One of these algorithms is inspired by Tarjan’s algorithm for directed graphs. The second algorithm follows a simple approach to compute the stronglyconnected components. This approach is based on the fact that two nodes of a graph that are strongly-connected can also reach the same nodes. In other words, the connected component of each node is the same. Both algorithms are empirically evaluated to compare their performances. To this end, we have produced a selection of random directed hypergraphs inspired by existent and well-known random graphs models like Erd˝os-Renyi and Newman-Watts-Strogatz. Besides the application examples that we mentioned earlier, directed hypergraphs have also been employed in the field of knowledge representation. In particular, they have been used to compute the modules of an ontology. An ontology is defined as a collection of axioms that provides a formal specification of a set of terms and their relationships; and a module is a subset of an ontology that completely captures the meaning of certain terms as defined in the ontology. In particular, we focus on the modules computed using the notion of syntactic locality. As ontologies can be very large, the computation of modules facilitates the reuse and maintenance of these ontologies. Analysing all modules of an ontology, however, is in general not feasible as the number of modules grows exponentially in the number of terms and axioms of the ontology. Nevertheless, the modules can succinctly be represented using the Atomic Decomposition of an ontology. Using this representation, an ontology can be partitioned into atoms, which are maximal sets of axioms that co-occur in every module. The Atomic Decomposition is then defined as a directed graph such that each node correspond to an atom and each edge represents a dependency relation between two atoms. In this thesis, we introduce the notion of an axiom dependency hypergraph which is a generalization of the atomic decomposition of an ontology. A module in the ontology corresponds to a connected component in the hypergraph, and the atoms of the ontology to the strongly-connected components. We apply our algorithms for directed hypergraphs to axiom dependency hypergraphs and in this manner, we compute the atoms of an ontology. To demonstrate the viability of this approach, we have implemented the algorithms in the application HyS which computes the modules of ontologies and calculate their atomic decomposition. In the thesis, we provide an experimental evaluation of HyS with a selection of large and prominent biomedical ontologies, most of which are available in the NCBO Bioportal. HyS outperforms state-of-the-art implementations in the tasks of extracting modules and computing the atomic decomposition of these ontologies.

Preferential interaction of the his pause RNA hairpin with RNA polymerase β subunit residues 904–950 correlates with strong transcriptional pausing

RNA secondary structures (hairpins) that form as the nascent RNA emerges from RNA polymerase are important components of many signals that regulate transcription, including some pause sites, all ρ-independent terminators, and some antiterminators. At the his leader pause site, a 5-bp-stem, 8-nt-loop pause RNA hairpin forms 11 nt from the RNA 3′ end and stabilizes a transcription complex conformation slow to react with NTP substrate. This stabilization appears to depend at least in part on an interaction with RNA polymerase. We tested for RNA hairpin interaction with the paused polymerase by crosslinking 5-iodoUMP positioned specifically in the hairpin loop. In the paused conformation, strong and unusual crosslinking of the pause hairpin to β904–950 replaced crosslinking to β′ and to other parts of β that occurred in nonpaused complexes prior to hairpin formation. These changes in nascent RNA interactions may inhibit reactive alignment of the RNA 3′ end in the paused complex and be related to events at ρ-independent terminators.

Immunization with live attenuated simian immunodeficiency virus induces strong type 1 T helper responses and β-chemokine production

Immunization with live attenuated simian immunodeficiency virus (SIV) strains has proved to be one of the most effective strategies to induce protective immunity in the SIV/macaque model. To better understand the role that CD4+ T helper responses may play in mediating protection in this model, we characterized SIV-specific proliferative and cytokine responses in macaques immunized with live attenuated SIV strains. Macaques chronically infected with live attenuated SIV had strong proliferative responses to SIV proteins, with stimulation indices of up to 74. The magnitude of the proliferative response to SIV Gag varied inversely with the degree of attenuation; Gag-specific but not envelope-specific responses were lower in animals infected with more highly attenuated SIV strains. SIV-specific stimulation of lymphocytes from vaccinated macaques resulted in secretion of interferon-γ, IL-2, regulated-upon-activation, normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α, and MIP-1β but not IL-4 or IL-10. Intracellular flow cytometric analysis documented that, in macaques vaccinated with SIVmac239Δnef, up to 2% of all CD4+T cells were specific for SIV p55. The ability of live attenuated SIV to induce a strong, sustained type 1 T helper response may play a role in the success of this vaccination approach to generate protection against challenge with wild-type SIV.

Cleavage planes in frog eggs are altered by strong magnetic fields

Early cleavages of Xenopus embryos were oriented in strong, static magnetic fields. Third-cleavage planes, normally horizontal, were seen to orient to a vertical plane parallel with a vertical magnetic field. Second cleavages, normally vertical, could also be oriented by applying a horizontal magnetic field. We argue that these changes in cleavage-furrow geometries result from changes in the orientation of the mitotic apparatus. We hypothesize that the magnetic field acts directly on the microtubules of the mitotic apparatus. Considerations of the length of the astral microtubules, their diamagnetic anisotropy, and flexural rigidity predict the required field strength for an effect that agrees with the data. This observation provides a clear example of a static magnetic-field effect on a fundamental cellular process, cell division.

Strong balancing selection at HLA loci: Evidence from segregation in South Amerindian families

The genotypic proportions for major histocompatibility complex loci, HLA-A and HLA-B, of progeny in families in 23 South Amerindian tribes in which segregation for homozygotes and heterozygotes could occur are examined. Overall, there is a large deficiency of homozygotes compared with Mendelian expectations (for HLA-A, 114 observed and 155.50 expected and for HLA-B 110 observed and 144.75 expected), consistent with strong balancing selection favoring heterozygotes. There is no evidence that these deficiencies were associated with particular alleles or with the age of the individuals sampled. When these families were divided into four mating types, there was strong selection against homozygotes, averaging 0.462 for three of the mating types over the two loci. For the other mating type in which the female parent is homozygous and shares one allele with the heterozygous male parent, there was no evidence of selection against homozygotes. A theoretical model incorporating these findings surprisingly does not result in a stable polymorphism for two alleles but does result in an excess of heterozygotes and a minimum fitness at intermediate allele frequencies. However, for more than two alleles, balancing selection does occur and the model approaches the qualities of the symmetrical heterozygote advantage model as the number of alleles increases.

Gonadotropin-releasing hormone analogue conjugates with strong selective antitumor activity

Conjugation of gonadotropin-releasing hormone (GnRH) analogues GnRH-III, MI-1544, and MI-1892 through lysyl side chains and a tetrapeptide spacer, Gly-Phe-Leu-Gly (X) to a copolymer, poly(N-vinylpyrrolidone-co-maleic acid) (P) caused increased antiproliferative activity toward MCF-7 and MDA-MB-231 breast, PC3 and LNCaP prostate, and Ishikawa endometrial cancer cell lines in culture and against tumor development by xenografts of the breast cancer cells in immunodeficient mice. MCF-7 cells treated with P-X-1544 and P-X-1892 displayed characteristic signs of apoptosis, including vacuoles in the cytoplasm, rounding up, apoptotic bodies, bleb formation, and DNA fragmentation. Conjugates, but not free peptides, inhibited cdc25 phosphatase and caused accumulation of Ishikawa and PC3 cells in the G2/M phase of the cell cycle after 24 h at lower doses and in the G1 and G2 phases after 48 h. Since P-X-peptides appear to be internalized, the increased cytotoxicity of the conjugates is attributed to protection of peptides from proteolysis, enhanced interaction of the peptides with the GnRH receptors, and/or internalization of P-X-peptide receptor complexes so that P can exert toxic effects inside, possibly by inhibiting enzymes involved in the cell cycle. The additional specificity of P-X-peptides compared with free peptides for direct antiproliferative effects on the cancer cells but not for interactions in the pituitary indicates the therapeutic potential of the conjugates.

CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice

Successful neonatal immunization of humans has proven difficult. We have evaluated CpG-containing oligonucleotides as an adjuvant for immunization of young mice (1–14 days old) against hepatitis B virus surface antigen. The protein-alum-CpG formulation, like the DNA vaccine, produced seroconversion of the majority of mice immunized at 3 or 7 days of age, compared with 0–10% with the protein-alum or protein-CpG formulations. All animals, from neonates to adults, immunized with the protein-alum vaccine exhibited strong T helper (Th)2-like responses [predominantly IgG1, weak or absent cytotoxic T lymphocytes (CTL)]. Th2-type responses also were induced in young mice with protein-CpG (in 1-, 3-, and 7-day-old mice) and protein-alum-CpG (in 1- and 3-day-old mice) but immunization carried out at older ages gave mixed Th1/Th2 (Th0) responses. DNA vaccines gave Th0-like responses when administered at 1 and 7 days of age and Th1-like (predominantly IgG2a and CTL) responses with 14-day-old or adult mice. Surprisingly, the protein-alum-CpG formulation was better than the DNA vaccine for percentage of seroconversion, speed of appearance, and peak titer of the antibody response, as well as prevalence and strength of CTL. These findings may have important implications for immunization of human infants.

An isolated, surface-expressed I domain of the integrin αLβ2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide bond

We introduced disulfide bonds to lock the integrin αLβ2 I domain in predicted open, ligand binding or closed, nonbinding conformations. Transfectants expressing αLβ2 heterodimers containing locked-open but not locked-closed or wild-type I domains constitutively adhered to intercellular adhesion molecule-1 (ICAM-1) substrates. Locking the I domain closed abolished constitutive and activatable adhesion. The isolated locked-open I domain bound as well as the activated αLβ2 heterodimer, and binding was abolished by reduction of the disulfide. Lovastatin, which binds under the conformationally mobile C-terminal α-helix of the I domain, inhibited binding to ICAM-1 by αLβ2 with wild-type, but not locked-open I domains. These data establish the importance of conformational change in the αL I domain for adhesive function and show that this domain is sufficient for full adhesive activity.

Y chromosome polymorphism is a strong determinant of male fitness in Drosophila melanogaster

In many species, the Y (or W) chromosome carries relatively few functional genes. This observation motivates the null hypothesis that the Y will be a minor contributor to genetic variation for fitness. Previous data and theory supported the null hypothesis, but evidence presented here shows that the Y of Drosophila melanogaster is a major determinant of a male's total fitness, with standing genetic variation estimated to be 68% of that of an entire X/autosome genomic haplotype. Most Y-linked genes are expressed during spermatogenesis, and correspondingly, we found that the Y influences fitness primarily through its effect on a male's reproductive success (sperm competition and/or mating success) rather than his egg-to-adult viability. But the fitness of a Y highly depended on the genetic makeup of its bearer, reverting from high to low in different genetic backgrounds. This pattern leads to large epistatic (inconsistent among backgrounds) but no additive (consistent among backgrounds) Y-linked genetic variance for fitness. On a microevolutionary scale, the observed large epistatic variation on the Y substantially reduces heritable variation for fitness among males, and on a macroevolutionary scale, the Y produces strong selection for genomic rearrangements that move interacting genes onto the nonrecombining region of the Y.