Augmenting PROV with Plans in P-PLAN: Scientific Processes as Linked Data

Provenance models are crucial for describing experimental results in science. The W3C Provenance Working Group has recently released the PROV family of specifications for provenance on the Web. While provenance focuses on what is executed, it is important in science to publish the general methods that describe scientific processes at a more abstract and general level. In this paper, we propose P-PLAN, an extension of PROV to represent plans that guid-ed the execution and their correspondence to provenance records that describe the execution itself. We motivate and discuss the use of P-PLAN and PROV to publish scientific workflows as Linked Data.

Preliminary approach to neutron instrument selecction at ESSB-Bilbao based on experience at ISIS molecular spectroscopy group

Collaborative efforts between the Neutronics and Target Design Group at the Instituto de Fusión Nuclear and the Molecular Spectroscopy Group at the ISIS Pulsed Neutron and Muon Source date back to 2012 in the context of the ESS-Bilbao project. The rationale for these joint activities was twofold, namely: to assess the realm of applicability of the low-energy neutron source proposed by ESS-Bilbao - for details; and to explore instrument capabilities for pulsed-neutron techniques in the range 0.05-3 ms, a time range where ESS-Bilbao and ISIS could offer a significant degree of synergy and complementarity. As part of this collaboration, J.P. de Vicente has spent a three-month period within the ISIS Molecular Spectroscopy Group, to gain hands-on experience on the practical aspects of neutron-instrument design and the requisite neutron-transport simulations. To date, these activities have resulted in a joint MEng thesis as well as a number of publications and contributions to national and international conferences. Building upon these previous works, the primary aim of this report is to provide a self-contained discussion of general criteria for instrument selection at ESS-Bilbao, the first accelerator-driven, low-energy neutron source designed in Spain. To this end, Chapter 1 provides a brief overview of the current design parameters of the accelerator and target station. Neutron moderation is covered in Chapter 2, where we take a closer look at two possible target-moderator-reflector configurations and pay special attention to the spectral and temporal characteristics of the resulting neutron pulses. This discussion provides a necessary starting point to assess the operation of ESSB in short- and long-pulse modes. These considerations are further explored in Chapter 3, dealing with the primary characteristics of ESS-Bilbao as a short- or long-pulse facility in terms of accessible dynamic range and spectral resolution. Other practical aspects including background suppression and the use of fast choppers are also discussed. The guiding principles introduced in the first three chapters are put to use in Chapter 4 where we analyse in some detail the capabilities of a small-angle scattering instrument, as well as how specific scientific requirements can be mapped onto the optimal use of ESS-Bilbao for condensed-matter research. Part 2 of the report contains additional supporting documentation, including a description of the ESSB McStas component, a detailed characterisation of moderator response and neutron pulses, and estimates ofparameters associated with the design and operation of neutron choppers. In closing this brief foreword, we wish to thank both ESS-Bilbao and ISIS for their continuing encouragement and support along the way.

Diseño de un Procesador de Membranas Paralelo para los Sistemas P de Transición

La computación con membranas surge como una alternativa a la computación tradicional. Dentro de este campo se sitúan los denominados Sistemas P de Transición que se basan en la existencia de regiones que contienen recursos y reglas que hacen evolucionar a dichos recursos para poder llevar a cada una de las regiones a una nueva situación denominada configuración. La sucesión de las diferentes configuraciones conforman la computación. En este campo, el Grupo de Computación Natural de la Universidad Politécnica de Madrid lleva a cabo numerosas investigaciones al amparo de las cuales se han publicado numerosos artículos y realizado varias tesis doctorales. Las principales vías de investigación han sido, hasta el momento, el estudio del modelo teórico sobre el que se definen los Sistemas P, el estudio de los algoritmos que se utilizan para la aplicación de las reglas de evolución en las regiones, el diseño de nuevas arquitecturas que mejoren las comunicaciones entre las diferentes membranas (regiones) que componen el sistema y la implantación de estos sistemas en dispositivos hardware que pudiesen definir futuras máquinas basadas en este modelo. Dentro de este último campo, es decir, dentro del objetivo de construir finalmente máquinas que puedan llevar a cabo la funcionalidad de la computación con Sistemas P, la presente tesis doctoral se centra en el diseño de dos procesadores paralelos que, aplicando variantes de algoritmos existentes, favorezcan el crecimiento en el nivel de intra-paralelismo a la hora de aplicar las reglas. El diseño y creación de ambos procesadores presentan novedosas aportaciones al entorno de investigación de los Sistemas P de Transición en tanto en cuanto se utilizan conceptos que aunque previamente definidos de manera teórica, no habían sido introducidos en el hardware diseñado para estos sistemas. Así, los dos procesadores mantienen las siguientes características: - Presentan un alto rendimiento en la fase de aplicación de reglas, manteniendo por otro lado una flexibilidad y escalabilidad medias que son dependientes de la tecnología final sobre la que se sinteticen dichos procesadores. - Presentan un alto nivel de intra-paralelismo en las regiones al permitir la aplicación simultánea de reglas. - Tienen carácter universal en tanto en cuanto no depende del carácter de las reglas que componen el Sistema P. - Tienen un comportamiento indeterminista que es inherente a la propia naturaleza de estos sistemas. El primero de los circuitos utiliza el conjunto potencia del conjunto de reglas de aplicación así como el concepto de máxima aplicabilidad para favorecer el intra-paralelismo y el segundo incluye, además, el concepto de dominio de aplicabilidad para determinar el conjunto de reglas que son aplicables en cada momento con los recursos existentes. Ambos procesadores se diseñan y se prueban mediante herramientas de diseño electrónico y se preparan para ser sintetizados sobre FPGAs. ABSTRACT Membrane computing appears as an alternative to traditional computing. P Systems are placed inside this field and they are based upon the existence of regions called “membranes” that contain resources and rules that describe how the resources may vary to take each of these regions to a new situation called "configuration". Successive configurations conform computation. Inside this field, the Natural Computing Group of the Universidad Politécnica of Madrid develops a large number of works and researches that provide a lot of papers and some doctoral theses. Main research lines have been, by the moment, the study of the theoretical model over which Transition P Systems are defined, the study of the algorithms that are used for the evolution rules application in the regions, the design of new architectures that may improve communication among the different membranes (regions) that compose the whole system and the implementation of such systems over hardware devices that may define machines based upon this new model. Within this last research field, this is, within the objective of finally building machines that may accomplish the functionality of computation with P Systems, the present thesis is centered on the design of two parallel processors that, applying several variants of some known algorithms, improve the level of the internal parallelism at the evolution rule application phase. Design and creation of both processors present innovations to the field of Transition P Systems research because they use concepts that, even being known before, were never used for circuits that implement the applying phase of evolution rules. So, both processors present the following characteristics: - They present a very high performance during the application rule phase, keeping, on the other hand, a level of flexibility and scalability that, even known it is not very high, it seems to be acceptable. - They present a very high level of internal parallelism inside the regions, allowing several rule to be applied at the same time. - They present a universal character meaning this that they are not dependent upon the active rules that compose the P System. - They have a non-deterministic behavior that is inherent to this systems nature. The first processor uses the concept of "power set of the application rule set" and the concept of "maximal application" number to improve parallelism, and the second one includes, besides the previous ones, the concept of "applicability domain" to determine the set of rules that may be applied in each moment with the existing resources.. Both processors are designed and tested with the design software by Altera Corporation and they are ready to be synthetized over FPGAs.

Escuela en Hunstanton de A+P Smithson: el Nuevo Brutalismo en Inglaterra

La tesis estudia en detalle la Hunstanton Secondary School y su trascendencia. Así, se trata de analizar el conjunto de procesos que hace que esta obra sea entendida como el manifiesto construido del Nuevo Brutalismo en Inglaterra. La Escuela en Hunstanton fue la primera obra proyectada y construida por los Smithson y, si se considera que el legado que dejaron Alison y Peter fue más de carácter teórico que constructivo, ésta se ha convertido en un edificio relevante dentro de su trayectoria profesional. Además, el rigor con el que fue realizado el proyecto y la ratificación de las ideas que subyacían tras él, a pesar del extenso intervalo temporal que caracterizó su proceso constructivo, hacen que esta obra se convierta en una síntesis de la filosofía arquitectónica gestada en Inglaterra tras la guerra. Por otro lado, hay que contemplar que la sencillez del lenguaje constructivo empleado, viene dada por la compleja reiteración de los sistemas proyectuales tipo que formulan para este proyecto y el establecimiento de una gramática casi matemática. La sistematización de su vocabulario hace que, tras el análisis de su arquitectura, se encuentren nuevos parámetros capaces de documentar este momento de la historia de la arquitectura en Inglaterra. La envolvente del edificio constituye al tiempo fachada y estructura. Esta característica ha pasado inadvertida cuando, en numerosas ocasiones y durante seis décadas, se han venido publicando las fotografías de la obra terminada y los dibujos que los Smithson habían realizado en la fase de proyecto. Como consecuencia, ha proliferado el conocimiento de la arquitectura de la escuela a un nivel más superficial, mostrando el resultado formal de la misma y con ello, simplemente se ha dejado intuir la gran influencia que Mies Van der Rohe provocó en los Smithson en los primeros años de desarrollo de su labor como arquitectos. El objetivo principal de esta tesis es, por tanto, facilitar el entendimiento del espacio que propusieron los Smithson a partir del análisis pormenorizado de los distintos sistemas constructivos empleados y del equipo personal que se vio implicado en su construcción. Para ello, es necesario abordar el estudio de los materiales y mecanismos proyectuales que hicieron posible que este conjunto de espacios –interiores y exteriores- resultase definido a través de la relación entre dos variables: una evidente austeridad en la utilización de los materiales y la combinación de los distintos sistemas intervinientes a partir del recurso de la repetición. La Escuela de Hunstanton, a pesar de las inoportunas intervenciones realizadas para adaptar el centro a unas necesidades derivadas de su número de alumnos actual (el doble que en su inicio), continúa proclamando su integridad espacial. Partiendo de la hipótesis de que la arquitectura de la Secondary School en Hunstanton, representa el manifiesto construido del Nuevo Brutalismo en Inglaterra, se concluye que el resultado de su construcción fue consecuencia de numerosas influencias que, en relación con los Smithson, estuvieron presentes durante los años en que se gestó. Algo que va más allá de la conclusión de aquellos debates arquitectónicos que se habían emprendido, por escrito, en las distintas revistas locales de arquitectura. Los mecanismos compositivos empleados, también habían tenido mucho que ver con lo que los historiadores del arte habían venido aportando a la historia de la arquitectura hasta ese momento. Desde los años 40, éstos últimos habían emprendido una nueva manera de contar la historia en la que quedaba fuertemente involucrada su capacidad crítica, provocando interferencias en la mentalidad de los arquitectos de nueva generación y otorgándoles un bagaje cultural subliminalmente determinado y subjetivo. Por supuesto, en el resultado arquitectónico final, también tuvieron mucho que ver los recursos materiales de que se disponía en aquel momento. Así como la optimización de los mismos a través de la adopción de nuevas metodologías de trabajo como puede ser la organización multidisciplinar. La inclusión del ingeniero Ronald Jenkins en el equipo de trabajo de los Smithson supuso una gran oportunidad. Este ingeniero, propuso poner en práctica la entonces innovadora Teoría Plástica en la metodología de cálculo estructural y, con ello consiguió enriquecer el resultado espacial, posibilitando la percepción de una arquitectura ligera –a pesar de sus grandes dimensiones- y vinculada al paisaje donde se inserta. Pero todos estos condicionantes fueron pasados a su vez por el filtro del deseo de una regeneración social, que buscaba el modelo de la sociedad americana. El Buen Vivir que propugnaban los americanos, viajaba a Europa de la mano de la publicidad. Y, al igual que la componente publicitaria tuvo algo que ver en el proceso creativo de la arquitectura de la escuela, también lo tuvo el conocimiento del arte pop y sus recursos compositivos. ABSTRACT The thesis examines in detail the project of Hunstanton Secondary School and the architectural language’s significance used in it. Thus, it is reinterpreting the set of processes that makes this work to be understood as the “built manifesto” of the English New Brutalism. Hunstanton School’s project was the first work designed and built by the Smithsons and, considering their legacy -more theoretical than constructed-, make of this building an important work within their career. In addition, the rigor with which it was carried out the project and the ratification of the ideas lying behind him, make this work becomes a synthesis of the architectural philosophy gestated in England after the war, despite the extensive time interval that characterized its construction process. On the other hand, it must be considered the simplicity of the constructive language used in this project. It is given by the complex projective repetition of the type systems and by the establishment of a quasi-mathematical grammar. The systematization of its vocabulary makes, after a deep analysis of its architecture, to recognize new parameters able to document this moment in the history of English architecture. The building envelope is, at the same time, facade and structure. This feature has been overlooked when many photographs of the finished work and its drawings -made by the Smithsons during the design phase- has been exposed over six decades. As a result, it has proliferated the knowledge of Hunstanton Secondary Modern School’s architecture as a more superficial level, just by showing the formal outcome of its project and thus simply been left the sensation of the great influence that Mies Van der Rohe provocated in the Smithson thinking during their first years of developing his work as architects. Therefore, the main objective of this thesis is to facilitate an understanding of the Smithsons’ proposed space. This is made possible through the detailed analysis of the different systems used in it and, by understanding the knowledge of the team involved in its construction. To prove this, it is necessary to pay attention to the study of the materials and to different project mechanisms that make possible to this group of spaces -inner and outer- be defined through the game played by two variables: an apparent austerity in the use of materials and the combination of the various participant systems through the resource of repetition. Despite the untimely interventions made in order to adapt the center to the new needs (the large increase in the number of students), Hunstanton School’s building continues proclaiming its spatial integrity. Assuming that Hunstanton Secondary School’s architecture represents the manifesto of New Brutalism in England, it is concluded that the result of its construction was the result of numerous influences that, in connection with the Smithsons, were present during the years in which its project was conceived. This meaning goes beyond the conclusions made from the architectural debate that was published in many of local architectural magazines. The compositional mechanisms employed, are also linked to what art historians had contributed to the history of architecture until then. Since the 40s, historians had undertaken a new way to tell History. This new mode strongly implied its critical capacity. All this, was causing interferences in the mentality of the architects of the new generation and, giving them a subliminally determined and very subjective cultural background. Of course, the final architectural result had much to do with the material resources available at that time and, with its optimization through the adoption of new working methods as the multidisciplinary organization. The inclusion of engineer Ronald Jenkins in the team of the Smithsons was a great opportunity. He proposed to implement the new Plastic Theory in the structural calculation and thereby he got enrich the spatial results achieved, by enabling the perception of a lightweight construction, despite its large size and, linked to the landscape where it is inserted. But all these conditions were passed through the filter of social regeneration’s desire, following the American society’s model. This American model travelled to Europe in the hands of advertising. And, in the same way that publicity had something to do with the creative process of this architecture, also had a lot to do the knowledge of pop art and its compositional resources.

Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin

Infection with Helicobacter pylori is associated with different human gastric diseases. Biochemical studies, in vitro adherence assays, and in vivo animal models revealed that epithelial attachment of H. pylori can be mediated by the blood-group antigen-binding adhesin (BabA) targeting human Lewisb surface epitopes. Studies with transgenic mice expressing the Lewisb epitope have shown that such attachment can alter disease outcome. In the current study, the presence of the babA2 gene encoding the adhesin was investigated in clinical isolates from a German population by using PCR and reverse transcription–PCR. A positive genotype was correlated to allelic variations in the genes encoding VacA and CagA and also to the prevalence of duodenal ulcer, distal gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and antral gastritis. The presence of babA2 was significantly associated with duodenal ulcer (P = 0.0002) and adenocarcinoma (P = 0.033). In contrast, type 1 strains (vacAs1- and cagA-positive) were associated with only duodenal ulcer (P = 0.004) but not adenocarcinoma (P = 0.235). Genotype presence of babA2, vacAs1, and cagA (“triple-positive” strains) showed a highly significant correlation to the prevalence of ulcer (P = 0.000002) and adenocarcinoma (P = 0.014) and discriminated significantly better between disease outcome than did the current type 1 classification. These results indicate that the babA2 gene is of high clinical relevance and would be a useful marker to identify patients who are at higher risk for specific H. pylori-related diseases.

Lipoxin A4 stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin

Three different stable lipoxin A4 (LXA4) analogs (i.e., 16-phenoxy-LXA4-Me, 15-cyclohexyl-LXA4-Me, and 15-R/S-methyl-LXA4-Me) were studied for their ability to modulate leukocyte-endothelial cell interactions in the rat mesenteric microvasculature. Superfusion of the rat mesentery with 50 μmol/liter NG-nitro-l-arginine methyl ester (l-NAME) caused a significant, time-dependent increase in leukocyte rolling (56 ± 8 cells/min; P < 0.01 vs. control) and leukocyte adherence (12.5 ± 1.2 cells/100 μm length of venule; P < 0.01 vs. control) after 120 min of superfusion. Concomitant superfusion of the rat mesentery with 10 nmol/liter of each of three lipoxin analogs consistently and markedly attenuated l-NAME-induced leukocyte rolling to 10 ± 4 (P < 0.01), 4 ± 1 (P < 0.01), and 32 ± 7 (P < 0.05) cells/min, and adherence to 4 ± 0.8 (P < 0.01), 1.1 ± 0.4 (P < 0.01), and 7 ± 0.7 (P < 0.05) cells/100 μm length of venule (16-phenoxy-LXA4-Me, 15-cyclohexyl-LXA4-Me, and 15-R/S- methyl-LXA4-Me, respectively). No alterations of systemic blood pressure or mesenteric venular shear rates were observed in any group. Immunohistochemical up-regulation of P-selectin expression on intestinal venular endothelium was significantly increased (P < 0.01) after exposure to l-NAME, and this was significantly attenuated by these lipoxin analogs (P < 0.01). Thus, in vivo superfusion of the rat mesentery with stable lipoxin analogs at 10 nmol/liter reduces l-NAME-induced leukocyte rolling and adherence in the mesenteric rat microvasculature by attenuating P-selectin expression. This anti-inflammatory mechanism may represent a novel and potent regulatory action of lipoxins on the immune system.

Cockayne syndrome group B protein enhances elongation by RNA polymerase II

Cockayne syndrome (CS) is characterized by impaired physical and mental development. Two complementation groups, CSA and CSB, have been identified. Here we report that the CSB gene product enhances elongation by RNA polymerase II. CSB stimulated the rate of elongation on an undamaged template by a factor of about 3. A thymine-thymine cyclobutane dimer located in the template strand is known to be a strong block to transcription. Addition of CSB to the blocked polymerase resulted in addition of one nucleotide to the nascent transcript. Finally, addition of transcription factor IIS is known to cause polymerase blocked at a thymine-thymine cyclobutane dimer to digest its nascent transcript, and CSB counteracted this transcript shortening action of transcription factor IIS. Thus a deficiency in transcription elongation may contribute to the CS phenotype.

Efficient Trafficking of TGN38 from the Endosome to the trans-Golgi Network Requires a Free Hydroxyl Group at Position 331 in the Cytosolic Domain

TGN38 is one of the few known resident integral membrane proteins of the trans-Golgi network (TGN). Since it cycles constitutively between the TGN and the plasma membrane, TGN38 is ideally suited as a model protein for the identification of post-Golgi trafficking motifs. Several studies, employing chimeric constructs to detect such motifs within the cytosolic domain of TGN38, have identified the sequence 333YQRL336 as an autonomous signal capable of localizing reporter proteins to the TGN. In addition, one group has found that an upstream serine residue, S331, may also play a role in TGN38 localization. However, the nature and degree of participation of S331 in the localization of TGN38 remain uncertain, and the effect has been studied in chimeric constructs only. Here we investigate the role of S331 in the context of full-length TGN38. Mutations that abolish the hydroxyl moiety at position 331 (A, D, and E) lead to missorting of endocytosed TGN38 to the lysosome. Conversely, mutation of S331 to T has little effect on the endocytic trafficking of TGN38. Together, these findings indicate that the S331 hydroxyl group has a direct or indirect effect on the ability of the cytosolic tail of TGN38 to interact with trafficking and/or sorting machinery at the level of the early endosome. In addition, mutation of S331 to either A or D results in increased levels of TGN38 at the cell surface. The results confirm that S331 plays a critical role in the intracellular trafficking of TGN38 and further reveal that TGN38 undergoes a signal-mediated trafficking step at the level of the endosome.

Inhibition of RNase P RNA cleavage by aminoglycosides

A number of aminoglycosides have been reported to interact and interfere with the function of various RNA molecules. Among these are 16S rRNA, the group I intron, and the hammerhead ribozymes. In this report we show that cleavage by RNase P RNA in the absence as well as in the presence of the RNase P protein is inhibited by several aminoglycosides. Among the ones we tested, neomycin B was found to be the strongest inhibitor with a Ki value in the micromolar range (35 μM). Studies of lead(II)-induced cleavage of RNase P RNA suggested that binding of neomycin B interfered with the binding of divalent metal ions to the RNA. Taken together, our findings suggest that aminoglycosides compete with Mg2+ ions for functionally important divalent metal ion binding sites. Thus, RNase P, which is an essential enzyme, is indeed a potential drug target that can be used to develop new drugs by using various aminoglycosides as lead compounds.

The C9 methyl group of retinal interacts with glycine-121 in rhodopsin

The visual pigment rhodopsin is a prototypical G protein-coupled receptor. These receptors have seven transmembrane helices and are activated by specific receptor–ligand interactions. Rhodopsin is unusual in that its retinal prosthetic group serves as an antagonist in the dark in the 11-cis conformation but is rapidly converted to an agonist on photochemical cis to trans isomerization. Receptor–ligand interactions in rhodopsin were studied in the light and dark by regenerating site-directed opsin mutants with synthetic retinal analogues. A progressive decrease in light-dependent transducin activity was observed when a mutant opsin with a replacement of Gly121 was regenerated with 11-cis-retinal analogues bearing progressively larger R groups (methyl, ethyl, propyl) at the C9 position of the polyene chain. A progressive decrease in light activity was also observed as a function of increasing size of the residue at position 121 for both the 11-cis-9-ethyl- and the 11-cis-9-propylretinal pigments. In contrast, a striking increase of receptor activity in the dark—i.e., without chromophore isomerization—was observed when the molecular volume at either position 121 of opsin or C9 of retinal was increased. The ability of bulky replacements at either position to hinder ligand incorporation and to activate rhodopsin in the dark suggests a direct interaction between these two sites. A molecular model of the retinal-binding site of rhodopsin is proposed that illustrates the specific interaction between Gly121 and the C9 methyl group of 11-cis-retinal. Steric interactions in this region of rhodopsin are consistent with the proposal that movement of transmembrane helices 3 and 6 is concomitant with receptor activation.

Investigation by Parkinson’s Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson’s disease: further results of randomised trial and confidential inquiry

Objective: To determine whether the excess mortality observed in patients who received both levodopa and selegiline in a randomised trial could be explained by revised diagnosis of Parkinson’s disease, autonomic or cardiovascular effects, more rapid disease progression, or drug interactions.

Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members

The development of Alzheimer's disease (AD) later in life may be reflective of environmental factors operating over the course of a lifetime. Educational and occupational attainments have been found to be protective against the development of the disease but participation in activities has received little attention. In a case-control study, we collected questionnaire data about 26 nonoccupational activities from ages 20 to 60. Participants included 193 people with probable or possible AD and 358 healthy control-group members. Activity patterns for intellectual, passive, and physical activities were classified by using an adaptation of a published scale in terms of “diversity” (total number of activities), “intensity” (hours per month), and “percentage intensity” (percentage of total activity hours devoted to each activity category). The control group was more active during midlife than the case group was for all three activity categories, even after controlling for age, gender, income adequacy, and education. The odds ratio for AD in those performing less than the mean value of activities was 3.85 (95% confidence interval: 2.65–5.58, P < 0.001). The increase in time devoted to intellectual activities from early adulthood (20–39) to middle adulthood (40–60) was associated with a significant decrease in the probability of membership in the case group. We conclude that diversity of activities and intensity of intellectual activities were reduced in patients with AD as compared with the control group. These findings may be because inactivity is a risk factor for the disease or because inactivity is a reflection of very early subclinical effects of the disease, or both.

Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme

Bacteriophage lytic enzymes quickly destroy the cell wall of the host bacterium to release progeny phage. Because such lytic enzymes specifically kill the species in which they were produced, they may represent an effective way to control pathogenic bacteria without disturbing normal microflora. In this report, we studied a murein hydrolase from the streptococcal bacteriophage C1 termed lysin. This enzyme is specific for groups A, C, and E streptococci, with little or no activity toward several oral streptococci or other commensal organisms tested. Using purified lysin in vitro, we show that 1,000 units (10 ng) of enzyme is sufficient to sterilize a culture of ≈107 group A streptococci within 5 seconds. When a single dose of lysin (250 units) is first added to the oral cavity of mice, followed by 107 live group A streptococci, it provides protection from colonization (28.5% infected, n = 21) compared with controls without lysin (70.5% infected, n = 17) (P < 0.03). Furthermore, when lysin (500 units) was given orally to 9 heavily colonized mice, no detectable streptococci were observed 2 h after lysin treatment. In all, these studies show that lysin represents a unique murein hydrolase that has a rapid lethal effect both in vitro and in vivo on group A streptococci, without affecting other indigenous microorganisms analyzed. This general approach may be used to either eliminate or reduce streptococci from the upper respiratory mucosal epithelium of either carriers or infected individuals, thus reducing associated disease.

Behavior predicts genes structure in a wild primate group.

The predictability of genetic structure from social structure and differential mating success was tested in wild baboons. Baboon populations are subdivided into cohesive social groups that include multiple adults of both sexes. As in many mammals, males are the dispersing sex. Social structure and behavior successfully predicted molecular genetic measures of relatedness and variance in reproductive success. In the first quantitative test of the priority-of-access model among wild primates, the reproductive priority of dominant males was confirmed by molecular genetic analysis. However, the resultant high short-term variance in reproductive success did not translate into equally high long-term variance because male dominance status was unstable. An important consequence of high but unstable short-term variance is that age cohorts will tend to be paternal sibships and social groups will be genetically substructured by age.

Different cleavage sites are aligned differently in the active site of M1 RNA, the catalytic subunit of Escherichia coli RNase P.

We have studied RNase P RNA (M1 RNA) cleavage of model tRNA precursors that are cleaved at two independent positions. Here we present data demonstrating that cleavage at both sites depends on the 2'-OH immediately 5' of the respective cleavage site. However, we show that the 2-amino group of a guanosine at the cleavage site plays a significant role in cleavage at one of these sites but not at the other. These data suggest that these two cleavage sites are handled differently by the ribozyme. This theory is supported by our finding that the cross-linking pattern between Ml RNA and tRNA precursors carrying 4-thioU showed distinct differences, depending on the location of the 4-thioU relative to the respective cleavage site. These findings lead us to suggest that different cleavage sites are aligned differently in the active site, possibly as a result of different binding modes of a substrate to M1 RNA. We discuss a model in which the interaction between the 3'-terminal "RCCA" motif (first three residues interact) of a tRNA precursor and M1 RNA plays a significant role in this process.