It includes the most emblematic texts from the blog and lots of previously unpublished content! I hope you find her. I'm serious. I hope you find that person who makes the hours fly by, who paints your world in color and who makes you live it. Someone who doesn't care about the past and who insists on creating a present that is magical, with hints of the future. Someone who understands how you are, who loves you that way, and who does not try to change anything about you.
Esta es la historia de los hombres y mujeres fascinantes--los emperadores, sus esposas, padres, hermanos, hermanas e hijos--que constituyen el atractivo de este imperio. Todas menos seis han sido devueltas a sus hogares. Pero cuando ve a Aspen en los alrededores de palacio, los recuerdos de la vida que planeaban tener juntos se agolpan en su memoria. Dicen que en el amor y en la guerra todo se vale,?
Si te gustan las historias en las que el protagonista es un macho, muy macho. Este libro es para ti. Mi querido lector, en este libro voy a volcar todas mis experiencias y conocimientos con los cuales he logrado ser poseedora de la abundancia que he decidido obtener.
- De String Theory Schools.
- Usuario discusión:Barcex.
- bacterias liofilizadas como: Topics by qyjywolu.tk.
Si deseas esa libertad financiera, ser feliz, estar saludable, tener una figura de envidia, etc. Pues entonces este libro es para ti. No hay nada que podamos alcanzar si primero no fortalecemos nuestro yo. Vamos tu momento es ahora!!!! Mi pregunta es? Spanish Edition David Valois. Da igual la edad que tengas. No te rindas ahora. Un sencillo truco para creerse y volverse joven. La gente no se hace rica porque no utiliza su mente lo suficiente.
Enfadado o contento? Pero es mentira. Es lo que necesitamos en este tiempo para ser cristianos que lleven fruto, y fruto en abundancia. Fue el primer intento conocido sobre lecciones de guerra. La estrategia ofensiva4. Las nueve variables9. El terreno Las nueve clases de terreno Ataque de fuego Ambos ocultan grandes secretos. Los dos esconden sus sentimientos. Amor por Chile y una gran nostalgia son el origen de este libro: la presencia continuada del pasado, el sentimiento de verse ausente de la patria, la conciencia de haber sido peregrina y forastera Evocados con gracia, cobran vida de nuevo su original familia, la casa de los abuelos, el ceremonial de las comidas, las historias de infidelidades Desde que vio a Marianne por primera vez estuvo determinado a hacerla suya.
Mientras Reel se enfrenta a una crisis personal, un nuevo adversario acosa a la pareja de asesinos: una mujer desconocida, adiestrada durante toda su vida para matar y con su propia lista de objetivos, una lista que incluye a Will Robie y a Jessica Reel. Each fourteen-page, full-color booklet is richly illustrated and carries a selfexplanatory title and serves as an always-ready reference tool for personal use or on the mission field. Diario de Greg 3. Esto es el colmo!
Spanish Edition Jeff Kinney. Resulta que Frank Heffley cree que su hijo puede cambiar. Sin embargo cuando su padre amenaza con enviarlo a una academia militar, Greg se da cuenta de que va a tener que ponerse las pilas. Ya no tienes que leer y resumir todo el libro, nosotros lo hemos hecho por ti! Toma una dosis de literatura acelerada con ResumenExpress. Por su amor, el monarca se vio obligado a abdicar en Spanish Edition Anastasia Hawkins.
Te preocupa el exceso de grasa y la cantidad de carbohidratos que pones en tu cuerpo pero llevas una vida agitada y ocupada y nunca logras encontrar el tiempo para preparar comidas nutritivas? Nosotros lo hicimos. Obtienes exactamente lo que necesitas para vivir el estilo de vida keto que es sorprendentemente simple; planes de comidas, listas de compras, apoyo, y muchas recetas sin complicaciones. Comienza a perder peso y adquiere un estilo de vida saludable hoy. Paula Spanish Edition Isabel Allende. An outstanding success around the world, The Time in Between has sold more than two million copies and inspired the Spanish television series based on the book, dubbed by the media as the "Spanish Downton Abbey.
La joven modista Sira Quiroga abandona el Madrid agitado de los meses previos al alzamiento arrastrada por el amor desbocado hacia un hombre a quien apenas conoce. Ciertamente ni a sus talentos ni a su fuerza de voluntad. English version: My Wife is an Aloof Beauty. Hay muchas maneras de lograr perder peso y mejorar la salud, pero?
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Comience ahora. Obtenga Su Copia Ahora!! Nos guste o no, vivimos en un mundo regido por el conflicto y la competencia feroz. Tomando como base las ideas y el ejemplo de grandes personalidades de la historia y recurriendo a casos reales, Greene nos revela las claves que permiten alcanzar, conquistar y defender el poder. Dos hombres que son, de manera significativa, polos opuestos. Preparados para emprender un vuelo directo al amor? Diario de Greg 2. Y es que todos los secretos acaban saliendo a la luz La compositora Linda Conti, responsable de haber escrito canciones exitosas para cantantes famosos, ha sido encontrada muerta en su casa.
Todo indica que fue un asesinato. Su hija Caroline no es encontrada en ninguna parte por lo cual se presume que ha sido secuestrada. El best seller mundial para los que quieren obtener, estudiar o combatir el poder absoluto. Pero, nos guste o no, todas tienen aplicaciones en la vida cotidiana. Su Hermano. Incluye el libro! Iba a decirles la verdad. Que se acostaba conmigo.? Sale conmigo. Deseas tener habilidades que tus amigos no tienen?? Quieres ver lo que otros no pueden ver?? Todo el mundo tiene un tercer ojo.
Buen apetito! Un thriller de misterio del detective HensleyUna trampa de langostas es encontrada a las orillas de una playa de Bar Harbor, Maine. Lo peculiar del descubrimiento es que dentro de ella hay una mano mutilada. El Sr. Jaguar Romance gay Spanish Edition K. Ya adelantamos Todo el mundo es parte de un equipo.
Probablemente el autor fue simpatizante de las ideas erasmistas. Todo por la vida de su padre. Todo estaba claro. Claro, mientras no te enamores Estaba jodida. Secretos, mentiras y pasados tormentosos que amenazan con arruinarlo todo. Take an interesting look at all kinds of boats, from early canoes to powerful icebreakers to boats of the future.
Hudson Watt era el mejor amigo de Makayla Tarrant. Ella quiere odiarlo. Quiere demostrarle que es inmune a su atractivo. Pero, sobre todo, Mak quiere La literatura vuelve realidad todo. Aquello inexplicable, la presencia de lo raro, eso que o logramos entender En Las 21 leyes irrefutables del liderazgo, John C. El experto en liderazgo reconocido internacionalmente, conferencista y autor John C. Amazon Echo Show eBook contains all the information you need to know about the Amazon's most in news product "Echo Show".
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What is coming in near future and enhancements? And much more Clase a clase Spanish Edition C. Aunque "machos alfa" enfrentados nunca es una buena mezcla. No cargues con una pesada maleta de duelos no resueltos, llena de rencores, "no perdones" y resentimientos; limpia de una vez esa tristeza y heridas que marcan tu vida. Spanish Edition Mark Gates. Alguna vez has amado a alguien? Spanish Edition Mano Book. Perfect for the serious fan - buy them a notebook they'll use and love. This beautifully designed and practical notebook has lined pages and includes a 12 month goals planner as well as index pages to organize your notes.
Classic quality cream coloured pages for that affordable luxury look that's easy to write on and use - great as a journal, diary or to keep all those todo lists in one place. Makes a great birthday gift. Una novela mayor del Premio Nobel de Literatura Casement fue uno de los primeros europeos en denunciar los horrores del colonialismo. Pilotajes para controlar la realidad financiera. Desarrolla tu clarividencia para prever un futuro de abundancia.
Maravilloso para autodidactas del desarrollo espiritual y personal. En este libro el se enfoca en los negocios, los cuales juegan un rol vital para el desarrollo espiritual personal y colectivo de la humanidad. Pide tres deseos Sin embargo, eso mismo me ha hecho olvidarme de mi misma, pocas veces me alimento bien, no compro ropa por no tener dinero, e incluso, ni si quiera tengo citas, hasta ahora no he perdido mi virginidad. No, no, no, esto no puede ser, yo estoy en contra de todo eso? En sus paginas la literatura lleva al lector por una aventura candente y sensual.
Sus protagonistas chocan desde dos mundos distintos, pero el amor se encarga de liberarlos de los prejuicios y lograr que esta historia tenga su merecido final feliz. Los autores se detienen sobre todo en los mecanismos mentales que buscan y crean belleza. Atentamente,Rodrigo MarquesEl Autor. Con frecuencia esto provoca que atletas obtengan un conocimiento incorrecto. Debido a que mucha de la data que corre por las redes es falsa.
As garotas De Marttino sempre foram criadas com muito amor. El ascenso de los robots Spanish Edition Martin Ford. Independiente, sin ataduras, superviviente y libre. Muy libre. Alrededor del mundo se encuentran tradiciones y culturas que han utilizado y siguen utilizando las plantas medicinales para prevenir, tratar y aliviar enfermedades de todo tipo. Si eres una persona que busca alternativas medicinales, este es un manual para ti: consejos y recetas alternativas medicinales para mejorar tu salud. Por lo tanto, este manual pretende ser una ayuda clara que sirva para subsanar los errores que todos hemos cometido alguna vez cuando nos ha tocado escribir algo.
Si digo que todo me sale mal, miento. Si digo que puedo con todo, miento. Por lo tanto, miento continuamente. Sigo atrincherada dentro de mi talante borde y desabrido, para luchar contra mis propias inseguridades. Ese es el rasgo que mejor me define. Empiezo a estar cansada de no sentir nada al besar dos veces al mismo sapo. Empiezo a estar cansada de no sentir nada Antes de empezar a revelar los 25 poderes con los que toda mujer debe contar, tenemos que derribar los prejuicios que tenemos contra nosotras mismas.
Ese es el primer paso. En esta obra hemos abordado los distintos aspectos y facetas de la miel de abeja. Del mismo modo abordamos lo tocante a la pureza de los animales productores de carne, y la limpieza de los vegetales. El Arte de la Cocina Peruana Vol. El arte de la cocina peruana vol. A senhorita Juliette Smith sempre se orgulhou de seguir seus instintos e desejos. Pastor Gonzalo Sanabria.. Never lose data again!
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Malware Recovery the Easy Way Backups are great for more than just hardware problems. Why spend hours scouring the internet for instructions on how to remove that virus that somehow made it past your anti-malware tools? And then, hoping that: the instructions work the process doesn't do even more damage the results don't leave your machine just as infected as before You'll remove malware the easy way instead: restore your machine to the state it was in before it was infected and you're done!
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That is, of course, unless you have help. Backing Up in Windows 10 is here to help you get backed up. Tools you already have Backing Up in Windows 10 shows you how to use the tools you already have -- the tools built in to Windows 10 itself -- to protect yourself with a top-to-bottom backup. Making and restoring Image Backups to save absolutely everything on your computer. Restoring individual files from an Image Backup, so you don't have to restore everything just to get a few things.
Setting up File History to make nearly continuous backups as you work, and well as restore files it's saved for you. How to use OneDrive to act as your automatic off-site backup.
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- The House That KIlls.
- Le Mali de Mobido Keïta (Points de vue) (French Edition).
- S T R A V A G A N Z A: LA COCINA Y LOS PUEBLOS - COCINA HISPANORROMANA Y VISIGODA!
How to use all three -- Image Backups, File History, and OneDrive -- to recover from the nastiest of the nasty: ransomware! But that's not all. Inexplicably, Microsoft may be removing some backup tools from future versions of Windows Not a problem! I've got you covered. Tools you can get for free In preparation for Microsoft's can I say "boneheaded"?
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As the book is updated, corrections made, or even new editions published, you'll have immediate access to the digital downloads. Todo va bien hasta que uno de los objetivos se resiste a aceptar su destino. Las consecuencias de estos nuevos datos son imprevisibles! El correo has olvidado?!!
Pero el caracol se mantuvo tan tranquilo como pudo. Los monstruos aprendieron que la paciencia tiene recompensa. Espero que usted y sus hijos se diviertan al leerla y aprendan de ella. No obstante Todo ello, bajo una perspectiva cristiana. Estas historias son realistas, divertidas e instructivas! Junio 18 Spanish Edition Alison Oropeza.
Un inocente like en las redes sociales hizo que sus caminos volvieran a cruzarse. Muchas cosas han cambiado. La otra, casada y con dos hijos. Desde que se conocieron en la escuela preparatoria, Victoria Bettley y Shannon Leger se convirtieron en las mejores amigas. Explore the beauty of desert plants, animals and vistas. This Discover Series book features 24 full-color images with simple titles beneath. Babies and toddlers will love the brightly colored plants and animals. Explore la belleza de las plantas del desierto, los animales y las vistas.
Actualmente, en nuestra sociedad hiperdesarrollada, estamos viviendo un momento en el que la disponibilidad y la seguridad de los alimentos es mayor que en cualquier otro momento de nuestra historia. Cuenta con miles de seguidores en redes sociales, sobre todo en su cuenta de Instagram comida. Quieres convertirte en un experto de Python? Compra este libro y sigue mis explicaciones paso a paso! El lenguaje Python es ampliamente usado en todo el globo. Hay mucha palabreja rara y pocas cosas concretas. Confiaremos nosotros en Dios, como lo hizo Job, sin importar lo que suceda?
Pastor Gonzalo Sanabria. La luz tras la ventana Spanish Edition Lucinda Riley. Londres, Separada de su contacto en Francia, conoce a una acaudalada familia atrapada en un terrible juego de mentiras. Ahora en un solo volumen, la serie best seller de John C. Este libro incluye materiales que, en el estilo de Maxwell, han ayudado a muchos lectores a alcanzar su potencial en cualquier etapa de su carrera. Para empezar, porque Emma lo odia. Es posible que las segundas oportunidades existan para ellos?
Luego analizamos los Verbos Modales y los fastidiosos 'Phrasal Verbs'. Gracias por fijarte en mi libro. Apunta bien! Este es un libro original, inteligente y con mucho humor. Spanish Edition Dennis Jones. Los libros de la serie,! Disponible por primera vez en eBook! Toma este libro, mejora tus habilidades de dibujo y lleva tus retratos a un nivel avanzado! Aprende como usar el verbo to be, el presente simple, el presente continuo, el pasado simple, los adjetivos, los verbos, las preguntas y negaciones! Cuando los chicos grandes lo golpean, Vic se encierra en el cobertizo a comer insectos.
Vic no comprende la naturaleza de sus sentimientos. Although Gram positive, acid-fast bacteria do not take the crystal violet into the wall well, appearing very light purple rather than the deep purple of normal Gram-positive bacteria. Transformation of gram positive bacteria by sonoporation.
The present invention provides a sonoporation-based method that can be universally applied for delivery of compounds into Gram positive bacteria. Gram positive bacteria which can be transformed by sonoporation include, for example, Bacillus, Streptococcus, Acetobacterium, and Clostridium. Compounds which can be delivered into Gram positive bacteria via sonoporation include nucleic acids DNA or RNA , proteins, lipids, carbohydrates, viruses, small organic and inorganic molecules, and nano-particles.
Magnetotactic bacteria at the geomagnetic equator. Magnetotatic bacteria are observed in freshwater and marine sediments of Fortaleza, Brazil, situated close to the geomagnetic equator. Both South-seeking and North-seeking bacteria are present in roughly equal numbers in the same samples.
This observation is consistent with the hypothesis that the vertical component of the geomagnetic field selects the predominant polarity type among magnetotactic bacteria in natural environments. Author [pt. Las javieradas como caso de estudio. Full Text Available This text sets out to illustrate types of basic analysis in researching a question as intrinsically human as perception. In the analysis of a construction, the aspects relative to perception allow us to access interesting information as to how a construction functions and what is implied by its different spaces, information which is in direct relation to more human, living aspects of architecture.
These analyses complement formal analyses, as while these allow us to describe a construction in time and space, analyses of perception seek to stress the existing relationship between the human being and the construction, understanding architecture as a physical element to be experienced and which has been constructed to create a favourable atmosphere for certain perceptions. The study first shows the most basic elements in perception analysis and how these support a methodology that attempts to understand a construction in all its aspects formal, social, symbolic, giving as an example a Neolithic Galician burial mound.
Bioenergetics of photoheterotrophic bacteria in the oceans. Photoheterotrophic microbes, such as proteorhodopsin PR -based phototrophic PRP and aerobic anoxygenic phototrophic AAP bacteria , are well known to be abundant in the oceans, potentially playing unique roles in biogeochemical cycles. However, the contribution of phototrophy to the energy requirements of these bacteria has not been quantitatively examined to date.
To better understand the implications of photoheterophy in the oceans, we calculated energy benefits and costs of phototrophy and compared net benefits with maintenance costs. Benefits depend on the number of photosynthetic units PSUs , absorption cross-section area of each PSU as function of wavelength, the in situ light quality, and the energy yield per absorbed photon.
For costs we considered the energy required for the synthesis of pigments, amino acids and proteins in each PSU. Still, the net energy gained by AAP bacteria is often sufficient to meet maintenance costs, while that is not the case for PRP bacteria except with high light intensities and large numbers of proteorhodopsin molecules per cell. The low costs and simplicity of PR-based phototrophy explain the high abundance of proteorhodopsin genes in the oceans. However, even for AAP bacteria , the net energy yield of phototrophy is apparently too low to influence the distribution of photoheterotrophic bacteria among various marine systems.
Quorum sensing in gram-negative bacteria. Bacteria can communicate with each other by means of signal molecules to coordinate the behavior of the entire community, and the mechanism is referred to as quorum sensing QS. Signal systems enable bacteria to sense the size of their densities by monitoring the concentration of the signal Among Gram-negative bacteria N-acyl-L-homoserine lactone acyl-HSL -dependent quorum sensing systems are particularly widespread.
These systems are used to coordinate expression of phenotypes that are fundamental to the interaction of bacteria with each other and with their environment Isolation and characterization of methanogenic bacteria from Isolation and characterization of methanogenic bacteria from brewery wastewater in Kenya.
Fewer bacteria in warm water. There has been many suggestions to how the ideal warm water system should be. Particularly whether warm water containers or heat exchangers in larger houses are the best solutions in order to maintain a water quality with low levels of bacteria. In an investigation made by Statens Byggeforskningsinstitutt Denmark regarding ''Bacterial growth in warm water installations with heat exchangers'' there were used several heat exchangers made by Gjelsted and Lund of three of which had HWAT heating cables. The bacterial content was low from these exchangers compared to exchangers with circulation.
The article presents promising results from a study where the method was investigated over a longer period in two new larger warm water systems. Some energy conservation aspects are discussed. Modeling Political Populations with Bacteria.
Results from lattice-based simulations of micro-environments with heterogeneous nutrient resources reveal that competition between wild-type and GASP rpoS strains of E. Coli offers mutual benefit, particularly in nutrient deprived regions. Our computational model spatially maps bacteria populations and energy sources onto a set of 3D lattices that collectively resemble the topology of North America.
By implementing Wright-Fishcer re- production into a probabilistic leap-frog scheme, we observe populations of wild-type and GASP rpoS cells compete for resources and, yet, aid each other's long term survival. The connection to how spatial political ideologies map in a similar way is discussed.
Cell Size Regulation in Bacteria. Various bacteria such as the canonical gram negative Escherichia coli or the well-studied gram positive Bacillus subtilis divide symmetrically after they approximately double their volume. Their size at division is not constant, but is typically distributed over a narrow range. Here, we propose an analytically tractable model for cell size control, and calculate the cell size and interdivision time distributions, as well as the correlations between these variables.
We suggest ways of extracting the model parameters from experimental data, and show that existing data for E. This hypothesis accounts for the experimentally observed correlations between mother and daughter cells as well as the exponential dependence of size on growth rate. Antioxidant Properties of Probiotic Bacteria.
Oxidative stress defines a condition in which the prooxidant-antioxidant balance in the cell is disturbed, resulting in DNA hydroxylation, protein denaturation, lipid peroxidation, and apoptosis, ultimately compromising cells' viability. Probiotics have been known for many beneficial health effects, and the consumption of probiotics alone or in food shows that strain-specific probiotics can present antioxidant activity and reduce damages caused by oxidation. However, the oxidation-resistant ability of probiotics, especially the underling mechanisms, is not properly understood.
In this view, there is interest to figure out the antioxidant property of probiotics and summarize the mode of action of probiotic bacteria in antioxidation. Therefore, in the present paper, the antioxidant mechanisms of probiotics have been reviewed in terms of their ability to improve the antioxidant system and their ability to decrease radical generation. Since in recent years, oxidative stress has been associated with an altered gut microbiota, the effects of probiotics on intestinal flora composition are also elaborated.
Sterol Synthesis in Diverse Bacteria. Sterols are essential components of eukaryotic cells whose biosynthesis and function has been studied extensively. However, production of these lipids is not restricted to the eukaryotic domain as a few bacterial species also synthesize sterols. Phylogenomic studies have identified genes encoding homologs of sterol biosynthesis proteins in the genomes of several additional species, indicating that sterol production may be more widespread in the bacterial domain than previously thought. Although the occurrence of sterol synthesis genes in a genome indicates the potential for sterol production, it provides neither conclusive evidence of sterol synthesis nor information about the composition and abundance of basic and modified sterols that are actually being produced.
Here, we coupled bioinformatics with lipid analyses to investigate the scope of bacterial sterol production. We identified oxidosqualene cyclase Osc , which catalyzes the initial cyclization of oxidosqualene to the basic sterol structure, in 34 bacterial genomes from five phyla Bacteroidetes, Cyanobacteria, Planctomycetes, Proteobacteria, and Verrucomicrobia and in metagenomes. Our data indicate that bacterial sterol synthesis likely occurs in diverse organisms and environments and also provides evidence that there are as yet uncultured groups of bacterial sterol producers.
Phylogenetic analysis of bacterial and eukaryotic Osc sequences confirmed a complex evolutionary history of sterol synthesis in this domain. Finally, we characterized the lipids produced by Osc-containing bacteria and found that we could generally predict the ability to synthesize sterols. However, predicting the final modified sterol based on our current knowledge of sterol synthesis was difficult. Some bacteria. Como Perseu se defendeu de Medusa? E quando esta falta? O que acontece? La cultura como verdad: pobreza latinoamericana.
Hume: a teoria social como sistema. In his Enquiry on Human Understanding Hume proposes a rule of parcimony in the use of explanatory principles. This essay is an attempt to show how the philosopher managed to follow that rule in his writings on moral sentiments, history, politics and economics.
At the same time, it explores the systematic character of the project described in the presentation of the Treatise on Human Nature. El atal como ambiente de aprendizaje inclusivo. CSOR sobre las trayectorias de estos dispositivos. Taxonomia como elemento estruturante em portais corporativos.
Palavras-chave Taxonomia. Portais Corporativos. Abstract This article discusses the objectives and requirements necessary for a corporate portal and how to build a taxonomy allows for to reach them, becoming a model of representation information and knowledge in this context. Shows the evolution of intranets into the portal, building a common access point to information organizational. Presents an overview of the features that an enterprise portal should present. Conceptualizes and describes the different types of taxonomy and the way it organizes and represents information.
Finally, the taxonomy as a tool for determining the conceptual categories and semantic relationships of an area, as well as the navigational structure, allowing the process to qualify for retrieval. Keywords Taxonomy. Enterprise Portal. Information Representation. Information Organization. El paisaje como archivo del territorio.
XIX, principios del XX, todas las prendas externas de la indumentaria sayaguesa cfr. El desarrollo organizacional como facilitador del cambio. Como reescribir funciones aleatorias multivariadas como univariadas para hacer cokrigeage. Two hundred and fifty bacterial strains were isolated from pinyon rhizosphere and screened for biosurfactants production. Among them, six bacterial strains were selected for their potential to produce biosurfactants using two low cost wastes, crude glycerol and lactoserum, as raw material.
Both wastes were useful for producing biosurfactants because of their high content in fat and carbohydrates. All strains assayed were able to grow and showed halos around the colonies as evidence of biosurfactants production on Cetyl Trimethyl Ammonium Bromide agar with crude glycerol and lactoserum as substrate. In a mineral salt liquid medium enriched with both wastes, the biosurfactants were produced and collected from free cell medium after 72 h incubation.
The results suggest that biosurfactants produced by rhizosphere bacteria from pinyon have promising environmental applications. Characterization of per chlorate-reducing bacteria. Some bacteria can use per chlorateas terminal electron acceptor for growth. These bacteria convert perchlorate via chlorate and chlorite into chloride and molecular oxygen. Oxygen formation in microbial respiration is unique. In this study two chlorate-reducing strains. Rapid methods for detection of bacteria. Traditional methods for detection of bacteria in drinking water e.
New rapid methods for detection of bacteria are needed to protect the consumers against contaminations. Two rapid methods Rock-degrading endophytic bacteria in cacti. A plant-bacterium association of the cardon cactus Pachycereus pringlei and endophytic bacteria promotes establishment of seedlings and growth on igneous rocks without soil. These bacteria weather several rock types and minerals, unbind significant amounts of useful minerals for plants from the rocks, fix in vitro N2. Comparative Genomics of Green Sulfur Bacteria. Eleven completely sequenced Chlorobi genomes were compared in oligonucleotide usage, gene contents, and synteny.
The green sulfur bacteria GSB are equipped with a core genome that sustains their anoxygenic phototrophic lifestyle by photosynthesis, sulfur oxidation, and CO 2 fixation. Analyzing Arthropods for the Presence of Bacteria. Bacteria within arthropods can be identified using culture-independent methods. This unit describes protocols for surface sterilization of arthropods, DNA extraction of whole bodies and tissues, touchdown PCR amplification using 16S rDNA general bacteria primers and profiling the bacterial community using denaturing gradient gel electrophoresis.
Resuscitation effects of catalase on airborne bacteria. Catabolism of lysine by mixed rumen bacteria. Metabolites arising from the catabolism of lysine by the mixed rumen bacteria were chromatographically examined by using radioactive lysine. Most of the ether-soluble substances produced from radioactive lysine was volatile fatty acids VFAs. Fractionation of VFAs revealed that the peaks of butyric and acetic acids coincided with the strong radioactive peaks. Small amounts of radioactivities were detected in propionic acid peak and a peak assumed to be caproic acid.
The rumen bacteria appeared to decompose much larger amounts of lysine than the rumen ciliate protozoa did. Biodiversity of Bacteria Isolated from Different Soils. Morphological, cultural, biochemical, and molecular methods were used for bacteria identification. The following bacteria Bacillus thuringiensis 6, Bacillus cereus 8, Bacillus anthrachis 1, Bacillus circulans 1, Bacillus weihenstephanensis 1, Pseudomonas putida 1, Azotobacter chroococcum 1, Brevibacterium frigoritolerans 1, Burkholderia sp.
The Maximum Likelihood method was used to produce a molecular phylogenetic analysis and a phylogenetic tree was constructed. These bacteria can produce polyhydroxybutyrate PHB which is an organic polymer with commercial potential as a biodegradable thermoplastic. PHB can be used instead of petrol derivated non-degradable plastics. For this reason, PHB producing microorganisms are substantial in industry. These bacteria were isolated from extremely polluted petroleum hydrocarbon contaminated soils.
Biodegradation was measured using each organism individually and in combination. Both bacteria were shown to degrade each of the BTEX compounds. Biosurfactant production was observed by culture techniques. In addition 3-hydroxy fatty acids, important in biosurfactant production, was observed by FAME analysis. In addition, the test results indicate that the bacteria could contribute to bioremediation of aromatic hydrocarbons BTEX pollution increase biodegradation through the action by biosurfactants. Coryneform bacteria associated with canine otitis externa. This study aims to investigate the occurrence of coryneform bacteria in canine otitis externa.
A combined case series and case-control study was carried out to improve the current knowledge on frequency and clinical significance of coryneform bacteria in samples from canine otitis externa. A total Coryneform bacteria were identified by partial 16S rRNA gene sequencing. Corynebacterium auriscanis was the most common coryneform species Small colony variants of this species were also observed.
Other coryneform isolates were identified as Corynebacterium amycolatum 3 cases , Corynebacterium freneyi 2 cases and an Arcanobacterium-like species 1 case. The coryneform bacteria were in all cases isolated together with other Hyphae colonizing bacteria associated with Penicillium bilaii. But it is unknown if the comparable relationship exist between the non-mycorrhizal fungus P.
In the current PhD thesis, we assumed that hyphae-associated microbiome of P. Therefore, we aimed to isolate bacteria associated with the P. For this purpose, most of the work within the current project was carried out by development of suitable model systems by mimicking the natural soil habitat to reach to the reliable performance in soil In connection with the Chernobyl Nuclear Power Plant ChNPP accident and the negative ecological after-effects for biota in this zone the interest has arisen to radioresistant bacteria , as to the most dynamic model of the given ecosystem, and to mechanisms which provide resistance of bacteria to ionizing radiation.
The analysis of published data has shown that the radioresistant bacteria are not interrelated taxonomically and phylogenetically. The extreme radioresistant bacteria are represented by the Deinococcus species, which form a group phylogenetically close to the line Thermus-Meiothermus. Other radioresistant bacteria are the representatives of the genera Rubrobacter, Methylobacterium, Kocuria, Bacillus and some archebacteria.
Data on natural habitats, of radioresistant bacteria are not numerous. In a number of cases it is difficult to distinguish their natural habitats, as they were isolated from the samples which were previously exposed to X-ray or gamma-irradiation, or from the ecosystems with the naturally raised radioactivity.
To understand the strategy of survival of radioresistant bacteria , we briefly reviewed the mechanism of action of various species of radiation on cells and macromolecules; physiological signs of the cell damage caused by radiation; mechanisms eliminating repairing these damages. More details on mechanisms of the DNA repair in D.
The extreme resistance of D. Literary and own data on the effect of radiation on survival of various groups of bacteria in natural ecosystems are summarized. The ecological consequences of the ChNPP accident for soil bacteria in this region were estimated. The reduction of the number of soil bacteria and recession of microbial diversity under the effect of.
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De como os alunos entendem os textos. El budismo como una espiritualidad no religiosa. El ego con sus necesidades y deseos genera un acceso a la realidad relativo a nosotros. Como obter vantagem competitiva utilizando business intelligence? Daimien Hirst : el artista como preparador.
Hirst trabaja desde el cuerpo muerto, como medio y material de trabajo, para cuestionar el posicionamiento del cuerpo en el discurso de la medicina. The body, beyond its biological meaning, is a space of projection of cultural and scientific norms and values. The medicine constitutes a scopic regime, where an imaginary of body is built up which normalizes its perception by the modern subject.
Therefore, he works with body images placed on the border line between Medicine and Art. La moneda como ofrenda en los manantiales. Comparative cytotoxicity of periodontal bacteria. The direct cytotoxicity of sonic extracts SE from nine periodontal bacteria for human gingival fibroblasts HGF was compared. The cytotoxic potential of each SE was assessed by its ability to 1 inhibit HGF proliferation, as measured by direct cell counts; 2 inhibit 3H-thymidine incorporation in HGF cultures; or 3 cause morphological alterations of the cells in challenged cultures.
The data suggest that the outcome of the interaction between bacterial components and normal resident cells of the periodontium is, at least in part, a function of the bacterial species. Tape Cassette Bacteria Detection System. The design, fabrication, and testing of an automatic bacteria detection system with a zero-g capability and based on the filter-capsule approach is described.
This system is intended for monitoring the sterility of regenerated water in a spacecraft. The principle of detection is based on measuring the increase in chemiluminescence produced by the action of bacterial porphyrins i. Since viable as well as nonviable organisms initiate this luminescence, viable organisms are detected by comparing the signal of an incubated water sample with an unincubated control. Higher signals for the former indicate the presence of viable organisms.
System features include disposable sealed sterile capsules, each containing a filter membrane, for processing discrete water samples and a tape transport for moving these capsules through a processing sequence which involves sample concentration, nutrient addition, incubation, a 4 Molar Urea wash and reaction with luminol-hydrogen peroxide in front of a photomultiplier tube.
Liquids are introduced by means of a syringe needle which pierces a rubber septum contained in the wall of the capsule. Detection thresholds obtained with this unit towards E. Full Text Available Many pathogenic bacteria live in close association with protozoa. New evidence indicates that protozoa and not bacteria control the packaging process.
It is possible that packaging is more common than suspected and may play a major role in the persistence and transmission of pathogenic bacteria. To confirm the role of packaging in the propagation of infections, it is vital that the molecular mechanisms governing the packaging of bacteria by protozoa be identified as well as elements related to the ecology of this process in order to determine whether packaging acts as a Trojan Horse. En contraste, las bacterias grampositivas como Streptomyces lividans ofrecen la ventaja de secr De ellos, De los 70 casos, tres 4. La mortalidad general y postoperatoria fue de 7.
La participacion ciudadana como fuente de democracia. Palabras claves:Democracia Participativa. Abstract:Citizen participation is a deliberative body where all the real power to decide on aspects such as the developmentplan, development plan and budget according to the local authority where it is established, this model is itself atrue development the concept of participatory democracy enshrined in our Constitution, is an example of popularsovereignty enshrined in the third article of the Charter goes beyond the legal formalities and vericuetos the intricaciesof the law of which have never been allowed to put ongoing development of a true participatorydemocracy, and they finally get out of this backward scheme of representation and of course that through this modelto create a real social contract comes from the grassroots.
Keywords:Participatory Democracy. Charter Politics, Society, Politics, democratic, Constitution. Teresa Wilms Montt: la visceralidad como activismo. Bacteria classification using Cyranose electronic nose. Full Text Available Abstract Background An electronic nose e-nose, the Cyrano Sciences' Cyranose , comprising an array of thirty-two polymer carbon black composite sensors has been used to identify six species of bacteria responsible for eye infections when present at a range of concentrations in saline solutions.
Readings were taken from the headspace of the samples by manually introducing the portable e-nose system into a sterile glass containing a fixed volume of bacteria in suspension. Gathered data were a very complex mixture of different chemical compounds. Using these three data clustering algorithms simultaneously better 'classification' of six eye bacteria classes were represented.
A comparative evaluation of the classifiers was conducted for this application. Conclusion This type of bacteria data analysis and feature extraction is very difficult. But we can conclude that this combined use of three nonlinear methods can solve the feature extraction problem with very complex data and enhance the performance of Cyranose Folate Production by Probiotic Bacteria.
Full Text Available Probiotic bacteria , mostly belonging to the genera Lactobacillus and Bifidobacterium, confer a number of health benefits to the host, including vitamin production. On the basis of physiological studies and genome analysis, wild-type lactobacilli cannot synthesize folate, generally require it for growth, and provide a negative contribution to folate levels in fermented dairy products. Lactobacillus plantarum constitutes an exception among lactobacilli, since it is capable of folate production in presence of para-aminobenzoic acid pABA and deserves to be used in animal trials to validate its ability to produce the vitamin in vivo.
On the other hand, several folate-producing strains have been selected within the genus Bifidobacterium, with a great variability in the extent of vitamin released in the medium. Most of them belong to the species B. Rats fed a probiotic formulation of folate-producing bifidobacteria exhibited increased plasma folate level, confirming that the vitamin is produced in vivo and absorbed.
In a human trial, the same supplement raised folate concentration in feces. The use of folate-producing probiotic strains can be regarded as a new perspective in the specific use of probiotics. They could more efficiently confer protection against inflammation and cancer, both exerting the beneficial effects of probiotics and preventing the folate deficiency that is associated with premalignant changes in the colonic epithelia. Magnetotactic Bacteria from Extreme Environments. Full Text Available Magnetotactic bacteria MTB represent a diverse collection of motile prokaryotes that biomineralize intracellular, membrane-bounded, tens-of-nanometer-sized crystals of a magnetic mineral called magnetosomes.
MTB are known to mainly inhabit the oxic—anoxic interface OAI in water columns or sediments of aquatic habitats and it is currently thought that magnetosomes function as a means of making chemotaxis more efficient in locating and maintaining an optimal position for growth and survival at the OAI. Known cultured and uncultured MTB are phylogenetically associated with the Alpha-, Gamma- and Deltaproteobacteria classes of the phylum Proteobacteria, the Nitrospirae phylum and the candidate division OP3, part of the Planctomycetes-Verrucomicrobia-Chlamydiae PVC bacterial superphylum.
MTB are generally thought to be ubiquitous in aquatic environments as they are cosmopolitan in distribution and have been found in every continent although for years MTB were thought to be restricted to habitats with pH values near neutral and at ambient temperature. Apparently, fermentative bacteria are competitive for the electron donor and thereby alter the ratio of available substrates for nitrate reduction.
The Microworld of Marine- Bacteria. Microsensor studies show that the marine environment in the size scale of bacteria is physically and chemically very different from the macroenvironment. The microbial world of the sediment-water interface is thus dominated by water viscosity and steep diffusion gradients. Because of the diverse The communities of giant, filamentous sulfur bacteria that live in the deep-sea hydrothermal vents or along the Pacific coast of South America are presented here as examples Labelling of bacteria with indium chelates.
Both gram-positive Streptococcus, Staphylococcus and gram-negative bacteria Escherichia coli can be labelled. The reproductive capacity of the bacteria was not impaired. The application of indium labelled bacteria allows to show the distribution of microorganisms within the living organism and to investigate problems of bacterial adherence.
Mortality of fecal bacteria in seawater. The authors propose a method for determining the mortality rate for allochthonous bacteria released in aquatic environments without interference due to the loss of culturability in specific culture media. This method consists of following the disappearance of radioactivity from the trichloracetic acid-insoluble fraction in water samples to which [ 3 H]thymidine-prelabeled allochthonous bacteria have been added. In coastal seawater, they found that the actual rate of disappearance of fecal bacteria was 1 order of magnitude lower than the rate of loss of culturability on specific media.
Minor adaptation of the procedure may facilitate assessment of the effect of protozoan grazing and bacteriophage lysis on the overall bacterial mortality rate. Pu sorption to activated conglomerate anaerobic bacteria. The sorption of Pu to the anaerobic bacteria activated under specific conditions of temperature, pH and depleted nutrients after long dormant period was investigated. After 4 h at neutral pH, the distribution coefficient K d between bacteria and aqueous phase at and K had around 10 3 to 10 4.
After over 5 days, however, the K d at only K had increased to over 10 5. Sterilized dead and dormant anaerobic bacteria adsorbed Pu to the same extent. Tuberculosis como enfermedad ocupacional Tuberculosis as occupational disease. Sin embargo, los mecanismos de estas interacciones son pobremente entendidos. Also, the knowledge of specific interactions between bacteria and microalgae will allow the optimization of productive systems in aquaculture. However, until date the mechanisms involved in these interactions are poorly understood.
Therefore, future investigations should be directed towards understanding the mode of action of such interactions at a molecular level. What is a Bacteria Culture Test? Bacteria are a large group of Burkholderia tropica una bacteria con gran potencial parasu uso en la agricultura. Contabilidade gerencial como apoio ao "just in time". Finalmente discorre sobre um estudo de Como optimizar? Abstract: The tests used in the diagnosis of tuberculosis latent infection, the tuberculin skin test TST and the interferon-gamma assays IGRA, identify the existence of an adaptive immune response towards mycobacterial antigens.
Considering the limitations of the two tests, the best solution is to take advantage of the best characteristics of each one. The operative characteristics of TST depend on the prevalence of the illness in the community and the aim of its use its operative characteristics are higher when used in the tracing scope or as a diagnostic test.
To interpret correctly a TST, the physician must know the epidemiology of tuberculosis in the community and correctly define the indications for its use. Palavras-chave: Tuberculose, teste tubercul. Full Text Available This study presents a synthetic and personal view of the consequences arising from the notion of law as justice. For Kelsen, in this "Theory of pure law", human conduct produce facts, justly or injust1y, that become characterized as legal norms. Human behavior is determined by acts of reason, that are defined by a representative a judge, and then are used as valid norms of justice.
The conception of law is, therefore, represented by an ideal object, rational and only apprehensible through abstract processes, following the views of Kelsenians. Without any intent to criticize the "great master of Vienna", a search of the text demonstrates that a neutral ideology, concerning the comprehension and application of law, does not and can not exists law can not depart from empirical reality when following its purpose of promoting the liberty and development of society.
Flow cytometry, fluorescent probes, and flashing bacteria. Key words: fluorescent probes, flow cytometry, CSLM, viability, survival, microbial physiology, lactic acid bacteria , Lactococcus lactis , Lactobacillus plantarum , cheese, milk,. Effect of leukocyte hydrolases on bacteria. Leukocyte extracts, trypsin, and lysozyme are all capable of releasing the bulk of the LPS from S.
Bacteria which have been killed by heat, ultraviolet irradiation, or by a variety of metabolic inhibitors and antibiotics which affect protein, DNA, RNA, and cell wall synthesis no longer yield soluble LPS following treatment with the releasing agents. On the other hand, bacteria which are resistant to certain of the antibiotics yield nearly the full amount of soluble LPS following treatment, suggesting that certain heatabile endogenous metabolic pathways collaborate with the releasing agents in the release of LPS from the bacteria.
It is suggested that some of the beneficial effects of antibiotics on infections with gram-negative bacteria may be the prevention of massive release of endotoxin by leukocyte enzymes in inflammatory sites. Systemic resistance induced by rhizosphere bacteria. Nonpathogenic rhizobacteria can induce a systemic resistance in plants that is phenotypically similar to pathogen-induced systemic acquired resistance SAR.
Rhizobacteria-mediated induced systemic resistance ISR has been demonstrated against fungi, bacteria , and viruses in Arabidopsis, bean,. Lactic acid bacteria : microbiological and functional aspects. Comparative genomics of the lactic acid bacteria. Makarova, K. Lactic acid-producing bacteria are associated with various plant and animal niches and play a key role in the production of fermented foods and beverages. We report nine genome sequences representing the phylogenetic and functional diversity of these bacteria.
The small genomes of lactic acid bacteria encode a broad repertoire of transporters for efficient carbon and nitrogen acquisition from the nutritionally rich environments they inhabit and reflect a limited range of biosynthetic capabilities that indicate both prototrophic and auxotrophic strains. Phylogenetic analyses, comparison of gene content across the group, and reconstruction of ancestral gene sets indicate a combination of extensive gene loss and key gene acquisitions via horizontal gene transfer during the coevolution of lactic acid bacteria with their habitats.
Do bacteria , not fish, produce 'fish kairomone'? Fish-associated chemicals enhance phototactic downward swimming in Daphnia. If perch were treated with the antibiotic ampicillin, this enhancement was significantly decreased. Therefore, not fish, but bacteria associated with fish, seem to produce this kairomone. Bacteria -mediated bisphenol A degradation. Bisphenol A BPA is an important monomer in the manufacture of polycarbonate plastics, food cans, and other daily used chemicals.
Moreover, BPA has been identified as an environmental endocrine disruptor for its estrogenic and genotoxic activity. Thus, BPA contamination in the environment is an increasingly worldwide concern, and methods to efficiently remove BPA from the environment are urgently recommended. Although many factors affect the fate of BPA in the environment, BPA degradation is mainly depended on the metabolism of bacteria. Metabolic pathways of BPA degradation in specific bacterial strains were proposed, based on the metabolic intermediates detected during the degradation process.
In this review, the BPA-degrading bacteria were summarized, and the proposed BPA degradation pathway mediated by bacteria were referred. Abundance, viability and culturability of Antarctic bacteria. Previously it considered that leucine has some problem when comuele jet. Co-milling processes can be selected specifically for the active and carrier particles.
For example, the active particles may comoler jet or can be homogenized with the additive, while the carrier particles can be mecanofundir with the additive. Co-milling processes according to the present invention can be carried out in two or more stages, to provide beneficial effects. Within each step, multiple combinations can be used and co-grinding further processing steps. In one embodiment of the present invention, the milling process is a two step process comprising first jet milling the drug in itself to a suitable grinding pressure to obtain the required particle sizes.
Then, the milled drug is comuele with an additive material. Preferably, this second step is carried out at a lower grinding pressure, so that the effect achieved is the coating of small active particles with the additive material. This two step process may produce better results than simply comoler the active material and additive material at a high grinding pressure.
The same type of milling process two stages can be carried out with the carrier particles, although these particles, as a rule, have to be ground to such small particle sizes. In another embodiment of the present invention, the composite particles, which optionally may have been produced using the process of co-grinding two stages discussed above, subsequently undergo mechanofusion. This final mechanofusion step may "polish" the composite particles, further rubbing the additive material into the particles. This provides beneficial properties afforded by mechanofusion, in combination with very small particle sizes obtained by co-grinding jet.
Such additional mechanofusion step is particularly attractive for active composite particles, especially when they are very small. Reducing the particle size can be increased by carrying out the co-grinding jet at lower temperatures. The benefits of the methods according to the present invention are illustrated by the experimental data set forth below. This example studied magnesium stearate processed with budesonide. The magnesium stearate used was a standard grade supplied by Avocado Research Chemicals Ltd.
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The drug used was micronised budesonide. Las propiedades del polvo se ensayaron usando el Miat Monohaler. The powder properties were tested using the Miat Monohaler. Las mezclas de budesonida y estearato de magnesio se prepararon a diferentes porcentajes en peso de estearato de magnesio. Blends of budesonide and magnesium stearate were prepared at different weight percentages of magnesium stearate. The results, summarized below, indicate a high aerosolisation efficiency.
However, this powder had poor flow properties, and not easily handled, giving high device retention. El aditivo o agente de control de fuerzas usado fue estearato de magnesio Avocado , y la lactosa fina fue Sorbolac Meggle. The additive or control agent used was magnesium stearate forces Avocado and the fine lactose was Sorbolac Meggle. The mixtures were prepared by mechanofusion of the three components together using the AMS-MINI, carrying out mixing for 60 minutes at about rpm.
Las formulaciones se prepararon usando las siguientes concentraciones de budesonida, estearato de magnesio y Sorbolac Formulations were prepared using the following concentrations of budesonide, magnesium stearate and Sorbolac The results, summarized below, indicate that, as increasing the amount of budesonide in the blends increased the FPF results. Se prepararon dos formulaciones en el Glen Creston Grindomix.
As an extension to this work, they were further investigated different mixing methods of budesonide, magnesium stearate and Sorbolac were prepared in two formulations Glen Creston Grindomix the. Esta mezcladora es una mezcladora de cuchillas de estilo procesador de alimentos convencional, con dos cuchillas paralelas. This mixer is a blade mixer conventional processor style food, with two parallel blades. The formulation was tested by TSI and the results, when compared with those for mecanofundidas mixtures showed the Grindomix blend gives lower FPF results see table below.
It was also observed that this formulation had notably good flow properties for a material comprising such fine particles. It is believed to be associated with the process mechanofusion. El aditivo o agente de control de fuerzas usado fue estearato de magnesio, y la lactosa fina fue Sorbolac Meggle.
The additive or control agent used was magnesium stearate forces, and the fine lactose was Sorbolac Meggle. The drug used was micronised salbutamol sulphate from. Las formulaciones preparadas fueron: Formulations prepared were:. They were carried out on the NGI mixtures, and the results are shown below. The port is sealed and the cooling water was turned on. The equipment was switched off, and dismantled and the resulting formulation recovered mechanically. Above these levels, experience suggests that there could be a significant tackiness within the device, and the amounts used were unnecessary for further performance improvement.
First, 15 g of micronised apomorphine and 0. The equipment is then switched off, dismantled and the resulting formulation recovered mechanically. Then, 19g of Sorbolac lactose and 1g leucine are weighed into the Hosokawa system mechanofusion AMS-MINI of via a funnel attached to the largest port in the lid, the computer running at 3. The equipment was switched off, dismantled and the resulting formulation recovered mechanically. The active agent used in this example, theophylline, may be replaced by other phosphodiesterase inhibitors, including phosphodiesterase type 3 inhibitors, 4 or 5, as well as other non-specific.
These micronised drugs included budesonide, formoterol, salbutamol, glycopyrrolate, heparin, insulin and clobazam. Other compounds are considered suitable, including the classes of active agents and the specific examples listed above. It is expected that the results of these experiments show that the powder formulations prepared using the method according to the present invention showing additional improved properties such as FPD, FPF, as well as good fluidity and retention device and deposition in the reduced throat.
First, when the additive material is added to the drug, the amount used is preferably in the range of 0. Secondly, when the additive material is added to the carrier particles, the amount used is preferably in the range of 0. A study was conducted to characterize the changes in the properties of the fine particles of the vehicle, and the ultrafine particles of the drug, when comuelen with an additive material. As a model for a drug, ultrafine micronized lactose was selected, since it is now available in a micronized form and has a reduced compared to handling pharmaceutically active substances danger.
Ultrathin lactose is also regarded as a particularly cohesive material, hence improving its dispersibility represents a major challenge. Sorbolac Meggle Meggle Extra Fine were selected as the degrees of fine vehicle, since they are already available. However, other grades can be used lactose, such as those produced by DMV, Borculo, Foremost and other suppliers, or a degree as obtained for this purpose, while satisfying the size range indicated. The literature reveals various possible types of tests, including measuring powder flowability, powder cohesion, powder shear and powder dustiness.
In the first case, several basic powder characteristics were tested. Malvern, UK. This was followed examining several standard powder properties using the measuring apparatus Hosokawa powder. The microporosity of the lactose particles is also shown in the graph of Figure 1. Although the total pore volume does not increase significantly with processing, insufficient differences are seen in the different pore sizes to use porosity testing as a measure of the process.
Therefore, also it carried out as the Malvern particle size of a dispersion of wet powder. The results are summarized below. Although the surface area does not decrease with increasing processing time, this can probably be explained because the magnesium stearate over the surface. Se ensayaron diversos polvos usando este sistema, y los datos resultantes se resumen en las Tablas 1 a 5, mostrados en las Figuras 2 a 6, respectivamente. As you can be seen from the data, processing with magnesium stearate Mg St , virtually all of the powders showed a tendency to decrease the angle of repose and the angle of fall, and to increase bulk density and dispersibility.
For the Sorbolac lactose and ultrathin lactose, which are within the size range considered suitable for use as the vehicle of the present invention, powders mecanofundidos with magnesium stearate show very considerable drops in the angle of repose and the angle of fall as well as increases in aerated bulk density, compared to the raw material see Tables 1 and 2. When the powder is mixed using a low shear mixing was used in this study a Turbula mixer, none of these changes see Table 1 it was observed.
La Tabla 3 muestra Sorbolac ciclomezclada con estearato de magnesio. Table 3 shows Sorbolac ciclomezclada with magnesium stearate. In these examples, considerable drops in the angle of repose and the angle of fall, as well as increases in aerated bulk density are observed. Sin embargo, estos cambios generalmente son ligeramente menores que los observados cuando la Sorbolac y el estearato de magnesio se mecanofunden.
However, these changes are generally slightly less than those observed when the Sorbolac and magnesium stearate are mecanofunden. This is consistent with the increasing intensity of the processing methods producing increasing levels of effect. Table 4 shows micronised lactose, which in these trials was used to represent a model micronised drug. Unfortunately, the variability of the results was higher and the data provided, especially for the angle of repose and the angle of fall for the raw material, not considered reliable. The density increased but was still relatively low.
It was observed that these powders are highly cohesive. Even after mechanofusion, only slight improvements were seen, in contrast to visible drastic changes for Sorbolac and powder lactose ultrathin. SV Table 5 shows, a carrier material traditional large lactose. In this case, the mecanofundido powder with magnesium stearate shows smaller drops in the angle of repose and no change in the camber angle in which it remains in an already low level in its original state.
Similarly, the aerated bulk density increased slightly, but from an already high level. Thus, the results indicate that the carrier particles comolidas within the preferred size for the present invention range, and particles comolidas model drug, showed a tendency to decrease in angle of repose, to increase the apparent density, ea increase dispersibility.
These properties would have anticipated in conjunction with reduced cohesion one. It was observed that this improvement increases with increasing intensity of the co-milling methods and with increasing of levels of additive material magnesium stearate. This result is an improvement in performance of a formulation containing the carrier in an inhaler, in terms of improved emitted dose and in terms of improved fine particle dose, especially the fine particle dose of metered dose.
The metered dose MD of a dry powder formulation is the total mass of active agent present in the metered form presented by the inhaler device in question. La dosis emitida ED es la masa total del agente activo emitido desde el dispositivo tras el accionamiento. The emitted dose ED is the total mass of the active agent emitted from the device after actuation.
Does not include the material left on the internal or external surfaces of the device or in the measurement system, including, for example, the capsule or blister. The ED is measured by collecting the total emitted mass from the device in a commonly identified as an apparatus sampling dose uniformity DUSA apparatus, and recovering this by a chemical assay validated quantitative wet possible a gravimetric method, but this is less accurate.
The fine particle dose FPD is the total mass of active agent which is emitted from the device following actuation which is present in a size smaller than a defined limit aerodynamic particle. Each impactor has cutoffs collection predetermined sizes for each stage aerodynamic particles. The value of FPD is obtained by interpretation of the recovery of the active agent phase by quantized step by a chemical assay validated quantitative wet possible a gravimetric method, but this is less precise where a cut single stage is used to determine FPD or a more complex mathematical interpolation of the stage by stage deposition is used.
The Flodex provides an index, over a scale of 4 to 40 mm, the flowability of the powders. The analysis can be performed by placing 50 g of a formulation in the holding chamber Flodex via a funnel, allowing the formulation to stand for 1 minute, and then releasing the trap door of the Flodex to open an orifice at the base of the chamber retention. They can be used hole diameters of 4 to 34 mm, to measure the rate of flow capacity.
The flowability of a given formulation is determined as the smallest orifice diameter through which flow of the formulation is smooth. The apparent volume and apparent density can be tested according to the method described in the European Pharmacopoeia Eur.
The flowability properties were tested according to the method described in Eur. Powder mixtures about g were then poured into a dry funnel equipped with an orifice of suitable diameter that is blocked by suitable means. The bottom opening of the funnel is unblocked and the time needed for the entire sample out of the funnel recorded. The flowability is expressed in seconds and tenths of seconds relative to g of sample.
An index of less than 25 is considered Carr usually indicative of good flowability characteristics. The uniformity of distribution of active ingredient can be evaluated by removing 10 samples, each equivalent to about a single dose, from different parts of the mixture. The amount of active ingredient of each sample can be determined by liquid chromatography high performance HPLC. An amount of powder for inhalation may be tested by loading it into a dry powder inhaler and firing the dose into an impactor, using the methods as defined in the European Pharmacopoeia or United States.
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These techniques may be useful for quantifying the surface energy and production of amorphous material during the processing of the powder particles. Amorphous material is regarded as potentially harmful to the long-term stability of powder formulations, making them tending to recrystallization. We have considered dust characterization parameters such as flowability indices or forms of surface characterization.
The test apparatus Hosokawa powder provided a good test to qualify changes in powder properties. The mecanofundidos powders showed a tendency to decrease the angle of repose, to increase the bulk density and increase dispersibility. However, as the particles approach the micron size, these assays with the test apparatus Hosokawa powder were less equivocal. Also, these parameters can not be directly related to the behavior during aerosolization.
And characterization of powders drug component and fine vehicle, these assays with the test apparatus powder Hosokawa are also useful characterizing the final combined formulation, where the properties of the final formulation are advantageously similar to the comolido properties of fine vehicle. Accordingly, the combined formulation will have good flow properties and provide good retention of the device. Further, the good dispersibility of the drug component is retained, providing high levels of fine particle fraction and fine particle dose, as measured by standard in vitro assays.
Such improvements are also consistent, providing less variability in the test results obtained than for traditional formulations approaches. Another very important advantage of the system of the present invention is the consistency of the high performance. One of the many benefits of consistency is that it can also lead to reduction in adverse side effects experienced, as it will allow to administer a total smaller dose than possible when based on conventional levels of inhaler's efficiency or other routes of administration.
In particular, to select as targets specific dosing windows wherein the therapeutic effect is maximized, while that create minimum side effects. According to a second aspect of the present invention, formulations which are obtainable by methods according to the first aspect of the invention are provided.
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In powder compositions of the present invention, at least some of the composite particles may be in the form of agglomerates, preferably unstable agglomerates. However, when active particles composed are included in a pharmaceutical composition the additive material promotes the dispersal of the composite active particles by administering this composition to a patient, via actuation of an inhaler.
In the turbulence created upon actuation of the inhaler device, the agglomerate, releasing the composite particles of respirable size breaks. The powder particles according to the present invention can be prepared as described herein are particles not "low density", as tend to be favored in the prior art. Such low density particles can be difficult and expensive to prepare. Indeed, previously, those skilled in the art have only disclosed a high performance in connection with powder particles that have been prepared using techniques imaginative processing such as drying complex spray, which results in low density particles.
In contrast, the particles of the present invention are obtained using simple and economic processes. In contrast to the suggestion in the prior art, it may be advantageous not produce significantly holed or wrinkled particles as these can yield low density powders, with very high number of voids between particles. Has been reported as such powders have good flow characteristics and dispersion, but they occupy a large volume relative to their mass as a consequence of their shape and can result in packaging problems, ie, may require Blisters or much larger capsules to hold a given mass of powder.
In one embodiment of the present invention, the powders have a tapped density percussion at least 0. The objective of the analysis is to identify the presence of magnesium stearate on the surface of a model co-micronized powder. The model powders were processed in two different ways, representing a conventional pharmaceutical process mixing, and the other being the intensive mechanofusion process which is the object of the invention.
El objetivo fue mostrar el contraste en la eficacia del revestimiento de la superficie. The aim was to show the contrast in the effectiveness of surface coating. In this case the model material was micronised lactose, which could represent a micronised drug or a fine carrier. TOF-SIMS provides a mass spectrum of the outermost nanometer of the surface, and is used here to evaluate if the coating with magnesium stearate lactose is complete or in patches is. XPS provides a spectrum representative of the 10 outermost surface of the sample nm, and is used here in comparison to the TOF-SIMS data to assess the depth of the coating of the magnesium stearate on the lactose surface.
Each sample was tested in cyclohexane, and zeta potential measurements were obtained. Se prepararon las siguientes muestras de polvo para el ensayo: The following powder samples were prepared for testing:. SIMS is a qualitative surface analytical technique that is capable of producing a spectrum of high resolution mass outermost nanometro a surface. De forma breve, el proceso de SIMS implica bombardear la superficie de la muestra con un haz de iones primarios por ejemplo cesio o galio. Briefly, the process involves bombarding the surface SIMS of the sample with a primary ion beam for example cesium or gallium.
Collision of these ions with atoms and molecules in the surface results in the transfer of energy to them, causing their emission from the surface. The types of particles emitted from the surface include positive and negative ions termed secondary ions , neutral species and electrons. Only secondary ions are measured in SIMS. Depending on the type of bias applied to the sample positive or negative ions are directed towards a mass spectrometer.
Different fragments will be diagnostic of different components of the surface. SIMS operating in static mode to determine the chemical composition of the top monolayer of the surface was used. La presencia de lactosa en los espectros indica que el recubrimiento de la superficie de estearato de magnesio es incompleto. The presence of lactose in the spectra indicates that the surface coverage of magnesium stearate is incomplete. La presencia de lactosa en los espectros indica que el recubrimiento superficial de estearato de magnesio es incompleto.
Importantly SIMS spectra are not quantitative, and thus the intensities of the peaks can not be taken as a reflection of degree of surface coating.