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While Pancharatnam discovered the geometric phase in 1956, his work was not widely recognized until its endorsement by Berry in 1987, after which it received wide appreciation. However, because Pancharatnam's paper is unusually difficult to follow, his work has often been misinterpreted as referring to an evolution of states of polarization, just as Berry's work focused on a cycle of states, even though this consideration does not appear in Pancharatnam's work. We walk the reader through Pancharatnam's original derivation and show how Pancharatnam's approach connects to recent work in geometric phase. It is our hope to make this widely cited classic paper more accessible and better understood.

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We revisit the application of neural networks techniques to quantum state tomography. We confirm that the positivity constraint can be successfully implemented with trained networks that convert outputs from standard feed-forward neural networks to valid descriptions of quantum states. Any standard neural-network architecture can be adapted with our method. Our results open possibilities to use state-of-the-art deep-learning methods for quantum state reconstruction under various types of noise., Comment: 8 pages, 4 color figures. Comments are most welcome

El libro contiene caracter��sticas que aportan hacia la digitalizaci��n de los procesos, nos introduce sobre los beneficios de los aplicativos de la tecnolog��a emergente en las peque��as y medianas empresas del Per��, surge de la necesidad de digitalizar y recopilar datos de una manera m��s eficiente, con el fin de optimizar la productividad y minimizar tiempos de trabajo en una empresa. El COVID 19 aceler�� a migrar sus negocios a plataformas virtuales, la metodolog��a de Posicionamiento Web de sus Servicios o Productos ayud�� a lograr m��s clientes, contribuyendo a la comunidad empresarial y sobre todo a Latinoam��rica para ubicar sus negocios f��sicos en Google. La incorporaci��n de procesos digitales en internet en un mediano plazo logra aumentar la demanda, aquello implica otras amenazas con relaci��n a la calidad del producto o servicio, por ello es importante considerar la acreditaci��n o certificaci��n para asegurar las expectativas de los clientes. Asimismo, las empresas deben incorporar procesos digitales para los procedimientos de fiscalizaci��n, venta, log��sticas y otras ��reas para reducir el tiempo efectivo y costo, estos cambios deben responder a los lineamientos del dise��o estrat��gico, procesos y estructura organizacional. La finalidad es proponer una metodolog��a de redise��o organizacional hacia la transformaci��n digital en las empresas p��blicas y privadas, con un enfoque estrat��gico y operativo para orientar hacia la digitalizaci��n de los procesos, impulsando la transformaci��n digital.

Bacterial vaginosis; Hyaluronic acid and prebiotic-based gel; Non-hormonal Centella asiatica Vaginitis bacteriana; Àcid hialurònic i gel a base de prebiòtics; Centella asiàtica no hormonal Vaginitis bacteriana; Gel a base de ácido hialurónico y prebióticos; Centella asiática no hormonal Bacterial vaginosis (BV) affects nearly one-third of women worldwide and may predispose patients to sexually transmitted infections or pelvic inflammatory disease. Currently recommended treatment is based on antibiotic use, which poses problems such as antibiotic resistance and the development of secondary vaginal candidiasis. Palomacare® is a non-hormonal vaginal gel containing hyaluronic acid, Centella asiatica and prebiotics, with repairing and moisturizing properties used for dysbiosis healing as an adjuvant treatment. A series of 3 cases using the vaginal gel as a monotherapy showed that symptoms improved and even disappeared in women with initial or recurrent BV, suggesting that this vaginal gel is effective for BV monotherapy in women of reproductive age.

Introduction: Frailty is a multifactorial syndrome that increases vulnerability to stressors, leading to a higher risk of adverse health events. Several non-pharmacological interventions, including lifestyle changes, have been studied as alternatives to reduce or attenuate frailty in older adults. Older adults with cognitive impairment (CI) have higher multimorbidity and frailty prevalence, lower functional status, and, consequently, an increased likelihood to develop dementia, non-cognitive deficits (e.g., falls, physical disability), and adverse health-related events (e.g., hospitalization, institutionalization). Nevertheless, intervention studies on frail individuals frequently exclude persons with CI. +AGIL, a real-world program for frail older adults in a primary care area of Barcelona, is a pragmatic, multicomponent intervention implemented since 2016. It includes a multifactorial intervention (i.e., physical activity, nutrition, sleep hygiene, revision and adequacy of pharmacological treatment, detection of undesired loneliness and screening for CI) to improve physical function in community-dwelling older adults. Empowerment of the participants and fostering of their community engagement are also critical component of the intervention. Its implementation was based on three main principles: integrated care (among geriatric team, primary care physician, and community and third sector resources), co-design with end-users, and sustainability over time.Objectives: To assess the longitudinal impact on physical function among community-dwelling frail older persons with CI. Results: 194 participants (68% women), screening with the Gerontopole FST, were included (82 with CI, 112 without CI, based on previous diagnosis or the Mini-COG screening tool), with mean age(SD)=81,6(5,8) years old. Participants were mostly independent in Activities of Daily Living (mean Barthel Index=92,4, SD=11,1). They had relatively high prevalence of comorbidities and polypharmacy; 47,4% had experiences at least one fall in the last year. A physical activity program (10 weekly sessions by an expert physical therapist in the whole sample) showed high adherence (87.6% attended ≥75% sessions). At three months, there was a clinically and statistically significant improvement at the Short Physical Performance Battery (SPPB) and its subcompenents in the whole sample and after stratification for CI. At six months, SPPB and gait speed remained stable in the study sample and subgroups. CI had no significant impact on the improvement of the SPPB or gait speed. Conclusion: Our results suggest that older adults with CI can benefit from a multidisciplinary integrated and comprehensive geriatric intervention to improve physical function, a component of frailty.Sustainability and transferability: +AGIL has changed the usual clinical practice in the involved centers. Also, older adults with frailty and CI, an increasing population usually excluded from these interventions, receive benefits from this program. Following the principles of care integration and users’ involvement, which lead to sustainability over time, +AGIL can be quickly adopted, adapted, and replicated in other areas and contexts.

Orientador: Sergio Marangoni Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia Resumo: Através de metodologias otimizadas de purificação em HPLC, foram purificadas novas toxinas a partir do veneno total de Crotalus durissus collilineatus (V-1), Bothrops jararacussus PLA2 D49 Bj-V (isoforma de Bj-IV) obtida da fração BthTX-II e Bothrops alternatus PLA2 K49 Bt II-2; com um alto grau de pureza e homogeneidade molecular, sem perda da atividade biológica. A nova neurotoxina V-1 de Crotalus durissus collilineatus caracterizada físico-quimicamente como desprovida de atividade catalítica, ácida e com uma massa molecular de 9859.45 Da, uma única cadeia polipeptídica, induz uma facilitação contínua no modelo biológico nervo frênico diafragma isolado de camundongo e uma facilitação pronunciada seguida de um bloqueio súbito em biventer cervicis de pintainho, na junção neuromuscular. Os estudos estruturais, neurotóxicos e miotóxicos da PLA2 F6 do complexo crotoxina de Crotalus durissus collilineatus mostram que a PLA2 F6 precisa da crotapotina (estudos de re-associação) para potencializar seu efeito neurotóxico na preparação nervo frênico diafragma isolado de camundongo, mas a PLA2 F6 é capaz de induzir neurotoxicidade in vitro na ausência de crotapotina na preparação biventer cervicis de pintainho. Foram purificadas, a partir da fração BthTX-II, duas PLA2 D49 Bj-IV e V, sendo consideradas como isoformas devido ao fato de que compartilham de várias características físico-químicas, tais como: massa molecular, tempo de retenção na re-purificação em HPLC de fase reversa, análise de composição de aminoácidos, pI e estrutura primária, embora a isoforma Bj-V apresente algumas mutações com respeito à isoforma Bj-IV: W3 -> F3, Q4 -> E4, F5 -> W5, I16 -> N16 e G41 -> 41D; importantes para a atividade catalítica, os efeitos neurotóxicos in vitro foram mantidos e, quando foram inibidas cataliticamente por crotapotinas crotálicas de Crotalus durissus collilineatus (F3 e F4), continuaram diminuindo a resposta contrátil na junção neuromuscular nas preparações nervo frênico diafragma isolado de camundongo e biventer cervicis de pintainho, mostrando que são mais pronunciadas no músculo esquelético de camundongo. A nova toxina Bt II-2 purificada, com um alto grau de pureza e homogeneidade molecular, do veneno de Bothrops alternatus, foi caracterizada como uma PLA2 básica K49, em função das características físico-químicas, evidenciadas: massa de 13898.71 Da, possui caráter básico e uma alta homologia seqüencial na sua estrutura primária, quando comparada com outras PLA2 K49 procedentes de veneno de serpentes.Essa nova PLA2 K49 Bt II-2 revelou um potente efeito neurotóxico in vitro na preparação nervo frênico diafragma isolado de camundongo (1 µg/mL) pré-sináptico, como foi mostrado nos estudos de estímulo indireto via nervo e potencial de membrana ou repouso, diferentemente de qualquer PLA2 neurotóxica botrópica que, para causar um efeito neurotóxico, precisa de dosagem acima de 50 µg/mL. Outros perfis biológicos foram estudados para a Bt II-2, que mostrou uma miotoxicidade local ¿in vivo¿, citotoxicidade em mioblastos e miotubos C2C12, atividade inflamatória e letalidade, corroborando que se enquadra dentro da família de proteínas PLA2 homólogas K49, mas com características únicas nos estudos de neurotoxicidade in vitro. A reprodutibilidade da atividade biológica, através dos efeitos farmacológicos, só é possível com a utilização de frações quimicamente homogêneas que mantenham a integridade da função biológica. Essas frações são obtidas com metodologias de alta eficiência: HPLC, LC, espectrometria de massa, cujos resultados podem ser associados com sua atividade biológica, eliminando a subjetividade causada por veneno total ou frações impuras. Essa abordagem pode ser aplicada nos estudos bioquímicos, estrutura-função, fisiológicos e farmacológicos, podendo revelar mecanismos ainda desconhecidos na relação estrutura-função das PLA2 procedentes de veneno de serpentes. A presença de um sítio farmacológico distinto do sítio catalítico presente nas PLA2 pode ser usada como ferramenta molecular para o reconhecimento dos receptores de membrana desconhecidos em células ou tecidos Abstract: Through optimized methodologies of purification in HPLC, new toxins were purified from total venom of Crotalus durissus collilineatus (V-1), Bothrops jararacussus PLA2 D49 Bj-V (Bj-IV isoform) obtained from the fraction BthTX-II and Bothrops alternatus PLA2 K49 Bt II-2; with a high level of purity and molecular homogeneity, with no loss of biological activity. The new neurotoxin V-1 of Crotalus durissus collilineatus, chemically and physically characterized as unproved of catalytic, acid activity and with a molecular mass of 9859.45 Da, an only polypeptide sequence, induces to a continual facilitation in the biological isolated mouse phrenic nerve diaphragm model of mouse and a pronunciated facility of a subital block in chick biventer cervicis preparation en, in the neuromuscular junction. The structural, neurotoxic and miotoxic studies on PLA2 F6 from crotoxin complex of Crotalus durissus collineatus show crotapotin is necessary (re-association studies) to increase its neurotoxic effect in nerve phrenic diaphragm isolated preparation of mouse, but the PLA2 F6 is able to induce neurotoxity in vitro in ausency of crotopatin in the preparation chick biventer cervicis. Two PLA2 D49 Bj-IV and V were purified from the fraction BthTX-II and considered isoform because they share several chemical and physical characteristics, such as molecular mass, retention time in re-purification in reverse phase HPLC, analyses of amino acid composition, pI and primary structure, although the Bj-V isoform shows some mutations regarding Bj-IV: W3 -> F3, Q4 -> E4, F5 -> W5, I16 -> N16 e G41 -> 41D isoform. Important for the catalytic activity, neurotoxic in vitro effects were maintained and, when catalytically inhibited by crotapotin crotalic of Crotalus durissus collilineatus (F3 e F4), they continued dimishing the contractile reply in neuromuscular junction in nerve phrenic diaphragm isolated preparations of mouse and preparation chick biventer cervicis, which shows they are more pronunciated in the skeleton muscle of the mouse. The new and purified BtII-2 toxin of venom of Bothrops alternatus, with a high level of purity and molecular homogeneity, was characterized as a PLA2 basic K49, because its chemical and physical evidenced characteristics, mass of 13898.71 Da, basic character and a high sequential homology in its primary structure, when it is compared with other PLA2 K49 from venom of serpents. This new PLA2 K49 Bt II-2 has revealed a potent neurotoxic effect in vitro in neuromuscular junction in nerve phrenic diaphragm isolated preparation of mouse (1 µg/mL) ante-synaptic, as it was proved by studies on indirect stimulus through nerve and potential of membrane or rest, differently of some neurotoxic botropic PLA2 that needs a dose above 50 µg/mL to cause a neurotoxic effect. Other biological profiles were studied for the Bt II-2, and the conclusion was a local myotoxic ¿living¿, a cytotoxic in myoblasts and myotubes C2C12, imflammatory and letality activity, showing they are fitted in the family of proteins PLA2 homologous K49, but with particular characteristics in studies on neurotoxic in vitro. The reprodubility of biological activity, through pharmacological effects, is just possible with the utilization of chemically homogenous fractions that maintain the integrity of biological function. These fractions were obtained with high efficient methodologies as HPLC, LC, and mass spectrometry, whose results may be associated with their biological activities, eliminating the subjectivity caused by total venom or impure fractions. This approximation may be applied in the biochemical studies, structure-function, physiological and pharmacological, and it may reveal still unknown mechanisms in the relation structure-function of PLA2 from the venom of serpents. The presence of a pharmacological site different of the catalytic one in the PLA2 may be used as a molecular instrument to the recognition of the receptors of unknown membranes in cells or tissues Doutorado Bioquímica Doutor em Biologia Funcional e Molecular

Las dificultades en el aprendizaje de las matemáticas se reflejan en los altos índices de reprobación de esta asignatura en diversas instituciones educativas de nivel medio superior en nuestro país siendo una de las materias con el menor porcentaje de aprobación. El fenómeno descrito se evidencia con los resultados obtenidos por los alumnos en el Plan Nacional para la Evaluación de los Aprendizajes (PLANEA), donde se observa que “en Matemáticas, 6 de cada 10 estudiantes se ubica en el Nivel I (66%) de conocimiento” (Secretaría Educación Pública, 2018). La problemática descrita es latente en la Escuela de Bachilleres de la Universidad Autónoma de Querétaro (EBUAQ) donde el 50% de los alumnos de nuevo ingreso reprueban alguna materia de ciencias básicas (Vázquez, 2013).

In this article, I present and develop a reading and interpretation hypothesis, in a philosophical way, of Roland Barthes’s work. My starting point is to examine the sign, in its different manifestations (specifically, words and images and their combinations) and dimensions (sign, signifier, signified, referent), in its relationships with the real, i.e., as appearance and / or appearance of the real, as it appears in Barthes’ texts. In my opinion, in his writings, it is possible to point out four lines of work (criticism, science, aesthetics, ethics), linked by a common denominator of philosophy. In sum, without excluding other interpretations, I try to defend the plausibility of seeing Barthes as a philosopher and reading his work as a philosophy. En este trabajo, presentamos y desarrollamos una hipótesis de lectura e interpretación, en clave filosófica de la obra de Roland Barthes. Nuestro punto de partida consiste en examinar el signo, en sus diferentes manifestaciones (concretamente, palabras e imágenes y sus combinaciones) y dimensiones (signo, significante, significado, referente), en sus relaciones con lo real, i.e., como apariencia y/o aparición de lo real, tal y como aparece en los textos de Barthes. En nuestra opinión, en su obra, es posible señalar cuatro líneas de trabajo (la crítica, la ciencia, la estética, la ética), vinculadas por el común denominador de la filosofía. En suma, sin excluir otras interpretaciones, intentamos defender la plausibilidad de ver a Barthes como filósofo y leer su obra como filosofía.

5D physics in 55 pages

CubeSats and SmallSats have seen increasing success in Low Earth Orbit (LEO). However, there is a desire to send small, low cost missions beyond LEO into harsher environments. Additionally, most bus architectures do not currently have the on-board processing capa-bilities to handle high-speed science data and autonomous operations. MARES, currently under development at NASA’s Goddard Space Flight Center, is a capabilities driven design and architecture with an emphasis on reliability, scalability, and high performance process-ing. Its applicability is broad including SmallSat missions, CubeSat missions, and high performance instrument processors. The highly integrated architecture reduces mass, volume, and power but still provides the flexibility of a modular system. Mission critical functions are handled by the Command and Data Handling (C&DH) Processor and Auxiliary cards, which are radiation hardened up to 100krad. SpaceCube™ Mini 3 processor card is primarily used for instrument data processing but its versatility and processing power provides a digital platform to reduce the SWaP of components and applications such as above-the-constellation GPS, software defined radio and LIDAR. This can be achieved by utilizing the same Mini card for various applications but multiple units can be utilized on the same bus if needed via a backplane design for the bus avionics. The catalog of new cards and features for MARES continues to grow, and the architecture can be expanded further with the design of mission-specific cards that plug into the same backplane as the rest of the bus. Standardized backplane configurations will reduce resources spent on customization and ensure a robust and compatible system.

We introduce the 5th dimension of scalar space-time. To prove the scientific existence of a space-time dimension we need to find "a metric co-invariant function that relates its space-time parameters allowing to travel through it". (Klein). The metric of the 5th dimension is deceptively simple: Si (Size/ Space Volume) x Tƒ (cyclic frequency=speed of its time clocks) = C¡: Constant Plane of timespace (ab.∆¡) 5D metric is then used to analyze with the same laws all scales of space-time each one studied by a stience, whose species are not in an abstract background of Newtonian absolute space-time, but are made as Leibniz & Einstein wanted of 3 relative elements: ∆-scales of Space=Form & Time=Motion mirrored in all ‘Stiences’ by its main parameters: In mathematics Non-E fractal points of Space grow in lines=networks; 3 of which form a topologic space-time plane=organism. Numbers represent ∆-scalar groups and Algebraic operands Time motions. In physics ∆ST is proved because its 3 elements correspond to its 3 conserved quantities: S=angular momentum, T=lineal momentum & 3 Energy forms, ∆-1: Internal, ∆ø-kinetic &∆+1 potential energy. Thus ST: 2 |+O momenta integrate into ∆+1 work=energy: ∫p=E or dissolve=derivate into the ∂p=Forces scale. In biology we travel through the 5th dimension of scalar space & cyclical time by growing organically in ‘space size’ through cellular/atomic/social networks 'while slowing down the ‘speed of our metabolic time cycles, which is exactly what happens in the worldcycle of life and death of any universal species as all are born in a smaller seed with faster time cycles, evolve as an organism emerging as a bigger ∆ºnetwork organism, to live within a larger ∆+1world of slower ‘Deep time cycles’, to die back dissolving its information back into its lower cellular/atomic ∆-1 plane; from the smallest black hole born with a huge ‘metabolic temperature’ (Hawking), to the new species, born as small individuals (1st placental mammal shrew, first digital brain=chips; 1st modern human brain, Homo Floresiensis). Then a reproductive radiation multiplies the crystal, DNA cell or species creating an ∆º supœrganism that lives 3 ages of growing information till death dissolves back into ∆-1 ((∆-1: plasma>T-gas, S=T-liquid, S-olid states «E=mc2). Organic worldcycles happen in all stiences. They define the key system of reality, an ∆ST Supœrganism whose simultaneous parts in space become synchronous in time, across 3 5D scales, the ∆-1, atomic, cellular and individual scale, the ∆º, thermodynamic, organic and social scale, and the ∆+1, gravitational ecosystemic and global scale of physical, biologic and social systems, whose metrics allows the symbiotic transfer of spacetime energy made of cyclical information and lineal motion. As all scales have the same value and properties, hence the Universe is absolutely relative. In 5D metric, smaller systems in space have faster time clocks that store more information in the frequency and form of its cycles, coding larger wholes: genes code cells, memes societies and particles code atoms and molecules. But larger wholes are stronger envelopes, membranes (static, dimensional view) or angular momenta (dynamic view as time=motions) which enclose and control in synchronicity its faster smaller parts. They also have more ‘scales of ∆-energy’. So they exchange energy for information with its parts, through 3 ∆º T-motion, ∆-Energy & S-informative networks that travel through the 5th dimension, harmonizing the co-existence of organic scales whose vital Universal constants are 5D metric ratios of information & energy exchanges. Thus the Universe is a nested, fractal 5D superorganism that organizes 'vital spacetime forms with motion' through networks into larger organic systems that emerge as new planes of ST¡ence, from particles into atoms, molecules, cells, matter states, organisms, solar systems & galaxies. As each new 'ST-organism'' become a ‘fractal point’ unit of a new '5D space-time network'. Thus space laws are Topologic laws that put together 3 type of networks: |-moving limbs/fields>Ø-reproductive waves/bodies & O-informative particle/heads. Time laws study life-death worldcycles that evolve ∆-1 seeds into ∆ø-organisms made of those 3 topologies that ‘age’ in 3 ST-ages dominated by each network till the S-head exhaust all motion and a ‘fast’ entropic=death dissolves its information into an ∆st 0-sum. Finally ∆±¡ scalar laws study ∆-energy exchanges thru 3±¡ ‘∆ctions’ of Tt-entropic feeding, Ts-motion, §∏-reproduction, St-information & Ss-mind mirror languages that revolve and project order in a larger ∆+1 world. Those are the ∆ST-events & forms of space-time described by each species in each stience. "New scientific models never spring from a communal body, but from the head of an individual researcher who struggles with his ideas in lonely thought and unites them all in a single point which becomes the whole world." Planck.Luis So=To; 5Сlogic humind ¬∆@st of Time§pace≈fractal point.

Resumen basado en el de la publicación Título, resumen y palabras clave en español e inglés Se aborda un problema de pensamiento numérico basado en la relación de orden con fracciones propias, teniendo en cuenta los diferentes procesos utilizados por los alumnos para dar solución a los interrogantes propuestos y definiendo la relación de orden como a/b < c/d si a · d < b · c. Se tomó un grupo de sexto grado de educación básica conformado por alumnos de 11 a 13 años de edad. Envuelve los distintos momentos, antes, durante y después, de los métodos utilizados para solucionar el problema. El aporte de esta propuesta metodológica es la generación de conocimiento nuevo basado en los saberes previos, haciendo que los alumnos logren construir sus propias conclusiones a cerca de la relación de orden con fracciones propias y facilitar de esta forma los procesos evaluativos del docente en el aula. ESP

For years, planktologists considered the chaetognaths as great predators of other zooplankters. In this study, we analyzed the feeding rates upon copepods of the chaetognath Flaccisagitta enflata. Additionally, we sought signs of predatory competition with gelatinous zooplankton for copepod prey. Zooplankton samples collected in a Bongo net (333 µm mesh) in the southern Gulf of Mexico were analyzed in the laboratory. Results indicated that on average, a F. enflata individual eats 0.8 copepod.day-1. We suggest that competition for prey between chaetognaths and gelatinous zooplankton does not occur or is negligible because the feeding activity in chaetognaths does not increase with prey abundance, no habitat partitioning was observed between the two predator types, and that predator species can turn to alternative food items. The low intake of copepods and the fact that feeding rates do not increase with food concentration led us to hypothesize that chaetognaths are not voracious predators as previously suggested.

We demonstrate that the multipoles associated with the density matrix are truly observable quantities that can be unambiguously determined from intensity moments. Given their correct transformation properties, these multipoles are the natural variables to deal with a number of problems in the quantum domain. In the case of polarization, the moments are measured after the light has passed through two quarter-wave plates, one half-wave plate, and a polarizing beam splitter for specific values of the angles of the waveplates. For more general two-mode problems, equivalent measurements can be performed., 4 pages. Accepted for publication in Optics Letters

Stellar bow shocks result from relative motions between stars and their environment. The interaction of the stellar wind and radiation with gas and dust in the interstellar medium produces curved arcs of emission at optical, infrared, and radio wavelengths. We recently proposed a new two-dimensional classification scheme for the shape of such bow shocks, which we here apply to three very different observational datasets: mid-infrared arcs around hot OB stars; far-infrared arcs around luminous cool stars; and H alpha emission-line arcs around proplyds and other young stars in the Orion Nebula. For OB stars, the average shape is consistent with simple thin-shell models for the interaction of a spherical wind with a parallel stream, but the diversity of observed shapes is many times larger than such models predict. We propose that this may be caused by time-dependent oscillations in the bow shocks, due to either instabilities or wind variability. Cool star bow shocks have markedly more closed wings than hot star bow shocks, which may be due to the dust emission arising in the shocked stellar wind instead of the shocked interstellar medium. The Orion Nebula arcs, on the other hand, have both significantly more open wings and significantly flatter apexes than the hot star bow shocks. We test several possible explanations for this difference (divergent ambient stream, low Mach number, observational biases, and influence of collimated jets), but the evidence for each is inconclusive., Comment: 21 pages, 16 figures. MNRAS submitted

El interés por la desigualdad económica ha aumentado como consecuencia de la crisis financiera de 2008. No obstante, no son muchos los estudios sobre este campo a muy largo plazo principalmente por la complejidad en cuanto a la obtención de fuentes. Este documento proporciona información sobre la desigualdad económica en la meseta norte castellana para la etapa preindustrial; trata de explicar su relación con el crecimiento económico del siglo XVI, con la larga etapa recesiva del XVII, así como sus posibles causas y consecuencias. Toda la información que sirve de base para este estudio procede de registros fiscales originales e inéditos, Interest over economic inequality has risen as a consequence of the 2008 financial crisis. Nevertheless, there are not so many study cases on this field that take into account the long term mainly due to the scarcity of sources. This working paper provides information about economic inequality in the Castile North “Meseta” during the preindustrial period; explaining its relation with the economic growth of the 1500´s, with the 1600´s long-lasting crisis and also the possible causes and consequences. All the information that serves as basis of this work comes from original and unpublished tax sources., Departamento de Fundamentos del Análisis Económico e Historia e Instituciones Económicas, Grado en Economía

Agradecimentos: The author's thanks to Mr. Paulo A. Baldasso for technical assistance, to Prof. Dr. Stephen Hyslop for reviewing and correcting the English language, and the Mass Spectrometry Laboratory at Brazilian Biosciences National Laboratory, CNPEM/ABTLUS, Campinas, Brazil, for its support with the MS analyses Abstract: A new weak hemorrhagic metalloproteinase named BtaMP-1 was purified from Bothriopsis taeniata snake venom by molecular exclusion followed by anion exchange chromatographies. This protein showed a molecular mass of 25,968.16 Da and is composed of 218 amino acid residues. The multiple alignments of its partial amino acid sequence showed high structural identity with other P-I class SVMP. BtaMP-1 showed caseinolytic activity that was enhanced by Ca2+ ion, completely inhibited by chelating and reducing agents and can be classified as an a-fibrinogenolytic enzyme. Locally, BtaMP-1 induces hemorrhage and edema, but not myotoxicity. These findings were confirmed by histological analysis of mouse gastrocnemius muscle. "In vitro" studies suggest that BtaMP-1 induce cytotoxicity in myoblast C2C12 but not in the myotubes cell line. BtaMP-1 induced systemic alterations in mice with one MHD and two hours exposure; histological analysis of lungs showed hemorrhagic areas, congestion, and increase the thickness of alveolar septum. Also, this protein induced mild effects on kidney and disruption of coagulation by depletion of fibrinogen plasma levels. This work provides insights into the importance of BtaMP-1 biological effects in envenomation by Bothropsis taeniata snake venom and providing further evidence to understand the role of P-I class SVMP in ophidian envenomation Fechado

Regular Finalizado FONDECYT-REGULAR FONDECYT FONDECYT

Dellingr, NASA Goddard Space Flight Center’s (GSFC) first 6U CubeSat, was deployed from the International Space Station (ISS) on November 20, 2017. The primary objective of the mission was to apply and appropriately tailor GSFC knowledge and capability to design and build a CubeSat that increased resiliency and capability, while containing costs. The Dellingr spacecraft is a mixture of COTS and in-house components and includes two science instruments – an advanced gated time-of-flight ion-neutral mass spectrometer (INMS) and a boom mounted fluxgate. While a traditional GSFC spacecraft approach includes detailed analysis, design, testing, and extensive reviews, the Dellingr team adopted a “build, test, fix” approach to identify and correct potential mission ending issues. Yet, despite extensive testing, Dellingr immediately experienced unexpected major anomalies once on orbit. Using a flatsat and the insight gained from extensive on-orbit engineering data, the team was able to alleviate some of these anomalies and recover some of the lost functionality. The extensive set of lessons-learned is driving changes to our systems architecture, flight software, and testing approaches, and has provided valuable insight into what is required to produce a NASA CubeSat science mission with a moderate assurance of mission success, while containing resource requirements.

Hydrothermal vent communities are distributed along mid-ocean spreading ridges as isolated patches. While distance is a key factor influencing connectivity among sites, habitat characteristics are also critical. The Pescadero Basin (PB) and Alarcón Rise (AR) vent fields, recently discovered in the southern Gulf of California, are bounded by previously known vent localities (e.g. Guaymas Basin and 21° N East Pacific Rise); yet, the newly discovered vents differ markedly in substrata and vent fluid attributes. Out of 116 macrofaunal species observed or collected, only three species are shared among all four vent fields, while 73 occur at only one locality. Foundation species at basalt-hosted sulfide chimneys on the AR differ from the functional equivalents inhabiting sediment-hosted carbonate chimneys in the PB, only 75 km away. The dominant species of symbiont-hosting tubeworms and clams, and peripheral suspension-feeding taxa, differ between the sites. Notably, the PB vents host a limited and specialized fauna in which 17 of 26 species are unknown at other regional vents and many are new species. Rare sightings and captured larvae of the 'missing' species revealed that dispersal limitation is not responsible for differences in community composition at the neighbouring vent localities. Instead, larval recruitment-limiting habitat suitability probably favours species differentially. As scenarios develop to design conservation strategies around mining of seafloor sulfide deposits, these results illustrate that models encompassing habitat characteristics are needed to predict metacommunity structure.

Balanced homodyning, heterodyning and unbalanced homodyning are the three well-known sampling techniques used in quantum optics to characterize all possible photonic sources in continuous-variable quantum information theory. We show that for all quantum states and all observable-parameter tomography schemes, which includes the reconstructions of arbitrary operator moments and phase-space quasi-distributions, localized sampling with unbalanced homodyning is always tomographically more powerful (gives more accurate estimators) than delocalized sampling with heterodyning. The latter is recently known to often give more accurate parameter reconstructions than conventional marginalized sampling with balanced homodyning. This result also holds for realistic photodetectors with subunit efficiency. With examples from first- through fourth-moment tomography, we demonstrate that unbalanced homodyning can outperform balanced homodyning when heterodyning fails to do so. This new benchmark takes us one step towards optimal continuous-variable tomography with conventional photodetectors and minimal experimental components., Comment: 9 pages, 4 figures

Supplementary figures and tables are provided

América Central es un territorio relativamente pequeño, conformado por 7 países cuya extensión total cubre un área de 498,533 km2. Por su tamaño, todo este territorio podría contar con una única normativa de diseño sísmico, que representara el esfuerzo individual que hoy se realiza en cada país, trabajando de manera conjunta. Un ejemplo de esfuerzo conjunto fue llevado a cabo entre los años 2007 y 2009 en donde expertos de la región trabajaron unidos bajo la dirección de la Profesora Belén Benito para la realización del Proyecto de Amenaza Sísmica de América Central (RESIS II), cuyos valiosos resultados han sido tomados como referencia para la realización de este trabajo. La amenaza presente en América Central es proporcionada para todos los países por fuentes sismogenéticas comunes, siendo las principales: La subducción de la Placa Tectónica de Coco por debajo de la Placa Tectónica Caribe, la Cadena Volcánica, así como por formaciones geológicas y fallamientos superficiales localizados de manera distribuida en cada territorio de la región. A pesar de su tamaño y la similitud sobre fuentes sismogenéticas, dentro de América Central existen diferencias en las normativas de diseño sísmico entre sus países, que resultan en divergencias significativas en las demandas de diseño de obras de infraestructura de un país a otro. Nicaragua y Costa Rica, ambos países de América Central, han sido históricamente afectados por terremotos muy destructivos que han ocasionado, en ambos países, grandes pérdidas humanas y económicas. Uno de los eventos sísmicos más marcados de la historia de Nicaragua fue el terremoto ocurrido en su capital Managua, la noche del 23 de diciembre del año 1972, borrando casi en toda su totalidad a la ciudad. En Costa Rica se destaca la ocurrencia del terremoto de Limón (zona caribeña de Costa Rica) en el año 1991 en donde la pérdida de obras de infraestructura generó un gran impacto en la economía del país. En este trabajo se realiza una comparación entre las normativas vigentes en Nicaragua y Costa Rica, ante los aspectos más influyentes en el cálculo de la demanda sísmica sobre las edificaciones, tales como: cargas inercialmente participativas, clasificación estructural según la importancia y ductilidad, clasificación de suelos y amenaza sísmica propiemaente dicha, con la respectiva elaboración de espectros de diseño sísmico. En el territorio nicaragüense, para un periodo de retorno de 500 años se identifican valores máximos de PGA en torno a 0.56 g, mientras en el territorio costarricense los valores más altos de PGA son levemente superiores a tal aceleración. A lo largo de su historia, Nicaragua ha contado con tres normativas sísmicas de diseño para edificaciones. La primera de ellas data del año 1973, la segunda de 1983 y la que actualmente está vigente fue elaborada en el año 2007. Transcurrieron 24 años desde la entrada en vigencia del pasado reglamento (RNC-83) para la elaboración y publicación del actual Reglamento Nacional de la Construcción RNC-07. Esta última normativa establece los requerimientos aplicables al diseño y construcción de nuevas edificaciones, así como la reparación y refuerzo de obras existentes, todo ello con los siguientes objetivos: - Evitar la pérdida de vidas y disminuir la posibilidad de daños físicos a personas. - Resistir seismos menores sin daños. - Resistir seismos moderados con daños estructurales leves y daños no estructurales moderados. - Evitar el colapso por efectos de seismos de gran intensidad, disminuyendo los daños a niveles económicamente admisibles. - Resistir efectos de vientos y otras acciones accidentales sin daños. En el territorio Nicaraguense se establecen, tres zonas con niveles de amenaza crecientes, para un periodo de retorno de 500 años. La zona A, situada hacia el caribe y parte norte del país, se caracteriza por tener un nivel de sismicidad relativamente bajo, con aceleración máxima del terreno (a0) igual a 0.1 g. La zona B se localiza en la zona central de Nicaragua y se caracteriza por presentar un nivel medio de sismicidad, en donde la aceleración máxima del terreno (a0) propuesta es igual a 0.2 g. Finalmente, la zona C, de alta sismicidad, situada en la costa pacífica del país, es influenciada por la actividad sísmica de subducción entre las placas tectónicas y la generada por el cordón volcánico presente en Nicaragua. Para esta última zona sísmica el RNC-07 propone una aceleración máxima de terreno (a0) igual a 0.3 g. Para considerar los efectos de amplificación sísmica debido a las condiciones locales el RNC-07 clasifica los suelos en cuatro tipos según la velocidad de onda de corte (Vs) que presenten. Considerando que en Nicaragua se establecen tres zonas sísmicas y tres categorías de suelos, así como cinco tipologías estructurales y cuatro factores modificadores por irregularidad; al combinar cada una de estas situaciones es posible generar 180 espectros de diseño con la misma forma espectral, de los cuales únicamente varían las amplitudes u ordenadas espectrales. Por su parte, Costa Rica a lo largo de su historia ha contado con cuatro normativas sísmicas de diseño para edificaciones. La primera de ellas fue elaborada en el año 1974, la segunda en 1986, la tercera en 2002 y finalmente la actualmente vigente fue elaborada en el año 2010. Cada una de las disposiciones contenidas en el Código Sísmico de Costa Rica 2010 es un requisito mínimo para lograr un adecuado desempeño ante los efectos sísmicos sobre las estructuras, en busca de los siguientes objetivos: - Proteger la vida humana y la integridad física de las personas. - Reducir los daños materiales y las pérdidas económicas ocasionadas por los seismos. - Minimizar el impacto social y económico ante terremotos. Los espectros de diseño sísmicos establecidos por el CSCR-10 dependen de la ubicación de la edificación dentro del mapa de zonificación sísmica de Costa Rica y del tipo de suelo donde se cimente la obra. La zonificación sísmica de Costa Rica propuesta está conformada por tres zonas sísmicas llamadas zonas II, III y IV, de orden creciente de amenaza, donde se establecen valores de aceleración pico efectiva (aef) en función de la zona y tipo de suelo donde se cimenta la edificación. El CSCR-10 establece factores espectrales dinámicos que son definidos para cada zona sísmica en los diferentes sitios de cimentación y para las distintas ductilidades globales. Por lo que, al establecerse en el CSCR-10 tres zonas sísmicas, cuatro tipos de suelos y cinco tipologías estructurales, resultan 72 combinaciones o posibles espectros para la determinación del factor espectral dinámico. Para determinar las variaciones (definidas en porcentaje) de los requerimientos plasmados en ambas normativas de diseño sísmico, ha sido necesario tomar una de ellas como base. Ambas normativas sísmicas de diseño exponen una filosofía y objetivos similares, principalmente orientados a la protección de la vida humana y reducción de daños materiales mediante un mejor desempeño estructural. Considerando que todos los requerimientos mínimos plasmados en ambas normativas conducen el cálculo estructural de una edificación al cumplimiento de objetivos, y al ser éstos muy similares entre sí, se facilita la comparación entre ambas regulaciones. Esta comparación y la determinación de la magnitud de las variaciones se realiza sobre los siguientes aspectos: - Sobrecargas de uso y participativas - Combinaciones de acciones - Clasificación estructural y factores influyentes en el cálculo de la acción sísmica - Espectros de diseño - Métodos de análisis - Límites de desplazamiento Del análisis de las comparaciones realizadas, se ha identificado que en las edificaciones de alta y mediana ocupación (tales como casas, apartamentos, hoteles, escuelas, universidades, hospitales, centros de salud, salas de archivo y lugares de espectáculo), las sobrecargas de uso mínimas establecidas por ambas normativas tienen valores idénticos. Sin embargo, las sobrecargas de uso participativas que actúan durante la acción sísmica, presentan valores extremadamente diferentes entre sí, encontrándose variaciones en la mayoría de los casos, superiores a 150% e incluso algunas veces mayores a 400%. Se han determiando grupos de combinaciones de acciones equivalentes, donde no existen diferencias entre ambas normativas de diseño. Sin embargo en otros se encuentran grandes discrepancias, del orden de -100% y 60%. Las mayores diferencias en estos últimos grupos radican principalmente en las acciones representadas por empujes laterales, las cuales no siempre son frecuentes en el diseño de edificaciones o bien no todos los elementos se ven afectados por tales acciones, mientras que para las acciones gravitacionales y sísmicas, que siempre están presentes, las diferencias son muy bajas. Tal como se indicó, el CSCR-10 establece para edificaciones de uso normal o especial un seismo fuerte con un periodo de retorno de 475 años, mientras que el RNC-07 define para estructuras de esta misma categoría un periodo de retorno de 500 años. Un periodo de retorno de 500 años, representa una sacudida sísmica ligeramente mayor que la correspondiente a un periodo retorno de 475 años. Conforme a las estimaciones realizadas, considerando el factor de importancia y la aceleración pico del suelo, se determina que la diferencia de considerar periodos de retorno de 475 años (punto de partida del CSCR-10) y 500 años (punto de partida del RNC-07) podría causar variaciones en la acción sísmica no mayores al 1.85%. La comparación entre estas dos normativas de diseño sísmico, en cuanto a las consideraciones de ductilidad e irregularidad, se realizó mediante la comparación de los correspondientes espectros de diseño. Se presenta en este proyecto una comparación a nivel de espectros elásticos (con factores modificadores de ductilidad e irregularidad iguales a uno), que son base para cualquier combinación posible. En Nicaragua, el Reglamento Nacional de la Construcción 2007 establece por separado los requerimientos de localización y tipo de suelo para la determinación de la amenaza sísmica, mientras que en Costa Rica, el Código Sísmico, toma ambos elementos de forma conjunta en un único parámetro. Por ello su comparación deberá realizarse considerando en ambas normativas el aporte conjunto de la localización y el tipo de suelo. Al comparar los mapas de amenaza sísmica de Nicaragua y Costa Rica, presentados en el Reglamento Nacional de la Construcción de Nicaragua y en el Código Sísmico de Costa Rica, resultan evidentes grandes discontinuidades en las zonificaciones sísmicas de ambos países, no existiendo una transición gradual a lo largo de la línea fronteriza y en las áreas aledañas. Ha sido necesario seleccionar las zonas sísmicas de Nicaragua y Costa Rica que presenten la mejor correspondencia, para proceder con ello a la realización de una comparación entre estas reglamentaciones en aspectos de localización y tipo de suelo. Esta selección de las zonas sísmicas con mejor correspondencia se ha realizado bajo el seguimiento de los siguientes aspectos: - Apreciación visual a nivel regional y a nivel de detalle de cada país de los resultados del estudio de Amenaza Sísmica en America Central (Benito et al , 2010) - Resultados de aceleración pico en roca obtenidos en el citado estudio en las capitales de ambos países: Managua y San José . - Valores de isoaceleraciones en roca obtenidas de cada país, usadas como información base para la definición de la zonificación sísmica planteada dentro de estas normativas de diseño. Cabe mencionar y destacar que las aceleraciones pico en roca para un periodo de retorno de 500 años presentadas por el estudio de la amenaza sísmica de América Central son 507 gal (0.516 g) para Managua y 513 gal (0.523 g) para San José, mientras que las obtenidas por medio de las isoaceleraciones en roca, presentadas como referencia para estas normativas, son 0.310 g y 0.375 g para Managua y San José respectivamente. Es notable una gran diferencia entre las aceleraciones pico en roca plasmadas por el estudio de la amenaza sísmica de América Central y las tomadas como base en estas dos normativas de diseño, presentado variaciones entre el 30% y 40%. Esto sugiere que es necesario realizar una cuidadosa revisión de las aceleraciones pico a considerar para la siguiente actualización de estas reglamentaciones. De los resultados comparativos obtenidos, se aprecia que para los grupos de zonas sísmicas correspondientes y para los tipos de suelo Tipo 1 (RNC-07) y S1 (CSCR-10), no existen diferencias entre ambas normativas de diseño. Sin embargo, en todos los demás tipos de suelos, si existen grandes discrepancias que van desde 36.4% hasta el 66.7%, siendo mayores las aceleraciones dadas por la normativa nicaragüense. Estas grandes variaciones se deben a que el Reglamento Nacional de la Construcción de Nicaragua expone valores de modificación para los suelos Tipo II y Tipo III muy superiores a los previstos implícitamente en el Código Sísmico de Costa Rica. Por otra parte, se ha realizado una comparación de los espectros elásticos de ambas normativas, resultando grandes diferencias, siendo notablemente mayores los de la normativa nicaragüense. Estas variaciones oscilan, en promedio, entre un 22% y 98% en edificaciones con periodos de vibración entre 0 y 2 segundos, las cuales son las más comunes en ambos países. Las diferencias se acortan para edificaciones más flexibles, con periodos de vibración mayores a 2 segundos, en donde las variaciones promedio se encuentran entre 10 y 35%. Con el propósito de lograr una comparación más detallada entre ambas normativas de diseño sísmico, se han elegido dos pares de sitios en donde se asume que se construirá una edificación típica con características idénticas en ambos países. Los sitios escogidos han sido los siguientes: - Sitios 1 y 2: Ubicados en San Carlos de Nicaragua (Sitio 1) y Río Frio de los Chiles de Costa Rica (Sitio 2). Estos sitios se caracterizan por estar situados en la Zonas B según el Reglamento Nacional de la Construcción (RNC-07) y la Zona II según el Código Sísmico de Costa Rica (CSCR-10) respectivamente. - Sitios 3 y 4: Ubicados en Peñas Blancas de Nicaragua (Sitio 3) y Peñas Blancas de Costa Rica (Sitio 4). Estos sitios se caracterizan por estar situados en la Zona C asignada por el Reglamento Nacional de la Construcción (RNC-07) y la Zona III asignada por el Código Sísmico de Costa Rica (CSCR-10), respectivamente. Estos pares de sitios seleccionados son de vital importancia para ambos países, ya que en éllos se ubican los dos únicos puestos fronterizos oficiales de tránsito de personas y de mercancías de comercialización. Ambos pares no sólo permiten el paso entre estos dos países, sino también entre toda la región de América Central. En cada sitio seleccionado se han hecho consideraciones de dos tipos de suelos soportantes diferentes, que corresponden a las clases II y III según el Reglamento Nacional de la Construcción (RNC-07) y sus equivalentes S2 y S3 según el Código Sísmico de Costa Rica (CSCR-10). El edificio cuya construcción se contempla tiene una estructura típica de 4 niveles de altura, conformado estructuralmente por pórticos de hormigón armado con cerramientos y divisiones internas de material liviano que no aportan resistencia lateral a la edificación. Para la determinación de las sobrecargas de uso y del nivel de importancia de la edificación se considera que esta estructura será utilizada como hotel, lo que significa una estructura de uso normal. Para fines de esta comparación, los parámetros evaluados y confrontados en cada sitio son las reacciones principales (acciones internas) sobre una serie de elementos estructurales seleccionados, donde estas reacciones resultan de la aplicación sobre toda la edificación de todas las acciones externas (acción permanente, sobrecargas de uso y la acción sísmica) y de su análisis dinámico en un modelo teórico estructural. De los resultados se observan variaciones en los valores promedio de diferentes parámetros, siendo siempre superiores los de las edificaciones calculadas con la normativa nicaraguense. Estas variaciones promedio son:  16% en la reacción axial en los pilares  entre 35% y 45% en el cortante en los pilares  entre 26% y 41% en el momento flector en los pilares.  entre 10% y 15 % en el cortante en las vigas  16% en el momento flector en las vigas. Es de destacar que las variaciones en las reacciones de cortante y momento flector en todos los pilares son muy superiores a las variaciones de estas mismas reacciones en los elementos tipo viga, debido a una mayor influencia de la acción sísmica sobre los pilares. De manera general, se ha determinado que entre estos dos países vecinos, que presentan niveles de amenaza muy similares debido a fuentes sismogenéticas comunes o de características similares, existen variaciones significativas en sus normativas de diseño sísmico, lo que justifica la necesidad de trabajar en un código sísmico regional que dé solución a todas las discrepancias presentes entre las normativas existentes en los países de Centroamérica.

Optical beams with topological singularities have a Schmidt decomposition. Hence, they display features typically associated with bipartite quantum systems; in particular, these classical beams can exhibit entanglement. This classical entanglement can be quantified by a Bell inequality formulated in terms of Wigner functions. We experimentally demonstrate the violation of this inequality for Laguerre-Gauss (LG) beams and confirm that the violation increases with increasing orbital angular momentum. Our measurements yield negativity of the Wigner function at the origin for $\LG_{10}$ beams, whereas for $\LG_{20}$ we always get a positive value., Comment: 6 pages, 4 eps-color figures. Comments welcome!

The complex reflected and transmitted amplitudes from a Fabry-Perot interferometer are analyzed using a phase-space approach, in which the real and imaginary parts of those amplitudes are taken as basic variables. As functions of the optical path length of the cavity, the reflected amplitude describes a circle, whereas the transmitted is given by a hippopede. The system performance can be directly related to the geometrical parameters of these curves., Comment: Comments welcome!

Agradecimentos: This research was financially supported by 'Secretaría General de Ciencia y Tecnica, Universidad Nacional del Nordeste' SGCyT, UNNE (P.I. B013-2010) and 'Agencia de Promocion Cient ífica y Tecnologica ', FonCyT (PICTO 2007- 00143). The authors are grateful to Lic. Laura Rey from 'Centro de Produccion de Sueros Antiof ídicos' (CEPSAN; Corrientes, Argentina) for providing venoms from Bothrops alternatus species and to M.V. Holovate, R. for experimental help. María Emilia Garcia Denegri is the recipient of a postdoctoral fellowship from 'Consejo Nacional de Investigaciones Científicas y Tecnicas (CONICET) ', Argentina Abstract: Basic phospholipases A2 (PLA2) are toxic and induce a wide spectrum of pharmacological effects, although the acidic enzyme types are not lethal or cause low lethality. Therefore, it is challenging to elucidate the mechanism of action of acidic phospholipases. This study used the acidic non-toxic Ba SpII RP4 PLA2 from Bothrops alternatus as an antigen to develop anti-PLA2 IgG antibodies in rabbits and used in vivo assays to examine the changes in crude venom when pre-incubated with these antibodies. Using Ouchterlony and western blot analyses on B. alternatus venom, we examined the specificity and sensitivity of phospholipase A2 recognition by the specific antibodies (anti-PLA2 IgG). Neutralisation assays using a non-toxic PLA2 antigen revealed unexpected results. The (indirect) haemolytic activity of whole venom was completely inhibited, and all catalytically active phospholipases A2 were blocked. Myotoxicity and lethality were reduced when the crude venom was pre-incubated with anti-PLA2 immunoglobulins. CK levels in the skeletal muscle were significantly reduced at 6 h, and the muscular damage was more significant at this time-point compared to 3 and 12 h. When four times the LD50 was used (224 µg), half the animals treated with the venom-anti PLA2 IgG mixture survived after 48 h. All assays performed with the specific antibodies revealed that Ba SpII RP4 PLA2 had a synergistic effect on whole-venom toxicity. IgG antibodies against the venom of the Argentinean species B. alternatus represent a valuable tool for elucidation of the roles of acidic PLA2 that appear to have purely digestive roles and for further studies on immunotherapy and snake envenoming in affected areas in Argentina and Brazil Fechado

A través de la obra de Aristóteles, en especial la Constitución de Atenas y la Política, podemos hacernos una imagen no demasiado habitual de la democracia ateniense. Esta aparece como un modelo jurídico-político, que aún hoy puede dar que pensar: como una «utopía real». En concreto, nos interesan dos aspectos: la justicia tributaria y la justicia social. Ambas justicias tienen en la democracia ateniense, y en la visión de Aristóteles, un notabilísimo desarrollo. Por eso, hablamos de «fragmentos» de una utopía real. Abstract: Aristotle’s work, especially, in The Constitution of the Athenians and the Politics, sheds light on what we can see as an uncommon view of Athenian democracy. Such model of democracy appears as a juridico political one which can still be regarded as food for thought, and can be aptly described as a «true utopia». Two points are particularly interesting for this approach: financial justice and social justice. Both justices are significantly developed both in Athenian democracy and in Aristotle’s approach. For this reason I will describe them as «fragments» of a true utopia

Orientador : José Antonio Perez Gediel Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Jurídicas, Programa de Pós-Graduação em Direito. Defesa: Curitiba, 29 de fevereiro de 2008. Inclui bibliografia e notas

Gammaropsis (Podoceropsis) grasslei new species Figs. 1���4 Material examined. Holotype: one male specimen deposited in the Crustacean Collection of the Institute of Biology, UNAM cat. no.CNCR- 24664, DSRV ALVIN 3207 -(2)- 7. Allotype: DSRV ALVIN 3207 (2) 9. Specimens sent to the U.S. Museum of Natural History, Smithsonian Institution Wash. D.C. Type locality. Guaymas Basin, Gulf of California, 27 �� 00.679���N 111 �� 24.413 ���W at a depth between 2000��� 2100 m near the site known as Rebeccas���s Roost, DSRV ALVIN dive 3208. Six amphipod epibionts obtained from the lithodid crab Neolithodes diomedeae collected on May 1, 1998. Diagnosis- Head without rostrum, ocular lobes pointed, eyes not distinctly present. Antennae subequal and slender, shorter than half body length, a longer palm in the second gnathopod of male and dense ornamentation in maxillas. Telson entire and fleshy, with a group of annulate setae and spines on both posterolateral inner borders (Fig. 1). Description. �� 9.7 mm. Head without rostrum, ocular lobes pointed, eye bright white diffuse in lateral lobes mass pigment observed on fresh specimens under light microscope, in preserved organisms, eye mass under cephalic cuticle seems absent. Antenna 1, peduncle longer than flagellum, article 1 shorter than 2 and 3, posterior margin setose bearing bundles of aesthetascs at article joints, accessory flagellum scale-like. Flagellum, 13 articulate. Antenna 2 nearly equal to antenna 1, peduncle longer that its flagellum, article 3 shorter that 4 and 5, posterior margin of antenna 2 less setose than that of antenna 1, calceoli absent. Flagellum, 11 articulate. Mandibles normal, molar and raker spines conical, accessory plumose setae, palp moderately stout, three articulate, article 3 clavate, ventral margin setose, setae plumose. Rigth mandible with a molar flake represented by three strong serrate setae and a few plumose setae (Fig. 2). Lower lip shoulders well developed and with small setae, inner lobes evident with setae, mandibular process pointed (Fig. 2). Maxilla 1 palp two articulate, second article rounded with strong apical spines; outer plate quadrate with nine spines, inner plate triangular, with one apical spine and one long plumose seta plus cluster of additional setae. Maxilla 2 outer plate broader than inner plate. Outer plate bearing slightly longer plumose setae on its apical border. Inner plate with a facial row of 13 annulate setae without setules along its distal end (Fig. 2). F 1. Gamaropsis (Podoceropsis) grasslei Soto & Corona n. sp. (��), 9.7 mm, Guaymas Basin, Gulf of California. Lateral view of entire body. Mouth parts and gills not shown. Scale bar = 1 mm Maxilliped palp with 4 articles, articles 2���4 with long annulate setae (some with setules) mostly distributed along inner margin, article 2 longest, dactyl normal. Outer plate with a series of strong marginal spines progressively diminishing in size towards inner end, inner plate with marginal setae and 3���7 apical spines (Fig. 2). Coxal plates normally overlapping, of medium length, rounded and uniform, coxa 1 small in contrast with coxa 2���4, coxa 4 excavate posteriorly, coxa 5 bilobed, coxae 6���7 smaller than anterior coxae. Oostegites not conspicuous in female specimens. Gnathopod 1 subchelate, posterior margin setose, article 2 of male gnathopod not dilated, article 6 shorter than 5, inner margin of dactyl serrated. Gnathopod 2 subchelate, weakly setose, enlarged and stronger than gnathopod 1, coxal plate large and oval, article 2 with antero distal border weakly dilated, article 6 much longer than 5, palm long with a distal platform and a small finger, its inner border finely serrated; dactyl long, inner margin bearing a row of small spines (Fig. 3). Pereopods 3���4 normal, smaller that gnathopods, slender. Setation is sparse along lateral margins but denser at the points of articulations; 2 article narrow, slightly longer than article 4, borders straight; article 4 weakly dilated, 5 article small and laterally compressed; articles 5 and 6 no longer than 4, dactyls short, sharp curved backwards. Pereopods 5���7, pereopod 5 shorter than 6���7, posterior margin of basis bilobed, anterior margin with two spines, dactyl turned backwards to facilitate attachment to host setae; pereopods 6���7 similar with basis expanded, outer surface weakly setose and slightly concave, lateral margins of article 4 straight, distally expanding, shorter than articles 5 and 6; dactyls sharp curved forwards. F 2. Gamaropsis (Podoceropsis) grasslei Soto & Corona n. sp. Mouth parts. Labrum (L). Left (LFT Md) and right (RT Md) Mandibles. Maxilla 1 (Mx 1), Maxilla 2 (Mx 2), Maxilliped (Mxpd). Scale bar = 1mm Epimeral plates, dorsal margin of pleonites 1���3 scarcely bicarinate, posterior margin weakly setose; epimeral plate 1 half-size plates 2 and 3, its distal end acuminate; epimeral plates 2���3 lateral margins slightly sinuous and distal ends amply rounded, epimeral plate 2 overlapping plate 3 (Fig. 4). Pleopods 1���3 normal, peduncle 1 and 2 subequal, 3 shorter; retinaculae absent; both rami fringed with long plumose setae. Urosome: urosomite 1 scarcely bicarinate, urosomites 2���3 smooth, urosomite 2 with one pair of setae on mid-dorsal distal margin. Uropod 1 normal, stout biramous, peduncle longer than ramus, with an inter-ramal spine, ramus subequal. Uropod 2 normal, stout, biramous, peduncle subequal to inner ramus, which is slightly longer than outer ramus (Fig. 4). Uropod 3 normal, stout, biramous, peduncle subequal to outer ramus, inner ramus shorter than outer ramus, inner ramus with three marginal spines and one terminal spine, outer ramus with two spines on midlength and two terminal spines and plumose long setae. Telson fleshy and entire, apically pointed bearing a dorso-lateral facial group of four long annulate setae and small 4���5 small rounded spine-like structures (Fig. 4). Female. Smaller than male, body and appendages less setose. Gnathopods small, gnathopod 2 larger than 1, subchelate, article 6 nearly 2 x longer than 5; article 5 triangular in shape, palm without platform or finger but indented, dactyl half the length of palm (Fig. 3). F 3. Gamaropsis (Podoceropsis) grasslei Soto & Corona n. sp. Gnathopods 1���2 (G 1���2 �� ��). F 4. Gamaropsis (Podoceropsis) grasslei Soto & Corona n. sp. Epimeral plates (Pl), Uropods 1���3 (U), Telson (T). Scale bar = 1mm. Etymology. The new species is named to honor J.F. Grassle, pioneer scientist in the ecological study of deep hydrothermal systems. He laid the foundation and promoted the interdisciplinary exploration of Guaymas Basin, in the Gulf of California. Habitat. The deep-sea hydrothermal system located in the Southern Trough of the Guaymas Basin 27 �� N, 111.5 �� W, located in the central portion of the Gulf of California. This unique sedimentary environment supports a complex deep-sea ecosystem essentially driven by sulfur-based chemosynthesis. Taxonomic commentary. Gammaropsis (Podoceropsis) grasslei differs from other Gammaropsis by having a longer palm in the male second gnathopod, a highly ornamented entired and fleshy telson, and densely ornamented maxillas. The new species exhibits white bright diffuse eyes while those of other members of the subgenus Gammaropsis (Podoceropsis) are either faceted and unpigmented as is the case of G. (P.) ocellata Conlan and G. (P.) angulosa (Chevreux) or simply remain unpigmented as in G. (P.) kermadeci Stebbing. The body of Gammaropsis (Podoceropsis) grasslei is smooth and laterally compressed, with epimeral plates and urosomite 1 scarcely bicarinate, while that of Gammaropsis (Podoceropsis) kermadeci is dorsally setose. The new species here described differs from Gammaropsis (Podoceropsis) ocellata in having a gnathopod 2 of male with propodus devoid of protuberance near dactyl and no spine in palmar corner. Gammaropsis (Podoceropsis) miri Vinogradov, represents a blind species that closely resembles Gammaropsis (Podoceropsis) grasslei but both can be separated by mouth parts and telson characters. Spines on 3 rd article of mandible are fine and long in G. (P.) m i r i while in the new species plumose setae predominate. Pereopods 3 and 4 are long and fine in G. (P.) m i r i but in G. (P.) grasslei these are normal and fine. In G. (P.) m i r i the telson is small and rounded bearing two pairs of subapical setae. In G. (P.) grasslei the telson is fleshy, entire and armed with long setae and spine-like structures. Rami of uropod 3 is stout armed with spines in G. (P.) grasslei and in G. (P.) miri they are long and thin., Published as part of Soto, Luis A. & Corona, Adriana, 2007, Gammaropsis (Podoceropsis) grasslei (Amphipoda: Photidae) a new species of commensal amphipod of the deep-water lithodid Neolithodes diomedeae from the Guaymas Basin, Gulf of California, pp. 33-39 in Zootaxa 1406 on pages 34-38, DOI: 10.5281/zenodo.175510

Se reportan en este artículo los primeros resultados de una investigación en curso sobre algunas dificultades de aprendizaje relacionadas con el concepto de función lineal. La investigación está basada en los aportes teóricos de R. Duval sobre registros de representación semiótica y tiene dos propósitos: se trata de detectar las dificultades enfrentadas por los estudiantes para transformar una representación en otra (de una función lineal) y además diseñar una serie actividades didácticas que les ayuden a superar las dificultades detectadas. Los resultados reportados aquí provienen de la aplicación de un cuestionario a nueve estudiantes de segundo semestre de licenciatura del área económico administrativa. Se expone el cuestionario aplicado, las respuestas de los estudiantes y se analizan estas respuestas a la luz de la teoría de Duval.

El presente trabajo examina las propuestas de Castelao, político y pensador gallego (1886-1950), acerca de la relación entre Galicia, España y Europa. Exactamente, mostramos cómo vincula las tres cuestiones y procesos políticos siguientes: la autonomía de Galicia, la federación de España y la Unión de Europa. A nuestro entender, su aportación representa una exitosa combinación de liberalismo, republicanismo y federalismo.

A 109/086(17)

A 109/086(19)

The transition taking place between two metastable phases in 2-O-adamantane, namely the [Formula: see text] cubic, rotator phase and the lower temperature P21/c, Z = 4 substitutionally disordered crystal is studied by means of muon spin rotation and relaxation techniques. Measurements carried out under zero, weak transverse and longitudinal fields reveal a temperature dependence of the relaxation parameters strikingly similar to those exhibited by structural glass[Formula: see text]liquid transitions (Bermejo et al 2004 Phys. Rev. B 70 214202; Cabrillo et al 2003 Phys. Rev. B 67 184201). The observed behaviour manifests itself as a square root singularity in the relaxation rates pointing towards some critical temperature which for amorphous systems is located some tens of degrees above that shown as the characteristic transition temperature if studied by thermodynamic means. The implications of such findings in the context of current theoretical approaches concerning the canonical liquid-glass transition are discussed.

All Supplemental figures, tables, and references therein

All Supplemental figures, tables, and references therein

Participants in three international cohort studies on mechanical ventilation (1998, 2004 and 2010). National coordinators recruited local investigators from eligible intensive care units. The research ethics board of each participating institution approved the protocol and need for informed consent was according to local rules.

The dynamics of the pure compounds and mixed crystals formed between cycloheptanol (cC7-ol) and cyclooctanol (cC8-ol) has been studied by means of broadband dielectric spectroscopy at temperatures near and above the orientational glass transition temperature. Both compounds are known to display at least one orientationally disordered (OD) phase of simple cubic symmetry, and within this phase, a continuous formation of mixed crystals was demonstrated in the past (Rute, M. A. et al. J. Phys. Chem. B 2003, 107, 5914). The dielectric loss spectra of cC7-ol and cC8-ol show, in addition to the well-pronounced α-relaxation peaks with a continuous temperature shift (characteristic of the freezing of the molecular dynamics), secondary relaxations ( β and γ for cC8-ol and γ for cC7-ol) which are intramolecular in nature. The dynamics of several OD mixed crystals was recently studied (Singh, L. P.; Murthy, S. S. N. J. Phys. Chem. B 2008, 112, 2606), and surprisingly enough one of the secondary relaxations was not evidenced. We show here by means of a careful set of measurements for several mixed crystals and of a detailed analysis procedure the existence of the secondary relaxations for the mixed crystals. The results, moreover, doubtless reinforce the physical origin of each of the secondary relaxations.

Participants in three international cohort studies on mechanical ventilation (1998, 2004 and 2010). National coordinators recruited local investigators from eligible intensive care units. The research ethics board of each participating institution approved the protocol and need for informed consent was according to local rules.

Orientadores: Sergio Marangoni, Luis Alberto Ponce Soto Dissertação ( mestrado) - Universidade Estadual de Campinas, Instituto de Biologia Resumo: Os venenos de serpentes contêm uma variedade de proteínas que são estudadas no mundo pela importância biológica e farmacológica. Dentro de sua complexa composição, o veneno apresenta enzimas proteases, como as metaloproteases e serinoproteases que estão envolvidas em distúrbios hemostáticos e coagulantes, interferindo na agregação plaquetária. O presente trabalho teve como objetivo purificar, caracterizar bioquimicamente e avaliar as atividades farmacológicas de uma serinoprotease com atividade coagulante, do veneno de Bothrops barnetti nomeada TLBbar. A purificação envolveu dois passos cromatográficos, exclusão molecular em Sephadex G-75 e HPLC de fase reversa em coluna analítica Supelco C8, obtendo-se um alto grau de pureza e homogeneidade, revelado com SDSPAGE e com Mr ~ 28,5 kDa. TLBbar mostrou homlogia sequêncial com outras serinoproteases de veneno de serpentes, evidenciado através de espectrometria de massas MS/MS, como a trombina-like denominada Calobin, isolada e caracterizada a partir de Agkistrodon caliginosus (Korean Viper), Crotalase (Crotalus adamanteus), flavoxobin (Trimeresurus flavoviridis) entre outras. Observa-se na homologia que as serinoproteases, com as quais foi comparada a TLBbar, apresentam os aminoácidos conservados do sítio catalítico (His57, Asp102, Ser195), já na sequencia da TLBbar demonstra-se a presença do aminoácido histidina na posição 57 da tríada catalítica. Este resultado em conjunto com as atividades enzimáticas e biológicas, confirmam que TLBbar pertence ao grupo de enzimas serinoproteases com atividade trombina-like. A enzima apresenta sua maior atividade proteolítica a 37oC e em pH 8, sendo essa alterada na presença de íons divalentes por interações eletrostáticas entre enzima e substrato. TLBbar apresenta um comportamento michaeliano segundo os estudos cinéticos realizados com o substrato BApNA, revelando um Vmax e Km de 0,42nmol/min e 0,433mM, respectivamente. Em presença de heparina mantem 80% de sua atividade, e apresenta relativa estabilidade frente a SBT-I e agentes quelantes como EDTA e EGTA. TLBbar tem atividade coagulante sobre fibrinogênio bovino (atividade fibrigenolítica), formando um coágulo semi-rígido, pois não ativa o fator XIII da cascata de coagulação como faz a trombina que resulta na formação de um coágulo consistente. Sua atividade fibrigenolítica foi evidenciada pela liberação dos fibrinopeptídios A, pela degradação da cadeia A? do fibrinogênio, a qual foi inibida por PMSF e Leupeptina, confirmando sua classificação no grupo das serinoproteases. A eficiência desta atividade fibrigenolítica foi observada entre 30 oC e 40oC durante 2 horas de incubação e alterada em presença de íons divalentes como cálcio, magnésio e bário, ressaltando a maior atividade fibrigenolítica com o cálcio. A enzima purificada TLBbar foi capaz de agregar plaquetas e em concentração de 2,5?g evidenciou comportamento semelhante à trombina. Interessante que TLBbar estimula a agregação plaquetária assim como também retarda dita atividade no tempo quando comparado com o controle (trombina). Este fato é devido a sua mudança de conformação estrutural que corresponde à ativação plaquetaria a qual ocorre com mais lentidão (nos primeiros minutos), em comparação a transformação causada pela trombina, tendo como conseqüência a liberação mais lenta de agentes como ADP e tromboxanos A2, necessários para alcançar a adesão plaquetária. A serinoprotease TLBbar não apresenta toxicidade, pois não possui atividades edematogênica, hemorrágica e miotóxica in vivo. Por outro lado, TLBbar evidencia capacidade de dissolver o coágulo de fibrina gerado pela trombina após 36 horas de incubação a 37oC, esta atividade foi inibida com PMSF nas mesmas condições, estes dados sugerem a presença de atividade fibrinolítica Abstract: The snake venoms contain variety of proteins and are studied in the world for biological and pharmacological importance, within their complex composition of the venom protease enzymes present, as metalloproteases and serineproteases that cause hemostatic disorders, coagulantes and platelet aggregation. The present dissertation aimed to purify, biochemically characterize and evaluate the pharmacological activities of a serine protease with coagulant activity named TLBbar from Bothrops barnetti. Its purification involved two chromatographic steps, molecular exclusion in Sephadex G-75 and reversedphase HPLC with a Supelco C8 analytical column, obtaining high purity and homogeneity revealed by SDS-PAGE with Mr ~ 28.5 kDa. The enzyme has its highest proteolytic activity at 37 °C and at pH 8, which is altered in the presence of divalent ions by electrostatic interactions between enzyme and substrate. TLBbar presents a Michaelis-Menten behavior according the kinetic studies revealing a Km and Vmax of 0.433 mM and 0.42 nmol/min, respectively. TLBbar in the presence of heparin maintains its activity around 80%, although has relative stability compared with SBT-I and chelating agents such as EDTA and EGTA. TLBbar has coagulant activity on bovine fibrinogen, forming a clot semi-rigid, different the action of thrombin that results in the formation of a clot consistent. Its fibrigenolytic activity was evidenced by the release of fibrinopeptides A, by degradation of fibrinogen A? chain, which was inhibited by PMSF and Leupeptin, confirming its classification in the group of serineproteases. The efficiency of this activity was observed between 30 and 40 °C during 2 hours of incubation and changed in the presence of divalents ions such as calcium, magnesium and barium, brings out the greatest fibrigenolytic activity with calcium. The purified enzyme TLBbar was capable of aggregating platelets; 2.5?g of concentration evidence similar behavior to thrombin, TLBbar interesting stimulates platelet aggregation as well as delay time in such activity when compared with control (thrombin). We suggest that structural process of platelet activation occurs over a longer period of time with TLBbar as a result of release of ADP and thromboxane A2 agents that happen that occur with less speed to achieve platelet adhesion compared with thrombin. This enzyme not showed edematogenic-activity when compared with the activity caused by B. Barnetti snake venom, did not induce hemorrhagic nor myotoxic effect in vivo. On the other hand, TLBbar had proteolytic activity similar to thrombin, proven in the fibrigenolytic activity on bovine fibrinogen as measured in the release of fibrinopeptides in times of release similar to the control, the proteolytic activity was also evidenced by the ability to dissolve fibrin clot generated by Thrombin after 36 hours of incubation at 37 °C, the activity was inhibited with PMSF under the same conditions, these data suggest the presence of fibrinolytic activity Mestrado Bioquímica Mestre em Biologia Funcional e Molecular

Orientadores: Sergio Marangoni, Luis Alberto Ponce Soto Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia Resumo: Uma grande variedade de toxinas provenientes de venenos animais tem sido largamente utilizada no estudo de mecanismos de ação e processos fisiológicos, sendo consideradas valiosas ferramentas moleculares. As serpentes peçonhentas expressam no veneno diversas proteínas muito estudadas e utilizadas clinicamente, apresentando diferentes graus de variabilidade inter e intraespecífica em suas composições e nos seus efeitos biológicos. O conhecimento obtido com os estudos destas moléculas tem grande importância clínica na compreensão dos processos fisiopatológicos envolvidos nos envenenamentos ofidicos e também acadêmico-tecnológica, devido à possibilidade do desenvolvimento de novos instrumentos moleculares utilizados na pesquisa e também de novos modelos moleculares para princípios ativos de drogas. Neste trabalho pesquisamos as atividades neurotóxica, miotóxica e inflamatória de uma PLA2 básica, D49, purificada do veneno da serpente Bothrops roedingeri após duas etapas cromatográficas, exclusão molecular em Sephadex G-75 e hidrofobicidade em HPLC de fase reversa em coluna 'mi'-Bondapak C-18. A BrTX-I apresentou massa molecular relativa em tomo de ~14 kDa (SDS-PAGE) e confirmada por espectrometria de massas (ESI-MS), em 14.358,69 Da. A análise da composição de aminoácidos da BrTX-I, revelou que esta é constituída aproximadamente por 120 resíduos aminoacídicos, com alto conteúdo de aminoácidos básicos e hidrofóbicos, resultando em um valor calculado de pI de 8,63. A presença de 14 resíduos de cisteína sugere a formação de sete pontes dissulfeto. A análise estrutural da BrTX-I foi realizada por ESI-MS e as regiões analisadas mostraram semelhança com outras PLA2 miotóxicas isoladas de venenos botrópicos. A BrTX-I apresentou alta atividade PLA2 e um comportamento tipo sigmoidal em baixas concentrações do substrato. Atividade PLA2 ótima da BrTX-I foi em pH 8,0 e temperatura de 37°C. A BrTX-I mostrou-se dependente de Ca2+ (mM) e na sua substituição por zn+2, Mn+2, Mg+2 e Cd+2 a atividade foi reduzida. O estudo da homologia sequencial da BrTX-I mostrou posições extremamente conservadas na molécula. Nas posições 1 e 2 há predominância da sequência de aminoácidos (DL), na posição 4 (Q). Uma das regiões altamente conservadas na sequência de aminoácidos das PLA2 é a alça de ligação ao cálcio, segmento ...YGCYCGXGG. Resíduos formando a alça de ligação ao cálcio e a rede catalítica da BrTX-I mostraram um alto grau de conservação, refletindo na manutenção da atividade. A região relacionada à atividade neurotóxica pré-sináptica (80-11 O) apresentou principalmente resíduos hidrofóbicos. Em preparações ex vivo, o veneno e a BrTX-I causaram rápido bloqueio da neurotransmissão na preparação biventer cervicis de pintainho de modo similar a outras Bothrops, sem alterar significativamente as respostas contraturantes à adição de AChe de KCl (5 e 20 'mi'g/mL), indicando atividade neurotóxica pré-sináptica. Em camundongos, a BrTX-I induziu miotoxicidade local, determinada pelo aumento nos níveis plasmáticos de CK e mostrou efeito pró-inflamatório analisado através da formação do edema de pata e liberação das citocinas IL-1 , IL-6 e TNF-'alfa'. Como BrTX-I produz um efeito inflamatório, a hidrólise de fosfolipídios pode ser relevante na fisiopatología do envenenamento Abstract: A great variety of animal venom toxins has been widely used in the study of action mechanisms and metabolic processes, thus considered valuable molecular tools. Poisonous snakes contains in their venom several well studied and clinically used proteins, showing these venoms different intra or interspecific variability degrees in their composition and biological effects. The knowledge obtained with these molecules study, has a great clinical relevancy understanding pathophysiological process regarding snake envenomations, and also academic technological, due to the possibility to develop new molecular tools and new molecular models to study active principies of some drugs. ln this work, we study neurotoxic, myotoxic and inflammatory activities of BrTX-I, a basic PLA2, purified from Bothrops roendigeri snake venom after two chromatographic steps, using molecular exclusion chromatography (Sephadex G-75) and reverse phase HPLC on 'mi'-Bondapak C-18 column. BrTX-I showed relative molecular mass around 14 kDa (PAGE) and specific molecular mass of 14,358.69 Da was determined by ESl-MS mass spectrometry. The amino acid composition analysis showed that BrTX-I contains 120 aminoacidic residues with high content of basic and hydrophobic amino acids, resulting in a calculated pi value of 8. 63. The presence of 14 Cysteine residues, suggests the formation of seven dissulfide bonds. Structural analysis of BrTX-I PLA2, performed by ESI-MS showed high identity values when compared to other myotoxic PLA2, isolated from Bothrops snakes venoms. BrTX-I presented high PLA2 activity and showed a sigmoidal behavior at low substrate concentrations. The BrTX-I reached its maximal PLA2 activity at pH 8.0 and 37 °C. Maximum PLA2 activity required Ca2+ (mM) and substitution of Ca2+ by zn+2, Mn+2, Mg+2 or Cd+2 showed reduced enzymatic activity. Sequence homology studies of BrTX-I showed extremely conserved positions in the molecule. ln positions 1 and 2, there is a predominance of the amino acids sequence (DL), and in position 4 (Q). One of the highly conserved regions in the amino acid sequences of PLA2 is the Ca2+ -binding loop, segment ... YGCYCGXGG. Residues forming the Ca2+-binding loop and the catalytic network of BrTX-I PLA2 showed a high conservation grade, reflecting the non-decreased catalytic activity. The region related to the presynaptic neurotoxic activity (80-110), showed mainly the presence of hydrophobic residues. ln ex vivo studies, the whole venom and BrTX-I caused a fast blockade of the neuromuscular transmission in young chick biventer cervicis preparations m a similar way to other Bothrops species, without alters significantly the contractures induced by ACh and KCL at doses of 5 and 20 'mi'g/mL, respectively, indicating presynaptic neurotoxic activity. ln mice, BrTX-I induced local myotoxicity, determined by increase in CK serum leveis, and showed proinflammatory effects analyzed through edema-forming activity and citokines IL-1 , IL-6, and TNF'alpha' release. Once BrTX-I induces a strong pro-inflammatory effect, the enzymatic phospholipid hydrolysis may be relevant for envenomation pathophysiology Doutorado Bioquímica Doutor em Biologia Funcional e Molecular