The FXII c.-4T > C Polymorphism as a Disease Modifier in Patients With Hereditary Angioedema Due to the FXII p.Thr328Lys Variant

Background: Hereditary angioedema due to the Thr328Lys variant in the coagulation factor XII (HAE-FXII) affects mainly women in whom the symptomatology is dependent on high estrogen levels. Clinical variability and incomplete penetrance are challenging features that hinder the diagnosis and management of HAE-FXII. The c.-4T>C Kozak polymorphism is the only common variation accounting for FXII plasma levels and was previously shown to modify the course of HAE due to C1-Inhibitor deficiency. Objectives: To assess the influence of the c.-4T>C polymorphism on disease expression in 39 Spanish HAE-FXII index patients. Methods: The c.-4T>C polymorphism was sequenced by the standard Sanger method, and HAE severity was calculated according to the score by Cumming et al. (2003) The activation of the contact system was quantified by the kallikrein-like activity of plasma in chromogenic assays upon activation with high-molecular-weight dextran sulfate. Results: The c.-4CC genotype was overrepresented in the studied cohort: 82% were CC-homozygous (expected frequency = 59%) and 18% were CT-heterozygous (expected frequency = 39%) (p = 0.001). Patients with a c.-4CC genotype exhibited higher kallikrein-like activity (0.9659 +/- 0.1136) than those with a c.-4TC genotype (0.7645 +/- 0.1235) (p = 0.024) or healthy donors. Moreover, the polymorphism influenced HAE-FXII severity score (c.-4CC = 4.43 +/- 2.28 vs c.-4TC = 2.0 +/- 1.15; p = 0.006) but not the degree of estrogen dependence or time until remission. Conclusion: The c.-4T>C polymorphism is overrepresented in a Spanish HAE-FXII cohort and significantly influences the degree of contact system activation and the clinical severity of the disease

The Effect of Pre-Main Sequence Stars on Star Cluster Dynamics

We investigate the effects of the addition of pre-main sequence evolution to star cluster simulations. We allowed stars to follow pre-main sequence tracks that begin at the deuterium burning birthline and end at the zero age main sequence. We compared our simulations to ones in which the stars began their lives at the zero age main sequence, and also investigated the effects of particular choices for initial binary orbital parameters. We find that the inclusion of the pre-main sequence phase results in a slightly higher core concentration, lower binary fraction, and fewer hard binary systems. In general, the global properties of star clusters remain almost unchanged, but the properties of the binary star population in the cluster can be dramatically modified by the correct treatment of the pre-main sequence stage.Comment: 40 pages ApJ preprint style Accepted by Ap

Topological phases from higher gauge symmetry in 3+1 dimensions

We propose an exactly solvable Hamiltonian for topological phases in 3 + 1 dimensions utilizing ideas from higher lattice gauge theory, where the gauge symmetry is given by a finite 2-group. We explicitly show that the model is a Hamiltonian realization of Yetter's homotopy 2-type topological quantum field theory whereby the ground-state projector of the model defined on the manifold M 3 is given by the partition function of the underlying topological quantum field theory for M 3 × [ 0 , 1 ] . We show that this result holds in any dimension and illustrate it by computing the ground state degeneracy for a selection of spatial manifolds and 2-groups. As an application we show that a subset of our model is dual to a class of Abelian Walker-Wang models describing 3 + 1 dimensional topological insulators

Proteomic analysis of Chromobacterium violaceum and its adaptability to stress

Chromobacterium violaceum (C. violaceum) occurs abundantly in a variety of ecosystems, including ecosystems that place the bacterium under stress. This study assessed the adaptability of C. violaceum by submitting it to nutritional and pH stresses and then analyzing protein expression using bi-dimensional electrophoresis (2-DE) and Maldi mass spectrometry. Chromobacterium violaceum grew best in pH neutral, nutrient-rich medium (reference conditions); however, the total protein mass recovered from stressed bacteria cultures was always higher than the total protein mass recovered from our reference culture. The diversity of proteins expressed (repressed by the number of identifiable 2-DE spots) was seen to be highest in the reference cultures, suggesting that stress reduces the overall range of proteins expressed by C. violaceum. Database comparisons allowed 43 of the 55 spots subjected to Maldi mass spectrometry to be characterized as containing a single identifiable protein. Stress-related expression changes were noted for C. violaceum proteins related to the previously characterized bacterial proteins: DnaK, GroEL-2, Rhs, EF-Tu, EF-P; MCP, homogentisate 1,2-dioxygenase, Arginine deiminase and the ATP synthase β-subunit protein as well as for the ribosomal protein subunits L1, L3, L5 and L6. The ability of C. violaceum to adapt its cellular mechanics to sub-optimal growth and protein production conditions was well illustrated by its regulation of ribosomal protein subunits. With the exception of the ribosomal subunit L3, which plays a role in protein folding and maybe therefore be more useful in stressful conditions, all the other ribosomal subunit proteins were seen to have reduced expression in stressed cultures. Curiously, C. violeaceum cultures were also observed to lose their violet color under stress, which suggests that the violacein pigment biosynthetic pathway is affected by stress. Analysis of the proteomic signatures of stressed C. violaceum indicates that nutrient-starvation and pH stress can cause changes in the expression of the C. violaceum receptors, transporters, and proteins involved with biosynthetic pathways, molecule recycling, energy production. Our findings complement the recent publication of the C. violeaceum genome sequence and could help with the future commercial exploitation of C. violeaceum

Production of volatile fatty acids from slaughterhouse blood by mixed-culture fermentation

The volatile fatty acids (VFA) production potential from animal blood and the factors affecting this process were investigated in this study. In order to simulate an industrial process different operation modes, batch, fed batch and semi-continuous, were also evaluated. Due to high ammonia concentration in fermentation broth, VFA concentration up to 100 g L-1 was achieved without addition of buffer and methanogen inhibitor. In general, acetic, n-butyric and iso-valeric acids were the most predominant species, although different operational conditions affected the VFA concentration, profile, production rate and yield. The microbial community analysis was conducted on the reactors with the best performance, revealing that 70-90% of the microbial population was from the Clostridiales order with a strong presence from the Sporanaerobacter genus. These results demonstrated the feasibility of a VFA-platform bio-refinery using high-protein wastes as substrate via mixed-culture fermentation under non-sterilised conditions

Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV

Results are presented from a search for physics beyond the standard model based on events with large missing transverse energy, at least three jets, and at least one, two, or three b-quark jets. The study is performed using a sample of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS detector at the LHC in 2011. The integrated luminosity of the sample is 4.98 inverse femtobarns. The observed number of events is found to be consistent with the standard model expectation, which is evaluated using control samples in the data. The results are used to constrain cross sections for the production of supersymmetric particles decaying to b-quark-enriched final states in the context of simplified model spectra.Comment: Submitted to Physical Review

Identidad, territorio y promocion de la salud

El presente trabajo se enmarca dentro de un proyecto de extensión que se desarrolla durante el 2012, acreditado y financiado por la UNLP, denominado “Identidad, territorio y salud. Construcción de identidades colectivas y transferencia institucional en torno al primer nivel de atención en el Barrio Federal de Ensenada”. Este barrio cuenta con una población aproximada de 480 habitantes y está ubicado en la zona de Gran La Plata, Pcia. de Buenos Aires. El objetivo del trabajo consiste en fortalecer la apropiación y promoción de la salud colectiva, entendida ésta como un proceso construido históricamente por cada sociedad, que se crea y recrea en todos los aspectos de la vida cotidiana de los sujetos. La propuesta metodológica se sustenta en un proceso dialógico entre los sujetos involucrados: vecinos de barrio Federal y los integrantes del equipo del trabajo extensionista. Desde este marco (pedagógico horizontal) desarrollamos actividades grupales de carácter lúdico-recreativo, que a primera vista no aparentan tener una relación con el proceso salud-enfermedad, propio del imaginario social, pero implícitamente, estarían abarcando y generando cambios en el significado asignado del mismo. Partimos de la idea de fortalecer el sentirse bien, no en el estricto sentido biológico, sino como aquella capacidad para crear momentos y actividades con pares en un mismo territorio y generando lazos entre vecinos y entre éstos y la institución de salud del barrio. De este modo, las actividades se desarrollan principalmente en la sala de espera de la unidad sanitaria y en la plaza circundante. Hemos definido tres líneas de trabajo: artístico, narrativo-plástico y de producción audiovisual y medioambiente. En los encuentros se trabaja con diferentes recursos, propios de disciplinas como música, plástica, teatro, danza, escultura, circo, artes audiovisuales, literatura, entre otros. El carácter interdisciplinario de este proyecto, conformado por estudiantes de las carreras de Trabajo Social y Antropología, un artista escultor y dirigido y coordinado por docentes y graduados de las Facultades de Ciencias Medicas, Humanidades y Ciencias de la Educación y Trabajo Social, enriquece las perspectivas de abordaje y fortalece la visión social, integral y colectiva de la salud. Consolidar acciones identitarias del barrio, generadas a partir de la promoción de la salud, es el principal desafío a alcanzar

Double blind, randomized controlled trial, to evaluate the effectiveness of a controlled nitric oxide releasing patch versus meglumine antimoniate in the treatment of cutaneous leishmaniasis [NCT00317629]

BACKGROUND: Cutaneous Leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis. METHODS AND DESIGN: A double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for Leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be daily administered and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The healing process of the ulcer, the health of the participants, recidivisms and/or reinfection will also be assessed. The evolution of the ulcers will be photographically registered. In case that the effectiveness of the patches is demonstrated, a novel and safe therapeutic alternative for one of the most important public health problems in many countries will be available to patients