963 resultados para Triple helix
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Carte du Ciel (from French, map of the sky) is a part of a 19th century extensive international astronomical project whose goal was to map the entire visible sky. The results of this vast effort were collected in the form of astrographic plates and their paper representatives that are called astrographic maps and are widely distributed among many observatories and astronomical institutes over the world. Our goal is to design methods and algorithms to automatically extract data from digitized Carte du Ciel astrographic maps. This paper examines the image processing and pattern recognition techniques that can be adopted for automatic extraction of astronomical data from stars’ triple expositions that can aid variable stars detection in Carte du Ciel maps.
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Bituminous substances in metalliferous sediments from the region of the triple junction in the Indian Ocean were studied. Specific peculiarities of their structure confirming location in "hot conditions" were revealed. Hydrocarbons are genetically connected with hydrothermal matter, and thus they could be considered as a geochemical indicator of hydrothermal processes in the ocean.
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Un porcentaje no desdeñable de mujeres jóvenes con cáncer de mama esporádico son portadoras de mutaciones germinales en BRCA1/2. Esta prevalencia está estrechamente condicionada por otras variables como el tipo de población, fenotipo tumoral y edad de diagnóstico de cáncer de mama. La presencia de una estructura familiar no informativa es una variable predictiva de la presencia de mutaciones en BRCA1/2 en estas pacientes, pero este hallazgo no ha sido debidamente validado en cohortes independientes. Existe una fuerte asociación entre las mutaciones en BRCA1 y los tumores mamarios de tipo triple negativo (TN). En el presente trabajo analizamos la utilidad de las variables estructura familiar no informativa y fenotipo TN como variables predictivas de mutaciones germinales en BRCA1/2 en una cohorte de mujeres jóvenes ( 35 años) con cáncer de mama esporádico previamente remitidas (1998-2012) a unidades de asesoramiento genético españolas (n = 341). Retrospectivamente, la estructura familiar fue clasificada en informativa, no informativa o no clasificable mediante la revisión centralizada de los pedigrees disponibles en el momento de realizarse los respectivos estudios genéticos. Asimismo, los tumores de mama fueron clasificados en TN, no-TN y no clasificables mediante la revisión de las historias clínicas. Veinticuatro pacientes (7.12 %) fueron portadoras de mutaciones patogénicas, 14 en BRCA1 y 10 en BRCA2. Tanto la estructura familiar no informativa (OR = 3.61, p = 0.027) como el subtipo TN (OR = 3.14, p = 0.013) fueron variables independientes de la presencia de mutaciones germinales en BRCA1/2. La prevalencia de mutaciones en el subgrupo de mujeres con al menos un factor predictivo (estructura familiar no informativa, subtipo TN o ambos) fue del 13.5 %, frente al 2.8 % en aquellas mujeres con estrucutra familiar informativa y tumores no-TN (OR = 5.31, p = 0.006). Demostramos, con la información disponible en un contexto de práctica clínica rutinaria, la utilidad de la estructura familiar y el fenotipo TN como modelo predictivo de mutaciones germinales en BRCA1/2 en mujeres jóvenes con cáncer de mama esporádico. Nuestro estudio sugiere que restringir el análisis tan solo a aquellas mujeres con al menos un factor predicitivo podría ser una estrategia válida para optimizar la realización de estudios genéticos en este subgrupo de mujeres.
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Peer reviewed
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Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.
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An abstract of a thesis devoted to using helix-coil models to study unfolded states.\\
Research on polypeptide unfolded states has received much more attention in the last decade or so than it has in the past. Unfolded states are thought to be implicated in various
misfolding diseases and likely play crucial roles in protein folding equilibria and folding rates. Structural characterization of unfolded states has proven to be
much more difficult than the now well established practice of determining the structures of folded proteins. This is largely because many core assumptions underlying
folded structure determination methods are invalid for unfolded states. This has led to a dearth of knowledge concerning the nature of unfolded state conformational
distributions. While many aspects of unfolded state structure are not well known, there does exist a significant body of work stretching back half a century that
has been focused on structural characterization of marginally stable polypeptide systems. This body of work represents an extensive collection of experimental
data and biophysical models associated with describing helix-coil equilibria in polypeptide systems. Much of the work on unfolded states in the last decade has not been devoted
specifically to the improvement of our understanding of helix-coil equilibria, which arguably is the most well characterized of the various conformational equilibria
that likely contribute to unfolded state conformational distributions. This thesis seeks to provide a deeper investigation of helix-coil equilibria using modern
statistical data analysis and biophysical modeling techniques. The studies contained within seek to provide deeper insights and new perspectives on what we presumably
know very well about protein unfolded states. \\
Chapter 1 gives an overview of recent and historical work on studying protein unfolded states. The study of helix-coil equilibria is placed in the context
of the general field of unfolded state research and the basics of helix-coil models are introduced.\\
Chapter 2 introduces the newest incarnation of a sophisticated helix-coil model. State of the art modern statistical techniques are employed to estimate the energies
of various physical interactions that serve to influence helix-coil equilibria. A new Bayesian model selection approach is utilized to test many long-standing
hypotheses concerning the physical nature of the helix-coil transition. Some assumptions made in previous models are shown to be invalid and the new model
exhibits greatly improved predictive performance relative to its predecessor. \\
Chapter 3 introduces a new statistical model that can be used to interpret amide exchange measurements. As amide exchange can serve as a probe for residue-specific
properties of helix-coil ensembles, the new model provides a novel and robust method to use these types of measurements to characterize helix-coil ensembles experimentally
and test the position-specific predictions of helix-coil models. The statistical model is shown to perform exceedingly better than the most commonly used
method for interpreting amide exchange data. The estimates of the model obtained from amide exchange measurements on an example helical peptide
also show a remarkable consistency with the predictions of the helix-coil model. \\
Chapter 4 involves a study of helix-coil ensembles through the enumeration of helix-coil configurations. Aside from providing new insights into helix-coil ensembles,
this chapter also introduces a new method by which helix-coil models can be extended to calculate new types of observables. Future work on this approach could potentially
allow helix-coil models to move into use domains that were previously inaccessible and reserved for other types of unfolded state models that were introduced in chapter 1.
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Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.
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Petrographic and geochemical analyses of basaltic rocks dredged from the first segment of the Southwest Indian Ridge near the Rodriguez Triple Junction have been completed in order to investigate water-rock interaction processes during mid-ocean ridge (MOR) hydrothermal alteration in the Indian Ocean. In the study area, we have successfully recovered a serial section of upper oceanic crust exposed along a steep rift valley wall which was uplifted and emplaced along a low angle normal fault. On the basis of microscopic observation, dredged samples are classified into three types: fresh lavas, low-temperature altered rocks, and high-temperature altered rocks. The fresh lavas have essentially the same chemical composition as typical N-MORB, although LILE and Nb are slightly enriched and depleted, respectively. Low temperature alteration brought about the enrichment of K2O, Rb, and U due to the presence of K-rich celadonite and U-adsorption onto Fe-oxyhydroxide and clay minerals. On the other hand, chloritization, albitization, and addition of base metals by high temperature hydrothermal alteration result in enrichments of MnO, MgO, Na2O, Cu, and Zn and depletions of CaO, K2O, Cr, Co, Ni, Rb, Sr, and Ba. In addition, U-enrichment is also observable in the high temperature altered rocks probably due to the decrease of uranite solubility in the reducing high-temperature hydrothermal solution. These petrological and geochemical features are comparable to those of the volcanic zone to transition zone rocks in the DSDP/ODP Hole 504B, indicating that our samples were recovered from the upper ~1000 m section of the oceanic crust. Only the alteration minerals related to off-axis alteration are absent in our samples dredged from near the spreading axis. The similarity of alteration between our samples from the Indian Ocean and the Hole 504B rocks from the Pacific Ocean suggests that MOR hydrothermal systems are probably similar across all world oceans.
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This paper presents the layout and results of a compact inkjet-printed filtenna operating at the S-band, ISM and UWB frequencies. The filtenna has a wide passband and, alongside, rejects WiMAX 3.5 GHz, WLAN 5.8 GHz and ITU service 8.2 GHz bands. The filtenna is simulated, printed using silver nanoparticle ink on flexible Kapton substrate and measured. Obtained simulation and measurement results agree well with each other. Measured return loss of the filtenna is more than 10 dB for 1.6–10.85 GHz and triple bandnotch, measuring at an average of 1.87 dB, are present at the unwanted bands. Radiation patterns, as well as the gain and efficiency of the filtenna have also been presented; with the average values being 3.4 dBi and 90 % respectively for the passband and averaging at −1.0 dBi and 22 % respectively for the three rejected bands.
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Given recent demands for more co-creational university technology commercialisation
processes involving industry and end users, this paper adopts a micro level approach to explore
the challenges faced by universities when managing quadruple helix stakeholders within the
technology commercialisation processes. To explore this research question, a qualitative
research methodology which relies upon comparative case analysis was adopted to explore the
technology commercialisation process in two universities within a UK region. The findings
revealed that university type impacts Quadruple Helix stakeholder salience and engagement
and consequently university technology commercialisation activities and process. This is
important as recent European regional policy fails to account for contextual influences when
promoting Quadruple Helix stakeholder relationships in co-creational university technology
commercialisation.
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The androgen receptor (AR) is expressed in 60-80% of breast cancers (BC) across all molecular phenotypes, with a higher incidence in oestrogen receptor positive (ER+) BC compared to ER negative tumours. In ER+ disease, AR-expression has been linked to endocrine resistance which might be reversed with combined treatment targeting ER and AR. In triple negative BCs (TNBC), preclinical and clinical investigations have described a subset of patients that express the AR and are sensitive to androgen blockade, providing a novel therapeutic target. Enzalutamide, a potent 2nd generation anti-androgen, has demonstrated substantial preclinical and clinical anti-tumour activity in AR+ breast cancer. Short-term preoperative window of opportunity studies are a validated strategy for novel treatments to provide proof-of-concept and define the most appropriate patient population by directly assessing treatment effects in tumour tissue before and after treatment. The ARB study aims to assess the anti-tumour effects of enzalutamide in early ER+ breast cancer and TNBC, to identify the optimal target population for further studies and to directly explore the biologic effects of enzalutamide on BC and stromal cells. Methods: ARB is an international, investigator sponsored WOO phase II study in women with newly diagnosed primary ER+ BC or AR+ TNBC of ≥ 1cm. The study has two cohorts. In the ER+ cohort, postmenopausal patients will be randomised 2:1 to receive either enzalutamide (160mg OD) plus exemestane (50mg OD) or exemestane (25mg OD). In the TNBC cohort, AR+ will receive single agent treatment with enzalutamide (160mg OD). Study treatment is planned for 15–29 days, followed by surgery or neo-adjuvant therapy. Tissue and blood samples are collected before treatment and on the last day of study treatment. The primary endpoint is inhibition of tumour-cell proliferation, as measured by change in Ki67 expression, determined centrally by 2 investigators. Secondary endpoints include induction of apoptosis (Caspase3), circulating hormone levels and safety. ARB aims to recruit ≈235 patients from ≈40 sites in the UK, Germany, Spain and USA. The study is open to recruitment.
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Triple Negative Breast Cancer (TNBC) is defined by the lack of ERα, PR expression and HER2 overexpression and is the breast cancer subtype with the poorest clinical outcomes. Our aim was to identify genes driving TNBC proliferation and/or survival which could represent novel therapeutic targets. We performed microarray profiling of primary TNBCs and generated differential genelists based on clinical outcomes following the chemotherapy regimen FEC (5-Fluorouracil/Epirubicin/Cyclophosphamide -‘good’ outcome no relapse > 3 years; ‘poor’ outcome relapse < 3 years). Elevated expression of thromboxane A2 receptor (TBXA2R) was observed in ‘good’ outcome TNBCs. TBXA2R expression was higher specifically in TNBC cell lines and TBXA2R knockdowns consistently showed dramatic cell killing in TNBC cells. TBXA2R mRNA and promoter activities were up-regulated following BRCA1 knockdown, with c-Myc being required for BRCA1-mediated transcriptional repression. We demonstrated that TBXA2R enhanced TNBC cell migration, invasion and activated Rho signalling, phenotypes which could be reversed using Rho-associated Kinase (ROCK) inhibitors. TBXA2R also protected TNBC cells from DNA damage by negatively regulating reactive oxygen species levels. In summary, TBXA2R is a novel breast cancer-associated gene required for the survival and migratory behaviour of a subset of TNBCs and could provide opportunities to develop novel, more effective treatments.