Gamma-ray emission from massive young stellar objects

Context.Massive stars form in dense and massive molecular cores. The exact formation mechanism is unclear, but it is possible that some massive stars are formed by processes similar to those that produce the low-mass stars, with accretion/ejection phenomena occurring at some point of the evolution of the protostar. This picture seems to be supported by the detection of a collimated stellar wind emanating from the massive protostar IRAS 16547-4247. A triple radio source is associated with the protostar: a compact core and two radio lobes. The emission of the southern lobe is clearly non-thermal. Such emission is interpreted as synchrotron radiation produced by relativistic electrons locally accelerated at the termination point of a thermal jet. Since the ambient medium is determined by the properties of the molecular cloud in which the whole system is embedded, we can expect high densities of particles and infrared photons. Because of the confirmed presence of relativistic electrons, inverse Compton and relativistic Bremsstrahlung interactions are unavoidable. Aims.We aim to make quantitative predictions of the spectral energy distribution of the non-thermal spots generated by massive young stellar objects, with emphasis on the particular case of IRAS 16547-4247. Methods.We study the high-energy emission generated by the relativistic electrons which produce the non-thermal radio source in IRAS 16547-4247. We also study the result of proton acceleration at the terminal shock of the thermal jet and make estimates of the secondary gamma rays and electron-positron pairs produced by pion decay. Results.We present spectral energy distributions for the southern lobe of IRAS 16547-4247, for a variety of conditions. We show that high-energy emission might be detectable from this object in the gamma-ray domain. The source may also be detectable in X-rays through long exposures with current X-ray instruments. Conclusions.Gamma-ray telescopes such as GLAST, and even ground-based Cherenkov arrays of new generation can be used to study non-thermal processes occurring during the formation of massive stars.

Cardiologie [Cardiology update in 2014].

Important clinical trials and therapeutic advances in the field of cardiology have been presented in 2014. New evidences on the management of acute myocardial infarction and the duration of dual antiplatelet therapy after coronary stent implantation have been published. A new class of therapeutic agents seems to offer promising perspectives for patients with heart failure and reduced ejection fraction. The new generation of subcutaneous or MRI-compatible implantable defibrillators is a major technological breakthrough. Finally, the European Society of Cardiology published new recommendations for the management of patients with cardiovascular diseases. This selective review of the literature summarizes the most important studies in the field of interventional cardiology, rhythmology, heart failure and cardiac imaging.

Lidar measurement of surface melt for a temperate Alpine glacier at the seasonal and hourly scales

This study shows how a new generation of terrestrial laser scanners can be used to investigate glacier surface ablation and other elements of glacial hydrodynamics at exceptionally high spatial and temporal resolution. The study area is an Alpine valley glacier, Haut Glacier d'Arolla, Switzerland. Here we use an ultra-long-range lidar RIEGL VZ-6000 scanner, having a laser specifically designed for measurement of snow- and ice-cover surfaces. We focus on two timescales: seasonal and daily. Our results show that a near-infrared scanning laser system can provide high-precision elevation change and ablation data from long ranges, and over relatively large sections of the glacier surface. We use it to quantify spatial variations in the patterns of surface melt at the seasonal scale, as controlled by both aspect and differential debris cover. At the daily scale, we quantify the effects of ogive-related differences in ice surface debris content on spatial patterns of ablation. Daily scale measurements point to possible hydraulic jacking of the glacier associated with short-term water pressure rises. This latter demonstration shows that this type of lidar may be used to address subglacial hydrologic questions, in addition to motion and ablation measurements.

Understanding academics' popular science publishing : institution culture and management style effects

Most universities and higher education systems have formally taken up a third mission, which involves various public outreach and engagement activities. Little is known regarding how higher education institutions' organisations interact with academic's level of public outreach. This article examines to which extent the perceptions academics have of their institutions' culture and management style, as well as some of their own individual and statutory characteristics interact with their level of public outreach. Using the Academic Profession in Europe comparative and quantitative research database, this article focuses on two countries on the extremities of the spectrum - Switzerland and the United Kingdom.

Procedural Results and Clinical Outcomes of Transcatheter Aortic Valve Implantation in Switzerland: An Observational Cohort Study of Sapien 3 Versus Sapien XT Transcatheter Heart Valves.

BACKGROUND: New generation transcatheter heart valves (THV) may improve clinical outcomes of transcatheter aortic valve implantation. METHODS AND RESULTS: In a nationwide, prospective, multicenter cohort study (Swiss Transcatheter Aortic Valve Implantation Registry, NCT01368250), outcomes of consecutive transfemoral transcatheter aortic valve implantation patients treated with the Sapien 3 THV (S3) versus the Sapien XT THV (XT) were investigated. An overall of 153 consecutive S3 patients were compared with 445 consecutive XT patients. Postprocedural mean transprosthetic gradient (6.5±3.0 versus 7.8±6.3 mm Hg, P=0.17) did not differ between S3 and XT patients, respectively. The rate of more than mild paravalvular regurgitation (1.3% versus 5.3%, P=0.04) and of vascular (5.3% versus 16.9%, P<0.01) complications were significantly lower in S3 patients. A higher rate of new permanent pacemaker implantations was observed in patients receiving the S3 valve (17.0% versus 11.0%, P=0.01). There were no significant differences for disabling stroke (S3 1.3% versus XT 3.1%, P=0.29) and all-cause mortality (S3 3.3% versus XT 4.5%, P=0.27). CONCLUSIONS: The use of the new generation S3 balloon-expandable THV reduced the risk of more than mild paravalvular regurgitation and vascular complications but was associated with an increased permanent pacemaker rate compared with the XT. Transcatheter aortic valve implantation using the newest generation balloon-expandable THV is associated with a low risk of stroke and favorable clinical outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01368250.

Whole-body MRI: comprehensive evaluation on a 48-channel 3T MRI system in less than 40 minutes. Preliminary results

OBJECTIVE: To evaluate a comprehensive MRI protocol that investigates for cancer, vascular disease, and degenerative/inflammatory disease from the head to the pelvis in less than 40 minutes on a new generation 48-channel 3T system. MATERIALS AND METHODS: All MR studies were performed on a 48-channel 3T MR scanner. A 20-channel head/neck coil, two 18-channel body arrays, and a 32-channel spine array were employed. A total of 4 healthy individuals were studied. The designed protocol included a combination of single-shot T2-weighted sequences, T1-weighted 3D gradient-echo pre- and post-gadolinium. All images were retrospectively evaluated by two radiologists independently for overall image quality. RESULTS: The image quality for cancer was rated as excellent in the liver, pancreas, kidneys, lungs, pelvic organs, and brain, and rated as fair in the colon and breast. For vascular diseases ratings were excellent in the aorta, major branch vessel origins, inferior vena cava, portal and hepatic veins, rated as good in pulmonary arteries, and as poor in the coronary arteries. For degenerative/inflammatory diseases ratings were excellent in the brain, liver and pancreas. The inter-observer agreement was excellent. CONCLUSION: A comprehensive and time efficient screening for important categories of disease processes may be achieved with high quality imaging in a new generation 48-channel 3T system.

Characterization of local and systemic immune-modulation in melanoma patients

Le mélanome cutané est un des cancers les plus agressifs et dont l'incidence augmente le plus en Suisse. Une fois métastatique, le pronostic de survie moyenne avec les thérapies actuelles est d'environ huit mois, avec moins de 5% de survie à cinq ans. Les récents progrès effectués dans la compréhension de la biologie de la cellule tumorale mais surtout dans l'importance du système immunitaire dans le contrôle de ce cancer ont permis le développement de nouveaux traitements novateurs et prometteurs. Ces thérapies, appelées immunothérapies, reposent sur la stimulation et l'augmentation de la réponse immunitaire à la tumeur. Alors que les derniers essais cliniques ont démontré l'efficacité de ces traitements chez les patients avec des stades avancés de la maladie, le contrôle de la maladie à long- terme est seulement atteint chez une minorité des patients. La suppression locale et systémique de la réponse immunitaire spécifique anti-tumorale apparaitrait comme une des raisons expliquant la persistance d'un mauvais pronostic clinique chez ces patients. Des études sur les souris ont montré que les vaisseaux lymphatiques joueraient un rôle primordial dans ce processus en induisant une tolérance immune, ce qui permettrait à la tumeur d'échapper au contrôle du système immunitaire et métastatiser plus facilement. Ces excitantes découvertes n'ont pas encore été établi et prouvé chez l'homme. Dans cette thèse, nous montrons pour la première fois que les vaisseaux lymphatiques sont directement impliqués dans la modulation de la réponse immunitaire au niveau local et systémique dans le mélanome chez l'homme. Ces récentes découvertes montrent le potentiel de combiner des thérapies visant le système lymphatique avec les immunothérapies actuellement utilisées afin d'améliorer le pronostic des patients atteint du mélanome. -- Cutaneous melanoma is one of the most invasive and metastatic human cancers and causes 75% of skin cancer mortality. Current therapies such as surgery and chemotherapy fail to control metastatic disease, and relapse occurs frequently due to microscopic residual lesions. It is, thus, essential to develop and optimize novel therapeutic strategies to improve curative responses in these patients. In recent decades, tumor immunologists have revealed the development of spontaneous adaptive immune responses in melanoma patients, leading to the accumulation of highly differentiated tumor-specific T cells at the tumor site. This remains one of the most powerful prognostic markers to date. Immunotherapies that augment the natural function of these tumor-specific T cells have since emerged as highly attractive therapeutic approaches to eliminate melanoma cells. While recent clinical trials have demonstrated great progress in the treatment of advanced stage melanoma, long-term disease control is still only achieved in a minority of patients. Local and systemic immune suppression by the tumor appears to be responsible, in part, for this poor clinical evolution. These facts underscore the need for a better analysis and characterization of immune- related pathways within the tumor microenvironment (TME), as well as at the systemic level. The overall goal of this thesis is, thus, to obtain greater insight into the complexity and heterogeneity of the TME in human melanoma, as well as to investigate immune modulation beyond the TME, which ultimately influences the immune system throughout the whole body. To achieve this, we established two main objectives: to precisely characterize local and systemic immune modulation (i) in untreated melanoma patients and (ii) in patients undergoing peptide vaccination or checkpoint blockade therapy with anti-cytotoxic T- lymphocyte-asisctaed protein-4 (CTLA-4) antibody. In the first and main part of this thesis, we analyzed lymphatic vessels in relation to anti-tumor immune responses in tissues from vaccinated patients using a combination of immunohistochemistry (IHC) techniques, whole slide scanning/analysis, and an automatic quantification system. Strikingly, we found that increased lymphatic vessel density was associated with high expression of immune suppressive molecules, low functionality of tumor-infiltrating CD8+ T cells and decreased cytokine production by tumor-antigen specific CD8+ T cells in the blood. These data revealed a previously unappreciated local and systemic role of lymphangiogenesis in modulating T cell responses in human cancer and support the use of therapies that target lymphatic vessels combined with existing and future T cell based therapies. In the second objective, we describe a metastatic melanoma patient who developed pulmonary sarcoid-like granulomatosis following repetitive vaccination with peptides and CpG. We demonstrated that the onset of this pulmonary autoimmune adverse event was related to the development of a strong and long-lasting tumor-specific CD8+ T cell response. This constitutes the first demonstration that a new generation tumor vaccine can induce the development of autoimmune adverse events. In the third objective, we assessed the use of Fourier Transform Infrared (FTIR) imaging to identify melanoma cells and lymphocyte subpopulations in lymph node (LN) metastasis tissues, thanks to a fruitful collaboration with researchers in Brussels. We demonstrated that the different cell types in metastatic LNs have different infrared spectral features allowing automated identification of these cells. This technic is therefore capable of distinguishing known and novel biological features in human tissues and has, therefore, significant potential as a tool for histopathological diagnosis and biomarker assessment. Finally, in the fourth objective, we investigated the role of colony- stimulating factor-1 (CSF-1) in modulating the anti-tumor response in ipilimumab-treated patients using IHC and in vitro co-cultures, revealing that melanoma cells produce CSF-1 via CTL-derived cytokines when attacked by cytotoxic T lymphocytes (CTLs), resulting in the recruitment of immunosuppressive monocytes. These findings support the combined use of CSF-1R blockade with T cell based immunotherapy for melanoma patients. Taken together, our results reveal the existence of novel mechanisms of immune modulation and thus promote the optimization of combination immunotherapies against melanoma. -- Le mélanome cutané est un des cancers humains les plus invasifs et métastatiques et est responsable de 75% de la mortalité liée aux cancers de la peau. Les thérapies comme la chirurgie et la chimiothérapie ont échoué à contrôler le mélanome métastatique, par ailleurs les rechutes sous ces traitements ont été montrées fréquentes. Il est donc essentiel de développer et d'optimiser de nouvelles stratégies thérapeutiques pour améliorer les réponses thérapeutiques de ces patients. Durant les dernières décennies, les immunologistes spécialisés dans les tumeurs ont démontré qu'un patient atteint du mélanome pouvait développer spontanément une réponse immune adaptative à sa tumeur et que l'accumulation de cellules T spécifiques tumorales au sein même de la tumeur était un des plus puissants facteurs pronostiques. Les immunothérapies qui ont pour but d'augmenter les fonctions naturelles de ces cellules T spécifiques tumorales ont donc émergé comme des approches thérapeutiques très attractives pour éliminer les cellules du mélanome. Alors que les derniers essais cliniques ont démontré un progrès important dans le traitement des formes avancées du mélanome, le contrôle de la maladie à long-terme est seulement atteint chez une minorité des patients. La suppression immune locale et systémique apparaitrait comme une des raisons expliquant la persistance d'un mauvais pronostic clinique chez ces patients. Ces considérations soulignent la nécessité de mieux analyser et caractériser les voies immunitaires non seulement au niveau local dans le microenvironement tumoral mais aussi au niveau systémique dans le sang des patients. Le but de cette thèse est d'obtenir une plus grande connaissance de la complexité et de l'hétérogénéité du microenvironement tumoral dans les mélanomes mais aussi d'investiguer la modulation immunitaire au delà du microenvironement tumoral au niveau systémique. Afin d'atteindre ce but, nous avons établi deux objectifs principaux : caractériser précisément la modulation locale et systémique du système immunitaire (i) chez les patients atteints du mélanome qui n'ont pas reçu de traitement et (ii) chez les patients qui ont été traités soit par des vaccins soit par des thérapies qui bloquent les points de contrôles. Dans la première et majeure partie de cette thèse, nous avons analysé les vaisseaux lymphatiques en relation avec la réponse immunitaire anti-tumorale dans les tissus des patients vaccinés grâce à des techniques d'immunohistochimie et de quantification informatisé et automatique des marquages. Nous avons trouvé qu'une densité élevée de vaisseaux lymphatiques dans la tumeur était associée à une plus grande expression de molécules immunosuppressives ainsi qu'à une diminution de la fonctionnalité des cellules T spécifiques tumoral dans la tumeur et dans le sang des patients. Ces résultats révèlent un rôle jusqu'à là inconnu des vaisseaux lymphatiques dans la modulation directe du système immunitaire au niveau local et systémique dans les cancers de l'homme. Cette recherche apporte finalement des preuves du potentiel de combiner des thérapies visant le système lymphatique avec des autres immunothérapies déjà utilisées en clinique. Dans le second objectif, nous rapportons le cas d'un patient atteint d'un mélanome avec de multiples métastases qui a développé à la suite de plusieurs vaccinations répétées et consécutives avec des peptides et du CpG, un évènement indésirable sous la forme d'une granulomatose pulmonaire sarcoid-like. Nous avons démontré que l'apparition de cet évènement était intimement liée au développement d'une réponse immunitaire durable et spécifique contre les antigènes de la tumeur. Par là- même, nous prouvons pour la première fois que la nouvelle génération de vaccins est aussi capable d'induire des effets indésirables auto-immuns. Pour le troisième objectif, nous avons voulu savoir si l'utilisation de la spectroscopie infrarouge à transformée de Fourier (IRTF) était capable d'identifier les cellules du mélanome ainsi que les différents sous-types cellulaires dans les ganglions métastatiques. Grâce à nos collaborateurs de Bruxelles, nous avons pu établir que les diverses composantes cellulaires des ganglions atteints par des métastases du mélanome présentaient des spectres infrarouges différents et qu'elles pouvaient être identifiées d'une façon automatique. Cette nouvelle technique permettrait donc de distinguer des caractéristiques biologiques connues ou nouvelles dans les tissus humains qui auraient des retombées pratiques importantes dans le diagnostic histopathologique et dans l'évaluation des biomarqueurs. Finalement dans le dernier objectif, nous avons investigué le rôle du facteur de stimulation des colonies (CSF-1) dans la modulation de la réponse immunitaire anti-tumorale chez les patients qui ont été traités par l'Ipilimumab. Nos expériences in vivo au niveau des tissus tumoraux et nos co-cultures in vitro nous ont permis de démontrer que les cytokines secrétées par les cellules T spécifiques anti-tumorales induisaient la sécrétion de CSF-1 dans les cellules du mélanome ce qui résultait en un recrutement de monocytes immunosuppresseurs. Dans son ensemble, cette thèse révèle donc l'existence de nouveaux mécanismes de modulation de la réponse immunitaire anti-tumorale et propose de nouvelles optimisations de combinaison d'immunothérapies contre le mélanome.

Terapia fotodinâmica: aspectos farmacológicos, aplicações e avanços recentes no desenvolvimento de medicamentos

Photodynamic Therapy (PDT) is a clinical procedure, which utilize a photosensitive compound and light. This is a new modality of treatment for cancer, aged related macular degenerescence (AMD), psoriasis, arthritis, arterial restenosis, etc which exhibits efficiency, less traumatic effects, low recovery time and few co-lateral effects. The first officially approved drug for PDT by the Food and Drug Administration (EUA) is Photofrinâ, which is applied for cancer. A new generation drug for PDT, Visudyneâ was recently approved to treat AMD; its photoactive compound is BPDMA, a benzoporphyrin mono-acid derivative (chlorin-type molecule). A concise history, technical information and some drugs for PDT are reported.

Los derechos de participación política y administrativa en la Constitución y en los Estatutos de Autonomía: especial referencia al Estatuto de Autonomía de Cataluña

[spa] El estudio afronta la regulación de los derechos de participación en los Estatutos de Autonomía de nueva generación. La novedad que representan estas normas respecto a sus predecesoras es la incorporación de una carta de derechos que vinculan de forma más explícita y detallada a los poderes públicos autonómicos. Los estatuyentes han interiorizado el creciente auge del fenómeno participativo regulando, junto a los tradicionales derechos de participación política, nuevos instrumentos y técnicas participativas, que se enmarcan en el concepto de democracia participativa. Significativa es, en este sentido, la voluntad política plasmada en la competencia que asumen algunos de ellos (Cataluña, Andalucía y Aragón)para la regulación de las consultas populares en cualquiera de sus modalidades ("encuestas, audiencias públicas, foros de participación") distintas el referéndum.

Characterization of Microparticle Retention Systems with Retention Process Analyzer

In the literature survey retention mechanisms, factors effecting retention and microparticles were studied. Also commercial microparticle retention systems and means to measure retention were studied. Optical retention measurement with RPA and Lasentec FBRM was studied. The experimental part contains study of different cationic polyacrylamides, anionic silica, bentonite and new generation micropolymer. In these studies the dosage, dosing order and dosing history were changing factors. The experimental work was done with RPA-apparatus with which, the retention process can be followed in real time. In testing was found that silica yielded better retention, when dosed nontraditionally before the polymer. Also silica was very dependant on the polymer dosage. With bentonite good colloidal retention was achieved with relatively low doses. Unlike silica bentonite was not dependant on polymer dosage. The relation of bentonite and polymer dosage is more defining when high retention is wanted. With 3-component systems using bentonite very high retention was achieved. With silica no improvement in retention was found in 3-component systems compared to dual component systems.

Quantum suppression of shot noise in field emitters

We have analyzed the shot noise of electron emission under strong applied electric fields within the Landauer-Bttiker scheme. In contrast to the previous studies of vacuum-tube emitters, we show that in new generation electron emitters, scaled down to the nanometer dimensions, shot noise much smaller than the Schottky noise is observable. Carbon nanotube field emitters are among possible candidates to observe the effect of shot-noise suppression caused by quantum partitioning.

Fases estacionárias monolíticas para separações cromatográficas

Monolithic stationary phases represent a new generation of chromatographic separation media. These phases consist of a continuous separation bed prepared by in situ polymerization or consolidation inside the column tubing. In recent years, their simple preparation procedure, unique properties and excellent performance have attracted quite remarkable attention in liquid chromatography and capillary electrochromatography. This review summarizes the preparation, characterization and applications of monolithic stationary phases. The analytical potential of these columns is demonstrated with separations involving various families of compounds in different separation modes.

Fourier-based registration for robust forward-looking sonar mosaicing in low-visibility underwater environments

Vehicle operations in underwater environments are often compromised by poor visibility conditions. For instance, the perception range of optical devices is heavily constrained in turbid waters, thus complicating navigation and mapping tasks in environments such as harbors, bays, or rivers. A new generation of high-definition forward-looking sonars providing acoustic imagery at high frame rates has recently emerged as a promising alternative for working under these challenging conditions. However, the characteristics of the sonar data introduce difficulties in image registration, a key step in mosaicing and motion estimation applications. In this work, we propose the use of a Fourier-based registration technique capable of handling the low resolution, noise, and artifacts associated with sonar image formation. When compared to a state-of-the art region-based technique, our approach shows superior performance in the alignment of both consecutive and nonconsecutive views as well as higher robustness in featureless environments. The method is used to compute pose constraints between sonar frames that, integrated inside a global alignment framework, enable the rendering of consistent acoustic mosaics with high detail and increased resolution. An extensive experimental section is reported showing results in relevant field applications, such as ship hull inspection and harbor mapping

Standardised innovation management systems: a case study of the Spanish Standard UNE 166002:2006

This paper describes the experience of a Spanish manufacturing firm that implemented the UNE 166002:2006 standard, which is the first in the world to offer a certifiable standardised management system for innovation. After a brief review of innovation management in general, the paper describes the history, objectives, and content of the UNE 166002:2006 Spanish standard and the family of standards to which it belongs. The paper then presents a case study of the implementation of the standard in a manufacturing company, describing the benefits and difficulties of the implementation as detected by the company personnel involved. The paper concludes with a discussion of the desirability and feasibility of creating an international innovation management standard and a new generation of innovation management processes based on a standard for innovation

Filtros digitais por transformadas de Fourier aplicados em eletroquímica

The electrochemical properties of micro and nano-electrodes are widely investigated due to their low faradaic and capacitive currents, leading to a new generation of smart and implantable devices. However, the current signals obtained in low-dimensional devices are strongly influenced by noise sources. In this paper, we show the evaluation of filters based on Fast Fourier Transform (FFT) and their implementation in a graphical user interface (GUI) in MATLAB®. As a case study, we evaluated an electrochemical reaction process of charge transfer via outer-sphere. Results showed successful removal of most of the noise in signals, thus proving a promising tool for low-scale measurement.