Spontaneous Emergence of Chirality in the Limited Enantioselectivity Model: Autocatalytic Cycle Driven by an External Reagent

The emergence of chirality in enantioselective autocatalysis for compounds unable to transform according to the Frank-like reaction network is discussed with respect to the controversial limited enantioselectivity (LES) model composed of coupled enantioselective and non-enantioselective autocatalyses. The LES model cannot lead to spontaneous mirror symmetry breaking (SMSB) either in closed systems with a homogeneous temperature distribution or in closed systems with a stationary non-uniform temperature distribution. However, simulations of chemical kinetics in a two-compartment model demonstrate that SMSB may occur if both autocatalytic reactions are spatially separated at different temperatures in different compartments but coupled under the action of a continuous internal flow. In such conditions, the system can evolve, for certain reaction and system parameters, toward a chiral stationary state; that is, the system is able to reach a bifurcation point leading to SMSB. Numerical simulations in which reasonable chemical parameters have been used suggest that an adequate scenario for such a SMSB would be that of abyssal hydrothermal vents, by virtue of the typical temperature gradients found there and the role of inorganic solids mediating chemical reactions in an enzyme-like role.

Grafting of Araucaria angustifolia (BERTOL.) kuntze through the four seasons of the year

Araucaria angustifolia is an endangered conifer species of South America that has been over exploited for timber. To incentivize Araucaria angustifolia planting is essential and may play a key role on the conservation of this species and the ecosystems that depend on it. Hence, techniques that allow the production of seedlings with attributes that may entice farmers to plant A. angustifolia trees are very important. Grafting may permit the selection of female trees and the production of precocious plants that will produce high quality seeds. The aim of this study was to determine the best season of the year to graft. Three-year-old seedlings were used as rootstock and orthotropic branches of young plants were used for scion collection. The technique used for the grafting was the bark patch. This procedure was carried out in the beginning of each season in 2007 and 2008, with a total of 160 grafted plants. Grafting carried out in the beginning of autumn had a 50 % success rate. Grafting success was negligible for all remaining seasons. In conclusion, grafting through bark patching is a viable technique for the production of A. angustifolia seedlings. Future research should be carried out to produce grafted seedlings in large-scale.

Breeding, genetic and genomic of citrus for disease resistance

Although the citriculture is one of the most important economic activities in Brazil, it is based on a small number of varieties. This fact has contributed for the vulnerability of the culture regarding the phytosanitary problems. A higher number of varieties/genotypes with potential for commercial growing, either for the industry or fresh market, has been one of the main objectives of citrus breeding programs. The genetic breeding of citrus has improved, in the last decades, due to the possibility of an association between biotechnological tools and classical methods of breeding. The use of molecular markers for early selection of zygotic seedlings from controlled crosses resulted in the possibility of selection of a high number of new combination and, as a consequence, the establishment of a great number of hybrids in field experiments. The faster new tools are incorporated in the program, the faster is possibility to reach new genotypes that can be tested as a new variety. Good traits should be kept or incorporate, whereas bad traits have to be excluded or minimized in the new genotype. Scion and rootstock can not be considered separately, and graft compatibility, fruit quality and productivity are essential traits to be evaluated in the last stages of the program. The mapping of QTLs has favored breeding programs of several perennial species and in citrus it was possible to map several characteristics with qualitative and quantitative inheritance. The existence of linkage maps and QTLs already mapped, the development of EST and BAC library and the sequencing of the Citrus complete genome altogether make very demanding and urgent the exploration of such data to launch a wider genetic study of citrus. The rising of information on genome of several organisms has opened new approaches looking for integration between breeding, genetic and genome. Genome assisted selection (GAS) involves more than gene or complete genome sequencing and is becoming an import support in breeding programs of annual and perennial species. An huge information amount can be derivate from genome analysis. The use and benefit of such informations will depend on the genetic basis of the breeding program.

Sildenafil as a therapeutic option for digital ischemic ulceration: case report.

We report the case of a 37-year-old woman who developed critical upper limb ischemia caused by a cervical rib. Because the malformation was initially undiagnosed, a vascular bypass was performed, and failure occurred. Following a 6-month therapy with sildenafil, revascularization of the arm was successful and amputation was avoided. A 6-year follow-up shows a rich collateral network at the compression site and normal values of digital plethysmography. Because hand surgeons often see patients with digital ulcerations and other manifestations of peripheral vascular pathology, therapy of ischemia with sildenafil could be an effective treatment option in patients not responding to classic drugs.

Analysis of flow dynamics in right ventricular outflow tract.

BACKGROUND: The mechanism behind early graft failure after right ventricular outflow tract (RVOT) reconstruction is not fully understood. Our aim was to establish a three-dimensional computational fluid dynamics (CFD) model of RVOT to investigate the hemodynamic conditions that may trigger the development of intimal hyperplasia and arteriosclerosis. METHODS: Pressure, flow, and diameter at the RVOT, pulmonary artery (PA), bifurcation of the PA, and left and right PAs were measured in 10 normal pigs with a mean weight of 24.8 ± 0.78 kg. Data obtained from the experimental scenario were used for CFD simulation of pressure, flow, and shear stress profile from the RVOT to the left and right PAs. RESULTS: Using experimental data, a CFD model was obtained for 2.0 and 2.5-L/min pulsatile inflow profiles. In both velocity profiles, time and space averaged in the low-shear stress profile range from 0-6.0 Pa at the pulmonary trunk, its bifurcation, and at the openings of both PAs. These low-shear stress areas were accompanied to high-pressure regions 14.0-20.0 mm Hg (1866.2-2666 Pa). Flow analysis revealed a turbulent flow at the PA bifurcation and ostia of both PAs. CONCLUSIONS: Identified local low-shear stress, high pressure, and turbulent flow correspond to a well-defined trigger pattern for the development of intimal hyperplasia and arteriosclerosis. As such, this real-time three-dimensional CFD model may in the future serve as a tool for the planning of RVOT reconstruction, its analysis, and prediction of outcome.

Observation of VHE γ-rays from Cassiopeia A with the MAGIC telescope

Aims:We searched for very high energy (VHE) γ-ray emission from the supernova remnant Cassiopeia A Methods: The shell-type supernova remnant Cassiopeia A was observed with the 17 m MAGIC telescope between July 2006 and January 2007 for a total time of 47 h. Results: The source was detected above an energy of 250 GeV with a significance of 5.2σ and a photon flux above 1 TeV of (7.3 ± 0.7_stat ± 2.2_sys) × 10-13 cm-2s-1. The photon spectrum is compatible with a power law dN/dE ∝ E-Γ with a photon index Γ = 2.3 ± 0.2_stat ± 0.2_sys. The source is point-like within the angular resolution of the telescope.

Transition en transplantation rénale [Transition in kidney transplantation].

La transition en transplantation rénale constitue une étape importante dans la vie d'un jeune adolescent greffé. Durant cette période, les impératifs de la greffe se heurtent aux changements physiologiques et psychologiques de l'adolescence, avec un risque augmenté de non-observance thérapeutique et donc de perte du greffon. Il n'existe pas encore un modèle optimal de transition unanimement accepté, mais il a été démontré que la mise en place d'une équipe multidisciplinaire de professionnels pédiatres et adultes, ayant une formation dans la gestion des adolescents et jeunes adultes, est bénéfique. Cette équipe doit assurer une transition progressive des jeunes patients vers la clinique adulte selon un plan bien défini. Transition from pediatric to adult care in renal transplantation has emerged as a critical step in the life of a young kidney recipient. During this phase, young patients are faced with the physiological and psychological changes associated with adolescence that can lead to non-compliance and potentially graft loss. To date, there is not a unique accepted model of transition, however it has been proved that the presence of a multidisciplinary team including specialists in adolescent management and in the transition from pediatric to adult transplant care is beneficial during this at-risk phase. The goal of this team is to ensure a progressive transition of the patients according to a precise plan and time line.

Is the matching function Cobb-Douglas?

[cat] Estudiem les propietats teòriques que una funció d.emparellament ha de satisfer per tal de representar un mercat laboral amb friccions dins d'un model d'equilibri general amb emparellament aleatori. Analitzem el cas Cobb-Douglas, CES i altres formes funcionals per a la funció d.emparellament. Els nostres resultats estableixen restriccions sobre els paràmetres d'aquests formes funcionals per assegurar que l.equilibri és interior. Aquestes restriccions aporten raons teòriques per escollir entre diverses formes funcionals i permeten dissenyar tests d'error d'especificació de model en els treballs empírics.

Is the matching function Cobb-Douglas?

[cat] Estudiem les propietats teòriques que una funció d.emparellament ha de satisfer per tal de representar un mercat laboral amb friccions dins d'un model d'equilibri general amb emparellament aleatori. Analitzem el cas Cobb-Douglas, CES i altres formes funcionals per a la funció d.emparellament. Els nostres resultats estableixen restriccions sobre els paràmetres d'aquests formes funcionals per assegurar que l.equilibri és interior. Aquestes restriccions aporten raons teòriques per escollir entre diverses formes funcionals i permeten dissenyar tests d'error d'especificació de model en els treballs empírics.

Novel therapeutic strategies targeting regulatory T cells and downstream TCR signaling in transplantation

Avec plus de 100000 transplantations d'organes solides (TOS) par année dans le monde, la transplantation d'organes reste actuellement l'un des meilleurs traitements disponibles pour de nombreuses maladies en phase terminale. Bien que les médicaments immunosuppresseurs couramment utilisés soient efficaces dans le contrôle de la réponse immune engendrant le rejet aigu d'une greffe, la survie du greffon à long terme ainsi que la présence d'effets secondaires indésirables restent un enjeu considérable en clinique. C'est pourquoi il est nécessaire de trouver de nouvelles approches thérapeutiques innovantes permettant de contrôler la réponse immunitaire et ainsi d'améliorer les résultats à long terme. L'utilisation des lymphocytes T régulateurs (Treg), suppresseurs naturels de la réponse inflammatoire, a fait l'objet de nombreuses études ces dix dernières années, et pourrait être considérée comme un moyen intéressant d'améliorer la tolérance immunologique de la greffe. Cependant, l'un des obstacles de l'utilisation des Treg comme agent thérapeutique est leur nombre insuffisant non seulement en conditions normales, mais en particulier lors d'une forte réponse immune avec expansion de cellules immunitaires alloréactives. En raison des limitations techniques connues pour l'induction des Treg ex-vivo ou in vitro, nous avons dédié la première partie du travail de thèse à la détermination de l'efficacité de l'induction des Treg in vivo grâce à l'utilisation d'un complexe protéique IL-2/JES6-1 (IL2c). Nous avons montré que l'expansion des Treg par IL2c permettait d'augmenter la survie du greffon sur un modèle murin de transplantation de peau avec mismatch entre le donneur et le receveur pour le complexe majeur d'histocompatibilité (CMH). De plus, nous avons vu qu'en combinant IL2c à une inhibition à court terme de la voie de co-stimulation CD40L-CD40 (anti-CD154/MRl, administré au moment de la transplantation) pour empêcher l'activation des lymphocytes T, il est possible d'induire une tolérance robuste à long terme. Finalement, nos résultats soulignent l'importance de cibler une voie de co-stimulation bien particulière. En effet, l'utilisation d'IL2c combinée au blocage de la co-stimulation CD28-B7.1/2 (CTLA-4 Ig) n'induit qu'une faible prolongation de la survie de la greffe et n'induit pas de tolérance. L'application chez l'humain des traitements induisant la tolérance dans des modèles expérimentaux murins ou de primates n'a malheureusement pas montré de résultats probants en recherche clinique ; une des principales raisons étant la présence de lymphocytes B et T mémoires provenant du systeme d immunité acquise. C est pourquoi nous avons testé si la combinaison d'IL2c et MR1 améliorait la survie de la greffe dans des souris pré¬sensibilisées. Nous avons trouvé qu'en présence de lymphocytes B et T mémoires alloréactifs, l'utilisation d'IL2c et MR1 permettait une amélioration de la survie de la greffe de peau des souris immunocompétentes mais comparé aux souris receveuses naïves, aucune tolérance n'a pu être induite. Toutefois, l'ajout d'un traitement anti-LFA-1 (permettant de bloquer la circulation des lymphocytes T activées) a permis d'améliorer de manière significative la survie de la greffe. Cependant, le rejet chronique, dû à la présence de lymphocytes B activés/mémoires et la production d'anticorps donneur-spécifiques, n'a pas pu être évité. Cibler l'activation des lymphocytes T est la stratégie immunothérapeutique prépondérente après une TOS. C'est pourquoi dans la deuxième partie de cette thèse nous nous sommes intéressés au système de signalisation d'un récepteur des lymphocytes T qui dépend de la paracaspase Malti en tant que nouvelle stratégie immunosuppressive pour le contrôle des lymphocytes T alloréactifs. Nous avons montré que bien que l'inhibition de la signalisation du lymphocyte T en aval de Malti induise une tolérance envers un greffon de peau avec incompatibilités antigéniques mineures, cela ne permet cependant qu'une régulation partielle de l'alloréponse contre des antigènes du CMH. Nous nous sommes aussi intéressés spécifiquement à l'activité protéolytique de Malti. L'inhibition constitutive de l'activité protéolytique de Malti chez les souris Malti-ki s'est révélée délétère pour l'induction de la tolérance car elle diminue la fonction des Treg et augmente l'alloréactivité des cellules Thl. Cependant, lors de l'utilisation d'un inhibiteur peptidique de l'activité protéase de Malti in vitro, il a été possible d'observer une atténuation de l'alloéactivité des lymphocytes T ainsi qu'un maintien de la population des Treg existants. Ces résultats nous laissent penser que des études plus poussées sur le rôle de la signalisation médiée par Malti seraient à envisager dans le domaine de la transplantation. En résumé, les résultats obtenus durant cette thèse nous ont permis d'élucider certains mécanismes immunologiques propres à de nouvelles stratégies thérapeutiques potentielles dont le but est d'induire une tolérance lors de TOS. De plus, ces résultats nous ont permis de souligner l'importance d'utiliser des modèles davantage physiologiques contenant, notamment en tenant compte des lymphocytes B et T mémoires alloréactifs. -- Organ transplantation remains the best available treatment for many forms of end-stage organ diseases, with over 100,000 solid organ transplantations (SOT) occurring worldwide eveiy year. Although the available immunosuppressive (IS) drugs are efficient in controlling acute immune activation and graft rejection, the off-target side effects as well as long-term graft and patient survival remain a challenge in the clinic. Hence, innovative therapeutic approaches are needed to improve long-term outcome across immunological barriers. Based on extensive experimental data obtained over the last decade, it is tempting to consider immunotherapy using Treg; the natural suppressors of overt inflammatory responses, in promoting transplantation tolerance. The first hurdle for the therapeutic use of Treg is their insufficient numbers in non- manipulated individuals, in particular when facing strong immune activation and expanding alloreactive effector cells. Because of the limitations associated with current protocols aiming at ex-vivo expansion or in vitro induction of Treg, the aim of the first part of this thesis was to determine the efficacy of direct in vivo expansion of Treg using the IL-2/JES6- 1 immune complex (IL2c). We found that whilst IL2c mediated Treg expansion alone allowed the prolonged graft survival of fìlli MHC-mismatched skin grafts, its combination with short-term CD40L-CD40 co-stimulation blockade (anti-CD 154/MR1) to inhibit T cell activation administered at the time of transplantation was able to achieve long-term robust tolerance. This study also highlighted the importance of combining Treg based therapies with the appropriate co-stimulation blockade as a combination of IL2c and CD28-B7.1/2 co- stimulation blockade (CTLA-4 Ig) only resulted in slight prolongation of graft survival but not tolerance. The translation of tolerance induction therapies modelled in rodents into non-human primates or into clinical trials has seldom been successful. One main reason being the presence of pre-existing memory T- and B-cells due to acquired immunity in humans versus laboratory animals. Hence, we tested whether IL2c+MRl could promote graft survival in pre-sensitized mice. We found that in the presence of alloreactive memory T- and B-cells, IL2c+MRl combination therapy could prolong MHC-mismatched skin graft survival in immunocompetent mice but tolerance was lost compared to the naïve recipients. The addition of anti-LF A-1 treatment, which prevents the trafficking of memory T cells worked synergistically to significantly further enhance graft survival. However, late rejection mediated by activated/memory B cells and persistent donor-specific alloantibodies still occurred. Immunotherapeutic strategies targeting the activation of T cells are the cornerstone in the current immunosuppressive management after SOT. Therefore, in the next part of this thesis we investigated the paracaspase Malti-dependent T-cell receptor signalling as a novel immunosuppressive strategy to control alloreactive T cells in transplantation. We observed that although the inhibition of Malti downstream T signalling lead to tolerance of a minor H- mismatch skin grafts, it was however not sufficient to regulate alloresponses against MHC mismatches and only prolonged graft survival. Furthermore, we investigated the potential of more selectively targeting the protease activity of Malti. Constitutive inhibition of Malti protease activity in Malti-ki mice was detrimental to tolerance induction as it diminished Treg function and increased Thl alloreactivity. However, when using a small peptide inhibitor of Malti proteolytic activity in vitro, we observed an attenuation of alloreactive T cells and sparing of the pre-existing Treg pool. This indicates that further investigation of the role of Malti signalling in the field of transplantation is required. Collectively, the findings of this thesis provide immunological mechanisms underlying novel therapeutic strategies for the promotion of tolerance in SOT. Moreover, we highlight the importance of testing tolerance induction therapies in more physiological models with pre-existing alloreactive memory T and B cells.

Long-term X-ray variability of the microquasar system LS5039/RX J1826.2-1450

We report on the results of the spectral and timing analysis of a BeppoSAX observation of the microquasar system LS 5039/RX J1826.2-1450. The source was found in a low-flux state with Fx(1-10 keV)= 4.7 x 10^{-12} erg cm^{-2} s^{-1}, which represents almost one order of magnitude lower than a previous RXTE observation 2.5 years before. The 0.1--10 keV spectrum is described by an absorbed power-law continuum with photon-number spectral index Gamma=1.8+-0.2 and hydrogen column density of NH=1.0^{+0.4}_{-0.3} x 10^{22} cm^{-2}. According to the orbital parameters of the system the BeppoSAX observation covers the time of an X-ray eclipse should one occur. However, the 1.6-10 keV light curve does not show evidence for such an event, which allows us to give an upper limit to the inclination of the system. The low X-ray flux detected during this observation is interpreted as a decrease in the mass accretion rate onto the compact object due to a decrease in the mass-loss rate from the primary.

Traumatic injuries after mechanical cardiopulmonary resuscitation (LUCAS?2): a forensic autopsy study.

AIM: The aim of our study was to compare traumatic injuries observed after cardiopulmonary resuscitation (CPR) by means of standard (manual) or assisted (mechanical) chest compression by Lund University Cardiopulmonary Assist System, 2nd generation (LUCAS?2) device. METHODS: A retrospective study was conducted including cases from 2011 to 2013, analysing consecutive autopsy reports in two groups of patients who underwent medicolegal autopsy after unsuccessful CPR. We focused on traumatic injuries from dermal to internal trauma, collecting data according to a standardised protocol. RESULTS: The study group was comprised of 26 cases, while 32 cases were included in the control group. Cardiopulmonary resuscitation performed by LUCAS?2 was longer than manual CPR performed in control cases (study group: mean duration 51.5 min; controls 29.4 min; p = 0.004). Anterior chest lesions (from bruises to abrasions) were described in 18/26 patients in the LUCAS?2 group and in 6/32 of the control group. A mean of 6.6 rib fractures per case was observed in the LUCAS?2 group, but this was only 3.1 in the control group (p = 0.007). Rib fractures were less frequently observed in younger patients. The frequency of sternal factures was similar in both groups. A few trauma injuries to internal organs (mainly cardiac, pulmonary and hepatic bruises), and some petechiae (study 46 %; control 41 %; p = 0.79) were recorded in both groups. CONCLUSION: LUCAS?2-CPR is associated with more rib fractures than standard CPR. Typical round concentric skin lesions were observed in cases of mechanical reanimation. No life-threatening injuries were reported. Petechiae were common findings.

MAGIC TeV Gamma-Ray Observations of Markarian 421 during Multiwavelength Campaigns in 2006

Wide-range spectral coverage of blazar-type active galactic nuclei is of paramount importance for understanding the particle acceleration mechanisms assumed to take place in their jets. The Major Atmospheric Gamma Imaging Cerenkov (MAGIC) telescope participated in three multiwavelength (MWL) campaigns, observing the blazar Markarian (Mkn) 421 during the nights of April 28 and 29, 2006, and June 14, 2006. Aims. We analyzed the corresponding MAGIC very-high energy observations during 9 nights from April 22 to 30, 2006 and on June 14, 2006. We inferred light curves with sub-day resolution and night-by-night energy spectra. Methods. MAGIC detects γ-rays by observing extended air showers in the atmosphere. The obtained air-shower images were analyzed using the standard MAGIC analysis chain. Results. A strong γ-ray signal was detected from Mkn 421 on all observation nights. The flux (E > 250 GeV) varied on night-by-night basis between (0.92±0.11) × 10-10 cm-2 s-1 (0.57 Crab units) and (3.21±0.15) × 10-10 cm-2 s-1 (2.0 Crab units) in April 2006. There is a clear indication for intra-night variability with a doubling time of 36± min on the night of April 29, 2006, establishing once more rapid flux variability for this object. For all individual nights γ-ray spectra could be inferred, with power-law indices ranging from 1.66 to 2.47. We did not find statistically significant correlations between the spectral index and the flux state for individual nights. During the June 2006 campaign, a flux substantially lower than the one measured by the Whipple 10-m telescope four days later was found. Using a log-parabolic power law fit we deduced for some data sets the location of the spectral peak in the very-high energy regime. Our results confirm the indications of rising peak energy with increasing flux, as expected in leptonic acceleration models.

Discovery of a High-Energy Gamma-Ray-Emitting Persistent Microquasar

Microquasars are stellar x-ray binaries that behave as a scaled down version of extragalactic quasars. The star LS 5039 is a new microquasar system with apparent persistent ejection of relativistic plasma at a 3 kiloparsec distance from the sun. It may also be associated with a gamma-ray source discovered by the Energetic Gamma Ray Experiment Telescope (EGRET) on board the COMPTON-Gamma Ray Observatory satellite. Before the discovery of LS 5039, merely a handful of microquasars had been identified in the Galaxy, and none of them was detected in high-energy gamma-rays.

Deep GMRT radio observations and a multi-wavelength study of the region around HESS J1858+020

Context. There are a number of very high energy sources in the Galaxy that remain unidentified. Multi-wavelength and variability studies, and catalogue searches, are powerful tools to identify the physical counterpart, given the uncertainty in the source location and extension. Aims. This work carries out a thorough multi-wavelength study of the unidentified, very high energy source HESS J1858+020 and its environs. Methods. We have performed Giant Metrewave Radio Telescope observations at 610 MHz and 1.4 GHz to obtain a deep, low-frequency radio image of the region surrounding HESS J1858+020. We analysed archival radio, infrared, and X-ray data as well. This observational information, combined with molecular data, catalogue sources, and a nearby Fermi gamma-ray detection of unidentified origin, are combined to explore possible counterparts to the very high energy source. Results. We provide with a deep radio image of a supernova remnant that might be related to the GeV and TeV emission in the region. We confirm the presence of an H ii region next to the supernova remnant and coincident with molecular emission. A potential region of star formation is also identified. We identify several radio and X-ray sources in the surroundings. Some of these sources are known planetary nebulae, whereas others may be non-thermal extended emitters and embedded young stellar objects. Three old, background Galactic pulsars also neighbour HESS J1858+020 along the line of sight. Conclusions. The region surrounding HESS J1858+020 is rich in molecular structures and non-thermal objects that may potentially be linked to this unidentified very high energy source. In particular, a supernova remnant interacting with nearby molecular clouds may be a good candidate, but a star forming region, or a non-thermal radio source of yet unclear nature, may also be behind the gamma-ray source. The neighbouring pulsars, despite being old and distant, cannot be discarded as candidates. Further observational studies are needed, however, to narrow the search for a counterpart to the HESS source.