Hubble-Lema\^itre fragmentation and the path to equilibrium of merger-driven cluster formation

This paper discusses a new method to generate self-coherent initial conditions for young substructured stellar cluster. The expansion of a uniform system allows stellar sub-structures (clumps) to grow from fragmentation modes by adiabatic cooling. We treat the system mass elements as stars, chosen according to a Salpeter mass function, and the time-evolution is performed with a collisional N-body integrator. This procedure allows to create a fully-coherent relation between the clumps' spatial distribution and the underlying velocity field. The cooling is driven by the gravitational field, as in a cosmological Hubble-Lema\^itre flow. The fragmented configuration has a `fractal'-like geometry but with a self-grown velocity field and mass profile. We compare the characteristics of the stellar population in clumps with that obtained from hydrodynamical simulations and find a remarkable correspondence between the two in terms of the stellar content and the degree of spatial mass-segregation. In the fragmented configuration, the IMF power index is ~0.3 lower in clumps in comparison to the field stellar population, in agreement with observations in the Milky Way. We follow in time the dynamical evolution of fully fragmented and sub-virial configurations, and find a soft collapse, leading rapidly to equilibrium (timescale of 1 Myr for a ~ 10^4 Msun system). The low-concentration equilibrium implies that the dynamical evolution including massive stars is less likely to induce direct collisions and the formation of exotic objects. Low-mass stars already ejected from merging clumps are depleted in the end-result stellar clusters, which harbour a top-heavy stellar mass function.Comment: 22 pages, accepted for publication in MNRA

RSCA genotyping of MHC for high-throughput evolutionary studies in the model organism three-spined stickleback Gasterosteus aculeatus

<p>Abstract</p> <p>Background</p> <p>In all jawed vertebrates, highly polymorphic genes of the major histocompatibility complex (MHC) encode antigen presenting molecules that play a key role in the adaptive immune response. Their polymorphism is composed of multiple copies of recently duplicated genes, each possessing many alleles within populations, as well as high nucleotide divergence between alleles of the same species. Experimental evidence is accumulating that MHC polymorphism is a result of balancing selection by parasites and pathogens. In order to describe MHC diversity and analyse the underlying mechanisms that maintain it, a reliable genotyping technique is required that is suitable for such highly variable genes.</p> <p>Results</p> <p>We present a genotyping protocol that uses Reference Strand-mediated Conformation Analysis (RSCA), optimised for recently duplicated MHC class IIB genes that are typical for many fish and bird species, including the three-spined stickleback, <it>Gasterosteus aculeatus</it>. In addition we use a comprehensive plasmid library of MHC class IIB alleles to determine the nucleotide sequence of alleles represented by RSCA allele peaks. Verification of the RSCA typing by cloning and sequencing demonstrates high congruency between both methods and provides new insight into the polymorphism of classical stickleback MHC genes. Analysis of the plasmid library additionally reveals the high resolution and reproducibility of the RSCA technique.</p> <p>Conclusion</p> <p>This new RSCA genotyping protocol offers a fast, but sensitive and reliable way to determine the MHC allele repertoire of three-spined sticklebacks. It therefore provides a valuable tool to employ this highly polymorphic and adaptive marker in future high-throughput studies of host-parasite co-evolution and ecological speciation in this emerging model organism.</p

Evolution dynamique des amas stellaires jeunes

Comprendre le processus de formation stellaire est un objectif majeur en astronomie. Sur ce sujet les observations ne donnent que très peu d'information, et les modèles numériques sont donc naturellement privilégiés. De tels modèles s'attachent à suivre la dynamique du gaz, sous l'effet de processus physique variés, ce qui nécessite un temps de calcul très important et ne permet pas de modéliser l'évolution au delà de 0.2 Myr environ. Or les résultats observationnels sont essentiellement issus du champ galactique proche, des amas évolués, voire des regions jeunes ou associations d'étoiles, dont l'âge peut varier de 1 Myr à quelques Gyr. Par conséquent, il est nécessaire pour comparer les résultats des modèles aux observations de comprendre ce qu'il se passe durant cet intervalle de temps. La formation stellaire tend à produire des étoiles en groupes, à partir de l'effondrement gravitationnel d'un nuage moléculaire turbulent. A mesure que les étoiles se forment, le gaz est éjecté et l'évolution est dominée par les interactions gravitationnelles. Suivre l'évolution sous l'effet de ces interactions est couramment utilisé afin de contraindre les modèles et de mieux comprendre l'origine des populations stellaires observées. Les étoiles se forment en sous-groupes ou structures hiérarchisées, qui peuvent ensuite fusionner pour donner des amas stellaires proche des amas ouverts, ou au contraire finir en associations distinctes. Dans ma thèse, je me suis intéressé à l'évolution dynamique de petits groupes d'étoiles, jusqu'alors peu étudiés par rapport aux groupes à 1000 ou 10^4 étoiles. J'ai simulé l'évolution de groupes à N < 100, dans le but d'en étudier la dynamique d'un point de vue statistique, grâce notamment au grand nombre de simulations effectuées, et afin d'identifier les signatures observationnelles propres à une situation initiale donnée. A partir d'un grand nombre de configurations initiales (avec N=20, 50, 100, un rayon typique de 0.025 pc à 1 pc) et 500 simulations par configurations, j'ai étudié l'évolution dynamique de groupes composés d'étoiles de même masse ou comprenant un spectre de masse, et sans population de binaire initiale. L'évolution de tels groupes s'est révélée similaire à celle de groupes plus grands, mais avec une phase d'effondrement plus rapide et surtout moins prononcée. Je décris le comportement moyen menant à une lente expansion de l'amas, ainsi qu'une voie d'évolution très différente, apparaissant dans 17% des cas étudiés, où l'amas est complètement dispersé suite à l'éjection d'une binaire centrale serrée. J'ai également recherché dans quelle mesure les données en densité et en vitesse 3D pouvaient permettre d'identifier l'état dynamique initial d'un groupe. L'utilisation de ces seules données suffisait dans certain cas à déterminer la densité initiale, mais elles devraient être complétées par des données concernant la population de binaire. Ce travail pourra être mis en application pour étudier l'origine dynamique d'association ou de groupes stellaires connus. Enfin, j'ai effectué un grand nombre de simulations numériques dans le but de reproduire l'état observé de l'amas eta Chamaeleontis par pure évolution dynamique à partir de conditions initiales standards. Cette association présente des caractéristiques d'amas évolué, telle que son spectre de masse pauvre en objets de faible masse et l'absence de binaires larges. Je montre que ces propriétés ne peuvent pas être reproduites uniquement par la dynamique, et sont donc les traces d'un processus de formation non standard.Understanding the star formation process is a key issue in astronomy. Since direct observation provide only very limited information, this issue is investigated by models. Such models need to take into account complex physical processes while following the gas dynamics, so that simulations need a lot of time to run and do not follow the star formation process for longer than 0.2 Myr. The best known observational results concerns the field population, evolved open clusters or younger clusters or associations, which are between 1 Myr and a few Gyr old. Therefore in order to compare the results from models to known observations, we need to bridge the gap between the two. Star formation appears to produce groups of stars from the collapse of turbulent molecular clouds. As stars form, the gas is progressively ejected from the cluster, and the evolution is dominated by gravitational interactions. Following the dynamical evolution of a group of star using N-Body codes is a standard way used to constraint the models and understand the origin of the different populations. Star formation may produce sub-structure or small groups that merge to form bigger entities, or end up as loose association. In my thesis I focused on the dynamics of small groups, that have not been investigated as thoroughly as 1000 or 10^4 star groups. I performed N-Body simulations of small stellar groups, with N<100, in order to study their dynamics using a statistical approach, made possible by running a large number of simulations, and to find some observational signatures of given initial conditions. This approach enable to take full account of stochastic effects due to dynamical interactions. Using a large number of initial configurations (with N=20, 50, 100, a typical radius from 0.025 pc to 1 pc) and a sample of 500 simulations per configuration, I looked at equal mass groups as well as groups having a mass spectrum, without any binary initially. Such small groups show similar evolution to bigger groups, but with faster and less pronounced collapse phase. I described the average behaviour of slow expansion of the cluster, and an alternative evolution, occurring with 17% probability, that ended in the complete dissolution of the group due to ejection of a central binary. Searching for a way to identify the initial configuration from observational measure, I looked at the complementarity of density and 3D velocity and was able to show that it could be sufficient in some cases to determine the initial density. Further investigations are needed to take into account the information on the binary population and will be used to investigate the formation of known associations or young regions. Finally, I ran a large number of simulations, aiming at reproducing the observed state of the eta Chamaeleontis from standard initial conditions and pure dynamical evolution. This association properties are consistent with a dynamical evolved cluster, namely low-mass object poor and having only tight binaries. I showed that these properties cannot be reproduced with pure dynamical evolution from standard initial mass function and binary population, meaning that its particular features must have been pristine.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Image-guided multipolar radiofrequency ablation of liver tumours: initial clinical results

The local effectiveness and clinical usefulness of multipolar radiofrequency (RF) ablation of liver tumours was evaluated. Sixty-eight image-guided RF sessions were performed using a multipolar device with bipolar electrodes in 53 patients. There were 45 hepatocellular carcinomas (HCC) and 42 metastases with a diameter ≤3cm (n = 55), 3.1-5cm (n = 29) and >5cm (n = 3); 26 nodules were within 5mm from large vessels. Local effectiveness and complications were evaluated after RF procedures. Mean follow-up was 17 ± 10months. Recurrence and survival rates were analysed by the Kaplan-Meier method. The primary and secondary technical effectiveness rate was 82% and 95%, respectively. The major and minor complication rate was 2.9%, respectively. The local tumour progression at 1- and 2-years was 5% and 9% for HCC nodules and 17% and 31% for metastases, respectively; four of 26 nodules (15%) close to vessels showed local progression. The survival at 1year and 2years was 97% and 90% for HCC and 84% and 68% for metastases, respectively. Multipolar RF technique creates ablation zones of adequate size and tailored shape and is effective to treat most liver tumours, including those close to major hepatic vessel

Two phase I studies of BI 836880, a vascular endothelial growth factor/angiopoietin-2 inhibitor, administered once every 3 weeks or once weekly in patients with advanced solid tumors

Vascular endothelial growth factor; Advanced solid tumors; NanobodyFactor de crecimiento endotelial vascular; Tumores sólidos avanzados; NanocuerpoFactor de creixement endotelial vascular; Tumors sòlids avançats; NanocosBackground BI 836880 is a humanized bispecific nanobody® that inhibits vascular endothelial growth factor and angiopoietin-2. Here, we report results from two phase I, nonrandomized, dose-escalation studies (NCT02674152 and NCT02689505; funded by Boehringer Ingelheim) evaluating BI 836880 in patients with confirmed locally advanced or metastatic solid tumors, refractory to standard therapy, or for which standard therapy was ineffective. Patients and Methods Patients aged ≥18 years, with an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function received escalating intravenous doses of BI 836880 once every 3 weeks (Q3W; Study 1336.1) or once weekly (QW; Study 1336.6). Primary objectives were maximum tolerated dose (MTD) and recommended phase II dose of BI 836880, based on dose-limiting toxicities (DLTs) during the first cycle. Results Patients received one of five dosages of 40-1000 mg Q3W (29 patients) or 40-240 mg QW (24 patients). One DLT occurred with Q3W treatment [Grade (G) 3 pulmonary embolism (1000 mg)]. Five DLTs occurred in four patients treated QW [G2 proteinuria (120 mg); G3 hypertension (180 mg); G3 proteinuria and G3 hypertension (240 mg); and G4 respiratory distress (240 mg)]. All patients experienced adverse events, most commonly hypertension with Q3W treatment (89.7%; G3 41.4%), and asthenia with QW treatment (62.5%). Two patients treated Q3W (both 1000 mg) and three patients treated QW (120 mg, 2 patients; 180 mg, 1 patient) experienced partial response. Conclusions The MTD of BI 836880 was 720 mg Q3W and 180 mg QW. BI 836880 was generally manageable and demonstrated preliminary efficacy.This work was supported by Boehringer Ingelheim International GmbH. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Hannah Simmons, MSc, of Ashfield MedComms, an Ashfield Health company and funded by Boehringer Ingelheim

Vibration dependent branching and photoelectron angular distributions observed across the Cooper minimum region of bromobenzene

Vibrational state-resolved photoelectron anisotropy parameters, beta, for the ~X 2B1, ~B 2B2, and ~C2B1 state ionizations of bromobenzene have been recorded at photon energies ranging from 20.5 to 94 eV, so spanning the region of the expected bromine Cooper minimum (CM). The ~X state displays no CM and its beta value is also independent of vibrational level, in accord with the Franck-Condon Approximation. The ~B and ~ C state beta values display the CM to differing degrees, but both show a vibrational dependence that extends well below the obvious CM dip. Calculations are presented that replicate these observations of Franck-Condon Approximation breakdown spanning an extended photon energy range. This is the first demonstration of such wide-ranging breakdown detected in the beta anisotropy parameter in the absence of any resonance. Measured and calculated vibrational branching ratios for these states are also presented. Although the ~B state branching ratios remain constant, in accord with Franck-Condon expectations, the ~X and (especially) the ~C state ratios display weak, quasi-linear variations across the studied range of photon energy, but with no apparent correlation with the CM position

Studies Needed to Address Public Health Challenges of the 2009 H1N1 Influenza Pandemic: Insights from Modeling

In light of the 2009 influenza pandemic and potential future pandemics, Maria Van Kerkhove and colleagues anticipate six public health challenges and the data needed to support sound public health decision making.The authors acknowledge support from the Bill & Melinda Gates Foundation (MDVK, CF, NMF); Royal Society (CF); Medical Research Council (MDVK, CF, PJW, NMF); EU FP7 programme (NMF); UK Health Protection Agency (PJW); US National Institutes of Health Models of Infectious Disease Agent Study program through cooperative agreement 1U54GM088588 (ML); NIH Director's Pioneer Award, DP1-OD000490-01 (DS); EU FP7 grant EMPERIE 223498 (DS); the Wellcome Trust (DS); 3R01TW008246-01S1 from Fogerty International Center and RAPIDD program from Fogerty International Center with the Science & Technology Directorate, Department of Homeland Security (SR); and the Institut de Veille Sanitaire Sanitaire funded by the French Ministry of Health (J-CD). The funders played no role in the decision to submit the article or in its preparation

Dorsoventral differences in intrinsic properties in developing CA1 pyramidal cells.

The dorsoventral and developmental gradients of entorhinal layer II cell grid properties correlate with their resonance properties and with their hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel current characteristics. We investigated whether such correlation existed in rat hippocampal CA1 pyramidal cells, where place fields also show spatial and temporal gradients. Resonance was absent during the first postnatal week, and emerged during the second week. Resonance was stronger in dorsal than ventral cells, in accord with HCN current properties. Resonance responded to cAMP in ventral but not in dorsal cells. The dorsoventral distribution of HCN1 and HCN2 subunits and of the auxiliary protein tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) could account for these differences between dorsal and ventral cells. The analogous distribution of the intrinsic properties of entorhinal stellate and hippocampal cells suggests the existence of general rules of organization among structures that process complementary features of the environment

Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions

BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate

Differential dorso-ventral distributions of Kv4.2 and HCN proteins confer distinct integrative properties to hippocampal CA1 pyramidal cell distal dendrites.

The dorsal and ventral regions of the hippocampus perform different functions. Whether the integrative properties of hippocampal cells reflect this heterogeneity is unknown. We focused on dendrites where most synaptic input integration takes place. We report enhanced backpropagation and theta resonance and decreased summation of synaptic inputs in ventral versus dorsal CA1 pyramidal cell distal dendrites. Transcriptional Kv4.2 down-regulation and post-transcriptional hyperpolarization-activated cyclic AMP-gated channel (HCN1/2) up-regulation may underlie these differences, respectively. Our results reveal differential dendritic integrative properties along the dorso-ventral axis, reflecting diverse computational needs