The production of
Δ
++ baryons has been measured using 3.5 million hadronic Z
0 decays collected with the OPAL detector at LEP. The production rate and fragmentation function are presented. A total ...of
0.22 ± 0.04 ± 0.04 Δ
++ + (
Δ)
−−
per hadronic Z
0 decay is observed. The fragmentation function is found to be softer than that predicted by the JETSET and HERWIG Monte Carlo event generators. With this measurement of
Δ
++ production, at least one baryon of each strangeness level in the lightest baryon decuplet has now been measured at LEP.
Tau trigger at the ATLAS experiment Benslama, K; Belanger-Champagne, C; Bosman, M ...
arXiv (Cornell University),
10/2008
Paper, Journal Article
Open access
Many theoretical models, like the Standard Model or SUSY at large tan(beta), predict Higgs bosons or new particles which decay more abundantly to final states including tau leptons than to other ...leptons. At the energy scale of the LHC, the identification of tau leptons, in particular in the hadronic decay mode, will be a challenging task due to an overwhelming QCD background which gives rise to jets of particles that can be hard to distinguish from hadronic tau decays. Equipped with excellent tracking and calorimetry, the ATLAS experiment has developed tau identification tools capable of working at the trigger level. This contribution presents tau trigger algorithms which exploit the main features of hadronic tau decays and describes the current tau trigger commissioning activities.
Fifteen per cent of cancers maintain telomere length independently of telomerase by the homologous recombination (HR)-associated alternative lengthening of telomeres (ALT) pathway. A unifying feature ...of these tumours are mutations in ATRX. Here we show that expression of ectopic ATRX triggers a suppression of the pathway and telomere shortening. Importantly ATRX-mediated ALT suppression is dependent on the histone chaperone DAXX. Re-expression of ATRX is associated with a reduction in replication fork stalling, a known trigger for HR and loss of MRN from telomeres. A G-quadruplex stabilizer partially reverses the effect of ATRX, inferring ATRX may normally facilitate replication through these sequences that, if they persist, promote ALT. We propose that defective telomere chromatinization through loss of ATRX promotes the persistence of aberrant DNA secondary structures, which in turn present a barrier to DNA replication, leading to replication fork stalling, collapse, HR and subsequent recombination-mediated telomere synthesis in ALT cancers.
This study offers some general remarks on the interpretation of the tophet-phenomenon in the light of the current debate. The importance of interpretative models based on a comprehensive knowledge ...and use of all sources is stressed, together with the need of organic theories, not limited to individual aspects, but seeking to tackle the entire range of issues. In particular, the relationship between urns and stelae is reconsidered, concluding that the interment of the urns and the erection of the votive markers were the final act of a unique ceremony. The issue of the presence of infant burials in a necropolis located in the vicinity of a tophet is raised again, in the light of new data provided by the recent excavations at Motya (Sicily): a circumstance that the theory of the tophet as an infant necropolis fails to explain adequately. On the contrary, the hypothesis of the tophet as a cult-place where newborns or very young children (and lambs and kids) were sacrificed to the gods as a consequence of a vow matches all our sources, and can answer many questions that would otherwise remain unsolved.
Cette étude propose des remarques générales concernant l’interprétation du phénomène tophet à la lumière des débats récents. L’on insiste sur la nécéssité d’interprétations fondées sur la ...connaissance et l’exploitation de toutes les sources, ainsi que des théories qui abordent tous les volets du problème, sans se limiter à des aspects particuliers. L’on reconsidère la question des rapports entre urnes et stèles, en concluant que la déposition des urnes et l’érection des marqueurs votifs sont les actes conclusifs d’une cérémonie unitaire. L’on aborde enfin la question de la présence de sépultures infantiles dans les nécropoles proches d’un tophet, à la lumières des résultats récents issus des fouilles menées à Motyé (Sicile), une donnée qui ne peut pas être expliquée de manière adéquate par la théorie du tophet comme nécropole infantile. Par contre, l’interprétation du tophet comme lieu de culte où les nouveau-nés ou les bébés (et des animaux) étaient sacrifiés aux dieux suite à un vœu est compatible avec toutes les sources et fournit des réponses convaincantes à des questions qui resteraient autrement sans explication.
The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular ...progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently been identified in tumours which maintain their telomeres by a telomerase independent pathway involving homologous recombination thought to be triggered by DNA damage. It is as yet unknown whether there is a central underlying mechanism associated with ATRX dysfunction which can explain the numerous cellular phenomena observed. There is, however, growing evidence for its role in the replication of various repetitive DNA templates which are thought to have a propensity to form secondary structures. Using a mouse knockout model we demonstrate that ATRX plays a direct role in facilitating DNA replication. Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells.
Driven by the necessity to survive environmental pathogens, the human immune system has evolved exceptional diversity and plasticity, to which several factors contribute including inheritable ...structural polymorphism of the underlying genes. Characterizing this variation is challenging due to the complexity of these loci, which contain extensive regions of paralogy, segmental duplication and high copy-number repeats, but recent progress in long-read sequencing and optical mapping techniques suggests this problem may now be tractable. Here we assess this by using long-read sequencing platforms from PacBio and Oxford Nanopore, supplemented with short-read sequencing and Bionano optical mapping, to sequence DNA extracted from CD14
+
monocytes and peripheral blood mononuclear cells from a single European individual identified as HV31. We use this data to build a
de novo
assembly of eight genomic regions encoding four key components of the immune system, namely the human leukocyte antigen, immunoglobulins, T cell receptors, and killer-cell immunoglobulin-like receptors. Validation of our assembly using k-mer based and alignment approaches suggests that it has high accuracy, with estimated base-level error rates below 1 in 10 kb, although we identify a small number of remaining structural errors. We use the assembly to identify heterozygous and homozygous structural variation in comparison to GRCh38. Despite analyzing only a single individual, we find multiple large structural variants affecting core genes at all three immunoglobulin regions and at two of the three T cell receptor regions. Several of these variants are not accurately callable using current algorithms, implying that further methodological improvements are needed. Our results demonstrate that assessing haplotype variation in these regions is possible given sufficiently accurate long-read and associated data. Continued reductions in the cost of these technologies will enable application of these methods to larger samples and provide a broader catalogue of germline structural variation at these loci, an important step toward making these regions accessible to large-scale genetic association studies.
In the development of cell-based cancer therapies, quantitative mathematical models of cellular interactions are instrumental in understanding treatment efficacy. Efforts to validate and interpret ...mathematical models of cancer cell growth and death hinge first on proposing a precise mathematical model, then analyzing experimental data in the context of the chosen model. In this work, we present the first application of the sparse identification of non-linear dynamics (SINDy) algorithm to a real biological system in order discover cell-cell interaction dynamics in
experimental data, using chimeric antigen receptor (CAR) T-cells and patient-derived glioblastoma cells. By combining the techniques of latent variable analysis and SINDy, we infer key aspects of the interaction dynamics of CAR T-cell populations and cancer. Importantly, we show how the model terms can be interpreted biologically in relation to different CAR T-cell functional responses, single or double CAR T-cell-cancer cell binding models, and density-dependent growth dynamics in either of the CAR T-cell or cancer cell populations. We show how this data-driven model-discovery based approach provides unique insight into CAR T-cell dynamics when compared to an established model-first approach. These results demonstrate the potential for SINDy to improve the implementation and efficacy of CAR T-cell therapy in the clinic through an improved understanding of CAR T-cell dynamics.
Pediatric medulloblastoma (MB) is the most common solid malignant brain neoplasm, with Group 3 (G3) MB representing the most aggressive subgroup. MYC amplification is an independent poor prognostic ...factor in G3 MB, however, therapeutic targeting of the MYC pathway remains limited and alternative therapies for G3 MB are urgently needed. Here we show that the RNA-binding protein, Musashi-1 (MSI1) is an essential mediator of G3 MB in both MYC-overexpressing mouse models and patient-derived xenografts. MSI1 inhibition abrogates tumor initiation and significantly prolongs survival in both models. We identify binding targets of MSI1 in normal neural and G3 MB stem cells and then cross referenced these data with unbiased large-scale screens at the transcriptomic, translatomic and proteomic levels to systematically dissect its functional role. Comparative integrative multi-omic analyses of these large datasets reveal cancer-selective MSI1-bound targets sharing multiple MYC associated pathways, providing a valuable resource for context-specific therapeutic targeting of G3 MB.
PDF
