Effects of Heat-Producing Elements on the Stability of Deep Mantle Thermochemical Piles

©2020. American Geophysical Union. All Rights Reserved. Geochemical observations of ocean island and mid-ocean ridge basalts suggest that abundances of heat-producing elements (HPEs: U, Th, and K) vary within the mantle. Combined with bulk silicate Earth models and constraints on the Earth's heat budget, these observations suggest the presence of a more enriched (potentially deep and undepleted) reservoir in the mantle. Such a reservoir may be related to seismically observed deep mantle structures known as large low shear velocity provinces (LLSVPs). LLSVPs might represent thermochemical piles of an intrinsically denser composition, and many studies have shown such piles to remain stable over hundreds of Myr or longer. However, few studies have examined if thermochemical piles can remain stable if they are enriched in HPEs, a necessary condition for them to constitute an enriched HPE reservoir. We conduct a suite of mantle convection simulations to examine the effect of HPE enrichment up to 25× the ambient mantle on pile stability. Model results are evaluated against present-day pile morphology and tested for resulting seismic signatures using self-consistent potential pile compositions. We find that stable piles can form from an initial basal layer of dense material even if the layer is enriched in HPEs, depending on the density of the layer and degree of HPE enrichment, with denser basal layers requiring increased HPE enrichment to form pile-like morphology instead of a stable layer. Thermochemical piles or LLSVPs may therefore constitute an enriched reservoir in the deep mantle

8th International Conference: Primary Therapy of Early Breast Cancer, St Gallen, Switzerland, March 12–15 2003

The International St Gallen Breast Cancer Conference concentrates almost exclusively on adjuvant, multimodal primary therapy for early breast cancer. Begun 25 years ago, this meeting was initially held every 4 years, but therapeutic progress, new strategies and provocative trials data have accelerated to the extent that conferences are now held biennially. The meeting this year was attended by almost 3000 delegates. Major topics included new prognostic and predictive markers in early breast cancer, the best use of adjuvant chemotherapy and endocrine therapy, and innovations in local surgery and radiation therapy

Report on the 4th European Breast Cancer Conference, Hamburg, Germany, 16–20 March 2004

The 4th European Breast Cancer Conference, organized under the auspices of the European Organization for Research and Treatment of Cancer Breast Cancer Group, of the European Breast Cancer Coalition (Europa Donna) and of the European Society of Mastology (EUSOMA), was held in Hamburg, Germany on 16–20 March 2004. The leading theme of the conference was partnership among scientists, clinicians, carers, advocates and patients. The present article provides a brief description of the most important conference presentations on molecular biology, epidemiology, prevention, pathology, diagnosis and treatment at all stages of breast cancer

Identification of β-Secretase (BACE1) Substrates Using Quantitative Proteomics

β-site APP cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease with a lumenal active site that sheds the ectodomains of membrane proteins through juxtamembrane proteolysis. BACE1 has been studied principally for its role in Alzheimer's disease as the β-secretase responsible for generating the amyloid-β protein. Emerging evidence from mouse models has identified the importance of BACE1 in myelination and cognitive performance. However, the substrates that BACE1 processes to regulate these functions are unknown, and to date only a few β-secretase substrates have been identified through candidate-based studies. Using an unbiased approach to substrate identification, we performed quantitative proteomic analysis of two human epithelial cell lines stably expressing BACE1 and identified 68 putative β-secretase substrates, a number of which we validated in a cell culture system. The vast majority were of type I transmembrane topology, although one was type II and three were GPI-linked proteins. Intriguingly, a preponderance of these proteins are involved in contact-dependent intercellular communication or serve as receptors and have recognized roles in the nervous system and other organs. No consistent sequence motif predicting BACE1 cleavage was identified in substrates versus non-substrates. These findings expand our understanding of the proteins and cellular processes that BACE1 may regulate, and suggest possible mechanisms of toxicity arising from chronic BACE1 inhibition

A randomised pilot Phase II study of doxorubicin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC) given 2 weekly with pegfilgrastim (accelerated) vs 3 weekly (standard) for women with early breast cancer

Accelerated (dose-dense) chemotherapy, in which the frequency of administration is increased without changing total dose or duration, may increase the efficacy of cancer chemotherapy. We performed a randomised Phase II study to assess the safety and relative toxicity of AC (doxorubicin; cyclophosphamide) vs E(epirubicin)C given by conventional or accelerated schedules as neoadjuvant or adjuvant chemotherapy for early breast cancer. Furthermore, the relative toxicity of doxorubicin and epirubicin remains uncertain. Patients were randomised to one of four arms; four courses of standard 3 weekly cyclophosphamide 600 mg m−2 in combination with doxorubicin 60 mg m−2 (AC) vs epirubicin 90 mg m−2 (EC) 3 weekly vs the same regimens administered every 2 weeks with pegfilgrastim (G-CSF). A total of 126 patients were treated, 42 with standard AC, 42 with accelerated AC, 19 with standard EC and 23 with accelerated EC. Significantly more grade 3/4 day one neutropenia was seen with standard (6/61, 10%) compared to accelerated (0/65,) regimens (P=0.01). A trend towards more neutropenic sepsis was seen in the combined standard and accelerated AC arms (12/84, 14%) compared to the combined EC arms (1/42, 2%), P=0.06. Falls in left ventricular ejection fraction were not increased with accelerated treatment. Accelerated AC and EC with pegfilgrastim are safe and feasible regimens in the treatment of early breast cancer with less neutropenia than conventional 3 weekly schedules

Multiparticle azimuthal correlations for extracting event-by-event elliptic and triangular flow in Au + Au collisions at sNN =200 GeV

We present measurements of elliptic and triangular azimuthal anisotropy of charged particles detected at forward rapidity 1<|η|<3 in Au + Au collisions at sNN=200 GeV, as a function of centrality. The multiparticle cumulant technique is used to obtain the elliptic flow coefficients v2{2},v2{4},v2{6}, and v2{8}, and triangular flow coefficients v3{2} and v3{4}. Using the small-variance limit, we estimate the mean and variance of the event-by-event v2 distribution from v2{2} and v2{4}. In a complementary analysis, we also use a folding procedure to study the distributions of v2 and v3 directly, extracting both the mean and variance. Implications for initial geometrical fluctuations and their translation into the final-state momentum distributions are discussed

Beam Energy and Centrality Dependence of Direct-Photon Emission from Ultrarelativistic Heavy-Ion Collisions.

The PHENIX collaboration presents first measurements of low-momentum (0.41  GeV/c) direct-photon yield dN_{γ}^{dir}/dη is a smooth function of dN_{ch}/dη and can be well described as proportional to (dN_{ch}/dη)^{α} with α≈1.25. This scaling behavior holds for a wide range of beam energies at the Relativistic Heavy Ion Collider and the Large Hadron Collider, for centrality selected samples, as well as for different A+A collision systems. At a given beam energy, the scaling also holds for high p_{T} (>5  GeV/c), but when results from different collision energies are compared, an additional sqrt[s_{NN}]-dependent multiplicative factor is needed to describe the integrated-direct-photon yield

Pseudorapidity Dependence of Particle Production and Elliptic Flow in Asymmetric Nuclear Collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200 GeV.

Asymmetric nuclear collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200  GeV provide an excellent laboratory for understanding particle production, as well as exploring interactions among these particles after their initial creation in the collision. We present measurements of charged hadron production dN_{ch}/dη in all such collision systems over a broad pseudorapidity range and as a function of collision multiplicity. A simple wounded quark model is remarkably successful at describing the full data set. We also measure the elliptic flow v_{2} over a similarly broad pseudorapidity range. These measurements provide key constraints on models of particle emission and their translation into flow

Nonperturbative transverse-momentum-dependent effects in dihadron and direct photon-hadron angular correlations in p+p collisions at s =200 GeV

Dihadron and isolated direct photon-hadron angular correlations are measured in p+p collisions at s=200 GeV. The correlations are sensitive to nonperturbative initial-state and final-state transverse momenta kT and jT in the azimuthal nearly back-to-back region Δφ∼π. To have sensitivity to small transverse momentum scales, nonperturbative momentum widths of pout, the out-of-plane transverse-momentum component perpendicular to the trigger particle, are measured. In this region, the evolution of pout can be studied when several different hard scales are measured. These widths are used to investigate possible effects from transverse-momentum-dependent factorization breaking. When accounting for the longitudinal-momentum fraction of the away-side hadron with respect to the near-side trigger particle, the widths are found to increase with the hard scale; this is qualitatively similar to the observed behavior in Drell-Yan and semi-inclusive deep-inelastic scattering interactions, where factorization is predicted to hold. The momentum widths are also studied as a function of center-of-mass energy by comparing to previous measurements at s=510 GeV. The nonperturbative jet widths also appear to increase with s at a similar xT, which is qualitatively consistent to similar measurements in Drell-Yan interactions. Future detailed global comparisons between measurements of processes where transverse-momentum-dependent factorization is predicted to hold and be broken will provide further insight into the role of color in hadronic interactions