Compositional Variations in Apatite and Petrogenetic Significance: Examples from Peraluminous Granites and Related Pegmatites and Hydrothermal Veins from the Central Iberian Zone (Spain and Portugal)

Apatite can be used as an archive of processes occurring during the evolution of granitic magmas and as a pegmatite exploration tool. With this aim, a detailed compositional study of apatite was performed on different Variscan granites, pegmatites and quartz veins from the Central Iberian Zone. Manganese in granitic apatite increases with increasing evolution degree. Such Mn increase would not be related to changes in the fO(2) during evolution but rather to a higher proportion of Mn in residual melts, joined to an increase in SiO2 content and peraluminosity. In the case of pegmatitic apatite, the fO(2) and the polymerization degree of the melts seem not to have influenced the Mn and Fe contents but the higher availability of these transition elements and/or the lack of minerals competing for them. The subrounded Fe-Mn phosphate nodules, where apatite often occurs in P-rich pegmatites and P-rich quartz dykes, probably crystallized from a P-rich melt exsolved from the pegmatitic melt and where Fe, Mn and Cl would partition. The low Mn and Fe contents in the apatite from the quartz veins may be attributed either to the low availability of these elements in the late hydrothermal fluids derived from the granitic and pegmatitic melts, or to a high fO(2). The Rare Earth Elements, Sr and Y are the main trace elements of the studied apatites. The REE contents of apatite decrease with the evolution of their hosting rocks. The REE patterns show in general strong tetrad effects that are probably not related to the fluids' activity in the system. On the contrary, the fluids likely drive the non-CHARAC behavior of apatite from the most evolved granitic and pegmatitic units. Low fO(2) conditions seem to be related to strong Eu anomalies observed for most of the apatites associated with different granitic units, barren and P-rich pegmatites. The positive Eu anomalies in some apatites from leucogranites and Li-rich pegmatites could reflect their early character, prior to the crystallization of feldspars. The increase in the Sr content in apatite from Li-rich pegmatites and B-P +/- F-rich leucogranites could be related to problems in accommodating this element in the albite structure, favoring its incorporation into apatite. The triangular plots sigma REE-Sr-Y and U-Th-Pb of apatites, as well as the Eu anomaly versus the TE1,3 diagram, seem to be potentially good as petrogenetic indicators, mainly for pegmatites and, to a lesser extent, for granites from the CIZ

Charge density distributions and related form factors in neutron-rich light exotic nuclei

Charge form factors corresponding to proton density distributions in exotic nuclei, such as $^{6,8}$He, $^{11}$Li, $^{17,19}$B and $^{14}$Be are calculated and compared. The results can be used as tests of various theoretical models for the exotic nuclei structure in possible future experiments using a colliding electron-exotic nucleus storage ring. The result of such a comparison would show the effect of the neutron halo or skin on the proton distributions in exotic nuclei.Comment: 11 pages, 4 figures, to be published in International Journal of Modern Physics

Sensitivities of the Proton-Nucleus Elastical Scattering Observables of 6He and 8He at Intermediate Energies

We investigate the use of proton-nucleus elastic scattering experiments using secondary beams of 6He and 8He to determine the physical structure of these nuclei. The sensitivity of these experiments to nuclear structure is examined by using four different nuclear structure models with different spatial features using a full-folding optical potential model. The results show that elastic scattering at intermediate energies (<100 MeV per nucleon) is not a good constraint to be used to determine features of structure. Therefore researchers should look elsewhere to put constraints on the ground state wave function of the 6He and 8He nuclei.Comment: To be published in Phys. Rev.

Cellular Immunity to Predict the Risk of Cytomegalovirus Infection in Kidney Transplantation: A Prospective, Interventional, Multicenter Clinical Trial

Background: Improving cytomegalovirus (CMV) immune-risk stratification in kidney transplantation is highly needed to establish guided preventive strategies. Methods: This prospective, interventional, multicenter clinical trial assessed the value of monitoring pretransplant CMV-specific cell-mediated immunity (CMI) using an interferon-γrelease assay to predict CMV infection in kidney transplantation. One hundred sixty donor/recipient CMV-seropositive (D+/R+) patients, stratified by their baseline CMV (immediate-early protein 1)-specific CMI risk, were randomized to receive either preemptive or 3-month antiviral prophylaxis. Also, 15-day posttransplant CMI risk stratification and CMI specific to the 65 kDa phosphoprotein (pp65) CMV antigen were investigated. Immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids in 80% of patients, whereas 20% received thymoglobulin induction therapy. Results: Patients at high risk for CMV based on pretransplant CMI developed significantly higher CMV infection rates than those deemed to be at low risk with both preemptive (73.3% vs 44.4%; odds ratio [OR], 3.44 [95% confidence interval {CI}, 1.30-9.08]) and prophylaxis (33.3% vs 4.1%; OR, 11.75 [95% CI, 2.31-59.71]) approaches. The predictive capacity for CMV-specific CMI was only found in basiliximab-treated patients for both preemptive and prophylaxis therapy. Fifteen-day CMI risk stratification better predicted CMV infection (81.3% vs 9.1%; OR, 43.33 [95% CI, 7.89-237.96]). Conclusions: Pretransplant CMV-specific CMI identifies D+/R+ kidney recipients at high risk of developing CMV infection if not receiving T-cell-depleting antibodies. Monitoring CMV-specific CMI soon after transplantation further defines the CMV infection prediction risk. Monitoring CMV-specific CMI may guide decision making regarding the type of CMV preventive strategy in kidney transplantation. Clinical Trials Registration: NCT02550639

Indication for the disappearance of reactor electron antineutrinos in the Double Chooz experiment

The Double Chooz Experiment presents an indication of reactor electron antineutrino disappearance consistent with neutrino oscillations. A ratio of 0.944 $\pm$ 0.016 (stat) $\pm$ 0.040 (syst) observed to predicted events was obtained in 101 days of running at the Chooz Nuclear Power Plant in France, with two 4.25 GW$_{th}$ reactors. The results were obtained from a single 10 m$^3$ fiducial volume detector located 1050 m from the two reactor cores. The reactor antineutrino flux prediction used the Bugey4 measurement as an anchor point. The deficit can be interpreted as an indication of a non-zero value of the still unmeasured neutrino mixing parameter \sang. Analyzing both the rate of the prompt positrons and their energy spectrum we find \sang = 0.086 $\pm$ 0.041 (stat) $\pm$ 0.030 (syst), or, at 90% CL, 0.015 $<$ \sang $\ <$ 0.16.Comment: 7 pages, 4 figures, (new version after PRL referee's comments

Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited. OBJECTIVE: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC and to determine their association with overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: From 100 patients, mCRPC biopsies were assayed by whole exome sequencing, targeted next-generation sequencing, RNA sequencing, tumor mutational burden, T-cell-inflamed gene expression profile (TcellinfGEP) score (Nanostring), and immunohistochemistry for programmed cell death 1 ligand 1 (PD-L1), ataxia-telangiectasia mutated (ATM), phosphatase and tensin homolog (PTEN), SRY homology box 2 (SOX2), and the presence of neuroendocrine features. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The phi coefficient determined correlations between biomarkers of interest. OS was assessed using Kaplan-Meier curves and adjusted hazard ratios (aHRs) from Cox regression. RESULTS AND LIMITATIONS: PD-L1 and SOX2 protein expression was detected by immunohistochemistry (combined positive score ≥1 and >5% cells, respectively) in 24 (33%) and 27 (27%) mCRPC biopsies, respectively; 23 (26%) mCRPC biopsies had high TcellinfGEP scores (>-0.318). PD-L1 protein expression and TcellinfGEP scores were positively correlated (phi 0.63 [0.45; 0.76]). PD-L1 protein expression (aHR: 1.90 [1.05; 3.45]), high TcellinfGEP score (aHR: 1.86 [1.04; 3.31]), and SOX2 expression (aHR: 2.09 [1.20; 3.64]) were associated with worse OS. CONCLUSIONS: PD-L1, TcellinfGEP score, and SOX2 are prognostic of outcome from the mCRPC setting. If validated, predictive biomarker studies incorporating survival endpoints need to take these findings into consideration. PATIENT SUMMARY: This study presents an analysis of immune biomarkers in biopsies from patients with metastatic prostate cancer. We describe tumor alterations that predict prognosis that can impact future studies

Isotopic Composition of Light Nuclei in Cosmic Rays: Results from AMS-01

The variety of isotopes in cosmic rays allows us to study different aspects of the processes that cosmic rays undergo between the time they are produced and the time of their arrival in the heliosphere. In this paper we present measurements of the isotopic ratios 2H/4He, 3He/4He, 6Li/7Li, 7Be/(9Be+10Be) and 10B/11B in the range 0.2-1.4 GeV of kinetic energy per nucleon. The measurements are based on the data collected by the Alpha Magnetic Spectrometer, AMS-01, during the STS-91 flight in 1998 June.Comment: To appear in ApJ. 12 pages, 11 figures, 6 table

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

HER3 Is an Actionable Target in Advanced Prostate Cancer.

It has been recognized for decades that ERBB signaling is important in prostate cancer, but targeting ERBB receptors as a therapeutic strategy for prostate cancer has been ineffective clinically. However, we show here that membranous HER3 protein is commonly highly expressed in lethal prostate cancer, associating with reduced time to castration resistance (CR) and survival. Multiplex immunofluorescence indicated that the HER3 ligand NRG1 is detectable primarily in tumor-infiltrating myelomonocytic cells in human prostate cancer; this observation was confirmed using single-cell RNA sequencing of human prostate cancer biopsies and murine transgenic prostate cancer models. In castration-resistant prostate cancer (CRPC) patient-derived xenograft organoids with high HER3 expression as well as mouse prostate cancer organoids, recombinant NRG1 enhanced proliferation and survival. Supernatant from murine bone marrow-derived macrophages and myeloid-derived suppressor cells promoted murine prostate cancer organoid growth in vitro, which could be reversed by a neutralizing anti-NRG1 antibody and ERBB inhibition. Targeting HER3, especially with the HER3-directed antibody-drug conjugate U3-1402, exhibited antitumor activity against HER3-expressing prostate cancer. Overall, these data indicate that HER3 is commonly overexpressed in lethal prostate cancer and can be activated by NRG1 secreted by myelomonocytic cells in the tumor microenvironment, supporting HER3-targeted therapeutic strategies for treating HER3-expressing advanced CRPC. SIGNIFICANCE: HER3 is an actionable target in prostate cancer, especially with anti-HER3 immunoconjugates, and targeting HER3 warrants clinical evaluation in prospective trials