Direct mass measurements beyond the proton drip-line

First on-line mass measurements were performed at the SHIPTRAP Penning trap mass spectrometer. The masses of 18 neutron-deficient isotopes in the terbium-to-thulium region produced in fusion-evaporation reactions were determined with relative uncertainties of about $7\cdot 10^{-8}$, nine of them for the first time. Four nuclides ($^{144, 145}$Ho and $^{147, 148}$Tm) were found to be proton-unbound. The implication of the results on the location of the proton drip-line is discussed by analyzing the one-proton separation energies

Intelligent Sensors and Components for On-Board ISHM

A viewgraph presentation on the development of intelligent sensors and components for on-board Integrated Systems Health Health Management (ISHM) is shown. The topics include: 1) Motivation; 2) Integrated Systems Health Management (ISHM); 3) Intelligent Components; 4) IEEE 1451; 5)Intelligent Sensors; 6) Application; and 7) Future Direction

Position-sensitive ion detection in precision Penning trap mass spectrometry

A commercial, position-sensitive ion detector was used for the first time for the time-of-flight ion-cyclotron resonance detection technique in Penning trap mass spectrometry. In this work, the characteristics of the detector and its implementation in a Penning trap mass spectrometer will be presented. In addition, simulations and experimental studies concerning the observation of ions ejected from a Penning trap are described. This will allow for a precise monitoring of the state of ion motion in the trap.Comment: 20 pages, 13 figure

New Method to Prepare Mitomycin C Loaded PLA-Nanoparticles with High Drug Entrapment Efficiency

The classical utilized double emulsion solvent diffusion technique for encapsulating water soluble Mitomycin C (MMC) in PLA nanoparticles suffers from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. In this paper, MMC loaded PLA nanoparticles were prepared by a new single emulsion solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of MMC by formation of MMC–SPC complex. Four main influential factors based on the results of a single-factor test, namely, PLA molecular weight, ratio of PLA to SPC (wt/wt) and MMC to SPC (wt/wt), volume ratio of oil phase to water phase, were evaluated using an orthogonal design with respect to drug entrapment efficiency. The drug release study was performed in pH 7.2 PBS at 37 °C with drug analysis using UV/vis spectrometer at 365 nm. MMC–PLA particles prepared by classical method were used as comparison. The formulated MMC–SPC–PLA nanoparticles under optimized condition are found to be relatively uniform in size (594 nm) with up to 94.8% of drug entrapment efficiency compared to 6.44 μm of PLA–MMC microparticles with 34.5% of drug entrapment efficiency. The release of MMC shows biphasic with an initial burst effect, followed by a cumulated drug release over 30 days is 50.17% for PLA–MMC–SPC nanoparticles, and 74.1% for PLA–MMC particles. The IR analysis of MMC–SPC complex shows that their high liposolubility may be attributed to some weak physical interaction between MMC and SPC during the formation of the complex. It is concluded that the new method is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and longer sustained drug release in comparison to classical method

The Current Landscape of Antibody-based Therapies in Solid Malignancies

Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies. The development of a therapeutic mAb with long-lasting clinical impact demands a prodigious understanding of target antigen, effective mechanism of action, gene engineering technologies, complex interplay between tumor and host immune system, and biomarkers for prediction of clinical response. This review discusses the various approaches used by mAbs for tumor targeting and mechanisms of therapeutic resistance that is not only caused by the heterogeneity of tumor antigen, but also the resistance imposed by tumor microenvironment (TME), including inefficient delivery to the tumor, alteration of effector functions in the TME, and Fc-gamma receptor expression diversity and polymorphism. Further, this article provides a perspective on potential strategies to overcome these barriers and how diagnostic and prognostic biomarkers are being used in predicting response to mAb-based therapies. Overall, understanding these interdependent parameters can improve the current mAb-based formulations and develop novel mAb-based therapeutics for achieving durable clinical outcomes in a large subset of patients

Blocking c-MET/ERBB1 Axis Prevents Brain Metastasis in ERBB2+ Breast Cancer

Brain metastasis (BrM) remains a significant cause of cancer-related mortality in epidermal growth factor receptor 2-positive (ERBB2+) breast cancer (BC) patients. We proposed here that a combination treatment of irreversible tyrosine kinase inhibitor neratinib (NER) and the c-MET inhibitor cabozantinib (CBZ) could prevent brain metastasis. To address this, we first tested the combination treatment of NER and CBZ in the brain-seeking ERBB2+ cell lines SKBrM3 and JIMT-1-BR3, and in ERBB2+ organoids that expressed the c-MET/ERBB1 axis. Next, we developed and characterized an orthotopic mouse model of spontaneous BrM and evaluated the therapeutic effect of CBZ and NER in vivo. The combination treatment of NER and CBZ significantly inhibited proliferation and migration in ERBB2+ cell lines and reduced the organoid growth in vitro. Mechanistically, the combination treatment of NER and CBZ substantially inhibited ERK activation downstream of the c-MET/ERBB1 axis. Orthotopically implanted SKBrM3+ cells formed primary tumor in the mammary fat pad and spontaneously metastasized to the brain and other distant organs. Combination treatment with NER and CBZ inhibited primary tumor growth and predominantly prevented BrM. In conclusion, the orthotopic model of spontaneous BrM is clinically relevant, and the combination therapy of NER and CBZ might be a useful approach to prevent BrM in BC