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1.
J Geophys Res Atmos ; 127(15): e2022JD036597, 2022 Aug 16.
Article in English | MEDLINE | ID: mdl-36245641

ABSTRACT

Abrupt and large-scale climate changes have occurred repeatedly and within decades during the last glaciation. These events, where dramatic warming occurs over decades, are well represented in both Greenland ice core mineral dust and temperature records, suggesting a causal link. However, the feedbacks between atmospheric dust and climate change during these Dansgaard-Oeschger events are poorly known and the processes driving changes in atmospheric dust emission and transport remain elusive. Constraining dust provenance is key to resolving these gaps. Here, we present a multi-technique analysis of Greenland dust provenance using novel and established, source diagnostic isotopic tracers as well as results from a regional climate model including dust cycle simulations. We show that the existing dominant model for the provenance of Greenland dust as sourced from combined East Asian dust and Pacific volcanics is not supported. Rather, our clay mineralogical and Hf-Sr-Nd and D/H isotopic analyses from last glacial Greenland dust and an extensive range of Northern Hemisphere potential dust sources reveal three most likely scenarios (in order of probability): direct dust sourcing from the Taklimakan Desert in western China, direct sourcing from European glacial sources, or a mix of dust originating from Europe and North Africa. Furthermore, our regional climate modeling demonstrates the plausibility of European or mixed European/North African sources for the first time. We suggest that the origin of dust to Greenland is potentially more complex than previously recognized, demonstrating more uncertainty in our understanding dust climate feedbacks during abrupt events than previously understood.

2.
Ann Oncol ; 33(9): 916-928, 2022 09.
Article in English | MEDLINE | ID: mdl-35690221

ABSTRACT

BACKGROUND: Anti-CD19 chimeric antigen receptor T-cell immunotherapy (CAR-T) is now a standard treatment of relapsed or refractory B-cell non-Hodgkin lymphomas; however, a significant portion of patients do not respond to CAR-T and/or experience toxicities. Lymphodepleting chemotherapy is a critical component of CAR-T that enhances CAR-T-cell engraftment, expansion, cytotoxicity, and persistence. We hypothesized that the lymphodepletion regimen might affect the safety and efficacy of CAR-T. PATIENTS AND METHODS: We compared the safety and efficacy of lymphodepletion using either fludarabine/cyclophosphamide (n = 42) or bendamustine (n = 90) before tisagenlecleucel in two cohorts of patients with relapsed or refractory large B-cell lymphomas treated consecutively at three academic institutions in the United States (University of Pennsylvania, n = 90; Oregon Health & Science University, n = 35) and Europe (University of Vienna, n = 7). Response was assessed using the Lugano 2014 criteria and toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and, when possible, the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. RESULTS: Fludarabine/cyclophosphamide led to more profound lymphocytopenia after tisagenlecleucel infusion compared with bendamustine, although the efficacy of tisagenlecleucel was similar between the two groups. We observed significant differences, however, in the frequency and severity of adverse events. In particular, patients treated with bendamustine had lower rates of cytokine release syndrome and neurotoxicity. In addition, higher rates of hematological toxicities were observed in patients receiving fludarabine/cyclophosphamide. Bendamustine-treated patients had higher nadir neutrophil counts, hemoglobin levels, and platelet counts, as well as a shorter time to blood count recovery, and received fewer platelet and red cell transfusions. Fewer episodes of infection, neutropenic fever, and post-infusion hospitalization were observed in the bendamustine cohort compared with patients receiving fludarabine/cyclophosphamide. CONCLUSIONS: Bendamustine for lymphodepletion before tisagenlecleucel has efficacy similar to fludarabine/cyclophosphamide with reduced toxicities, including cytokine release syndrome, neurotoxicity, infectious and hematological toxicities, as well as reduced hospital utilization.


Subject(s)
Bendamustine Hydrochloride , Immunotherapy, Adoptive , Lymphocyte Depletion , Lymphoma, Large B-Cell, Diffuse , Receptors, Antigen, T-Cell , Bendamustine Hydrochloride/adverse effects , Bendamustine Hydrochloride/therapeutic use , Cyclophosphamide/therapeutic use , Cytokine Release Syndrome/drug therapy , Humans , Immunotherapy, Adoptive/methods , Lymphocyte Depletion/methods , Lymphoma, Large B-Cell, Diffuse/therapy , Receptors, Antigen, T-Cell/therapeutic use
4.
Sci Rep ; 6: 19535, 2016 Jan 29.
Article in English | MEDLINE | ID: mdl-26822309

ABSTRACT

Established and already commercialized energetic materials, such as those based on Ni/Al for joining, lack the adequate combination of high energy density and ductile reaction products. To join components, this combination is required for mechanically reliable bonds. In addition to the improvement of existing technologies, expansion into new fields of application can also be anticipated which triggers the search for improved materials. Here, we present a comprehensive characterization of the key parameters that enables us to classify the Ru/Al system as new reactive material among other energetic systems. We finally found that Ru/Al exhibits the unusual integration of high energy density and ductility. For example, we measured reaction front velocities up to 10.9 (± 0.33) ms(-1) and peak reaction temperatures of about 2000 °C indicating the elevated energy density. To our knowledge, such high temperatures have never been reported in experiments for metallic multilayers. In situ experiments show the synthesis of a single-phase B2-RuAl microstructure ensuring improved ductility. Molecular dynamics simulations corroborate the transformation behavior to RuAl. This study fundamentally characterizes a Ru/Al system and demonstrates its enhanced properties fulfilling the identification requirements of a novel nanoscaled energetic material.

5.
Phys Rev E Stat Nonlin Soft Matter Phys ; 86(6 Pt 2): 066314, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23368045

ABSTRACT

The effect of polymers on the bouncing behavior of droplets in a highly viscous, vertically shaken silicone oil bath was investigated in this study. Droplets of a sample liquid were carefully placed on a vibrating bath that was maintained well below the threshold of Faraday waves. The bouncing threshold of the plate acceleration depended on the acceleration frequency. For pure water droplets and droplets of aqueous polymer solutions, a minimum acceleration amplitude was observed in the acceleration threshold curves as a function of frequency. The bouncing acceleration amplitude for a droplet of a dilute aqueous polymer solution was higher than the acceleration amplitude for a pure water droplet. Measurements of the center of mass trajectory and the droplet deformations showed that the controlling parameter in the bouncing process was the oscillating elongational rate of the droplet. This parameter can be directly related to the elongational viscosity of the polymeric samples. The large elongational viscosity of the polymer solution droplets suppressed large droplet deformations, resulting in less chaotic bouncing.

6.
Cancer Res ; 58(5): 863-6, 1998 Mar 01.
Article in English | MEDLINE | ID: mdl-9500439

ABSTRACT

Germ-line mutations of the BRCA2 gene account for the majority of families with both male and female breast cancer. However, among independently ascertained families with the same mutation, cases of male breast cancer often appear to cluster in a single family or in a particular branch of one family. This suggests that the risk of male breast cancer conferred by BRCA2 mutations may be modified by other genetic or environmental factors. We report a family in which three brothers with breast cancer carry in their germ line two genetic abnormalities: an insertion A at nucleotide 2041 in exon 10 of BRCA2, which leads to premature termination of the encoded protein at codon 615, and a tandem interstitial duplication involving chromosome bands 9p23-24. We propose that the coexistence of this rare chromosomal abnormality with BRCA2 mutation may be augmenting the risk of male breast cancer conferred by the BRCA2 mutation.


Subject(s)
Breast Neoplasms, Male/genetics , Chromosomes, Human, Pair 9 , Germ-Line Mutation , Neoplasm Proteins/genetics , Transcription Factors/genetics , BRCA2 Protein , DNA Transposable Elements/genetics , Humans , Male , Middle Aged , Multigene Family , Pedigree
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