A5063631964- Salivary Gland Tumors Diagnosis and Treatment
- Climate variability and models
- Atmospheric and Environmental Gas Dynamics
- Meteorological Phenomena and Simulations
- Tropical and Extratropical Cyclones Research
- Head and Neck Surgical Oncology
- Protist diversity and phylogeny
- Atmospheric Ozone and Climate
- Cancer-related gene regulation
- Chromatin Remodeling and Cancer
- Electrochemical sensors and biosensors
- Biofuel production and bioconversion
- Geology and Paleoclimatology Research
- Vitamin C and Antioxidants Research
- Cancer, Hypoxia, and Metabolism
- Enzyme Catalysis and Immobilization
- Oceanographic and Atmospheric Processes
- Head and Neck Cancer Studies
- Tumors and Oncological Cases
- PI3K/AKT/mTOR signaling in cancer
- Cryospheric studies and observations
- Cancer Cells and Metastasis
- Arctic and Antarctic ice dynamics
- Chemokine receptors and signaling
- Atmospheric chemistry and aerosols
Columbia University
2005-2022
Goddard Institute for Space Studies
2012-2022
Polyphor (Switzerland)
2014-2015
Earth Island Institute
2005
Graz University of Technology
1998-2002
Hamburg University of Technology
1997-2000
Universität Hamburg
1997
University of Kaiserslautern
1996
We use a global climate model to compare the effectiveness of many forcing agents for producing change. find substantial range in “efficacy” different forcings, where efficacy is temperature response per unit relative CO 2 forcing. Anthropogenic CH 4 has ∼110%, which increases ∼145% when its indirect effects on stratospheric H O and tropospheric 3 are included, yielding an effective ∼0.8 W/m period 1750–2000 making largest anthropogenic other than . Black carbon (BC) aerosols from biomass...
This paper describes the GISS-E2.1 contribution to Coupled Model Intercomparison Project, Phase 6 (CMIP6). model version differs from predecessor (GISS-E2) chiefly due parameterization improvements atmospheric and ocean components, while keeping resolution same. skill when compared modern era climatologies is significantly higher than in previous versions. Additionally, updates forcings have a material impact on results. In particular, there been specific representations of modes variability...
We use numerical climate simulations, paleoclimate data, and modern observations to study the effect of growing ice melt from Antarctica Greenland. Meltwater tends stabilize ocean column, inducing amplifying feedbacks that increase subsurface warming shelf melting. Cold meltwater induced dynamical effects cause surface cooling in Southern Ocean North Atlantic, thus increasing Earth's energy imbalance heat flux into most global ocean's surface. cooling, while lower latitudes are warming,...
Abstract Simulations of the CMIP6 historical period 1850–2014, characterized by emergence anthropogenic climate drivers like greenhouse gases, are presented for different configurations NASA Goddard Institute Space Studies (GISS) Earth System ModelE2.1. The GISS‐E2.1 ensembles more sensitive to gas forcing than their CMIP5 predecessors (GISS‐E2) but warm less during recent decades due a reduction that is attributed greater longwave opacity in pre‐industrial simulations. This results an...
Abstract We introduce a new climate model (GISS E2.2) that has been specially optimized for the middle atmosphere and whose output is being contributed to CMIP6 archive. The top of at geopotential altitude 89 km, parameterizations moist convection various forms gravity wave drag based on tropospheric processes are chosen specifically this optimization. first evaluate in its configuration as coupled atmosphere‐chemistry with respect simulation mean state atmosphere, from mesosphere down...
Abstract This paper presents the response to anthropogenic forcing in GISS‐E2.1 climate models for 21st century Shared Socioeconomic Pathways emission scenarios within Coupled Model Intercomparison Project Phase 6 (CMIP6). The experiments were performed using an updated and improved version of NASA Goddard Institute Space Studies (GISS) coupled general circulation model that includes two different versions atmospheric composition: A non‐interactive (NINT) with prescribed composition a tuned...
CB-103 selectively inhibits the CSL-NICD (Notch intracellular domain) interaction leading to transcriptional downregulation of oncogenic Notch pathway activation. This dose-escalation/expansion study aimed determine safety, pharmacokinetics, and preliminary antitumor activity.
The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line previous reports, we found that tumoral expression patients locally advanced cancer was increased metastases rapid tumor progression. Moreover, high identified a group of bone marrow-disseminated cells (DTC)-negative at risk for death. protein epitope mimetic (PEM) POL5551, novel antagonist, inhibited binding to CXCR4, had...
Abstract. There is evidence of ice melt, sea level rise to +5–9 m, and extreme storms in the prior interglacial period that was less than 1 °C warmer today. Human-made climate forcing stronger more rapid paleo forcings, but much can be learned by combining insights from paleoclimate, modeling, on-going observations. We argue sheets contact with ocean are vulnerable non-linear disintegration response warming, we posit sheet mass loss approximated a doubling time up at least several meters....
// Amy Barone 1,* , Rajarshi Sengupta Nicole M. Warrington 1 Erin Smith 2,3 Patrick Y. Wen 4,5 Rolf A. Brekken 6 Barbara Romagnoli 7 Garry Douglas Eric Chevalier Michael P. Bauer Klaus Dembowsky David Piwnica-Worms 2,3,8,9 and Joshua B. Rubin 1,10 Department of Pediatrics, Washington University School Medicine, 660 South Euclid Ave, St. Louis, MO 2 BRIGHT Institute 3 Molecular Imaging Center, Mallinckrodt Radiology 4 Center for Neuro-Oncology, Dana Farber/Brigham Women's Cancer Brookline...
3020 Background: CB-103 selectively inhibits the CSL-NICD interaction leading to down-regulation of mediated oncogenic pathway activation downstream NOTCH receptor/ligand signaling, and has shown potent anti-cancer activity as single agent in combination with targeted/chemotherapies preclinical models. The aim this dose escalation/expansion phase 1/2a study is assess safety, maximum tolerated (MTD) recommended 2 (RP2D), preliminary activity, pharmacokinetics pharmacodynamics CB-103. Methods:...
Relapsed T cell acute lymphoblastic leukaemia (T-ALL) has a very poor prognosis. A 24-year-old patient with relapsed high-risk T-ALL (PTEN gene deletion; NOTCH1 mutation), was treated the NOTCH inhibitor CB-103. Within 1 week of starting CB-103, bone marrow free blast infiltration (MRD+) and successfully underwent allogeneic hematopoietic stem transplantation (allo-HSCT). Sequential samples ctDNA to monitor disease after allo-HSCT showed decrease circulating Notch1 PTEN alterations. This is...
Notch is a key oncogenic pathway in several human cancers and to date, no targeted treatment of activated available patients. Therapeutic targeting has been an unresolved challenge due severe on-target dose limiting toxicities associated with pan-Notch inhibition by either γ-secretase inhibitors or receptor/ligand MAbs. At Cellestia Biotech, we have identified novel series small molecule the transcription complex. These molecules act as do not cause commonly first- second-generation...
TPS2619 Background: NOTCH signalling is a key development pathway whose aberrant activation recognised to play an oncogenic role in human cancers. When inappropriately activated by genetic alterations, it becomes driver for NOTCH-dependent cancers, while upregulation of receptors linked resistance standard care. CB-103 new small molecule protein-protein interaction (PPI) inhibitor able target assembly the transcription complex cell nucleus leading downregulation genes (c-MYC, CCND1, HES1)...
Three proteins containing 138 amino acids (psaD protein), 80 (psaC protein) and 66 (psaE of the photosystem I (PS I) complex cyanobacterium Fremyella diplosiphon (Calothrix sp PCC 7601) were isolated sequenced. Comparison with previously known sequences showed a close relationship to homologous Nostoc, another filamentous cyanobacterium.
Abstract Background: Bone is the most common site of metastasis for patients with breast cancer. Tumor cells migrate to and reside in protective bone marrow microenvironment niche through adhesive interaction between tumor CXCR4 stromal CXCL12 (SDF1). produced by activated osteoblasts, lung cells, endothelial cells. Nearly 60% cancers express this associated decreased survival. We hypothesized that a Protein Epitope Mimetic (PEM) POL5551, novel antagonist, will limit extent disrupting...
The synthesis of an NAD+ derivative (2-N3-N6-SL-NAD+) and the corresponding ATP analog (2-N3-N6-SL-ATP) is described, where a spin label (SL) (2,2,6,6-tetramethyl-piperidine-1-yloxy radical, tempamine) attached to N6-position azido function C2-atom adenine ring. Both compounds were shown be active coenzymes or substrates for various enzymes could covalently incorporated into upon irradiation (photoaffinity labeling). In complex with appropriate enzymes, exhibited ESR spectra typical highly...