- Computational Fluid Dynamics and Aerodynamics
- Turbomachinery Performance and Optimization
- Fluid Dynamics and Turbulent Flows
- Combustion and flame dynamics
- Advanced Numerical Methods in Computational Mathematics
- Bladed Disk Vibration Dynamics
- Hepatitis B Virus Studies
- Numerical methods for differential equations
- Aerodynamics and Acoustics in Jet Flows
- Brake Systems and Friction Analysis
- Vibration and Dynamic Analysis
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Hepatitis C virus research
- Liver Disease Diagnosis and Treatment
- Tribology and Lubrication Engineering
- Sepsis Diagnosis and Treatment
- Cardiac, Anesthesia and Surgical Outcomes
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- Intensive Care Unit Cognitive Disorders
- Cell death mechanisms and regulation
- Frailty in Older Adults
- PARP inhibition in cancer therapy
- Respiratory Support and Mechanisms
Ideaya Biosciences (United States)
2018-2025
Deutsches Zentrum für Luft- und Raumfahrt e. V. (DLR)
2015-2024
Linde (Germany)
2016-2024
Heinrich Heine University Düsseldorf
2021-2024
Düsseldorf University Hospital
2021-2024
Bundeswehrkrankenhaus
2023
University Hospital of Larissa
2021
Gilead Sciences (United States)
2011-2020
University Hospital Bonn
2016
Ford (Germany)
2015
Chronic HBV (CHB) infection suppresses virus-specific T cells, but its impact on humoral immunity has been poorly analyzed. Here, we developed a dual-staining method that utilizes hepatitis B virus (HBV) surface antigens (HBsAg) labeled with fluorochromes as "baits" for specific ex vivo detection of HBsAg-specific cells and analysis their quantity, function, phenotype. We studied healthy vaccinated subjects (n = 18) patients resolved 21), acute 11), or chronic 96) observed frequencies...
Background and Aims GS‐9688 (selgantolimod) is a toll‐like receptor 8 agonist in clinical development for the treatment of chronic hepatitis B (CHB). Antiviral activity has previously been evaluated vitro HBV‐infected hepatocytes vivo woodchuck model CHB. Here we potential to boost responses contributing viral control modulate regulatory mediators. Approach Results We characterized effect on immune cell subsets peripheral blood mononuclear cells healthy controls patients with activated...
ABSTRACT Tenofovir alafenamide fumarate (TAF) is an oral phosphonoamidate prodrug of the HIV reverse transcriptase nucleotide inhibitor tenofovir (TFV). Previous studies suggested a principal role for lysosomal serine protease cathepsin A (CatA) in intracellular activation TAF. Here we further investigated CatA and other human hydrolases metabolism Overexpression or liver carboxylesterase 1 (Ces1) HEK293T cells increased TAF hydrolysis 2- 5-fold, respectively. Knockdown expression with RNA...
Abstract Background Increasing evidence suggests that secondary sclerosing cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a hepatobiliary long-term complication of COVID-19. The aim this study was estimate the frequency and outcome COVID-19 sequela identify possible risk factors. Methods This observational study, conducted at University Hospital Charité Berlin Unfallkrankenhaus Berlin, Germany, involved hospitalized patients with pneumonia, including 1082 ventilated...
CD95 (APO-1/Fas)-mediated apoptosis of hepatocytes plays a central role in the pathophysiology various human liver diseases. Hepatocyte growth factor (HGF) was shown to exert antiapoptotic functions rodent hepatocytes. We previously showed that primary (PHH) are valuable tool for investigation apoptotic processes cells. In this study, we analyzed influence HGF on CD95-mediated PHH and its molecular determinants. significantly inhibited as well cleavage caspase-8 poly (ADP-ribose)polymerase....
AbstractBackground: Glucocorticoids have been used widely in conjunction with cancer therapy due to their ability induce apoptosis hematological cells and prevent nausea emesis. However, recent data including ours, suggest induction of therapy-resistance by glucocorticoids solid tumors, although it is unclear whether this happens only few carcinomas or a more common cell type specific phenomenon.Material Methods: We performed an overall statistical analysis our new obtained 157 tumor probes...
GS-9620 [8-(3-(pyrrolidin-1-ylmethyl)benzyl)-4-amino-2-butoxy-7,8-dihydropteridin-6(5<i>H</i>)-one] is a potent, orally bioavailable small-molecule agonist of Toll-like receptor 7 (TLR7) developed for finite treatment chronic hepatitis B viral (HBV) infection, with the goal inducing liver-targeted antiviral effect without adverse effects associated current systemic interferon-<i>α</i> (IFN-<i>α</i>) therapies. We characterized pharmacodynamic response in CD-1 mice and cynomolgus monkeys...
This article describes a nonlinear frequency domain method for the simulation of unsteady blade row interaction problems across several rows in turbomachinery. The capability to efficiently simulate such interactions is crucial improvement prediction vibrations, tonal noise, and impact unsteadiness on aerodynamic performance. technique presented here based harmonic balance approach has been integrated into an existing flow solver. A nontrivial issue application methods turbomachinery flows...
GS-9620 is a potent and selective oral Toll-like receptor 7 (TLR7) agonist that directly activates plasmacytoid dendritic cells (pDCs). suppressed hepatitis B virus (HBV) in animal models of chronic infection transiently activated HIV expression ex vivo latently infected peripheral blood mononuclear (PBMCs) from virally patients. Currently, under clinical evaluation for treating HBV reducing latent reservoirs HIV-infected Here, we investigated the vitro anti-HIV-1 activity GS-9620. potently...
Cyclophilin inhibition has been a target for the treatment of hepatitis C and other diseases, but generation potent, drug-like molecules through chemical synthesis challenging. In this study, set macrocyclic cyclophilin inhibitors was synthesized based on core structure natural product sanglifehrin A. Initial compound optimization identified valine-m-tyrosine-piperazic acid tripeptide (Val-m-Tyr-Pip) in core, stereocenters at C14 C15, hydroxyl group m-tyrosine (m-Tyr) residue as key...
Antibody-mediated clearance of hepatitis B surface antigen (HBsAg) from the circulation chronically infected patients (i.e., seroconversion) is usually associated with increased HBV-specific T cell responsiveness. However, a causative link between serum HBsAg levels and impairment intrahepatic CD8+ cells has not been established. Here we addressed this issue by using HBV replication-competent transgenic mice that are depleted circulating HBsAg, via either spontaneous seroconversion or...
Abstract Background Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission very old patients and mortality rates are high. However, impact pre-existing physical cognitive function on long-term outcome ICU ≥ 80 years (very (VIPs)) with sepsis unclear. Objective To investigate both short- VIPs admitted assess relation function. Design Prospective cohort study. Setting 241 ICUs from 22 European countries in a six-month period between May 2018 2019. Subjects...
Abstract Background Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to ICU. The aim this study was determine such premorbid on 6 month survival. Methods Prospective cohort in 242 ICUs from 22 countries including or above, a months period an ICU between May 2018 2019. Only emergency (acute) admissions ≥ age were eligible. Patients after planned/elective surgery excluded. We measured Clinical Frailty Scale (CFS), Informant...
GS-9620 is a novel oral agonist of Toll-like receptor 7 (TLR7) in development for the treatment chronic viral hepatitis. TLR7 highly conserved innate immune expressed primarily on plasmacytoid dendritic cells and B lymphocytes. The aim this double-blind, placebo-controlled, single ascending-dose study was to investigate safety, tolerability, pharmacokinetics pharmacodynamics healthy volunteers.In total, 75 volunteers (8 subjects each 10 cohorts; 5 participated two cohorts) were randomized...
A computational method for performing aeroelastic analysis using either a time-linearized or an unsteady time-accurate solver the compressible Reynolds averaged Navier--Stokes (RANS) equations is described. The employs assumption of small time-harmonic perturbations and implemented via finite differences nonlinear flux routines solver. resulting linear system solved parallelized generalized minimal residual (GMRES) with block-local preconditioning. time accurate uses dual stepping algorithm...
Development of an adaptive, International Classification Functioning, Disability and Health (ICF)-oriented patient questionnaire on mobility self-care based item response theory model (MOSES questionnaire).Using reconstruction rules, items were developed for the ICF chapters "mobility", "self-care" "domestic life". The resulting instrument, together with other instruments (SF-36, Short Musculoskeletal Function Assessment Questionnaire (SMFA), MacNew, Functional Independence Measure (FIM),...
Primary cicatricial alopecias (PCA) encompass several autoimmune disorders characterized by scarring hair loss. Many of these conditions are lymphocytic and thought to be driven T cell populations. Here, we sought characterize potential cell-hair follicle communication pathways in the microanatomical niche using spatial transcriptomics across 3 mammalian species including a novel mouse model, spontaneous disease companion dogs human archival diagnostic biopsies. Flow cytometry model skin...
Methylthioadenosine phosphorylase (MTAP) is co-deleted with the tumor suppressor CDKN2A in approximately 15% of solid tumors. Loss MTAP blocks cellular 1-carbon salvage pathway activity due to an inability convert MTA into adenine and methionine. Accumulation MTAP’s substrate, MTA, coincident depletion products, methionine precursors, results two distinct targetable vulnerabilities: direct S-Adenosyl (SAM)-competitive inhibition essential methyltransferase Protein arginine 5 (PRMT5), reduced...
Abstract The formation of cancer and responsiveness to therapy is governed by a constantly evolving balance between somatic variation dynamic epigenetic regulation. This evolution has been recognized as significant obstacle confronting the development durable therapies. Thus, targeting reprogramming in human cancers key focus for design new drugs potentially deliver robust anti-tumor activity. Lysine acetyltransferases (KATs) are promising class targets that operate within interchangeable...
Abstract Poly (ADP-Ribose) glycohydrolase (PARG) is an emerging oncology drug target with a unique role in the resolution of DNA damage repair and replication fork restart through hydrolysis (ADP-ribose) (PAR) chains. IDE161 potent, orally bioavailable, small molecule that directly binds active site PARG to impede PAR chain exhibits robust anti-tumor activity preclinical models associated stress. Molecular profiling baseline cell states across 257 tumor lines indicated innate immune...