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Book ; Thesis: The role of PPAR-γ in establishment of GC-induced anti-inflammatory phenotype in macrophages

Heming, Michael Oleg

2017

Title variant	The role of PPAR-gamma in establishment of GC-induced anti-inflammatory phenotype in macrophages ; PPARgamma ; PPAR gamma
Institution	Westfälische Wilhelms-Universität Münster
Author's details	vorgelegt von Heming, Michael Oleg aus Essen
Language	English
Size	XIV, 117 Blätter, Illustrationen, Diagramme
Publishing place	Münster
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Dissertation, Westfälische Wilhelms-Universität Münster, 2017
Note	Zusammenfassung in deutscher Sprache
HBZ-ID	HT019445886
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Learning multiple sclerosis immunopathogenesis from anti-CD20 therapy.

Heming, Michael / Wiendl, Heinz

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 6, Page(s) e2221544120

MeSH term(s)	Humans ; Multiple Sclerosis/drug therapy ; Antigens, CD20 ; Antibodies, Monoclonal, Humanized ; Learning
Chemical Substances	Antigens, CD20 ; Antibodies, Monoclonal, Humanized
Language	English
Publishing date	2023-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2221544120
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Zs.A 1148: Show issues

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: High-dimensional investigation of the cerebrospinal fluid to explore and monitor CNS immune responses.

Heming, Michael / Börsch, Anna-Lena / Wiendl, Heinz / Meyer Zu Hörste, Gerd

Genome medicine

2022 Volume 14, Issue 1, Page(s) 94

Abstract: The cerebrospinal fluid (CSF) features a unique immune cell composition and is in constant contact with the brain borders, thus permitting insights into the brain to diagnose and monitor diseases. Recently, the meninges, which are filled with CSF, were ... ...

Abstract	The cerebrospinal fluid (CSF) features a unique immune cell composition and is in constant contact with the brain borders, thus permitting insights into the brain to diagnose and monitor diseases. Recently, the meninges, which are filled with CSF, were identified as a neuroimmunological interface, highlighting the potential of exploring central nervous system (CNS) immunity by studying CNS border compartments. Here, we summarize how single-cell transcriptomics of such border compartments advance our understanding of neurological diseases, the challenges that remain, and what opportunities novel multi-omic methods offer. Single-cell transcriptomics studies have detected cytotoxic CD4
MeSH term(s)	Brain/pathology ; CD8-Positive T-Lymphocytes ; Central Nervous System/pathology ; Humans ; Immunity ; Multicenter Studies as Topic ; Multiple Sclerosis
Language	English
Publishing date	2022-08-17
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2484394-5
ISSN	1756-994X ; 1756-994X
ISSN (online)	1756-994X
ISSN	1756-994X
DOI	10.1186/s13073-022-01097-9
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Article ; Online: Alemtuzumab treatment exemplifies discordant immune effects of blood and cerebrospinal fluid in multiple sclerosis.

Müller-Miny, Louisa / Heming, Michael / Lautwein, Tobias / Ruck, Tobias / Lu, I-Na / Wiendl, Heinz / Meyer Zu Hörste, Gerd

Journal of neuroimmunology

2023 Volume 378, Page(s) 578088

Abstract: Background and objectives: Immune responses in the central nervous system (CNS) are highly compartmentalized and cerebrospinal fluid (CSF) in particular often reflects CNS pathology better than peripheral blood. While CSF leukocytes are known to be ... ...

Abstract	Background and objectives: Immune responses in the central nervous system (CNS) are highly compartmentalized and cerebrospinal fluid (CSF) in particular often reflects CNS pathology better than peripheral blood. While CSF leukocytes are known to be distinct from blood, the immediate effects of peripheral leukocyte depletion on CSF leukocytes have not been studied in humans. Methods: We here analyzed CSF and blood from two relapsing-remitting multiple sclerosis (RRMS) patients early after peripheral leukocyte depletion with the anti-CD52 antibody alemtuzumab compared to untreated RRMS and control patients using single cell RNA-sequencing. Results: As expected for alemtuzumab, most leukocyte lineages including T cells were synchronously depleted from CSF and blood, while - surprisingly - pDCs were maintained in CSF but depleted from blood by alemtuzumab. Transcriptionally, genes associated with migration were elevated only in the CSF after alemtuzumab. Predicted cellular interactions indicated a central role of pDCs and enhanced migration signaling in the CSF after alemtuzumab. Discussion: The CSF and blood compartments are thus partially uncoupled, emphasizing that the CNS is only partially accessible even for treatments profoundly affecting the blood.
MeSH term(s)	Humans ; Alemtuzumab/adverse effects ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/chemically induced ; Multiple Sclerosis, Relapsing-Remitting ; Central Nervous System
Chemical Substances	Alemtuzumab (3A189DH42V)
Language	English
Publishing date	2023-04-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	8335-5
ISSN	1872-8421 ; 0165-5728
ISSN (online)	1872-8421
ISSN	0165-5728
DOI	10.1016/j.jneuroim.2023.578088
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Zs.A 1646: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis.

Tian, Dai-Shi / Qin, Chuan / Dong, Ming-Hao / Heming, Michael / Zhou, Luo-Qi / Wang, Wen / Cai, Song-Bai / You, Yun-Fan / Shang, Ke / Xiao, Jun / Wang, Di / Li, Chun-Rui / Zhang, Min / Bu, Bi-Tao / Meyer Zu Hörste, Gerd / Wang, Wei

EMBO molecular medicine

2024 Volume 16, Issue 4, Page(s) 966–987

Abstract: B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly ... ...

Abstract	B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly relapsed and refractory myasthenia gravis (one with AChR-IgG, and one with MuSk-IgG). Both patients exhibited favorable safety profiles and persistent clinical improvements over 18 months. Reconstitution of B-cell lineages with sustained reduced pathogenic autoantibodies might underlie the therapeutic efficacy. To identify the possible mechanisms underlying the therapeutic efficacy of CAR-T cells in these patients, longitudinal single-cell RNA and TCR sequencing was conducted on serial blood samples post infusion as well as their matching infusion products. By tracking the temporal evolution of CAR-T phenotypes, we demonstrated that proliferating cytotoxic-like CD8 clones were the main effectors in autoimmunity, whereas compromised cytotoxic and proliferation signature and profound mitochondrial dysfunction in CD8
MeSH term(s)	Humans ; Immunotherapy, Adoptive ; Multiple Myeloma/genetics ; Multiple Myeloma/pathology ; Multiple Myeloma/therapy ; B-Cell Maturation Antigen/genetics ; Cell Lineage ; Myasthenia Gravis/therapy ; T-Lymphocytes ; Immunoglobulin G
Chemical Substances	B-Cell Maturation Antigen ; Immunoglobulin G
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.1038/s44321-024-00043-z
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Zs.A 6784: Show issues

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Article ; Online: Supporting the differential diagnosis of connective tissue diseases with neurological involvement by blood and cerebrospinal fluid flow cytometry.

Heming, Michael / Müller-Miny, Louisa / Rolfes, Leoni / Schulte-Mecklenbeck, Andreas / Brix, Tobias J / Varghese, Julian / Pawlitzki, Marc / Pavenstädt, Hermann / Kriegel, Martin A / Gross, Catharina C / Wiendl, Heinz / Meyer Zu Hörste, Gerd

Journal of neuroinflammation

2023 Volume 20, Issue 1, Page(s) 46

Abstract: Objective: Neurological manifestations of autoimmune connective tissue diseases (CTD) are poorly understood and difficult to diagnose. We here aimed to address this shortcoming by studying immune cell compositions in CTD patients with and without ... ...

Abstract	Objective: Neurological manifestations of autoimmune connective tissue diseases (CTD) are poorly understood and difficult to diagnose. We here aimed to address this shortcoming by studying immune cell compositions in CTD patients with and without neurological manifestation. Methods: Using flow cytometry, we retrospectively investigated paired cerebrospinal fluid (CSF) and blood samples of 28 CTD patients without neurological manifestation, 38 CTD patients with neurological manifestation (N-CTD), 38 non-inflammatory controls, and 38 multiple sclerosis (MS) patients, a paradigmatic primary neuroinflammatory disease. Results: We detected an expansion of plasma cells in the blood of both N-CTD and CTD compared to non-inflammatory controls and MS. Blood plasma cells alone distinguished the clinically similar entities N-CTD and MS with high discriminatory performance (AUC: 0.81). Classical blood monocytes indicated higher disease activity in systemic lupus erythematosus (SLE) patients. Surprisingly, immune cells in the CSF did not differ significantly between N-CTD and CTD, while CD4 Conclusion: We here find that blood flow cytometry alone surprisingly suffices to distinguish CTD with neurological manifestations from clinically similar entities, suggesting that a rapid blood test could support clinicians in the differential diagnosis of N-CTD.
MeSH term(s)	Humans ; Flow Cytometry ; Diagnosis, Differential ; Retrospective Studies ; Connective Tissue Diseases/diagnosis ; Lupus Erythematosus, Systemic ; Multiple Sclerosis
Language	English
Publishing date	2023-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2156455-3
ISSN	1742-2094 ; 1742-2094
ISSN (online)	1742-2094
ISSN	1742-2094
DOI	10.1186/s12974-023-02733-w
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Article ; Online: Snow Parameters Inversion from Passive Microwave Remote Sensing Measurements by Deep Convolutional Neural Networks.

Yao, Heming / Zhang, Yanming / Jiang, Lijun / Ewe, Hong Tat / Ng, Michael

Sensors (Basel, Switzerland)

2022 Volume 22, Issue 13

Abstract: This paper proposes a novel inverse method based on the deep convolutional neural network (ConvNet) to extract snow's layer thickness and temperature via passive microwave remote sensing (PMRS). The proposed ConvNet is trained using simulated data ... ...

Abstract	This paper proposes a novel inverse method based on the deep convolutional neural network (ConvNet) to extract snow's layer thickness and temperature via passive microwave remote sensing (PMRS). The proposed ConvNet is trained using simulated data obtained through conventional computational electromagnetic methods. Compared with the traditional inverse method, the trained ConvNet can predict the result with higher accuracy. Besides, the proposed method has a strong tolerance for noise. The proposed ConvNet composes three pairs of convolutional and activation layers with one additional fully connected layer to realize regression, i.e., the inversion of snow parameters. The feasibility of the proposed method in learning the inversion of snow parameters is validated by numerical examples. The inversion results indicate that the correlation coefficient (R2) ratio between the proposed ConvNet and conventional methods reaches 4.8, while the ratio for the root mean square error (RMSE) is only 0.18. Hence, the proposed method experiments with a novel path to improve the inversion of passive microwave remote sensing through deep learning approaches.
MeSH term(s)	Microwaves ; Neural Networks, Computer ; Remote Sensing Technology/methods ; Snow
Language	English
Publishing date	2022-06-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s22134769
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Book ; Online: AgentCoder

Huang, Dong / Bu, Qingwen / Zhang, Jie M. / Luck, Michael / Cui, Heming

Multi-Agent-based Code Generation with Iterative Testing and Optimisation

2023

Abstract: The advancement of natural language processing (NLP) has been significantly boosted by the development of transformer-based large language models (LLMs). These models have revolutionized NLP tasks, particularly in code generation, aiding developers in ... ...

Abstract	The advancement of natural language processing (NLP) has been significantly boosted by the development of transformer-based large language models (LLMs). These models have revolutionized NLP tasks, particularly in code generation, aiding developers in creating software with enhanced efficiency. Despite their advancements, challenges in balancing code snippet generation with effective test case generation and execution persist. To address these issues, this paper introduces Multi-Agent Assistant Code Generation (AgentCoder), a novel solution comprising a multi-agent framework with specialized agents: the programmer agent, the test designer agent, and the test executor agent. During the coding procedure, the programmer agent will focus on the code generation and refinement based on the test executor agent's feedback. The test designer agent will generate test cases for the generated code, and the test executor agent will run the code with the test cases and write the feedback to the programmer. This collaborative system ensures robust code generation, surpassing the limitations of single-agent models and traditional methodologies. Our extensive experiments on 9 code generation models and 12 enhancement approaches showcase AgentCoder's superior performance over existing code generation models and prompt engineering techniques across various benchmarks. For example, AgentCoder achieves 77.4% and 89.1% pass@1 in HumanEval-ET and MBPP-ET with GPT-3.5, while SOTA baselines obtain only 69.5% and 63.0%. Comment: 21 pages, 12 figures
Keywords	Computer Science - Computation and Language
Subject code	005
Publishing date	2023-12-20
Publishing country	us
Document type	Book ; Online
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Article ; Online: Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data meta-analysis.

Campana, Mattia / Yakimov, Vladislav / Moussiopoulou, Joanna / Maurus, Isabel / Löhrs, Lisa / Raabe, Florian / Jäger, Iris / Mortazavi, Matin / Benros, Michael E / Jeppesen, Rose / Meyer Zu Hörste, Gerd / Heming, Michael / Giné-Servén, Eloi / Labad, Javier / Boix, Ester / Lennox, Belinda / Yeeles, Ksenija / Steiner, Johann / Meyer-Lotz, Gabriela /

Dobrowolny, Henrik / Malchow, Berend / Hansen, Niels / Falkai, Peter / Siafis, Spyridon / Leucht, Stefan / Halstead, Sean / Warren, Nicola / Siskind, Dan / Strube, Wolfgang / Hasan, Alkomiet / Wagner, Elias

Brain, behavior, and immunity

2024 Volume 119, Page(s) 353–362

Abstract: Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, ... ...

Abstract	Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptomś severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.
Language	English
Publishing date	2024-04-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2024.04.011
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Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 327: Show issues

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Article ; Online: Confronting the Convective Gray Zone in the Global Configuration of the Met Office Unified Model

Lorenzo Tomassini / Martin Willett / Alistair Sellar / Adrian Lock / David Walters / Michael Whitall / Claudio Sanchez / Julian Heming / Paul Earnshaw / José M. Rodriguez / Duncan Ackerley / Prince Xavier / Charmaine Franklin / Catherine A. Senior

Journal of Advances in Modeling Earth Systems, Vol 15, Iss 5, Pp n/a-n/a (2023)

2023

Abstract: Abstract In atmospheric models with kilometer‐scale grids the resolution approaches the scale of convection. As a consequence the most energetic eddies in the atmosphere are partially resolved and partially unresolved. The modeling challenge to represent ...

Abstract	Abstract In atmospheric models with kilometer‐scale grids the resolution approaches the scale of convection. As a consequence the most energetic eddies in the atmosphere are partially resolved and partially unresolved. The modeling challenge to represent convection partially explicitly and partially as a subgrid process is called the convective gray zone problem. The gray zone issue has previously been discussed in the context of regional models, but the evolution in regional models is constrained by the lateral boundary conditions. Here we explore the convective gray zone starting from a defined global configuration of the Met Office Unified Model using initialized forecasts and comparing different model formulations to observations. The focus is on convection and turbulence, but some aspects of the model dynamics are also considered. The global model is run at nominal 5 km resolution and thus contributions from both resolved and subgrid turbulent and convective fluxes are non‐negligible. The main conclusion is that in the present assessment, the configurations which include scale‐aware turbulence and a carefully reduced and simplified mass‐flux convection scheme outperform both the configuration with fully parameterized convection as well as a configuration in which the subgrid convection parameterization is switched off completely. The results are more conclusive with regard to convective organization and tropical variability than extratropical predictability. The present study thus endorses the strategy to further develop scale‐aware physics schemes and to pursue an operational implementation of the global 5 km‐resolution model to be used alongside other ensemble forecasts to allow researchers and forecasters to further assess these simulations.
Keywords	kilometer‐scale global atmospheric modeling ; convective gray zone ; convection‐circulation interaction ; atmospheric variability and predictability ; Physical geography ; GB3-5030 ; Oceanography ; GC1-1581
Subject code	551
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	American Geophysical Union (AGU)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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