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Article ; Online: Design of the first fusion experiment to achieve target energy gain G>1.

Kritcher, A L / Zylstra, A B / Weber, C R / Hurricane, O A / Callahan, D A / Clark, D S / Divol, L / Hinkel, D E / Humbird, K / Jones, O / Lindl, J D / Maclaren, S / Strozzi, D J / Young, C V / Allen, A / Bachmann, B / Baker, K L / Braun, T / Brunton, G /

Casey, D T / Chapman, T / Choate, C / Dewald, E / Di Nicola, J-M G / Edwards, M J / Haan, S / Fehrenbach, T / Hohenberger, M / Kur, E / Kustowski, B / Kong, C / Landen, O L / Larson, D / MacGowan, B J / Marinak, M / Millot, M / Nikroo, A / Nora, R / Pak, A / Patel, P K / Ralph, J E / Ratledge, M / Rubery, M S / Schlossberg, D J / Sepke, S M / Stadermann, M / Suratwala, T I / Tommasini, R / Town, R / Woodworth, B / Van Wonterghem, B / Wild, C

Physical review. E

2024 Volume 109, Issue 2-2, Page(s) 25204

Abstract: ... target gain G>1 N221204 (5 December 2022) [Phys. Rev. Lett. 132, 065102 (2024)10.1103/PhysRevLett.132 ...

Abstract	In this work we present the design of the first controlled fusion laboratory experiment to reach target gain G>1 N221204 (5 December 2022) [Phys. Rev. Lett. 132, 065102 (2024)10.1103/PhysRevLett.132.065102], performed at the National Ignition Facility, where the fusion energy produced (3.15 MJ) exceeded the amount of laser energy required to drive the target (2.05 MJ). Following the demonstration of ignition according to the Lawson criterion N210808, experiments were impacted by nonideal experimental fielding conditions, such as increased (known) target defects that seeded hydrodynamic instabilities or unintentional low-mode asymmetries from nonuniformities in the target or laser delivery, which led to reduced fusion yields less than 1 MJ. This Letter details design changes, including using an extended higher-energy laser pulse to drive a thicker high-density carbon (also known as diamond) capsule, that led to increased fusion energy output compared to N210808 as well as improved robustness for achieving high fusion energies (greater than 1 MJ) in the presence of significant low-mode asymmetries. For this design, the burnup fraction of the deuterium and tritium (DT) fuel was increased (approximately 4% fuel burnup and a target gain of approximately 1.5 compared to approximately 2% fuel burnup and target gain approximately 0.7 for N210808) as a result of increased total (DT plus capsule) areal density at maximum compression compared to N210808. Radiation-hydrodynamic simulations of this design predicted achieving target gain greater than 1 and also the magnitude of increase in fusion energy produced compared to N210808. The plasma conditions and hotspot power balance (fusion power produced vs input power and power losses) using these simulations are presented. Since the drafting of this manuscript, the results of this paper have been replicated and exceeded (N230729) in this design, together with a higher-quality diamond capsule, setting a new record of approximately 3.88MJ of fusion energy and fusion energy target gain of approximately 1.9.
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.109.025204
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A new type of pharmacological chaperone for G

Schalli, Michael / Weber, Patrick / Tysoe, Christina / Pabst, Bettina M / Thonhofer, Martin / Paschke, Eduard / Stütz, Arnold E / Tschernutter, Marion / Windischhofer, Werner / Withers, Stephen G

Bioorganic & medicinal chemistry letters

2017 Volume 27, Issue 15, Page(s) 3431–3435

Abstract: ... and, for the first time, could be shown to act as pharmacological chaperones for G ...

Abstract	N-Functionalized amino(hydroxymethyl)cyclopentanetriols are potent inhibitors of β-d-galactosidases and, for the first time, could be shown to act as pharmacological chaperones for G
MeSH term(s)	Amination ; Animals ; Cattle ; Cyclopentanes/chemistry ; Cyclopentanes/pharmacology ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Gangliosidosis, GM1/drug therapy ; Gangliosidosis, GM1/enzymology ; Humans ; Lysosomes/drug effects ; Lysosomes/enzymology ; Methylation ; beta-Galactosidase/antagonists & inhibitors ; beta-Galactosidase/metabolism
Chemical Substances	Cyclopentanes ; Enzyme Inhibitors ; acid beta-galactosidase (EC 3.2.1.23) ; beta-Galactosidase (EC 3.2.1.23)
Language	English
Publishing date	2017--01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2017.05.086
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Article ; Online: Pharmacological Chaperones for β-Galactosidase Related to G

Stütz, Arnold E / Thonhofer, Martin / Weber, Patrick / Wolfsgruber, Andreas / Wrodnigg, Tanja M

Chemical record (New York, N.Y.)

2021 Volume 21, Issue 11, Page(s) 2980–2989

Abstract: A short survey on selected β-galactosidase inhibitors as potential pharmacological chaperones for G ...

Abstract	A short survey on selected β-galactosidase inhibitors as potential pharmacological chaperones for G
MeSH term(s)	Gangliosidoses ; Gangliosidosis, GM1/drug therapy ; Humans ; Lysosomes ; Mucopolysaccharidosis IV/drug therapy ; beta-Galactosidase/antagonists & inhibitors
Chemical Substances	beta-Galactosidase (EC 3.2.1.23)
Language	English
Publishing date	2021-11-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2044646-9
ISSN	1528-0691 ; 1527-8999
ISSN (online)	1528-0691
ISSN	1527-8999
DOI	10.1002/tcr.202100269
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Article ; Online: Stability assessment of anti-bacterial antibodies in immunoglobulin G-depleted serum with validated immunoassays.

Engelmaier, Andrea / Butterweck, Harald A / Weber, Alfred

Immunotherapy

2023 Volume 15, Issue 17, Page(s) 1459–1476

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Humans ; Immunoglobulin G ; Immunoassay ; Enzyme-Linked Immunosorbent Assay ; Immunoglobulins, Intravenous ; Antibodies, Bacterial
Chemical Substances	Immunoglobulin G ; Immunoglobulins, Intravenous ; Antibodies, Bacterial
Language	English
Publishing date	2023-09-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2495964-9
ISSN	1750-7448 ; 1750-743X
ISSN (online)	1750-7448
ISSN	1750-743X
DOI	10.2217/imt-2023-0127
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Article ; Online: Helquat dyes targeting G-quadruplexes as a new class of anti-HIV-1 inhibitors.

Pávová, Marcela / Reyes-Gutiérrez, Paul Eduardo / Kozák, Jaroslav / Dobiaš, Juraj / Yurenko, Yevgen / Lepšík, Martin / Teplý, Filip / Weber, Jan

Scientific reports

2023 Volume 13, Issue 1, Page(s) 6096

Abstract: The secondary structure of nucleic acids containing quartets of guanines, termed G-quadruplexes, is ... known to regulate the transcription of many genes. Several G-quadruplexes can be formed in the HIV-1 ... stop and FRET melting assays, we have demonstrated their ability to stabilize G-quadruplexes ...

Abstract	The secondary structure of nucleic acids containing quartets of guanines, termed G-quadruplexes, is known to regulate the transcription of many genes. Several G-quadruplexes can be formed in the HIV-1 long terminal repeat promoter region and their stabilization results in the inhibition of HIV-1 replication. Here, we identified helquat-based compounds as a new class of anti-HIV-1 inhibitors that inhibit HIV-1 replication at the stage of reverse transcription and provirus expression. Using Taq polymerase stop and FRET melting assays, we have demonstrated their ability to stabilize G-quadruplexes in the HIV-1 long-terminal repeat sequence. Moreover, these compounds were not binding to the general G-rich region, but rather to G-quadruplex-forming regions. Finally, docking and molecular dynamics calculations indicate that the structure of the helquat core greatly affects the binding mode to the individual G-quadruplexes. Our findings can provide useful information for the further rational design of inhibitors targeting G-quadruplexes in HIV-1.
MeSH term(s)	G-Quadruplexes ; Promoter Regions, Genetic ; Terminal Repeat Sequences ; Reverse Transcription ; HIV-1/genetics
Language	English
Publishing date	2023-04-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-33263-3
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Article ; Online: Identification of a defensin as novel allergen in celery root: Api g 7 as a missing link in the diagnosis of celery allergy?

Wangorsch, Andrea / Lidholm, Jonas / Mattsson, Lars A / Larsson, Håkan / Reuter, Andreas / Gubesch, Michaela / Gadermaier, Gabriele / Bures, Peter / Scheurer, Stephan / Ballmer-Weber, Barbara / Vieths, Stefan

Allergy

2021 Volume 77, Issue 4, Page(s) 1294–1296

MeSH term(s)	Allergens/immunology ; Antigens, Plant/immunology ; Apium/immunology ; Cross Reactions ; Defensins/immunology ; Food Hypersensitivity/diagnosis ; Food Hypersensitivity/immunology ; Humans ; Hypersensitivity/diagnosis ; Hypersensitivity/immunology
Chemical Substances	Allergens ; Antigens, Plant ; Defensins
Language	English
Publishing date	2021-12-21
Publishing country	Denmark
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15196
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Article ; Online: Modelling altered signalling of G-protein coupled receptors in inflamed environment to advance drug design.

Thies, Arne / Sunkara, Vikram / Ray, Sourav / Wulkow, Hanna / Celik, M Özgür / Yergöz, Fatih / Schütte, Christof / Stein, Christoph / Weber, Marcus / Winkelmann, Stefanie

Scientific reports

2023 Volume 13, Issue 1, Page(s) 607

Abstract: ... on mathematical modelling of extracellular interactions between G-protein coupled receptors (GPCRs) and ligands, recognizing ... and novel stochastic model of GPCR function that includes intracellular dissociation of G ... to the effect of fentanyl. For increasing radical concentrations, we find enhanced constitutive G-protein ...

Abstract	We previously reported the successful design, synthesis and testing of the prototype opioid painkiller NFEPP that does not elicit adverse side effects. The design process of NFEPP was based on mathematical modelling of extracellular interactions between G-protein coupled receptors (GPCRs) and ligands, recognizing that GPCRs function differently under pathological versus healthy conditions. We now present an additional and novel stochastic model of GPCR function that includes intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels and their dependence on parameters of inflamed and healthy tissue (pH, radicals). The model is validated against in vitro experimental data for the ligands NFEPP and fentanyl at different pH values and radical concentrations. We observe markedly reduced binding affinity and calcium channel inhibition for NFEPP at normal pH compared to lower pH, in contrast to the effect of fentanyl. For increasing radical concentrations, we find enhanced constitutive G-protein activation but reduced ligand binding affinity. Assessing the different effects, the results suggest that, compared to radicals, low pH is a more important determinant of overall GPCR function in an inflamed environment. Future drug design efforts should take this into account.
MeSH term(s)	Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; GTP-Binding Proteins/metabolism ; Fentanyl/pharmacology ; Drug Design ; Ligands
Chemical Substances	Receptors, G-Protein-Coupled ; GTP-Binding Proteins (EC 3.6.1.-) ; Fentanyl (UF599785JZ) ; Ligands
Language	English
Publishing date	2023-01-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-27699-w
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Article ; Online: Association of Intrathecal Immunoglobulin G Synthesis With Disability Worsening in Multiple Sclerosis.

JAMA neurology

2019 Volume 76, Issue 7, Page(s) 841–849

Abstract: Importance: Reliable biomarkers associated with disability worsening in multiple sclerosis (MS) are still needed.: Objective: To determine a possible association of intrathecal IgG synthesis and early disability worsening as measured by Expanded ... ...

Abstract	Importance: Reliable biomarkers associated with disability worsening in multiple sclerosis (MS) are still needed. Objective: To determine a possible association of intrathecal IgG synthesis and early disability worsening as measured by Expanded Disability Status Scale (EDSS) scoring in patients with relapsing-remitting MS or clinically isolated syndrome. Design, setting, and participants: Cerebrospinal fluid measurements and clinical data from the observational longitudinal German national multiple sclerosis cohort were analyzed. Patients were recruited between August 2010 and November 2015 from 18 centers. Data analysis was completed from August 2018 to December 2018. Exposure: Patients were offered standard immunotherapies per national treatment guidelines. Main outcomes and measures: A possible association between intrathecal IgG synthesis and risk of EDSS worsening 4 years after study inclusion was tested as the primary end point by multivariable binomial regression analysis. Kaplan-Meier analysis with a log-rank test was used to assess the association of intrathecal IgG synthesis with the time to EDSS worsening. Associations between intrathecal IgM or IgA synthesis and other cerebrospinal fluid parameters and EDSS worsening were analyzed as exploratory end points. Data collection began before the hypotheses were formulated. Results: Of all 1376 patients in the German Competence Network of Multiple Sclerosis cohort, 703 patients were excluded owing to missing cerebrospinal fluid or EDSS data. Of the 673 included patients, 459 (68.2%) were women. The mean (SD) age at baseline was 34 (10) years. Intrathecal IgG synthesis was associated with a higher risk of EDSS worsening after 4 years (odds ratio, 2.02 [95% CI, 1.15-3.58]; P = .01), independent of the occurrence of relapses and disease-modifying therapy. Additionally, intrathecal IgG synthesis was associated with earlier EDSS worsening; 4 years after study entry, worsening occurred in 28.4% (95% CI, 22.7%-34.1%) and 18.1% (95% CI, 12.4%-23.9%) of patients with and without intrathecal IgG synthesis, respectively. No association of other routine cerebrospinal fluid parameters with EDSS worsening was found. Conclusions and relevance: Patients with new diagnoses of relapsing-remitting multiple sclerosis or clinically isolated syndrome with intrathecal IgG synthesis had a higher risk of and shorter time to EDSS worsening across a 4-year period of follow-up. Intrathecal IgG synthesis is a potentially useful marker for disability worsening in patients with multiple sclerosis and may be useful for early treatment decisions.
MeSH term(s)	Adult ; Cohort Studies ; Demyelinating Diseases/cerebrospinal fluid ; Demyelinating Diseases/physiopathology ; Female ; Humans ; Immunoglobulin A/biosynthesis ; Immunoglobulin A/cerebrospinal fluid ; Immunoglobulin G/biosynthesis ; Immunoglobulin G/cerebrospinal fluid ; Immunoglobulin M/biosynthesis ; Immunoglobulin M/cerebrospinal fluid ; Male ; Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid ; Multiple Sclerosis, Relapsing-Remitting/physiopathology ; Oligoclonal Bands/cerebrospinal fluid ; Prospective Studies ; Severity of Illness Index
Chemical Substances	Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Oligoclonal Bands
Language	English
Publishing date	2019-04-25
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2019.0905
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Article: Mindestmengen G-BA: Sündenfall TAVI

Weber, Michael A. / Stellbrink, Christoph / Schächinger, Volker / Hoffmeister, Hans Martin

Das Krankenhaus

2020 Volume 112, Issue 8, Page(s) 652

Language	German
Document type	Article
ZDB-ID	3262-1
ISSN	0340-3602
Database	Current Contents Medicine

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Article: Regulator of G protein signaling 6 (RGS6) in ventral tegmental area (VTA) dopamine neurons promotes EtOH seeking, behavioral reward and susceptibility to relapse.

Spicer, Mackenzie M / Weber, Matthew A / Luo, Zili / Yang, Jianqi / Narayanan, Nandakumar S / Fisher, Rory A

bioRxiv : the preprint server for biology

2023

Abstract: Mesolimbic dopamine (DA) transmission is believed to play a critical role in mediating reward responses to drugs of abuse, including alcohol (EtOH). EtOH is the most abused substance worldwide with chronic consumption often leading to the development of ... ...

Abstract	Mesolimbic dopamine (DA) transmission is believed to play a critical role in mediating reward responses to drugs of abuse, including alcohol (EtOH). EtOH is the most abused substance worldwide with chronic consumption often leading to the development of dependence and abuse. Unfortunately, the neurobiological mechanisms underlying EtOH-seeking behavior and dependence are not fully understood, and abstinence remains the only effective way to prevent alcohol use disorders (AUDs). Here, we developed novel RGS6
Language	English
Publishing date	2023-10-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.24.563844
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