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Article ; Conference proceedings ; Online: LIPASE CATALYSED RESOLUTION OF BICYCLIC BUILDING BLOCKS FOR LEUKOTRIENE SYNTHESIS

Spreitz, J. / Grobbauer, R. / Griengl, H. / Faber, K.

ADVANTAGES OF ORGANIC MEDIA

2024

Abstract: The bicyclic bromohydrins rac-la,b were conveniently resolved with lipases from Pseudomonas (Amano P) and Candida cylindracea (Amano AY-30) using vinyl acetate as acyl donor and solvent. Both enantiomers could be obtained with >96% e.e. ...

Abstract	The bicyclic bromohydrins rac-la,b were conveniently resolved with lipases from Pseudomonas (Amano P) and Candida cylindracea (Amano AY-30) using vinyl acetate as acyl donor and solvent. Both enantiomers could be obtained with >96% e.e.
Language	English
Publishing date	2024-03-27
Publisher	GBF Gesellschaft für Biotechnologische Forschung mbH, Braunschweig
Publishing country	de
Document type	Article ; Conference proceedings ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: On the importance of the humidity flux for the surface mass balance in the accumulation zone of the Greenland Ice Sheet

L. J. Dietrich / H. C. Steen-Larsen / S. Wahl / A.-K. Faber / X. Fettweis

The Cryosphere, Vol 18, Pp 289-

2024 Volume 305

Abstract: It is highly uncertain how the humidity flux between the snow surface and the atmosphere contributes to the surface mass balance (SMB) of the interior Greenland Ice Sheet (GrIS). Due to sparse observations, evaluations of the simulated humidity flux are ... ...

Abstract	It is highly uncertain how the humidity flux between the snow surface and the atmosphere contributes to the surface mass balance (SMB) of the interior Greenland Ice Sheet (GrIS). Due to sparse observations, evaluations of the simulated humidity flux are limited. Model-based estimates of the humidity flux contribution to the SMB are, therefore, unconstrained and even disagree in magnitude and sign. In this study, we evaluate the regional climate model MAR at the EGRIP (East Greenland Ice-Core Project) site in the accumulation zone of the GrIS. We use a combined dataset of continuous one-level bulk estimates of the humidity flux covering the period of May 2016–August 2019 and eddy-resolving eddy-covariance humidity flux measurements from all four summer seasons. In summer, we document a bias of too little sublimation ( − 1.3 W m −2 , − 1.65 mm w.e.) caused by a cold bias in both air and surface temperature, leading to a reduced humidity gradient. In winter, MAR overestimates vapor deposition by about 1 order of magnitude. This is a consequence of an overestimated temperature gradient in too stable atmospheric conditions compared to observations. Both systematic errors cause a large discrepancy in the annual net humidity flux between the model and observations of − 9 mm w.e. yr −1 . Remarkably, the simulated net annual humidity flux contributes positively to the SMB, contrary to observations documenting a net sublimation flux. We correct the systematic errors by applying a simple but effective correction function to the simulated latent heat flux. Using this correction, we find that 5.1 % of the annual mass gain at the EGRIP site sublimates again, and 4.3 % of the total mass gain is deposited vapor from the near-surface air. The estimated net humidity flux contribution to the annual SMB is about − 1 % (net sublimation) compared to + 5.6 % for the uncorrected simulation. In summer, the corrected MAR simulation shows that vapor deposition accounts for 9.6 % of the total mass gain and that 31 % of the total mass gain ...
Keywords	Environmental sciences ; GE1-350 ; Geology ; QE1-996.5
Subject code	333
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Copernicus Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Enhanced Transport at High Plasma Pressure and Subthreshold Kinetic Ballooning Modes in Wendelstein 7-X.

Mulholland, P / Aleynikova, K / Faber, B J / Pueschel, M J / Proll, J H E / Hegna, C C / Terry, P W / Nührenberg, C

Physical review letters

2023 Volume 131, Issue 18, Page(s) 185101

Abstract: High-performance fusion plasmas, requiring high pressure β, are not well understood in stellarator-type experiments. Here, the effect of β on ion-temperature-gradient-driven (ITG) turbulence is studied in Wendelstein 7-X (W7-X), showing that subdominant ... ...

Abstract	High-performance fusion plasmas, requiring high pressure β, are not well understood in stellarator-type experiments. Here, the effect of β on ion-temperature-gradient-driven (ITG) turbulence is studied in Wendelstein 7-X (W7-X), showing that subdominant kinetic ballooning modes (KBMs) are unstable well below the ideal MHD threshold and get strongly excited in the turbulence. By zonal-flow erosion, these subthreshold KBMs (stKBMs) affect ITG saturation and enable higher heat fluxes. Controlling stKBMs will be essential to allow W7-X and future stellarators to achieve maximum performance.
Language	English
Publishing date	2023-11-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.131.185101
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Article ; Online: Berufliche Zukunftsperspektive von Augenärzten unter 49 Jahren : Eine Umfrage in Deutschland aus dem Jahr 2022.

Hartmann, A / Bertram, B / Siebelmann, S / Böhm, M / Faber, H / Zhour, A / Schuster, A K

Die Ophthalmologie

2023 Volume 120, Issue 7, Page(s) 726–733

Abstract: Objective: The need for care in ophthalmology is constantly increasing due to demographic changes. The study analyzed the current professional situation and future prospects of ophthalmologists under 49 years old.: Methods: The survey of members of ... ...

Title translation	Career prospects for ophthalmologists under 49 years old : A survey in Germany from 2022.
Abstract	Objective: The need for care in ophthalmology is constantly increasing due to demographic changes. The study analyzed the current professional situation and future prospects of ophthalmologists under 49 years old. Methods: The survey of members of the German Association of Ophthalmologists (Berufsverband der Augenärzte Deutschlands) and the German Ophthalmologic Society (Deutsche Ophthalmologische Gesellschaft) was conducted in 2022. All members under the age of 49 years received an online questionnaire on the current professional situation as well as future perspectives (desired working hours, form of organization). The results of the survey were additionally compared with the 2016 survey of the German Association of Ophthalmologists. A similar questionnaire was used at that time. Results: A total of 1014 people participated in the survey (62.7% women, mean age 39.3 ± 8 years, 75.6% specialists). The response rate to the survey was 25%. Specialist practice from 0 to 5 years showed a higher number of employed ophthalmologists (21% self-employed vs. 32% employed); over time the number of self-employed ophthalmologists increased (6-10 years: 40%, > 10 years: 59.3%). Overall, 46% of women were employed in a practice compared with 33% of men. Of the self-employed specialists, 95.9% said they planned to work in the same type of employment in 10 years as currently. Regarding ophthalmologists' career future, the other employment types showed a desire to move to independent practice. Compared to the 2016 survey, gender differences related to the current type of employment were evident. The number of self-employed women decreased from 43% to 26% and self-employed men decreased from 63% to 39%. The number of ophthalmologists in ambulatory healthcare centers was doubled compared to 2016. Ophthalmologists reported similar future perspectives at both survey times. Conclusion: The results of the survey of ophthalmologists under 49 years in Germany showed similar perceptions as in 2016. It became clear that the desire to be self-employed in 10 years is very high; however, ophthalmologists expected large practices or medical care centers to prevail in the market. The number of self-employed doctors is decreasing and the desire for self-employment is difficult to realize.
MeSH term(s)	Male ; Humans ; Female ; Adult ; Middle Aged ; Ophthalmologists ; Surveys and Questionnaires ; Ophthalmology ; Employment ; Physicians
Language	German
Publishing date	2023-02-02
Publishing country	Germany
Document type	English Abstract ; Journal Article
ISSN	2731-7218
ISSN (online)	2731-7218
DOI	10.1007/s00347-022-01806-0
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Article ; Online: Utilizing flow cytometry sorting signal width to enrich for cells positive to endogenous gene integration of fluorescent proteins.

Faber, Gabriel P / Hauschner, Hagit / Atrash, Mohammad K / Bilinsky, Liat / Shav-Tal, Yaron

Cytometry. Part A : the journal of the International Society for Analytical Cytology

2023 Volume 103, Issue 8, Page(s) 664–669

Abstract: Endogenous gene knock-in using CRIPSR is becoming the standard for fluorescent tagging of endogenous proteins. Some protocols, particularly those that utilize insert cassettes that carry a fluorescent protein tag, can yield many types of cells with off- ... ...

Abstract	Endogenous gene knock-in using CRIPSR is becoming the standard for fluorescent tagging of endogenous proteins. Some protocols, particularly those that utilize insert cassettes that carry a fluorescent protein tag, can yield many types of cells with off-target insertions that have diffuse fluorescent signal throughout the whole cell in addition to scarce cells with on-target gene insertions that show the correct sub-cellular localization of the tagged protein. As such, when searching for cells with on-target integration using flow cytometry, the off-target fluorescent cells yield a high percentage of false positives. Here, we show that by changing the gating used to select for fluorescence during flow cytometry sorting, namely utilizing the width of the signal as opposed to the area, we can highly enrich for positively integrated cells. Reproducible gates were created to select even minuscule percentages of correct subcellular signal, and these parameters were validated by fluorescence microscopy. This method is a powerful tool to rapidly enhance the generation of cell lines with correctly integrated gene knock-ins encoding endogenous fluorescent proteins.
MeSH term(s)	Flow Cytometry ; Proteins ; Cell Line ; Microscopy, Fluorescence ; Coloring Agents
Chemical Substances	Proteins ; Coloring Agents
Language	English
Publishing date	2023-05-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2099868-5
ISSN	1552-4930 ; 0196-4763 ; 1552-4922
ISSN (online)	1552-4930
ISSN	0196-4763 ; 1552-4922
DOI	10.1002/cyto.a.24735
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Article: Imaging of pleural disease.

Hassan, Maged / Touman, Abdelfattah A / Grabczak, Elżbieta M / Skaarup, Søren H / Faber, Katarzyna / Blyth, Kevin G / Pochepnia, Svitlana

Breathe (Sheffield, England)

2024 Volume 20, Issue 1, Page(s) 230172

Abstract: The pleural space is a "potential" anatomical space which is formed of two layers: visceral and parietal. It normally contains a trace of fluid (∼10 mL in each hemithorax). Diseases of the pleura can manifest with thickening of the pleural membranes or ... ...

Abstract	The pleural space is a "potential" anatomical space which is formed of two layers: visceral and parietal. It normally contains a trace of fluid (∼10 mL in each hemithorax). Diseases of the pleura can manifest with thickening of the pleural membranes or by abnormal accumulation of air or liquid. Chest radiographs are often the first imaging tests to point to a pleural pathology. With the exception of pneumothorax, and due to the inherent limitations of chest radiographs, ultrasound and/or computed tomography are usually required to further characterise the pleural pathology and guide management. This review summarises the utility of different imaging tools in the management of pleural disease and discusses new and evolving tools in imaging of the pleura.
Language	English
Publishing date	2024-03-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2562899-9
ISSN	2073-4735 ; 1810-6838
ISSN (online)	2073-4735
ISSN	1810-6838
DOI	10.1183/20734735.0172-2023
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Article ; Online: Semi-automatic standardized analysis method to objectively evaluate near-infrared fluorescent dyes in image-guided surgery.

Dijkhuis, Tom H / Bijlstra, Okker D / Warmerdam, Mats I / Faber, Robin A / Linders, Daan G J / Galema, Hidde A / Broersen, Alexander / Dijkstra, Jouke / Kuppen, Peter J K / Vahrmeijer, Alexander L / Mieog, Jan Sven David

Journal of biomedical optics

2024 Volume 29, Issue 2, Page(s) 26001

Abstract: Significance: Near-infrared fluorescence imaging still lacks a standardized, objective method to evaluate fluorescent dye efficacy in oncological surgical applications. This results in difficulties in translation between preclinical to clinical studies ... ...

Abstract	Significance: Near-infrared fluorescence imaging still lacks a standardized, objective method to evaluate fluorescent dye efficacy in oncological surgical applications. This results in difficulties in translation between preclinical to clinical studies with fluorescent dyes and in the reproduction of results between studies, which in turn hampers further clinical translation of novel fluorescent dyes. Aim: Our aim is to develop and evaluate a semi-automatic standardized method to objectively assess fluorescent signals in resected tissue. Approach: A standardized imaging procedure was designed and quantitative analysis methods were developed to evaluate non-targeted and tumor-targeted fluorescent dyes. The developed analysis methods included manual selection of region of interest (ROI) on white light images, automated fluorescence signal ROI selection, and automatic quantitative image analysis. The proposed analysis method was then compared with a conventional analysis method, where fluorescence signal ROIs were manually selected on fluorescence images. Dice similarity coefficients and intraclass correlation coefficients were calculated to determine the inter- and intraobserver variabilities of the ROI selections and the determined signal- and tumor-to-background ratios. Results: The proposed non-targeted fluorescent dyes analysis method showed statistically significantly improved variabilities after application on indocyanine green specimens. For specimens with the targeted dye SGM-101, the variability of the background ROI selection was statistically significantly improved by implementing the proposed method. Conclusion: Semi-automatic methods for standardized quantitative analysis of fluorescence images were successfully developed and showed promising results to further improve the reproducibility and standardization of clinical studies evaluating fluorescent dyes.
MeSH term(s)	Humans ; Fluorescent Dyes ; Reproducibility of Results ; Neoplasms/diagnostic imaging ; Neoplasms/surgery ; Surgery, Computer-Assisted/methods ; Optical Imaging/methods ; Indocyanine Green
Chemical Substances	Fluorescent Dyes ; Indocyanine Green (IX6J1063HV)
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1309154-2
ISSN	1560-2281 ; 1083-3668
ISSN (online)	1560-2281
ISSN	1083-3668
DOI	10.1117/1.JBO.29.2.026001
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Article: Atmosphere-Snow Exchange Explains Surface Snow Isotope Variability.

Wahl, S / Steen-Larsen, H C / Hughes, A G / Dietrich, L J / Zuhr, A / Behrens, M / Faber, A-K / Hörhold, M

Geophysical research letters

2022 Volume 49, Issue 20, Page(s) e2022GL099529

Abstract: The climate signal imprinted in the snow isotopic composition allows to infer past climate variability from ice core stable water isotope records. The concurrent evolution of vapor and surface snow isotopic composition between precipitation events ... ...

Abstract	The climate signal imprinted in the snow isotopic composition allows to infer past climate variability from ice core stable water isotope records. The concurrent evolution of vapor and surface snow isotopic composition between precipitation events indicates that post-depositional atmosphere-snow humidity exchange influences the snow and hence the ice core isotope signal. To date, however, this is not accounted for in paeleoclimate reconstructions from isotope records. Here we show that vapor-snow exchange explains 36% of the summertime day-to-day δ
Language	English
Publishing date	2022-10-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	7403-2
ISSN	0094-8276
ISSN	0094-8276
DOI	10.1029/2022GL099529
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Article: Itraconazole Nanosuspensions via Dual Centrifugation Media Milling: Impact of Formulation and Process Parameters on Particle Size and Solid-State Conversion as Well as Storage Stability.

Willmann, Ann-Cathrin / Berkenfeld, Kai / Faber, Thilo / Wachtel, Herbert / Boeck, Georg / Wagner, Karl G

Pharmaceutics

2022 Volume 14, Issue 8

Abstract: Nanocrystal suspensions proved to be a potent enabling principle for biopharmaceutics classification system class II drugs with dissolution limited bioavailability. In the example of itraconazole (ITZ) as a model drug combined with electrosteric ... ...

Abstract	Nanocrystal suspensions proved to be a potent enabling principle for biopharmaceutics classification system class II drugs with dissolution limited bioavailability. In the example of itraconazole (ITZ) as a model drug combined with electrosteric stabilization using hydroxypropyl cellulose (HPC-SL), sodium dodecyl sulfate (SDS) and polysorbate 80 (PS80), the impacts of formulation and process parameters of a dual centrifugal mill on material attributes such as particle size, zeta potential, particle morphology, storage stability and especially solid-state characteristics were evaluated. A minimal concentration of 0.9% (
Language	English
Publishing date	2022-07-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14081528
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Article ; Online: Targeting Oncogenic Mutant p53 and BCL-2 for Small Cell Lung Cancer Treatment.

Neely, Victoria / Manchikalapudi, Alekhya / Nguyen, Khanh / Dalton, Krista / Hu, Bin / Koblinski, Jennifer E / Faber, Anthony C / Deb, Sumitra / Harada, Hisashi

International journal of molecular sciences

2023 Volume 24, Issue 17

Abstract: Through a unique genomics and drug screening platform with ~800 solid tumor cell lines, we have found a subset of SCLC cell lines are hypersensitive to venetoclax, an FDA-approved inhibitor of BCL-2. SCLC-A (ASCL1 positive) and SCLC-P (POU2F3 positive), ... ...

Abstract	Through a unique genomics and drug screening platform with ~800 solid tumor cell lines, we have found a subset of SCLC cell lines are hypersensitive to venetoclax, an FDA-approved inhibitor of BCL-2. SCLC-A (ASCL1 positive) and SCLC-P (POU2F3 positive), which make up almost 80% of SCLC, frequently express high levels of BCL-2. We found that a subset of SCLC-A and SCLC-P showed high BCL-2 expression but were venetoclax-resistant. In addition, most of these SCLC cell lines have TP53 missense mutations, which make a single amino acid change. These mutants not only lose wild-type (WT) p53 tumor suppressor functions, but also acquire novel cancer-promoting activities (oncogenic, gain-of-function). A recent study with oncogenic mutant (Onc)-p53 knock-in mouse models of SCLC suggests gain-of-function activity can attenuate chemotherapeutic efficacy. Based on these observations, we hypothesize that Onc-p53 confers venetoclax resistance and that simultaneous inhibition of BCL-2 and Onc-p53 induces synergistic anticancer activity in a subset of SCLC-A and SCLC-P. We show here that (1) down-regulation of Onc-p53 increases the expression of a BH3-only pro-apoptotic BIM and sensitizes to venetoclax in SCLC-P cells; (2) targeting Onc-p53 by the HSP90 inhibitor, ganetespib, increases BIM expression and sensitizes to venetoclax in SCLC-P and SCLC-A cells. Although there are currently many combination studies for venetoclax proposed, the concept of simultaneous targeting of BCL-2 and Onc-p53 by the combination of venetoclax and HSP90 inhibitors would be a promising approach for SCLC treatment.
MeSH term(s)	Animals ; Mice ; Cell Line, Tumor ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Proto-Oncogene Proteins c-bcl-2/genetics ; Small Cell Lung Carcinoma/drug therapy ; Small Cell Lung Carcinoma/genetics ; Tumor Suppressor Protein p53/genetics
Chemical Substances	Proto-Oncogene Proteins c-bcl-2 ; Tumor Suppressor Protein p53 ; venetoclax (N54AIC43PW)
Language	English
Publishing date	2023-08-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241713082
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