289 research outputs found
A Pioneering Career in Catalysis: Manfred T. Reetz
No full textIn this invited Account, we highlight the enormous scientific breadth of our mentor Professor Manfred T. Reetz. It stretches from the development of organometallic reagents and transition metal catalysts to the adventurous idea of directed evolution of chemo-, stereo-, and regioselective enzymes, which he considered to be most important. We hope to show that Reetz did not consider these research areas to be totally unrelated realms, and attempt to reveal his transdisciplinary way of thinking about methodology development. Since biocatalysis has become crucial for chemical synthesis, we mainly focus on Reetz's contributions in this area. Some personal reflections from some of his former co-workers are also included, which reveal the stimulating atmosphere in the Reetz group in terms of science, career advice, and the importance of ethical considerations. BT/Biocatalysi
Rekonstruktion der BRTF von komplexen lichtlenkenden oder lichtstreuenden Materialien durch Merkmals-Extraktion und Interpolation goniometrischer Messdaten
No full textDiplomarbeit an der Heinrich-Heine-Universität Düsseldorf. In Zusammenarbeit mit dem Fraunhofer-Institut für Solare Energiesysteme -ISE-, Freibur
Prospective randomized trial to investigate the effect of fibrin glue on the development of postoperative lymphatic fistulas after axillary lymph node dissection in patients with malignant melanoma
No full textMaligne Melanome sind bösartige Tumoren mit weltweit zunehmender Inzidenz. Nur
in frühen Stadien sind maligne Melanome kurativ behandelbar. Am häufigsten ist
eine Metastasierung in die für die jeweiligen Regionen zuständigen,
drainierenden regionalen Lymphknoten, den sogenannten Wächter-Lymphknoten. Bei
Nachweis eines Lymphknotenbefalles im primären lymphogenen Abstromgebiet des
Primarius ist die radikale Dissektion aller dort befindlichen Lymphknoten
indiziert. Nach einer radikalen axillären Lymphknotendissektion können
postoperative Komplikationen, wie Lymphfisteln, Lymphozelen, Lymphödeme und
Seromformationen, mit einer verlängerten Drainageliegedauer, einer verzögerten
Wundheilung und letztlich einem erhöhtem Risiko für die Entstehung von
Wundinfektionen verbunden sein. Diese Komplikationen stellen eine nicht
unwesentliche Herausforderung für den Chirurgen dar und bedingen teilweise
einen erheblich verlängerten Krankenhausaufenthalt. In mehreren publizierten
Studien, die allerdings nur relativ geringe Fallzahlen betrachteten, wurde
untersucht, ob durch die intraoperative Applikation eines Fibrinklebers in die
operativ entstandene Wundhöhle eine Senkung der Drainageliegedauer sowie eine
Verringerung der Inzidenz postoperativer Komplikationen und somit eine
signifikante Verkürzung des Krankenhausaufenthaltes erreicht werden kann.
Wegen der unterschiedlichen, zum Teil widersprüchlichen Aussagen der
publizierten Arbeiten war das Ziel dieser Studie, mit Hilfe einer prospektiv
randomisierten, klinischen, einfach-verblindeten Studie den Effekt eines
herkömmlichen Fibrinklebers auf die Inzidenz postoperativer Lymphfisteln nach
radikaler axillärer Lymphadenektomie zu evaluieren. Von September 2003 bis
einschließlich Juli 2005 wurde bei 58 Patienten eine radikale axilläre
Lymphadenektomie durchgeführt. Bei 29 Patienten (Fibringruppe) wurde vor
Wundverschluss die Wunde intraoperativ mit einem Fibrinkleber (Tissucol® Duo S
2 ml Immuno) über einen Sprühapplikator benetzt. Bei den anderen 29 Patienten
(Kontrollgruppe) erfolgte nur die bei allen Patienten standardisiert
durchgeführte Wundspülung mit Ringer-Lösung. Von allen Patienten wurden: 1\.
die Drainageliegedauer, 2\. das Drainagegesamtvolumen, 3\. die
Krankenhausverweildauer und 4\. die postoperativen Komplikationen erfasst.
Nach Auswertung der Ergebnisse war festzustellen, dass die intraoperative
Applikation von 2 ml Tissucol® Duo S Immuno weder einen Einfluss auf die
Drainageliegedauer (5 vs. 5 Tage) noch auf das Drainagegesamtvolumen (503 vs.
410 ml) sowie auf die Rate postoperativer Komplikationen hatte. Eine
signifikante Verkürzung der Krankenhausverweildauer (7 vs. 6 Tage) konnte
durch die intraoperative Fibrinapplikation ebenfalls nicht erreicht werden.The world wide incidence of malignant melanoma – the most malignant tumor of
the skin - is rising. Metastases of the tumor occurs frequently in the
corresponding draining area of the lymph nodes. In the regional node basin the
sentinel node plays a key role in the course of the disease. Only in early
stages curative treatment of the tumor is possible. In case of lymph node
metastases in the regional node basin a radical lymph node dissection of the
regional node area is indicated. Following radical axillary lymph node
dissection postoperative complications such as lymph fistulas, edema or seroma
may occur, thus resulting in a prolonged placement of wound drains, diminished
wound healing and finally an increased risk of minor or major wound
infections. The described complications can challenge the treating surgeon and
can be a reason for a prolonged hospital stay of the patient. Because of
different published results concerning the described problem we conducted a
blinded prospective trial to study the influence of a commercial available
fibrin glue on the incidence of postoperative lymph fistula after radical
axillary lymph node dissection. From Sept. 2003 to July 2005 in 58 patients a
radical axillary lymph node dissection was performed. In 29 patients prior to
wound closure fibrin glue (Tissucol® Duo S 2cc Immuno) were sprayed into the
wound. In the other group of 29 patients only wound irrigation with ringer
solution was performed. In all patients we recognized the 1\. length of
drainage 2\. drainage volume 3\. lentgh of hospital stay 4\. postoperative
complications. After statistical evaluation of the obtained results it
appaered, that the intraoperative application of 2 cc Tissucol® Duo S Immuno
did not influence the lentgh of drainage (5 vs 5 days), the drainage volume
(503 cc vs 410 cc) or the rate of postoperative complications. In addtion to
this a significant reduction of the hospital stay was not achieved
Kinder als Teilnehmer*innen medizinischer Forschung: Eine Fragebogenstudie zu Verstehen und Motivation von Minderjährigen
No full textDie Arbeit untersucht den informed-consent-Prozess Minderjähriger im Kontext medizinischer Forschung. Es ist die erste Fragebogenstudie zu diesem Thema mit einer größeren Anzahl von Teilnehmer*innen im deutschsprachigen Raum. Es handelt sich hierbei um eine explorative quantitative Studie. Mithilfe eines selbsterstellten Fragebogens wurden 279 Schüler*innen zu verschiedenen Aspekten des Aufklärungsprozesses befragt. Ein Schwerpunkt der Arbeit ist die Evaluation der Zweckmäßigkeit eines Mustertextes des Arbeitskreises Deutscher Ethik-Kommissionen, der zur Aufklärung jugendlicher Minderjähriger für eine Teilnahme an medizinischer Forschung empfohlen wird. Es konnte gezeigt werden, dass der AKEK-Mustertext Kernaspekte und Informationen für eine Entscheidung im Sinne der informierten Einwilligung altersadäquat vermittelt. Der zweite Schwerpunkt der Arbeit liegt auf den persönlichen Ansichten der Befragten bezüglich einer Studienteilnahmeentscheidung. Hierbei zeigte sich, dass vor allem positiv konnotierte direkt-persönliche Faktoren (wie „verbesserte Heilungschancen“, „Schmerzlosigkeit“ und „Geheimhaltung persönlicher Daten“) und indirekt-soziale Argumente (Altruismus bzw. Solidarität) zu einer Studienteilnahme motivieren. Eher gegen eine Studienteilnahme sprechen negativ konnotierte direkt-persönliche Faktoren, etwa die „Schmerzhaftigkeit“ und eine mangelnde Datensicherheit. Auch direkt-soziale Einflüsse (insbesondere die Haltung von Arzt/Ärztin und Eltern) beeinflussen die Teilnahmeentscheidung.. Die Ergebnisse der Arbeit deuten auf ein hohes Verstehen von Minderjährigen hinsichtlich des AKEK-Aufklärungsbogens hin sowie auf eine multifaktorielle Entscheidungsfindung, die maßgeblich durch das Studiendesign und den Aufklärungsprozess beeinflusst wird
Controlling the Selectivity and Stability of Proteins by New Strategies in Directed Evolution: The Case of Organocatalytic Enzymes
No full textThe directed evolution of functional enzymes as catalysts in organic reactions has emerged as a powerful method of protein engineering. This includes the directed evolution of enantioselective enzymes as pioneered by the author. In recent years the challenges in this new area of asymmetric catalysis has shifted to solving the problem of probing protein sequence space more efficiently than before. Iterative saturation mutagenesis (ISM) is one way of addressing this crucial question. This chapter reviews the concept of ISM and its application in controlling the enantioselectivity and thermostability of enzymes, specifically those that have an organocatalytic mechanism. Illustrative examples include the directed evolution of lipases, Baeyer-Villigerases and epoxide hydrolases
Profiles of blood-brain barrier and neurodegeneration markers in cerebrospinal fluid of patients with cerebral amyloid angiopathy
No full textPinho J, Reich A, Nikoubashman O, Schulz JB, Reetz K, Costa AS. Profiles of blood-brain barrier and neurodegeneration markers in cerebrospinal fluid of patients with cerebral amyloid angiopathy. Alzheimer's & Dementia . 2025;17(4): e70221.INTRODUCTION: There are few studies analyzing cerebrospinal fluid (CSF) in patients with cerebral amyloid angiopathy (CAA). Our goal was to compare blood-brain barrier and neurodegeneration markers in CSF in CAA patients with and without hemorrhagic markers.; METHODS: In a retrospective study of patients with CAA (Boston criteria version 2.0) identified from the Aachen Memory Database and from in-hospital admission records, we compared CSF neurodegeneration markers and albumin ratio (a blood-brain barrier permeability marker) in patients with and without hemorrhagic markers.; RESULTS: Among 371 patients with CAA, 113 patients had hemorrhagic markers (30.5%). Lower amyloid beta (Abeta) 42, lower Abeta40, and higher albumin ratio were independently associated with the presence of hemorrhagic markers and an increasing number of lobar microbleeds. Cortical superficial siderosis and a higher imaging burden of CAA were associated with total tau protein.; DISCUSSION: Presence of hemorrhagic markers in CAA patients is associated with lower CSF Abeta42 and Abeta40 and higher blood-brain barrier permeability.; HIGHLIGHTS: New diagnostic criteria allow for the diagnosis of CAA without hemorrhagic markers.CAA hemorrhagic markers are associated with lower Abeta42 and Abeta40 in CSF.CAA hemorrhagic markers are associated with higher blood-brain barrier permeability.Higher imaging burden of CAA is associated with higher total tau protein in CSF. © 2025 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association
Biocatalysis in Organic Chemistry and Biotechnology: Past, Present, and Future
No full textEnzymes as catalysts in synthetic organic chemistry gained importance in the latter half of the 20th century, but nevertheless suffered from two major limitations. First, many enzymes were not accessible in large enough quantities for practical applications. The advent of recombinant DNA technology changed this dramatically in the late 1970s. Second, many enzymes showed a narrow substrate scope, often poor stereo- and/or regioselectivity and/or insufficient stability under operating conditions. With the development of directed evolution beginning in the 1990s and continuing to the present day, all of these problems can be addressed and generally solved. The present Perspective focuses on these and other developments which have popularized enzymes as part of the toolkit of synthetic organic chemists and biotechnologists. Included is a discussion of the scope and limitation of cascade reactions using enzyme mixtures in vitro and of metabolic engineering of pathways in cells as factories for the production of simple compounds such as biofuels and complex natural products. Future trends and problems are also highlighted, as is the discussion concerning biocatalysis versus nonbiological catalysis in synthetic organic chemistry. This Perspective does not constitute a comprehensive review, and therefore the author apologizes to those researchers whose work is not specifically treated her
Pathogenic or Likely Pathogenic GRN Variants Are Found in 0.1% of Parkinson's Disease Patients
No full textAbstract Background Parkinsonism may be observed in multiple neurodegenerative diseases, including GRN ‐associated frontotemporal dementia (FTD‐ GRN ), complicating the differential diagnosis of Parkinson's disease (PD). Objectives To investigate the presence of GRN variants in a large group of PD patients. Methods We analyzed GRN variants in >18,500 PD patients and compared sociodemographic, genetic, and clinical data between individuals with and without GRN variants. Results Twenty‐four (0.13%) PD patients harbored 16 unique pathogenic or likely pathogenic GRN variants. Our GRN variant‐positive PD patients had a higher male‐to‐female ratio and a younger age at onset compared with FTD‐ GRN patients reported in the literature. Patients with GRN variants showed higher rates of impaired olfactory function and more severe motor symptoms than GRN variant‐negative patients. Conclusions FTD‐ GRN may be indistinguishable from PD. Therefore, comprehensive genetic testing, including GRN analysis, is recommended for patients with clinically diagnosed parkinsonism/PD to guide disease management and prognosis. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Denali Therapeutics https://doi.org/10.13039/10001711
Combinatorial Libraries Reloaded<sup>[1]</sup>
No full textThis essay constitutes a personal assessment of two quite different projects that the author has initiated during the last two decades, both involving combinatorial libraries of catalysts. The first encounter with combinatorial catalysis involved the use of a mixture of two different monodentate ligands in asymmetric transition metal catalysis, especially when one ligand is chiral and the other achiral. The reason for abandoning this approach as a research topic, although (industrially) successful, is outlined herein. The second and distinctly more significant approach concerns the directed evolution of stereo‐ and regioselective enzymes as catalysts in organic chemistry. It is not only a prolific source of catalysts for a variety of synthetically useful selective transformations, but has also produced several fundamentally important insights. The lessons learned include mechanistic intricacies of enzyme catalysis as well insights regarding cooperative mutational effects which are distinctly more than additive. The Darwinian approach to generating stereoselective enzymes is compared with evolution as it occurs in Nature
Literatura mundial costera: Encuentros en las orillas de Europa
No full textShorelines are at the forefront when it comes to the effects of climate change. They are equally a preferred leisure destination for global northerners to seek respite and some sort of ecological reconnection. This article argue that the coast offers valuable insight as a literary site of disruptive encounters. At the coast, economic, ecological, and cultural disparity interweave, and can therefore carry manifold connotations, emotions, and prospects dependent of your vantage point. As such, I argue, the coastal site offers fundamentally different temporalities and experiences depending on the vantage point. To exemplify this point, the article examines contemporary registrations of the southernmost European shore in the wake of the so-called migrant crisis that occurred as the Arab Spring revolutions was met by autocratic pushbacks. Furthermore, the article presents the term ‘coastal world literature’ as a methodology of interpreting literature at the dynamic littoral zone between land and sea. Readings of the novel What Strange Paradise (2021) by Egyptian-Canadian author Omar El Akkad, the collection of poems Mare Nostrum (2019) by Libyan-American author Khaled Mattawa , the novel Til stranden (2017; To the Beach) by Danish author Peter Højrup, and the collection of poems titled Bag bakkerne, kysten (2017; Behind the Dunes, the Coast) by Danish author Peter Clement-Woetmann support the assertion that coastal texts are informed by their position within the world-system. In effect, coastal world literature reveals valuable first encounters of disparity, unevenness, and the range of accompanied affective responses. Consequently, what happens at the shore and how we tell it matters immensely.
Las costas están en primera línea en lo que respecta a los efectos del cambio climático. También son uno de los destinos de ocio preferidos de los habitantes del norte global en busca de descanso y conexión ecológica. Este artículo sostiene que la costa también ofrece una valiosa perspectiva como lugar literario de encuentros disruptivos. En la costa, las disparidades económicas, ecológicas y culturales se entrelazan y, por tanto, pueden acarrear múltiples connotaciones, emociones y perspectivas según la situación de la persona. Para ejemplificar este punto, el artículo examina las representaciones literarias contemporáneas de la costa más al sur de Europa a raíz de la llamada crisis migratoria que se produjo cuando las revoluciones de la Primavera Árabe se confrontaron con retrocesos autocráticos. Además, el artículo presenta el término “literatura del mundo costero” como metodología de interpretación de la literatura en la dinámica zona litoral entre la tierra y el mar. Lecturas de la novela What Strange Paradise (2021) del autor egipcio-canadiense Omar El Akkad, el poemario Mare Nostrum (2019) del autor libio-estadounidense Khaled Mattawa, la novela Til stranden (2017; To the Beach) del autor danés Peter Højrup, y la colección de poemas titulada Bag bakkerne, kysten (2017; Behind the Dunes, the Coast) del autor danés Peter Clement-Woetmann apoyan la afirmación de que los textos costeros están informados por su posición dentro del sistema-mundo. En efecto, la literatura del mundo costero revela valiosos primeros encuentros de disparidad, desnivel y la gama de respuestas afectivas acompañadas. En consecuencia, lo que ocurre en la costa y cómo lo contamos importa enormemente.
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