Publications by authors named "Sebald M"

Introduction: Patient specific quality assurance (QA) in MR-Linacs can be performed with MR-compatible ion chamber arrays. However, the presence of a static magnetic field can alter the angular response of such arrays substantially. This works investigates the suitability of two ion chamber arrays, an air-filled and a liquid-filled array, for patient specific QA at a 0.

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Our genomes harbor conserved DNA sequences, known as common fragile sites (CFSs), that are difficult to replicate and correspond to regions of genome instability. Following replication stress, CFS loci give rise to breaks or gaps (termed CFS expression) where under-replicated DNA subsequently undergoes mitotic DNA synthesis (MiDAS). We show that loss of the structure-selective endonuclease GEN1 reduces CFS expression, leading to defects in MiDAS, ultrafine anaphase bridge formation, and DNA damage in the ensuing cell cycle due to aberrant chromosome segregation.

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Article Synopsis
  • POLQ is an important protein for repairing DNA double-strand breaks (DSBs) through a process called microhomology-mediated end-joining (MMEJ) and is found at higher levels in various cancers.
  • Inhibiting POLQ leads to synthetic lethality in cancer cells that lack certain repair mechanisms (like HR and Shieldin), suggesting a strong reliance on MMEJ for repair.
  • The study reveals that when POLQ is absent, cells accumulate gaps in their DNA, and POLQ works in a way that could drive genetic changes in cancer, highlighting its role in both gap sealing and overall cell survival.
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The ubiquitous genus is responsible for the spoilage of vast amounts of cereals and fruits. Besides the economic damage, the danger to human and animal health by the concomitant exposure to mycotoxins represents a serious problem. A large number of species produce a variety of different mycotoxins of which the class of trichothecenes are of particular importance due to their toxicity.

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MutSα and MutSβ play important roles in DNA mismatch repair and are linked to inheritable cancers and degenerative disorders. Here, we show that MSH2 and MSH3, the two components of MutSβ, bind SLX4 protein, a scaffold for the assembly of the SLX1-SLX4-MUS81-EME1-XPF-ERCC1 (SMX) trinuclease complex. SMX promotes the resolution of Holliday junctions (HJs), which are intermediates in homologous recombinational repair.

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Purpose: To assess the incidence and evolution of biliary alterations adjacent to the ablation area in patients with hepatic malignancies during the first 3 months after percutaneous irreversible electroporation (IRE) and to investigate associated changes in laboratory values.

Material And Methods: Bile ducts located within a ≤1.0 cm radius of the ablation zone were analyzed in 45 patients by preinterventional and postinterventional MRI (1-3 days, 6 weeks, and 3 months after IRE).

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The incidence and evolution of venous thrombosis adjacent to the ablation zone after percutaneous irreversible electroporation (IRE) were evaluated to identify potential risk factors in patients with hepatic malignancies. 205 venous structures (in 87 patients) within a ≤1.0 cm radius of the ablation zone were assessed after IRE of 112 hepatic lesions (74 primary, 38 secondary hepatic malignancies) by pre-interventional and post-interventional (1-3 days, 6 weeks and 3 months after IRE) contrast-enhanced magnetic resonance imaging.

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Metabolites from fungi exhibit a variety of biological properties such as phytotoxic, cytotoxic, or antimicrobial activity. Optimization of a literature procedure culminated in an efficient total synthesis of -altenuene as well as a stable isotope-labeled derivative suitable for implementation in a LC-MS/MS method for mycotoxin analysis.

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Bone Morphogenetic Proteins are key signaling molecules in vertebrate development. Little is known about Bmp gene regulation in any organ. In Drosophila, the Bmp gene, dpp is regulated by Dorsal, the invertebrate homologue of Rel-NF-kB.

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Background: Congenital diaphragmatic hernia (CDH) is often associated with severe pulmonary hypoplasia resulting in hypoxemic respiratory failure unresponsive to advanced medical management including the use of inhaled nitric oxide (iNO). For these patients, extracorporeal membrane oxygenation (ECMO) serves as the last potentially effective treatment choice. Since the efficacy of iNO in this patient population is not known and since most neonatal intensive care units using iNO for the treatment of these critically ill neonates do not provide ECMO, the ability to more accurately predict which patient is at risk for failing medical management with iNO and requires a timely transfer to an ECMO center can be life saving.

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Objective: To describe the response to high-frequency jet ventilation in infants with hypoxemic respiratory failure unresponsive to high-frequency oscillatory ventilation.

Methods: This was a retrospective analysis of chart records on demographics, ventilator settings, blood gas analysis and calculated oxygenation index prior to and during the first 7 days of high-frequency jet ventilation in ten consecutive infants.

Results: Before the initiation of high-frequency jet ventilation, the ventilatory mean airway pressure (MAP; cmH2O), fraction of inspired oxygen (FiO2) and oxygenation index on high-frequency oscillatory ventilation were 14.

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Tissue-type plasminogen activator (t-PA) is a serine protease that plays a central role in the regulation of intravascular thrombolysis. The acute release of t-PA in vivo is induced by a variety of stimuli including exercise, trauma, and neural stimulation. These types of stimuli also result in sympathoadrenal activation and exocytotic release of amines and proteins from catecholamine storage vesicles of the adrenal medulla and sympathetic neurons.

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An enterotoxigenic strain of Bacteroides fragilis was the sole organism isolated from the cerebrospinal fluid of a two-and-a-half-month neonate who had a medullary-colonic fistula as part of a complex congenital malformation, but no brain abscess. A rapid latex particle agglutination test for detection of bacterial antigen was positive for Haemophilus influenzae type b, suggesting that Bacteroides fragilis and Haemophilus influenzae type b might share some capsular antigens. In order to determine the role of the enterotoxin with respect to virulence of the strain, antibodies to a 20 kDa protein were sought in the patient's serum, but Western blot of the culture supernatant revealed only antibodies to a 45 kDa bacterial protein.

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The genetic organization of two different 5-nitroimidazole (5-Ni) resistance genes was investigated: nimC and nimD from Bacteroides plasmids pIP419 and pIP421, respectively. The nimC gene (492 bp) and the nimD gene (495 bp) directed the synthesis of polypeptides with deduced molecular masses of 18.37 kDa and 18.

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Lp(a) competes with plasminogen for binding to cells but it is not known whether this competition is due to the ability of Lp(a) to interact directly with plasminogen receptors. In the present study, we demonstrate that Lp(a) can interact directly with plasminogen binding sites on monocytoid U937 cells and endothelial cells. The interaction of Lp(a) with these sites was time dependent, specific, saturable, divalent ion independent and temperature sensitive, characteristics of plasminogen binding to these sites.

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As a biochemist, Louis Pasteur focused on fermentation, demonstrating that it was a vital process. In 1860, he discovered anaerobic life and the strict anaerobes, particularly those responsible for butyric fermentation. Then, in spite of his lack of medical background, Pasteur turned to investigating the role of bacteria in human and animal diseases.

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This review focuses on genetic and molecular data regarding antibiotic resistance in anaerobes, particularly Clostridium perfringens, Clostridium difficile, Bacteroides species, and Prevotella species. The determinants of resistance are frequently transferable through a conjugation-like process; plasmid self-transfer, plasmid mobilization, or (in Bacteroides species) chromosomal conjugative elements can be involved. The determinants can be localized on transposons.

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DNA sequence analysis of regions from plasmid pIP417 and chromosome BF8 which encode 5-nitroimidazole resistance in Bacteroides strains allowed the identification of two open reading frames corresponding to new genes, nimA (528 bp) and nimB (492 bp). Either gene may confer 5-nitroimidazole resistance to susceptible strains of Bacteroides. The encoded polypeptides have deduced molecular masses of 20.

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The recent finding that Bacillus stearothermophilus adenylate kinase contains a zinc atom coordinated to four cysteines prompted us to investigate the metal-binding properties of the enzyme from various bacteria. We conclude that zinc was present only in adenylate kinase from gram-positive species and that this property is correlated with the presence of three or four Cys residues in the sequence Cys-X2-Cys-X16-Cys-X2-Cys/Asp, in which X stands for different amino acid residues.

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Fecal samples of 120 children (2 weeks to 3.5 year old) hospitalized in a pediatrical ward were investigated. In 56 of them diarrhea was observed.

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We measured serum antibodies to botulinum toxin (ABT) in 96 patients with focal dystonia who had been treated with type A botulinum toxin. The frequency of detectable ABT was 3% (three patients). Patients with ABT had received more than 50 ng of botulinum toxin, and the shortest time between two injections was significantly less than in patients without ABT.

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Thirty-three clinical isolates of Bacteroides strains with a moderate-to-high level of resistance to 5-nitroimidazole were compared with three strains previously studied by Southern blotting of their DNA. Whether plasmid-borne or chromosomally determined, all genetic determinants that are resistant to 5-nitroimidazole belong to two hybridization groups.

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A new type II restriction endonuclease, named BfrBI, was detected in two strains of Bacteroides fragilis, BE3 and AIP 10006 (NCTC 9343T). The enzyme BfrBI, an isoschizomer of NsiI and AvaIII, recognized the hexanucleotide sequence [5'-ATG decreases CAT-3'], with a cleavage site generating blunt ends.

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Strain BF8 is a plasmid-free Bacteroides fragilis, resistant to 5-nitroimidazole (5-Ni) antibiotics (metronidazole, ornidazole and tinidazole). The resistance was transferable by conjugation into Bacteroides fragilis BF638R. The total DNA of a Nir transconjugant was used for the construction of a Sau3A genomic library in a B.

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This report describes a genetic and molecular analysis of two transferable Bacteroides plasmids, pIP417 and pIP419, which carry genetic determinants conferring low-level resistance to 5-nitroimidazoles. The restriction endonuclease cleavage sites for each plasmid were localized. The NiR genetic determinants of pIP417 and pIP419 plasmids have been cloned into the Bacteroides cloning vector pBI191 (C.

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