Publications by authors named "Kempf J"

Sensitivity is often the Achilles' heel of liquid-state nuclear magnetic resonance (NMR) experiments. This problem is perhaps most pressing at the lowest fields (e.g.

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Article Synopsis
  • * This study specifically investigates the high-concentration monoclonal antibody pembrolizumab (Keytruda) and its behavior in frozen solutions using advanced techniques like dynamic nuclear polarization (DNP) and solid-state NMR (ssNMR).
  • * Findings reveal how these methods allow detailed analysis of the protein's structure, dynamics, and the behavior of its excipients at low temperatures, highlighting their potential for improving the stability assessment of biological drugs in frozen conditions.
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Repeatable hyperpolarization of high concentrations of mobile protons (>6 M) using parahydrogen in protic methanol/water mixtures is reported here. Different ammonium buffers with increasing mobile proton concentrations were added to an IrCl(COD)(IMes) catalyst in the presence of pyridine. We reach a maximum molar polarization of 1.

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Obtaining atomic-level information on components in the cell is a major focus in structural biology. Elucidating specific structural and dynamic features of proteins and their interactions in the cellular context is crucial for understanding cellular processes. We introduce F dynamic nuclear polarization (DNP) combined with fast magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy as a powerful technique to study proteins in mammalian cells.

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Purpose: Lutetium-177-Dotatate (Lutathera) is a combined radionuclide-peptide that is FDA-approved for the treatment of well-differentiated, somatostatin receptor-positive, gastroenteropancreatic neuroendocrine tumors. Carcinoid crisis is a rare, but potentially life-threatening risk of this radiopharmaceutical, of which prompt recognition and treatment is essential to reducing morbidity. This manuscript provides an overview of the topic to promote awareness of this adverse event, with emphasis on early recognition and management.

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Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) provides the opportunity to dramatically increase the weak nuclear magnetic resonance (NMR) signal of liquid molecular targets using the high polarization of electron radicals. Unfortunately, the solution-state hyperpolarization can only be accessed once since freezing and melting of the hyperpolarized sample happen in an irreversible fashion. A way to expand the application horizon of dDNP can therefore be to find a recyclable DNP alternative.

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Purpose: Altered F-fluorodeoxyglucose (FDG) biodistribution due to patient factors such as exercise and inadequate fasting are well established causes of limited diagnostic efficacy. In addition, medications such as G-CSF are known to affect uptake of FDG by bone marrow and spleen. In this study, we present a case of increased white adipose uptake in a pediatric lymphoma patient who recently received high dose dexamethasone and review the relevant literature regarding this rare and poorly understood pattern of altered FDG biodistribution.

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To date, the appropriate training required for the reproducible operation of multispectral optoacoustic tomography (MSOT) is poorly discussed. Therefore, the aim of this study was to assess the teachability of MSOT imaging. Five operators (two experienced and three inexperienced) performed repositioning imaging experiments.

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Background And Aims: In obesity, depletion of KCs expressing CRIg (complement receptor of the Ig superfamily) leads to microbial DNA accumulation, which subsequently triggers tissue inflammation and insulin resistance. However, the mechanism underlying obesity-mediated changes in KC complement immune functions is largely unknown.

Approach And Results: Using KC-specific deactivated Cas9 transgenic mice treated with guide RNA, we assessed the effects of restoring CRIg or the serine/arginine-rich splicing factor 3 (SRSF3) abundance on KC functions and metabolic phenotypes in obese mice.

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Mediterranean forests represent critical areas that are increasingly affected by the frequency of droughts and fires, anthropic activities and land use changes. Optical remote sensing data give access to several essential biodiversity variables, such as species traits (related to vegetation biophysical and biochemical composition), which can help to better understand the structure and functioning of these forests. However, their reliability highly depends on the scale of observation and the spectral configuration of the sensor.

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Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach.

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Aim of this study was to assess the influence of intermitted negative pressure (INP) therapy on the foot microcirculation in patients with no-option CLTI. CLTI patients defined as no option for revascularization on the basis of an interdisciplinary vascular board decision (interventional radiology, vascular surgery) were included in this study. INP therapy was performed at home.

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Fisheries waste is used by many seabirds as a supplementary source of food, but interacting with fishing vessels to obtain this resource puts birds at risk of entanglement in fishing gear and mortality. As a result, bycatch is one of the leading contributors to seabird decline worldwide, and this risk may increase over time as birds increasingly associate fishing vessels with food. Light-level geolocators mounted on seabirds can detect light emitted from vessels at night year-round.

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We propose a mechanism for dynamic nuclear polarization that is different from the well-known Overhauser effect, solid effect, cross effect, and thermal mixing processes. We term it , and we show that it arises from the evolution of the density matrix for a simple electron-nucleus coupled spin pair subject to weak microwave irradiation, the same interactions as the solid effect. However, the SE is optimal when the microwave field is off-resonance, whereas RM is optimal when the microwave field is on-resonance and involves the mixing of states by the microwave field together with the electron-nuclear coupling.

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Emerging evidence indicates the critical roles of microbiota in mediating host cardiac functions in ageing, however, the mechanisms underlying the communications between microbiota and cardiac cells during the ageing process have not been fully elucidated. Bacterial DNA was enriched in the cardiomyocytes of both ageing humans and mice. Antibiotic treatment remarkably reduced bacterial DNA abundance in ageing mice.

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Rationale And Objectives: Over 20% of the Lesbian, Gay, Bisexual, Queer or Questioning, Intersex, Asexual or Ally, and more (LGBTQIA+) community reports experiencing discrimination upon accessing health care, causing many to defer access to care and resulting in poorer outcomes. While members of this community routinely undergo imaging studies, little formal education exists within the field of radiology to review the unique health care needs of this population and the specific relevance to imaging, in addition to actionable methods to promote inclusion.

Materials And Methods: A 1-hour educational conference was held for a cohort of radiology resident physicians at our institution, in which topics including LGBTQIA+ health care disparities, clinical nuances relevant to the field of radiology, and actionable suggestions that both academic and private-practice centers can adopt to foster inclusion were presented.

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Amino acids (AAs) and ammonia are metabolic markers essential for nitrogen metabolism and cell regulation in both plants and humans. NMR provides interesting opportunities to investigate these metabolic pathways, yet lacks sensitivity, especially in case of N. In this study, spin order embedded in p-H is used to produce on-demand reversible hyperpolarization in N of pristine alanine and ammonia under ambient protic conditions directly in the NMR spectrometer.

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We recently used selective H labeling of BDPA to investigate the Overhauser Effect (OE) dynamic nuclear polarization (DNP) mechanism in insulating solids doped with 1,3-bis(diphenylene)-2-phenylallyl (BDPA), and established that the α and γ H spins on the fluorene rings are responsible for generating a zero quantum (ZQ) mediated bulk polarization. Here, we establish that the phenyl H spins relax via double-quantum (DQ) processes and therefore contribute enhancements which attenuate the OE-DNP. With measurements at different magnetic field strengths, we show that phenyl--BDPA offers >50% improvement in OE-DNP enhancement compared to -BDPA attaining a maximum of ∼90 at 14.

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The joint U.S. Department of Defense (DoD) - Department of Veterans Affairs (VA) Integrated Disability Evaluation System is the process by which DoD determines fitness for duty and separation or retirement of service members because of disability.

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NMR-based analysis of metabolite mixtures provides crucial information on biological systems but mostly relies on 1D H experiments for maximizing sensitivity. However, strong peak overlap of H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution dynamic nuclear polarization (d-DNP) improves NMR sensitivity by several orders of magnitude, which enables C NMR-based analysis of metabolites at natural abundance.

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Objectives: This practice parameter (PP) for Lutetium-177 (Lu-177) DOTATATE peptide receptor radionuclide therapy (PRRT) aims to guide authorized users in selection of appropriate adult candidates with gastroeneropancreatic neuroendocrine tumors (GEP-NETs) from foregut, midgut, and hindgut. The essential selection criteria include somatostatin receptor-positive GEP-NETs, which are usually inoperable and progressed despite standard therapy. Lu-177 DOTATATE is a radiopharmaceutical with high avidity for somatostatin receptors that are overexpressed by these tumors.

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Objectives: This practice parameter (PP) for Lutetium-177 (Lu-177) DOTATATE peptide receptor radionuclide therapy (PRRT) aims to guide authorized users in selection of appropriate adult candidates with gastroeneropancreatic neuroendocrine tumors (GEP-NETs) from foregut, midgut, and hindgut. The essential selection criteria include somatostatin receptor-positive GEP-NETs, which are usually inoperable and progressed despite standard therapy. Lu-177 DOTATATE is a radiopharmaceutical with high avidity for somatostatin receptors that are overexpressed by these tumors.

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Hyperpolarization using signal amplification by reversible exchange (SABRE) relies on target molecules and parahydrogen coordinating to a transition metal catalyst. Identification of this coordinated state becomes increasingly important, especially since bio-relevant targets such as pyruvate and amino acids exhibiting multiple binding sites are becoming compatible with SABRE. In this report, we present a fingerprinting method to discriminate and identify ligand binding sites without requiring the presence of a sensitive or isotope-labeled heteroatom.

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Development of novel therapeutics to treat antibiotic-resistant infections, especially those caused by ESKAPE pathogens, is urgent. One of the most critical pathogens is , which is able to develop a large number of factors associated with antibiotic resistance, including high level of impermeability. Gram-negative bacteria are protected from the environment by an asymmetric Outer Membrane primarily composed of lipopolysaccharides (LPS) at the outer leaflet and phospholipids in the inner leaflet.

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