68034 research outputs found
Sort by
A homogeneous immunoassay technology based on liposomes and the complement system enables one-step, no-wash, rapid diagnostics directly in serum
Get PDFLiposomes are a well-established carrier and controlled release system in medicine and bioanalysis. Their biomimetic capabilities are harnessed for the development of a reliable homogeneous assay platform technology that lends itself to high-throughput screening and point-of-care applications since no wash or separation steps are needed. It was developed for fluorescent, chemiluminescent, and electrochemical detection strategies and applied to antibodies directed against small or polymeric molecules and peptides as model analytes. The simplicity of the approach is achieved as mere binding of analytes or analyte-associated entities to the liposome surface leads to the activation of the complement system, which in turn lyses the liposomes. Released encapsulated marker molecules are quantified and directly correlated to the analytes. Control over the liposome chemistry, including cholesterol content, surface chemistry, and encapsulants, was identified to be key to ensure their general serum and storage stability (more than 40 months at 4 °C and up to 4 weeks at 37 °C) and their efficient and specific response to complement activity. Additional assay conditions of relevance included the concentration of liposomes and their ratio to serum proteins, the amount of complement trigger per liposome, and the activity of complement proteins. Understanding and being able to control the liposomes enable various analysis strategies including the quantification of analytes, determination of complement activity, and evaluation of the therapeutic application potential of antibodies. A time-resolved version of the assay even allows the study of the complex actions of the complement system
Polyphosphorus Ligand Complexes of Coinage Metals for Multiple Capturing of Intact P4 Tetrahedra
Get PDFTwo- and three-component self-assembly reactions of [CpRFe(η5-P5)] (CpR = C5(CH3)5 (Cp*, 1a), C5(4-EtC6H4)5) (CpPEt, 1b)) with the coinage metal salts [Cu(CH3CN)4][SbF6] or AgSbF6 were investigated to study the prerequisites for the potential coordination of white phosphorus by using a sterically encumbered CpR ligand and noncoordinating anions. In the self-assembly reactions with white phosphorus, either 0D or 1D coordination complexes are formed, all of which feature coordinated intact P4 tetrahedra and thus comprise an unprecedented class of mixed polyphosphorus ligand complexes capable of complete release of P4 in solution confirmed by NMR studies. The bulkiness of the used CpR ligand and the correctly chosen solvent allowed for obtaining more beneficial structural motifs, the first discrete tetra- and penta-coordinated cyclo-P5 ligand complexes, that provide the maximal content of coordinated P4 molecules per species known so far. All products are characterized by single-crystal X-ray diffraction, NMR spectroscopy, and mass spectrometry
USEFUSE: Uniform stride for enhanced performance in fused layer architecture of deep neural networks
Get PDFConvolutional Neural Networks (CNNs) are crucial in various applications, but deploying them on resource-constrained edge devices poses challenges. This study presents the Sum-of-Products (SOP) units for convolution, which utilize low-latency left-to-right bit-serial arithmetic to minimize response time and enhance overall performance. The study proposes a methodology for fusing multiple convolution layers to reduce off-chip memory communication and increase the overall performance. An effective mechanism detects and skips inefficient convolutions after ReLU layers, minimizing power consumption without compromising accuracy. Additionally, efficient tile movement guarantees uniform access to the fusion pyramid. An analysis demonstrates the uniform stride strategy improves operational intensity. Two designs cater to varied demands: one focuses on minimal response time for mission-critical applications, and another focuses on resource-constrained devices with comparable latency. This approach notably reduced redundant computations, improving the efficiency of CNN deployment on edge devices
Clinical and Genomic Landscape of FGFR3 Alterations Across Different Stages of Urothelial Cancer
Get PDFBackground and objective
Our aim was to provide a comprehensive analysis of the prevalence of potentially targetable activating FGFR3 alterations and their impact on oncological outcomes across different urothelial carcinoma (UC) stages.
Methods
We retrospectively analyzed clinical data and FGFR3 results for 1509 formalin-fixed, paraffin-embedded tissue specimens. Actionable activating FGFR3 mutations were assessed using a well-established multiplex SNaPshot polymerase chain reaction approach. FGFR3 fusion testing was performed with a Qiagen Therascreen kit.
Key findings and limitations
In the study population of 1509 patients, 202 (13%) had stage pTa, 380 (25%) had stage pT1, 258 (17%) had localized muscle-invasive bladder cancer (MIBC), 556 (37%) had locally advanced MIBC, 91 (6.0%) had metastatic UC of the bladder (mUCB), and 22 (1.5%) had metastatic upper tract UC (mUTUC). Of the FGFR3 alterations detected in 373 patients (25%), 104 (52%) were in stage pTa, 158 (42%) were in pT1, 42 (16%) were in localized MIBC, 53 (9.5%) were in locally advanced MIBC, nine (9.9%) were in mUCB, and seven (32%) were in mUTUC. FGFR3 alterations were associated with better progression-free survival and overall survival in the overall population (p < 0.001), but not in subgroup analyses for different disease stages. Study limitations include the retrospective design and heterogeneous patient cohort.
Conclusions and clinical implications
FGFR3 alterations occur at a stage-dependent frequency and are more prevalent in lower tumor stages. We were unable to demonstrate an independent prognostic effect of FGFR3 alterations on oncological outcomes after adjusting for tumor stage.
Patient summary
We analyzed a protein called fibroblast growth factor receptor 3 (FGFR3) in patients with cancer of the urinary tract. We found that more aggressive tumors had fewer genetic changes in FGFR3 in comparison to less aggressive tumors. However, genetic changes in FGFR3 were not related to survival for these patients
Ultrafast multi-terahertz control of two-dimensional quantum systems
No full textThis thesis presents major advances in the ultrafast multi-THz control of two dimensional quantum systems, which may become important for future optoelectronic devices and quantum information technology.
First, the coherent nonlinear sub-cycle dynamics of excitons in a TMDC monolayer are investigated. Resonant multi-THz excitation of the 1s-2p transition leads to the generation of sidebands in a regime of light-matter interaction where field-driven effects and electronic correlations are in balance. The temporal structure of the sideband emission provides evidence of
carrier-wave Rabi-flopping and the involvement of higher-lying states of the excitonic multi-level system in the coherent dynamics.
Second, intersubband polariton-polariton scattering is observed for the first time. Ultrafast noncollinear multi-THz pump-probe spectroscopy traces the polariton dynamics in a dispersive microcavity directly in the band structure. The stimulated scattering process creates a coherent population at the polaritonic ground state and puts Bose-Einstein condensation of intersubband polaritons within reach.
To achieve these goals, novel THz photonics are implemented. In particular, a newly developed ultrabroadband electro-optic detector enables the etalon-free characterization of phase-stable multi-THz waveforms. Furthermore, a dedicated optical setup provides strong-field multi-THz pulses at high laser repetition rates suitable for the lightwave control of electrons, as demonstrated by high-harmonic generation in a nanostructured device and by multi-THz-induced tunneling currents at an electronic interface
Segmental Variation in English Non-Native Accents in Russia: The Influence of Some Local Indigenous Languages
No full textThis study examines the pronunciation of English vowels and consonants (i.e., segmental level) among four ethnic groups in Russia: Russians, Tatars, Bashkirs, and Udmurts, focusing on the influence of the ethnic first languages (L1s) and the role of Russian as an additional L1. It provides a sociolinguistic context by exploring Russia’s ethnolinguistic diversity, language policies, and the role of English within its multilingual society. A contrastive analysis of the phonetic and phonological systems of English and the ethnic languages of the studied groups (Bashkir, Russian, Tatar, and Udmurt) helps identify potential areas of L1 transfer and variation. The core of the study consists of empirical research, based on recordings from 98 informants reading the “The boy who cried wolf” passage, which were analyzed using acoustic and auditory methods. The findings reveal tendencies of intra- and inter-group variation, demonstrating how factors such as L1 transfer, the role of Russian as a secondary L1, exposure to English, and standardized English teaching in Russia contribute to these differences. Overall, the study provides valuable insights into the complexities of English pronunciation across different ethnic groups in Russia and deepens our understanding of non-native accent formation and language transfer in multilingual contexts
HF-Ultrasonography to Quantify Skin Atrophy in Patients with Inflammatory Rheumatic Diseases Treated with Courses of Glucocorticoids
No full textBackground: Prolonged courses of glucocorticoids (GCs) for patients suffering
from inflammatory rheumatic diseases (IRDs) are associated with adverse effects. Highfrequency ultrasonography (HFUS) has been utilized to quantify skin changes during short-term topical GC treatment. We aimed to quantify skin atrophy in IRD patients treated systemically with prolonged courses of GCs.
Methods: We performed a cross-sectional study comparing patients with IRDs and GC treatment who presented with clinically evident skin atrophy to a matched cohort (1:1) without IRDs and GC treatment. Skinfold measurements, utilizing a standardized caliper, and B-mode HFUS images, utilizing an
18 MHz linear sonography probe, were acquired at back-of-hand, cubital, and dorsal midfoot regions and then compared between both groups. Results: A total of 53 GCtreated IRD patients (33 (62%) women, mean age 66.4 (±10.0) years, GC treatment median 8.0 (1.0–47.0) years) were compared to 53 subjects without IRDs and GC treatment (32 (60%) women, 65.9 (±11.3) years). Skinfold thickness measured at the back of hands [1.7 (±0.4) vs. 2.1 (±0.5) mm, p < 0.001], but not at the cubital [6.7 (±2.7) vs. 7.1 (±3.0) mm] or dorsal
midfoot [3.6 (±3.7) vs. 4.1 (±3.4) mm] areas, showed a significant difference between the groups. In comparison, all areas displayed statistically significant different cutaneous thickness in the evaluation by HFUS: hand 0.66 (±0.12) vs. 0.82 (±0.18), p < 0.001; cubital 0.86 (±0.15) vs. 1.00 (±0.21), p < 0.001; and midfoot 0.76 (±0.16) vs. 0.94 (±0.18), p < 0.001.
Conclusions: This study revealed significantly lower values in the measured cutaneous thickness by HFUS for GC-treated patients with IRDs compared to persons without IRD and GC treatment
Measurement of inferior colliculus volume based on MRI image stacks and its relationship with age and hearing status
No full textThe inferior colliculus is a key nucleus in the central auditory pathway, integrating acoustic stimuli from both cochleae and playing a crucial role in sound localization. It undergoes functional and structural development in childhood and experiences age-related degeneration later in life, contributing to the progression of age-related hearing loss. This study aims at finding out, whether the volume of the human inferior colliculus can be determined by analysis of routinely performed MRIs and whether there is any age-related variation. A further goal is to detect correlations between volume and existing hearing loss of the patients. A retrospective search in the data of the Regensburg ENT department was done. 123 MRI datasets were used to mark the voxels of the inferior colliculus on the MRI layers. The volumes could then be calculated by using the respective DICOM data and were correlated with age, gender and hearing status of the patients. Results suggested that a voxel-based method on routine clinical MRI stacks to determine the volume of the inferior colliculus is possible. The volume shows an age-dependency. There is a growth from infancy until adulthood and a significant decrease in patients over the age of 60 years. Left and right inferior colliculi do not show any systematic asymmetry in volume. There is no difference between females and males. In the group with asymmetric hearing (n = 13) a significant reduction of the volume on the deprived side (p = 0.036) was found. The proportion of subjects with severe hearing loss at least on one side was significantly higher in the old (>60 years) as compared to younger adults (10 to 60 years), suggesting that severe hearing loss may be associated with a reduced volume of the inferior colliculus in aged humans
Einfluss des „skeletal muscle mass index“ auf das Überleben bei Patienten mit Hirnmetastasen
No full textBei 20% aller Krebspatienten wird im Verlaufe der Erkrankung eine Hirnmetastase diagnostiziert. Es wird davon ausgegangen, dass die wahre Hirnmetastasierungsrate noch höherliegt, da nicht jede Metastase diagnostiziert oder behandelt wird. In Autopsiestudienwurden Hirnmetastasierungsraten von bis zu 40% festgestellt. Das mediane Überleben bei Hirnmetastasen liegt zwischen 3 und 12 Monaten mit steigender Tendenz, wobei es große Unterschiede in Abhängigkeit der Grunderkrankung, der Stadien und Therapieoptionen gibt. Das Einschätzen der Prognose ist ein komplexer und mehrstufiger Prozess. Für Hirnmetastasen relevante prognostische Faktoren sind der karnofsky performance score (KPS) und der Metastasenstatus.
Eine kurative Therapie gelingt selten.
Sarkopenie wird als zunehmender und generalisierter Verlust an Muskelmasse, -stärke und -funktion definiert und ist mit negativen Folgen assoziiert, so auch physische Limitationen, reduzierte Lebensqualität und der Tod. Ein Zusammenhang zur Prognose wurde bei vielen Erkrankungen bereits bewiesen. Die vollständige Diagnose der Sarkopenie ist ein komplexer, mehrstufiger Prozess.
Der skeletel muscle mass index (SMI) wird häufig als Surrogatmarker für die Sarkopenie verwendet, so auch in dieser Arbeit. Ziel dieser Arbeit ist es zu untersuchen, ob bei Patienten mit Hirnmetastasen
eine potentielle Sarkopenie vorliegt und ob es einen prognostischen Zusammenhang des SMI mit dem Gesamtüberleben gibt.
Es wurde Patienten mit Hirnmetastasen, die an der Universitätsklinik Regensburg von
2010 bis 2019 in Behandlung waren, retrospektiv analysiert. Die lokale Ethikkommission erteilte die Genehmigung zur
Durchführung der Studie.
Die Bestimmung der Muskelfläche zur Berechnung des SMI wurde anhand von CT-Bildern mit Horos Version 3.3.6 durchgeführt. Die Schichtdicke der axialen Schnittbilder betrug 3 bis 5 mm. Es wurden drei
aufeinanderfolgende axiale Schichten auf der Höhe von LWK 3 ausgewählt.
Die Rumpfmuskulatur wurde basierend auf den Hounsefield Einheiten (HU) automatisch segmentiert und anschließend einer manuellen Korrektur unterzogen. Alle Patienten erhielten eine chirurgische Therapie der Hirnmetastase. Die Größe und das Gewicht der Patienten wurde aus den Anästhesieprotokollen der Hirnoperationen entnommen. Hieraus wurde
ebenfalls der BMI errechnet. Anschließend wurde der SMI errechnet (SMI= lumbale
Muskelfläche (cm2) / Körpergröße (m)2).
Die statistischen Analysen wurde mit Stata Version 16.0 von Stata Corp durchgeführt.
Die Tabellen und Abbildungen wurden mit dem Programm Stata Version 16.0,
Microsoft Power Point 2021 und Microsoft Word 2021 erstellt.
Der Zusammenhang der Variablen zum Overall survival (OS) wurde mit Hilfe einer Regression, dem Log-Rank-Test und einer multivariaten Cox-Regressionsanalyse untersucht. Es wurden die Odds-Ratio (OR), das 95% Konfidenzintervall (95%-CI) und die zugehörige Signifikanz (p) bestimmt.
In der Kohorte von 146 Patienten waren 68 Männer (46.58%) und 78 Frauen (53.42%). Der häufigste Primärtumor war das Lungenkarzinom mit 45 Fällen (30.82%), gefolgt vom Mammakarzinom mit 32 Fällen (21.92%) und dem malignen Melanom mit 20 Fällen (21.92%). Die restlichen Fälle verteilten sich auf weitere Primärtumoren zu
kleineren Anteilen. 27 Patienten (18.49%) hatten eine einzige Hirnmetastase. In 47 Fällen (32.19%) lag eine Hirnmetastase bei weiteren Metastasen im restlichen Körper vor (maximal 4). In 72 Fällen (49.32%) lagen eine oder mehr Hirnmetastase(n) mit weiteren Metastasen
im restlichen Körper vor (insgesamt mehr als 4).
Der Metastasenstatus zeigte im Log-Rank-Test einen statistisch signifikanten
Zusammenhang zum OS (p= 0.0046). Des Weiteren zeigten der SMI (p=0.036) und
der KPS (p=0.018) einen statistisch signifikanten Zusammenhang mit dem OS.
In der multivariaten Cox-Regressionsanalyse zeigte sich eine statistisch signifikante Korrelation (HR 0.98; 95%-CI 0.95-1.00; p=0.048) des SMI mit dem OS. Der Metastasenstatus zeigte ebenfalls einen signifikanten Zusammenhang (HR 1.52; 95%-CI 1.19 – 1.96; p=0.001) mit dem OS. Der KPS hingegen zeigte keinen statistisch signifikanten Zusammenhang mit dem OS.
Die Regressionsanalyse ergab, dass der lumbale SMI nicht signifikant mit dem
präoperativen KPS korreliert (p=0.087; ß=0.245) und somit eine unabhängige Aussage trifft.
Zusammenfassend besteht in dieser Arbeit eine signifikante Korrelationen zwischen dem OS und jeweils dem SMI und dem Metastasenstatus bei Patienten mit Hirnmetastasen. Hierbei zeigt den stärksten Zusammenhang zum Überleben der Metastasenstatus, welcher aus großen Studien einer der bekannten, relevantesten Prognosefaktoren für das OS bei zerebral metastasiertem Tumor ist. Der SMI zeigt eine signifikante Korrelation mit dem OS und stellt eine sinnvolle Alternative zu etablierten prognostischen Faktoren dar. Der SMI ist
leicht zu bestimmen und ein vielversprechender Surrogatmarker für die Sarkopenie.
Somit stellt der SMI eine vielversprechende Alternative zur Abschätzung einer
Prognose dar
Characterization of [3H]Propionylated Human Peptide YY-A New Probe for Neuropeptide Y Y2 Receptor Binding Studies
No full textThe neuropeptide Y (NPY) Y2 receptor (Y2R) is a G-protein-coupled receptor that is involved in the regulation of various physiological processes such as neurotransmitter release, bone metabolism, and memory. Consequently, the Y2R represents a potential drug target, e.g., for the treatment of epilepsy and mood disorders. Until now, the determination of the Y2R binding affinities of Y2R ligands has primarily been performed using 125I-labeled derivatives of the endogenous Y2R agonists NPY and peptide YY (PYY). A tritium-labeled NPY derivative has also been used; however, its suitability for binding assays in sodium-containing buffer is doubtful. We synthesized a tritium-labeled PYY derivative by [3H]propionylation at Lys4 ([3H]2). The radioligand was characterized by saturation binding, association, and dissociation kinetics and was applied in competition binding assays. Specific binding of [3H]2 at intact Chinese hamster ovary cells expressing the hY2R was saturable in both sodium-free buffer (apparent Kd = 0.016–0.067 nM) and sodium-containing buffer (175 mM Na+, apparent Kd = 0.16–0.18 nM). Competition binding experiments with Y2R reference ligands yielded Ki values, which are in good agreement with the reported Y2R binding affinities, showing that [3H]2 represents a useful tritiated tool compound for the determination of Y2R binding affinities also in buffers containing sodium at physiological concentrations