Search arXivSearch

arXiv · 1811.09115

Quantification of sulfated polysaccharides in urine by the Heparin Red mix-and-read fluorescence assay

Abstract

Quantification of sulfated polysaccharides in urine samples is relevant to pharmacokinetic studies in drug development projects and to the non-invasive diagnosis and therapy monitoring of mucopolysaccharidoses. The Heparin Red Kit is a particularly simple and user friendly fluorescence assay for the quantification of sulfated polysaccharides and has recently emerged as a novel tool for the monitoring of their blood levels during pharmacokinetic studies in clinical trials. The standard protocol for the blood plasma matrix is, however, not suited for urine samples due to matrix interference. The present study identifies inorganic sulfate as the interfering component in urine. The sulfate level of urine is typically 1-2 orders of magnitude higher compared with the blood plasma level. Addition of either hydrochloric acid or magnesium chloride counteracts sulfate interference but still enables sensitive detection of sulfated polysaccharides such as heparin, heparan sulfate and dermatan sulfate at low microgramm per milliliter levels. This study extends the application range of the Heparin Red Kit by a simple modification of the assay protocol to the direct quantification of various sulfated polysaccharides in human urine.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ulrich Warttinger, Roland Krämer. 2018-11-22. Quantification of sulfated polysaccharides in urine by the Heparin Red mix-and-read fluorescence assay. https://arxiv.org/abs/1811.09115

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

High Reconstruction Quality and Restart Repeatability Do Not Guarantee Recovery of Ground-Truth Muscle Synergies

High reconstruction quality and agreement across repeated fits do not necessarily establish recovery of muscle synergies. We tested whether a variance-accounted-for (VAF)/elbow rule recovers the generating synergy count and spatial vectors, whether high restart repeatability indicates recovery, and how five design factors affect recovery. Non-negative matrix factorisation was applied to 4,320 synthetic 16-muscle datasets varying generating rank, noise, trial count, spatial similarity and activation overlap. Combined recovery required the correct rank and cosine similarity of at least 0.80 for every matched spatial vector. Factor effects and two-factor interactions were assessed using exploratory heteroscedastic Wald tests with Benjamini-Hochberg adjustment. Rank selection was exact in 17.6% of datasets, too low in 54.9% and too high in 27.5%; combined recovery was 13.9%. Among fits with VAF at least 0.90, only 11.3% achieved combined recovery. Among 3,762 datasets with spatial repeatability at least 0.95, 19.6% had the correct rank and 15.7% achieved combined recovery. All five factors were associated with recovery (adjusted p < 0.001). Recovery declined from 26.2% to 1.7% with increasing spatial similarity and from 26.2% to 2.2% with increasing activation overlap. It was lower at ranks 7-9 than at 3-5, increased from 11.0% with 3 trials to 15.8% with 80 trials, and varied non-monotonically with noise. Five noiseless signals synthesised from measured-sEMG reference factors also showed under-selection despite VAF above 0.918. Under this selector, high reconstruction quality and restart agreement were insufficient indicators of correct rank and spatial recovery. Muscle-synergy interpretation should account for rank sensitivity and the separability of spatial and activation patterns.

q-bio.QM

A hierarchical memory architecture overcomes context limits in long-horizon multi-agent computational modeling

Large language models (LLMs) demonstrate remarkable reasoning capabilities, yet their stateless architecture fundamentally limits deployment in long-horizon research workflows requiring multi-session continuity and quantitative rigor. Here we present Ensemble QSP, a multi-agent framework featuring a three-layer hierarchical memory architecture that bounds injected context (median 301 tokens, max 4,050) by capping state categories and evicting completed work. This enables continuous autonomous operation without context degradation. The system orchestrates five specialist worker agents under domain-expert principal investigators (PIs), enforcing physical constraints through physics-based checklists and structured domain knowledge. Comprehensive benchmarking demonstrates autonomous pharmacokinetic-pharmacodynamic (PKPD) model selection, improved parameter recovery relative to single-agent baselines, and robust interpretation of linguistically diverse prompts. Replication with open-weight models (DeepSeek-V4-Flash/Pro, Llama 3.1 70B) confirmed these architectural conclusions across PKPD modeling, literature synthesis, and PBPK model implementation, proving the framework is independent of proprietary LLMs. Feature-level ablations show that memory, retrieval, and PI oversight address distinct scientific failure modes, though underlying LLM capability remains consequential for stringent physical-consistency checks. The architecture is structurally agnostic to computational biology; adding a new scientific domain requires only a new PI-agent configuration.

q-bio.QM

Foundation-model-based multi-label phenotyping of combined hyperkinetic movement disorders

Movement disorders (MDs) frequently co-occur, yet phenomenological and severity assessment shows substantial inter-rater variability. Markerless video could improve reproducibility, but prior work is largely single-symptom, depends on standardized acquisition, and lacks validation and transfer across ages and sites. We combined two foundation models into one frozen backbone: Segment Anything Model 3 (SAM 3) for dense, per-frame markerless segmentation summarized into geometric, contour and grid kinematic signals, and TabICLv2, a tabular foundation model, for in-context multi-label classification of eight hyperkinetic MD phenomenologies. Trained on standardized recordings of 21 adults and 4 controls, it transferred unchanged to two independent datasets, pediatric (n=12) and tremor-dominant adult (n=20), assessed with the CODY-SAMP scale; only the patient-level decision step was recalibrated per site. Under clinician consensus labels, false positives fell to zero in both datasets. Dystonia recovered perfectly (7/7 pediatric; 15/15 adult held-out), chorea fully in children (3/3), and tremor was recovered in adults (11/15) once a tremor-rich cohort made it evaluable, through recalibration alone. Per-region effect-size analysis gave clinically coherent, phenomenology-specific signals and identified myoclonus as the principal failure. Against YOLOv8 sparse keypoints, the dense representation matched under clinician permissive labels (Jaccard 0.63 vs 0.63) and was markedly more robust under clinician-label consensus (0.93 vs 0.76). This frozen foundation-model backbone with light per-site calibration yields transferable, interpretable, conservative multi-label phenotyping of co-occurring hyperkinetic MDs across ages and from standardized to routine video, adding robustness on high-confidence, clinician-agreed labels. Prospective multi-centre validation is required before clinical use.

q-bio.QM