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At least 19 recordsLinked to original sources

Optimal transport on complex networks.

We present a heuristic algorithm for the optimization of transport on complex networks. Previously proposed network transport optimization algorithms aim at avoiding or reducing link overload. Our algorithm balances traffic on a network by minimizing the maximum node betweenness with as little path lengthening as possible, thus being useful in cases when networks are jamming due to node congestion. By using the resulting routing, a network can sustain significantly higher traffic without jamming than in the case of shortest path routing.

Journal Article↗

GenOT: generative optimal transport enables spatiotemporal interpolation and generation in cross-platform spatial transcriptomics.

Spatial transcriptomics technologies have revolutionized the analysis of spatial gene expression, yet integrating spatial information and generating data across heterogeneous samples remain challenging. We present GenOT, a generative framework combining multi-scale graph self-supervised contrastive learning with optimal transport barycenter theory for efficient cross-slice and cross-platform spatiotemporal interpolation. The core innovation of GenOT lies in introducing an optimal transport barycenter-based interpolation algorithm, which mathematically models spatial distribution differences across heterogeneous samples to reconstruct spatiotemporal gene expression dynamics. Extensive evaluations demonstrate that GenOT consistently outperforms existing approaches in spatial domain identification, cross-platform interpolation, and developmental trajectory reconstruction.

Spatial Transcriptomics↗

Inferring cell trajectories of spatial transcriptomics via optimal transport analysis.

The integration of cell transcriptomics and spatial position to organize differentiation trajectories remains a challenge. Here, we introduce SpaTrack, which leverages optimal transport to reconcile both gene expression and spatial position from spatial transcriptomics into the transition costs, thereby reconstructing cell differentiation. SpaTrack can construct detailed spatial trajectories that reflect the differentiation topology and trace cell dynamics across multiple samples over temporal intervals. To capture the dynamic drivers of differentiation, SpaTrack models cell fate as a function of expression profiles influenced by transcription factors over time. By applying SpaTrack, we successfully disentangle spatiotemporal trajectories of axolotl telencephalon regeneration and mouse midbrain development. Diverse malignant lineages expanding within a primary tumor are uncovered. One lineage, characterized by upregulated epithelial mesenchymal transition, implants at the metastatic site and subsequently colonizes to form a secondary tumor. Overall, SpaTrack efficiently advances trajectory inference from spatial transcriptomics, providing valuable insights into differentiation processes.

Animals↗

NoisyFlow: differentially private optimal transport using neural networks for secure biomedical data sharing across multiple institutions.

MOTIVATION: Biomedical models improve when trained on data pooled across institutions, but sensitive patient records (e.g. genomics, clinical data, and medical images) are difficult to share due to privacy constraints. Moreover, data collected at different sites often have shifted distributions because of covariate differences (including batch effects), so privacy-preserving sharing alone cannot simply resolve cross-site mismatch. Methods that protect individuals while explicitly aligning distributions are needed to enable reliable multi-institutional analyses. RESULTS: We present NoisyFlow, a three-stage differentially private framework for cross-institutional harmonization under distribution shift. In stage I, each site learns a differentially private flow-based generator of its local labeled distribution. In stage II, it learns a neural optimal transport map to a shared reference distribution. In stage III, a central server composes the released models to generate reference-aligned pseudo-data for downstream analysis without accessing raw records. Across four biomedical settings spanning single-cell genomics, histopathology, neurogenomics, and wearable sensing, NoisyFlow reduces distribution shift while preserving downstream utility under formal differential privacy guarantees. AVAILABILITY AND IMPLEMENTATION: The implementation of NoisyFlow is available at https://github.com/gersteinlab/NoisyFlow.

Information Dissemination↗

Determination of optimal transport conditions for biopsies of human articular cartilage as well as for suspensions of cultured chondrocytes used in autologous transplantation.

Autologous transplantation of chondrocytes is currently being promoted as a novel approach for the treatment of deep cartilage lesions. Briefly, the method involves enzyme-mediated release of chondrocytes from cartilage biopsies, the expansion of cells by in vitro cultivation and their re-implantation into the defect. The success of this technique depends on many factors including transport conditions for both, cartilage biopsies from the operating hall to the laboratory and the return transport of final suspension of cultured chondrocytes. To determine the extent of cellular damage in biopsies, chondrocytes were enzymatically isolated following a few days of tissue preservation in different tissue culture media. The proportion of dead cells was assessed by Trypan blue staining and counting. The viability was not dependant of the type of the medium used and remained approximately 50% in all samples, even after 72 h. To develop optimal conditions for transport of final chondrocyte suspension, isolated cells were firstly grown in monolayer cultures. Cell suspensions in media with different additives were injected into special glass containers used for the transport and left at 4 degrees C or 25 degrees C for up to 3 days. During this period every 24 h the samples were taken and viability as well as apoptosis levels were assessed. Viability of cells in suspensions at 25 degrees C decreased significantly and became inadequate already after 48 h. In contrast to that, the proportion of viable cells at 4 degrees C remained above 80% even after 48 h. In the majority of the samples, culture medium containing serum and vitamin C provided the best conditions for long-term preservation of chondrocytes.

Apoptosis↗

Architecture of optimal transport networks.

We analyze the structure of networks minimizing the global resistance to flow (or dissipative energy) with respect to two different constraints: fixed total channel volume and fixed total channel surface area. First, we show that channels must be straight and have uniform cross-sectional areas in such optimal networks. We then establish a relation between the cross-sectional areas of adjoining channels at each junction. Indeed, this relation is a generalization of Murray's law, originally established in the context of local optimization. We establish a relation too between angles and cross-sectional areas of adjoining channels at each junction, which can be represented as a vectorial force balance equation, where the force weight depends on the channel cross-sectional area. A scaling law between the minimal resistance value and the total volume or surface area value is also derived from the analysis. Furthermore, we show that no more than three or four channels meet at each junction of optimal bidimensional networks, depending on the flow profile (e.g., Poiseuille-like or pluglike) and the considered constraint (fixed volume or surface area). In particular, we show that sources are directly connected to wells, without intermediate junctions, for minimal resistance networks preserving the total channel volume in case of plug flow regime. Finally, all these results are compared with the structure of natural networks.

Journal Article↗

Determination of the optimal transport system for Helicobacter pylori cultures.

A range of solid and liquid media was evaluated for the ability to maintain survival of Helicobacter pylori strains under different conditions. Chocolate agar slopes maintained survival of most strains for longer than 3 days, some strains surviving for up to 9 days, despite a decreased number of viable cells. Temperature and atmosphere did not significantly influence the performance of these slopes. The BBL Campy Pouch system also achieved a considerable recovery rate of H. pylori after storage for 3 days at the same range of temperatures. Brain-heart infusion broth with horse serum was superior among the liquid media tested, maintaining the viability of H. pylori for c. 3 days at temperatures ranging from -4 degrees C to 21 degrees C. Chocolate agar slopes are recommended as suitable for transport of H. pylori strains.

Culture Media↗

Optimizing transport in a homogeneous network.

Many situations in physics, biology, and engineering consist of the transport of some physical quantity through a network of narrow channels. The ability of a network to transport such a quantity in every direction can be described by the average conductivity associated with it. When the flow through each channel is conserved and derives from a potential function, we show that there exists an upper bound of the average conductivity and explicitly give the expression for this upper bound as a function of the channel permeability and channel length distributions. Moreover, we express the necessary and sufficient conditions on the network structure to maximize the average conductivity. These conditions are found to be independent of the connectivity of the vertices.

Journal Article↗

Optimal transport parameters of the inner medullary collecting duct in interaction between urine concentrating and urea excreting mechanisms: a computer simulation study.

Although the accumulation of urea in the renal medulla is essential for the formation of concentrated urine, it is also necessary for the kidney to excrete considerable amounts of urea into the urine as a waste product of protein degradation. Thus, the urine concentrating capacity is attained by the interaction with the efficiency of urea excretion. To seek the best condition for this phenomenon, we developed an objective function for evaluating urea excreting capacity relative to urine concentrating capacity by using a mathematical model consisting of components of the countercurrent multiplication system: the ascending thin limb, capillary network, and inner medullary collecting duct. The values of the objective functions were calculated as three-dimensional functions of transport parameters for the inner medullary collecting duct, including hydraulic conductivity, urea permeability, and reflection coefficient for urea. The results of the computer analysis revealed that the maximum value of the objective function was attained when values for transport parameters of the inner medullary collecting duct corresponded to those experimentally obtained values reported previously. We conclude that the maximum urine concentrating capacity is limited by the efficiency of urea excreting capacity of the kidney, and vice versa.

Biological Transport↗

Intensity modulation optimization, lateral transport of radiation, and margins.

Intensity modulation provides greatly increased control, leading to superior dose distributions with a potential for improved clinical outcome. It also allows us to compensate for deviations from the expected patterns in dose distributions caused by the lateral transport of radiation. This is important not only to produce more homogeneous dose distributions in the target volume but also, more importantly, to allow a reduction in the margins for the penumbra and a corresponding reduction in the volume of normal tissue irradiated. Potentially, this would permit escalation of doses to higher levels and further improve local control for the same or lower normal tissue complications. The intensity-modulated treatment design process, regardless of the specific method used, involves the tracing of rays from the source of radiation through the target volume. Intensities of rays are adjusted iteratively in an attempt to produce a desired homogeneous dose within the target volume, while at the same time striving to maintain normal tissue exposure within the limits of tolerance. If the lateral transport of scattered radiation is ignored, as is commonly done because of the complexities of incorporating it, the resulting dose distribution within the target volume may be considerably different from the anticipated pattern. This would be particularly true if there are high gradients in fluence patterns within the field to shield a normal anatomic structure. Similarly, the lateral transport of radiation would lead to a dose deficit just inside the boundary of the planning target volume (PTV) and a dose excess just outside it. The conventional remedy to make up for the loss of dose near the boundaries, thereby ensuring complete coverage of the target volume, would be to employ a margin for the "penumbra." We demonstrate that, with intensity modulation, we have an important new tool to improve target coverage, namely an appropriate increase in fluence just inside the boundary. Most suitably, a combination of increased fluence and a smaller than conventional margin should be employed. We have used an iterative scheme to compensate for lateral transport in the intensity modulation optimization process. In each iteration, the intensity distribution is first designed ignoring lateral transport. At the end of each iteration, the dose distribution is calculated using a pencil beam convolution method, thereby incorporating lateral transport and revealing the deviations from the anticipated dose distribution caused by lateral transport. In the next iteration, ray intensities are further adjusted to rectify the deviations. In general, only a few iterations are needed to adequately account for the lateral transport of radiation. We have applied this method to intensity-modulated prostate treatment plans and demonstrate that this methodology allows the use of smaller margins, improves target dose homogeneity, and provides greater protection for normal tissues. We examine the variation of the magnitude of the gain from one patient to another. The methodology described in this paper has been introduced into routine clinical use.

Biophysical Phenomena↗

scACCorDiON: a clustering approach for explainable patient level cell-cell communication graph analysis.

MOTIVATION: Combining single-cell sequencing with ligand-receptor (LR) analysis paves the way for the characterization of cell communication events in complex tissues. In particular, directed weighted graphs naturally represent cell-cell communication events. However, current computational methods cannot yet analyze sample-specific cell-cell communication events, as measured in single-cell data produced in large patient cohorts. Cohort-based cell-cell communication analysis presents many challenges, such as the nonlinear nature of cell-cell communication and the high variability given by the patient-specific single-cell RNAseq datasets. RESULTS: Here, we present scACCorDiON (single-cell Analysis of Cell-Cell Communication in Disease clusters using Optimal transport in Directed Networks), an optimal transport algorithm exploring node distances on the Markov Chain as the ground metric between directed weighted graphs. Benchmarking indicates that scACCorDiON performs a better clustering of samples according to their disease status than competing methods that use undirected graphs. We provide a case study of pancreas adenocarcinoma, where scACCorDion detects a sub-cluster of disease samples associated with changes in the tumor microenvironment. Our study case corroborates that clusters provide a robust and explainable representation of cell-cell communication events and that the expression of detected LR pairs is predictive of pancreatic cancer survival. AVAILABILITY AND IMPLEMENTATION: The code of scACCorDiON is available at https://scaccordion.readthedocs.io/en/latest/. and https://doi.org/10.5281/zenodo.15267648. The survival analysis package can be found at https://github.com/CostaLab/scACCorDiON.su.

Humans↗

Denitrifying Pseudomonas aeruginosa: some parameters of growth and active transport.

Optimal cell yield of Pseudomonas aeruginosa grown under denitrifying conditions was obtained with 100 mM nitrate as the terminal electron acceptor, irrespective of the medium used. Nitrite as the terminal electron acceptor supported poor denitrifying growth when concentrations of less than 15 mM, but not higher, were used, apparently owing to toxicity exerted by nitrite. Nitrite accumulated in the medium during early exponential phase when nitrate was the terminal electron acceptor and then decreased to extinction before midexponential phase. The maximal rate of glucose and gluconate transport was supported by 1 mM nitrate or nitrite as the terminal electron acceptor under anaerobic conditions. The transport rate was greater with nitrate than with nitrite as the terminal electron acceptor, but the greatest transport rate was observed under aerobic conditions with oxygen as the terminal electron acceptor. When P. aeruginosa was inoculated into a denitrifying environment, nitrate reductase was detected after 3 h of incubation, nitrite reductase was detected after another 4 h of incubation, and maximal nitrate and nitrite reductase activities peaked together during midexponential phase. The latter coincided with maximal glucose transport activity.

Aerobiosis↗

Reducing long-term remedial costs by transport modeling optimization.

The Department of Defense (DoD) Environmental Security Technology Certification Program and the Environmental Protection Agency sponsored a project to evaluate the benefits and utility of contaminant transport simulation-optimization algorithms against traditional (trial and error) modeling approaches. Three pump-and-treat facilities operated by the DoD were selected for inclusion in the project. Three optimization formulations were developed for each facility and solved independently by three modeling teams (two using simulation-optimization algorithms and one applying trial-and-error methods). The results clearly indicate that simulation-optimization methods are able to search a wider range of well locations and flow rates and identify better solutions than current trial-and-error approaches. The solutions found were 5% to 50% better than those obtained using trial-and-error (measured using optimal objective function values), with an average improvement of approximately 20%. This translated into potential savings ranging from 600,000 dollars to 10,000,000 dollars for the three sites. In nearly all cases, the cost savings easily outweighed the costs of the optimization. To reduce computational requirements, in some cases the simulation-optimization groups applied multiple mathematical algorithms, solved a series of modified subproblems, and/or fit "meta-models" such as neural networks or regression models to replace time-consuming simulation models in the optimization algorithm. The optimal solutions did not account for the uncertainties inherent in the modeling process. This project illustrates that transport simulation-optimization techniques are practical for real problems. However, applying the techniques in an efficient manner requires expertise and should involve iterative modification to the formulations based on interim results.

Algorithms↗

Hexose transport in human adipocytes: factors influencing the response to insulin and kinetics of methylglucose and glucose transport.

Optimal experimental conditions were defined for measuring the initial uptake rate of the non-metabolizable sugar analogue 3-O-methylglucose in non-stimulated and insulin-stimulated human adipocytes. The permeability of the adipocyte plasma membrane for tracer methylglucose (100 mumol/l) was 2.9 X 10(-7) cm X s-1 at 37 degrees C and slightly lower at 20 degrees C. At 37 degrees C and pH 7.4 insulin (5 nmol/l) increased the permeability about twofold (range 1.5 to fivefold) with half maximal effect at about 100 pmol/l). At pH 7.0 the dose response curve for the insulin effect on the uptake rate of methylglucose was shifted about 2.5-fold to the right. The permeability to L-glucose due to simple diffusion was estimated as 3.0 X 10(-10) cm X s-1 suggesting that uptake of methylglucose occurs almost exclusively by facilitated diffusion. The Km for methylglucose equilibrium exchange in insulin stimulated cells was about 4.8 mmol/l. The initial uptake of tracer methylglucose in insulin-stimulated cells was inhibited by unlabelled methylglucose and by D-glucose with inhibition constants of about 3.8 and 7.7 mmol/l respectively. Uptake of tracer 2-deoxyglucose (50 mumol/l) in insulin-stimulated adipocytes was linear from 10 s to 5 min whereas the rate of uptake in the presence of 3 mmol/l of D-glucose was markedly decreased suggesting that deoxyglucose uptake after a few minutes is mainly limited by hexokinase in the presence of glucose.

Adipose Tissue↗

Monitoring of optimal oxygen Transport by the transcutaneous oxygen tension method in the pig.

The validity of the transcutaneous oxygen tension (PaO2) method as opposed to measurement of arterial oxygen tension (PaO2) and mixed venous oxygen saturation (SVO2), for monitoring optimal oxygen transport, was studied in six mechanically ventilated pigs with an oleic acid lung injury. With stepwise increments in positive end-expiratory pressure (PEEP) from zero to 20 cmH2O maximum oxygen flux was found at a PEEP of 8 cmH2O and named "optimal PEEP". With increasing PEEP, cardiac output (CO) was maintained up to a PEEP of 8 cmH2O, when it began to decline, while venous admixture decreased at all respiratory settings up to a PEEP of 16, when it was about one-fourth of the value (38.7%) at a PEEP of zero. PaO2 increased with rising PEEP and reached a steady level at a PEEP of 16 cmH2O. PtCO2 and SVO2 parallelled each other and rose steeply up to a PEEP of 8 cmH2O. They showed a further slight increase up to a PEEP of 12 and after that a tendency to decrease. It is concluded that PtCO2 and SVO2 both seem to distinguish the optimal PEEP and give more adequate information than does PaO2. The PtCO2 method has the advantage of being non-invasive.

Animals↗

Optimal absorptive transport of the dipeptide glycylsarcosine is dependent on functional Na+/H+ exchange activity.

Optimal nutrient absorption across the intestinal epithelium is dependent on the co-ordinated activity of a number of membrane transporters. Di/tripeptide transport across the luminal membrane of the intestinal enterocyte is mediated by the H(+)-coupled di/tripeptide transporter hPepT1. hPepT1 function is dependent on the existence of a pH gradient (maintained, in part, by the action of the Na(+)/H(+) exchanger NHE3) across the apical membrane of the small intestinal epithelium. The physiological problem addressed here was to determine how two transporters (hPepT1 and NHE3), involved in nutrient absorption and pH(i) homeostasis, function co-operatively to maximise dipeptide absorption when both operate sub-optimally at typical mucosal surface pH values (pH 6.1-6.8). Functional hPepT1 activity in human intestinal epithelial (Caco-2) cell monolayers was determined by measurement of apical uptake and apical-to-basolateral transport of the dipeptide glycylsarcosine. The dependence of hPepT1 on NHE3 activity was measured (either after Na(+) removal or addition of the NHE3-selective inhibitor S1611) using both Caco-2 cell monolayers and hPepT1-expressing Xenopus laevis oocytes. Apical glycylsarcosine uptake in Caco-2 cell monolayers was modulated by apical pH, extracellular Na(+), incubation time and S1611. Uptake in hPepT1-expressing oocytes was independent of Na(+) or S1611. We conclude that functional NHE3 activity is required to allow optimal absorption of dipeptides across the human intestinal epithelium.

Absorption↗

A review of drug use during air medical transport to optimize an air ambulance formulary.

INTRODUCTION: The advent of air medical transport has pushed the delivery of critical care medicine into the prehospital arena. As a result, a wide variety of pharmacologic agents must be available in the air medical setting. PURPOSE: The purpose of this study was to conduct a retrospective review of drugs used during air medical transport to allow a streamlining of the air ambulance formulary. METHODS: All flights completed since the inception of the study's helicopter air ambulance program in 1985 through September 1991 were analyzed to determine which medications were used in flight. Drugs were counted if they were administered while in flight for either a scene or interhospital transport. RESULTS: Review of 2,694 flights showed that 45 individual drugs had been routinely carried during the study period. Many of these agents were administered fewer than five times during the six years, and 10 drugs were not used at all. CONCLUSION: As a result of this investigation, the formulary for our air medical transport service was modified. The authors recommend similar critical audits of drugs carried in flight be performed by other air ambulance services.

Air Ambulances↗