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At least 73 records · Page 4Linked to original sources

Uniform regional heating of the lower trunk: numerical evaluation of tumor temperature distributions.

The temperature distributions in deep seated tumors resulting from uniform heating of the abdominal and pelvic regions of the trunk are predicted from a one dimensional numerical solution of the bio-heat transfer equation. The effect of tumor size and location are investigated for two tumor perfusion models: uniform perfusion and a concentric annulus perfusion model. Tumor temperature distributions are considered acceptable if the range of temperatures in the tumor lie between 42 degrees C and 60 degrees C. This range of tumor temperatures is defined as Tave +/- 2 sigma where sigma is the population standard deviation of tumor temperatures from the average computed at the nodal points in the finite difference array. To simulate practical clinical restrictions, muscle and fat temperatures are not allowed to exceed 44 degrees C, significant portions of the viscera are not allowed to exceed 42 degrees C, and the total absorbed power required to maintain steady state cannot exceed two kilowatts. Over 100 possible cases are presented in a compact form. From this study it appears that heating systems with power deposition patterns approximately uniform are promising for heating deep-seated tumors. Small, detectable tumors (approximately 2 cm in size) are adequately heated for a wider range of conditions than are larger tumors. Excessively high temperatures in deep-seated, normal tissue could be a significant limitation for this technique.

Abdominal Neoplasms↗

A stochastic model describes the heterogeneous pharmacokinetics of cyclosporin.

The pharmacokinetics of cyclosporin (CsA) are unusual because of several heterogeneous features which include the presence of more than one conformer, considerable accumulation in erythrocytes and lipoproteins, extensive plasma protein binding, distribution into deep tissues, biliary secretion and hepatic clearance involving a large number of metabolites. In this study, a stochastic compartmental model was developed to describe the heterogeneous elimination kinetics of CsA. This new approach relies on a probabilistic transfer model with a gamma distributed probability intensity coefficient for drug elimination. For comparative purposes both the stochastic model and compartmental deterministic models were fitted to real post infusion data from patients receiving CsA as a 2-hr intravenous infusion. The criteria for selecting the best model showed that the stochastic model, although simpler than the compartmental deterministic models, is more flexible and gives a better fit to the kinetic data of CsA than the compartmental deterministic models. The stochastic model with a random rate intensity coefficient adequately describes the heterogeneous pharmacokinetics of CsA.

Cyclosporine↗

Mechanisms of deep brain stimulation and future technical developments.

Possible mechanisms underlying the therapeutic effect of deep brain stimulation (DBS) are reviewed, particularly the notion that DBS is inhibitory. Computer simulations are described that model the effect of different frequencies and regularity of neuronal activity (target neuron), either spontaneous or stimulated, on information transfer between two other neurons. Most simulations resulted in a loss of information. These were the least with high frequency and regular activity or stimulation of the target neuron with regularity having the least deleterious effect on information transfer. The simulations suggest that irregular activity in neurons converging with other neurons can result in a loss of information transfer. This may explain why increased irregularity in globus pallidus activity associated with Parkinson's disease, dystonia and hemiballismus may result in symptoms. Further, the therapeutic effect of DBS may be due to driving neurons at higher and perhaps more importantly, regular frequencies. There were simulations in which information transfer was augmented suggesting the presence of stochastic resonance. This most often occurred with low frequency activity in the target neuron. It is hypothesized that low frequency activity, either spontaneous or stimulated, could account for involuntary movements, including tremor. Future directions and challenges to DBS are also discussed.

Animals↗

Deriving inherent optical properties from water color: a multiband quasi-analytical algorithm for optically deep waters.

For open ocean and coastal waters, a multiband quasi-analytical algorithm is developed to retrieve absorption and backscattering coefficients, as well as absorption coefficients of phytoplankton pigments and gelbstoff. This algorithm is based on remote-sensing reflectance models derived from the radiative transfer equation, and values of total absorption and backscattering coefficients are analytically calculated from values of remote-sensing reflectance. In the calculation of total absorption coefficient, no spectral models for pigment and gelbstoff absorption coefficients are used. Actually those absorption coefficients are spectrally decomposed from the derived total absorption coefficient in a separate calculation. The algorithm is easy to understand and simple to implement. It can be applied to data from past and current satellite sensors, as well as to data from hyperspectral sensors. There are only limited empirical relationships involved in the algorithm, and they are for less important properties, which implies that the concept and details of the algorithm could be applied to many data for oceanic observations. The algorithm is applied to simulated data and field data, both non-case1, to test its performance, and the results are quite promising. More independent tests with field-measured data are desired to validate and improve this algorithm.

Journal Article↗

Differences between two feline epilepsy models in sleep and waking state disorders, state dependency of seizures and seizure susceptibility: amygdala kindling interferes with systemic penicillin epilepsy.

The objective of the study was to determine whether contemporary feline models of petit mal (systemic penicillin epilepsy) or temporal lobe epilepsy (amygdala kindling) resemble human seizure disorders with respect to disturbances of sleep and waking states, the state dependency of seizures, and transference of seizure susceptibility. These variables were examined in 6-h polygraphic recordings before and during exposure to both seizure models in 24 cats; 12 cats had intramuscular (i.m.) injections of 300,000 or 400,000 IU/kg of penicillin prior to kindling, and 12 were kindled before penicillin challenge. Results were as follows. First, penicillin increased light slow wave sleep (SWS) and drowsiness, during which spike-wave (SW) activity was maximal. Generalized tonic-clonic convulsions (GTCs) occurred predominantly in drowsiness after awakening from SWS. Second, kindling produced more deep SWS than did penicillin; susceptibility to kindled GTCs peaked during deep SWS, especially in transition to rapid eye movement sleep (REM). Third, penicillin did not influence subsequent sleep disorders or seizure susceptibility during kindling; kindling interfered with penicillin-induced GTCs, SW activity, and sleep disorders. Collectively, the findings suggest distinct state disorders and state-dependent seizure profiles in the two models. These differences parallel human analogues and may have contributed to the transference results. Kindling is a chronic model with persistent sleep and seizure abnormalities that differ from and may have discouraged penicillin epilepsy. Penicillin is an acute model with transient state and seizure disorders, a fact that may account for the absence of penicillin transference to kindling.

Amygdala↗

Intrinsic tyrosine fluorescence as a tool to study the interaction of the shaker B "ball" peptide with anionic membranes.

Steady-state and time-resolved fluorescence from the single tyrosine in the inactivating peptide of the Shaker B potassium channel (ShB peptide) and in a noninactivating peptide mutant, ShB-L7E, has been used to characterize their interaction with anionic phospholipid membranes, a model target mimicking features of the inactivation site on the channel protein. Partition coefficients derived from steady-state anisotropy indicate that both peptides show a high affinity for anionic vesicles, being higher in ShB than in ShB-L7E. Moreover, differential quenching by lipophilic spin-labeled probes and fluorescence energy transfer using trans-parinaric acid as the acceptor confirm that the ShB peptide inserts deep into the membrane, while the ShB-L7E peptide remains near the membrane surface. The rotational mobility of tyrosine in membrane-embedded ShB, examined from the decay of fluorescence anisotropy, can be described by two different rotational correlation times and a residual constant value. The short correlation time corresponds to fast rotation reporting on local tyrosine mobility. The long rotational correlation time and the high residual anisotropy suggest that the ShB peptide diffuses in a viscous and anisotropic medium compatible with the aliphatic region of a lipid bilayer and support the hypothesis that the peptide inserts into it as a monomer, to configure an intramolecular beta-hairpin structure. Assuming that this hairpin structure behaves like a rigid body, we have estimated its dimensions and rotational dynamics, and a model for the peptide inserted into the bilayer has been proposed.

Amino Acid Sequence↗

The concerted mechanism of photo-induced biprotonic transfer in 7-azaindole dimers: a model for the secondary evolution of the classic C2h dimer and comparison of four mechanisms.

A mechanism is proposed for the formation in gas phase, during a short time, of the delicately symmetrical coplanar C(2h) classic 7-azaindole (7AI) doubly hydrogen-bonded dimer. Of the five card-pack or otherwise random geometry structures most likely to be formed in the supersonic jet expansion molecular beam, none would be an obvious precursor to the C(2h) dimer. One unstable dimer with dipole-dipole, van der Waals, and plane-to-plane hydrogen bonding is shown to be capable of unhinging about the hydrogen-bond pair as an axis, from 0 degrees to 90 degrees to 180 degrees, yielding a deep minimum for the C(2h) structure with its delicate geometry and symmetry. This relaxation mechanism is feasible in the 3-micros interval between the nozzle escape and the first laser pulse interception of the molecular beam. In the second part of the paper four published mechanisms are compared for concerted vs. two-step biprotonic phototransfer for the 7AI dimers. The dependence of the latter two models on H-atom instead of proton-transfer as an intermediate step negates the mechanism in a singlet (pi,pi*) electronic state by the valency repulsion, in the 3-electron orbital that would be generated. The concerted mechanism for biprotonic phototransfer is reaffirmed by the analysis of the quantum mechanical conditions set on the biprotonic transfer in the photo-excited molecular 7AI pair.

Dimerization↗

Blood mitochondrial heteroplasmic variants and cognitive performance in late midlife: REGARDS study.

BACKGROUND: Studies linking mitochondrial DNA (mtDNA) variants to cognition yielded inconsistent findings, and the underlying mechanisms remain unclear. We investigated whether mtDNA heteroplasmic variants were associated with cognitive outcomes, including the Montreal Cognitive Assessment (MoCA), in 197 late midlife adults from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort with complete data. METHODS: MtDNA was sequenced from blood using targeted deep sequencing. Adjusted linear and mixed-effects models examined the associations by functional regions, genes, total variant burden, nonsynonymous variants, and control regions. RESULTS: Heteroplasmic variants in the control region (β = -0.44, 95% CI: -0.83, -0.05, p = 0.027) and transfer RNA (tRNA) genes (β = -1.34, 95% CI: -2.58, -0.11, p = 0.034) were associated with MoCA baseline scores. Individual variants in cytochrome c oxidase subunit 1 (CO1) (β = -1.51, 95% CI: -2.54, -0.47, p = 0.005), NADH dehydrogenase subunit 1 (ND1) (β = -2.63, 95% CI: -4.56, -0.70, p = 0.008), and Displacement Loop (D-LOOP2) (β = -2.25, 95% CI: -4.20, -0.30, p = 0.025) was associated with reduced baseline MoCA scores. The ND6 (β = −1.23, 95% CI: −2.09, − 0.37, p = 0.006), ND4 (β = −1.11, 95% CI: −2.02, − 0.20, p = 0.018), ATP Synthase Membrane Subunit 8 (ATP8; β = −1.38, 95% CI: −2.63, − 0.13, p = 0.031), and D-LOOP1 (β = −0.61, 95% CI: −1.20, − 0.01, p = 0.045) genes suggested a potential association with executive function. Longitudinal Animal Fluency Test (AFT) scores were inversely associated with heteroplasmic variants in coding regions (β = -0.10, 95% CI: -0.19, -0.006, p = 0.049), the total number of variants (β = -0.06, 95% CI: -0.11, -0.003, p = 0.037) and total nonsynonymous variants (β = -0.11, 95% CI: -0.21, -0.01, p = 0.040). Variants in the control region were associated with the greatest decline in verbal fluency (β = −0.20, 95% CI: −0.39 to − 0.002, p = 0.049). No associations were observed between mitochondrial variants and verbal memory performance or the MoCA composite scores. CONCLUSIONS: Our study indicates that mitochondrial variants measured in blood may provide insight into cognitive function during midlife. However, additional studies are needed to validate these associations and to address potential power limitations in our study.

Humans↗

Free diffusion of steroid hormones across biomembranes: a simplex search with implicit solvent model calculations.

Steroid hormones such as progesterone, testosterone, and estradiol are derived from cholesterol, a major constituent of biomembranes. Although the hormones might be expected to associate with the bilayer in a fashion similar to that of cholesterol, their biological action in regulating transcription of target genes involves transbilayer transfer by free diffusion, which is not observed for cholesterol. We used a novel combination of a continuum-solvent model and the downhill simplex search method for the calculation of the free energy of interaction of these hormones with lipid membranes, and compared these values to that of cholesterol-membrane interaction. The hormones were represented in atomic detail and the membrane as a structureless hydrophobic slab embedded in implicit water. A deep free-energy minimum of approximately -15 kcal/mol was obtained for cholesterol at its most favorable location in the membrane, whereas the most favorable locations for the hormones were associated with shallower minima of -5.0 kcal/mol or higher. The free-energy difference, which is predominantly due to the substitution of cholesterol's hydrophobic tail with polar groups, explains the different manner in which cholesterol and the hormones interact with the membrane. Further calculations were conducted to estimate the rate of transfer of the hormones from the aqueous phase into hexane, and from hexane back into the aqueous phase. The calculated rates agreed reasonably well with measurements in closely related systems. Based on these calculations, we suggest putative pathways for the free diffusion of the hormones across biomembranes. Overall, the calculations imply that the hormones may rapidly cross biomembrane barriers. Implications for gastrointestinal absorption and transfer across the blood-brain barrier and for therapeutic uses are discussed.

Algorithms↗

Automated CEAP Classification of Venous Duplex Reports Using Multimodal Artificial Intelligence.

OBJECTIVE: To develop and internally validate a prototype multimodal artificial intelligence system for automated CEAP (Clinical, Etiological, Anatomical and Pathophysiological) classification of venous duplex ultrasound (VDUS) reports, integrating natural language processing of free-text components with computer vision analysis of hand-drawn anatomical diagrams. METHODS: Single centre retrospective observational study using routinely collected clinical data. One thousand consecutive venous duplex ultrasound reports from Cambridge University Hospitals NHS Foundation Trust, UK (July 2024 - May 2025) were labelled according to the CEAP classification, excluding the Etiological component, which could not be reliably determined from duplex reports alone. Transfer learning was applied using ClinicalBERT for text and MobileNetV3 for diagrammatic data. Clinical classes were predicted from request line text. Text- and image-based pathophysiological models were developed for four anatomical territories (Great Saphenous Vein, Small Saphenous Vein, Deep system, Perforators), combined using late fusion with probability averaging. RESULTS: The clinical CEAP model achieved accuracy of 0.91, macro-F1 of 0.82, and macro-AUC of 0.98. Pathophysiological prediction varied, with text models broadly outperforming image models. Fusion yielded heterogeneous benefits, improving SSV performance but reducing Deep system accuracy. The performance of the final pathophysiological CEAP fusion models varied across anatomical territories: accuracy ranged from 0.70-0.92 and macro-AUC from 0.80-0.92. CONCLUSION: This study demonstrates the feasibility of automated CEAP classification from VDUS reports. Despite class imbalance affecting minority class predictions, the strong discriminatory performance validates this multimodal ML model for extracting clinically meaningful information from real-world data. This approach offers potential, pending external validation, to streamline vascular services through automated triage and guideline-compliant decision making.

Artificial intelligence↗

Effects of (multi)branching of dipolar chromophores on photophysical properties and two-photon absorption.

To investigate the effect of branching on linear and nonlinear optical properties, a specific series of chromophores, epitome of (multi)branched dipoles, has been thoroughly explored by a combined theoretical and experimental approach. Excited-state structure calculations based on quantum-chemical techniques (time-dependent density functional theory) as well as a Frenkel exciton model nicely complement experimental photoluminescence and one- and two-photon absorption findings and contribute to their interpretation. This allowed us to get a deep insight into the nature of fundamental excited-state dynamics and the nonlinear optical (NLO) response involved. Both experiment and theory reveal that a multidimensional intramolecular charge transfer takes place from the donating moiety to the periphery of the branched molecules upon excitation, while fluorescence stems from an excited state localized on one of the dipolar branches. Branching is also observed to lead to cooperative enhancement of two-photon absorption (TPA) while maintaining high fluorescence quantum yield, thanks to localization of the emitting state. The comparison between results obtained in the Frenkel exciton scheme and ab initio results suggests the coherent coupling between branches as one of the possible mechanisms for the observed enhancement. New strategies for the rational design of NLO molecular assemblies are thus inferred on the basis of the acquired insights.

Absorption↗

Multicompartment kinetic models for the metabolism of americium, plutonium and uranium in rats.

To examine the kinetic behaviour of americium, plutonium and uranium in the different organs of male and female rats an extended mammillary model has been developed; the model is composed of 10 compartments connected with 17 linear transfer coefficients. The 10 compartments describe the behaviour of the three nuclides in the blood, skeleton, liver and kidney, whereas the remaining activity is assigned to one residual organ. Each organ is divided into two compartments, a short- and long-term compartment. Morphologically, in the skeleton the short-term compartment has been assumed to be the bone surface and bone marrow and the long-term compartment to be the deep bone, whereas in the liver there is some evidence to suggest that the short-term compartment is physiologically associated with lysosomes and the long-term compartment is identical with telolysosomes. The influence of age, sex and different nuclides on the transfer coefficients and the absorbed radiation dose have been discussed. Additionally, by using the transfer coefficients calculated for intravenous injection, the behaviour of the nuclides in skeleton and liver during continuous intake has been calculated. As a second example of the application of the model the behaviour of the three nuclides in skeleton and liver after intravenous injection has been calculated with the additional assumption that from the fifth day on the animals were treated continuously with a chelating agent.

Americium↗

Immunologic responses to Candida albicans. III. Effects of passive transfer of lymphoid cells or serum on murine candidiasis.

Passive transfer of immune serum gave a significant degree of protection against deep seated candidiasis in mice. Repeated attempts to transfer resistance by the transfer of sensitized lymphoid cells gave negative results, even though cutaneous delayed hypersensitivity was transferred by the cells. The results suggest that cell-mediated immunity is not of primary importance in this model of murine candidiasis, and that humoral immunity contributes to protection.

Animals↗

Investigation of epileptic structure properties by transfer function.

The paper deals with the possibility of applying linear control theory and the theory of statistical dynamics to the complex and quantitative analysis of electroencephalographic records. The aim is to specify signals in the brain environment, in particular sources, speed and direction of signals, and the determination from results gained of the model of signal transfer, The possibilities of applying Fourier analysis and correlation analysis are examined. The methodical approach of the transient analysis is suggested. Conditions are discussed for approximate application of linear theory. Experimental results, as well as the calculation of transfer parameters of signals are evaluated. The method of magnetic EEG records, the scanning and processing of data on analogue and digital computers are introduced. The method described of correlation and transient analysis arises from the necessity to detect epileptic structures from an evaluation of SEEG records of the deep brain structure.

Electroencephalography↗

Gas transfer from air diffusers.

The bubble and surface volumetric mass transfer coefficients for oxygen, k(L)a(b) and k(L)a(s), are separately determined for 179 aeration tests, with diffuser depths ranging from 2.25 to 32 m, using the DeMoyer et al. 12003. Impact of bubble and free surface oxygen transfer on diffused aeration systems. Water Res 37, 1890-1904] mass transfer model. Two empirical characterization equations are developed for k(L)a(b) and k(L)a(s), correlating the coefficients to air flow, Qa, diffuser depth, hd, cross-sectional area, Acs, and volume, V. The characterization equations indicate that the bubble transfer coefficient, k(L)a(b), increases with increasing gas flow rate and depth, and decreases with increasing water volume. For fine bubble diffusers, k(L)a(b) is approximately six times greater than k(L)a(b) for coarse bubble diffusers. The surface transfer coefficient, k(L)A(s), increases with increasing gas flow rate and diffuser depth. The characterization equations make it possible to predict the gas transfer that will occur across bubble interfaces and across the free surface with a bubble plume at depths up to 32 m and with variable air discharge in deep tanks and reservoirs.

Bioreactors↗

Transfer learning with multiomics integration and deep neural networks reveals drug resistance mechanisms in cancer.

Drug resistance remains one of the primary challenges in effective cancer therapy. In this study, we employed a deep neural network (DNN)-based transfer learning (TL) approach to predict drug response and uncover drug resistance mechanisms. We integrated gene expression, somatic mutation, and copy number aberration (CNA) data with drug response profiles using multi-omics integration (MI). We used the Genomics of Drug Sensitivity in Cancer (GDSC) data for training and incorporated drugs with same pathways into the training models. We then evaluated drug response predictions on independent in-vivo PDX Encyclopedia (PDX) and ex-vivo the Cancer Genome Atlas (TCGA) datasets. In addition, we conducted pathway enrichment analyses to elucidate the mechanisms underlying drug resistance for paclitaxel, 5-fluorouracil (5-FU), gemcitabine, and cetuximab. We also applied Fisher's exact test (FET) to assess potential associations between drug resistance and the presence of mutations or CNAs. Our pan-drug models outperformed other methods based on the area under the precision-recall curve (AUCPR). Our pathway enrichment analyses revealed LDHB-mediated pyruvate metabolism and FYN-mediated focal adhesion might have pivotal roles in paclitaxel resistance, while PINK1-mediated mitophagy might be critical in 5-FU resistance. In addition to transcriptional activation, FET suggested that CNAs in LDHB and PINK1 may also be associated with resistance to paclitaxel and 5-FU, respectively. Furthermore, enrichment results for paclitaxel and cetuximab indicated shared resistance mechanisms between the two drugs. Importantly, our findings are consistent with prior experimental studies, providing literature-based validation of our results. Overall, our DNN-based TL approach achieved strong predictive performance across PDX & TCGA datasets and enrichment analyses provided valuable biological insights into drug resistance mechanisms.

Humans↗

Deep learning-based annotation of plant abiotic stress resistance genes for crops.

The declining costs of DNA sequencing have expanded genomic data, crucial for understanding plant abiotic stress responses and crop improvement. However, accurate gene annotation remains challenging. To address this limitation, we propose the PASRGA, a deep learning approach that leverages transfer learning and contrastive learning to annotate genes related to drought, salt, cold, and UV resistance. PASRGA achieves high F1-scores, area under the receiver operating characteristic (AUROC), area under the precision-recall curve (AUPRC), and Matthews correlation coefficient (MCC) in annotating stress resistance genes, significantly outperforming the general protein annotation model CLEAN, the plant phosphatase gene annotation model PF-NET, the top-ranked model in the CAFA5 challenge NetGO 4.0, and four traditional machine learning methods. Its effectiveness was further validated with a salt stress treatment experiment in Eutrema salsugineum. To facilitate crop breeding practices, we utilized PASRGA to annotate the genomes of 17 major crops. To improve accessibility and utility, we incorporated both manually curated and PASRGA-predicted gene data, together with the PASRGA tool, into the PlantASRG database (https://bioinfor.nefu.edu.cn/PlantASRG/). This comprehensive resource aims to support crop breeding initiatives and ensure food security.

Crops, Agricultural↗

Extended, strategic therapy for recalcitrant mind/body healing: an integrative model.

The development of the power therapies, behavioral medicine, and short term interventions have reported such success even with trauma cases that it is relevant to question the justification for lengthy psychotherapy. Yet some patients with complex mind/body conditions impervious to medical treatment/hypnosis may require extended, multi-modal, integrative therapy. This paper details a single complex case of paruresis as a prototype for illustrating a holographic treatment model for recalcitrant conditions: Component features of the proposed model presented include: 1) the sequential utilization of hypnobehavioral and analytic approaches; 2) uncovering work providing access to the somatic ego state associated with the illness condition; 3) the extended treatment time frame required for deep psycho-physiological change; and 4) the stages of counter-transference expectably evoked by such patients (e.g. urgency, exuberant optimism, frustration, discouragement), and the transformation of such reactions to achieve maximum therapeutic efficacy.

Adult↗