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Results for “Deep generative model”

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PubMed1994

[Thyroid gland function and intrapulmonary temperature in tuberculosis].

The experiment on 140 albino mice examined the relationship between the pulmonary thermogenesis and the functional activity of the hypophyseal-thyroid system at different stages of pulmonary tuberculous inflammation development, during Staphylococcus-induced pneumonia, aseptic inflammation in lung tissue. Deep abnormalities of the heat-generating function of the lung were revealed just at the early periods of specific inflammation. The degree of hypothermal reactions of lung tissue correlated with the inhibition of hypophyseal-thyroidal function at all developmental stages of a tuberculous process. The changes were rather pronounced, stable and phasic. Spontaneous regression of the tuberculous process was not accompanied by recovery in the activity of the hypophyseal-thyroidal system, despite the fact that there was a clear-cut trend to normalization of pulmonary thermogenesis.

Animals↗

PubMed1995

A common protein fold and similar active site in two distinct families of beta-glycanases.

The structure of Clostridium thermocellum endoglucanase CelC, a member of the largest cellulase family (family A), has been determined at 2.15 A resolution. The protein folds into an (alpha/beta)8 barrel, with a deep active-site cleft generated by the insertion of a helical subdomain. The structure of the catalytic core of xylanase XynZ, which belongs to xylanase family F, has been determined at 1.4 A resolution. In spite of significant differences in substrate specificity and structure (including the absence of the helical subdomain), the general polypeptide folding pattern, architecture of the active site and catalytic mechanism of XynZ and CelC are similar, suggesting a common evolutionary origin.

Amino Acid Sequence↗

PubMed1985

The crystal structure of d(G-G-G-G-C-C-C-C). A model for poly(dG).poly(dC).

The structure of the DNA oligomer d(G-G-G-G-C-C-C-C) has been determined at a resolution of 2.5 A by single-crystal X-ray methods. There are two strands in the asymmetric unit, and these coil about each other to form a right-handed double-helix of the A-type with Watson-Crick hydrogen bonds between base-pairs. The helix has a shallow minor groove and a deep, water-filled major groove; almost all exposed functional groups on the DNA are hydrated, and 106 ordered solvent molecules have been found. The two d(G-G-G-G).d(C-C-C-C) segments in the octamer exhibit similar and uniform structures, but there is a slight discontinuity at the GpC step between them. A recurring feature of the structure is the overlap of adjacent guanine bases in each GpG step, with the five-membered ring of one guanine stacking on the six-membered ring of its neighbour. There is little or no overlap between adjacent cytosine rings. Conformational parameters for these GpG steps are compared with those from other single-crystal X-ray analyses. In general, GpG steps exhibit high slide, low roll and variable twist. Models for poly(dG).poly(dC) were generated by applying a simple rotation and translation to each of the unmodified d(G-G-G-G).d(C-C-C-C) units. Detailed features of these models are shown to be compatible with various assays of poly(dG).poly(dC) in solution, and are useful in understanding the polymorphic behaviour of this sequence under a variety of experimental conditions.

Chemical Phenomena↗

PubMed2026

Upcycling Vegetable Waste Into Functional Food Ingredients via Synergistic Microbial Engineering and Artificial Intelligence.

The escalating generation of global vegetable waste represents a critical loss of bioactive resources, necessitating a paradigm shift from passive disposal to active nutrient upcycling. However, the industrial conversion of this heterogeneous biomass into standardized functional food ingredients is currently impeded by significant techno-economic barriers, primarily structural recalcitrance, compositional inconsistency, and the presence of toxic fermentation inhibitors. This review provides a comprehensive analysis of the synergistic application of microbial engineering and artificial intelligence (AI) to resolve these bioprocessing bottlenecks within a food-to-food closed-loop framework (as shown in the graphical abstract). We evaluate recent advances in engineering food-grade microbial chassis (e.g., Saccharomyces cerevisiae and Escherichia coli) to enhance lignocellulose degradation and stress tolerance. Concurrently, we examine the integration of AI across the entire value chain, covering deep learning-based rational enzyme design, genome-scale metabolic modeling, and intelligent process control for precision fermentation. Current evidence demonstrates that the hardware-software coupling of engineered strains and AI algorithms significantly enhances conversion efficiency and process robustness. Key findings highlight that AI-driven Design-Build-Test-Learn cycles facilitate the de novo creation of enzymes with superior kinetics and strains with adaptive stress response capabilities against toxins. Moreover, dynamic digital twin models effectively mitigate the impact of substrate variability, ensuring the batch-to-batch consistency required for food applications. We conclude that this data-driven synergistic paradigm is pivotal for establishing a resilient circular bioeconomy, enabling the reliable bioconversion of waste into high-value single-cell proteins, natural flavor additives, and sustainable packaging materials.

Artificial Intelligence↗

PubMed1992

Mechanisms in the development of limbic status epilepticus and hippocampal neuron loss: an experimental study in a model of status epilepticus induced by kindling-like electrical stimulation of the deep prepyriform cortex in rats.

A new model of status epilepticus (SE), which was induced by intermittent electrical stimulation (20 Hz for 20 sec every min for 180 min) of the deep prepyriform cortex, has been developed in the conscious rat. SE was induced in 9 of 16 rats in the drug-free group. The number of stimulation trains required to induce SE in this status subgroup was 125.6 +/- 12.7 (mean +/- SEM) and the mean duration of self-sustained seizure activity (SSSA) occurring after cessation of the stimulation session was 295.4 +/- 111.4 min. Some animals showed secondary generalized seizures. Significant cell loss was observed in the hippocampal CA3 pyramidal cell layer ipsilateral to the stimulation site and bilateral CA1 areas in the status subgroup compared with the group subjected to sham operation. In addition, there was a significant negative correlation between the duration of SSSA subsequent to the stimulation session and the total number of intact pyramidal neurons observed in the bilateral CA1 and ipsilateral CA3 subfields of the status subgroup. There were significant differences between the status and non-status subgroups with respect to the number of afterdischarges (ADs) and the total AD duration during the stimulation session. Pretreatment with phenobarbital (30 mg/kg) prevented the development of SE and hippocampal cell loss completely. Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist (0.25 or 1 mg/kg), also prevented hippocampal cell loss, although it did not block SE generation completely, which suggests dissociation of the mechanisms underlying the development of SE and hippocampal damage. These results indicate that prolonged SSSA actually causes hippocampal damage and it is critically dependent upon NMDA receptor participation.

Animals↗

PubMed1985

From the spinning disc to the membrane oxygenator for open-heart surgery.

Gibbon's rotating cylinder could not be enlarged to oxygenate an animal larger than a cat. The spinning disc oxygenator, introduced in 1947, had the capacity to perfuse a dog and the potential to increase oxygenation capacity by addition of more discs. When centers began to do three to four open-heart operations per day, the disposable bubble oxygenator was more practical. Bubble size was optimized to decrease the flow of oxygen relative to the blood flow and reduce trauma to blood. The bubble oxygenator is the type most commonly used today. Use of deep hypothermia with whole blood at an esophageal temperature of 10 degrees C was initially complicated by brain damage due to aggregation of white blood corpuscles and platelets. The introduction of hemodilution permitted safe utilization of hypothermic perfusion. Perfusion of infants should not be carried out at hematocrit below 25 ml/100 m. Early membrane oxygenators used nonporous silicone, or modified silicone membranes. High priming volumes, high pressure drop and marginal gas transfer efficiency characterized these devices. Recent advances in membrane technology have spawned a new generation of membrane oxygenators utilizing microporous polypropylene. In these new oxygenators, with either microporous hollow fibers or sheet membrane, the gas transfer characteristics are far superior to those of types produced in the past. The hollow-fiber devices typically have larger surface areas and higher pressure drop than in the new state-of-the-art flat plate models. An evaluation of one of these new-generation membrane oxygenators gave optimal oxygen and carbon dioxide exchange at a gas flow of 1 l/min of 60% oxygen in air at 30 degrees C and 2 l/min of 80% oxygen in air at normal temperature and rewarming for an adult. Today, after almost 40 years of oxygenator development, these new membrane device can offer better platelet preservation and reduced blood trauma as compared with types developed in the past. The new membrane oxygenators are fast becoming the preferred choice for use in infants and in protracted perfusion.

Age Factors↗

PubMed1986

Microcorrosion casting of the human respiratory acinus.

Microcorrosion casts demonstrating the respiratory acini of human lungs were produced using Tensol Cement No. 70 (a methyl methacrylate mixture). Lung casts were made from foetuses of 19 weeks' gestation to term, a child of 5 years and two adults. Tensol Cement No. 70 was found to infuse the most peripheral airspaces without tissue penetration and could be airdried. Attempts using Batson's medium were hampered by permeation of the airway walls and inability to withstand airdrying. Despite the use of autopsy material, good cell impressions were seen. At 19 weeks' gestation, the respiratory acinus is simple with only two or three generations of rather tubular respiratory bronchioles. In later intra-uterine development, the number of generations of intra-acinar airways increases and the most peripheral airspaces expand to form initially shallow but later cup-shaped saccules. At all ages, the proximal airways of the acinus have regularly-spaced deep cell impressions suggesting a cuboidal/columnar epithelium while the distal airspaces have less frequent shallow cell impressions suggesting a flattened epithelium. Measurements of the maximum diameter of the most peripheral airspaces show an approximate doubling of size between 19 weeks' gestation and term and a further doubling by the age of 5 years.

Adult↗

PubMed1991

Localization of the P3 sources using magnetoencephalography and magnetic resonance imaging.

In this study, two related issues were addressed: first, whether the P3 component of auditory evoked responses, obtained in the context of an oddball paradigm, and its magnetoencephalographically recorded counterpart (P3m) are generated by the same intracranial sources; and, second, whether these sources, modeled as equivalent current dipoles, can be localized in particular brain structures using magnetic resonance imaging. The study involving 8 normal adult subjects resulted in the following findings. (1) Both the similarities and differences in wave form characteristics of the simultaneously recorded P3 and P3m can be best accounted for by common intracranial sources. (2) Several successively activated single-dipolar sources, rather than a single source, account for the entire evolution of the P3m component. (3) Most of these sources were localized in the vicinity of the auditory cortex in all subjects, although some sources appeared to be in deeper structures, possibly the lateral thalamus. (4) The successive activation of sources followed an orderly medial-to-lateral course. These results suggest that activity responsible for the surface-recorded P3 (and P3m) component may be initiated in deep structures, but it quickly spreads over and is sustained in areas near the auditory cortex.

Adult↗

PubMed2026

A Foundation Model Based CT Biomarker for Non-Invasive Prediction of Response to Neoadjuvant Immunochemotherapy in Non-Small Cell Lung Cancer.

Predicting pathological complete response (pCR) to neoadjuvant immunochemotherapy in non-small cell lung cancer (NSCLC) is clinically important yet remains challenging. Here, we introduce a foundation model-derived computed tomography (CT) imaging biomarker established from a multi-center cohort of 702 patients. Specifically, we developed and validated a non-invasive baseline CT-based model for risk stratification of pathological response. To address scanner and protocol heterogeneity, we first built a 3D Vision Mamba-based CT super-resolution model trained on 2494 cases for image standardization. We then fine-tuned a lung cancer-specific CT foundation model from a pretrained 3D model (VoCo) using 6643 chest CT scans. Finally, we constructed a multi-task Swin Transformer that jointly performs risk stratification and segments tumors to generate the imaging biomarker. Across five centers, the model achieved consistently strong generalization (AUC: 0.75-0.87) for pCR prediction. Genomic analysis revealed that the biomarker was independent of tumor mutational burden but significantly associated with TP53 mutations, suggesting an association with a radiogenomic phenotype related to this alteration. Together, these results demonstrate a generalizable and biologically meaningful foundation model-based biomarker for non-invasive risk stratification of pathological response in NSCLC.

Female↗

PubMed1995

Quantification of sodium lauryl sulfate penetration into the skin and underlying tissue after topical application--pharmacological and toxicological implications.

Sodium lauryl sulfate (SLS) is known to penetrate skin and cause cutaneous irritation. Some of these effects have been well-defined using bioengineering techniques. In this study, the ability of SLS to penetrate skin was quantified in a hairless rat model. In addition, local deep tissue penetration and systemic exposure to SLS were also evaluated to assess the toxic potential of topically applied SLS. SLS was observed to penetrate directly to a depth of about 5-6 mm below the applied site. Systemic redistribution was predominantly responsible in determining concentrations of SLS in tissues deeper than 5-6 mm. Epidermal concentrations of SLS after application of 1% (34 mM) aqueous SLS solution for 24 h were above the threshold levels which are known to evoke typical skin irritation responses. Deeper underlying tissues including dermis, subcutaneous, and muscle may also be exposed to high levels of SLS. Topically applied SLS was also observed in blood and contralateral tissues but the observed levels were not likely to elicit any systemic side effects at these doses. Traces of SLS were observed in tissues 7 days after single 24 h application of SLS, which supports the prolonged barrier disruption data generated using conventional bioengineering techniques. Cumulative treatment of SLS significantly increased the concentration of this compound in the underlying epidermis. The known preferential affinity of SLS for skin lipids and proteins was further confirmed by both in vitro and in vivo results. However, in vitro studies failed to predict the underlying tissue toxicity of SLS under the patch site when compared to the in vivo results. Such quantitative pharmacokinetic-pharmacodynamic correlations may be useful predictors for effective use of surfactants as penetration enhancers in cosmetic, pharmaceutical, and industrial applications.

Administration, Topical↗

PubMed1996

Prognostic significance of Ki-67 labeling indices obtained using MIB-1 monoclonal antibody in patients with supratentorial astrocytomas.

BACKGROUND: Identification of the prognosis of patients with gliomas is important for selecting and evaluating the effectiveness of treatment. The aim of this study was to evaluate the Ki-67 labeling index (LI) using the newly generated MIB-1 monoclonal antibody (MoAb) as a prognostic indicator for patients with astrocytomas. METHODS: Ki-67 immunohistochemistry was performed on paraffin sections to estimate the growth potential of 72 supratentorial astrocytomas using the MIB-1 MoAb after hydrated autoclaving treatment. Multivariate analysis using the Cox proportional hazard stepwise model was used to evaluate the influence of Ki-67 LI, as well as other prognostic factors, on the duration of survival of patients with supratentorial astrocytomas. RESULTS: The mean Ki-67 LI was 3.8% (+/- 2.7%; standard deviation [SD]) in Grade 2 gliomas (n = 19), 18.4% (+/- 9.7% SD) in Grade 3 gliomas (n = 25), and 31.6% (+/- 12.9% SD) in Grade 4 gliomas (n = 28). Multivariate survival analysis showed that histologic grade, Ki-67 LI, and Karnofsky performance status (KPS) score before and after treatment were independent, statistically significant prognostic factors for patients with all grades of astrocytomas. In high grade lesions, Ki-67 LI, tumor location (superficial vs. deep), and KPS score after treatment were significant prognostic variables, whereas histologic grade did not meet the significance level for entry into the stepwise model. CONCLUSIONS: These results indicate that the Ki-67 LI obtained using MIB-1 MoAb is an important and practical tool for estimating biologic behavior of gliomas, as well as for predicting survival.

Adolescent↗

PubMed1996

Site-directed mutants designed to test back-door hypotheses of acetylcholinesterase function.

The location of the active site of the rapid enzyme, acetylcholinesterase, near the bottom of a deep and narrow gorge indicates that alternative routes may exist for traffic of substrate, products or solute into and out of the gorge. Molecular dynamics suggest the existence of a shutter-like back door near Trp84, a key- residue in the binding site for acetylcholine, in the Torpedo californica enzyme. The homology of the omega loop, bearing Trp84, with the lid which sequesters the substrate in neutral lipases displaying structural homology with acetylcholinesterase, suggests a flap-like back door. Both possibilities were examined by site-directed mutagenesis. The shutter-like back door was tested by generating a salt bridge which might impede opening of the shutter. The flap-like back door was tested by de novo insertion of a disulfide bridge which tethered the omega loop to the body of the enzyme. Neither type of mutation produced significant changes in catalytic activity, thus failing to provide experimental support for either back door model. Molecular dynamics revealed, however, substantial mobility of the omega loop in the immediate vicinity of Trp84, even when the loop was tethered, supporting the possibility that access to the active site, involving limited movement of a segment of the loop, is indeed possible.

Acetylcholinesterase↗

PubMed1987

Simulation of chaotic EEG patterns with a dynamic model of the olfactory system.

The main parts of the central olfactory system are the bulb (OB), anterior nucleus (AON), and prepyriform cortex (PC). Each part consists of a mass of excitatory or inhibitory neurons that is modelled in its noninteractive state by a 2nd order ordinary differential equation (ODE) having a static nonlinearity. The model is called a KOe or a KOi set respectively; it is evaluated in the "open loop" state under deep anesthesia. Interactions in waking states are represented by coupled KO sets, respectively KIe (mutual excitation) and KIi (mutual inhibition). The coupled KIe and KIi sets form a KII set, which suffices to represent the dynamics of the OB, AON, and PC separately. The coupling of these three structures by both excitatory and inhibitory feedback loops forms a KIII set. The solutions to this high-dimensional system of ODEs suffice to simulate the chaotic patterns of the EEG, including the normal low-level background activity, the high-level relatively coherent "bursts" of oscillation that accompany reception of input to the bulb, and a degenerate state of an epileptic seizure determined by a toroidal chaotic attractor. An example is given of the Ruelle-Takens-Newhouse route to chaos in the olfactory system. Due to the simplicity and generality of the elements of the model and their interconnections, the model can serve as the starting point for other neural systems that generate deterministic chaotic activity.

Animals↗

PubMed1996

Characterization and molecular reaction scheme of a chloride channel expressed after axotomy in crayfish.

The nerve to the deep extensor abdominal muscle (DEAM) in crayfish species Astacus astacus, containing four excitatory and one inhibitory motor axons, was cut in the third segment on one side of the animal. The distal axon stump was not subject to phagocytosis but was present for months after the axotomy. The two lateral bundles of the DEAM were prepared 4-6 weeks after the axotomy. The gamma-aminobutyric-acid-(GABA-) activated chloride channel of these bundles was characterized by applying pulses of GABA to outside-out patches of the muscle membrane and measuring the responses. Based on the dose/response relationship of the peak current and of the rise time as well as on single-channel kinetics, a detailed molecular scheme for the reaction of the channel with GABA was derived. This scheme contains four binding steps of the agonist to the receptor and two open states. Simulations of the dose/response relationships with this model resulted in a set of rate constants which generate proper fits. In comparison to the channels present in innervated muscles, the channels of denervated muscles have a higher affinity for GABA, a lower single-channel conductance, four versus five binding steps, and non-cooperative binding. The first three of these adaptations of denervated muscles correspond to similar changes in denervated vertebrate muscles.

Abdominal Muscles↗

PubMedDate not supplied

Electrophysiological comparison between catechol- and urea-induced myoclonus models in the rat.

Catechol- and urea-induced myoclonus models in the rat were electrophysiologically compared to clarify pathophysiological differences. Catechol-induced myoclonus had various similarities with cortical reflex myoclonus in that there were electroencephalogram (EEG) discharges prior to myoclonic discharges, a spread of myoclonic discharges from the rostral to the caudal site, and a high amplitude somatosensory evoked potential (SEP). In urea-induced myoclonus, there were no EEG discharges related to myoclonic discharges and no enlarged SEP components as in reticular reflex myoclonus. Catechol-induced myoclonus had two evoked EMG responses of the biceps femoris at mean onsets of 8.0(C1) and 13.4 (C2) ms, and urea-induced myoclonus had a response (U1) at the mean onset of 10.2 ms. A study of the effects of various lesions in the central nervous system on these evoked EMG responses suggests that C1 is a monosynaptic spinal reflex. C2 which disappeared when the bilateral sensorimotor cortex for the hind limb had been resected and the lesion cooled is generated by the deep cerebral structures, such as the thalamus or basal ganglia, and U1 originates in the brain stem reticular formation. These results imply definitive differences of the pathophysiological mechanisms between catechol- and urea-induced myoclonus.

Animals↗

PubMed1989

How visual inputs to the ponto-bulbar reticular formation are used in the synthesis of premotor signals during orienting.

The primate superior colliculus (SC) is known as a structure subserving the transformation of visual information into "commands" for orienting eye movements. Collicular burst neurons discharging with short lead times in relation to visually triggered or spontaneous saccades are supposed to be the output elements linking the SC to immediately premotor pattern generators. In this paper we summarize some data available for the cat's SC neurones, identified as tecto-reticulo-spinal projection cells (TRSN), and reticulospinal neurones (RSN), identified as receiving excitatory collicular input. Some TRSNs respond to visual stimuli in the absence of orienting movements and, hence, their signals cannot be regarded as motor "commands", in spite of their proven connections with premotor pools in the brain stem and with the spinal cord. Moreover, a small fraction of RSNs belonging to polysynaptic descending collicular pathways also displays visual responses dissociated from movement, in addition to discharges related to the performance of orienting eye-head synergies. The processes of visual to motor transformation, assumed by current models as being definitively accomplished in the SC, appear thus to be partially performed in the reticular network incorporating the overlapping collaterals of tectal projection cells and their target neurons in the reticular core. It is concluded that, at least as for visuomotor transformations underlying orienting movements in the cat, the deep division of the SC and the brain stem reticular formation represent an ensemble, rather than a sequence of hierarchically arranged levels of processing.

Action Potentials↗

PubMed2026

Mechanisms linking the gut microbiota to colorectal cancer development and progression.

Colorectal cancer remains a leading cause of global cancer mortality, with a concerning rise in early-onset cases driven by complex interactions between environmental exposures, lifestyle factors, and host genetics. Mounting evidence indicates that gut microbiota dysbiosis critically modulates this oncogenic process, acting as an active participant rather than a passive bystander. This review systematically synthesizes the dichotomous roles of the intestinal microbiome in colorectal tumorigenesis through the conceptual framework of the driver-passenger model. We discuss how early initiating driver bacteria, such as Polyketide synthase-positive Escherichia coli and enterotoxigenic Bacteroides fragilis, compromise mucosal barriers, induce chronic mucosal inflammation, and inflict direct genomic instability. As the local tumor microenvironment undergoes profound metabolic remodeling, opportunistic passenger pathogens, notably Fusobacterium nucleatum, become enriched, further promoting cellular proliferation and facilitating tumor immune evasion. Conversely, protective commensals, exemplified by Clostridium butyricum and Streptococcus thermophilus, exert robust tumor-suppressive effects through multifaceted mechanisms. These beneficial microbes actively antagonize malignant progression by redirecting tumor metabolic fluxes toward oxidative stress, orchestrating deep epigenetic reprogramming, and degrading core oncoproteins to reverse chemoresistance. Transitioning from fundamental mechanisms to clinical application, we evaluate a comprehensive spectrum of microbiota-targeted interventions, encompassing non-invasive diagnostic biomarkers, fecal microbiota transplantation, engineered bacteria, phage therapy, and postbiotics. Finally, we critically address the formidable translational challenges associated with microbial heterogeneity, long-term safety, and regulatory standardization, aiming to provide a balanced perspective on integrating microbiome-based strategies into next-generation precision oncology for colorectal cancer.

Humans↗

PubMed1995

The RecA protein as a model molecule for molecular systematic studies of bacteria: comparison of trees of RecAs and 16S rRNAs from the same species.

The evolution of the RecA protein was analyzed using molecular phylogenetic techniques. Phylogenetic trees of all currently available complete RecA proteins were inferred using multiple maximum parsimony and distance matrix methods. Comparison and analysis of the trees reveal that the inferred relationships among these proteins are highly robust. The RecA trees show consistent subdivisions corresponding to many of the major bacterial groups found in trees of other molecules including the alpha, beta, gamma, delta, epsilon proteobacteria, cyanobacteria, high-GC gram-positives, and the Deinococcus-Thermus group. However, there are interesting differences between the RecA trees and these other trees. For example, in all the RecA trees the proteins from gram-positive species are not monophyletic. In addition, the RecAs of the cyanobacteria consistently group with those of the high-GC gram-positives. To evaluate possible causes and implications of these and other differences phylogenetic trees were generated for small-subunit rRNA sequences from the same (or closely related) species as represented in the RecA analysis. The trees of the two molecules using these equivalent species-sets are highly congruent and have similar resolving power for close, medium, and deep branches in the history of bacteria. The implications of the particular similarities and differences between the trees are discussed. Some of the features that make RecA useful for molecular systematics and for studies of protein evolution are also discussed.

Amino Acid Sequence↗