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Neurocomputing is computer modeling based, in part, upon simulation of the structure and function of the brain. Neural networks excel in pattern recognition, that is, the ability to recognize a set of previously learned data. Although their use is rapidly growing in engineering, they are new to the pharmaceutical community. This article introduces neurocomputing using the backpropagation network (BPN).
Conventional memory assessment may fail to identify memory dysfunction characterized by intact recall for a relatively brief period but rapid forgetting thereafter. This study assessed learning and retention after 30-min and 24-hr delays on auditory and visual selective reminding tests (SRTs) in right (n=20) and left (n=22) temporal lobe epilepsy (TLE) patients and controls (n=49). The left TLE group performed significantly worse than controls on all 3 trials of both tests. The right TLE group differed from the controls on all 3 visual SRT trials and on learning for the auditory SRT. There were no between-groups differences in rate of information lost at the 30-min versus the 24-hr delay. At the individual level, there was no difference in the percentage of patients versus controls who demonstrated isolated memory impairment at the 24-hr delay. Accelerated forgetting over 24 hr is uncommon in TLE patients.
Methodological and conceptual problems common in prenatal stress experiments were analyzed, and an experiment incorporating solutions to those problems were designed and executed. Rats were prenatally stressed or served as controls and then were cross-fostered within or between treatment groups. In adulthood, one male from each litter was tested over 20 trials in an open-field box and then tested over 20 successive discrimination reversals in a T-maze. A T-factor analysis was performed on each of the two sets of observations, and factors scores were subjected to elevational analyses. Major hypotheses generated from the results are the following: (a) Male rats subjected to prenatal stress acquire emotional reactivity levels in adulthood that are either elevated or reduced depending on the postnatal maternal environment. (b) Male rats subjected to prenatal stress acquire reversal learning sets in adulthood with a rapidity that parallels and indeed is produced by the pattern of emotional reactivity reflected in the above a and as mediated by cognitive processes. (c) T-factor analysis of trials is required in order to avoid construct validity problems as well as internal validity problems, both brought about by the confounding of trial variables, and in addition, it may generate valuable hypotheses giving further meaning to the dependent variables under observation.
Mathematical models were used to guide the UK foot-and-mouth disease (FMD) control policy during the 2001 epidemic. Based on data collected during the epidemic, prospective modelling using a variety of approaches gave the same conclusions: (i) that the epidemic had not been brought under control by 'traditional' methods, and (ii) that neighbourhood control measures (the contiguous cull) could bring the epidemic under control and result in a net saving of livestock. Retrospective analyses suggest that the subsequent course of the epidemic was consistent with a beneficial impact of the contiguous cull and that it would have been difficult to achieve a better outcome using reactive vaccination, which would have required very large-scale vaccination programmes to have been implemented quickly. Perhaps the most important lesson to be learned is the vital importance of rapid and decisive intervention in response to an outbreak, including the earliest possible implementation of a national ban on the movement of livestock once the presence of disease is confirmed.
The enzymes in the pathway for de novo pyrimidine biosynthesis, including those associated with the tri-functional CAD protein, show a marked increase in activity in rapidly growing cells and tissues. To learn more about the relationship of this pathway to cellular proliferation, we have studied changes in levels of CAD RNA, rates of CAD protein synthesis, and levels of aspartate transcarbamylase activity in Syrian hamster ts13 cells in response to serum starvation and serum stimulation. The steady-state level of CAD RNA and the synthetic rate of CAD protein decrease by 12- to 15-fold following 24 hr of serum starvation, as compared to exponentially growing cells. Upon serum stimulation of quiescent cells, steady-state CAD RNA levels increase substantially (13-fold), peaking during mid to late G1. Parallel increases occur in the synthesis of new CAD protein and in aspartate transcarbamylase activity. At the same time, the rate of CAD transcription increases only about twofold. These findings indicate that regulation of CAD expression in this system is primarily at the post-transcriptional level. This is in contrast to the transcriptional regulation of CAD previously reported in terminally differentiating HL60 cells (Rao et al., Mol. Cell. Biol. 7, 1961-1966, 1987). While both systems indicate that CAD gene expression is dependent on cell growth, there apparently are alternative mechanisms that can produce the same effect. Evidence is also presented that indicates that the accumulation of CAD transcripts during serum stimulation requires the synthesis of new proteins.
Most medical malpractice lawsuits that involve gynecologic endoscopy and laparoscopy result from either improper prevention, inadequate recognition, or delayed intervention. Continuing recognition of this will prevent many and mitigate most such cases. We can learn much from the events and rapid progress of the past decade. Although most laparoscopic improvements have been technical and instrument driven, a basic understanding of anatomy, physiology, and diagnostics remains essential to high-quality patient care and risk reduction.
A neural network control system has been designed for the control of cyclic movements in Functional Neuromuscular Stimulation (FNS) systems. The design directly addresses three major problems in FNS control systems: customization of control system parameters for a particular individual, adaptation during operation to account for changes in the musculoskeletal system, and attaining resistance to mechanical disturbances. The control system was implemented by a two-stage neural network that utilizes a combination of adaptive feedforward and feedback control techniques. A new learning algorithm was developed to provide rapid customization and adaptation. The control system was evaluated in a series of studies on a computer simulated musculoskeletal model. The model of electrically stimulated muscle used in the study included nonlinear recruitment, linear dynamics, and multiplicative nonlinear torque-angle and torque-velocity scaling factors. The skeletal model consisted of a one-segment planar system with passive constraints on joint movement. Results of the evaluation have demonstrated that the control system can provide automated customization of the feedforward controller parameters for a given musculoskeletal system. It can account for changes in the musculoskeletal system by adapting the feedforward controller parameters on-line and it can resist the effects of mechanical disturbances. These results suggest that this design may be suitable for the control of FNS systems and other dynamic systems.
Although the underlying mechanism is not elucidated, it has been postulated repeatedly that deprivation of sleep, particularly rapid eye movement (REM) sleep, affects learning. Here we report that memory for newly acquired information is impaired after a specific period of REM sleep deprivation (REMD). Memory retrieval-induced phosphorylation of protein kinases in the rat amygdala is abrogated by REMD that is associated with an increase in the expression of a dual protein/lipid phosphatase PTEN. REMD given before training is without effect, suggesting the lack of effect on the acquisition of memory. Intra-amygdala administration of antisense but not sense or scrambled oligonucleotides for PTEN prevents REMD-induced decrease in protein phosphorylation and impairment of fear memory. Thus, REMD interferes with the process of memory retention via the activation of PTEN.
The authors introduce Photoshop 6.0 for radiologists and demonstrate basic techniques of editing gray-scale cross-sectional images intended for publication and for incorporation into computerized presentations. For basic editing of gray-scale cross-sectional images, the Tools palette and the History/Actions palette pair should be displayed. The History palette may be used to undo a step or series of steps. The Actions palette is a menu of user-defined macros that save time by automating an action or series of actions. Converting an image to 8-bit gray scale is the first editing function. Cropping is the next action. Both decrease file size. Use of the smallest file size necessary for the purpose at hand is recommended. Final file size for gray-scale cross-sectional neuroradiologic images (8-bit, single-layer TIFF [tagged image file format] at 300 pixels per inch) intended for publication varies from about 700 Kbytes to 3 Mbytes. Final file size for incorporation into computerized presentations is about 10-100 Kbytes (8-bit, single-layer, gray-scale, high-quality JPEG [Joint Photographic Experts Group]), depending on source and intended use. Editing and annotating images before they are inserted into presentation software is highly recommended, both for convenience and flexibility. Radiologists should find that image editing can be carried out very rapidly once the basic steps are learned and automated.
We studied the severe acute respiratory syndrome (SARS) outbreak in Taiwan, using the daily case-reporting data from May 5 to June 4 to learn how it had spread so rapidly. Our results indicate that most SARS-infected persons had symptoms and were admitted before their infections were reclassified as probable cases. This finding could indicate efficient admission, slow reclassification process, or both. The high percentage of nosocomial infections in Taiwan suggests that infection from hospitalized patients with suspected, but not yet classified, cases is a major factor in the spread of disease. Delays in reclassification also contributed to the problem. Because accurate diagnostic testing for SARS is currently lacking, intervention measures aimed at more efficient diagnosis, isolation of suspected SARS patients, and reclassification procedures could greatly reduce the number of infections in future outbreaks.
Metabolic bioengineering has emerged as a transformative approach for reshaping plant defense by targeting intrinsic biosynthetic pathways to enhance immunity in modern agriculture. Moving beyond proof-of-concept metabolomics to broad-spectrum programmable pathway engineering addresses gaps in plant rational design and optimizes resilience in response to diverse environmental cues. This review aims to comprehensively highlight the transition of innovative approaches to phenolics, alkaloids, flavonoids, terpenoids, and benzoxazinoids, inferring adaptive reprogramming that mediates the growth-defense balance and functions as molecular sentinels in plants. Furthermore, decoding the volatile metabolome reveals a dynamic signaling interface that influences defense responses and stress-induced plant-microbe interactions, with the shikimate, jasmonate, and salicylate pathways functioning as central hubs for microbial deterrence and priming immune memory. Recent developments in multi-scalar genome-editing strategies, including CRISPR-driven combinatorial edits, enzyme orthogonalization, fluxomics, and spatially resolved multi-omics, reconfigure central and specialized metabolic fluxes toward improved defense function and regulation. Additionally, emerging tools, such as WUSCHEL2 and BABY BOOM transcriptional modules, and artificial engineering strategies integrating deep learning model-driven predictions facilitate rapid development of synthetic genetic circuits and support a predictive engineering of plants. Moreover, Mass spectrometry imaging (MSI) in spatial metabolomics enables to obtain structures and locations of unidentified endogenous metabolites within cells and tissues. Overall, this review emphasizes a diverse array of primary and secondary metabolites, spanning molecular concepts to recent advances in plant immune mechanisms. It also illustrates new frontiers in programmable metabolic engineering that accelerate the understanding of plant-microbe-metabolite cross-talks, offering strategies to improve plant resistance and advance sustainable agricultural solutions.
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We investigated the long-lasting effects of mechanical vibratory stimulation of the skin on the excitability of feline cortical neurons in the forelimb areas of the primary (SI) and secondary (SII) somatosensory cortices. Conditioning mechanical stimuli were 300 bursts of 10 pulses at 200 Hz delivered with a 10-s interburst interval from a mechanical stimulator. Test field potentials and unit discharges were evoked by electrical stimulation to the ventral posterolateral thalamic nucleus (VPL) or by single mechanical stimuli applied to the skin. In SII, the mechanical burst stimulation to the skin increased the amplitudes of field potentials and the frequency of unit discharges elicited by single mechanical stimuli applied to the skin. The vibratory conditioning stimulus also produced a similar potentiation of the VPL-evoked field potentials (126-139% increase in amplitude, P < 0.05) with an associated increase in firing rates of extracellularly recorded neuronal activity (117%, P < 0.001). These potentiations persisted through the entire experimental period of 120 min. The translaminar current source density analysis calculated from the VPL-evoked field potentials increased to 127% of the control value (P < 0.01). In contrast, in SI we observed no significant changes in the field potential amplitudes or in the currents generated in superficial layers (91-117%). Taken together with the previous finding that tetanic electrical stimulation of VPL induces long-lasting potentiation of the VPL-evoked cortical responses in SII but not of those in SI, the present results suggest that SII has a large capacity for the rapid functional plasticity involved in the learning that occurs during repeated tactile experiences.
The Child Health Accountability Initiative, a rapid-improvement collaborative for pediatrics, has learned valuable lessons about forming and sustaining the alliance.
BACKGROUND: In the fall of 2000, a nine-year-old child living in Montreal (Québec) died of rabies encephalitis. Cases of human rabies had not been reported in Canada for 15 years. The molecular characterization of viral nucleic acid implicated the Ln/Ps variant associated with the silver-haired bat and the eastern pipistrelle. This article describes and analyzes the intervention carried out by public health. INTERVENTION AND DISCUSSION: The investigation revealed that contact with the bat must have occurred while the child was sleeping. Following the search for close contacts of the reference case, rabies postexposure prophylaxis (RPEP) was recommended to 59 people (3 household contacts, 12 playmates and 44 health care workers). Discussion with other public health departments in the province was important because of the media coverage of this case, which led to a considerable increase in the number of reported exposures to bats and in RPEP administration. CONCLUSION: Lessons learned from this event are that rapid and coordinated action with all stakeholders is essential to the success of this type of public health intervention and that the population must be informed of the risk of rabies transmission from bats.
Many behaviors require rapid and precisely timed synaptic transmission. These include the determination of a sound's direction by detecting small interaural time differences and visual processing, which relies on synchronous activation of large populations of neurons. In addition, throughout the brain, concerted firing is required by Hebbian learning mechanisms, and local circuits are recruited rapidly by fast synaptic transmission. To achieve speed and precision, synapses must optimize the many steps between the firing of a presynaptic cell and the response of its postsynaptic targets. Until recently, the behavior of mammalian synapses at physiological temperatures was primarily extrapolated from studies at room temperature or from the properties of invertebrate synapses. Recent studies have revealed some of the specializations that make synapses fast and precise in the mammalian central nervous system at physiological temperatures.
This aim of this review is to describe the dynamics of learning-induced cellular modifications in the rat piriform (olfactory) cortex after olfactory discrimination learning and to describe their functional significance to long-term memory consolidation. The first change to occur is in the intrinsic properties of the neurons. One day after learning, pyramidal neurons show enhanced neuronal excitability. This enhancement results from reduction in calcium-dependent conductance that mediates the post burst after-hyperpolarization. Such enhanced excitability lasts for 3 days and is followed by a series of synaptic modifications. Several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons in the piriform cortex accompany olfactory learning. Enhanced synaptic release is indicated by reduced paired-pulse facilitation. Post-synaptic enhancement of synaptic transmission is indicated by reduced rise time of post-synaptic potentials and formation of new synaptic connections is indicated by increased spine density along dendrites of these neurons. Such modifications last for up to 5 days. Thus, olfactory discrimination rule learning is accompanied by a series of cellular modifications which occur and then disappear at different times. These modifications overlap partially, allowing the maintenance of the cortical system in a 'learning mode' in which memories for specific odors can be acquired rapidly and efficiently.
By changing the conditioned discrimination paradigm of Quinn et al. (1974) from an instrumental procedure to a classical (Pavlovian) one, we have demonstrated strong learning in wildtype flies. About 150 flies were sequestered in a closed chamber and trained by exposing them sequentially to two odors in air currents. Flies received twelve electric shock pulses in the presence of the first odor (CS+) but not in the presence of the second odor (CS-). To test for conditioned avoidance responses, flies were transported to a T-maze choice point, between converging currents of the two odors. Typically, 95% of trained flies avoided the shock-associated odor (CS+). Acquisition of learning was a function of the number of shock pulses received during CS+ presentation and was asymptotic within one training cycle. Conditioned avoidance increased with increasing shock intensity or odor concentration and was very resistant to extinction. Learning was best when CS+ presentations overlap shock (delay conditioning) and then decreased with increasing CS-US interstimulus intervals. Shocking flies immediately before CS+ presentation (backward conditioning) produced no learning. Nonassociative control procedures (CS Alone, US Alone and Explicitly Unpaired) produced slight decreases in avoidance responses, but these affected both odors equally and did not alter our associative learning index (A). Memory in wild-type flies decayed gradually over the first seven hours after training and still was present 24 h later. The mutants amnesiac, rutabaga and dunce showed appreciable learning acquisition, but their memories decayed very rapidly during the first 30 min. After this, the rates of decay slowed sharply; conditioned avoidance still was measureable at least three hours after training.