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At least 91 records · Page 5Linked to original sources

PubMed2002

The role of the thalamus in the flow of information to the cortex.

The lateral geniculate nucleus is the best understood thalamic relay and serves as a model for all thalamic relays. Only 5-10% of the input to geniculate relay cells derives from the retina, which is the driving input. The rest is modulatory and derives from local inhibitory inputs, descending inputs from layer 6 of the visual cortex, and ascending inputs from the brainstem. These modulatory inputs control many features of retinogeniculate transmission. One such feature is the response mode, burst or tonic, of relay cells, which relates to the attentional demands at the moment. This response mode depends on membrane potential, which is controlled effectively by the modulator inputs. The lateral geniculate nucleus is a first-order relay, because it relays subcortical (i.e. retinal) information to the cortex for the first time. By contrast, the other main thalamic relay of visual information, the pulvinar region, is largely a higher-order relay, since much of it relays information from layer 5 of one cortical area to another. All thalamic relays receive a layer-6 modulatory input from cortex, but higher-order relays in addition receive a layer-5 driver input. Corticocortical processing may involve these corticothalamocortical 're-entry' routes to a far greater extent than previously appreciated. If so, the thalamus sits at an indispensable position for the modulation of messages involved in corticocortical processing.

Animals↗

PubMed1992

Class E driver for transcutaneous power and data link for implanted electronic devices.

Magnetic transcutaneous coupling is frequently used for power and data transfer to implanted electronic devices. The paper describes a transmitter/coil driver based on the class E topology. The development of a 'high-Q approximation' simplifies the design procedure. A method of data modulation using synchronous frequency shifting is described. The class E circuit shows great promise, especially for circuits with unusually low coefficients of coupling. Transmitter coil currents of several amperes, at radio frequencies, with relatively low active device power dissipation, can easily be obtained.

Electric Power Supplies↗

PubMed2004

The burden of varicella in Germany. Potential risks and economic impact.

Varicella (chickenpox) has traditionally been regarded as a benign, inevitable disease of childhood. In Germany information on the clinical and economic impact of varicella is limited. This study assessed the health risks and economic burden of varicella with a special focus on the relevance of complications as a cost driver. We used an age-structured, dynamic infectious disease model for the spread of infection in the German population combined with a module modeling the course of disease and medical management in the case of infection. Model input data were derived mainly from a retrospective epidemiological survey of 1,334 varicella cases in Germany. This survey included detailed information on outpatient care, complications, inpatient treatment, and sick leave. In the base case analysis the model predicted approx. 740,000 varicella cases per year. Some 40,000 experienced complications, of which 5,700 required inpatient care. Total annual costs for payers, i.e., sickness funds, was 78 million euro, the largest portion of which was due to the significant coverage of work loss costs incurred by parents caring for their sick children ("Kinderpflegekrankengeld"). For the society total annual costs were 187.5 million euro, 82% of which was indirect. Complications account for disproportionate 32% (25%) of cost from the payers' (societal) perspective. However, the vast majority of costs are due to uncomplicated cases. The burden of varicella in Germany is thus significant, not only in terms of morbidity but also from an economic viewpoint. Vaccination strategies targeting groups with high risk of complications might fail to reduce the considerable burden of varicella substantially. Routine vaccination against varicella would be a meaningful measure to reduce the burden of VZV infection in Germany.

Adolescent↗

PubMed2001

What controls attention in natural environments?

The highly task-specific fixation patterns revealed in performance of natural tasks demonstrate the fundamentally active nature of vision, and suggest that in many situations, top-down processes may be a major factor in the acquisition of visual information. Understanding how a top-down visual system could function requires understanding the mechanisms that control the initiation of the different task-specific computations at the appropriate time. This is particularly difficult in dynamic environments, like driving, where many aspects of the visual input may be unpredictable. We therefore examined drivers' abilities to detect Stop signs in a virtual environment when the signs were visible for restricted periods of time. Detection performance is heavily modulated both by the instructions and the local visual context. This suggests that visibility of the signs requires active search, and that the frequency of this search is influenced by learnt knowledge of the probabilistic structure of the environment.

Attention↗

PubMed2003

Top-down modulation of lateral interactions in early vision: does attention affect integration of the whole or just perception of the parts?

Attention can modulate sensitivity to local stimuli in early vision. But, can attention also modulate integration of local stimuli into global visual patterns? We recently measured effects of attention on the phenomenon of lateral interactions between collinear elements, commonly thought to reflect long-range mechanisms in early visual cortex underlying contour integration. We showed improved detection of low-contrast central Gabor targets in the context of collinear flankers, but only when the collinear flankers were attended for a secondary task rather than ignored in favor of an orthogonal flanker pair. Here, we contrast two hypotheses for how attention might modulate flanker influences on the target: by changing just local sensitivity to the flankers themselves (flanker-modulation-only hypothesis), or by weighting integrative connections between flanker and target (connection-weighting hypothesis). Modeled on the known nonlinear dependence of target visibility on collinear flanker contrast, the first hypothesis predicts that an increase in physical flanker contrast should readily offset any reduction in their effective contrast when ignored, thus eliminating attentional modulation. Conversely, the second hypothesis predicts that attentional modulation should persist even for the highest flanker contrasts. Our results showed the latter outcome and indicated that attention modulates flanker-target integration, rather than just processing of local flanker elements.

Attention↗

PubMed2005

[Application of near infrared sensor to the technology of automobile transformation].

Using reflective near infrared sensor and voice record-reproducing assembly, the present article studies the voice anticollision-prompting device for backing an automobile. If there is a man or an object within a certain distance behind the backing automobile, part of the infrared signal will be reflected by the man or the object, and received by the photosensitive tube installed with a transmitting tube, and transformed to a similar frequency electric signal. The electric signal will be amplified, demodulated, and shaped by the circuit of module. After comparing and processing, the control signal will be output, which controls the work of voice record-reproducing assembly, and reminds the driver that there is a man or an object behind the backing automobile. With both the near infrared sensor and voice record-reproducing assembly being integrated, the distance-warning device has the advantages of low costs, simple wiring, strong anti-detonation ability, precise measuring, and working stability. It is suitable for being installed and used on the automobile.

Accidents, Traffic↗

PubMed1995

Backpropagation of action potentials generated at ectopic axonal loci: hypothesis that axon terminals integrate local environmental signals.

This review deals with the fascinating complexity of presynaptic axon terminals that are characterized by a high degree of functional distinctiveness. In vertebrate and invertebrate neurons, all-or-none APs can take off not only from the axon hillock, but also from ectopic axonal loci including terminals. Invertebrate neurons display EAPs, for instance alternating with somatic APs, during survival functions. In vertebrate, EAPs have been recorded in the peripheral and central nervous systems in time relationship with physiological or pathological neuronal activities. In motor or sensory axon, EAP generation may be the cause of motor dysfunctioning or sensory perceptions and pain respectively. Locomotion is associated with rhythmic depolarizations of the presynaptic axonal membrane of primary afferents, which are ridden by robust EAP bursts. In central axons lying within an epileptic tissue EAP discharges, coinciding with paroxysmal ECoG waves, get longer as somatic discharges get shorter during seizure progression. Once invaded by an orthodromic burst, an ectopic axonal locus can display an EAP after discharge. Such loci can also fire during hyperpolarization or the postinhibitory excitatory period of the parent somata, but not during their tonic excitation. Neurons are thus endowed with electrophysiological intrinsic properties making possible the alternate discharges of somatic APs and EAPs. In invertebrate and vertebrate neurons, ectopic axonal loci fire while the parent somata stop firing, further suggesting that axon terminal networks are unique and individual functional entities. The functional importance of EAPs in the nervous systems is, however, not yet well understood. Ectopically generated axonal APs propagate backwards and forwards along the axon, thus acting as a retrograde and anterograde signal. In invertebrate neurons, somatically and ectopically generated APs cannot have the same effect on the postsynaptic membrane. As suggested by studies related to the dorsal root reflex, EAPs may not only be implied in the presynaptic modulation of transmitter release but also contribute significantly during their backpropagation to a powerful control (collision process) of incoming volleys. From experimental data related to epileptiform activities it is proposed that EAPs, once orthodromically conducted, might potentiate synapses, initiate, spread or maintain epileptic cellular processes. For instance, paroxysmal discharges of EAPs would exert, like a booster-driver, a powerful synchronizing synaptic drive upon a large number of excitatory and inhibitory postsynaptic neurons. We have proposed that, once backpropagated, EAPs are likewise capable of initiating (and anticipating) threshold and low-threshold somatodendritic depolarizations. Interestingly, an antidromic EAP can modulate the excitability of the parent soma.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed2004

Eye movement detector calibration device.

Presented is a device developed for specifically calibrating and validating the operation of Eye Movement Detectors or Monitors. The Calibrator centers on two one inch diameter HPDE spheres representing the eyes. A Laser Module is embedded in the rear of each sphere emitting a beam against a target divided in equal measurement intervals mounted as part of the device. The device moves the "eyes" about its center axes enabling the user to validate any vertical, horizontal, or X-Y combination eye position in a plus or minus fifteen degree range. Although hand controlled, the Calibrator can be motorized with stepper motors or other desired drivers. Anatomically correct sized pupils are imbedded in the front of each "eye," thereby acting as the target for whichever system is under test by the very portable Calibrator. Currently, a simple battery controlled circuit controls the laser modules and other electric requirements with accommodation for additional circuit components if required in the future. Specifically designed for validating the operation of an IR Reflective Differencing Saccadic Eye Movement Measurement System, the Calibrator can also be used with little or no alteration for validation of camera systems and other types of devices.

Calibration↗

PubMed2025

Targeting phagocytosis for amyloid-β clearance: implications of morphology remodeling and microglia activation probed by bifunctional chimaeras.

Amyloid-β (Aβ), a key driver of Alzheimer's disease (AD) pathogenesis, possesses diverse harmful and clearance-resistant structures that present substantial challenges to therapeutic development. Here, we demonstrate that modulating Aβ morphology, rather than Toll-like receptor 2 (TLR2)-dependent microglia activation, is essential for effective phagocytosis of Aβ species by microglia. By developing a bifunctional mechanistic probe (P2CSKn) designed to remodel Aβ and activate TLR2, we show it restructures soluble Aβ (sAβ) and fibrillar Aβ (fAβ) into less toxic hybrid aggregates (hPAβ). Critically, this structural remodeling protects microglia from Aβ toxicity while enabling robust phagocytosis. Moreover, although TLR2 activation mildly enhances Aβ uptake, it concurrently triggers detrimental inflammation that negates its benefits. Our findings establish morphological remodeling as the critical determinant of effective Aβ clearance and suggest a morphology-focused strategy for developing safe therapeutics for Aβ-related diseases.

Microglia↗

PubMedDate not supplied

Development of a totally implantable total artificial heart controller.

Using a one chip microcontroller, 87C196 (One chip EPROM), and an erasable and programmable logic device (EPLD), an implantable control system to drive a pendulum type electromechanical total artificial heart was developed. This control system consists of four parts: a main management system, a motor driver with power regulator, a state monitoring system, and a communication portion. The main system has a speed detector, proportional and integral (PI) control, pulse width modulation (PWM) generation, serial communication, and an analog data processor. Two kinds of power system are used, separated by eight photocoupler arrays to improve system stability. When the performance of each compartment was compared with that of the previously used Z80 microprocessor based control system, good correspondence was shown. Logic power consumption was reduced to one third that of the previous controller. Using mock circulation tests, the overall performance of the control system was evaluated.

Blood Flow Velocity↗

PubMed1995

Whole-cell recordings from visualized C1 adrenergic bulbospinal neurons: ionic mechanisms underlying vasomotor tone.

The membrane properties of visually identified, DiI retrogradely labeled bulbospinal neurons of the C1 adrenergic cell group were studied by whole-cell recordings in brainstem slices from 7- to 10-day-old rats. A post-hoc histochemical analysis allowed us to evaluate the electrophysiological properties of the C1 adrenergic neurons, a group of cells known to project to the sympathetic preganglionic neurons. Two types of cells were labeled: pacemaker and non-pacemaker neurons. In voltage-clamp mode, C1 pacemaker neurons exhibited a TTX-sensitive, persistent inward current that was activated between -55 and -50 mV and reached a peak between -40 and -30 mV. This current was significantly larger in the pacemaker neurons as compared to the non-pacemaker neurons and appeared to be a principal conductance driving the C1 pacemaker activity. Two other conductances modulated the frequency of pacemaker discharge: (1) an anomalous rectifier accelerated pacemaker frequency by three synergistic actions: (a) depolarizing it at rest, (b) increasing the slope of the pacemaker potentials, and (c) limiting hyperpolarizing membrane excursions; and (2) an A-type current which had two opposing actions: (a) slowing it by decreasing the slope of the pacemaker potential, and (b) accelerating it by repolarizing the fast action potential. Persistent sodium current functions as the driver potential responsible for the tonic firing pattern of the C1 bulbospinal neurons providing a cellular mechanism responsible for the descending excitatory drive imposed onto sympathetic preganglionic neurons. Thus, it may explain how C1 neurons may function to maintain vasomotor tone or modulate other autonomic functions. This study is the first attempt to analyze voltage-activated membrane conductances of RVLM neurons of known phenotype and axonal connections.

Action Potentials↗

PubMed2025

Unraveling the Role of Mutations Outside the Basal Promoter and Precore Regions in the HBeAg-Negative Stage of Chronic Hepatitis B.

Hepatitis B e antigen (HBeAg) seroconversion is a crucial event in the natural history of chronic hepatitis B virus (HBV) infection, marked by a significant decrease in viral load and the emergence of mutations that suppress HBeAg expression. However, these mutations alone do not fully account for the reduction in viral load. This study investigated the biological features and pathogenic roles of mutations outside the basal core promoter (BCP) and precore regions during the HBeAg-negative stage of chronic infection. Full-length HBV genomes from HBeAg-positive (n = 180) and HBeAg-negative (n = 328) genotype D datasets were analyzed, revealing significantly higher genomic heterogeneity in HBeAg-negative sequences compared with HBeAg-positive genomes (50.4 ± 16.0 vs. 26.6 ± 10.5 nucleotide changes per genome). Twenty-six hotspot amino acid mutations associated with the HBeAg-negative stage were identified, with over half located in the Core region. Subsequently, full-length HBV genomes from six HBeAg-negative patient-derived serum samples were obtained by PCR amplification followed by Sanger sequencing. Infectious clones generated from these genomes, each carrying between 21 and 66 amino acid substitutions, were characterized, showing that mutations in this stage differentially affected viral fitness in vitro by up- or downregulating HBV-DNA levels (ranging from 0.2 to 5 times those of the wild-type isolate), modulating capsid assembly, and altering the expression, secretion, and subcellular localization of viral proteins. In conclusion, while mutations in the BCP and precore regions are the primary drivers of HBeAg seroconversion, mutations outside these regions significantly influence HBV biology and potentially contribute to viral pathogenicity, underscoring the complex interplay between host and virus during the HBeAg-negative stage of chronic infection.

Humans↗

PubMed2004

Configuration-specific attentional modulation of flanker- -target lateral interactions.

Elements of a contour are often easier to detect when they possess collinearity, with their local orientations matching the global orientation of the contour. We recently reported attentional modulation of such lateral interactions between a central near-threshold target Gabor patch and flanking high-contrast patches (Freeman et al, 2001 Nature Neuroscience 4 1032-1036). Here, we examined whether such attentional effects reflect specific modulation of mechanisms sensitive to collinear configurations, or instead more general modulation of sensitivity to either the global or local orientation-components of the stimulus. Thresholds for detecting a central Gabor target were measured, while observers also judged the Vernier alignment between one pair of flankers and ignored a second flanker pair (when present). Target contrast-thresholds were facilitated only when attending collinear flankers. There was no facilitation when attending flankers that shared only local orientation with the target, or flankers that fell on a global axis aligned with target orientation but having orthogonal local orientation. Ignored collinear flankers had no effect on target thresholds. These results demonstrate strong and specific attentional modulation of contour-integration mechanisms in early vision sensitive to collinear configurations.

Attention↗

PubMed2002

Effect of magnitopuncture on sympathetic and parasympathetic nerve activities in healthy drivers--assessment by power spectrum analysis of heart rate variability.

The object of this study was to assess the effects of magnitopuncture applied to Dazhui (DU14) point and Neiguan (PC6) points on sympathetic and parasympathetic nerve activities by power spectrum analysis of heart rate variability in healthy drivers during simulated driving. Using power spectrum analysis, the low frequency (LF) and high frequency (HF) components of heart rate variability can be calculated reflecting the sympathetic and parasympathetic activity. The 40 healthy male subjects were randomly divided into two groups: A (study group) and B (control group). All subjects were required to be well rested before the experiment. The subjects of both groups were required to perform a simulated driving task for 3 h. During the driving, magnitopunctures were applied to the DU14 and PC6 points for A while the subject performed the task for 2.5 h, and for B magnitopunctures were applied to non-acupuncture points which were 1.5 cm away from the two acupuncture points respectively over the same time. Subjective response to a questionnaire was obtained after the simulated task in the two groups. At the end of the driving task the LF component in normalized units (NU) had decreased significantly ( P<0.05) indicating a reduced sympathetic nerve activity and the HF component (NU) increased significantly ( P<0.05) indicating a increased parasympathetic nerve activity for A compared with pre-stimulation while for B no significant differences were observed. There were significant group differences in LF (NU), HF (NU) and LF:HF at the end of the driving task ( P<0.05). It was concluded that a modulating effect of magnitopuncture on sympathetic and parasympathetic nerve activities in healthy subjects was associated with the acupuncture points. The findings represent physiological evidence that magnitopuncture may reduce mental fatigue in healthy drivers.

Acupuncture↗

PubMed1994

Inhibition of red cell urea flux by anion exchange inhibitors.

When they studied the chemical properties of red cell anion exchange inhibitors such as DIDS (4,4'-diisothiocyanate-2,2'-stilbene disulfonate), Barzilay et al. (1979) Membr. Biochem. 2, 227-254 also examined the benzene sulfonates. These molecules are structurally similar to half a DIDS molecule and are also specific anion exchange inhibitors with ID50 values measured in mM, rather than microM, as for the stilbene disulfonates. We have studied several inhibitors of the benzene sulfonate (BS) class and found that they also inhibit red cell urea flux by up to 92% and stimulate water flux by up to 58%. The values of Kinhib,app for urea flux inhibition are the same as the ID50 values for anion flux inhibition; covalent DIDS completely suppresses the inhibition. These observations strongly suggest that the effect on urea flux is caused by BS binding at the stilbene site. Comparative studies on the short chain amides exclude lipid solubility and solute molar volume as factors that affect these BS actions. Kstim,app for water flux stimulation is also related to the anion exchange ID50 values; covalent DIDS suppresses the water flux stimulation. These observations on urea and water fluxes are consistent with a common driver, located at the stilbene site, which is responsible for the BS actions on urea, water and anion fluxes. The subsequent steps are independent with separate effectors to modulate each of the individual fluxes. These effectors are presumably located in different regions of the protein or proteins and carry out their separate processes by allosteric means.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2026

Decoding spatiotemporal fibrotic and cellular immunosuppression of therapeutic T cells in live pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is profoundly immunosuppressive. To help define this behavior, we present integrated experimental and computational frameworks to elucidate therapeutic T cell dynamics. Through the development of TME-CARTographer (TME-CART), a computational pipeline integrating high-dimensional data, graph theory, behavior analysis, and deep learning (DL), we present quantitative insights on 4D T cell-TME interactions in live PDA tumors. Mapping physical immunosuppression demonstrates that collagen fiber architectures direct migration while concomitantly limiting off-axis movement, creating immune exclusion zones. Expanding these findings, we establish that the collagen matrix harbors and spatially organizes immunosuppressive myeloid cells to serve as cooperative co-modulators of T cell behaviors, including migration, sampling, repulsion, and sequestration. Consistent with these findings, DL defines both linear and nonlinear collagen matrix and cellular neighborhood interactions as drivers of T cell behavior. The TME-CART DL framework also accurately predicts shifts in immunosuppression following depletion of myeloid cells. Overall, we identify synergistic barriers impeding anti-tumor T cell behaviors and present TME-CART as a discovery platform for interpreting complex 4D data to enhance the understanding and design of immunotherapies.

Journal Article↗

PubMed2005

Action modulates object-based selection.

Cueing attention to one part of an object can facilitate discrimination in another part (Experiment 1 [Duncan, J. (1984). Selective attention and the organization of visual information. Journal of Experimental Psychology: General, 113, 501-517]; [Egly, R., Driver, J., & Rafal, R. D. (1994). Shifting visual attention between objects and locations: evidence from normal and parietal lesion subjects. Journal of Experimental Psychology: Human Perception and Performance, 123, 161-177]). We show that this object-based mediation of attention is disrupted when a pointing movement is prepared to the cued part; when a pointing response is prepared to a part of an object, discrimination does not differ between (i) stimuli at locations in the same object but distant to the part where the pointing movement is programmed and (ii) stimuli at locations equidistant from the movement but outside the object (Experiment 2). This remains true even when the pointing movement cannot be performed without first coding the whole object (Experiment 3). Our results indicate that pointing either (i) emphasizes spatial selection at the expense of object-based selection, or (ii) changes the nature of the representation(s) mediating perceptual selection. In addition, the results indicate that there can be a distinct effect on attention of movement to a specific location, separate from the top-down cueing of attention to another position (Experiment 3). Our data highlight the interactivity between perception and action.

Adolescent↗

PubMed2026

CMAtlas: a comprehensive DNA methylation atlas for exploring epigenetic alterations in 34 human cancer types.

MOTIVATION: Aberrant DNA methylation is a fundamental epigenetic hallmark of cancer. However, existing resources often lack technological diversity and comprehensive cancer coverage. Furthermore, most platforms fail to achieve deep multi-omics integration and tend to ignore cancer-type-specific methylation features, limiting their utility in precision oncology and drug discovery. RESULTS: We developed Cancer Methylation Atlas (CMAtlas), a comprehensive platform integrating 13 753 samples across 34 cancer types. By applying technology-tailored pipelines to data from various profiling technologies, we identified 830 725 tumor-specific differentially methylated elements (DMEs) and 1 480 098 differentially methylated regions (DMRs), alongside 1 154 256 cancer-type-specific DMEs and 329 154 DMRs. The platform demonstrates high cross-platform consistency and strong concordance between tumor tissues and cell lines, ensuring the robustness of our findings. All DMEs and DMRs are annotated with multi-omics data (RNA expression, somatic mutations, and chromatin accessibility) and clinical relevance (survival associations and cell-free DNA profiling). We further demonstrate the utility of CMAtlas by identifying prognostic aberrant methylation in colorectal cancer driver genes. AVAILABILITY AND IMPLEMENTATION: CMAtlas is freely accessible at {{https://cmatlas.renlab.cn/}}. The platform offers an intuitive web interface supporting gene-centric and cancer-centric queries, alongside customizable analysis modules designed to facilitate user-specific research needs.

Humans↗