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At least 487 records · Page 27Linked to original sources
PubMed1989

Lever pressing for food reward and in vivo voltammetry: evidence for increases in extracellular homovanillic acid, the dopamine metabolite, and uric acid in the rat caudate nucleus.

Linear sweep voltammetry at chronically implanted carbon paste electrodes was used to study extracellular levels of homovanillic acid, a metabolite of dopamine, in the caudate nucleus of freely moving rats. Local infusion of homovanillic acid close to the electrode confirmed that peak 3, at about 550 mV, could be used for this purpose. Thirty minutes of lever pressing for food reward was followed by an increase in homovanillic acid, maximal about 30 min later (+42%). An earlier and larger (+51%) increase in peak 2 (350-400 mV) was seen, highly correlated (r = 0.98) with the rate of lever pressing across individuals. A smaller decrease (-23%) in peak 1 (200 mV; ascorbic acid) was seen 75 min after the behavioural session. Administration of allopurinol, an inhibitor of uric acid production, selectively abolished peak 2. Allopurinol prior to lever pressing reduced the increase in peak 2 very substantially (by 77%), confirming that this too was mainly due to uric acid. These results indicate that linear sweep voltammetry can be used to study the time course of changes in dopamine metabolism, and in other neurochemicals, in individual freely moving rats in relation to behaviour under experimental control. More specifically, they demonstrate directly that rewarded lever pressing increases dopamine metabolism in the caudate, which had previously only been inferred from indirect approaches. The level of uric acid is also increased, and it is suggested that this may serve as an index of metabolic activity.

Allopurinol↗
PubMed1999

Prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) in cytosols and pellet extracts derived from 892 breast cancer patients.

To evaluate the clinical relevance of urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) measured by a recently developed enzyme-linked immunosorbent assay (ELISA), we analysed both components in samples derived from 892 patients with primary breast cancer (median follow-up 99 months). The assays were performed in cytosolic extracts as well as in corresponding detergent extracts of pellets obtained after ultracentrifugation, which was carried out when preparing the cytosolic fractions for routine steroid hormone receptor determination. Statistically significant correlations were found between the cytosolic levels and those determined in the pellet extracts (Spearman correlation coefficient r = 0.60, P < 0.0001 for uPA and r = 0.65, P < 0.0001 for PAI-1). Furthermore, strong correlations were found between the levels of both uPA (r = 0.85, P < 0.0001) and PAI-1 (r = 0.90, P< 0.0001) in the cytosols and their levels previously measured with ELISAs based on commercial reagents. In both Cox univariate and multivariate analysis, high cytosolic levels of uPA or PAI-1 were significantly associated with increased rates of relapse and death. The levels of uPA and PAI-1 in the pellet extracts also provided prognostic information, although to a lesser extent compared with the cytosolic extracts. The prediction of prognosis on the basis of uPA and PAI-1 assessed by an alternative ELISA once again emphasizes the established prognostic role and usefulness of these parameters in selection of breast cancer patients at high or low risk of recurrence.

Adult↗
PubMed2005

[Electrochemical reduction of nitrobenzene under mild conditions].

Effect of cathode materials (S1, S2, AB5, graphite, Ni plate, Fe plate) on the electrochemical reduction of nitrobenzene of light concentration under mild conditions(current density less than 1.0 mA/cm2, pH in the range of 4 - 9), was experimentally studied. In aqueous solution, S1, S2 and AB5 electrodes showed high selectivity of nitrobenzene reduction to aniline, with the nitrobenzene conversion and aniline yield being over 85% and 75%, respectively. The results obtained by cyclic voltammograms and single sweep voltammograms showed that nitrobenzene was directly reduced at S1 and S2 electrodes, while reduced by hydrogen at AB5 electrode. The products electroreduced from nitrobenzene on S1, S2 and AB5 cathodes could be easily degraded by aniline degrading strain AN3 under aerobic condition.

Electrochemistry↗
PubMed1994

ARX filtering of single-sweep movement-related brain macropotentials in mono- and multi-channel recordings.

A technique of stochastic parametric identification and filtering is applied to the analysis of single-sweep event-related potentials. This procedure, called AutoRegressive with n eXogenous inputs (ARXn), models the recorded signal as the sum of n+1 signals: the background EEG activity, modeled as an autoregressive process driven by white noise, and n signals, one of which represents a filtered version of a reference signal carrying the average information contained in each sweep. The other (n-1) signals could represent various sources of noise (i.e., artifacts, EOG, etc.). An evaluation of the effects of both artifact suppression and accurate selection of the average signal on mono- or multi-channel scalp recordings is presented.

Brain Mapping↗
PubMed1992

Spectral selectivity of FM-FM neurons in the auditory cortex of the echolocating bat, Myotis lucifugus.

1. Spectral sensitivity was examined in delay-sensitive neurons in the auditory cortex of the awake FM bat, Myotis lucifugus. FM stimuli sweeping 60 kHz downward in 4 ms were used as simulated pulse-echo pairs to measure delay-dependent responses. At each neuron's best delay, the pulse and/or echo were divided into 4 FM quarters (Ist, IInd, IIIrd, and IVth), each sweeping 15 kHz in 1 ms, and quarters essential for delay sensitivity were determined for both pulse and echo. 2. For the pulse, the IVth quarter was essential for delay sensitivity in the majority of neurons. For the echo, the essential quarter for most neurons was the IInd, IIIrd, or IVth. 3. Different quarters of the pulse and echo were essential for delay sensitivity in 68% of the neurons examined. 4. This study provides neurophysiological evidence linking both spectral and temporal processing in delay-sensitive neurons of Myotis. Since spectral cues can provide target-shape information, sensitivity to both spectral and temporal parameters in single neurons may endow these neurons in FM bats with the potential for target analysis other than echo-ranging.

Acoustic Stimulation↗
PubMed2006

Classification of intramural metastases and lymph node metastases of esophageal cancer from gene expression based on boosting and projective adaptive resonance theory.

Esophageal cancer is a well-known cancer with poorer prognosis than other cancers. An optimal and individualized treatment protocol based on accurate diagnosis is urgently needed to improve the treatment of cancer patients. For this purpose, it is important to develop a sophisticated algorithm that can manage a large amount of data, such as gene expression data from DNA microarrays, for optimal and individualized diagnosis. Marker gene selection is essential in the analysis of gene expression data. We have already developed a combination method of the use of the projective adaptive resonance theory and that of a boosted fuzzy classifier with the SWEEP operator denoted PART-BFCS. This method is superior to other methods, and has four features, namely fast calculation, accurate prediction, reliable prediction, and rule extraction. In this study, we applied this method to analyze microarray data obtained from esophageal cancer patients. A combination method of PART-BFCS and the U-test was also investigated. It was necessary to use a specific type of BFCS, namely, BFCS-1,2, because the esophageal cancer data were very complexity. PART-BFCS and PART-BFCS with the U-test models showed higher performances than two conventional methods, namely, k-nearest neighbor (kNN) and weighted voting (WV). The genes including CDK6 could be found by our methods and excellent IF-THEN rules could be extracted. The genes selected in this study have a high potential as new diagnosis markers for esophageal cancer. These results indicate that the new methods can be used in marker gene selection for the diagnosis of cancer patients.

Algorithms↗
PubMed1992

Monosynaptic EPSPs elicited by single interneurones and spindle afferents in trigeminal motoneurones of anaesthetized rats.

1. Our aim has been to quantify the monosynaptic connections of trigeminal interneurones and spindle afferents onto jaw-elevator motoneurones as a step towards identifying common features in organization of monosynaptic inputs onto motoneurones. We have used the intracellular variant of the spike-triggered averaging method to examine the connections of single identified trigeminal interneurones and jaw-elevator muscle spindle afferents onto single jaw-elevator motoneurones. The interneurones examined lay in the region immediately caudal to the trigeminal motor nucleus. The experiments were performed on rats anaesthetized with pentobarbitone, paralysed and artificially ventilated. 2. Ten EPSPs and eight IPSPs were obtained from examining the connections of seventeen interneurones to thirty-six motoneurones, suggesting a functional connectivity of 50% for individual interneurones onto elevator motoneurones. Fourteen EPSPs were obtained from examining the connections of thirteen spindle afferents onto twenty-seven motoneurones, giving a functional connectivity of 52% for individual spindle afferents onto elevator motoneurones. The amplitudes of the EPSPs elicited by interneurones ranged from 7-48 microV (mean = 17, S.D. = 12.5, n = 10) and from 7 to 289 microV (mean = 64, S.D. = 76.0, n = 14) for the spindle-mediated EPSPs; the difference in the two means was not significant (P = 0.07). 3. However, the amplitude of averaged responses obtained by signal averaging methods are dependent on the assumption that the postsynaptic response occurs following every impulse in the presynaptic neurone. We therefore estimated the percentage of sweeps which contained EPSPs triggered by the presynaptic neurone under study. In essence the method used consisted of visual inspection of the individual sweeps comprising an average in order to assess the occurrence of EPSPs within six separate time windows, each of duration +/- 0.3 ms. Five windows were placed at randomly selected times on average and were used to provide an estimate of the frequency of occurrence of randomly triggered EPSPs. The sixth window was centred on the start of the averaged EPSP and the frequency of occurrence of randomly triggered EPSPs was subtracted from the frequency of occurrence of EPSPs in this window to produce an estimate of the incidence of EPSPs triggered by the presynaptic neurone under study. 4. Values of the incidence of occurrence of EPSPs triggered by the presynaptic neurones ranged from 4.3 to 92% for the fifteen averaged EPSPs which could be analysed in this manner (two elicited by interneurones and thirteen by spindle afferents).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

Beneficial mutations, hitchhiking and the evolution of mutation rates in sexual populations.

Natural selection acts in three ways on heritable variation for mutation rates. A modifier allele that increases the mutation rate is (i) disfavored due to association with deleterious mutations, but is also favored due to (ii) association with beneficial mutations and (iii) the reduced costs of lower fidelity replication. When a unique beneficial mutation arises and sweeps to fixation, genetic hitchhiking may cause a substantial change in the frequency of a modifier of mutation rate. In previous studies of the evolution of mutation rates in sexual populations, this effect has been underestimated. This article models the long-term effect of a series of such hitchhiking events and determines the resulting strength of indirect selection on the modifier. This is compared to the indirect selection due to deleterious mutations, when both types of mutations are randomly scattered over a given genetic map. Relative to an asexual population, increased levels of recombination reduce the effects of beneficial mutations more rapidly than those of deleterious mutations. However, the role of beneficial mutations in determining the evolutionarily stable mutation rate may still be significant if the function describing the cost of high-fidelity replication has a shallow gradient.

Alleles↗
PubMed1998

Laser desorption fast gas chromatography-mass spectrometry in supersonic molecular beams.

A novel method for fast analysis is presented. It is based on laser desorption injection followed by fast gas chromatography-mass spectrometry (GC-MS) in supersonic molecular beams. The sample was placed in an open air or purged laser desorption compartment, held at atmospheric pressure and near room temperature conditions. Desorption was performed with a XeCl Excimer pulsed laser with pulse energy of typically 3 mJ on the surface. About 20 pulses at 50 Hz were applied for sample injection, resulting in about 0.4 s injection time and one or a few micrograms sample vapor or small particles. The laser desorbed sample was further thermally vaporized at a heated frit glass filter located at the fast GC inlet. Ultrafast GC separation and quantification was achieved with a 50-cm-long megabore column operated with a high carrier gas flow rate of up to 240 mL/min. The high carrier gas flow rate provided effective and efficient entrainment of the laser desorbed species in the sweeping gas. Following the fast GC separation, the sample was analyzed by mass spectrometry in supersonic molecular beams. Both electron ionization and hyperthermal surface ionization were employed for enhanced selectivity and sensitivity. Typical laser desorption analysis time was under 10 s. The laser desorption fast GC-MS was studied and demonstrated with the following sample/matrices combinations, all without sample preparation or extraction: (a) traces of dioctylphthalate plasticizer oil on stainless steel surface and the efficiency of its cleaning; (b) the detection of methylparathion and aldicarb pesticides on orange leaves; (c) water surface analysis for the presence of methylparathion pesticide; (d) caffeine analysis in regular and decaffeinated coffee powder; (e) paracetamol and codeine drug analysis in pain relieving drug tablets; (f) caffeine trace analysis in raw urine; (g) blood analysis for the presence of 1 ppm lidocaine drug. The features and advantages of the laser desorption fast GC-MS are demonstrated and discussed.

Caffeine↗
PubMed2002

Enrichment and elimination of mutY mutators in Escherichia coli populations.

The kinetics of mutator sweeps was followed in two independent populations of Escherichia coli grown for up to 350 generations in glucose-limited continuous culture. A rapid elevation of mutation rates was observed in both populations within 120-150 generations, as was apparent from major increases in the proportion of the populations with unselected mutations in fhuA. The increase in mutation rates was due to sweeps by mutY mutators. In both cultures, the enrichment of mutators resulted from hitchhiking with identified beneficial mutations increasing fitness under glucose limitation; mutY hitchhiked with mgl mutations in one culture and ptsG in the other. In both cases, mutators were enriched to constitute close to 100% of the population before a periodic selection event reduced the frequency of unselected mutations and mutators in the cultures. The high proportion of mutators persisted for 150 generations in one population but began to be eliminated within 50 generations in the other. The persistence of mutator, as well as experimental data showing that mutY bacteria were as fit as near-isogenic mutY(+) bacteria in competition experiments, suggest that mutator load by deleterious mutations did not explain the rapidly diminishing proportion of mutators in the populations. The nonmutators sweeping out mutators were also unlikely to have arisen by reversion or antimutator mutations; the mutY mutations were major deletions in each case and the bacteria sweeping out mutators contained intact mutY. By following mgl allele frequencies in one population, we discovered that mutators were outcompeted by bacteria that had rare mgl mutations previously as well as additional beneficial mutation(s). The pattern of appearance of mutY, but not its elimination, conforms to current models of mutator sweeps in bacterial populations. A mutator with a narrow mutational spectrum like mutY may be lost if the requirement for beneficial mutations is for changes other than GC --> TA transversions. Alternatively, epistatic interactions between mutator mutation and beneficial mutations need to be postulated to explain mutator elimination.

DNA Glycosylases↗
PubMed2003

Cyclin-E is a strong predictor of endocrine therapy failure in human breast cancer.

Recently, cyclin-E was reported to be the most prominent prognostic factor for breast cancer outcome described so far, even surpassing axillary nodal involvement. Earlier studies on the prognostic value of cyclin-E in breast cancer, however, yielded heterogeneous results. Therefore, we set out to confirm and extend these results by quantitative Taqman RT-PCR of cyclin-E levels in 277 resectable breast cancers. Cyclin-E levels were not associated with relapse-free survival (RFS) or overall survival (OS) in the total cohort of patients, or in the subset of patients without involved lymph nodes that were not treated with adjuvant systemic therapy. Besides several classical clinicopathological factors, the interaction between cyclin-E and adjuvant endocrine therapy (P=0.01, HR=3.04, 95% CI: 1.30-7.09) was found to contribute significantly in multivariate analyses. Cyclin-E levels were associated with poor RFS specifically in patients treated with adjuvant endocrine therapy (n=108, P=0.001, HR=4.01, 95% CI: 1.76-9.12), independent of estrogen receptor status. In conclusion, cyclin-E is not a pure prognostic factor in breast cancer, but rather a predictor of failure of endocrine therapy. Differences in literature on the presumed prognostic value of cyclin-E may be due to differences in treatment. Assessment of cyclin-E levels can aid in improving adjuvant treatment selection.

Adult↗
PubMed2004

One-way calcium spill-over during signal transduction in Paramecium cells: from the cell cortex into cilia, but not in the reverse direction.

We asked to what extent Ca(2+) signals in two different domains of Paramecium cells remain separated during different stimulations. Wild-type (7S) and pawn cells (strain d4-500r, without ciliary voltage-dependent Ca(2+)-channels) were stimulated for trichocyst exocytosis within 80 ms by quenched-flow preparation and analysed by energy-dispersive X-ray microanalysis (EDX), paralleled by fast confocal fluorochrome analysis. We also analysed depolarisation-dependent calcium signalling during ciliary beat rerversal, also by EDX, after 80-ms stimulation in the quenched-flow mode. EDX and fluorochrome analysis enable to register total and free intracellular calcium concentrations, [Ca] and [Ca(2+)], respectively. After exocytosis stimulation we find by both methods that the calcium signal sweeps into the basis of cilia, not only in 7S but also in pawn cells which then also perform ciliary reversal. After depolarisation we see an increase of [Ca] along cilia selectively in 7S, but not in pawn cells. Opposite to exocytosis stimulation, during depolarisation no calcium spill-over into the nearby cytosol and no exocytosis occurs. In sum, we conclude that cilia must contain a very potent Ca(2+) buffering system and that ciliary reversal induction, much more than exocytosis stimulation, involves strict microdomain regulation of Ca(2+) signals.

Animals↗
PubMed1993

Role of integrins and other cell adhesion molecules in tumor progression and metastasis.

Despite rapid advances in our understanding of the biology of cell adhesion, the data available in the literature make it is difficult to propose one simple scheme in which cell adhesion molecules can be related to tumor growth and metastasis. This difficulty can be related to a number of factors. Some of the apparently conflicting experimental results that demonstrate both enhanced or diminished tumor cell adhesion during tumor progression may be attributed to the experimental systems used. Those studies that have injected tumor cells intravenously have, in general, shown that enhanced tumor cell adhesiveness correlates with metastatic ability. It should be recognized that this experimental approach bypasses many of the early stages of the metastatic cascade and is biased towards tumor cells with an enhanced ability to form aggregates with cells in the circulation and to adhere to distant vascular sites. On the other hand, studies that have implanted tumors into animals and allowed them to grow and metastasize (spontaneous metastasis) have generally demonstrated an inverse relationship between adhesive ability and the ability to metastasize. Another major obstacle in understanding the role of CAMs in metastasis is the well known problem of tumor heterogeneity and the phenotypic instability of metastatic cells over relatively short periods of time (141). The cells that make up a metastatic focus may thus be quite different from the tumor cells that originally formed the lesion. It is quite possible that the selective pressures that initially enable a cancer cell to form a metastatic lesion may be quite different than those that later favor rapid tissue growth. The major obstacle in making any sweeping generalizations about cell adhesion molecules and tumor progression, however, is that the process of successful metastasis is inherently complex, requiring tumor cells to possess decreased adhesive interactions with surrounding cells and extracellular matrix at some points in the cascade and increased adhesive interactions at other times. Based on the information available, the following scenario can be proposed. Using the schema shown in Figure 1, successful metastasis initially requires that normal cell-cell and cell-substratum adhesion be disrupted, causing release of neoplastic cells from the primary tumor (step 1). For epithelial tumors, down-regulation of cadherins and perhaps, integrins, appear to be involved. This loss of cell adhesion must be followed by migration of tumor cells into the vascular system (step 2), a step requiring efficient cell-substratum interactions. In melanomas, this step seems to require expression of the vitronectin receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1977

[External recording of His bundle electrical activity (author's transl)].

A noninvasive method to record His' potentials in man is described. In several patients who needed intracardiac recording, a bipolar lead was placed across the chest, directed as conveniently as possible for the recording of His bundle electrical activity. A signal filtered (70-300 Hz) and amplified (X 100.000), was processed by a multichannel analyzer for averaging. The temporal regime of the averager was determined by a trigger which established a fiducial point on the ECG. For this purpose a QRS detector fed to a normal peripheral bipolar lead was used. The temporal stability of the system was continually checked in order to reject the recordings over the limits of +/- 1 msec. The computer program was chosen in order to select a window (usually 200 msec) which occurred up to 150 msec prior and 50 msec after the trigger signal. The sampling rate was 5 KHz for 1024 samples and the sweep counts were fixed from 128 to 512. At the same time, the D1, D2 and D3 were recorded in the other three channels of the analyzer for a more accurate measurement of the HV interval. Then an example comparing the external and interval recording was presented. Finally several external recordings were measured and the exact reproducibility of the G wave was confirmed. In conclusion we can say that the G wave is significant and suggests the electrical activity of the bundle of His.

Bundle of His↗
PubMed2004

Decreased diversity but increased substitution rate in host mtDNA as a consequence of Wolbachia endosymbiont infection.

A substantial fraction of insects and other terrestrial arthropods are infected with parasitic, maternally transmitted endosymbiotic bacteria that manipulate host reproduction. In addition to imposing direct selection on the host to resist these effects, endosymbionts may also have indirect effects on the evolution of the mtDNA with which they are cotransmitted. Patterns of mtDNA diversity and evolution were examined in Drosophila recens, which is infected with the endosymbiont Wolbachia, and its uninfected sister species D. subquinaria. The level of mitochondrial, but not nuclear, DNA diversity is much lower in D. recens than in D. subquinaria, consistent with the hypothesized diversity-purging effects of an evolutionarily recent Wolbachia sweep. The d(N)/d(S) ratio in mtDNA is significantly greater in D. recens, suggesting that Muller's ratchet has brought about an increased rate of substitution of slightly deleterious mutations. The data also reveal elevated rates of synonymous substitutions in D. recens, suggesting that these sites may experience weak selection. These findings show that maternally transmitted endosymbionts can severely depress levels of mtDNA diversity within an infected host species, while accelerating the rate of divergence among mtDNA lineages in different species.

Animals↗
PubMed2003

Separation of structurally related synthetic peptides by capillary zone electrophoresis.

The separation of two different sets of synthetic peptides has been investigated by high-performance capillary zone electrophoresis utilising naked, fused silica capillaries. The effects of electrolyte pH, buffer concentration, capillary length and electric field strength on the separation efficiency and selectivity were systematically varied, with the highest resolution achieved with buffer electrolytes of low pH and relatively high ionic strength. Under optimised separation conditions utilising the "short end injection" separation approach with negative electric field polarity, a series of eight structurally-related synthetic peptides were baseline resolved within 4 min without addition of any modifier of the background electrolyte with separation efficiencies in the vicinity of 600000 theoretical plates/m. Further significant enhancement of separation efficiencies could be achieved by taking advantage of the "long end injection" approach with positive electric field polarity. The outcome of these experimental variations parallels the "sweeping" effect that has been observed in the capillary electrochromatographic and micellar electrokinetic separations of polar molecules and permits rapid resolution of peptides with focusing effects. In addition, small changes in the electrolyte buffer pH and concentration were found to have a significant impact on the selectivity of synthetic peptides of similar intrinsic charge. These observations indicate that multi-modal separation mechanisms operated under these conditions with the unmodified fused silica capillaries. This study, moreover, documents additional examples of peptide-specific multi-zoning behaviour in the high-performance capillary zone electrophoretic separation of synthetic peptides.

Buffers↗
PubMed1980

An improved selected ion recording system for precise isotope ratio determination.

An improved analog four-channel selected ion recording system is described, in which major modifications permit a decrease in the dwell time to 33 ms per channel, thus minimizing the mass cycling error. Synchronization with a sinusoidal sweep voltage superimposed on the normal accelerating voltage (8 kV) enables two channels to be monitored simultaneously in real time and each mass to be recorded continuously. These improvements allow measurement of ion current ratios with a precision of 0.2% over a wide dynamic range, permitting accurate determination of isotopic enrichment in biomedical assays even when this enrichment is derived from a single label. Use of the system is illustrated by the analysis of palmitate turnover in dogs (using [1--13C] palmitic acid) with an average standard deviation corresponding to the detection of 0.04% excess of [1--13C] palmitate.

Animals↗
PubMed1981

Time and Frequency domain processing in the inferior colliculus of echolocating bats.

Tone bursts and frequency-modulated (FM) signals were presented to Mexican free-tailed bats and tuning curves, discharge patterns, and discharge latencies of single units in the inferior colliculus were recorded. Cells were broadly tuned to tone bursts, with most Q 10 values ranging from 3 to 20. However, in response to FM stimulation the discharges of neurons were closely synchronized to the time of occurrence of restricted frequency components within the FM sweep. These excitatory frequencies (EFs) were generally unaffected by changes in the starting frequency or intensity of the stimulus. Thus, in response to FM signals, the cells exhibited a much greater frequency selectivity than that observed following tone burst stimulation. Across the population of neurons sampled, EFs covering a wide frequency range were found, and the different EFs were represented in a systematic fashion within the colliculus. The frequencies in an FM biosonar signal or echo will thus be neurally represented both by the time of occurrence of neuronal discharges and by the location of the discharging cells within the nucleus. The potential role of this dual frequency coding in spectral and temporal processing of biosonar signals and echoes is discussed, with emphasis on the neural coding of target range.

Acoustic Stimulation↗