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1.
J Biol Chem ; 298(6): 102009, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35525275

RESUMEN

G protein-sensitive inwardly rectifying potassium (GIRK) channels are important pharmaceutical targets for neuronal, cardiac, and endocrine diseases. Although a number of GIRK channel modulators have been discovered in recent years, most lack selectivity. GIRK channels function as either homomeric (i.e., GIRK2 and GIRK4) or heteromeric (e.g., GIRK1/2, GIRK1/4, and GIRK2/3) tetramers. Activators, such as ML297, ivermectin, and GAT1508, have been shown to activate heteromeric GIRK1/2 channels better than GIRK1/4 channels with varying degrees of selectivity but not homomeric GIRK2 and GIRK4 channels. In addition, VU0529331 was discovered as the first homomeric GIRK channel activator, but it shows weak selectivity for GIRK2 over GIRK4 (or G4) homomeric channels. Here, we report the first highly selective small-molecule activator targeting GIRK4 homomeric channels, 3hi2one-G4 (3-[2-(3,4-dimethoxyphenyl)-2-oxoethyl]-3-hydroxy-1-(1-naphthylmethyl)-1,3-dihydro-2H-indol-2-one). We show that 3hi2one-G4 does not activate GIRK2, GIRK1/2, or GIRK1/4 channels. Using molecular modeling, mutagenesis, and electrophysiology, we analyzed the binding site of 3hi2one-G4 formed by the transmembrane 1, transmembrane 2, and slide helix regions of the GIRK4 channel, near the phosphatidylinositol-4,5-bisphosphate binding site, and show that it causes channel activation by strengthening channel-phosphatidylinositol-4,5-bisphosphate interactions. We also identify slide helix residue L77 in GIRK4, corresponding to residue I82 in GIRK2, as a major determinant of isoform-specific selectivity. We propose that 3hi2one-G4 could serve as a useful pharmaceutical probe in studying GIRK4 channel function and may also be pursued in drug optimization studies to tackle GIRK4-related diseases such as primary aldosteronism and late-onset obesity.


Asunto(s)
Canales de Potasio Rectificados Internamente Asociados a la Proteína G , Indoles , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/agonistas , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/metabolismo , Humanos , Indoles/farmacología , Modelos Moleculares , Fosfatidilinositol 4,5-Difosfato/metabolismo
2.
Sensors (Basel) ; 23(6)2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36992051

RESUMEN

In the field of vision-based robot grasping, effectively leveraging RGB and depth information to accurately determine the position and pose of a target is a critical issue. To address this challenge, we proposed a tri-stream cross-modal fusion architecture for 2-DoF visual grasp detection. This architecture facilitates the interaction of RGB and depth bilateral information and was designed to efficiently aggregate multiscale information. Our novel modal interaction module (MIM) with a spatial-wise cross-attention algorithm adaptively captures cross-modal feature information. Meanwhile, the channel interaction modules (CIM) further enhance the aggregation of different modal streams. In addition, we efficiently aggregated global multiscale information through a hierarchical structure with skipping connections. To evaluate the performance of our proposed method, we conducted validation experiments on standard public datasets and real robot grasping experiments. We achieved image-wise detection accuracy of 99.4% and 96.7% on Cornell and Jacquard datasets, respectively. The object-wise detection accuracy reached 97.8% and 94.6% on the same datasets. Furthermore, physical experiments using the 6-DoF Elite robot demonstrated a success rate of 94.5%. These experiments highlight the superior accuracy of our proposed method.

3.
Plant J ; 102(4): 649-665, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32128922

RESUMEN

The plant Shaker K+ channel AtAKT2 has been identified as a weakly rectifying channel that can stabilize membrane potentials to promote photoassimilate phloem loading and translocation. Thus, studies on functional characterization and regulatory mechanisms of AtAKT2-like channels in crops are highly important for improving crop production. Here, we identified the rice OsAKT2 as the ortholog of Arabidopsis AtAKT2, which is primarily expressed in the shoot phloem and localized at the plasma membrane. Using an electrophysiological assay, we found that OsAKT2 operated as a weakly rectifying K+ channel, preventing H+ /sucrose-symport-induced membrane depolarization. Three critical amino acid residues (K193, N206, and S326) are essential to the phosphorylation-mediated gating change of OsAKT2, consistent with the roles of the corresponding sites in AtAKT2. Disruption of OsAKT2 results in delayed growth of rice seedlings under short-day conditions. Interestingly, the lipid second messenger phosphatidic acid (PA) inhibits OsAKT2-mediated currents (both instantaneous and time-dependent components). Lipid dot-blot assay and liposome-protein binding analysis revealed that PA directly bound with two adjacent arginine residues in the ANK domain of OsAKT2, which is essential to PA-mediated inhibition of OsAKT2. Electrophysiological and phenotypic analyses also showed the PA-mediated inhibition of AtAKT2 and the negative correlation between intrinsic PA level and Arabidopsis growth, suggesting that PA may inhibit AKT2 function to affect plant growth and development. Our results functionally characterize the Shaker K+ channel OsAKT2 and reveal a direct link between phospholipid signaling and plant K+ channel modulation.


Asunto(s)
Arabidopsis/genética , Oryza/genética , Ácidos Fosfatidicos/metabolismo , Canales de Potasio/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Membrana Celular/metabolismo , Oryza/metabolismo , Canales de Potasio/genética , Plantones/genética , Plantones/metabolismo
4.
Lasers Surg Med ; 53(7): 986-997, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33476051

RESUMEN

BACKGROUND AND OBJECTIVES: The number of perceptually independent channels to encode acoustic information is limited in contemporary cochlear implants (CIs) because of the current spread in the tissue. It has been suggested that neighboring electrodes have to be separated in humans by a distance of more than 2 mm to eliminate significant overlap of the electric current fields and subsequent interaction between the channels. It has also been argued that an increase in the number of independent channels could improve CI user performance in challenging listening environments, such as speech in noise, tonal languages, or music perception. Optical stimulation has been suggested as an alternative modality for neural stimulation because it is spatially selective. This study reports the results of experiments designed to quantify the interaction between neighboring optical sources in the cochlea during stimulation with infrared radiation. STUDY DESIGN/MATERIALS AND METHODS: In seven adult albino guinea pigs, a forward masking method was used to quantify the interaction between two neighboring optical sources during stimulation. Two optical fibers were placed through cochleostomies into the scala tympani of the basal cochlear turn. The radiation beams were directed towards different neuron populations along the spiral ganglion. Optically evoked compound action potentials were recorded for different radiant energies and distances between the optical fibers. The outcome measure was the radiant energy of a masker pulse delivered 3 milliseconds before a probe pulse to reduce the response evoked by the probe pulse by 3 dB. Results were compared for different distances between the fibers placed along the cochlea. RESULTS: The energy required to reduce the probe's response by 3 dB increased by 20.4 dB/mm and by 26.0 dB/octave. The inhibition was symmetrical for the masker placed basal to the probe (base-to-apex) and the masker placed apical to the probe (apex-to-base). CONCLUSION: The interaction between neighboring optical sources during infrared laser stimulation is less than the interaction between neighboring electrical contacts during electrical stimulation. Previously published data for electrical stimulation reported an average current spread in human and cat cochleae of 2.8 dB/mm. With the increased number of independent channels for optical stimulation, it is anticipated that speech and music performance will improve. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.


Asunto(s)
Cóclea , Implantes Cocleares , Animales , Estimulación Eléctrica , Cobayas , Rayos Infrarrojos , Fibras Ópticas
5.
Eur Arch Otorhinolaryngol ; 278(6): 1815-1820, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32767167

RESUMEN

PURPOSE: To assess whether there is an interference of the spread of excitation (SOE) on speech recognition. METHODS: Retrospective cross-sectional study, approved by the institution's ethics committee (CAAE03409212.8.0000.0068). Adult patients with intraoperative neural response telemetry (NRT) performed on electrodes 6, 11 and 16 implanted with Cochlear Ltd (Sydney, Australia) devices were selected. Patients with partial array insertion, pre-lingual hearing loss, deafness etiology due to and CI experience less than 12 months were excluded. SOE was recorded at 10 current units above the NRT threshold (tNRT) and its width in millimeters was collected at point 0.75 of the function. Speech recognition test was 25-recorded monosyllables list, presented at 65 dBHL at 0° azimuth in a sound treated booth. The analysis was divided into groups by electrode array type, regarding the tNRT, SOE width, SOE's peak amplitude and electrode peak. RESULTS: A 126 SOE measurements of the 3 tested electrodes were obtained from 43 patients. Patients with straight array had significantly wider SOE, greater peak amplitude at electrode 6 and higher tNRTs. In the perimodiolar array, there was a negative correlation between SOE and monosyllables recognition at electrodes 6 and 11, and in the combined average of the three electrodes, with a significant difference in electrode 11. Sixty-six percent of the SOE measurements had their peak shifted to adjacent electrodes. CONCLUSION: It was observed, in perimodiolar array, the greater the dispersion of electrical current, the worse the speech recognition, especially in the medial electrode.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Sordera , Percepción del Habla , Adulto , Australia , Estudios Transversales , Sordera/cirugía , Electrodos Implantados , Humanos , Estudios Retrospectivos
6.
Sensors (Basel) ; 21(5)2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33800438

RESUMEN

Aiming at the high cost of data labeling and ignoring the internal relevance of features in existing trademark retrieval methods, this paper proposes an unsupervised trademark retrieval method based on attention mechanism. In the proposed method, the instance discrimination framework is adopted and a lightweight attention mechanism is introduced to allocate a more reasonable learning weight to key features. With an unsupervised way, this proposed method can obtain good feature representation of trademarks and improve the performance of trademark retrieval. Extensive comparative experiments on the METU trademark dataset are conducted. The experimental results show that the proposed method is significantly better than traditional trademark retrieval methods and most existing supervised learning methods. The proposed method obtained a smaller value of NAR (Normalized Average Rank) at 0.051, which verifies the effectiveness of the proposed method in trademark retrieval.

7.
Entropy (Basel) ; 23(7)2021 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-34356451

RESUMEN

A robust vehicle speed measurement system based on feature information fusion for vehicle multi-characteristic detection is proposed in this paper. A vehicle multi-characteristic dataset is constructed. With this dataset, seven CNN-based modern object detection algorithms are trained for vehicle multi-characteristic detection. The FPN-based YOLOv4 is selected as the best vehicle multi-characteristic detection algorithm, which applies feature information fusion of different scales with both rich high-level semantic information and detailed low-level location information. The YOLOv4 algorithm is improved by combing with the attention mechanism, in which the residual module in YOLOv4 is replaced by the ECA channel attention module with cross channel interaction. An improved ECA-YOLOv4 object detection algorithm based on both feature information fusion and cross channel interaction is proposed, which improves the performance of YOLOv4 for vehicle multi-characteristic detection and reduces the model parameter size and FLOPs as well. A multi-characteristic fused speed measurement system based on license plate, logo, and light is designed accordingly. The system performance is verified by experiments. The experimental results show that the speed measurement error rate of the proposed system meets the requirement of the China national standard GB/T 21555-2007 in which the speed measurement error rate should be less than 6%. The proposed system can efficiently enhance the vehicle speed measurement accuracy and effectively improve the vehicle speed measurement robustness.

8.
Sensors (Basel) ; 20(6)2020 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-32168872

RESUMEN

We designed an end-to-end dual-branch residual network architecture that inputs a low-resolution (LR) depth map and a corresponding high-resolution (HR) color image separately into the two branches, and outputs an HR depth map through a multi-scale, channel-wise feature extraction, interaction, and upsampling. Each branch of this network contains several residual levels at different scales, and each level comprises multiple residual groups composed of several residual blocks. A short-skip connection in every residual block and a long-skip connection in each residual group or level allow for low-frequency information to be bypassed while the main network focuses on learning high-frequency information. High-frequency information learned by each residual block in the color image branch is input into the corresponding residual block in the depth map branch, and this kind of channel-wise feature supplement and fusion can not only help the depth map branch to alleviate blur in details like edges, but also introduce some depth artifacts to feature maps. To avoid the above introduced artifacts, the channel interaction fuses the feature maps using weights referring to the channel attention mechanism. The parallel multi-scale network architecture with channel interaction for feature guidance is the main contribution of our work and experiments show that our proposed method had a better performance in terms of accuracy compared with other methods.

9.
J Cell Biochem ; 115(4): 678-89, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24453044

RESUMEN

Auto-antibodies against cardiac proteins have been described in patients with dilated cardiomyopathy. Antibodies against the C-terminal part of KChIP2 (anti-KChIP2 [C-12]) enhance cell death of rat cardiomyocytes. The underlying mechanisms are not fully understood. Therefore, we wanted to explore the mechanisms responsible for anti-KChIP2-mediated cell death. Rat cardiomyocytes were treated with anti-KChIP2 (C-12). KChIP2 RNA and protein expressions, nuclear NF-κB, mitochondrial membrane potential Δψm, caspase-3 and -9 activities, necrotic and apoptotic cells, total Ca(2+) and K(+) concentrations, and the effects on L-type Ca(2+) channels were quantified. Anti-KChIP2 (C-12) induced nuclear translocation of NF-κB. Anti-KChIP2 (C-12)-treatment for 2 h significantly reduced KChIP2 mRNA and protein expression. Anti-KChIP2 (C-12) induced nuclear translocation of NF-κB after 1 h. After 6 h, Δψm and caspase-3 and -9 activities were not significantly changed. After 24 h, anti-KChIP2 (C-12)-treated cells were 75 ± 3% necrotic, 2 ± 1% apoptotic, and 13 ± 2% viable. Eighty-six ± 1% of experimental buffer-treated cells were viable. Anti-KChIP2 (C-12) induced significant increases in total Ca(2+) (plus 11 ± 2%) and K(+) (plus 18 ± 2%) concentrations after 5 min. Anti-KChIP2 (C-12) resulted in an increased Ca(2+) influx through L-type Ca(2+) channels. In conclusion, our results suggest that anti-KChIP2 (C-12) enhances cell death of rat cardiomyocytes probably due to necrosis.


Asunto(s)
Autoanticuerpos/farmacología , Proteínas de Interacción con los Canales Kv/inmunología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Animales , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Canales de Calcio Tipo L/metabolismo , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Muerte Celular/efectos de los fármacos , Células Cultivadas , Proteínas I-kappa B/metabolismo , Proteínas de Interacción con los Canales Kv/genética , Proteínas de Interacción con los Canales Kv/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Miocitos Cardíacos/metabolismo , FN-kappa B/metabolismo , Necrosis/tratamiento farmacológico , Potasio/metabolismo , Transporte de Proteínas/efectos de los fármacos , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología
10.
Audiol Res ; 14(4): 581-592, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39051193

RESUMEN

(1) Background: Cochlear implants (CIs) are widely applied to recover audition for patients with severe degrees of or total hearing loss. Electrical stimulation using the electrically evoked ABR (E-ABR) can be recorded in CI recipients through the device. This work was designed to study E-ABR recorded individually from different channels located at the apical, middle, and basal cochlear regions in comparison to their simultaneous separated or adjacent combined recordings. (2) Methods: This study included 17 children fitted with unilateral cochlear implants. All children were subjected to impedance measurement, electrical compound action potentials (ECAP), and E-ABR recording of three channels located at the apical, middle, and basal cochlear regions. This was followed by simultaneous E-ABR recording of the three "separated" channels in comparison to E-ABR recording from three adjacent channels located at the middle cochlear region. (3) Results: Similar E-ABR latencies and amplitudes were found using either individual or simultaneously separated or adjacent combined recording. However, the mean amplitude measures of E-ABR for combined adjacent channels showed a positive correlation with the applied current level. (4) Conclusions: Combined E-ABR recording from adjacent channels is a faster and more reliable technique that can be used effectively without compromising the results of the recorded E-ABR.

11.
Front Hum Neurosci ; 18: 1365838, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38584852

RESUMEN

Eye-tracking technology brings a different human-computer interaction experience to users because of its intuitive, natural, and hands-free operation characteristics. Avoiding the Midas touch problem and improving the accuracy of interaction are among the main goals of the research and development of eye-control systems. This study reviews the methods and limitations of research on avoiding the Midas touch problem. For typical control clicking operations with low fault tolerance, such as mode switching and state selection in an eye-control system, this study proposes Magilock, a more reliable control triggering method with a high success rate in multi-channel eye-control systems. Magilock adds a control pre-locked mechanism between the two interactive steps of eye-control channel positioning control and other interactive channel triggering controls in the multi-channel eye-control system. This effectively avoids incorrect control triggering caused by multi-channel coordination disorder and gaze-point drift. This study also conducted ergonomic experiments to explore the lock and unlock times of the control pre-locked mechanism in Magilock. Taking into account the experimental data and subjective evaluation of the participants, we recommend setting the lock time and the unlock time of Magilock to 200 ms.

12.
Cell Calcium ; 121: 102912, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38823351

RESUMEN

Anoctamin 1 (ANO1) binds to transient receptor potential (TRP) channels (protein-protein interaction) and then is activated by TRP channels (functional interaction). TRP channels are non-selective cation channels that are expressed throughout the body and play roles in multiple physiological functions. Studies on TRP channels increased after the identification of TRP vanilloid 1 (TRPV1) in 1997. Calcium-activated chloride channel anoctamin 1 (ANO1, also called TMEM16A and DOG1) was identified in 2008. ANO1 plays a major role in TRP channel-mediated functions, as first shown in 2014 with the demonstration of a protein-protein interaction between TRPV4 and ANO1. In cells that co-express TRP channels and ANO1, calcium entering cells through activated TRP channels causes ANO1 activation. Therefore, in many tissues, the physiological functions related to TRP channels are modulated through chloride flux associated with ANO1 activation. In this review, we summarize the latest understanding of TRP-ANO1 interactions, particularly interaction of ANO1 with TRPV4, TRP canonical 6 (TRPC6), TRPV3, TRPV1, and TRPC2 in the salivary glands, blood vessels, skin keratinocytes, primary sensory neurons, and vomeronasal organs, respectively.


Asunto(s)
Canales de Potencial de Receptor Transitorio , Humanos , Animales , Canales de Potencial de Receptor Transitorio/metabolismo , Anoctaminas/metabolismo , Unión Proteica , Anoctamina-1/metabolismo
13.
Otolaryngol Head Neck Surg ; 171(3): 849-857, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38774957

RESUMEN

OBJECTIVE: Cochlear implant (CI) electrode design has changed over time. Changes in intracochlear electrode design might influence the spread of neural activation along the auditory nerve and the number of independent channels. This study aimed to investigate the impact of intracochlear electrode design on the electrode-neuron interface using electrophysiological measures. STUDY DESIGN: Prospective cohort study. SETTING: A single tertiary hospital. METHODS: Fifty-two ears who were implanted with CI divided into 3 groups based on the design of intracochlear electrode arrays. Twenty-three ears were implanted with lateral wall straight electrodes. Eighteen ears were implanted with the slim perimodiolar electrode, and 11 ears were implanted with the old perimodiolar electrode. Various electrically-evoked compound action potential (ECAP) metrics were measured to quantify spread of excitation and channel interaction. RESULTS: ECAP threshold and slope were not significantly different among groups. ECAP spread of excitation (SOE) half-width and channel interaction index (CII) were significantly larger in subjects implanted with the lateral wall straight electrodes, indicating a wider spread of excitation compared to those with perimodiolar electrodes. Electrode impedance was significantly lower in subjects implanted with perimodiolar electrodes than those with lateral wall electrodes. CONCLUSION: Perimodiolar electrode groups yielded significantly narrower SOE half-widths and smaller CII than the lateral wall straight electrode group. This may indicate that the electrode array that hugged the modiolus had less overlap in neural excitation between adjacent electrodes, resulting in reduced channel interaction and potentially better spectral resolution than the electrode array positioned more laterally.


Asunto(s)
Potenciales de Acción , Implantes Cocleares , Diseño de Prótesis , Humanos , Estudios Prospectivos , Masculino , Femenino , Persona de Mediana Edad , Potenciales de Acción/fisiología , Adulto , Anciano , Implantación Coclear/métodos , Potenciales Evocados Auditivos/fisiología , Electrodos Implantados
14.
Hear Res ; 440: 108911, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37977051

RESUMEN

For individuals with severe to profound hearing loss resulting from irreversibly damaged hair cells, cochlear implants can be used to restore hearing by delivering electrical stimulation directly to the spiral ganglion neurons. However, current spread lowers the spatial resolution of neural activation. Since light can be easily confined, optogenetics is a technique that has the potential to improve the precision of neural activation, whereby visible light is used to stimulate neurons that are modified with light-sensitive opsins. This study compares the spread of neural activity across the inferior colliculus of the auditory midbrain during electrical and optical stimulation in the cochlea of acutely deafened mice with opsin-modified spiral ganglion neurons (H134R variant of the channelrhodopsin-2). Monopolar electrical stimulation was delivered via each of four 0.2 mm wide platinum electrode rings at 0.6 mm centre-to-centre spacing, whereas 453 nm wavelength light was delivered via each of five 0.22 × 0.27 mm micro-light emitting diodes (LEDs) at 0.52 mm centre-to-centre spacing. Channel interactions were also quantified by threshold changes during simultaneous stimulation by pairs of electrodes or micro-LEDs at different distances between the electrodes (0.6, 1.2 and 1.8 mm) or micro-LEDs (0.52, 1.04, 1.56 and 2.08 mm). The spread of activation resulting from single channel optical stimulation was approximately half that of monopolar electrical stimulation as measured at two levels of discrimination above threshold (p<0.001), whereas there was no significant difference between optical stimulation in opsin-modified deafened mice and pure tone acoustic stimulation in normal-hearing mice. During simultaneous micro-LED stimulation, there were minimal channel interactions for all micro-LED spacings tested. For neighbouring micro-LEDs/electrodes, the relative influence on threshold was 13-fold less for optical stimulation compared electrical stimulation (p<0.05). The outcomes of this study show that the higher spatial precision of optogenetic stimulation results in reduced channel interaction compared to electrical stimulation, which could increase the number of independent channels in a cochlear implant. Increased spatial resolution and the ability to activate more than one channel simultaneously could lead to better speech perception in cochlear implant recipients.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Sordera , Ratones , Animales , Optogenética/métodos , Cóclea/fisiología , Opsinas/genética , Estimulación Eléctrica , Sordera/terapia , Sordera/cirugía
15.
Phys Med Biol ; 68(13)2023 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-37253377

RESUMEN

Objective.Accurate polyp segmentation is vital for diagnosing colorectal cancer. However, it is still challenging for accurate polyp segmentation and several bottlenecks exist, such as incomplete boundary, localization bias and lack of micro blocks along with large fragmented boundaries in uncertain regions.Approach.To address the above issues, a novel polyp segmentation network with multiple branch series-parallel attention (MBSA) and channel interaction via edge distribution guidance is proposed. Initially, the edge distribution guidance strategy is proposed to generate the edge distribution following Cauchy distribution to capture complementary edges with sufficient details. Subsequently, a MBSA module is put forward to extract features from various receptive fields to pinpoint tiny polyps by a multiple kernel dilated convolution block, while combining semantics of different dimensions to filter out noise and refining the details of micro target. Ultimately, the channel interaction model is proposed to improve the segmentation accuracy of the polyps in uncertain area by splitting channels into groups and conducts group-wise interaction to excavate subtle clues contained in different channels.Main results.Extensive experimental results demonstrate that the proposed method is superior over the state-of-the-art methods with the mean dice of 0.8972, 0.9420, 0.8312, 0.8064 and 0.9214 on five public polyp datasets.Significance.The proposed method improves the integrity of the margins and internal details for polyp segmentation, which will provide a powerful aid for doctors to achieve accurate judgments, reducing the likelihood of colorectal cancer and improving the survival chances of patients.


Asunto(s)
Neoplasias Colorrectales , Semántica , Humanos , Probabilidad , Incertidumbre , Procesamiento de Imagen Asistido por Computador
16.
Biochem Pharmacol ; 199: 115023, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35358481

RESUMEN

Kv1.3 K+ channels play a central role in the regulation of T cell activation and Ca2+ signaling under physiological and pathophysiological conditions. Peptide toxins targeting Kv1.3 have a significant therapeutic potential in the treatment of autoimmune diseases; thus, the discovery of new toxins is highly motivated. Based on the transcriptome analysis of the venom gland of V. mexicanus smithi a novel synthetic peptide, sVmKTx was generated, containing 36 amino acid residues. sVmKTx shows high sequence similarity to Vm24, a previously characterized peptide from the same species, but contains a Glu at position 32 as opposed to Lys32 in Vm24. Vm24 inhibits Kv1.3 with high affinity (Kd = 2.9 pM). However, it has limited selectivity (~1,500-fold) for Kv1.3 over hKv1.2, hKCa3.1, and mKv1.1. sVmKTx displays reduced Kv1.3 affinity (Kd = 770 pM) but increased selectivity for Kv1.3 over hKv1.2 (~9,000-fold) as compared to Vm24, other channels tested in the panel (hKCa3.1, hKv1.1, hKv1.4, hKv1.5, rKv2.1, hKv11.1, hKCa1.1, hNav1.5) were practically insensitive to the toxin at 2.5 µM. Molecular dynamics simulations showed that introduction of a Glu instead of Lys at position 32 led to a decreased structural fluctuation of the N-terminal segment of sVmKTx, which may explain its increased selectivity for Kv1.3. sVmKTx at 100 nM concentration decreased the expression level of the Ca2+ -dependent T cell activation marker, CD40 ligand. The high affinity block of Kv1.3 and increased selectivity over the natural peptide makes sVmKTx a potential candidate for Kv1.3 blockade-mediated treatment of autoimmune diseases.


Asunto(s)
Enfermedades Autoinmunes , Venenos de Escorpión , Perfilación de la Expresión Génica , Humanos , Canal de Potasio Kv1.3/genética , Canal de Potasio Kv1.3/metabolismo , Péptidos/metabolismo , Péptidos/farmacología , Bloqueadores de los Canales de Potasio/química , Bloqueadores de los Canales de Potasio/farmacología , Venenos de Escorpión/química , Venenos de Escorpión/farmacología , Linfocitos T/metabolismo
17.
Hear Res ; 424: 108591, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35914395

RESUMEN

Channel interactions caused by spread of the intracochlear electric field and, thus, the spread of neural excitation constrain frequency selectivity and speech recognition in cochlear implant (CI) users. Studying the influence of the spread of electric field (SEF) on the spread of excitation (SOE) can help us better understand the electrical-neural interface. The primary aim of this study was to examine the influence of the SEF on the SOE. In 38 Nucleus (Cochlear Ltd. Sydney, Australia) CI recipients, we assessed the spatial SEF by measuring the voltage drop (transimpedance) and the SOE through neural responses (electrically evoked compound action potentials [eCAPs]) along the electrode array. Transimpedance was recorded using the monopolar (MP2) mode as the stimulation and recording mode. Biphasic square-wave pulses with an amplitude of 110 CL and duration of 37 µs were used for stimulation. SOE was measured at the probe active electrodes E5, E13, and E18. The stimulation amplitudes were set individually to the thresholds of the neural response telemetry (T-NRT), which were measured by the AutoNRT protocol. The transimpedance half-widths were between 0.00 electrodes and 8.55 electrodes. The SOE half-widths reached values between 0.54 electrodes and 5.70 electrodes. Considering individual transimpedance and SOE half-widths, the SEF and SOE showed a significant positive correlation only at electrode E13. Furthermore, this study shows a significant negative correlation of the SEF and SOE in consideration of mean half-widths.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Potenciales de Acción/fisiología , Cóclea/fisiología , Implantación Coclear/métodos , Estimulación Eléctrica , Potenciales Evocados , Potenciales Evocados Auditivos/fisiología
18.
J Clin Med ; 10(24)2021 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-34945115

RESUMEN

Broader intra-cochlear current spread (ICCS) implies higher cochlear implant (CI) channel interactions. This study aimed to investigate the relationship between ICCS and speech intelligibility in experienced CI users. Using voltage matrices collected for impedance measurements, an individual exponential spread coefficient (ESC) was computed. Speech audiometry was performed to determine the intelligibility at 40 dB Sound Pressure Level (SPL) and the 50% speech reception threshold: I40 and SRT50 respectively. Correlations between ESC and either I40 or SRT50 were assessed. A total of 36 adults (mean age: 50 years) with more than 11 months (mean: 34 months) of CI experience were included. In the 21 subjects for whom all electrodes were active, ESC was moderately correlated with both I40 (r = -0.557, p = 0.009) and SRT50 (r = 0.569, p = 0.007). The results indicate that speech perception performance is negatively affected by the ICCS. Estimates of current spread at the closest vicinity of CI electrodes and prior to any activation of auditory neurons are indispensable to better characterize the relationship between CI stimulation and auditory perception in cochlear implantees.

19.
Trends Hear ; 25: 23312165211020645, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34041983

RESUMEN

Two-electrode stimuli presented on adjacent mid-array contacts in cochlear-implant users elicit pitch percepts that are not consistent with a summation of the two temporal patterns. This indicates that low-rate temporal rate codes can be applied with considerable independence on adjacent mid-array electrodes. At issue in this study was whether a similar independence of temporal pitch cues can also be observed for more apical sites of stimulation, where temporal cues have been shown to be more reliable than place cues, in contrast to middle and basal sites. In cochlear-implant recipients with single-sided deafness implanted with long lateral-wall electrode arrays, pitch percepts were assessed by matching the pitch of dual-electrode stimuli with pure tones presented to the contralateral normal-hearing ear. The results were supported with an additional pitch-ranking experiment, in a different subject population with bilateral deafness. Unmodulated pulse trains with 100, 200, and 400 pulses per second were presented on three pairs of adjacent electrodes. Pulses were separated by the minimal interchannel delay (1.7 µs) in a short-delay configuration and by half the pulse period in a long-delay configuration. The hypothesis was that subjects would perceive a pitch corresponding to the doubled temporal pattern for the long-delay stimuli due to the summation of excitation patterns from adjacent apical electrodes, if those electrodes were to activate largely overlapping neural populations. However, we found that the mean matched acoustic pitch of the long-delay pulses was not significantly different from that of the short-delay pulses. These findings suggest that also in the apical region in long-array cochlear-implant recipients, temporal cues can be transmitted largely independently on adjacent electrodes.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Sordera , Estimulación Acústica , Cóclea , Humanos , Percepción de la Altura Tonal
20.
Trends Hear ; 25: 23312165211030166, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34461780

RESUMEN

Speech intelligibility in multitalker settings is challenging for most cochlear implant (CI) users. One possibility for this limitation is the suboptimal representation of vocal cues in implant processing, such as the fundamental frequency (F0), and the vocal tract length (VTL). Previous studies suggested that while F0 perception depends on spectrotemporal cues, VTL perception relies largely on spectral cues. To investigate how spectral smearing in CIs affects vocal cue perception in speech-on-speech (SoS) settings, adjacent electrodes were simultaneously stimulated using current steering in 12 Advanced Bionics users to simulate channel interaction. In current steering, two adjacent electrodes are simultaneously stimulated forming a channel of parallel stimulation. Three such stimulation patterns were used: Sequential (one current steering channel), Paired (two channels), and Triplet stimulation (three channels). F0 and VTL just-noticeable differences (JNDs; Task 1), in addition to SoS intelligibility (Task 2) and comprehension (Task 3), were measured for each stimulation strategy. In Tasks 2 and 3, four maskers were used: the same female talker, a male voice obtained by manipulating both F0 and VTL (F0+VTL) of the original female speaker, a voice where only F0 was manipulated, and a voice where only VTL was manipulated. JNDs were measured relative to the original voice for the F0, VTL, and F0+VTL manipulations. When spectral smearing was increased from Sequential to Triplet, a significant deterioration in performance was observed for Tasks 1 and 2, with no differences between Sequential and Paired stimulation. Data from Task 3 were inconclusive. These results imply that CI users may tolerate certain amounts of channel interaction without significant reduction in performance on tasks relying on voice perception. This points to possibilities for using parallel stimulation in CIs for reducing power consumption.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Percepción del Habla , Estimulación Acústica , Señales (Psicología) , Femenino , Humanos , Masculino , Inteligibilidad del Habla
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