Selective-Area Epitaxy of Bulk-Insulating (BixSb1-x)2Te3 Films and Nanowires by Molecular Beam Epitaxy.

Selective-area epitaxy (SAE) is a useful technique to grow epitaxial films with a desired shape on a prepatterned substrate. Although SAE of patterned topological-insulator (TI) thin films has been performed in the past, there has been no report of SAE-grown TI structures that are bulk-insulating. Here we report the successful growth of Hall-bars and nanowires of bulk-insulating TIs using the SAE technique. Their transport properties show that the quality of the selectively grown structures is comparable to that of bulk-insulating TI films grown on pristine substrates. In SAE-grown TI nanowires, we were able to observe Aharonov-Bohm-like magnetoresistance oscillations that are characteristic of the quantum-confined topological surface states. The availability of bulk-insulating TI nanostructures via the SAE technique opens the possibility to fabricate intricate topological devices in a scalable manner.

A novel NKp80-based strategy for universal identification of normal, reactive and tumor/clonal natural killer-cells in blood.

Purpose: Natural killer (NK) cells are traditionally identified by flow cytometry using a combination of markers (CD16/CD56/CD3), because a specific NK-cell marker is still missing. Here we investigated the utility of CD314, CD335 and NKp80, compared to CD16/CD56/CD3, for more robust identification of NK-cells in human blood, for diagnostic purposes. Methods: A total of 156 peripheral blood (PB) samples collected from healthy donors (HD) and patients with diseases frequently associated with loss/downregulation of classical NK-cell markers were immunophenotyped following EuroFlow protocols, aimed at comparing the staining profile of total blood NK-cells for CD314, CD335 and NKp80, and the performance of distinct marker combinations for their accurate identification. Results: NKp80 showed a superior performance (vs. CD314 and CD335) for the identification of NK-cells in HD blood. Besides, NKp80 improved the conventional CD16/CD56/CD3-based strategy to identify PB NK-cells in HD and reactive processes, particularly when combined with CD16 for further accurate NK-cell-subsetting. Although NKp80+CD16 improved the identification of clonal/tumor NK-cells, particularly among CD56- cases (53%), aberrant downregulation of NKp80 was observed in 25% of patients, in whom CD56 was useful as a complementary NK-cell marker. As NKp80 is also expressed on T-cells, we noted increased numbers of NKp80+ cytotoxic T-cells at the more advanced maturation stages, mostly in adults. Conclusion: Here we propose a new robust approach for the identification of PB NK-cells, based on the combination of NKp80 plus CD16. However, in chronic lymphoproliferative disorders of NK-cells, addition of CD56 is recommended to identify clonal NK-cells, due to their frequent aberrant NKp80- phenotype.

Data-driven gated positron emission tomography/computed tomography for radiotherapy.

Purpose: Software-based data-driven gated (DDG) positron emission tomography/computed tomography (PET/CT) has replaced hardware-based 4D PET/CT. The purpose of this article was to review DDG PET/CT, which could improve the accuracy of treatment response assessment, tumor motion evaluation, and target tumor contouring with whole-body (WB) PET/CT for radiotherapy (RT). Material and methods: This review covered the topics of 4D PET/CT with hardware gating, advancements in PET instrumentation, DDG PET, DDG CT, and DDG PET/CT based on a systematic literature review. It included a discussion of the large axial field-of-view (AFOV) PET detector and a review of the clinical results of DDG PET and DDG PET/CT. Results: DDG PET matched or outperformed 4D PET with hardware gating. DDG CT was more compatible with DDG PET than 4D CT, which required hardware gating. DDG CT could replace 4D CT for RT. DDG PET and DDG CT for DDG PET/CT can be incorporated in a WB PET/CT of less than 15 min scan time on a PET/CT scanner of at least 25 cm AFOV PET detector. Conclusions: DDG PET/CT could correct the misregistration and tumor motion artifacts in a WB PET/CT and provide the quantitative PET and tumor motion information of a registered PET/CT for RT.

Unveiling Gating Behavior in Piezoionic Effect: toward Neuromimetic Tactile Sensing.

The human perception system's information processing is intricately linked to the nonlinear response and gating effect of neurons. While piezoionics holds potential in emulating the pressure sensing capability of biological skin, the incorporation of information processing functions seems neglected. Here, ionic gating behavior in piezoionic hydrogels is uncovered as a notable extension beyond the previously observed linear responses. The hydrogel can generate remarkably high voltages (700 mV) and currents (7 mA) when indentation forces surpass the threshold. Through a comprehensive analysis involving simulations and experimental investigations, it is proposed that the gating behavior emerges due to significant diffusion differences between cations and anions. To showcase the practical implications of this breakthrough, the piezoionic hydrogels are successfully integrated with prostheses and robot hands, demonstrating that the gating effect enables accurate discrimination between gentle and harsh touch. The advancement in neuromimetic tactile sensing has significant potential for emerging applications such as humanoid robotics and biomedical engineering, offering valuable opportunities for further development of embodied neuromorphic intelligence.

Adipocyte ABCA1 expression analysis using flow cytometry.

Adipocyte characterization and assessing membrane proteins using flow cytometry has been proven to be challenging as adipocytes are fragile, especially in subjects with high BMI. We overcame these challenges through a protocol optimizing tissue digestion time by reducing intermediate steps to minimize adipocyte friction and breakage. We avoided requirement for specialized instrument configuration and used a modified gating strategy to prevent inclusion of lipid droplets during analysis. Up to 90% of the cell population were available in the gating area. We checked the expression level of ABCA1, a membrane protein reaffirming adipocyte selection. In summary, this protocol requires lesser tissue sample improving feasibility and cost efficiency. Thus, our flow cytometry method is an improvement for studying adipocyte membrane characteristics.

The effect of unliganded gating on agonist response in nicotinic receptors.

Understanding the agonist concentration-response curve (CRC) is the cornerstone in pharmacology. While CRC parameters, agonist potency (EC50) and efficacy (maximum response, Imax) are well-studied, the role of unliganded gating (minimum response, Imin) on CRC is often overlooked. This study explores the effect of unliganded gating on agonist response in muscle-type acetylcholine (ACh) receptors, focusing on the underexplored role of Imin in modulating EC50 and Imax. Three Gain-of-Function (GOF) mutations that increase, and two Loss-of-Function (LOF) mutations that decrease the unliganded gating equilibrium constant (L0) were studied using automated patch-clamp electrophysiology. GOF mutations enhanced agonist potency, whereas LOF mutations reduced it. The calculated CRC aligned well with empirical results, indicating that agonist CRC can be estimated from knowledge of L0. Reduction in agonist efficacy due to LOF mutations was calculated and subsequently validated using single-channel patch-clamp electrophysiology, a factor often obscured in normalized CRC. The study also evaluated the combined impact of mutations (L0) on CRC, confirming the predictive model. Further, no significant energetic coupling between distant residues (>15Å) was found, indicating that the mutations' effects are localized and do not alter overall agonist affinity. These findings substantiate the role of unliganded gating in modulating agonist responses and establishes a predictive model for estimating CRC parameters from known changes in L0. The study highlights the importance of intrinsic activity in receptor theory.

Deep learning based bilateral filtering for edge-preserving denoising of respiratory-gated PET.

BACKGROUND: Residual image noise is substantial in positron emission tomography (PET) and one of the factors limiting lesion detection, quantification, and overall image quality. Thus, improving noise reduction remains of considerable interest. This is especially true for respiratory-gated PET investigations. The only broadly used approach for noise reduction in PET imaging has been the application of low-pass filters, usually Gaussians, which however leads to loss of spatial resolution and increased partial volume effects affecting detectability of small lesions and quantitative data evaluation. The bilateral filter (BF) - a locally adaptive image filter - allows to reduce image noise while preserving well defined object edges but manual optimization of the filter parameters for a given PET scan can be tedious and time-consuming, hampering its clinical use. In this work we have investigated to what extent a suitable deep learning based approach can resolve this issue by training a suitable network with the target of reproducing the results of manually adjusted case-specific bilateral filtering. METHODS: Altogether, 69 respiratory-gated clinical PET/CT scans with three different tracers ( [ 18 F ] FDG, [ 18 F ] L-DOPA, [ 68 Ga ] DOTATATE) were used for the present investigation. Prior to data processing, the gated data sets were split, resulting in a total of 552 single-gate image volumes. For each of these image volumes, four 3D ROIs were delineated: one ROI for image noise assessment and three ROIs for focal uptake (e.g. tumor lesions) measurements at different target/background contrast levels. An automated procedure was used to perform a brute force search of the two-dimensional BF parameter space for each data set to identify the "optimal" filter parameters to generate user-approved ground truth input data consisting of pairs of original and optimally BF filtered images. For reproducing the optimal BF filtering, we employed a modified 3D U-Net CNN incorporating residual learning principle. The network training and evaluation was performed using a 5-fold cross-validation scheme. The influence of filtering on lesion SUV quantification and image noise level was assessed by calculating absolute and fractional differences between the CNN, manual BF, or original (STD) data sets in the previously defined ROIs. RESULTS: The automated procedure used for filter parameter determination chose adequate filter parameters for the majority of the data sets with only 19 patient data sets requiring manual tuning. Evaluation of the focal uptake ROIs revealed that CNN as well as BF based filtering essentially maintain the focal SUV max values of the unfiltered images with a low mean ± SD difference of δ SUV max CNN , STD = (-3.9 ± 5.2)% and δ SUV max BF , STD = (-4.4 ± 5.3)%. Regarding relative performance of CNN versus BF, both methods lead to very similar SUV max values in the vast majority of cases with an overall average difference of δ SUV max CNN , BF = (0.5 ± 4.8)%. Evaluation of the noise properties showed that CNN filtering mostly satisfactorily reproduces the noise level and characteristics of BF with δ Noise CNN , BF = (5.6 ± 10.5)%. No significant tracer dependent differences between CNN and BF were observed. CONCLUSIONS: Our results show that a neural network based denoising can reproduce the results of a case by case optimized BF in a fully automated way. Apart from rare cases it led to images of practically identical quality regarding noise level, edge preservation, and signal recovery. We believe such a network might proof especially useful in the context of improved motion correction of respiratory-gated PET studies but could also help to establish BF-equivalent edge-preserving CNN filtering in clinical PET since it obviates time consuming manual BF parameter tuning.

The role of the Ventral Nucleus of the Trapezoid Body in the auditory prepulse inhibition of the acoustic startle reflex.

Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the ISI of 50 ms, the OCB-lesioned group exhibited a significant increase in%PPI (p < 0.01), which did not occur in the OCB/VNTB-lesioned group. Therefore, the ablation of cholinergic non-olivocochlear neurons in the OCB/VNTB-lesioned group suggests that these neurons contribute to the mediation of auditory PPI at the 50 ms ISI through their cholinergic projections to CRNs. Our study strongly reinforces the notion that auditory PPI encompasses a complex mechanism of top-down cholinergic modulation, effectively attenuating the ASR across different interstimulus intervals within multiple pathways.

Parallel EEG assessment of different sound predictability levels in tinnitus.

Tinnitus denotes the perception of a non-environmental sound and might result from aberrant auditory prediction. Successful prediction of formal (e.g., type) and temporal sound characteristics facilitates the filtering of irrelevant information, also labelled as 'sensory gating' (SG). Here, we explored if and how parallel manipulations of formal prediction violations and temporal predictability affect SG in persons with and without tinnitus. Age-, education- and sex-matched persons with and without tinnitus (N = 52) participated and listened to paired-tone oddball sequences, varying in formal (standard vs. deviant pitch) and temporal predictability (isochronous vs. random timing). EEG was recorded from 128 channels and data were analyzed by means of temporal spatial principal component analysis (tsPCA). SG was assessed by amplitude suppression for the 2nd tone in a pair and was observed in P50-like activity in both timing conditions and groups. Correspondingly, deviants elicited overall larger amplitudes than standards. However, only persons without tinnitus displayed a larger N100-like deviance response in the isochronous compared to the random timing condition. This result might imply that persons with tinnitus do not benefit similarly as persons without tinnitus from temporal predictability in deviance processing. Thus, persons with tinnitus might display less temporal sensitivity in auditory processing than persons without tinnitus.

"Blocking-like" effects in attentional set-shifting: Redundant cues facilitate shifting in male rats with medial prefrontal cortex inactivation.

Without a functioning prefrontal cortex, humans and other animals are impaired in measures of cognitive control and behavioral flexibility, including attentional set-shifting. However, the reason for this is unclear with evidence suggesting both impaired and enhanced attentional shifting. We inhibited the medial prefrontal cortex (mPFC) of rats while they performed a modified version of an attentional set-shifting task to explore the nature of this apparent contradiction. Twelve adult male Lister hooded rats received AAV5-CaMKIIa-hM4D(Gi)-mCherry viral vector bilaterally into mPFC to express inhibitory 'Designer Receptors Exclusively Activated by Designer Drugs' (iDREADDs). The receptors were activated by systemic clozapine N-oxide (CNO) to inhibit mPFC function. The rats were tested in the standard attentional set-shifting task four times: twice after i.p. administration and twice after oral administration of vehicle or CNO (10 mg/kg). They were then tested twice in a modified task, with or without oral CNO. The modified task had an extra stage before the extradimensional shift, in which the relevant exemplars remained relevant and new exemplars that were fully predictive but redundant replaced the previous irrelevant exemplars. These exemplars then became relevant at the subsequent ED stage. In the standard task, mPFC inactivation impaired attentional set-shifting, consistent with previous findings. However, in the modified task, mPFC inactivation abolished ED shift-costs. The results support the suggestion that the mPFC is needed for the downregulation of attention that prevents learning about redundant and irrelevant stimuli. With mPFC inactivated, the rat learns more rapidly when previously redundant exemplars become the only relevant information.

Human Transient Receptor Potential Ankyrin 1 Channel: Structure, Function, and Physiology.

The transient receptor potential ion channel TRPA1 is a Ca2+-permeable nonselective cation channel widely expressed in sensory neurons, but also in many nonneuronal tissues typically possessing barrier functions, such as the skin, joint synoviocytes, cornea, and the respiratory and intestinal tracts. Here, the primary role of TRPA1 is to detect potential danger stimuli that may threaten the tissue homeostasis and the health of the organism. The ability to directly recognize signals of different modalities, including chemical irritants, extreme temperatures, or osmotic changes resides in the characteristic properties of the ion channel protein complex. Recent advances in cryo-electron microscopy have provided an important framework for understanding the molecular basis of TRPA1 function and have suggested novel directions in the search for its pharmacological regulation. This chapter summarizes the current knowledge of human TRPA1 from a structural and functional perspective and discusses the complex allosteric mechanisms of activation and modulation that play important roles under physiological or pathophysiological conditions. In this context, major challenges for future research on TRPA1 are outlined.

Insights into CLC-0's Slow-Gating from Intracellular Proton Inhibition.

The opening of the Torpedo CLC-0 chloride (Cl-) channel is known to be regulated by two gating mechanisms: fast gating and slow (common) gating. The structural basis underlying the fast-gating mechanism is better understood than that of the slow-gating mechanism, which is still largely a mystery. Our previous study on the intracellular proton (H+i)-induced inhibition of the CLC-0 anionic current led to the conclusion that the inhibition results from the slow-gate closure (also called inactivation). The conclusion was made based on substantial evidence such as a large temperature dependence of the H+i inhibition similar to that of the channel inactivation, a resistance to the H+i inhibition in the inactivation-suppressed C212S mutant, and a similar voltage dependence between the current recovery from the H+i inhibition and the recovery from the channel inactivation. In this work, we further examine the mechanism of the H+i inhibition of wild-type CLC-0 and several mutants. We observe that an anion efflux through the pore of CLC-0 accelerates the recovery from the H+i-induced inhibition, a process corresponding to the slow-gate opening. Furthermore, various inactivation-suppressed mutants exhibit different current recovery kinetics, suggesting the existence of multiple inactivated states (namely, slow-gate closed states). We speculate that protonation of the pore of CLC-0 increases the binding affinity of permeant anions in the pore, thereby generating a pore blockage of ion flow as the first step of inactivation. Subsequent complex protein conformational changes further transition the CLC-0 channel to deeper inactivated states.

Data driven surrogate signal extraction for dynamic PET using selective PCA: time windows versus the combination of components.

Respiratory motion correction is beneficial in PET, as it can reduce artefacts caused by motion and improve quantitative accuracy. Methods of motion correction are commonly based on a respiratory trace obtained through an external device (like the Real Time Position Management System) or a data driven method, such as those based on dimensionality reduction techniques (for instance PCA). PCA itself being a linear transformation to the axis of greatest variation. Data driven methods have the advantage of being non-invasive, and can be performed post-acquisition. However, their main downside being that they are adversely affected by the tracer kinetics of the dynamic PET acquisition. Therefore, they are mostly limited to static PET acquisitions. This work seeks to extend on existing PCA-based data-driven motion correction methods, to allow for their applicability to dynamic PET imaging. The methods explored in this work include; a moving window approach (similar to the Kinetic Respiratory Gating method from Schleyer et al.), extrapolation of the principal component from later time points to earlier time points, and a method to score, select, and combine multiple respiratory components. The resulting respiratory traces were evaluated on 22 data sets from a dynamic 18FFDG study on patients with Idiopathic Pulmonary Fibrosis. This was achieved by calculating their correlation with a surrogate signal acquired using a Real Time Position Management System. The results indicate that all methods produce better surrogate signals than when applying conventional PCA to dynamic data (for instance, a higher correlation with a gold standard respiratory trace). Extrapolating a late time point principal component produced more promising results than using a moving window. Scoring, selecting, and combining components held benefits over all other methods. This work allows for the extraction of a surrogate signal from dynamic PET data earlier in the acquisition and with a greater accuracy than previous work. This potentially allows for numerous other methods (for instance, respiratory motion correction) to be applied to this data (when they otherwise could not be previously used).

Glycine to valine substitution in the short intracellular linkers of domain II enhances I1011M-mediated sodium channel resistance to Type I pyrethroids, but not Type II pyrethroids.

Pyrethroids are widely used against agricultural pests and human disease vectors due to their broad insecticidal spectrum, fast action, and low mammalian toxicity. Unfortunately, overuse of pyrethroids has led to knockdown resistance (kdr) caused by mutations in voltage-gated sodium channels. Mutation I1011M was repeatedly detected in numerous pyrethroid-resistant Aedes aegypti populations from Latin American and Brazil. In addition, mutation G923V was first reported to coexist with I1011M in permethrin/DDT-resistant Ae. aegypti, whether G923V enhances the I1011M-mediated pyrethroid resistance in sodium channels remains unclear. In this study, we introduced mutations G923V and I1011M alone or in combination into the pyrethroid-sensitive sodium channel AaNav1-1 and examined the effects of these mutations on gating properties and pyrethroid sensitivity. We found mutations I1011M and G923V + I1011M shifted the voltage dependence of activation in the depolarizing direction, and none of mutations affect the voltage-dependence of inactivation. G923V and G923V + I1011M mutations reduced the channel sensitivity to both Type I and Type II pyrethroids. However, I1011M alone conferred resistance to Type I pyrethroids, not to Type II pyrethroids. Interestingly, significant synergism effects on Type I pyrethroids were observed between mutations G923V and I1011M. The effects of all mutations on channel sensitivity to DDT were identical with those to Type I pyrethroids. Our results confirm the molecular basis of resistance mediated by mutations G923V and I1011M and may contribute to develop molecular markers for monitoring pest resistance to pyrethroids.

GIGANTEA adjusts the response to shade at dusk by directly impinging on PHYTOCHROME INTERACTING FACTOR 7 function.

For plants adapted to bright light, a decrease in the amount of light received can be detrimental to their growth and survival. Consequently, in response to shade from surrounding vegetation, they initiate a suite of molecular and morphological changes known as the shade avoidance response through which stems and petioles elongate in search for light. Under sunlight-night cycles, the plant's responsiveness to shade varies across the day, being maximal at dusk time. While a role for the circadian clock in this regulation has long been proposed, mechanistic understanding of how it is achieved is incomplete. Here, we show that the clock component GIGANTEA (GI) directly interacts with the transcriptional regulator PHYTOCHROME INTERACTING FACTOR 7 (PIF7), a key player in the response to shade. GI represses PIF7 transcriptional activity and the expression of its target genes in response to shade, thereby fine-tuning the magnitude of the response to limiting light conditions. We find that under light/dark cycles, this function of GI is required to adequately modulate the gating of the response to shade at dusk. Importantly, we also show that this circuit primarily operates in epidermal cells, highlighting the relevance of tissue-specific clock-output connections for the regulation of plant development in resonance with the environment.

Manipulation of Helicity-Dependent Photocurrent and Stokes Parameter Detection in Topological Insulator Bi2Te3 Nanowires.

Helicity-dependent photocurrent (HDPC) and its modulation in topological insulator Bi2Te3 nanowires have been investigated. It is revealed that when the incident plane of a laser is perpendicular to the nanowire, the HDPC is an odd function of the incident angle, which is mainly contributed by the circular photogalvanic effect originating from the surface states of Bi2Te3 nanowire. When the incident plane of a laser is parallel to the nanowire, the HDPC is approximately an even function of the incident angle, which is due to the circular photon drag effect coming from the surface states. It is found that the HDPC can be effectively tuned by the back gate and the ionic liquid top gate. By analyzing the substrate dependence of the HDPC, we find that the HDPC of the Bi2Te3 nanowire on the Si substrate is an order of magnitude larger than that on SiO2, which may be due to the spin injection from the Si substrate to the Bi2Te3 nanowire. In addition, by applying different biases, the Stokes parameters of a polarized light can be extracted by arithmetic operation of the photocurrents measured in the Bi2Te3 nanowire. This work suggests that topological insulator Bi2Te3 nanowires may provide a good platform for opto-spintronic devices, especially in chirality and polarimtry detection.

Structural and theoretical basis for drug development targeting TMEM16A: Inhibition mechanism of tracheloside analogs.

Ion channels play a crucial role in the electrophysiological activities of organisms. The calcium-activated chloride channel TMEM16A is involved in various physiological processes. Therefore, inhibitors of TMEM16A are used to treat diseases caused by TMEM16A dysfunction. However, the unclear inhibition mechanism hinders the progress of drug development. Based on our previous study, we found that the molecular structures of TMEM16A inhibitors tracheloside, matairesinoside and arctigenin are similar. In this study, we conducted a structure-based virtual screening of tracheloside analogs from the PubChem database. The six tracheloside analogs with the highest affinity to TMEM16A were selected, and their inhibitory effects were detected by fluorescence and electrophysiological experiments. Subsequently, the interaction between the tracheloside analogs and TMEM16A was investigated through molecular docking and site-directed mutagenesis. Based on the above results, the mechanism of inhibition of TMEM16A gated conformation by tracheloside analogs was proposed. These findings provide a structural and theoretical basis for drug development targeting TMEM16A.

Inkjet-Printed, High-Performance MoS2 Transistors and Unipolar Logic Electronics.

Two-dimensional (2D) semiconductor field-effect film transistors combine large carrier mobility with mechanical flexibility and therefore can be ideally suitable for wearable electronics or at the sensor interfaces of smart sensor systems. However, such applications require large-area solution processing as opposed to single-flake devices, where the critical challenge to overcome is the high interflake resistance values. In this report, using a narrow-channel, near-vertical transport device architecture, we have fabricated inkjet-printed sub-20 nm channel electrolyte-gated transistors with predominantly intraflake carrier transport. Therefore, the electronics transport in these transistors is not dominated by the high interflake resistance, and the intraflake material properties including doping density, defect concentration, contact resistance, and threshold voltage modulation can be examined and optimized independently to achieve a current density as high as 280 µA·µm-1. In addition, through the passivation of the sulfur vacancies with a tailored surface treatment, we demonstrate an impressive On-Off current ratio exceeding 1 × 107, complemented by a low subthreshold swing of 100 mV·decade-1. Next, exploiting these high-performance transistors, unipolar depletion-load-type inverters have been fabricated that show a maximum gain of 31. Furthermore, we have realized NAND, NOR, and OR gates, demonstrating their seamless operation at a frequency of 1 kHz. Therefore, this work represents an important step forward to realize electronic circuits based on printed 2D thin film transistors.

GateNet: A novel neural network architecture for automated flow cytometry gating.

BACKGROUND AND OBJECTIVE: Flow cytometry is a widely used technique for identifying cell populations in patient-derived fluids, such as peripheral blood (PB) or cerebrospinal fluid (CSF). Despite its ubiquity in research and clinical practice, the process of gating, i.e., manually identifying cell types, is labor-intensive and error-prone. The objective of this study is to address this challenge by introducing GateNet, a neural network architecture designed for fully end-to-end automated gating without the need for correcting batch effects. METHODS: For this study a unique dataset is used which comprises over 8,000,000 events from N = 127 PB and CSF samples which were manually labeled independently by four experts. Applying cross-validation, the classification performance of GateNet is compared to the human experts performance. Additionally, GateNet is applied to a publicly available dataset to evaluate generalization. The classification performance is measured using the F1 score. RESULTS: GateNet achieves F1 scores ranging from 0.910 to 0.997 demonstrating human-level performance on samples unseen during training. In the publicly available dataset, GateNet confirms its generalization capabilities with an F1 score of 0.936. Importantly, we also show that GateNet only requires ≈10 samples to reach human-level performance. Finally, gating with GateNet only takes 15 microseconds per event utilizing graphics processing units (GPU). CONCLUSIONS: GateNet enables fully end-to-end automated gating in flow cytometry, overcoming the labor-intensive and error-prone nature of manual adjustments. The neural network achieves human-level performance on unseen samples and generalizes well to diverse datasets. Notably, its data efficiency, requiring only ∼10 samples to reach human-level performance, positions GateNet as a widely applicable tool across various domains of flow cytometry.