Alzheimer’s Disease Enhanced Tonic Inhibition is Correlated With Upregulated Astrocyte GABA Transporter-3/4 in a Knock-In APP Mouse Model

Cognitive decline is a major symptom in Alzheimer’s disease (AD), which is strongly associated with synaptic excitatory-inhibitory imbalance. Here, we investigated whether astrocyte-specific GABA transporter 3/4 (GAT3/4) is altered in APP knock-in mouse model of AD and whether this is correlated with changes in principal cell excitability. Using the APPNL-F/NL-F knock-in mouse model of AD, aged-matched to wild-type mice, we performed in vitro electrophysiological whole-cell recordings combined with immunohistochemistry in the CA1 and dentate gyrus (DG) regions of the hippocampus. We observed a higher expression of GAD67, an enzyme that catalyses GABA production, and GAT3/4 in reactive astrocytes labelled with GFAP, which correlated with an enhanced tonic inhibition in the CA1 and DG of 12–16 month-old APPNL-F/NL-F mice compared to the age-matched wild-type animals. Comparative neuroanatomy experiments performed using post-mortem brain tissue from human AD patients, age-matched to healthy controls, mirrored the results obtained using mice tissue. Blocking GAT3/4 associated tonic inhibition recorded in CA1 and DG principal cells resulted in an increased membrane input resistance, enhanced firing frequency and synaptic excitation in both wild-type and APPNL-F/NL-F mice. These effects exacerbated synaptic hyperactivity reported previously in the APPNL-F/NL-F mice model. Our data suggest that an alteration in astrocyte GABA homeostasis is correlated with increased tonic inhibition in the hippocampus, which probably plays an important compensatory role in restoring AD-associated synaptic hyperactivity. Therefore, reducing tonic inhibition through GAT3/4 may not be a good therapeutic strategy for A

Parallel Space-Mapping Based Yield-Driven em Optimization Incorporating Trust Region Algorithm and Polynomial Chaos Expansion

Space mapping (SM) methodology has been recognized as a powerful tool for accelerating electromagnetic (EM)-based yield optimization. This paper proposes a novel parallel space-mapping based yield-driven EM optimization technique incorporating trust region algorithm and polynomial chaos expansion (PCE). In this technique, a novel trust region algorithm is proposed to increase the robustness of the SM surrogate in each iteration during yield optimization. The proposed algorithm updates the trust radius of each design parameter based on the effectiveness of minimizing the $l_{1}$ objective function using the surrogate, thereby increasing the robustness of the SM surrogate. Moreover, for the first time, parallel computation method is incorporated into SM-based yield-driven design to accelerate the overall yield optimization process of microwave structures. The use of parallel computation allows the surrogate developed in the proposed technique to be valid in a larger neighborhood than that in standard SM, consequently increasing the speed of finding the optimal yield solution in SM-based yield-driven design. Lastly, the PCE approach is incorporated into the proposed technique to further speed up yield verification on the fine model. Compared with the standard SM-based yield optimization technique with sequential computation, the propose

Revisiting DETR Pre-training for Object Detection

Motivated by that DETR-based approaches have established new records on COCO detection and segmentation benchmarks, many recent endeavors show increasing interest in how to further improve DETR-based approaches by pre-training the Transformer in a self-supervised manner while keeping the backbone frozen. Some studies already claimed significant improvements in accuracy. In this paper, we take a closer look at their experimental methodology and check if their approaches are still effective on the very recent state-of-the-art such as $\mathcal{H}$-Deformable-DETR. We conduct thorough experiments on COCO object detection tasks to study the influence of the choice of pre-training datasets, localization, and classification target generation schemes. Unfortunately, we find the previous representative self-supervised approach such as DETReg, fails to boost the performance of the strong DETR-based approaches on full data regimes. We further analyze the reasons and find that simply combining a more accurate box predictor and Objects$365$ benchmark can significantly improve the results in follow-up experiments. We demonstrate the effectiveness of our approach by achieving strong object detection results of AP=$59.3\%$ on COCO val set, which surpasses $\mathcal{H}$-Deformable-DETR + Swin-L by +$1.4\%$. Last, we generate a series of synthetic pre-training datasets by combining the very recent image-to-text captioning models (LLaVA) and text-to-image generative models (SDXL). Notably, pre-training on these synthetic datasets leads to notable improvements in object detection performance. Looking ahead, we anticipate substantial advantages through the future expansion of the synthetic pre-training dataset

Axial wind effects on stratification and longitudinal sediment transport in a convergent estuary during wet season

Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research-Oceans 125(2), (2020): e2019JC015254, doi:10.1029/2019JC015254.The Coupled Ocean‐Atmosphere‐Wave‐Sediment Transport (COAWST) modeling system was used to examine axial wind effects on vertical stratification and sediment transport in a convergent estuary. The model demonstrated that stratification dynamics in the upper estuary (Kelvin number <1; Ke= fB/√ g'hs) are dominated by longitudinal wind straining, whereas the dominant mechanism governing estuarine stratification in the lower estuary (Kelvin number ~1) is lateral wind straining. Barotropic advection contributes to seaward sediment transport and peaks during spring tides, whereas estuarine circulation causes landward sediment transport with a maximum during neap tides. Down‐estuary winds impose no obvious effects on longitudinal sediment flux, whereas up‐estuary winds contribute to enhanced seaward sediment flux by increasing the tidal oscillatory flux. The model also demonstrates that bottom friction is significantly influenced by vertical stratification over channel regions, which is indirectly affected by axial winds.This research was funded by the National Natural Science Foundation of China (Grants 41576089, 51761135021, and 41890851), the National Key Research and Development Program of China (2016YFC0402603) and the Guangdong Provincial Water Conservancy Science and Technology Innovation Project (Grant 201719). We thank Professor Liangwen Jia at the Sun Yat‐sen University for his kindly providing the surficial sediment samples data in 2011. We also thank graduate students Guang Zhang and Yuren Chen from the Sun Yat‐sen University for their help in data analysis. We are grateful to two anonymous reviewers for their insightful comments to help improve this manuscript. The data related to this article is available online at the Zenodo website (https://zenodo.org/record/3606471).2020-07-1

Spatiotemporal access to emergency medical services in Wuhan, China: accounting for scene and transport time intervals

Background: Access as a primary indicator of Emergency Medical Service (EMS) efficiency has been widely studied over the last few decades. Most previous studies considered one-way trips, either getting ambulances to patients or transporting patients to hospitals. This research assesses spatiotemporal access to EMS at the shequ (the smallest administrative unit) level in Wuhan, China, attempting to fill a gap in literature by considering and comparing both trips in the evaluation of EMS access. Methods: Two spatiotemporal access measures are adopted here: the proximity-based travel time obtained from online map services and the enhanced two-step floating catchment area (E-2SFCA) which is a gravity-based model. First, the travel time is calculated for the two trips involved in one EMS journey: one is from the nearest EMS station to the scene (i.e. scene time interval (STI)) and the other is from the scene to the nearest hospital (i.e. transport time interval (TTI)). Then, the predicted travel time is incorporated into the E-2SFCA model to calculate the access measure considering the availability of the service provider as well as the population in need. For both access measures, the calculation is implemented for peak hours and off-peak hours. Results: Both methods showed a marked decrease in EMS access during peak traffic hours, and differences in spatial patterns of ambulance and hospital access. About 73.9% of shequs can receive an ambulance or get to the nearest hospital within 10 min during off-peak periods, and this proportion decreases to about 45.5% for peak periods. Most shequs with good ambulance access but poor hospital access are in the south of the study area. In general, the central areas have better ambulance, hospital and overall access than peripheral areas, particularly during off-peak periods. Conclusions: In addition to the impact of peak traffic periods on EMS access, we found that good ambulance access does not necessarily guarantee good hospital access nor the overall access, and vice versa

Rank-DETR for High Quality Object Detection

Modern detection transformers (DETRs) use a set of object queries to predict a list of bounding boxes, sort them by their classification confidence scores, and select the top-ranked predictions as the final detection results for the given input image. A highly performant object detector requires accurate ranking for the bounding box predictions. For DETR-based detectors, the top-ranked bounding boxes suffer from less accurate localization quality due to the misalignment between classification scores and localization accuracy, thus impeding the construction of high-quality detectors. In this work, we introduce a simple and highly performant DETR-based object detector by proposing a series of rank-oriented designs, combinedly called Rank-DETR. Our key contributions include: (i) a rank-oriented architecture design that can prompt positive predictions and suppress the negative ones to ensure lower false positive rates, as well as (ii) a rank-oriented loss function and matching cost design that prioritizes predictions of more accurate localization accuracy during ranking to boost the AP under high IoU thresholds. We apply our method to improve the recent SOTA methods (e.g., H-DETR and DINO-DETR) and report strong COCO object detection results when using different backbones such as ResNet-$50$, Swin-T, and Swin-L, demonstrating the effectiveness of our approach. Code is available at \url{https://github.com/LeapLabTHU/Rank-DETR}.Comment: NeurIPS 202

Rice plants respond to ammonium‐stress by adopting a helical root growth pattern

High levels of ammonium nutrition reduce plant growth and different plant species have developed distinct strategies to maximize ammonium acquisition while alleviate ammonium toxicity through modulating root growth. Up to now, the mechanism underlying plant tolerance or sensitivity towards ammonium remain unclear. Rice uses ammonium as its main N source. Here we show that ammonium supply restricts rice root elongation and induces a helical growth pattern, which is attributed to root acidification resulting from ammonium uptake. Ammonium-induced low pH triggers asymmetric auxin distribution in rice root tips through changes in auxin signaling, thereby inducing a helical growth response. Blocking auxin signaling completely inhibited this root response. In contrast, this root response is not activated in ammonium-treated Arabidopsis. Acidification of Arabidopsis roots leads to the protonation of IAA, and dampening the intracellular auxin signaling levels that are required for maintaining root growth. Our study suggests a different mode of action by ammonium on the root pattern and auxin response machinery in rice versus Arabidopsis, and the rice-specific helical root response towards ammonium is an expression of the ability of rice in moderating auxin signaling and root growth to utilize ammonium while confronting acidic stress

Improvement of current crowding effect in VCSEL arrays with non-uniform oxidation aperture design

A compact electro-opto-thermal model of 2-D vertical cavity surface emitting laser (VCSEL) arrays considering the current crowding effect in each array cell is established to study the impact of oxidation aperture on the device performance. Simulated results shows that increasing oxidation aperture of array cell is helpful to improve the uniformity of current density distribution. With careful design of non-uniform oxidation aperture layout, both the uniformity of the temperature distribution and the current distribution is improved by 36.52% and 42.08%, respectively. Furthermore, 3×3 VCSEL arrays with uniform oxidation aperture (array-1) and non-uniform oxidation aperture (array-2) are fabricated and the L-I-V curves of two types of VCSEL arrays at different biases are also measured. The peak output optical power of array-2 is enhanced to 1.83mW with an improvement of 8.91% when compared with that of array-1. Moreover, the total optical output power of array-2 is always superior to that of array-1 over a wide bias current range

Improvement of thermally induced current bifurcation in VCSEL arrays with non-uniform series resistance design

Non-uniform series resistance design of VCSEL arrays is studied to improve thermally induced current bifurcation based on an electro-opto-thermal model of VCSEL arrays. Taking an 850nm VCSEL array with 4×4 cells for example, the impact of series resistance on current bifurcation is investigated. Increasmg series resistance is helpful to enhance the critical current values of current bifurcation point (Irc) and hence delay the current bifurcation phenomenon. For VCSEL array with non-uniform series resistance, Irc is increased by 28.6% and the total output optical power is enhanced by 14.3% when compared with that of VCSEL array with uniform series resistance. Therefore, non-uniform series resistance design is a better method for delaying the current bifurcation phenomenon and enhancuig the output optical power of VCSEL arrays