69 research outputs found
Integrating Symmetry into Differentiable Planning with Steerable Convolutions
We study how group symmetry helps improve data efficiency and generalization
for end-to-end differentiable planning algorithms when symmetry appears in
decision-making tasks. Motivated by equivariant convolution networks, we treat
the path planning problem as \textit{signals} over grids. We show that value
iteration in this case is a linear equivariant operator, which is a (steerable)
convolution. This extends Value Iteration Networks (VINs) on using
convolutional networks for path planning with additional rotation and
reflection symmetry. Our implementation is based on VINs and uses steerable
convolution networks to incorporate symmetry. The experiments are performed on
four tasks: 2D navigation, visual navigation, and 2 degrees of freedom (2DOFs)
configuration space and workspace manipulation. Our symmetric planning
algorithms improve training efficiency and generalization by large margins
compared to non-equivariant counterparts, VIN and GPPN.Comment: Restructured main text and appendix. Renamed from "Integrating
Symmetry into Differentiable Planning
Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial
Objective To examine the impact of antenatal supplementation with multiple micronutrients or iron and folic acid compared with folic acid alone on birth weight, duration of gestation, and maternal haemoglobin concentration in the third trimester
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Targeting Metabolism in Cancer Cells and the Tumour Microenvironment for Cancer Therapy.
Targeting altered tumour metabolism is an emerging therapeutic strategy for cancer treatment. The metabolic reprogramming that accompanies the development of malignancy creates targetable differences between cancer cells and normal cells, which may be exploited for therapy. There is also emerging evidence regarding the role of stromal components, creating an intricate metabolic network consisting of cancer cells, cancer-associated fibroblasts, endothelial cells, immune cells, and cancer stem cells. This metabolic rewiring and crosstalk with the tumour microenvironment play a key role in cell proliferation, metastasis, and the development of treatment resistance. In this review, we will discuss therapeutic opportunities, which arise from dysregulated metabolism and metabolic crosstalk, highlighting strategies that may aid in the precision targeting of altered tumour metabolism with a focus on combinatorial therapeutic strategies
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Targeting codon 158 p53-mutant cancers via the induction of p53 acetylation
Abstract: Gain of function (GOF) DNA binding domain (DBD) mutations of TP53 upregulate chromatin regulatory genes that promote genome-wide histone methylation and acetylation. Here, we therapeutically exploit the oncogenic GOF mechanisms of p53 codon 158 (Arg158) mutation, a DBD mutant found to be prevalent in lung carcinomas. Using high throughput compound screening and combination analyses, we uncover that acetylating mutp53R158G could render cancers susceptible to cisplatin-induced DNA stress. Acetylation of mutp53R158G alters DNA binding motifs and upregulates TRAIP, a RING domain-containing E3 ubiquitin ligase which dephosphorylates IĸB and impedes nuclear translocation of RelA (p65), thus repressing oncogenic nuclear factor kappa-B (NF-ĸB) signaling and inducing apoptosis. Given that this mechanism of cytotoxic vulnerability appears inapt in p53 wild-type (WT) or other hotspot GOF mutp53 cells, our work provides a therapeutic opportunity specific to Arg158-mutp53 tumors utilizing a regimen consisting of DNA-damaging agents and mutp53 acetylators, which is currently being pursued clinically
Thalamic gating contributes to forward suppression in the auditory cortex.
The neural mechanisms underlying forward suppression in the auditory cortex remain a puzzle. Little attention is paid to thalamic contribution despite the important fact that the thalamus gates upstreaming information to the auditory cortex. This study compared the time courses of forward suppression in the auditory thalamus, thalamocortical inputs and cortex using the two-tone stimulus paradigm. The preceding and succeeding tones were 20-ms long. Their frequency and amplitude were set at the characteristic frequency and 20 dB above the minimum threshold of given neurons, respectively. In the ventral division of the medial geniculate body of the thalamus, we found that the duration of complete forward suppression was about 75 ms and the duration of partial suppression was from 75 ms to about 300 ms after the onset of the preceding tone. We also found that during the partial suppression period, the responses to the succeeding tone were further suppressed in the primary auditory cortex. The forward suppression of thalamocortical field excitatory postsynaptic potentials was between those of thalamic and cortical neurons but much closer to that of thalamic ones. Our results indicate that early suppression in the cortex could result from complete suppression in the thalamus whereas later suppression may involve thalamocortical and intracortical circuitry. This suggests that the complete suppression that occurs in the thalamus provides the cortex with a "silence" window that could potentially benefit cortical processing and/or perception of the information carried by the preceding sound
Primitive auditory memory is correlated with spatial unmasking that is based on direct-reflection integration.
In reverberant rooms with multiple-people talking, spatial separation between speech sources improves recognition of attended speech, even though both the head-shadowing and interaural-interaction unmasking cues are limited by numerous reflections. It is the perceptual integration between the direct wave and its reflections that bridges the direct-reflection temporal gaps and results in the spatial unmasking under reverberant conditions. This study further investigated (1) the temporal dynamic of the direct-reflection-integration-based spatial unmasking as a function of the reflection delay, and (2) whether this temporal dynamic is correlated with the listeners' auditory ability to temporally retain raw acoustic signals (i.e., the fast decaying primitive auditory memory, PAM). The results showed that recognition of the target speech against the speech-masker background is a descending exponential function of the delay of the simulated target reflection. In addition, the temporal extent of PAM is frequency dependent and markedly longer than that for perceptual fusion. More importantly, the temporal dynamic of the speech-recognition function is significantly correlated with the temporal extent of the PAM of low-frequency raw signals. Thus, we propose that a chain process, which links the earlier-stage PAM with the later-stage correlation computation, perceptual integration, and attention facilitation, plays a role in spatially unmasking target speech under reverberant conditions
Improving the Performance of Continuous-Variable Measurement-Device-Independent Quantum Key Distribution via a Noiseless Linear Amplifier
In the continuous variable measurement-device-independent quantum key distribution (CV-MDI-QKD) protocol, both Alice and Bob send quantum states to an untrusted third party, Charlie, for detection through the quantum channel. In this paper, we mainly study the performance of the CV-MDI-QKD system using the noiseless linear amplifier (NLA). The NLA is added to the output of the detector at Charlie’s side. The research results show that NLA can increase the communication distance and secret key rate of the CV-MDI-QKD protocol. Moreover, we find that the more powerful the improvement of the performance with the longer gain of NLA and the optimum gain is given under different conditions
Intra-Aortic Balloon Occlusion Decreases Blood Loss During Open Reduction and Internal Fixation for Delayed Acetabular Fractures: A Retrospective Study of 43 Patients
Aim: It is difficult to treat delayed acetabular fractures due to massive blood loss during operation. Temporary balloon occlusion of the abdominal aorta was introduced into sacral tumor surgery to reduce intraoperative hemorrhage. The aim of this study was to investigate the effect of this method on reduction of intraoperative blood loss and analyze the complications of this technique in the treatment of delayed acetabular fracture. Methods: We retrospectively reviewed 43 patients with delayed acetabular fracture who were surgically treated through combined approaches. Nineteen patients underwent temporary balloon occlusion of the abdominal aorta; 10 patients had type B fracture and 9 patients had type C fracture according to the Müller AO classification. The remaining 24 patients were classified into a control group; 14 patients had type B fracture and 10 patients had type C fracture. Surgical time, intraoperative blood loss, blood transfusion, satisfactory reduction rate, and functional recovery were recorded and compared between two groups. Merle d'Aubigné and Postel scoring was applied to evaluate the patients. Results: The patients treated with intra-aortic balloon occlusion had a shorter surgical time (p = 0.008), less intraoperative blood loss (p = 0.005), and less transfused blood units (p = 0.001). No complications caused by balloon occlusion. No significant difference were observed in the outcomes and the complications related to acetabular fractures between two groups. Conclusions: Temporary balloon occlusion of the abdominal aorta is a reliable technique to control bleeding for the surgery of delayed acetabular fracture
Frequency-specific corticofugal modulation of the dorsal cochlear nucleus in mice
The primary auditory cortex (AI) modulates the sound information processing in the lemniscal subcortical nuclei, including the anteroventral cochlear nucleus, in a frequency-specific manner. The dorsal cochlear nucleus (DCN) is a non-lemniscal subcortical nucleus but it is tonotopically organized like the anteroventral cochlear nucleus. However, it remains unclear how the AI modulates the sound information processing in the DCN. This study examined the impact of focal electrical stimulation of AI on the auditory responses of the DCN neurons in mice. We found that the electrical stimulation induced significant changes in the best frequency (BF) of DCN neurons. The changes in the BFs were highly specific to the BF differences between the stimulated AI neurons and the recorded DCN neurons. The DCN BFs shifted higher when the AI BFs were higher than the DCN BFs and the DCN BFs shifted lower when the AI BFs were lower than the DCN BFs. The DCN BFs showed no change when the AI and DCN BFs were similar. Moreover, the BF shifts were linearly correlated to the BF differences. Thus, our data suggest that corticofugal modulation of the DCN is also highly specific to frequency information, similar to the corticofugal modulation of the anteroventral cochlear nucleus. The frequency-specificity of corticofugal modulation does not appear limited to the lemniscal ascending pathway
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