SGLFormer: Spiking Global-Local-Fusion Transformer with high performance.

Introduction: Spiking Neural Networks (SNNs), inspired by brain science, offer low energy consumption and high biological plausibility with their event-driven nature. However, the current SNNs are still suffering from insufficient performance. Methods: Recognizing the brain's adeptness at information processing for various scenarios with complex neuronal connections within and across regions, as well as specialized neuronal architectures for specific functions, we propose a Spiking Global-Local-Fusion Transformer (SGLFormer), that significantly improves the performance of SNNs. This novel architecture enables efficient information processing on both global and local scales, by integrating transformer and convolution structures in SNNs. In addition, we uncover the problem of inaccurate gradient backpropagation caused by Maxpooling in SNNs and address it by developing a new Maxpooling module. Furthermore, we adopt spatio-temporal block (STB) in the classification head instead of global average pooling, facilitating the aggregation of spatial and temporal features. Results: SGLFormer demonstrates its superior performance on static datasets such as CIFAR10/CIFAR100, and ImageNet, as well as dynamic vision sensor (DVS) datasets including CIFAR10-DVS and DVS128-Gesture. Notably, on ImageNet, SGLFormer achieves a top-1 accuracy of 83.73% with 64 M parameters, outperforming the current SOTA directly trained SNNs by a margin of 6.66%. Discussion: With its high performance, SGLFormer can support more computer vision tasks in the future. The codes for this study can be found in https://github.com/ZhangHanN1/SGLFormer.

Collaborative FFE-assisted simplified soft-output MLSE with LDPC for high-speed IM-DD transmissions.

In this paper, we propose a feed-forward equalizer (FFE)-assisted simplified soft-output MLSE (sMLSE) by collaborating the maximum likelihood sequence estimation (MLSE) with soft-decision low-density-parity-check (LDPC) decoding. The simplified sMLSE results in undetermined log-likelihood ratio (LLR) magnitudes when the reserved level is less than or equal to the half of modulation order. This severely degrades the performance of soft-decision forward error correction (SD-FEC) decoding. In the FFE-assisted simplified sMLSE, we use the LLRs calculated from pre-set FFE to replace these undetermined LLRs of simplified sMLSE. Thus, the proposed method eliminates the SD-FEC decoding performance degradation resulted from simplification. We conduct experiments to transmit 184-Gb/s PAM-4 or 255-Gb/s PAM-8 signal in IM-DD system at C-band to evaluate the performance of the proposed sMLSE. The results show that the proposed sMLSE can effectively compensate for the degradation of LLR quality. For 255-Gb/s PAM-8 signal transmissions, the FFE-assisted simplified sMLSE achieves almost the same SD-FEC decoding performance as the conventional sMLSE but with 85% complexity reduction.

Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy.

Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) disruption of substrate degradation with pathogenic changes in lysosomal function, (2) cellular dysfunction, secondary/tertiary accumulation (toxins such as GM2 or GM3 ganglioside, etc.), and inflammatory process, and (3) progressive tissue/organ damage and cell death (e.g., skeletal dysplasia, CNS impairment, etc.). For current and future treatment, several potential treatments for MPS that can penetrate the blood-brain barrier and bone have been proposed and/or are in clinical trials, including targeting peptides and molecular Trojan horses such as monoclonal antibodies attached to enzymes via receptor-mediated transport. Gene therapy trials with AAV, ex vivo LV, and Sleeping Beauty transposon system for MPS are proposed and/or underway as innovative therapeutic options. In addition, possible immunomodulatory reagents that can suppress MPS symptoms have been summarized in this review.

6,6'-Diheptyl-3,3'-bis-[(pyridin-3-yl)ethyn-yl]-5H,5'H-di-pyrrolo-[1,2-b:1',2'-g][2,6]naphthyridine-5,5'-dione.

The complete mol-ecule of the title compound, C42H42N4O2, is generated by a crystallographic centre of symmetry. The pendant heptyl chains adopt extended conformations and the dihedral angle between the pyrrole and pyridine rings is 8.18 (15)°. In the crystal, the mol-ecules are arranged in columnar stacks propagating in the [010] direction via slipped aromatic π-π stacking inter-actions.

CAR T Cells for Treating Severe Atopic Allergic Diseases.

The prevalence of allergic diseases is rising rapdly in the US and the world. While antibody drugs and corticosteroids can provide symptom relief, they cannot cure allergic diseases. Described herein is a novel approach to treating severe atopic allergic diseases - chimeric antigen receptor-engineered T cells - that target and eliminate the cells that produce the causative agent of all atopic allergic diseases, immunoglubulin E (IgE).

Modulation of Neuronal Activity and Saccades at Theta Rhythm During Visual Search in Non-human Primates.

Active exploratory behaviors have often been associated with theta oscillations in rodents, while theta oscillations during active exploration in non-human primates are still not well understood. We recorded neural activities in the frontal eye field (FEF) and V4 simultaneously when monkeys performed a free-gaze visual search task. Saccades were strongly phase-locked to theta oscillations of V4 and FEF local field potentials, and the phase-locking was dependent on saccade direction. The spiking probability of V4 and FEF units was significantly modulated by the theta phase in addition to the time-locked modulation associated with the evoked response. V4 and FEF units showed significantly stronger responses following saccades initiated at their preferred phases. Granger causality and ridge regression analysis showed modulatory effects of theta oscillations on saccade timing. Together, our study suggests phase-locking of saccades to the theta modulation of neural activity in visual and oculomotor cortical areas, in addition to the theta phase locking caused by saccade-triggered responses.

Cancer Cell-Derived Exosomes Promote HCC Tumorigenesis Through Hedgehog Pathway.

PURPOSE: Hepatocellular carcinoma (HCC) accounts for more than 80% of primary liver cancers and is one of the leading causes of cancer-related death in many countries. Cancer cell-derived exosomes are shown to mediate communications between cancer cells and the microenvironment, promoting tumorigenesis. Hedgehog signaling pathway plays important roles in cancer development of HCC. METHODS: Exosomes were isolated from culture medium of HCC cell lines PLC/PRF/5 and MHCC-97H and were found to promote cancer cell growth measured with cell proliferation and colony formation assay. HCC cells cultured with cancer cell-derived exosome had increased cancer stem cell (CSC) population demonstrated by increased cell sphere formation CSC marker expressions. Hedgehog protein Shh was found to be highly expressed in these two HCC cell lines and preferably carried by exosomes. When Shh was knocked down with shRNA, the resulting exosomes had a reduced effect on promoting cancer cell growth or CSC population increase compared to normal cell-derived exosomes. RESULTS: The ability of PLC/PRF/5 cells to form tumor in a xenograft model was increased by the addition of the exosomes from control cancer cells but not the exosomes from Shh knocked down cancer cells. Finally, the higher plasma Exo-Shh levels were associated with later tumor stages, higher histological grades, multiple tumors, and higher recurrence rates. CONCLUSION: This study demonstrated that HCC cells secreted Shh via exosome and promote tumorigenesis through the activated Hedgehog pathway.

[New Design of Revivent TC System].

Left ventricular aneurysm (LVA) is a common complication of myocardial infarction. Traditional medical and surgical treatments are not effective or require high doctors' operational skills and patients' physical fitness. With the development of minimally invasive medical devices, it becomes possible for revivent TC system to treat LVA and reconstruct the left ventricle. This study introduces an existing product and its defect when used. From the perspective of clinical needs, we propose a new design of revivent TC system which realizes accurate force measurement and simplifies surgery.

Stability of motor cortex network states during learning-associated neural reorganizations.

A substantial reorganization of neural activity and neuron-to-movement relationship in motor cortical circuits accompanies the emergence of reproducible movement patterns during motor learning. Little is known about how this tempest of neural activity restructuring impacts the stability of network states in recurrent cortical circuits. To investigate this issue, we reanalyzed data in which we recorded for 14 days via population calcium imaging the activity of the same neural populations of pyramidal neurons in layer 2/3 and layer 5 of forelimb motor and premotor cortex in mice during the daily learning of a lever-press task. We found that motor cortex network states remained stable with respect to the critical network state during the extensive reorganization of both neural population activity and its relation to lever movement throughout learning. Specifically, layer 2/3 cortical circuits unceasingly displayed robust evidence for operating at the critical network state, a regime that maximizes information capacity and transmission and provides a balance between network robustness and flexibility. In contrast, layer 5 circuits operated away from the critical network state for all 14 days of recording and learning. In conclusion, this result indicates that the wide-ranging malleability of synapses, neurons, and neural connectivity during learning operates within the constraint of a stable and layer-specific network state regarding dynamic criticality, and suggests that different cortical layers operate under distinct constraints because of their specialized goals.NEW & NOTEWORTHY The neural activity reorganizes throughout motor learning, but how this reorganization impacts the stability of network states is unclear. We used two-photon calcium imaging to investigate how the network states in layer 2/3 and layer 5 of forelimb motor and premotor cortex are modulated by motor learning. We show that motor cortex network states are layer-specific and constant regarding criticality during neural activity reorganization, and suggests that layer-specific constraints could be motivated by different functions.

Characteristics of longitudinal development of pupils’ loneliness:a follow-up study / 中国学校卫生

Objective@#To explore the development of children’s loneliness and their gender differences, and to provide references for elementary school students’ mental health education.@*Methods@#The Children’s Loneliness Scale was being used in this research. 771 students in grade 3 and 4 were investigated and followed for 2 years, a total of 5 waves of data were collected.@*Results@#The scores of pupils s loneliness in 5 times were(33.96±12.77)(31.13±12.82)(29.66±12.65)(28.67±11.97)(27.60±11.63) respectively. Feelings of loneliness decline rapidly in mid-childhood(eta1=-2.61, P<0.01), but in late childhood, it showed a significant upward trend(eta2=0.27, P<0.01). In the middle and late childhood, the level of loneliness of boys was significantly higher than that of girls at different points in time. But there was no significant gender difference in the pace of loneliness during childhood(β1=0.06, β2=0.01, P>0.05).@*Conclusion@#Childhood loneliness presents non-linear curve,decreasing with age during early childhood, but tends to increase in later childhood.

Cortical Circuit Dynamics Are Homeostatically Tuned to Criticality In Vivo.

Homeostatic mechanisms stabilize neuronal activity in vivo, but whether this process gives rise to balanced network dynamics is unknown. Here, we continuously monitored the statistics of network spiking in visual cortical circuits in freely behaving rats for 9 days. Under control conditions in light and dark, networks were robustly organized around criticality, a regime that maximizes information capacity and transmission. When input was perturbed by visual deprivation, network criticality was severely disrupted and subsequently restored to criticality over 48 h. Unexpectedly, the recovery of excitatory dynamics preceded homeostatic plasticity of firing rates by >30 h. We utilized model investigations to manipulate firing rate homeostasis in a cell-type-specific manner at the onset of visual deprivation. Our results suggest that criticality in excitatory networks is established by inhibitory plasticity and architecture. These data establish that criticality is consistent with a homeostatic set point for visual cortical dynamics and suggest a key role for homeostatic regulation of inhibition.

The Influence of Tool Rake Surface Geometry on the Hard Turning Process of AISI52100 Hardened Steel.

The hard turning process has been widely used in the field of hard material precision machining because of its high efficiency, low processing residual stress, and low environmental pollution. Due to its undesirably processing quality, it is still not a substitute for traditional grinding, so many studies have reported that the process has been optimized. However, there has been little research on the geometry optimization of hard cutting tools, which have a great influence on the traditional machining process. In this paper, two tools with different rake face shapes are designed. The finite element analysis method is used to compare their performance with a conventional plane tool while turning hardened steel. The results show that the cutting performance of the designed tool T1 and T2 (chip morphology, cutting force, and cutting temperature) and the quality of the machined surface are improved compared with the tool. The cutting force decreased by 12.72% and 14.74%, the cutting temperature decreased by 7.56% and 9.01%, respectively, and the surface residual stress decreased by 26.56% and 28.66%.

Poly (propylene fumarate)/ß-calcium phosphate composites for enhanced bone repair.

A composite based on poly (propylene fumarate) (PPF) was investigated as a potential bone repair material for clinical use and it showed low heat release, suitable mechanical property and good biocompatibility. The in situ curing process would finish in less than 10 min. Compared with PMMA, PPF/TCP showed great decrease in heat release as the maximum temperature during curing process was 54.7 °C ± 1.69 °C. The compressive strength was between 109 ± 2 and 133 ± 6 MPa and the compressive modulus was 146 ± 11 to 161 ± 27 MPa, which were believed to be compatible and further supportive to surrounding bone. Besides, the surface morphology and hydrophilicity could be tailored by adjusting the content of ß-calcium phosphate (ß-TCP). Relatively stable pH value during degradation in PBS solution implied that it would not bring about acidification when implanted in vivo. In addition, PPF/TCP would boost mineralization and the apatite-like deposits on surface may advance the integrity of bone and materials. Moreover, the PPF/TCP obviously degraded and new bone formed especially when loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) in vivo. In summary, PPF/TCP composites showed suitable physical and chemical properties as well as good bioactivity and may therefore be a promising material for bone repair.

A deep neural network approach to acoustic source localization in a shallow water tank experiment.

In this paper, an acoustic source localization method using the emerging technology of the deep neural network (DNN) is proposed. After the construction and training of the DNN, the capability of the DNN for source localization through a set of numerical simulations is verified. Next, experimental studies and demonstrations in a very shallow water tank with acoustic reflective walls are prepared, which enable the quick acquisition of a huge amount of experimental data for the training of a one-dimensional DNN-based source localization model. The development of the DNN-based source localization method and the corresponding numerical and experimental demonstration constitute the main contribution of this work. The associated performance is then evaluated at various frequencies. In particular, the localization results of the DNN are compared with readily available model-based localization methods, such as the conventional matched field processing method and the normal-mode based multiple signal classification method. The comparison shows that the proposed DNN approach is able to produce satisfactory accuracy in this reflective shallow water tank environment, for which a forward acoustic propagating model is not required. Last but not least, the generality of the proposed DNN approach from one-dimensional localization to progressively more complicated two-dimensional tasks is also considered.

Development of coping strategy and gender difference during childhood: a two-year follow-up study / 中国学校卫生

Objective@#To explore the development trajectory of coping strategy and gender difference during childhood.@*Methods@#A total of 355 children in grade 3 from 2 primary schools in Zhongshan of Guangdong Province and Dazhou of Sichuan Province were assessed with cooping strategy and followed up for 2 years.@*Results@#Positive and negative coping strategies have different developmental trajectories during childhood, with non-linear upward trend in positive coping strategies (eta11=0.11, 0.02, P>0.05) and non-linear downward trend in negative coping strategies (eta12=-0.70, -0.08, P<0.01). The development of positive coping strategies during childhood showed no significant gender difference (△χ2=5.19, df=4, P>0.05). While the initial average negative coping strategies was significant higher in boys(β=-0.56, P<0.01), and the decreasing velocity was faster than the girls(β=0.33, P<0.01).@*Conclusion@#The coping strategy during childhood shows great plasticity, with positive and negative coping strategy develops in different trajectory. The developmental trajectories of negative coping strategies during childhood illustrate significant sex difference, while it is not the case for positive coping strategy.

Chimeric Antigen Receptors Based on Low Affinity Mutants of FcεRI Re-direct T Cell Specificity to Cells Expressing Membrane IgE.

IgE is the key mediator of allergic responses. Omalizumab, an IgE-specific monoclonal antibody that depletes IgE, is effective for treating severe allergic asthma. The need for frequent administration of the expensive drug, however, limits its applications. Taking advantage of T cell memory, adoptive T cell therapy (ACT) targeting IgE-producing cells has the potential to achieve long-term suppression of IgE and relief of symptoms for severe allergic diseases. The transmembrane form of IgE (mIgE), which is present on all IgE-producing cells, serves as an excellent molecular target for ACT that employs chimeric antigen receptors (CARs). Here, we designed and tested CARs that use the extracellular domain of high affinity IgE receptor, FcεRIα, for mIgE recognition. When expressed on Jurkat T cells, FcεRIα-based CARs mediated robust responses in terms of CD69 upregulation to U266 myeloma cells expressing low levels of mIgE. FcεRIα-based CARs specifically recognized cells expressing mIgE, but not cells with secreted IgE captured through Fcε receptors. CAR+ Jurkat cells did not respond to LAD2 mast cells with secreted IgE bound through FcεRI or Ramos cells with secreted IgE bound through FcεRII. Co-culture of CAR+ Jurkat cells and LAD2 mast cells with IgE bound did not trigger LAD2 cell degranulation. The activity of CAR using wild type FcεRIα for mIgE binding was inhibited by the presence secreted IgE, which likely blocked CAR-mIgE interaction. The activities of CARs using low affinity mutants of FcεRIα, however, tolerated secreted IgE at relatively high concentrations. Moreover, primary human CD8+ T cells expressing a low affinity mutant CAR responded to U266 cells with INFγ production and cytotoxicity despite the presence of secreted IgE. The potency, specificity, and robustness of our CAR design, combined with repaid advances in the safety of ACT, hold promise for novel and highly effective cell-based therapies against severe allergic diseases.

Enhanced cell affinity of PHBHHx composite scaffold with polylactide-graft-hydroxyapatite as compatibilizer.

Poor interfacial bonding and liability to aggregation were the major obstacles for designing of composite scaffolds. Herein, hydroxyapatite (HA) surface-grafted with poly (l-lactide) via ring-opening polymerization was prepared and introduced into PHBHHx-based complex scaffold serving as oligomer compatibilizer. The physicochemical properties, including superficial roughness and wettability, mechanical strength, as well as in vitro bioactivity were systematically investigated. Improved cellular response was acquired owing to the favourable uniformity and interfacial compatibility, as well as the decreased contact angle and elevated roughness, through surface-modification strategy. Moreover, some of the osteogenic marker genes (COL I, Runx2, OCN and OPN) were up-regulated, thus made for the osteogenic differentiation. Our study extrapolated that the PHBHHx-based composite scaffold combined with surface-graft HA compatibilizer might be a potential candidate for bone repairing.

In vitro and in vivo degradation behavior of poly(trimethylene carbonate-co-d,l-lactic acid) copolymer.

We present P(TMC-co-DLLA) copolymer with the molar ratio of TMC: DLLA = 15: 85 was used to systematic study of in vivo and in vitro degradation behaviors. Dense homogeneous copolymer specimens were prepared by compression molding method. The in vitro and in vivo degradation were, respectively, performed at simulative body condition and implanted into rat's subcutaneous condition. Investigations were followed via physicochemical and histological analysis such as SEM, GPC, DSC, FTIR and H&E stain. The results demonstrate that copolymeric material can degrade in phosphate buffer solution (PBS) and in rat's body, and the in vivo degradation rate is faster. Obvious decline of molecule weight and mass loss has been observed, which led to the attenuation of mechanical strength. Furthermore, apart from the hydrolysis, macrophagocytes took part in the phagocytosis in vivo, indicating that degradation rate could be regulated by the combinational mechanism. It is concluded that P(TMC-co-DLLA) copolymer is a promising candidate for tissue repair.

Criticality predicts maximum irregularity in recurrent networks of excitatory nodes.

A rigorous understanding of brain dynamics and function requires a conceptual bridge between multiple levels of organization, including neural spiking and network-level population activity. Mounting evidence suggests that neural networks of cerebral cortex operate at a critical regime, which is defined as a transition point between two phases of short lasting and chaotic activity. However, despite the fact that criticality brings about certain functional advantages for information processing, its supporting evidence is still far from conclusive, as it has been mostly based on power law scaling of size and durations of cascades of activity. Moreover, to what degree such hypothesis could explain some fundamental features of neural activity is still largely unknown. One of the most prevalent features of cortical activity in vivo is known to be spike irregularity of spike trains, which is measured in terms of the coefficient of variation (CV) larger than one. Here, using a minimal computational model of excitatory nodes, we show that irregular spiking (CV > 1) naturally emerges in a recurrent network operating at criticality. More importantly, we show that even at the presence of other sources of spike irregularity, being at criticality maximizes the mean coefficient of variation of neurons, thereby maximizing their spike irregularity. Furthermore, we also show that such a maximized irregularity results in maximum correlation between neuronal firing rates and their corresponding spike irregularity (measured in terms of CV). On the one hand, using a model in the universality class of directed percolation, we propose new hallmarks of criticality at single-unit level, which could be applicable to any network of excitable nodes. On the other hand, given the controversy of the neural criticality hypothesis, we discuss the limitation of this approach to neural systems and to what degree they support the criticality hypothesis in real neural networks. Finally, we discuss the limitations of applying our results to real networks and to what degree they support the criticality hypothesis.