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"Ma, Wei Ji"
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قصة نجاح \علي بابا\ : حياة \جاك ما\ أغني رجل في الصين
طفل صغير لعائلة فقيرة تهوى التمثيل، طالب فاشل يتعلم الإنجليزية، مدرس متوسط المستوى، سائق عربة بضائع، عاطل عن العمل، يفشل في الالتحاق بأي وظيفة، مترجم لغة إنجليزية محترف، صاحب شركة ترجمة، صاحب موقع إلكتروني لجمع البيانات، مؤسس أكبر موقع متخصص في التجارة بين الشركات، صاحب مؤسسة \"علي بابا\" أكبر رجل أعمال في الصين، أغنى أغنياء الصين، كل هؤلاء في الحقيقة هم شخص واحد، أو بمعنى أصح هي قصة حياة أسطورة الصين حالياً، الرجل الذي غير خريطة التجارة العالمية، إنه \"ما يون\" حسب الاسم الصيني أو جاك ما حسب ما هو معروف به في العالم، والذي يحكي كتاب \"قصة نجاح علي بابا\"، قصة صعوده والتي هي أيضا قصة صعود الصين. يقترب المؤلف من عالم \"جاك ما\" الحقيقي ويحكي قصته منذ نعومة أظفاره، حتى صار إمبراطور التجارة في العالم، إنها قصة صعود شخص وصعود دولة بحجم الصين، قصة ترفض أن يكون هناك مستحيل، وتثبت أن الأفكار هي رأس المال الأكبر في العالم، قصة الفضائي كما يجب أن يسميه الصينيون، الذي جعل حياتهم أفضل، قصة رجل حفر اسمه في تاريخ البشرية، والذي يفتح لنا بتجربته آفاقا أرحب نرى بها العالم ونرى بها أنفسنا بشكل مختلف.
Book
A diverse range of factors affect the nature of neural representations underlying short-term memory
Sequential and persistent activity models are two prominent models of short-term memory in neural circuits. In persistent activity models, memories are represented in persistent or nearly persistent activity patterns across a population of neurons, whereas in sequential models, memories are represented dynamically by a sequential activity pattern across the population. Experimental evidence for both models has been reported previously. However, it has been unclear under what conditions these two qualitatively different types of solutions emerge in neural circuits. Here, we address this question by training recurrent neural networks on several short-term memory tasks under a wide range of circuit and task manipulations. We show that both sequential and nearly persistent solutions are part of a spectrum that emerges naturally in trained networks under different conditions. Our results help to clarify some seemingly contradictory experimental results on the existence of sequential versus persistent activity-based short-term memory mechanisms in the brain.Two qualitatively different neural mechanisms for maintaining information in short-term memory, experimentally observed in animal studies, emerge as part of a spectrum of solutions in recurrent neural networks trained on short-term memory tasks.
Journal Article
Confidence reports in decision-making with multiple alternatives violate the Bayesian confidence hypothesis
Decision confidence reflects our ability to evaluate the quality of decisions and guides subsequent behavior. Experiments on confidence reports have almost exclusively focused on two-alternative decision-making. In this realm, the leading theory is that confidence reflects the probability that a decision is correct (the posterior probability of the chosen option). There is, however, another possibility, namely that people are less confident if the best two options are closer to each other in posterior probability, regardless of how probable they are in absolute terms. This possibility has not previously been considered because in two-alternative decisions, it reduces to the leading theory. Here, we test this alternative theory in a three-alternative visual categorization task. We found that confidence reports are best explained by the difference between the posterior probabilities of the best and the next-best options, rather than by the posterior probability of the chosen (best) option alone, or by the overall uncertainty (entropy) of the posterior distribution. Our results upend the leading notion of decision confidence and instead suggest that confidence reflects the observer’s subjective probability that they made the best possible decision.
Conventional theory suggests that people’s confidence about a decision reflects their subjective probability that the decision was correct. By studying decisions with multiple alternatives, the authors show that confidence reports instead reflect the difference in probabilities between the chosen and the next-best alternative.
Journal Article
Uncertainty-based inference of a common cause for body ownership
Many studies have investigated the contributions of vision, touch, and proprioception to body ownership, i.e., the multisensory perception of limbs and body parts as our own. However, the computational processes and principles that determine subjectively experienced body ownership remain unclear. To address this issue, we developed a detection-like psychophysics task based on the classic rubber hand illusion paradigm, where participants were asked to report whether the rubber hand felt like their own (the illusion) or not. We manipulated the asynchrony of visual and tactile stimuli delivered to the rubber hand and the hidden real hand under different levels of visual noise. We found that: (1) the probability of the emergence of the rubber hand illusion increased with visual noise and was well predicted by a causal inference model involving the observer computing the probability of the visual and tactile signals coming from a common source; (2) the causal inference model outperformed a non-Bayesian model involving the observer not taking into account sensory uncertainty; (3) by comparing body ownership and visuotactile synchrony detection, we found that the prior probability of inferring a common cause for the two types of multisensory percept was correlated but greater for ownership, which suggests that individual differences in rubber hand illusion can be explained at the computational level as differences in how priors are used in the multisensory integration process. These results imply that the same statistical principles determine the perception of the bodily self and the external world.
Journal Article
Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway
Cisplatin-based chemotherapy was widely used in treating human malignancies. However, side effects and chemoresistance remains the major obstacle.
To verify whether natural borneol (NB) can enhance cisplatin-induced glioma cell apoptosis and explore the mechanism.
Cytotoxicity of cisplatin and/or NB towards U251 and U87 cells were determined with the MTT assay. Cells were treated with 0.25-80 μg/mL cisplatin and/or 5-80 μM NB for 48 h. The effects of NB and/or cisplatin on apoptosis and cell cycle distribution were quantified by flow cytometric analysis. Protein expression was detected by western blotting. ROS generation was conducted by measuring and visualising an oxidation-sensitive fluorescein DCFH-DA.
NB synergistically enhanced the anticancer efficacy of cisplatin in human glioma cells. Co-treatment of 40 μg/mL NB and 40 μg/mL cisplatin significantly inhibited U251 cell viability from 100% to 28.2% and increased the sub-G1 population from 1.4% to 59.3%. Further detection revealed that NB enhanced cisplatin-induced apoptosis by activating caspases and triggering reactive oxygen species (ROS) overproduction as evidenced by the enhancement of green fluorescence intensity from 265% to 645%. ROS-mediated DNA damage was observed as reflected by the activation of ATM/ATR, p53 and histone. Moreover, MAPKs and PI3K/AKT pathways also contributed to co-treatment-induced U251 cell growth inhibition. ROS inhibition by antioxidants effectively improved MAPKs and PI3K/AKT functions and cell viability, indicating that NB enhanced cisplatin-induced cell growth in a ROS-dependent manner.
Natural borneol had the potential to sensitise human glioma cells to cisplatin-induced apoptosis with potential application in the clinic.
Journal Article
Point-estimating observer models for latent cause detection
The spatial distribution of visual items allows us to infer the presence of latent causes in the world. For instance, a spatial cluster of ants allows us to infer the presence of a common food source. However, optimal inference requires the integration of a computationally intractable number of world states in real world situations. For example, optimal inference about whether a common cause exists based on N spatially distributed visual items requires marginalizing over both the location of the latent cause and 2 N possible affiliation patterns (where each item may be affiliated or non-affiliated with the latent cause). How might the brain approximate this inference? We show that subject behaviour deviates qualitatively from Bayes-optimal, in particular showing an unexpected positive effect of N (the number of visual items) on the false-alarm rate. We propose several “point-estimating” observer models that fit subject behaviour better than the Bayesian model. They each avoid a costly computational marginalization over at least one of the variables of the generative model by “committing” to a point estimate of at least one of the two generative model variables. These findings suggest that the brain may implement partially committal variants of Bayesian models when detecting latent causes based on complex real world data.
Journal Article
Clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in Chinese population with mismatch repair deficient urothelial carcinoma: a real-world study
Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.
Journal Article
Delta and Notch-like epidermal growth factor-related receptor suppresses human glioma growth by inhibiting oncogene TOR4A
Delta and Notch-like endothelial growth factor-related receptor (DNER) is a transmembrane protein that mediates signal communication between neurons and glial cells. This study was performed to elucidate the specific mechanism by which DNER inhibits human glioma growth. RNA sequencing was used to detect differentially expressed genes after DNER inhibition in glioma cells. The functions of the Torsin family 4 member A (TOR4A) gene were explored through cell proliferation and clonogenic assays, flow cytometric analysis, in vitro cell migration and invasion assays, in vivo glioma transplantation, and human glioma tissue analysis using the Chinese Glioma Genome Atlas database. Protein expression levels were determined using the western blot assay. We found that TOR4A was highly expressed after the inhibition of DNER in glioma cells. The prognosis of patients with gliomas that expressed high levels of TOR4A was worse than those with low levels of the protein. TOR4A promoted the proliferation of glioma cells and inhibited their apoptosis, likely by enhancing the expression of phosphorylated protein kinase B (p-AKT) and inhibiting that of antiapoptotic proteins. We confirmed that TOR4A is an oncogene and that DNER acts as a tumor suppressor gene by inhibiting TOR4A and its functions of promoting p-AKT and inhibiting antiapoptotic protein expression.
Journal Article
Trial-to-trial, uncertainty-based adjustment of decision boundaries in visual categorization
Categorization is a cornerstone of perception and cognition. Computationally, categorization amounts to applying decision boundaries in the space of stimulus features. We designed a visual categorization task in which optimal performance requires observers to incorporate trial-to-trial knowledge of the level of sensory uncertainty when setting their decision boundaries. We found that humans and monkeys did adjust their decision boundaries from trial to trial as the level of sensory noise varied, with some subjects performing near optimally. We constructed a neural network that implements uncertainty-based, near-optimal adjustment of decision boundaries. Divisive normalization emerges automatically as a key neural operation in this network. Our results offer an integrated computational and mechanistic framework for categorization under uncertainty.
Journal Article
A computational approach to the N-back task
The
N
-back task is one of the most popular paradigms for studying the cognitive mechanisms of working memory (WM). The task requires the observer to view a sequence of stimuli and judge whether the current stimulus (
probe
) matches the one presented
N
stimuli ago (
target
). A key phenomenon is that the intervening stimuli (
distractors
) interfere with task performance. Unfortunately, the classic
N
-back task uses complex categorical stimuli, making it unfit to quantify the effect of feature similarity on interference strength. Here, we introduce the “analog
N
-back task”, which utilizes stimuli varying continuously in orientation or color. This task variant enables us to measure interference strength on a continuum, providing data suitable for identifying the sources of interference using computational models. In the analog 2-back task, we found that interference increased with feature similarity between the probe and both task-relevant (1-back) and task-irrelevant (3-back) distractors. We next developed and evaluated three main models that each incorporated a Bayesian decision step and differed from an optimal non-interference model in one component only: an early-pooling model, a late-pooling model, and a substitution model. Model comparison suggests that interference emerges late in processing, most likely due to confusion between stimuli during WM retrieval. Our work puts the study of interference in the
N
-back task on a firmer computational footing and provides a unified framework for examining the sources of interference across domains.
Journal Article