Emergence of Gabor-like Receptive Fields in a Recurrent Network of Mixed-Signal Silicon Neurons

Mixed signal analog/digital neuromorphic circuits offer an ideal computational substrate for testing and validating hypotheses about models of sensory processing, as they are affected by low resolution, variability, and other limitations that affect in a similar way real neural circuits. In addition, their real-time response properties allow to test these models in closed-loop sensory-processing hardware setups and to get an immediate feedback on the effect of different parameter settings. Within this context we developed a recurrent neural network architecture based on a model of the retinocortical visual pathway to obtain neurons highly tuned to oriented visual stimuli along a specific direction and with a specific spatial frequency, with Gabor-like receptive fields. The computation performed by the retina is emulated by a Dynamic Vision Sensor (DVS) while the following feed-forward and recurrent processing stages are implemented by a Dynamic Neuromorphic Asynchronous Processor (DYNAP) chip that comprises adaptive integrate-and fire neurons and dynamic synapses. We show how the network implemented on this device gives rise to neurons tuned to specific orientations and spatial frequencies, independent of the temporal frequency of the visual stimulus. Compared to alternative feed-forward schemes, the model proposed produces highly structured receptive fields with a limited number of synaptic connections, thus optimizing hardware resources. We validate the model and approach proposed with experimental results using both synthetic and natural images

Role of doping agent degree of sulfonation and casting solvent on the electrical conductivity and morphology of pedot:Spaes thin films

Poly(3,4-ethylenedioxythiophene) (PEDOT) plays a key role in the field of electrically conducting materials, despite its poor solubility and processability. Various molecules and polymers carrying sulfonic groups can be used to enhance PEDOT’s electrical conductivity. Among all, sul-fonated polyarylether sulfone (SPAES), prepared via homogenous synthesis with controlled degree of sulfonation (DS), is a very promising PEDOT doping agent. In this work, PEDOT was synthesized via high-concentration solvent-based emulsion polymerization using 1% w/w of SPAES with different DS as dopant. It was found that the PEDOT:SPAESs obtained have improved solubility in the chosen reaction solvents, i.e., N, N-dimethylformamide, dimethylacetamide, dimethyl sulfoxide, and N-methyl-2-pyrrolidone and, for the first time, the role of doping agent, DS and polymerization solvents were investigated analyzing the electrical properties of SPAESs and PEDOT:SPAES samples and studying the different morphology of PEDOT-based thin films. High DS of SPAES, i.e., 2.4 meq R-SO3− × g−1 of polymer, proved crucial in enhancing PEDOT’s electrical conductivity. Furthermore, the DMSO capability to favor PEDOT and SPAES chains rearrangement and interaction results in the formation of a polymer film with more homogenous morphology and higher conductivity than the ones prepared from DMAc, DMF, and NMP. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

A Diverse Array of Cancer-Associated MTOR Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity

Genes encoding components of the PI3K–AKT–mTOR signaling axis are frequently mutated in cancer, but few mutations have been characterized in MTOR, the gene encoding the mTOR kinase. Using publicly available tumor genome sequencing data, we generated a comprehensive catalog of mTOR pathway mutations in cancer, identifying 33 MTOR mutations that confer pathway hyperactivation. The mutations cluster in six distinct regions in the C-terminal half of mTOR and occur in multiple cancer types, with one cluster particularly prominent in kidney cancer. The activating mutations do not affect mTOR complex assembly, but a subset reduces binding to the mTOR inhibitor DEPTOR. mTOR complex 1 (mTORC1) signaling in cells expressing various activating mutations remains sensitive to pharmacologic mTOR inhibition, but is partially resistant to nutrient deprivation. Finally, cancer cell lines with hyperactivating MTOR mutations display heightened sensitivity to rapamycin both in culture and in vivo xenografts, suggesting that such mutations confer mTOR pathway dependency. Significance: We report that a diverse set of cancer-associated MTOR mutations confer increased mTORC1/2 pathway activity and that cells harboring these mutations are highly sensitive to rapamycin in culture and in vivo. These findings are clinically relevant as the MTOR mutations characterized herein may serve as biomarkers for predicting tumor responses to mTOR inhibitors.Starr Cancer ConsortiumDavid H. Koch Institute for Integrative Cancer Research at MITAlexander and Margaret Stewart TrustNational Institutes of Health (U.S.) (Grant CA103866)National Institutes of Health (U.S.) (Grant CA129105)National Institutes of Health (U.S.) (Grant AI07389

Prognostic role of circulating tumor cell trajectories in metastatic colorectal cancer

Abstract: Background: A large amount of evidence from clinical studies has demonstrated that circulating tumor cells are strong predictors of outcomes in many cancers. However, the clinical significance of CTC enumeration in metastatic colorectal cancer is still questioned. The aim of this study was to evaluate the clinical value of CTC dynamics in mCRC patients receiving first-line treatments. Materials and methods: Serial CTC data from 218 patients were used to identify CTC trajectory patterns during the course of treatment. CTCs were evaluated at baseline, at a first-time point check and at the radiological progression of the disease. CTC dynamics were correlated with clinical endpoints. Results: Using a cut-off of ≥1 CTC/7.5 mL, four prognostic trajectories were outlined. The best prognosis was obtained for patients with no evidence of CTCs at any timepoints, with a significant difference compared to all other groups. Lower PFS and OS were recognized in group 4 (CTCs always positive) at 7 and 16 months, respectively. Conclusions: We confirmed the clinical value of CTC positivity, even with only one cell detected. CTC trajectories are better prognostic indicators than CTC enumeration at baseline. The reported prognostic groups might help to improve risk stratification, providing potential biomarkers to monitor first-line treatments

Inhibition of Polycomb Repressive Complex2 activity reduces trimethylation of H3K27 and affects development in Arabidopsis seedlings

Background: Polycomb repressive complex 2 (PRC2) is an epigenetic transcriptional repression system, whose catalytic subunit (ENHANCER OF ZESTE HOMOLOG 2, EZH2 in animals) is responsible for trimethylating histone H3 at lysine 27 (H3K27me3). In mammals, gain-of-function mutations as well as overexpression of EZH2 have been associated with several tumors, therefore making this subunit a suitable target for the development of selective inhibitors. Indeed, highly specific small-molecule inhibitors of EZH2 have been reported. In plants, mutations in some PRC2 components lead to embryonic lethality, but no trial with any inhibitor has ever been reported. Results: We show here that the 1,5-bis (3-bromo-4-methoxyphenyl)penta-1,4-dien-3-one compound (RDS 3434), previously reported as an EZH2 inhibitor in human leukemia cells, is active on the Arabidopsis catalytic subunit of PRC2, since treatment with the drug reduces the total amount of H3K27me3 in a dose-dependent fashion. Consistently, we show that the expression level of two PRC2 targets is significantly increased following treatment with the RDS 3434 compound. Finally, we show that impairment of H3K27 trimethylation in Arabidopsis seeds and seedlings affects both seed germination and root growth. Conclusions: Our results provide a useful tool for the plant community in investigating how PRC2 affects transcriptional control in plant development

A Weak Bargaining Set for Contract Choice Problems

In this paper, we consider the problem of choosing a set of multi-party contracts, where each coalition of agents has a non-empty finite set of feasible contracts to choose from. We call such problems, contract choice problems. The main result of this paper states that every contract choice problem has a non-empty weak bargaining set. The need for such a solution concept which is considerably weaker than the core arises, since it is well known that even for very simple contract choice problems, the core may be empty. We also show by means of an example that the bargaining set due to Mas-Colell (1989), as well as a weaker version of it, may be empty for contract choice problems, thereby implying that the weakening we suggest is in some ways tigh

Assessing REALTER simulator: analysis of ocular movements in simulated low-vision conditions with extended reality technology

Immersive technology, such as extended reality, holds promise as a tool for educating ophthalmologists about the effects of low vision and for enhancing visual rehabilitation protocols. However, immersive simulators have not been evaluated for their ability to induce changes in the oculomotor system, which is crucial for understanding the visual experiences of visually impaired individuals. This study aimed to assess the REALTER (Wearable Egocentric Altered Reality Simulator) system’s capacity to induce specific alterations in healthy individuals’ oculomotor systems under simulated low-vision conditions. We examined task performance, eye movements, and head movements in healthy participants across various simulated scenarios. Our findings suggest that REALTER can effectively elicit behaviors in healthy individuals resembling those observed in individuals with low vision. Participants with simulated binocular maculopathy demonstrated unstable fixations and a high frequency of wide saccades. Individuals with simulated homonymous hemianopsia showed a tendency to maintain a fixed head position while executing wide saccades to survey their surroundings. Simulation of tubular vision resulted in a significant reduction in saccade amplitudes. REALTER holds promise as both a training tool for ophthalmologists and a research instrument for studying low vision conditions. The simulator has the potential to enhance ophthalmologists’ comprehension of the limitations imposed by visual disabilities, thereby facilitating the development of new rehabilitation protocols

Ethnic Minorities Rewarded: Ethnostratification on the Wage Market in Belgium

Several previous researches have confirmed the hypothesis of ethnostratification, which holds that the labour market is divided into different ethnic layers. While people of a European origin are over-represented in the top layers (the primary market), people with non-European roots and/or nationalities are more concentrated in bottom layers (the secondary market). Relative to the primary market, this secondary market is characterized by a higher chance of unemployment, lower wages, poorer working conditions and greater job insecurity. This paper deals with a very important condition of work: the wage. Does origin have an impact on the level of wage? We make a distinction between nine origin groups: Belgians, North en West Europeans, South Europeans (from Greece, Spain, Portugal), Italians, East Europeans, Moroccans, Turks, Sub Sahara Africans and Asians. The first part of this article briefly describes the database used for the analyses and presents a few general figures for the total Belgian population. In the second part we examine the impact of origin on wage levels. For each origin group we will give an overview of the average daily wages and the partition over the wage classes. For the weaker populations, gender and age are taken into account. Finally, by means of a regression analysis, we will examine the influence of origin while controlling a few other variables that may influence the wage level