Miracle-dz/UniFAR-FTUs huggingface dataset:
Toward a conceptual framework for designing sustainable cyber-physical system architectures: A systematic mapping study

Cyber-physical systems (CPS) represent devices whose components enable interaction between machines and processes. One of the biggest challenges of these systems today is the ability to adjust to changes at the time of execution as they are implemented in environments with a multidimensional complexity, this challenge is currently addressed from the design of the systems themselves by integrating sustainability. With this problem in mind, the present document describes a systematic mapping study of the literature with the goal of demonstrating the current panorama of the frameworks, designs, and/or models used at the time of initiating the development of a cyber-physical system. As a result, it has been concluded that there is a lack of guidelines to construct sustainable, and evolvable cyber-physical systems. To address these issues, a framework for designing sustainable CPS architectures is outlined.
Improving the performance of supervised deep learning for regulatory genomics using phylogenetic augmentation

Motivation Supervised deep learning is used to model the complex relationship between genomic sequence and regulatory function. Understanding how these models make predictions can provide biological insight into regulatory functions. Given the complexity of the sequence to regulatory function mapping (the cis-regulatory code), it has been suggested that the genome contains insufficient sequence variation to train models with suitable complexity. Data augmentation is a widely used approach to increase the data variation available for model training, however current data augmentation methods for genomic sequence data are limited. Results Inspired by the success of comparative genomics, we show that augmenting genomic sequences with evolutionarily related sequences from other species, which we term phylogenetic augmentation, improves the performance of deep learning models trained on regulatory genomic sequences to predict high-throughput functional assay measurements. Additionally, we show that phylogenetic augmentation can rescue model performance when the training set is down-sampled and permits deep learning on a real-world small dataset, demonstrating that this approach improves experimental data efficiency. Overall, this data augmentation method represents a solution for improving model performance that is applicable to many supervised deep learning problems in genomics. Availability and implementation The open-source GitHub repository agduncan94/phylogenetic_augmentation_paper includes the code for rerunning the analyses here and recreating the figures. Contact alan.moses@utoronto.ca
Implications of ubiquitination and the maintenance of replication fork stability in cancer therapy

Abstract DNA replication forks are subject to intricate surveillance and strict regulation by sophisticated cellular machinery. Such close regulation is necessary to ensure the accurate duplication of genetic information and to tackle the diverse endogenous and exogenous stresses that impede this process. Stalled replication forks are vulnerable to collapse, which is a major cause of genomic instability and carcinogenesis. Replication stress responses, which are organized via a series of coordinated molecular events, stabilize stalled replication forks and carry out fork reversal and restoration. DNA damage tolerance and repair pathways such as homologous recombination and Fanconi anemia also contribute to replication fork stabilization. The signaling network that mediates the transduction and interplay of these pathways is regulated by a series of post-translational modifications, including ubiquitination, which affects the activity, stability, and interactome of substrates. In particular, the ubiquitination of replication protein A and proliferating cell nuclear antigen at stalled replication forks promotes the recruitment of downstream regulators. In this review, we describe the ubiquitination-mediated signaling cascades that regulate replication fork progression and stabilization. In addition, we discuss the targeting of replication fork stability and ubiquitination system components as a potential therapeutic approach for the treatment of cancer.
The Inherited KRAS-variant as a Biomarker of Cetuximab Response in NSCLC

Abstract Purpose: RTOG 0617 was a phase III randomized trial for patients with unresectable stage IIIA/IIIB non–small cell lung cancer comparing standard-dose (60 Gy) versus high-dose (74 Gy) radiotherapy and chemotherapy, plus or minus cetuximab. Although the study was negative, based on prior evidence that patients with the KRAS-variant, an inherited germline mutation, benefit from cetuximab, we evaluated KRAS-variant patients in RTOG 0617. Experimental Design: From RTOG 0617, 328 of 496 (66%) of patients were included in this analysis. For time-to-event outcomes, stratified log-rank tests and multivariable Cox regression models were used. For binary outcomes, Cochran—Mantel–Haenzel tests and multivariable logistic regression models were used. All statistical tests were two sided, and a P value <0.05 was considered significant. Results: A total of 17.1% (56/328) of patients had the KRAS-variant, and overall survival rates were similar between KRAS-variant and non-variant patients. However, there was a time-dependent effect of cetuximab seen only in KRAS-variant patients—while the hazard of death was higher in cetuximab-treated patients within year 1 [HR = 3.37, 95% confidence interval (CI): 1.13–10.10, P = 0.030], death was lower from year 1 to 4 (HR = 0.33, 95% CI: 0.11–0.97, P = 0.043). In contrast, in non-variant patients, the addition of cetuximab significantly increased local failure (HR = 1.59, 95% CI: 1.11–2.28, P = 0.012). Conclusions/Discussion: Although an overall survival advantage was not achieved in KRAS-variant patients, there is potential impact of cetuximab for this genetic subset of patients. In contrast, cetuximab seems to harm non-variant patients. These findings further support the importance of genetic patient selection in trials studying the addition of systemic agents to radiotherapy. Significance: The KRAS-variant is the first functional, inherited miRNA-disrupting variant identified in cancer. Our findings support that cetuximab has a potentially beneficial impact on KRAS-variant patients treated with radiation. The work confirms prior evidence that KRAS-variant patients are a subgroup who are especially sensitive to radiation. These findings further support the potential of this class of variants to enable true treatment personalization, considering the equally important endpoints of response and toxicity.
Fluctuations Hypothesize the New Explanation of Meridians in Living Systems

Biosystems are complex. Their physiology is well-controlled with various negative feedback signals and processes, it describes by opposite interfering effects which are characterized in the Eastern philosophy by Yin-Yang (Y-Y) pairs. Y-Y pairs could be described by the promoter-suppressor pairs in a wide range of physiologic signals creating the homeostasis of the complex system. This type of control appears as fluctuations from the average (mean) value of the signal. The mean carries an ineluctable fluctuation (called pink-noise or 1/f noise). All signals in homeostasis have equal entropy (SE = 1.8), which is the character of the complex equilibrium. The various controlling opposite signals (Y-Y) have different time-scales which change by aging. The processes with smaller time-scale are degraded by aging, but the pink-noise ensures that the deviations of the signals of the healthy homeostatic system remain constant. Meridians are connected to the general transport systems that combined the material and the information transport with the considerable transport networks, like blood, lymph, nerve, cell-junctions, mesenchymal “ground substance” cytoskeletons. The meridians in this meaning only virtual line averaged from multiple realized paths to connect two acupuncture points by the material, energy and information transport processes. The meridian network is designed by various coupling points (acupoints), which could be perturbed by actuating stimulus. Our objective is to describe the meridian system from complexity point of view.
Ventromedial Prefrontal Cortex and Basolateral Amygdala Projections to Ventromedial Striatum Encode Active Avoidance Behavior

Active avoidance is a fundamental defensive behavior, defined as performing a voluntary action to escape a noxious stimulus. Active avoidance serves as an adaptive response to threat, ensuring safety. In individuals with anxiety disorders and post-traumatic stress disorder, avoidance behavior can become maladaptive when even safe situations are avoided, at great psychosocial cost. Corticostriatal and amygdalostriatal pathways have been implicated in active avoidance, though their role in learning and expression of this behavior is not fully understood. Projections from the ventromedial prefrontal cortex (vmPFC) to the ventromedial striatum (VMS) have been shown to regulate a variety of defensive behaviors; however, their role in active avoidance has not previously been examined. Additionally, basolateral amygdala (BLA) projections to the VMS have been shown to promote active avoidance in studies utilizing pharmacological inactivation and optogenetic inhibition, though in vivo real time neural activity in this pathway has not been recorded during active avoidance learning. Here we utilized fiber photometry for in vivo recordings of neural activity in vmPFC-VMS and BLA-VMS projections during active avoidance learning and expression. We implemented a two-way signaled active avoidance paradigm in which a light cue served as the conditioned stimulus (CS) signaling an impending foot shock. We examined changes in neural activity in these two projections during CS presentation, onset of active avoidance, and conditioned freezing. We found that vmPFC-VMS projections develop learning-related increases in activity at CS onset across training, while BLA-VMS projections do not show learning-related encoding of the CS. Additionally, we found that both vmPFC-VMS and BLA-VMS projections develop an increase in activity at avoidance onset. No changes in neural activity were observed during cued freezing in either vmPFC-VMS or BLA-VMS projections. Together these results indicate that vmPFC-VMS projections encode both CS and avoidance, while BLA-VMS projections may simply encode avoidance. Finally, we utilized optogenetic inhibition of vmPFC-VMS projections during the CS to investigate the necessity of this pathway for expression of active avoidance behavior. We found that inhibition of vmPFC-VMS projections attenuates learned active avoidance behavior, indicating that activity in this pathway is required for proper active avoidance. In summary, our results demonstrate task-relevant encoding of active avoidance behavior in vmPFC-VMS and BLA-VMS projections.
Residual force depression is not related to positive muscle fascicle work during submaximal voluntary dorsiflexion contractions in humans

Residual force depression (rFD) following active muscle shortening is commonly assumed to strongly and linearly increase with increasing muscle work, but this has not been systematically tested during voluntary contractions in humans. Using dynamometry, we compared steady-state ankle joint torques (N=16) following tibialis anterior (TA) muscle-tendon unit (MTU) lengthening and shortening to the torque during submaximal voluntary fixed-end dorsiflexion reference contractions (REF) at a matched MTU length and EMG amplitude. B-mode ultrasound revealed that TA fascicle shortening amplitudes were significantly reduced (p<0.001) during MTU lengthening with no preload over small (LENsmall) and medium (LENmedium) amplitudes, respectively, relative to REF. MTU lengthening with a preload over a large (LENlargeP) amplitude significantly (p<0.001) increased fascicle shortening relative to REF, as well as stretch amplitudes relative to LENsmall and LENmedium (p≤0.001), but the significant (p≤0.028) steady-state fascicle force enhancement relative to REF was similar to LENsmall and LENmedium (3-5%). MTU shortening with and without a preload over small (SHOsmallP/SHOsmall) and large (SHOlargeP/SHOlarge) amplitudes significantly (p<0.001) increased positive fascicle and MTU work relative to REF, but significant (p≤0.006) rFD was observed in SHOsmallP and SHOlargeP (7-10%) only. rFD was linearly related to positive MTU work (rrm(47)=0.48, p<0.001), but not positive fascicle work (rrm(47)=0.16, p=0.277). Our findings indicate that MTU lengthening without substantial fascicle stretch enhances steady-state force output, which might be due to less shortening-induced rFD. Our findings also indicate that different amounts of positive fascicle and MTU work induce similar rFD, which cautions against using work to predict rFD during submaximal voluntary contractions.
Signatures of transposon-mediated genome inflation, host specialization, and photoentrainment in Entomophthora muscae and allied entomophthoralean fungi

Despite over a century of observations, the obligate insect parasites within the order Entomophthorales remain poorly characterized at the genetic level. This is in part due to their large genome sizes and difficulty in obtaining sequenceable material. In this manuscript, we leveraged a recently-isolated, laboratory-tractable Entomophthora muscae isolate and improved long-read sequencing to obtain a largely-complete entomophthoralean genome. Our E. muscae assembly is 1.03 Gb, consists of 7,810 contigs and contains 81.3% complete fungal BUSCOs. Using a comparative approach with other available (transcriptomic and genomic) datasets from entomophthoralean fungi, we provide new insight into the biology of these understudied pathogens. We offer a head-to-head comparison of morphological and molecular data for species within the E. muscae species complex. Our findings suggest that substantial taxonomic revision is needed to define species within this group and we provide recommendations for differentiating strains and species in the context of the existing body of E. muscae scientific literature. We show that giant genomes are the norm within Entomophthoraceae owing to extensive, but not recent, Ty3 retrotransposon activity, despite the presence of machinery to defend against transposable elements(RNAi). In addition, we find that E. muscae and its closest allies are enriched for M16A peptidases and possess genes that are likely homologs to the blue-light sensor white-collar 1, a Neurospora crassa gene that has a well-established role in maintaining circadian rhythms. We find that E. muscae has an expanded group of acid-trehalases, consistent with trehalose being the primary sugar component of fly (and insect) hemolymph. We uncover evidence that E. muscae diverged from other entomophthoralean fungi by expansion of existing families, rather than loss of particular domains, and possesses a potentially unique suite of secreted catabolic enzymes, consistent with E. muscae’s species-specific, biotrophic lifestyle. Altogether, we provide a genetic and molecular foundation that we hope will provide a platform for the continued study of the unique biology of entomophthoralean fungi.
Geometry of actions, expanders and warped cones

In this thesis we introduce a notion of graphs approximating actions of finitely generated groups on metric and measure spaces. We systematically investigate expansion properties of said graphs and we prove that, under mild conditions, a sequence of graphs approximating a fixed action ρ forms a family of expanders if and only if ρ is expanding in measure. We subsequently prove that the notion of expansion in measure for measure-preserving actions is equivalent to the well studied notion of spectral gap. This enables us to rely on a number of known results to construct numerous new families of expander (and superexpander) graphs. Proceeding in our investigation, we show that the graphs approximating an action Γ y X are uniformly quasi-isometric to the level sets of the associated warped cone OΓ(X). Warped cones are ‘cone like’ structures that were introduced by J. Roe to construct examples of metric spaces with interesting coarse geometry (it has recently been shown that they violate the coarse Baum-Connes conjecture). The existence of such a relation between approximating graphs and warped cones has twofold advantages: on the one hand it implies that warped cones arising from actions that are expanding in measure coarsely contain families of expanders, on the other hand it provides a geometric model for the approximating graphs allowing us to study the geometry of the expander thus obtained. The rest of the work is devoted to the study of the coarse geometry of warped cones (and approximating graphs). We do so in order to prove rigidity results which allow us to prove that our construction is flexible enough to produce a number of non coarsely equivalent new families of expanders. As a by-product, we also show that some of these expanders enjoy some rather peculiar geometric properties, e.g. we can construct expanders that are coarsely simply connected.
of the Annual Meeting of the Cognitive Science Society Title Modeling Causal Learning Using Bayesian Generic Priors on Generative and Preventive

We present a Bayesian model of causal learning that incorporates generic priors on distributions of weights representing potential powers to either produce or prevent an effect. These generic priors favor necessary and sufficient causes. Across three experiments, the model explains the systematic pattern of human judgments observed for questions regarding support for a causal link, for both generative and preventive causes.
El desarrollo económico de la América Latina y algunos de sus principales problemas

Este texto, encargado por la CEPAL a Prebisch como consultor para introducir el Estudio Economico de America Latina de 1948, es probablemente el mas importante para la teoria del desarrollo en la region y se transformo en la piedra angular de la teoria cepalina posterior. En el, su autor hace un analisis de la insercion de America Latina en la economia mundial a partir del concepto centro-periferia y formula la idea de que el deterioro de los terminos de intercambio de los bienes primarios en el largo plazo refuerza esa estructura asimetrica. Esto constituyo un ataque frontal a la division internacional del trabajo, que segun el planteaba, conducia a la concentracion de la renta en los paises del centro industrializado. Como consecuencia, llamaba a impulsar, por la via de una intervencion activa del Estado, el proceso de industrializacion que se habia iniciado en forma pragmatica en respuesta a las perturbaciones provocadas por las guerras mundiales y la crisis de 1929. Este texto es, sin duda, el puerto de llegada de las reflexiones de Prebisch previas a su etapa cepalina y constituye tambien el punto de partida del pensamiento de la CEPAL que daria a Prebisch su posicion de liderazgo dentro de la organizacion y de referente de la reflexion sobre el desarrollo economico mundial.
Probabilities from entanglement, Born's rule p{sub k}= vertical bar {psi}{sub k} vertical bar{sup 2} from envariance

I show how probabilities arise in quantum physics by exploring the implications of environment-assisted invariance or envariance, a recently discovered symmetry exhibited by entangled quantum systems. Envariance of perfectly entangled 'Bell-like' states can be used to rigorously justify complete ignorance of the observer about the outcome of any measurement on either of the members of the entangled pair. For more general states, envariance leads to Born's rule p{sub k}{proportional_to} vertical bar {psi}{sub k} vertical bar{sup 2} for the outcomes associated with Schmidt states. The probabilities derived in this manner are an objective reflection of the underlying state of the system--they represent experimentally verifiable symmetries, and not just a subjective 'state of knowledge' of the observer. This envariance-based approach is compared with and found to be superior to prequantum definitions of probability including the standard definition based on the 'principle of indifference' due to Laplace and the relative frequency approach advocated by von Mises. Implications of envariance for the interpretation of quantum theory go beyond the derivation of Born's rule: Envariance is enough to establish the dynamical independence of preferred branches of the evolving state vector of the composite system and, thus, to arrive at the environment-induced superselection (einselection) of pointermore » states, which was usually derived by an appeal to decoherence. The envariant origin of Born's rule for probabilities sheds light on the relation between ignorance (and, hence, information) and the nature of quantum states. « less
Kinematic Analysis of Open-Source 5 Degree of Freedom Robot Arm

Today, it is especially estimated that robots will be more than 2 million between 2018-2021, with their increasing use in the industry, in the world. In the industrial environment, robots are used to neutralize toxic substances, explosives, or to replace certain repetitive tasks in the industry for human intervention. On the other hand, robotic systems are used in different areas such as office environment, military duties, and use in hospital environments. It is widespread the use of open-source design robot day by day, in addition to the increasing use of robots, which have invaluable effective uses in complex or dangerous processes. The use of open-source robotic systems is cheaper, developable, and has no usage restrictions due to copyright compared to equivalent robots used in the industry. For these reasons, in our study, a robotic arm with 5 degrees of freedom, printed with 3D printers at industrial scales, was developed. The printed robotic arm was developed to be used as an auxiliary equipment for hospital staff, especially in today's hospital environment. Kinematic analysis is required to determine the working space of the developed robotic arm. The working space of the robotic arm, which is intended to be used as auxiliary equipment in the hospital environment, was revealed by kinematic analysis.
Sliding mode control as binary‐based quantizers

In recent years, sliding mode quantizers (SMQs), where signals are converted to switching signals represented by sequence of binary values −1's and +1's, are increasingly being used in various applications including control of power converters, networked control systems (NCSs), one‐bit control processing, etc. This paper derives the stability conditions of both continuous and discrete‐time switched control systems which are embedded with SMQs and quasi‐sliding mode quantizers (QSMQs), respectively. The optimal conditions of both SMQ and QSMQ, which assure that their outputs (binary values) optimally approximate their inputs, are established. The results of theoretical analysis are validated through numerical simulation.
Community diversity is associated with intra-species genetic diversity and 1 gene loss in the human gut microbiome 2 3

1. Département de sciences biologiques, Université de Montréal, Canada; 6 2. Computational and Systems Biology, University of California, Los Angeles 7 3. Bioinformatics and Systems Biology Program, University of California, San Diego 8 4. Department of Ecology and Evolutionary Biology, University of California, Los Angeles 9 5. Department of Microbiology and Immunology, McGill University, Canada; 10 6. McGill Genome Centre, McGill University, Canada 11 7. Quebec Centre for Biodiversity Science, Canada 12 8. Department of Human Genetics, University of California, Los Angeles 13 14 * Correspondence to jesse.shapiro@mcgill.ca and ngarud@ucla.edu. These authors contributed 15 equally. 16