Chimeric antigen receptors (CARs) and synthetic Notch (synNotch) are engineered cell-surface that sense a target respond by activating T cell receptor signaling or customized gene program, respectively. Here, to expand the targeting capabilities of these receptors, we develop "universal" systems for which specificity can be directed post-translationally via covalent attachment co-administered antibody bearing benzylguanine (BG) motif. A SNAPtag self-labeling enzyme is genetically fused...

The duration of T cell receptor contact with antigen modulates the pattern downstream signaling to determine CD4 + fate.

Abstract Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC). Changes in glycosylation the oncoprotein MUC1 commonly occur chronic inflammation, including colitis, and this abnormally glycosylated promotes development progression. It is not known what causes changes MUC1. Gene expression profiling myeloid cells inflamed malignant tissues showed levels inflammatory macrophage–associated cytokines compared normal tissues. We analyzed...

Due to the shrinking of feature size and reduction in supply voltages, nanoscale circuits have become more susceptible radiation induced transient faults. In this paper, we present a symbolic framework based on BDDs ADDs that enables analysis combinational circuit reliability from different aspects: output susceptibility error, influence individual gates outputs overall reliability, dependence glitch duration, amplitude, input patterns. This is demonstrated by set experimental results, which...

Transient faults in logic circuits are becoming an important reliability concern for future technology nodes. Radiation-induced have received significant attention recent years, while multiple transients originating from a single radiation hit predicted to occur more often. Furthermore, some effects, like reconvergent fanout-induced glitches, pronounced the case of faults. Therefore, guide design process and choice circuit optimization techniques, it is model their propagation through...

Due to the shrinking of feature size and significant reduction in noise margins, nanoscale circuits have become more susceptible manufacturing defects, noise-related transient faults, interference from radiation. Traditionally, soft errors been a much greater concern memories than logic circuits. However, as technology continues scale, are becoming memories. To estimate susceptibility combinational logic, use binary decision diagrams (BDDs) algebraic (ADDs) for unified symbolic analysis...

Due to reduction in device feature size and supply voltage, the sensitivity radiation-induced transient faults of digital systems dramatically increases. In this paper, we present two approaches evaluating susceptibility sequential circuits soft errors. The first approach uses Markov chain theory but can only provide steady-state behavior information. second symbolic modeling based on binary decision diagrams/algebraic diagrams circuit unrolling. soft-error rate (SER) evaluation using is...

Abstract Signaling via the Akt/mammalian target of rapamycin pathway influences CD4+ T cell differentiation; low levels favor regulatory induction and high Th induction. Although lipid phosphatase tensin homolog (PTEN) suppresses Akt activity, control PTEN activity is poorly studied in cells. In this study, we identify multiple mechanisms that regulate expression. During induction, function suppressed lower mRNA levels, protein an increase C-terminal phosphorylation. Conversely, during...

Computational modeling is important for understanding biological systems, however models of signaling networks are often constructed manually, limiting their size and complexity. Machine reading can extract molecular interactions cellular described in the scientific literature collected databases to provide extensive knowledge that could be incorporated automatically into executable if reliable methods assembly, extension evaluation were available. Here, we evaluated utility breadth-first...

In this work, our goal was twofold: (1) improve an existing glioblastoma multiforme (GBM) executable mechanistic model and (2) evaluate the effectivenes traditional natural language processing (NLP) pipeline generative AI approach in process of improvement. We used a suite graph metrics tools for interaction filtering classification to collect data conduct analysis. Our results suggest that more comprehensive literature search is necessary enough information through automated paper retrieval...

Due to reduction in device feature size and supply voltage, the sensitivity radiation induced transient faults (soft errors) of digital systems increases dramatically. Intensive research has been done so far modeling analysis combinational circuit susceptibility soft errors, while sequential circuits have received much less attention. In this paper, we present an approach for evaluating errors. The proposed uses symbolic based on BDDs/ADDs probabilistic analysis. SER evaluation is...

Due to the shrinking of feature size and reduction in supply voltages, nanoscale circuits have become more susceptible radiation induced transient faults. In this paper, we present a symbolic framework based on BDDs ADDs that enables analysis combinational circuit reliability from different aspects: output susceptibility error, influence individual gates outputs overall reliability, dependence glitch duration, amplitude, input patterns. This is demonstrated by set experimental results, which...

With technology scaling, the occurrence rate of not only single, but also multiple transients resulting from a single hit is increasing. In this work, we consider effect these multiple-event on outputs logic circuits. Our framework allows for analysis soft errors in circuits, including several aspects: estimation both and transient faults combinational sequential impact flip-flop upsets behavior error cycles following hit. The proposed can be used to estimate stemming radiation, other...

New discoveries and knowledge are summarized in thousands of published papers per year scientific domain, making it incomprehensible for scientists to account all available relevant their studies. In this paper, we present ACCORDION ( ACC elerating O ptimizing model R ecommen D at ION s), a novel methodology an expert system that retrieves selects from literature databases recommend models with correct structure accurate behavior, enabling mechanistic explanations predictions, advancing...

Due to reduction in device feature size and supply voltage, the sensitivity radiation induced transient faults (soft errors) of digital systems increases dramatically. Intensive research has been done so far modeling analysis combinational circuit susceptibility soft errors, while sequential circuits have received much less attention. In this paper, we present an approach for evaluating errors. The proposed uses symbolic based on BDDs/ADDs probabilistic analysis. SER evaluation is...

Abstract State-of-the-art machine reading methods extract, in hours, hundreds of thousands events from the biomedical literature. However, many extracted biomolecular interactions are incorrect or not relevant for computational modeling a system interest. Therefore, rapid, automated required to filter and select accurate useful information. The FiLter Understanding True Events (FLUTE) tool uses public protein interaction databases that have been by machines such as PubMed score them...

Due to reduction in device feature size and supply voltage, the sensitivity of digital systems transient faults is increasing dramatically. As technology scales further, increase transistor integration capacity also leads process environmental variations. Despite these difficulties, it expected that remain reliable while delivering required performance. Reliability variability are emerging as new design challenges, thus pointing importance modeling analysis variation sources for purpose...

We use computational modeling and formal analysis techniques to study temporal behavior of a discrete logical model the naïve T cell differentiation. The is analyzed formally automatically by performing logic queries via statistical checking. results obtained using checking provide details about relative timing events in system, which would otherwise be very cumbersome time consuming obtain through simulations only.

In this paper, we present DiSH, a simulator for large discrete models of biological signal transduction pathways, capable simulating networks with multi-valued elements in both deterministic and stochastic manner. The incorporates the timing molecular reactions, which are often not synchronized occur random order, it also takes into account difference between slow fast reactions. DiSH allows changes conditions during simulations, combined changes, uses concept delays models, similar to...

Due to the shrinking of feature size and reduction in supply voltages, nanoscale circuits have become more susceptible radiation induced transient faults. In this paper, authors use a symbolic framework based on BDDs ADDs that enables analysis sequential circuit reliability from different aspects: output susceptibility error, influence individual gates outputs overall reliability, dependence glitch duration, amplitude, input patterns. The can be used for selective gate sizing targeting...

Due to reduction in device feature size and supply voltage, the sensitivity of digital systems transient faults is increasing dramatically. As technology scales further, increase transistor integration capacity also leads process environmental variations. Despite these difficulties, it expected that remain reliable while delivering required performance. Reliability variability are emerging as new design challenges, thus pointing importance modeling analysis variation sources for purpose...

Models of biological networks have been studied through simulations using a number software tools. However, the intrinsic disparity between sequential nature microprocessor architecture used in software-based and highly parallel systems may result prohibitively long simulation times. In this work, we adopt an alternative approach to hardware-based emulation. Our results on Boolean network models show that such can provide speedup 17,000X when compared existing approaches.

The number of published results in biology and medicine is growing at an exceeding rate, thus, extracting relevant information for building useful models becoming very laborious. Furthermore, with the newly information, previously built need to be extended updated, voluminous literature, it necessary automate model extension process. In this work, we introduce a methodology extending logical cell signaling networks using Genetic Algorithm (GA). proposed procedure developed optimally search...

In this paper, we present DiSH, a simulator for large discrete models of biological signal transduction pathways, capable simulating networks with multi-valued elements in both deterministic and stochastic manner. The incorporates the timing molecular reactions, which are often not synchronized occur random order, it also takes into account difference between slow fast reactions. DiSH allows changes conditions during simulations, combined changes, uses concept delays models, similar to...