Building Enhancers from the Ground Up: A Synthetic Biology Approach

A challenge of the synthetic biology approach is to use our understanding of a system to recreate a biological function with specific properties. We have applied this framework to bacterial enhancers, combining a driver, transcription factor binding sites, and a poised polymerase to create synthetic modular enhancers. Our findings suggest that enhancer-based transcriptional control depends critically and quantitatively on DNA looping, leading to complex regulatory effects when the enhancer cassettes contain additional transcription factor binding sites for TetR, a bacterial transcription factor. We show through a systematic interplay of experiment and thermodynamic modeling that the level of gene expression can be modulated to convert a variable inducer concentration input into discrete or step-like output expression levels. Finally, using a different DNA-binding protein (TraR), we show that the regulatory output is not a particular feature of the specific DNA-binding protein used for the enhancer but a general property of synthetic bacterial enhancers

Scalable architecture for trapped-ion quantum computing using RF traps and dynamic optical potentials

Qubits based on ions trapped in linear radio-frequency traps form a successful platform for quantum computing, due to their high fidelity of operations, all-to-all connectivity and degree of local control. In principle there is no fundamental limit to the number of ion-based qubits that can be confined in a single 1D register. However, in practice there are two main issues associated with long trapped-ion crystals, that stem from the 'softening' of their modes of motion, upon scaling up: high heating rates of the ions' motion, and a dense motional spectrum; both impede the performance of high-fidelity qubit operations. Here we propose a holistic, scalable architecture for quantum computing with large ion-crystals that overcomes these issues. Our method relies on dynamically-operated optical potentials, that instantaneously segment the ion-crystal into cells of a manageable size. We show that these cells behave as nearly independent quantum registers, allowing for parallel entangling gates on all cells. The ability to reconfigure the optical potentials guarantees connectivity across the full ion-crystal, and also enables efficient mid-circuit measurements. We study the implementation of large-scale parallel multi-qubit entangling gates that operate simultaneously on all cells, and present a protocol to compensate for crosstalk errors, enabling full-scale usage of an extensively large register. We illustrate that this architecture is advantageous both for fault-tolerant digital quantum computation and for analog quantum simulations

Cognitive Flexibility Predicts PTSD Symptoms: Observational and Interventional Studies

Introduction: Post-Traumatic Stress Disorder (PTSD) is a prevalent, severe and tenacious psychopathological consequence of traumatic events. Neurobehavioral mechanisms underlying PTSD pathogenesis have been identified, and may serve as risk-resilience factors during the early aftermath of trauma exposure. Longitudinally documenting the neurobehavioral dimensions of early responses to trauma may help characterize survivors at risk and inform mechanism-based interventions. We present two independent longitudinal studies that repeatedly probed clinical symptoms and neurocognitive domains in recent trauma survivors. We hypothesized that better neurocognitive functioning shortly after trauma will be associated with less severe PTSD symptoms a year later, and that an early neurocognitive intervention will improve cognitive functioning and reduce PTSD symptoms.Methods: Participants in both studies were adult survivors of traumatic events admitted to two general hospitals’ emergency departments (EDs) in Israel. The studies used identical clinical and neurocognitive tools, which included assessment of PTSD symptoms and diagnosis, and a battery of neurocognitive tests. The first study evaluated 181 trauma-exposed individuals one-, six-, and 14 months following trauma exposure. The second study evaluated 97 trauma survivors 1 month after trauma exposure, randomly allocated to 30 days of web-based neurocognitive intervention (n = 50) or control tasks (n = 47), and re-evaluated all subjects three- and 6 months after trauma exposure.Results: In the first study, individuals with better cognitive flexibility at 1 month post-trauma showed significantly less severe PTSD symptoms after 13 months (p = 0.002). In the second study, the neurocognitive training group showed more improvement in cognitive flexibility post-intervention (p = 0.019), and lower PTSD symptoms 6 months post-trauma (p = 0.017), compared with controls. Intervention- induced improvement in cognitive flexibility positively correlated with clinical improvement (p = 0.002).Discussion: Cognitive flexibility, shortly after trauma exposure, emerged as a significant predictor of PTSD symptom severity. It was also ameliorated by a neurocognitive intervention and associated with a better treatment outcome. These findings support further research into the implementation of mechanism-driven neurocognitive preventive interventions for PTSD

Real-Time Sign Language Detection using Human Pose Estimation

We propose a lightweight real-time sign language detectionmodel, as we identify the need for such a case in videoconferencing. Weextract optical flow features based on human pose estimation and, usinga linear classifier, show these features are meaningful with an accuracyof 80%, evaluated on the Public DGS Corpus. Using a recurrent modeldirectly on the input, we see improvements of up to 91% accuracy,whilestill working under 4ms. We describe a demo application to signlanguagedetection in the browser in order to demonstrate its usage possibility invideoconferencing applications

Increased Bending Rigidity of Single DNA Molecules by H-NS, a Temperature and Osmolarity Sensor

Histonelike nucleoid structuring protein (H-NS) is an abundant prokaryotic protein participating in nucleoid structure, gene regulation, and silencing. It plays a key role in cell response to changes in temperature and osmolarity. Force-extension measurements of single, twist-relaxed λ-DNA-H-NS complexes show that these adopt more extended configurations compared to the naked DNA substrates. Crosslinking indicates that H-NS can decorate DNA molecules at one H-NS dimer per 15–20 bp. These results suggest that H-NS polymerizes along DNA, forming a complex of higher bending rigidity. These effects are not observed above 32°C or at high osmolarity, supporting the hypothesis that a direct H-NS-DNA interaction plays a key role in gene silencing. Thus, we propose that H-NS plays a unique structural role, different from that of HU and IHF, and functions as one of the environmental sensors of the cell