Opportunities to accelerate extracellular vesicle research with cell-free synthetic biology

Extracellular vesicles (EVs) are lipid-membrane nanoparticles that are shed or secreted by many different cell types. The extracellular vesicle (EV) research community has rapidly expanded in recent years and are leading efforts to deepen our understanding of EV biological functions in human physiology and pathology. These insights are also providing a foundation on which future EV-based diagnostics and therapeutics are poised to positively impact human health. However, current limitations in our understanding of EV heterogeneity, cargo loading mechanisms and the nascent development of EV metrology are all areas that have been identified as important scientific challenges. The field of synthetic biology is also contending with the challenge of understanding biological complexity as it seeks to combine multidisciplinary scientific knowledge with engineering principles, to build useful and robust biotechnologies in a responsible manner. Within this context, cell-free systems have emerged as a powerful suite of in vitro biotechnologies that can be employed to interrogate fundamental biological mechanisms, including the study of aspects of EV biogenesis, or to act as a platform technology for medical biosensors and therapeutic biomanufacturing. Cell-free gene expression (CFE) systems also enable in vitro protein production, including membrane proteins, and could conceivably be exploited to rationally engineer, or manufacture, EVs loaded with bespoke molecular cargoes for use in foundational or translational EV research. Our pilot data herein, also demonstrates the feasibility of cell-free EV engineering. In this perspective we discuss the opportunities and challenges for accelerating EV research and healthcare applications with cell-free synthetic biology

Evolution of central pattern generators for the control of a five-link bipedal walking mechanism

Central pattern generators (CPGs), with a basis is neurophysiological studies, are a type of neural network for the generation of rhythmic motion. While CPGs are being increasingly used in robot control, most applications are hand-tuned for a specific task and it is acknowledged in the field that generic methods and design principles for creating individual networks for a given task are lacking. This study presents an approach where the connectivity and oscillatory parameters of a CPG network are determined by an evolutionary algorithm with fitness evaluations in a realistic simulation with accurate physics. We apply this technique to a five-link planar walking mechanism to demonstrate its feasibility and performance. In addition, to see whether results from simulation can be acceptably transferred to real robot hardware, the best evolved CPG network is also tested on a real mechanism. Our results also confirm that the biologically inspired CPG model is well suited for legged locomotion, since a diverse manifestation of networks have been observed to succeed in fitness simulations during evolution.Comment: 11 pages, 9 figures; substantial revision of content, organization, and quantitative result

Simple scoring system to predict in-hospital mortality after surgery for infective endocarditis

BACKGROUND: Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. METHODS AND RESULTS: Outcomes of 361 consecutive patients (mean age, 59.1\ub115.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. CONCLUSIONS: A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE

Low-Complexity Energy-Efficient Resource Allocation for the Downlink of Cellular Systems

Energy efficiency (EE) is undoubtedly an important criterion for designing power-limited systems, and yet in a context of global energy saving, its relevance for power-unlimited systems is steadily growing. Equally, resource allocation is a well-known method for improving the performance of cellular systems. In this paper, we propose an EE optimization framework for the downlink of planar cellular systems over frequency-selective channels. Relying on this framework, we design two novel low-complexity resource allocation algorithms for the single-cell and coordinated multi-cell scenarios, which are EE-optimal and EE-suboptimal, respectively. We then utilize our algorithms for comparing the EE performance of the classic non-coordinated, orthogonal and coordinated multi-cell approaches in realistic power and system settings. Our results show that coordination can be a simple and effective method for improving the EE of cellular systems, especially for medium to large cell sizes. Indeed, by using a coordinated rather than a non-coordinated resource allocation approach, the per-sector energy consumption and transmit power can be reduced by up to 15% and more than 90%, respectively

Energy-efficient Power Allocation for Point-to-point MIMO Systems over the Rayleigh Fading Channel

It is well-established that transmitting at full power is the most spectral-efficient power allocation strategy for pointto- point (P2P) multi-input multi-output (MIMO) systems, however, can this strategy be energy efficient as well? In this letter, we address the most energy-efficient power allocation policy for symmetric P2P MIMO systems by accurately approximating in closed-form their optimal transmit power when a realistic MIMO power consumption model is considered. In most cases, being energy efficient implies a reduction in transmit and overall consumed powers at the expense of a lower spectral efficiency

An Accurate Closed-Form Approximation of the Distributed MIMO Outage Probability

The mutual information (MI) of multiple-input multiple-output (MIMO) system over Rayleigh fading channel is known to asymptotically follow a normal probability distribution. In this paper, we first prove that the MI of distributed MIMO (DMIMO) system is also asymptotically equivalent to a Gaussian random variable (RV) by deriving its moment generating function (MGF) and by showing its equivalence with the MGF of a Gaussian RV. We then derive an accurate closed-form approximation of the outage probability for DMIMO system by using the mean and variance of the MI and show the uniqueness of its formulation. Finally, several applications for our analysis are presented