EASINESS: E. coli Assisted Speedy affINity-maturation Evolution SyStem

Antibodies are one of the most important groups of biomolecules for both clinical and basic research and have been developed as potential therapeutics. Affinity is the key feature for biological activity and clinical efficacy of an antibody, especially of therapeutic antibodies, and thus antibody affinity improvement is indispensable and still remains challenging. To address this issue, we developed the E. coliAssisted Speed affINity-maturation Evolution SyStem (EASINESS) for continuous directed evolution of Ag–Ab interactions. Two key components of EASINESS include a mutation system modified from error-prone DNA polymerase I (Pol I) that selectively mutates ColE1 plasmids in E. coli and a protein–protein interaction selection system from mDHFR split fragments. We designed a GCN4 variant which barely forms a homodimer, and during a single round of evolution, we reversed the homodimer formation activity from the GCN4 variant to verify the feasibility of EASINESS. We then selected a potential therapeutic antibody 18A4Hu and improved the affinity of the antibody (18A4Hu) to its target (ARG2) 12-fold in 7 days while requiring very limited hands-on time. Remarkably, these variants of 18A4Hu revealed a significant improved ability to inhibit melanoma pulmonary metastasis in a mouse model. These results indicate EASINESS could be as an attractive choice for antibody affinity maturation.

New discussion on nonlocal controllability for fractional evolution system of order $1 < r < 2$

In this manuscript, we deal with the nonlocal controllability results for the fractional evolution system of $1< r<2$ 1 < r < 2 in a Banach space. The main results of this article are tested by using fractional calculations, the measure of noncompactness, cosine families, Mainardi’s Wright-type function, and fixed point techniques. First, we investigate the controllability results of a mild solution for the fractional evolution system with nonlocal conditions using the Mönch fixed point theorem. Furthermore, we develop the nonlocal controllability results for fractional integrodifferential evolution system by applying the Banach fixed point theorem. Finally, an application is presented for drawing the theory of the main results.

On the global existence and qualitative behaviour of one-dimensional solutions to a model for urban crime

We consider the no-flux initial-boundary value problem for the cross-diffusive evolution system: \begin{eqnarray*} \left\{ \begin{array}{ll} u_t = u_{xx} - \chi \big(\frac{u}{v} \partial_x v \big)_x - uv +B_1(x,t), \qquad & x\in \Omega, \ t>0, \\[1mm] v_t = v_{xx} +uv - v + B_2(x,t), \qquad & x\in \Omega, \ t>0, \end{array} \right. \end{eqnarray*} which was introduced by Short et al. in [40] with $\chi=2$ to describe the dynamics of urban crime. In bounded intervals $\Omega\subset\mathbb{R}$ and with prescribed suitably regular non-negative functions $B_1$ and $B_2$ , we first prove the existence of global classical solutions for any choice of $\chi>0$ and all reasonably regular non-negative initial data. We next address the issue of determining the qualitative behaviour of solutions under appropriate assumptions on the asymptotic properties of $B_1$ and $B_2$ . Indeed, for arbitrary $\chi>0$ , we obtain boundedness of the solutions given strict positivity of the average of $B_2$ over the domain; moreover, it is seen that imposing a mild decay assumption on $B_1$ implies that u must decay to zero in the long-term limit. Our final result, valid for all $\chi\in\left(0,\frac{\sqrt{6\sqrt{3}+9}}{2}\right),$ which contains the relevant value $\chi=2$ , states that under the above decay assumption on $B_1$ , if furthermore $B_2$ appropriately stabilises to a non-trivial function $B_{2,\infty}$ , then (u,v) approaches the limit $(0,v_\infty)$ , where $v_\infty$ denotes the solution of \begin{eqnarray*} \left\{ \begin{array}{l} -\partial_{xx}v_\infty + v_\infty = B_{2,\infty}, \qquad x\in \Omega, \\[1mm] \partial_x v_{\infty}=0, \qquad x\in\partial\Omega. \end{array} \right. \end{eqnarray*} We conclude with some numerical simulations exploring possible effects that may arise when considering large values of $\chi$ not covered by our qualitative analysis. We observe that when $\chi$ increases, solutions may grow substantially on short time intervals, whereas only on large timescales diffusion will dominate and enforce equilibration.

Strain evolution and novel downstream processing with integrated catalysis enable highly efficient co-production of 1,3-Propanediol and organic acid esters from crude glycerol

Bioconversion process with a single target product often lacks economic competitiveness owing to incomplete use of raw material and high costs of downstream processing (DSP). Here, we show with the microbial conversion of crude glycerol that an integrated strain engineering and catalytic conversion of the so-called byproducts can greatly improve DSP and the process economy. Specifically, Clostridium pasteurianum was first adapted to increased concentration of crude glycerol in a novel automatic laboratory evolution system. At m3 scale bioreactor the strain achieved a simultaneous production of 1,3-propanediol (PDO), acetic and butyric acids at 81.21, 18.72 and 11.09 g/L within only 19 h, respectively, representing the most efficient fermentation of crude glycerol to targeted products. A heterogeneous catalytic step was developed and integrated into the DSP process to obtain high-value methyl esters from acetic and butyric acids at high yields. The co-production of the esters also greatly simplified the recovery of PDO. For example, a cosmetic grade PDO (96% PDO) was easily obtained by a simple single-stage distillation process (with an overall yield more than 77%). This integrated approach provides an industrially attractive route for a complete use of the raw material with the simultaneous production of three appealing products which greatly improve the process economy and ecology.

Internet public opinion dissemination mechanism of COVID-19: evidence from the Shuanghuanglian event

PurposeThe sudden outbreak of COVID-19 has become a major public health emergency of global concern. Studying the Internet public opinion dissemination mechanism of public health emergencies is of great significance for creating a legalized network environment, and it is also helpful for managers to make scientific decisions when encountering Internet public opinion crisis.Design/methodology/approachBased on the analysis of the process of spreading the Internet public opinion in major epidemics, a dynamic model of the Internet public opinion spread system was constructed to study the interactive relationship among the public opinion events, network media, netizens and government and the spread of epidemic public opinion. The Shuanghuanglian event in COVID-19 in China was taken as a typical example to make simulation analysis.FindingsResearch results show three points: (1) the government credibility plays a decisive role in the spread of Internet public opinion; (2) it is the best time to intervene when Internet public opinion occurred at first time; (3) the management and control of social media are the key to public opinion governance. Besides, specific countermeasures are proposed to assist control of Internet public opinion dissemination.Originality/valueThe epidemic Internet public opinion risk evolution system is a complex nonlinear social system. The system dynamics model is used to carry out research to facilitate the analysis of the Internet public opinion propagation mechanism and explore the interrelationship of various factors.

Cognitive Matching of Design Subjects in Product Form Evolutionary Design

In actual product development, the cognitive differences between users and designers make it difficult for the designed products to be recognized by users. To reduce the cognitive differences between these two design subjects, this paper proposes a method of cognitive matching of the design subjects. First, we use the relevant methods of Kansei engineering to quantify the Kansei image cognition of the two design subjects and construct a cognitive matching model of the design subjects with information entropy and the technique for order preference by similarity to ideal solution (TOPSIS). Second, according to the Kansei image, the Kansei image prototype cluster is constructed, and the representative Kansei image prototype is obtained. Then, we combine an artificial neural network (ANN) with a cognitive matching model of the design subjects to construct a product Kansei image evaluation system; this is used to evaluate the evolved forms. Finally, a product Kansei image form evolution system is constructed based on the genetic algorithm (GA). To some extent, the system simulates the cognitive matching process between designers and users in product design, helps designers to more accurately understand the cognitive trends of the two design subjects, and provides a theoretical basis for the intelligent design of product forms through the cognitive balance of multiple design subjects. This paper takes a beverage bottle as an example to verify the feasibility of the model through a comparative study.

Versatile Dynamic Motion Generation Framework: Demonstration With a Crutch-Less Exoskeleton on Real-Life Obstacles at the Cybathlon 2020 With a Complete Paraplegic Person

Lower-limb exoskeletons are a promising option to increase the mobility of persons with leg impairments in a near future. However, it is still challenging for them to ensure the necessary stability and agility to face obstacles, particularly the variety that makes the urban environment. That is why most of the lower-limb exoskeletons must be used with crutches: the stability and agility features are deferred to the patient. Clinical experience shows that the use of crutches not only leads to shoulder pain and exhaustion, but also fully occupies the hands for daily tasks. In November 2020, Wandercraft presented Atalante Evolution, the first self-stabilized and crutch-less exoskeleton, to the powered exoskeleton race of the Cybathlon 2020 Global Edition. The Cybathlon aims at promoting research and development in the field of powered assistive technology to the public, contrary to the Paralympics where only participants with unpowered assistive technology are allowed. The race is designed to represent the challenges that a person could face every day in their environment: climbing stairs, walking through rough terrain, or descending ramps. Atalante Evolution is a 12 degree-of-freedom exoskeleton capable of moving dynamically with a complete paraplegic person. The challenge of this competition is to generate and execute new dynamic motions in a short time, to achieve different tasks. In this paper, an overview of Atalante Evolution system and of our framework for dynamic trajectory generation based on the direct collocation method will be presented. Next, the flexibility and efficiency of the dynamic motion generation framework are demonstrated by our tools developed for generating the important variety of stable motions required by the competition. A smartphone application has been developed to allow the pilot to choose between different modes and to control the motion direction according to the real situation to reach a destination. The advanced mechatronic design and the active cooperation of the pilot with the device will also be highlighted. As a result, Atalante Evolution allowed the pilot to complete four out of six obstacles, without crutches. Our developments lead to stable dynamic movements of the exoskeleton, hands-free walking, more natural stand-up and turning moves, and consequently a better physical condition of the pilot after the race compared to the challengers. The versatility and good results of these developments give hope that exoskeletons will soon be able to evolve in challenging everyday-life environments, allowing patients to live a normal life in complete autonomy.