The crystal structure of Cpf1 in complex with CRISPR RNA.

The CRISPR-Cas systems, as exemplified by CRISPR-Cas9, are RNA-guided adaptive immune systems used by bacteria and archaea to defend against viral infection. The CRISPR-Cpf1 system, a new class 2 CRISPR-Cas system, mediates robust DNA interference in human cells. Although functionally conserved, Cpf1 and Cas9 differ in many aspects including their guide RNAs and substrate specificity. Here we report the 2.38 Å crystal structure of the CRISPR RNA (crRNA)-bound Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1). LbCpf1 has a triangle-shaped architecture with a large positively charged channel at the centre. Recognized by the oligonucleotide-binding domain of LbCpf1, the crRNA adopts a highly distorted conformation stabilized by extensive intramolecular interactions and the (Mg(H2O)6)(2+) ion. The oligonucleotide-binding domain also harbours a looped-out helical domain that is important for LbCpf1 substrate binding. Binding of crRNA or crRNA lacking the guide sequence induces marked conformational changes but no oligomerization of LbCpf1. Our study reveals the crRNA recognition mechanism and provides insight into crRNA-guided substrate binding of LbCpf1, establishing a framework for engineering LbCpf1 to improve its efficiency and specificity for genome editing.

Inhibition mechanisms of CRISPR-Cas9 by AcrIIA25.1 and AcrIIA32.

In the ongoing arms race between bacteria and bacteriophages, bacteriophages have evolved anti-CRISPR proteins to counteract bacterial CRISPR-Cas systems. Recently, AcrIIA25.1 and AcrIIA32 have been found to effectively inhibit the activity of SpyCas9 both in bacterial and human cells. However, their molecular mechanisms remain elusive. Here, we report the cryo-electron microscopy structures of ternary complexes formed by AcrIIA25.1 and AcrIIA32 bound to SpyCas9-sgRNA. Using structural analysis and biochemical experiments, we revealed that AcrIIA25.1 and AcrIIA32 recognize a novel, previously-unidentified anti-CRISPR binding site on SpyCas9. We found that both AcrIIA25.1 and AcrIIA32 directly interact with the WED domain, where they spatially obstruct conformational changes of the WED and PI domains, thereby inhibiting SpyCas9 from recognizing protospacer adjacent motif (PAM) and unwinding double-stranded DNA. In addition, they may inhibit nuclease activity by blocking the dynamic conformational changes of the SpyCas9 surveillance complex. In summary, our data elucidate the inhibition mechanisms of two new anti-CRISPR proteins, provide new strategies for the modulation of SpyCas9 activity, and expand our understanding of the diversity of anti-CRISPR protein inhibition mechanisms.

Exploring the supramolecular chemistry of cyclopropeniums: halogen-bonding-induced electrostatic assembly of polymers.

Exploring new noncovalent synthons for supramolecular assembly is essential for material innovation. Accordingly, we herein report a unique type of cyclopropenium-based supramolecular motif and demonstrate its applications to polymer self-assembly. Because of the "ion pair strain" effect, trisaminocyclopropenium iodides complex strongly with fluoroiodobenzene derivatives, forming stable adducts. Crystal structure analysis reveals that halogen-bonding between the iodide anion and the iodo substituent of the fluoroiodobenzene is the driving force for the formation of these electrostatically complexed adducts. Such halogen-bonding-induced electrostatic interactions were further successfully applied to drive the assembly of polymers in solution, on surfaces, and in bulk, demonstrating their potential for constructing supramolecular polymeric materials.

Continuous mode adaptation for cable-driven rehabilitation robot using reinforcement learning.

Continuous mode adaptation is very important and useful to satisfy the different user rehabilitation needs and improve human-robot interaction (HRI) performance for rehabilitation robots. Hence, we propose a reinforcement-learning-based optimal admittance control (RLOAC) strategy for a cable-driven rehabilitation robot (CDRR), which can realize continuous mode adaptation between passive and active working mode. To obviate the requirement of the knowledge of human and robot dynamics model, a reinforcement learning algorithm was employed to obtain the optimal admittance parameters by minimizing a cost function composed of trajectory error and human voluntary force. Secondly, the contribution weights of the cost function were modulated according to the human voluntary force, which enabled the CDRR to achieve continuous mode adaptation between passive and active working mode. Finally, simulation and experiments were conducted with 10 subjects to investigate the feasibility and effectiveness of the RLOAC strategy. The experimental results indicated that the desired performances could be obtained; further, the tracking error and energy per unit distance of the RLOAC strategy were notably lower than those of the traditional admittance control method. The RLOAC strategy is effective in improving the tracking accuracy and robot compliance. Based on its performance, we believe that the proposed RLOAC strategy has potential for use in rehabilitation robots.

Unusually High and Anisotropic Thermal Conductivity in Amorphous Silicon Nanostructures.

Amorphous Si (a-Si) nanostructures are ubiquitous in numerous electronic and optoelectronic devices. Amorphous materials are considered to possess the lower limit to the thermal conductivity (κ), which is ∼1 W·m-1 K-1 for a-Si. However, recent work suggested that κ of micrometer-thick a-Si films can be greater than 3 W·m-1 K-1, which is contributed to by propagating vibrational modes, referred to as "propagons". However, precise determination of κ in a-Si has been elusive. Here, we used structures of a-Si nanotubes and suspended a-Si films that enabled precise in-plane thermal conductivity (κ∥) measurement within a wide thickness range of 5 nm to 1.7 µm. We showed unexpectedly high κ∥ in a-Si nanostructures, reaching ∼3.0 and 5.3 W·m-1 K-1 at ∼100 nm and 1.7 µm, respectively. Furthermore, the measured κ∥ is significantly higher than the cross-plane κ on the same films. This unusually high and anisotropic thermal conductivity in the amorphous Si nanostructure manifests the surprisingly broad propagon mean free path distribution, which is found to range from 10 nm to 10 µm, in the disordered and atomically isotropic structure. This result provides an unambiguous answer to the century-old problem regarding mean free path distribution of propagons and also sheds light on the design and performance of numerous a-Si based electronic and optoelectronic devices.

High-Performance Screen-Printed Thermoelectric Films on Fabrics.

Printing techniques could offer a scalable approach to fabricate thermoelectric (TE) devices on flexible substrates for power generation used in wearable devices and personalized thermo-regulation. However, typical printing processes need a large concentration of binder additives, which often render a detrimental effect on electrical transport of the printed TE layers. Here, we report scalable screen-printing of TE layers on flexible fiber glass fabrics, by rationally optimizing the printing inks consisting of TE particles (p-type Bi0.5Sb1.5Te3 or n-type Bi2Te2.7Se0.3), binders, and organic solvents. We identified a suitable binder additive, methyl cellulose, which offers suitable viscosity for printability at a very small concentration (0.45-0.60 wt.%), thus minimizing its negative impact on electrical transport. Following printing, the binders were subsequently burnt off via sintering and hot pressing. We found that the nanoscale defects left behind after the binder burnt off became effective phonon scattering centers, leading to low lattice thermal conductivity in the printed n-type material. With the high electrical conductivity and low thermal conductivity, the screen-printed TE layers showed high room-temperature ZT values of 0.65 and 0.81 for p-type and n-type, respectively.

Thermal transport in Si and Ge nanostructures in the 'confinement' regime.

Reducing semiconductor materials to sizes comparable to the characteristic lengths of phonons, such as the mean-free-path (MFP) and wavelength, has unveiled new physical phenomena and engineering capabilities for thermal energy management and conversion systems. These developments have been enabled by the increasing sophistication of chemical synthesis, microfabrication, and atomistic simulation techniques to understand the underlying mechanisms of phonon transport. Modifying thermal properties by scaling physical size is particularly effective for materials which have large phonon MFPs, such as crystalline Si and Ge. Through nanostructuring, materials that are traditionally good thermal conductors can become good candidates for applications requiring thermal insulation such as thermoelectrics. Precise understanding of nanoscale thermal transport in Si and Ge, the leading materials of the modern semiconductor industry, is increasingly important due to more stringent thermal conditions imposed by ever-increasing complexity and miniaturization of devices. Therefore this Minireview focuses on the recent theoretical and experimental developments related to reduced length effects on thermal transport of Si and Ge with varying size from hundreds to sub-10 nm ranges. Three thermal transport regimes - bulk-like, Casimir, and confinement - are emphasized to describe different governing mechanisms at corresponding length scales.

Sub-picowatt/kelvin resistive thermometry for probing nanoscale thermal transport.

Advanced instrumentation in thermometry holds the key for experimentally probing fundamental heat transfer physics. However, instrumentation with simultaneously high thermometry resolution and low parasitic heat conduction is still not available today. Here we report a resistive thermometry scheme with ~50 µK temperature resolution and ~0.25 pW/K thermal conductance resolution, which is achieved through schemes using both modulated heating and common mode noise rejection. The suspended devices used herein have been specifically designed to possess short thermal time constants and minimal attenuation effects associated with the modulated heating current. Furthermore, we have systematically characterized the parasitic background heat conductance, which is shown to be significantly reduced using the new device design and can be effectively eliminated using a "canceling" scheme. Our results pave the way for probing fundamental nanoscale thermal transport processes using a general scheme based on resistive thermometry.