Steerable Microinvasive Probes for Localized Drug Delivery to Deep Tissue

Enhanced understanding of neuropathologies has created a need for more advanced tools. Current neural implants result in extensive glial scarring and are not able to highly localize drug delivery due to their size. Smaller implants reduce surgical trauma and improve spatial resolution, but such a reduction requires improvements in device design to enable accurate and chronic implantation in subcortical structures. Flexible needle steering techniques offer improved control over implant placement, but often require complex closed‐loop control for accurate implantation. This study reports the development of steerable microinvasive neural implants (S‐MINIs) constructed from borosilicate capillaries (OD = 60 µm, ID = 20 µm) that do not require closed‐loop guidance or guide tubes. S‐MINIs reduce glial scarring 3.5‐fold compared to prior implants. Bevel steered needles are utilized for open‐loop targeting of deep‐brain structures. This study demonstrates a sinusoidal relationship between implant bevel angle and the trajectory radius of curvature both in vitro and ex vivo. This relationship allows for bevel‐tipped capillaries to be steered to a target with an average error of 0.23 mm ± 0.19 without closed‐loop control. Polished microcapillaries present a new microinvasive tool for chronic, predictable targeting of pathophysiological structures without the need for closed‐loop feedback and complex imaging.     

Computing Hitting Set Kernels By AC0-Circuits

Theory of Computing Systems - Given a hypergraph H = (V,E), what is the smallest subset $X \subseteq V$ such that e ∩ X≠∅ holds for all e ∈ E? This problem, known as the...     

Nonribosomal Peptides Produced by Minimal and Engineered Synthetases with Terminal Reductase Domains

Nonribosomal peptide synthetases (NRPSs) use terminal reductase domains for 2-electron reduction of the enzyme-bound thioester releasing the generated peptides as C-terminal aldehydes. Herein, we reveal the biosynthesis of a pyrazine that originates from an aldehyde-generating minimal NRPS termed ATRed in entomopathogenic Xenorhabdus indica. Reductase domains were also investigated in terms of NRPS engineering and, although no general applicable approach was deduced, we show that they can indeed be used for the production of similar natural and unnatural pyrazinones.     

Detection and mitigation of monitor identification attacks in collaborative intrusion detection systems

Collaborative defensive approaches such as collaborative intrusion detection system (CIDS) have emerged as a response to the continuous increase in the sophistication of cyberattacks. Such systems utilize a plethora of heterogeneous monitors to create a holistic picture of the monitored network. A number of research institutes deploy CIDSs that publish their alert data publicly over the Internet. This is important for researchers and security administrators, as such systems provide a source of real‐world alert data for experimentation. However, a class of identification attacks exists, namely probe‐response attacks (PRAs), which can significantly reduce the benefits of a CIDS. In particular, such attacks allow an adversary to detect the network location of the monitors of a CIDS. This article discusses the state of the art, with an emphasis on our previous and ongoing work, with regard to the detection and the mitigation of PRAs. We compare the most promising defensive mechanisms with respect to their effectiveness and the possible negative effects they might introduce to the CIDS. Finally, we provide a thorough discussion of research gaps and possible future directions for the field.     

The dorsolateral pre‑frontal cortex bi‑polar error‑related potential in a locked‑in patient implanted with a daily use brain–computer interface

While brain computer interfaces (BCIs) offer the potential of allowing those suffering from loss of muscle control to once again fully engage with their environment by bypassing the affected motor system and decoding user intentions directly from brain activity, they are prone to errors. One possible avenue for BCI performance improvement is to detect when the BCI user perceives the BCI to have made an unintended action and thus take corrective actions. Error-related potentials (ErrPs) are neural correlates of error awareness and as such can provide an indication of when a BCI system is not performing according to the user’s intentions. Here, we investigate the brain signals of an implanted BCI user suffering from locked-in syndrome (LIS) due to late-stage ALS that prevents her from being able to speak or move but not from using her BCI at home on a daily basis to communicate, for the presence of error-related signals. We first establish the presence of an ErrP originating from the dorsolateral pre-frontal cortex (dLPFC) in response to errors made during a discrete feedback task that mimics the click-based spelling software she uses to communicate. Then, we show that this ErrP can also be elicited by cursor movement errors in a continuous BCI cursor control task. This work represents a first step toward detecting ErrPs during the daily home use of a communications BCI.     

Optimized etching of porcelain and polycrystalline alumina with a glass phase

Chemical and thermal etching techniques are commonly used in ceramography to enhance microstructural features. While thermal etching works well for high purity ceramic systems, this technique may not be appropriate where glass is present. Porcelain and industrial alumina both contain a glass phase, typically 40?60 vol% and 4?30 vol%, respectively, and these glass chemistries are proposed to be similar. Chemical etching of porcelain is common, but the images published in the literature are frequently over-etched. When glass is present in the grain boundaries of alumina, thermal etching can cause the glass to disappear or to recrystallize, obscuring the microstructure. Because of this, it is proposed that both chemical and thermal etching are necessary to prepare an industrial alumina microstructure for grain size measurements. In addition, it was observed that chemical etching is sensitive to the residual stress in the glass phase, becoming more aggressive when there is residual tension in the glass.     

Direct gradient projection method with transformation of variables technique for structural topology optimization

This paper proposes an efficient and reliable topology optimization method that can obtain a black and white solution with a low objective function value within a few tens of iterations. First of all, a transformation of variables technique is adopted to eliminate the constraints on the design variables. After that, the optimization problem is considered as aiming at the minimum compliance in the space of design variables which is supposed to be solved by iterative method. Based on the idea of the original gradient projection method, the direct gradient projection method (DGP) is proposed. By projecting the negative gradient of objective function directly onto the hypersurface of the constraint, the most promising search direction from the current position is obtained in the vector space spanned by the gradients of objective and constraint functions. In order to get a balance between efficiency and reliability, the step size is constrained in a rational range via a scheme for step size modification. Moreover, a grey elements suppression technique is proposed to lead the optimization to a black and white solution at the end of the process. Finally, the performance of the proposed method is demonstrated by three numerical examples including both 2D and 3D problems in comparison with the typical SIMP method using the optimality criteria algorithm.