Molecular basis of synaptic vesicle cargo recognition by the endocytic sorting adaptor stonin 2

Journal ArticleSynaptic transmission depends on clathrin-mediated recycling of synaptic vesicles (SVs). How select SV proteins are targeted for internalization has remained elusive. Stonins are evolutionarily conserved adaptors dedicated to endocytic sorting of the SV protein synaptotagmin. Our data identify the molecular determinants for recognition of synaptotagmin by stonin 2 or its Caenorhabditis elegans orthologue UNC-41B

Clinically Approved Antibiotics from 2010 to 2022

This review discusses small molecule antibiotics approved for clinical use in the time frame 2010-2022. This time span saw the approval of four synthetic antibiotics (bedaquiline, pretomanid, delafloxacin, tedizolid), nine natural product derivatives (ceftaroline fosamil, cefiderocol, plazomicin, omadacycline, eravacycline, sarecycline, lefamulin, dalbavancin, oritavancin), and one natural product (fidaxomicin)

HDL modeling for analysis and optimization of asynchronous controllers

Journal ArticleWe propose a simulation-based technique for analysis and optimization of extended burst-mode (XBM) asynchronous controllers. In asynchronous controllers of this sort, timing information on control signals is significant both for performance enhancement and timing validation. Timing information, specifically information about relative signal arrival times, helps us improve the controller's response time and to detect delay faults within controllers in the early synthesis stage. If the timing information of the controller's environment is also known, we can use this information to identify fundamental mode violations. Our approach uses stochastic simulation of HDL programs derived from the original XBM specifications to gather information about signal timing and long-term transition probabilities

Self-timed circuits using DCVSL semi-bundled delay wrappers

Journal ArticleWe present a technique for generating robust self-timed completion signals for general dynamic datapath circuits. The wrapper circuit is based on our previous domino semi-bundled delay (SBD) circuits, but uses DCVSL circuits in the wrapper for higher performance. We describe the basic SBD-DCVSL building blocks in the template with respect to their circuit structures and operational behavior. These DCVSL SBD circuits show better performance, exhibit reduced overhead, and require reduced operating margins for the matched delay compared with the domino version. The DCVSL wrapper can also identify a class of delay faults in the data path

Recent Advances in Mode of Action and Biosynthesis Studies of the Clinically Used Antibiotic Fidaxomicin

The natural product antibiotic fidaxomicin is a marketed drug for the treatment of bacterial infections in the gut. Due to its promising in vitro activities against Mycobacterium tuberculosis, the development of next generation fidaxomicin analogs is of great interest. This article reviews the most recent advances, including the elucidation of a unique mode of action by cryo-EM structures, and the efforts towards the clarification of the biosynthetic pathway. Moreover, known fidaxomicin analogs and their reported antibacterial activities are summarized

Self-timed design with dynamic domino circuits

Journal ArticleWe introduce a simple hierarchical design technique for building high-performance self-timed components using dynamic domino-style circuits. This technique is useful for building handshaking style functional blocks and for self-timed data path components. We wrap the dynamic domino circuit in a wrapper that communicates using a request/acknowledge protocol and mediates the precharge/ evaluate cycle of the dynamic logic. We apply standard bundled delay matching for completion detection but add an early completion feature that can signal completion if function validity can be determined from the output value. The circuit overhead required for this early-acknowledge feature is relatively small, but can provide measurable speedup in some situations. We call this approach semi-bundled delay (SBD)

Combining model-based diagnosis and data-driven anomaly classifiers for fault isolation

Machine learning can be used to automatically process sensor data and create data-driven models for prediction and classification. However, in applications such as fault diagnosis, faults are rare events and learning models for fault classification is complicated because of lack of relevant training data. This paper proposes a hybrid diagnosis system design which combines model-based residuals with incremental anomaly classifiers. The proposed method is able to identify unknown faults and also classify multiple-faults using only single-fault training data. The proposed method is verified using a physical model and data collected from an internal combustion engine.Funding agencies: Volvo Car Corporation in Gothenburg, Sweden</p

Stability-Informed Initialization of Neural Ordinary Differential Equations

This paper addresses the training of Neural Ordinary Differential Equations (neural ODEs), and in particular explores the interplay between numerical integration techniques, stability regions, step size, and initialization techniques. It is shown how the choice of integration technique implicitly regularizes the learned model, and how the solver's corresponding stability region affects training and prediction performance. From this analysis, a stability-informed parameter initialization technique is introduced. The effectiveness of the initialization method is displayed across several learning benchmarks and industrial applications

Clinically Approved Antibiotics from 2010 to 2022

This review discusses small molecule antibiotics approved for clinical use in the time frame 2010-2022. This time span saw the approval of four synthetic antibiotics (bedaquiline, pretomanid, delafloxacin, tedizolid), nine natural product derivatives (ceftaroline fosamil, cefiderocol, plazomicin, omadacycline, eravacycline, sarecycline, lefamulin, dalbavancin, oritavancin), and one natural product (fidaxomicin)