Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL^pro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL^pro. Moreover, we report the discovery of isoindolines as a new class of potent PL^pro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL^pro are valuable starting points for the development of new pan-coronaviral inhibitors.     

Muscular fatigue and maximum endurance time assessment for male and female industrial workers

A single arm pushing experiment was conducted in an electronic factory in Yantai, China to assess muscular fatigue using the theoretical models of muscular strength and maximum endurance time (MET) developed by Ma et al. (2009). Seventy seven workers, including 38 males and 39 females, participated in the study. The muscular strength of pushing was measured after the subject pushed a stick, with a force of 2.5 kgf, for 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 min. Fatigue rate was determined based on a regression approach. In addition to the theoretical model, the MET for such a pushing task was also determined using four empirical models in the literature. The results indicated that females were more resistant to muscular fatigue than males in the pushing task. The results of the muscular strength prediction show that the predictability of the muscular strength model is acceptable. The prediction errors for muscular strength for female subjects were significantly lower than those of the male subjects. The predicted MET using the theoretical model, with a group constant k, was highly correlated with those using the empirical models compared in the current study.     

On detecting co-resident cloud instances using network flow watermarking techniques

Virtualization is the cornerstone of the developing third-party compute industry, allowing cloud providers to instantiate multiple virtual machines (VMs) on a single set of physical resources. Customers utilize cloud resources alongside unknown and untrusted parties, creating the co-resident threat—unless perfect isolation is provided by the virtual hypervisor, there exists the possibility for unauthorized access to sensitive customer information through the exploitation of covert side channels. This paper presents co-resident watermarking, a traffic analysis attack that allows a malicious co-resident VM to inject a watermark signature into the network flow of a target instance. This watermark can be used to exfiltrate and broadcast co-residency data from the physical machine, compromising isolation without reliance on internal side channels. As a result, our approach is difficult to defend against without costly underutilization of the physical machine. We evaluate co-resident watermarkingunder a large variety of conditions, system loads and hardware configurations, from a local laboratory environment to production cloud environments (Futuregrid and the University of Oregon’s ACISS). We demonstrate the ability to initiate a covert channel of 4 bits per second, and we can confirm co-residency with a target VM instance in $<$ 10 s. We also show that passive load measurement of the target and subsequent behavior profiling is possible with this attack. We go on to consider the detectability of co-resident watermarking, extending our scheme to create a subtler watermarking attack by imitating legitimate cloud customer behavior. Our investigation demonstrates the need for the careful design of hardware to be used in the cloud.     

Kinetic analysis of cellular internalization and expulsion of unstructured D-chirality cell penetrating peptides

Most cell penetrating peptides (CPPs) are unstructured and susceptible to proteolytic degradation. One alternative is to incorporate D-chirality amino acids into unstructured CPPs to allow for enhanced uptake and intracellular stability. This work investigates CPP internalization using a series of time, concentration, temperature, and energy dependent studies, resulting in a three-fold increase in uptake and 50-fold increase in stability of D-chirality peptides over L-chirality counterparts. CPP internalization occurred via a combination of direct penetration and endocytosis, with a percentage of internalized CPP expelling from cells in a time-dependent manner. Mechanistic studies identified that cells exported the intact internalized D-chirality CPPs via an exocytosis independent pathway, analogous to a direct penetration method out of the cells. These findings highlight the potential of a D-chirality CPP as bio-vector in therapeutic and biosensing applications, but also identify a new expulsion method suggesting a relationship between uptake kinetics, intracellular stability, and export kinetics.     

Perception of Hand Force in Power Grip for Females

Borg's rating of perceived exertion (RPE) and category ratio (CR‐10) scales are commonly used to quantify perceived muscular exertion for body segments. Twenty females participated in an experiment to study the power grip force at four perceived exertion levels using either dominant or nondominant hand under two posture conditions. It was found that the subjects tended to apply a higher power grip force (100% of perceived maximum voluntary contraction) than the levels they were requested to apply. The power grip forces between dominant and nondominant hands at low hand exertion levels were negligible. The grip forces between the two hands were significantly different when the exertion level was nearly maximal. Linear regression models were established for the subjects to link the relationship between the perceived hand exertion and measured grip force, hand used, and hand/arm posture. All the models were statistically significant (p < 0.0001) with R² values 0.97 or higher. These models provided better estimates in perceived hand exertion for dominant hand than for nondominant hand. A follow‐up experiment was conducted to measure the subjective rating of both the CR‐10 and RPE when a 98 N grip force was applied. It was found that the subjects reported higher exertion levels when they were using the CR‐10 scale than when they were using the RPE scale. © 2011 Wiley Periodicals, Inc.     

Using Courseware Discussion Boards to Engage Graduate Students in Online Library Workshops

ABSTRACT

Librarians at Oregon State University (OSU) Libraries used the discussion board features of Blackboard courseware to create an interactive experience for graduate students at a distance who could not attend the on-campus “Literature Review Workshops.” These recently developed workshops have been extremely popular with graduate students across the disciplines and have generated a growing demand from distance education graduate students and faculty to offer similar information online. Reluctant to simply deliver content via an online tutorial, librarians sought to duplicate the workshop atmosphere by making the sessions available for a short time-period online, asking participants to respond to discussion questions at specific points in the workshop, and offering audio-mediated online demonstrations of tools and resources. Student feedback and follow-up requests for more workshops support the perception that this approach offered a rewarding learning experience that addressed their specific adult learning needs.     

Trailfinders—curating an interactive city promenade experience with mobile phones

Abstract

With a growing number of embedded digital experiences in arts and heritage settings, creating a broad global field, this article focuses on the use of mobile phones in the engagement of humans with the cultural heritage of public spaces, specifically those that require a promenade from one outdoor space to another. This article discusses findings from a recent promenade initiative, commissioned for a UK arts festival, along with a review of literature, to critically engage with growing evidence of the diverse ways in which technology is integrated at direct user level. Concepts of ‘hybrid spaces’ and ‘user agency’ are discussed, along with the ‘performativity’ of spaces. Central to the discussion is the function of narrative in engaging the participant to construct new perspectives, which are facilitated by the mediating role of personal media devices between subject, narrative, space and community.