A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

A small-scale, portable method for extracting microplastics from marine sediments

• Cheap, effective method for microplastic extraction from sediments. • High, reproducible recovery rates - 95.8%. • Comparison of three commonly used floatation media. • Zinc chloride (1.5 g cm−3) deemed an effective floatation medium. • Method applied to environmental samples across a range of sediment types

MPC-Based Haptic Shared Steering System: A Driver Modeling Approach for Symbiotic Driving

Advanced Driver Assistance Systems (ADAS) aim to increase safety and reduce mental workload. However, the gap in the understanding of the closed-loop driver-vehicle interaction often leads to reduced user acceptance. In this study, an optimal torque control law is calculated online in the Model Predictive Control (MPC) framework to guarantee continuous guidance during the steering task. The research contribution is in the integration of an extensive prediction model covering cognitive behaviour, neuromuscular dynamics, and the vehicle- steering dynamics, within the MPC-based haptic controller to enhance collaboration. The driver model is composed of a preview cognitive strategy based on a Linear-Quadratic-Gaussian, sensory organs, and neuromuscular dynamics, including muscle co-activation and reflex action. Moreover, an adaptive cost-function algorithm enables dynamic allocation of the control authority. Experiments were performed in a fixed-base driving simulator at Toyota Motor Europe involving 19 participants to evaluate the proposed controller with two different cost functions against a commercial Lane Keeping Assist (LKA) system as an industry benchmark. The results demonstrate the proposed controller fosters symbiotic driving and reduces driver-vehicle conflicts with respect to a state-of-the-art commercial system, both subjectively and objectively, while still improving path-tracking performance. Summarising, this study tackles the need to blend human and ADAS control, demonstrating the validity of the proposed strategy

Radially restricted linear energy transfer for high-energy protons: A new analytical approach

Radially restricted linear energy transfer (LET) is a basic physical parameter relevant to radiation biology and radiation protection. In this report a convenient method is presented for the analytical computation of this quantity without the need for complicated simulation. The method uses the energy-re-stricted LETL, as recently redefined in a 1993 ICRU draft document and supplements it by a relatively simple term that represents the energy of fast rays lost within distancer from the track core. The method provides a better fit than other models and is valid over the entire range of radial distance from track center to the maximum radial distance traveled by the most energetic secondary electrons.L r computed by this approach differs only a few percent from the values Contribution to the international symposium on heavy ions research: space, radiation protection and therapy, 21–24 March 1994, Sophia-Antipolis, Franc

MPC-Based Haptic Shared Steering System: A Driver Modeling Approach for Symbiotic Driving

Advanced Driver Assistance Systems (ADAS) aim to increase safety and reduce mental workload. However, the gap in the understanding of the closed-loop driver-vehicle interaction often leads to reduced user acceptance. In this study, an optimal torque control law is calculated online in the Model Predictive Control (MPC) framework to guarantee continuous guidance during the steering task. The research contribution is in the integration of an extensive prediction model covering cognitive behaviour, neuromuscular dynamics, and the vehicle- steering dynamics, within the MPC-based haptic controller to enhance collaboration. The driver model is composed of a preview cognitive strategy based on a Linear-Quadratic-Gaussian, sensory organs, and neuromuscular dynamics, including muscle co-activation and reflex action. Moreover, an adaptive cost-function algorithm enables dynamic allocation of the control authority. Experiments were performed in a fixed-base driving simulator at Toyota Motor Europe involving 19 participants to evaluate the proposed controller with two different cost functions against a commercial Lane Keeping Assist (LKA) system as an industry benchmark. The results demonstrate the proposed controller fosters symbiotic driving and reduces driver-vehicle conflicts with respect to a state-of-the-art commercial system, both subjectively and objectively, while still improving path-tracking performance. Summarising, this study tackles the need to blend human and ADAS control, demonstrating the validity of the proposed strategy

Microplastics alter feeding selectivity and faecal density in the copepod, Calanus helgolandicus

Microplastics (1 μm–5 mm) are a ubiquitous marine contaminant of global concern, ingested by a wide range of marine taxa. Copepods are a key component of marine food webs, providing a source of food for higher trophic levels, and playing an important role in marine nutrient cycling. Microplastic ingestion has been documented in copepods, but knowledge gaps remain over how this affects feeding preference and faecal density. Here, we use exposure studies incorporating algal prey and microplastics of varying sizes and shapes at a concentration of 100 microplastics mL−1 to show: (1) prey selection by the copepod Calanus helgolandicus was affected by the size and shape of microplastics and algae they were exposed to; Exposure to nylon fibres resulted in a 6% decrease in ingestion of similar shaped chain-forming algae, whilst exposure to nylon fragments led to an 8% decrease in ingestion of a unicellular algae that were similar in shape and size. (2) Ingestion of microplastics with different densities altered the sinking rates of faecal pellets. Faeces containing low-density polyethylene sank significantly more slowly than controls, whilst sinking rates increased when faeces contained high-density polyethylene terephthalate. These results suggest that C. helgolandicus avoid ingesting algae that are similar in size and/or shape to the microplastic particles they are exposed to, potentially in a bid to avoid consuming the plastic

Critical animal and media studies: Expanding the understanding of oppression in communication research

Critical and communication studies have traditionally neglected the oppression conducted by humans towards other animals. However, our (mis)treatment of other animals is the result of public consent supported by a morally speciesist-anthropocentric system of values. Speciesism or anthroparchy, as much as any other mainstream ideologies, feeds the media and at the same time is perpetuated by them. The goal of this article is to remedy this neglect by introducing the subdiscipline of Critical Animal and Media Studies. Critical Animal and Media Studies takes inspiration both from critical animal studies – which is so far the most consolidated critical field of research in the social sciences addressing our exploitation of other animals – and from the normative-moral stance rooted in the cornerstones of traditional critical media studies. The authors argue that the Critical Animal and Media Studies approach is an unavoidable step forward for critical media and communication studies to engage with the expanded circle of concerns of contemporary ethical thinking