Turtle excluder devices -- Are the escape openings large enough?

All five species of sea turtles in continental U.S. waters are protected under the Endangered Species Act of 1973 and the population sizes of all species remain well below historic levels. Shrimp trawling was determined to be the largest source of anthropogenic mortality of many of the species. As a mechanism to reduce the incidental catch of turtles in trawl nets, turtle excluder devices have been required intermittently in the shrimp fishery since 1987, and at all times since 1994. The expanded turtle excluder device (TED) regulations, implemented in 1994, were expected to reduce shrimp trawl capture of sea turtles by 97%. Recent evidence has indicated that the sizes of turtles stranding were not representative of the animals subjected to being captured by the shrimp trawlers. The purpose of our study was to compare the sizes of stranded sea turtles with the size of the TED openings. We compared the sizes of stranded loggerhead (Caretta caretta), green (Chelonia mydas), and Kemp’s ridley (Lepidochelys kempii) sea turtles, the three species most commonly found stranded, to the minimum widths and heights of TED openings. We found that annually a large proportion of stranded loggerhead turtles (33–47%) and a small proportion of stranded green turtles (1–7%) are too large to fit through the required minimum-size TED openings. The continued high mortality of sea turtles caused by bottom trawling is reason for concern, especially for the northern subpopulation of loggerhead turtles, which currently is not projected to achieve the federal recovery goal of reaching and maintaining prelisting levels of nesting.

Morphine withdrawal affects both delayed-escape behaviour in Morris water maze and hippocampal NR2A/2B expression ratio

Repeated low-dose morphine treatment facilitates delayed-escape behaviour of hippocampus-dependent Morris water maze and morphine withdrawal influences hippocampal NMDA receptor-dependent synaptic plasticity. Here, we examined whether and how morphine wit

TUNNELING ESCAPE TIME OF ELECTRONS FROM A QUANTUM-WELL WITH GAMMA-X MIXING EFFECT

By using the envelope function method we calculated the tunneling escape time of electrons from a quantum well. We adopted a simplified interface matrix to describe the GAMMA-X mixing effect, and employed a wave packet method to determine the tunneling escape time. When the GAMMA state in the well was in resonance with the X state in the barrier, the escape time reduced remarkably. However, it was possible that the wave functions in two different channels, i.e., GAMMA-GAMMA-GAMMA and GAMMA-X-GAMMA, could interfere destructively, leading the escape time greater than that of pure GAMMA-GAMMA-GAMMA tunneling.

TUNNELING ESCAPE TIME OF ELECTRONS THROUGH DOUBLE-BARRIER RESONANT-TUNNELING STRUCTURES

Tunneling escape of electrons from quantum wells (QWs) has systematically been studied in an arbitrarily multilayered heterostructures, both theoretically and experimentally. A wave packet method is developed to calculate the bias dependence of tunneling escape time (TET) in a three-barrier, two-well structure. Moreover, by considering the time variation of the band-edge profile in the escape transient, arising from the decay of injected electrons in QWs, we demonstrate that the actual escape time of certain amount of charge from QWs, instead of single electron, could be much longer than that for a single electron, say, by two orders of magnitude at resonance. The broadening of resonance may also be expected from the same mechanism before invoking various inhomogeneous and homogeneous broadening. To perform a close comparison between theory and experiment, we have developed a new method to measure TET by monitoring transient current response (TCR), stemming from tunneling escape of electrons out of QWs in a similar heterostructure. The time resolution achieved by this new method reaches to several tens ns, nearly three orders of magnitude faster than that by previous transient-capacitance spectroscopy (TCS). The measured TET shows an U-shaped, nonmonotonic dependence on bias, unambiguously indicating resonant tunneling escape of electrons from an emitter well through the DBRTS in the down-stream direction. The minimum value of TET obtained at resonance is accordance with charging effect and its time variation of injected electrons. A close comparison with the theory has been made to imply that the dynamic build-up of electrons in DBRTS might play an important role for a greatly suppressed tunneling escape rate in the vicinity of resonance.

STUDIES ON TUNNELING ESCAPE TIME OF ELECTRONS FROM A QUANTUM-WELL IN MULTILAYERED HETEROSTRUCTURES

By considering the time variation of band-edge profile arising from the decay of injected charge in quantum wells(QWs), we employ a wave packet method to verify that the actual escape time of certain amount of electrons from QWs could be much larger than that for a single electron. The theoretical result is also in agreement with our measurement of escape time, performed by using a newly developed method--transient current response.

Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing.

We used ultra-deep sequencing to obtain tens of thousands of HIV-1 sequences from regions targeted by CD8+ T lymphocytes from longitudinal samples from three acutely infected subjects, and modeled viral evolution during the critical first weeks of infection. Previous studies suggested that a single virus established productive infection, but these conclusions were tempered because of limited sampling; now, we have greatly increased our confidence in this observation through modeling the observed earliest sample diversity based on vastly more extensive sampling. Conventional sequencing of HIV-1 from acute/early infection has shown different patterns of escape at different epitopes; we investigated the earliest escapes in exquisite detail. Over 3-6 weeks, ultradeep sequencing revealed that the virus explored an extraordinary array of potential escape routes in the process of evading the earliest CD8 T-lymphocyte responses--using 454 sequencing, we identified over 50 variant forms of each targeted epitope during early immune escape, while only 2-7 variants were detected in the same samples via conventional sequencing. In contrast to the diversity seen within epitopes, non-epitope regions, including the Envelope V3 region, which was sequenced as a control in each subject, displayed very low levels of variation. In early infection, in the regions sequenced, the consensus forms did not have a fitness advantage large enough to trigger reversion to consensus amino acids in the absence of immune pressure. In one subject, a genetic bottleneck was observed, with extensive diversity at the second time point narrowing to two dominant escape forms by the third time point, all within two months of infection. Traces of immune escape were observed in the earliest samples, suggesting that immune pressure is present and effective earlier than previously reported; quantifying the loss rate of the founder virus suggests a direct role for CD8 T-lymphocyte responses in viral containment after peak viremia. Dramatic shifts in the frequencies of epitope variants during the first weeks of infection revealed a complex interplay between viral fitness and immune escape.

The impact of host immune status on the within-host and population dynamics of antigenic immune escape.

Antigenically evolving pathogens such as influenza viruses are difficult to control owing to their ability to evade host immunity by producing immune escape variants. Experimental studies have repeatedly demonstrated that viral immune escape variants emerge more often from immunized hosts than from naive hosts. This empirical relationship between host immune status and within-host immune escape is not fully understood theoretically, nor has its impact on antigenic evolution at the population level been evaluated. Here, we show that this relationship can be understood as a trade-off between the probability that a new antigenic variant is produced and the level of viraemia it reaches within a host. Scaling up this intra-host level trade-off to a simple population level model, we obtain a distribution for variant persistence times that is consistent with influenza A/H3N2 antigenic variant data. At the within-host level, our results show that target cell limitation, or a functional equivalent, provides a parsimonious explanation for how host immune status drives the generation of immune escape mutants. At the population level, our analysis also offers an alternative explanation for the observed tempo of antigenic evolution, namely that the production rate of immune escape variants is driven by the accumulation of herd immunity. Overall, our results suggest that disease control strategies should be further assessed by considering the impact that increased immunity--through vaccination--has on the production of new antigenic variants.

Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation.

BACKGROUND: Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses. RESULTS: The T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, the fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations. CONCLUSIONS: Our results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.

Safer by design: simulating fire and escape at sea

When designing a new passenger ship or modifying an existing design, how do we ensure that the proposed design and crew emergency procedures are safe from an evacuation resulting from fire or other incident? In the wake of major maritime disasters such as the Scandinavian Star, Herald of Free Enterprise, Estonia and in light of the growth in the numbers of high density, high-speed ferries and large capacity cruise ships, issues concerning the evacuation of passengers and crew at sea are receiving renewed interest. Fire and evacuation models with features such as the ability to realistically simulate the spread of fire and fire suppression systems and the human response to fire as well as the capability to model human performance in heeled orientations linked to a virtual reality environment that produces realistic visualisations of the modelled scenarios are now available and can be used to aid the engineer in assessing ship design and procedures. This paper describes the maritimeEXODUS ship evacuation and the SMARTFIRE fire simulation model and provides an example application demonstrating the use of the models in performing fire and evacuation analysis for a large passenger ship partially based on the requirements of MSC circular 1033. The fire simulations include the action of a water mist system.

Role of hypoxia and hypoxia-inducible factor-1 in tumour immune escape

Previous studies revealed that, upon exposure to hypoxia, tumour cells acquire resistance to the cytolytic activity of IL-2-activated lymphocytes. The MHC class I chain-related (MIC) molecules – comprised of MICA and MICB – are ligands for the activating NKG2D receptor on Natural Killer (NK) and CD8+ T cells. MIC-NKG2D interactions lead to the activation of NK and CD8+ T cells and the subsequent lysis of the tumour cells. The study also showed that the mechanism of the hypoxia-mediated immune escape involves the shedding of MIC, specifically MICA, from the tumour cell surface. The objective of the present study was to determine whether the shedding of MICA requires the expression of hypoxia inducible factor-1 (HIF-1), a transcription factor that regulates cellular adaptations to hypoxia. Exposure to hypoxia (0.5% O2 vs. 20% O2) led to the shedding of MIC from the surface of MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells as determined by flow cytometry. Knockdown of HIF-1α mRNA using siRNA technology resulted in inhibition of HIF-1α accumulation under hypoxic conditions as determined by Western blot analysis. Parallel study revealed that knockdown of HIF-1α also blocked the shedding of MICA from the surface of MDA-MB-231 cells exposed to hypoxia. These results indicate that HIF-1 is required for the hypoxia-mediated shedding of MICA and, consequently, that HIF-1 may play an important role in tumour immune escape. Ongoing studies aim to determine the HIF-1 target genes involved in the shedding of MICA under hypoxia.