Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge

Influenza HA is the primary target of neutralizing antibodies during infection, and its sequence undergoes genetic drift and shift in response to immune pressure. The receptor binding HA1 subunit of HA shows much higher sequence variability relative to the metastable, fusion-active HA2 subunit, presumably because neutralizing antibodies are primarily targeted against the former in natural infection. We have designed an HA2-based immunogen using a protein minimization approach that incorporates designed mutations to destabilize the low pH conformation of HA2. The resulting construct (HA6) was expressed in Escherichia coli and refolded from inclusion bodies. Biophysical studies and mutational analysis of the protein indicate that it is folded into the desired neutral pH conformation competent to bind the broadly neutralizing HA2 directed monoclonal 12D1, not the low pH conformation observed in previous studies. HA6 was highly immunogenic in mice and the mice were protected against lethal challenge by the homologous A/HK/68 mouse-adapted virus. An HA6-like construct from another H3 strain (A/Phil/2/82) also protected mice against A/HK/68 challenge. Regions included in HA6 are highly conserved within a subtype and are fairly well conserved within a clade. Targeting the highly conserved HA2 subunit with a bacterially produced immunogen is a vaccine strategy that may aid in pandemic preparedness.

Short-range-order effects on intrinsic plasticity of metallic glasses

Through a systematical analysis of the elastic moduli for 137 metallic glasses (MGs) and 56 polycrystalline metals, we use a simple model developed by Knuyt et al. [J. Phys. F: Met. Phys. 16 (1986) p.1989; Phil. Mag. B 64 (1991) p.299] based on a Gaussian distribution for the first-neighbor distance to reveal the short-range-order (SRO) structural conditions for plasticity of MGs. It is found that the SRO structure with dense atomic packing, large packing dispersion and a significant anharmonicity of atomic interaction within an MG is favorable for its global plasticity. Although these conditions seem paradoxical, their perfect matching is believed to be a key for designing large plastic bulk MGs not only in compression but also in tension.

Wilmington gray to blue

Wilmington is situated on the divide of two major watersheds, the Cape Fear River and the Atlantic Intracoastal Waterway. All surface waters in Wilmington drain to one of these two water bodies and are divided into two groups: tidal creeks and Cape Fear River tributaries. Cape Fear River tributaries drain directly to the Cape Fear River and comprise the western portion of Wilmington’s surface waters. Tidal creeks drain directly into the Atlantic Intracoastal Waterway and make up the eastern portion of Wilmington’s surface waters. (PDF contains 4 pages)

Catches of Humpback Whales, Megaptera novaeangliae, by the Soviet Union and Other Nations in the Southern Ocean, 1947–1973

From 1947 to 1973, the U.S.S.R. conducted a huge campaign of illegal whaling worldwide. We review Soviet catches of humpback whales, Megaptera novaeangliae, in the Southern Ocean during this period, with an emphasis on the International Whaling Commission’s Antarctic Management Areas IV, V, and VI (the principal regions of illegal Soviet whaling on this species, south of Australia and western Oceania). Where possible, we summarize legal and illegal Soviet catches by year, Management Area, and factory fleet, and also include information on takes by other nations. Soviet humpback catches between 1947 and 1973 totaled 48,702 and break down as follows: 649 (Area I), 1,412 (Area II), 921 (Area III), 8,779 (Area IV), 22,569 (Area V), and 7,195 (Area VI), with 7,177 catches not currently assignable to area. In all, at least 72,542 humpback whales were killed by all operations (Soviet plus other nations) after World War II in Areas IV (27,201), V (38,146), and VI (7,195). More than one-third of these (25,474 whales, of which 25,192 came from Areas V and VI) were taken in just two seasons, 1959–60 and 1960–61. The impact of these takes, and of those from Area IV in the late 1950’s, is evident in the sometimes dramatic declines in catches at shore stations in Australia, New Zealand, and at Norfolk Island. When compared to recent estimates of abundance and initial population size, the large removals from Areas IV and V indicate that the populations in these regions remain well below pre-exploitation levels despite reported strong growth rates off eastern and western Australia. Populations in many areas of Oceania continue to be small, indicating that the catches from Area VI and eastern Area V had long-term impacts on recovery.

A Whale of a Deception

In late October of 1966, an imposing ship steamed quietly through the placid waters of the Suez Canal. Clad in drab industrial gray, and flying a Soviet hammer and sickle flag at her masthead, the vessel was accompanied by a large fleet of smaller craft. Any observer able to decipher Cyrillic script could have read, in rusting metallic letters on her bow, the name Sovetskaya Ukraina. The more experienced would perhaps have identified her as a whaling factory ship, traveling with her attendant fleet of catcher boats and scouting vessels on a transit that would take them south into the Red Sea and beyond.

Report of the Workshop on Blue Crab Stock Dynamics in Chesapeake Bay, December 13-15, 1982, Chesapeake Biological Laboratory

This workshop was convened to begin building a foundation of understanding for developing and evaluating proposed measures for the rational management of the blue crab fishery in Chesapeake Bay. Our goal was to generate a summary of knowledge of blue crab stock dynamics. Specifically, we intended to address, and hoped to estimate, the basic parameters of an exploited stock - growth, mortality, natality, migration rates, sex ratios and abundance. In one sense these objectives were simply a means for organizing our discussions. A second objective was to compile at the workshop pertinent data held by the major research institutions on Chesapeake Bay so all participants could see the kinds and extent of existing data. As with many stock assessment problems, tailoring an estimating procedure around known existing data can be more productive than deciding on a procedure and then trying to find the required data in someone else's files. Authors of papers contributed to the report: B.S. Hester and P.R. Mundy (p. 50); Qisheng Tang (p. 86); L. Eugene Cronin (p. 111); J.R. McConaugha (p. 128); Cluney Stagg and Phil Jones (p. 153).

Percentage composition of Brachyuran larvae collected during 1994 in Manora Channel, Karachi, Pakistan

Brachyuran larvae are the most common zooplankton component of the Manora Channel, Karachi, Pakistan. The identification of these larvae would assist in the assessment of brachyuran species and provide information on percentage composition, occurrence, abundance and breeding habits of the brachyuran species in the Manora Channel area. However plankton caught larvae is not easily identified. An accurate identification of such material is only possible by the comparison with larvae reared under laboratory conditions and documented with illustrations. The identifications for this present study were based on the works of Gurney (1938); Atkins (1954); Chhapgar (1955); Raja Bai (1960); Hashmi (1969, 1970a, b); Baba and Miyata (1971); Kakati and Sankolli (1975); Rice (1975); Kakati (1977); Lim and Tan (1981); Yatsuzuka and Sakai (1984); Fielder, et al (1984); Amir (1989, M. Phil thesis unpublished); Ingle (1992); Siddiqui and Tirmizi (1992); Tirmizi et al (1993); Bano (1999, M. Phil thesis unpublished); Ghory and Siddiqui (2001); Ghory (2002, M. Phil thesis unpublished); Ghory and Siddiqui (2002).

Marine Vertebrates and Low Frequency Sound: Technical Report for LFA EIS

Over the past 50 years, economic and technological developments have dramatically increased the human contribution to ambient noise in the ocean. The dominant frequencies of most human-made noise in the ocean is in the low-frequency range (defined as sound energy below 1000Hz), and low-frequency sound (LFS) may travel great distances in the ocean due to the unique propagation characteristics of the deep ocean (Munk et al. 1989). For example, in the Northern Hemisphere oceans low-frequency ambient noise levels have increased by as much as 10 dB during the period from 1950 to 1975 (Urick 1986; review by NRC 1994). Shipping is the overwhelmingly dominant source of low-frequency manmade noise in the ocean, but other sources of manmade LFS including sounds from oil and gas industrial development and production activities (seismic exploration, construction work, drilling, production platforms), and scientific research (e.g., acoustic tomography and thermography, underwater communication). The SURTASS LFA system is an additional source of human-produced LFS in the ocean, contributing sound energy in the 100-500 Hz band. When considering a document that addresses the potential effects of a low-frequency sound source on the marine environment, it is important to focus upon those species that are the most likely to be affected. Important criteria are: 1) the physics of sound as it relates to biological organisms; 2) the nature of the exposure (i.e. duration, frequency, and intensity); and 3) the geographic region in which the sound source will be operated (which, when considered with the distribution of the organisms will determine which species will be exposed). The goal in this section of the LFA/EIS is to examine the status, distribution, abundance, reproduction, foraging behavior, vocal behavior, and known impacts of human activity of those species may be impacted by LFA operations. To focus our efforts, we have examined species that may be physically affected and are found in the region where the LFA source will be operated. The large-scale geographic location of species in relation to the sound source can be determined from the distribution of each species. However, the physical ability for the organism to be impacted depends upon the nature of the sound source (i.e. explosive, impulsive, or non-impulsive); and the acoustic properties of the medium (i.e. seawater) and the organism. Non-impulsive sound is comprised of the movement of particles in a medium. Motion is imparted by a vibrating object (diaphragm of a speaker, vocal chords, etc.). Due to the proximity of the particles in the medium, this motion is transmitted from particle to particle in waves away from the sound source. Because the particle motion is along the same axis as the propagating wave, the waves are longitudinal. Particles move away from then back towards the vibrating source, creating areas of compression (high pressure) and areas of rarefaction (low pressure). As the motion is transferred from one particle to the next, the sound propagates away from the sound source. Wavelength is the distance from one pressure peak to the next. Frequency is the number of waves passing per unit time (Hz). Sound velocity (not to be confused with particle velocity) is the impedance is loosely equivalent to the resistance of a medium to the passage of sound waves (technically it is the ratio of acoustic pressure to particle velocity). A high impedance means that acoustic particle velocity is small for a given pressure (low impedance the opposite). When a sound strikes a boundary between media of different impedances, both reflection and refraction, and a transfer of energy can occur. The intensity of the reflection is a function of the intensity of the sound wave and the impedances of the two media. Two key factors in determining the potential for damage due to a sound source are the intensity of the sound wave and the impedance difference between the two media (impedance mis-match). The bodies of the vast majority of organisms in the ocean (particularly phytoplankton and zooplankton) have similar sound impedence values to that of seawater. As a result, the potential for sound damage is low; organisms are effectively transparent to the sound – it passes through them without transferring damage-causing energy. Due to the considerations above, we have undertaken a detailed analysis of species which met the following criteria: 1) Is the species capable of being physically affected by LFS? Are acoustic impedence mis-matches large enough to enable LFS to have a physical affect or allow the species to sense LFS? 2) Does the proposed SURTASS LFA geographical sphere of acoustic influence overlap the distribution of the species? Species that did not meet the above criteria were excluded from consideration. For example, phytoplankton and zooplankton species lack acoustic impedance mis-matches at low frequencies to expect them to be physically affected SURTASS LFA. Vertebrates are the organisms that fit these criteria and we have accordingly focused our analysis of the affected environment on these vertebrate groups in the world’s oceans: fishes, reptiles, seabirds, pinnipeds, cetaceans, pinnipeds, mustelids, sirenians (Table 1).

Kelvin-Helmholtz-like instabilities in turbulent flows over complex surfaces

Riblets are small surface protrusions aligned with the flow direction, which confer an anisotropic roughness to the surface [6]. We have recently reported that the transitional-roughness effect in riblets, which limits their performance, is due to a Kelvin–Helmholtz-like instability of the overlying mean flow [7]. According to our DNSs, the instability sets on as the Reynolds number based on the roughness size of the riblets increases, and coherent, elongated spanwise vortices begin to develop immediately above the riblet tips, causing the degradation of the drag-reduction effect. This is a very novel concept, since prior studies had proposed that the degradation was due to the interaction of riblets with the flow as independent units, either to the lodging of quasi-streamwise vortices in the surface grooves [2] or to the shedding of secondary streamwise vorticity at the riblet peaks [9]. We have proposed an approximate inviscid analysis for the instability, in which the presence of riblets is modelled through an average boundary condition for an overlying, spanwise-independent mean flow. This simplification lacks the accuracy of an exact analysis [4], but in turn applies to riblet surfaces in general. Our analysis succeeds in predicting the riblet size for the onset of the instability, while qualitatively reproducing the wavelengths and shapes of the spanwise structures observed in the DNSs. The analysis also connects the observations with the Kelvin–Helmholtz instability of mixing layers. The fundamental riblet length scale for the onset of the instability is a ‘penetration length,’ which reflects how easily the perturbation flow moves through the riblet grooves. This result is in excellent agreement with the available experimental evidence, and has enabled the identification of the key geometric parameters to delay the breakdown. Although the appearance of elongated spanwise vortices was unexpected in the case of riblets, similar phenomena had already been observed over other rough [3], porous [1] and permeable [11] surfaces, as well as over plant [5,14] and urban [12] canopies, both in the transitional and in the fully-rough regimes. However, the theoretical analyses that support the connection of these observations with the Kelvin–Helmholtz instability are somewhat scarce [7, 11, 13]. It has been recently proposed that Kelvin–Helmholtz-like instabilities are a dominant feature common to “obstructed” shear flows [8]. It is interesting that the instability does not require an inflection point to develop, as is often claimed in the literature. The Kelvin-Helmholtz rollers are rather triggered by the apparent wall-normal-transpiration ability of the flow at the plane immediately above the obstructing elements [7,11]. Although both conditions are generally complementary, if wall-normal transpiration is not present the spanwise vortices may not develop, even if an inflection point exists within the roughness [10]. REFERENCES [1] Breugem, W. P., Boersma, B. J. & Uittenbogaard, R. E. 2006 J. Fluid Mech. 562, 35–72. [2] Choi, H., Moin, P. & Kim, J. 1993 J. Fluid Mech. 255, 503–539. [3] Coceal, O., Dobre, A., Thomas, T. G. & Belcher, S. E. 2007 J. Fluid Mech. 589, 375–409. [4] Ehrenstein, U. 2009 Phys. Fluids 8, 3194–3196. [5] Finnigan, J. 2000 Ann. Rev. Fluid Mech. 32, 519–571. [6] Garcia-Mayoral, R. & Jimenez, J. 2011 Phil. Trans. R. Soc. A 369, 1412–1427. [7] Garcia-Mayoral, R. & Jimenez, J. 2011 J. Fluid Mech. doi: 10.1017/jfm.2011.114. [8] Ghisalberti, M. 2009 J. Fluid Mech. 641, 51–61. [9] Goldstein, D. B. & Tuan, T. C. 1998 J. Fluid Mech. 363, 115–151. [10] Hahn, S., Je, J. & Choi, H. 2002 J. Fluid Mech. 450, 259–285. [11] Jimenez, J., Uhlman, M., Pinelli, A. & G., K. 2001 J. Fluid Mech. 442, 89–117. [12] Letzel, M. O., Krane, M. & Raasch, S. 2008 Atmos. Environ. 42, 8770–8784. [13] Py, C., de Langre, E. & Moulia, B. 2006 J. Fluid Mech. 568, 425–449. [14] Raupach, M. R., Finnigan, J. & Brunet, Y. 1996 Boundary-Layer Meteorol. 78, 351–382.

It's not interaction, it's make believe.

A principal, but largely unexplored, use of our cognition when using interacting technology involves pretending. To pretend is to believe that which is not the case, for example, when we use the desktop on our personal computer we are pretending, that is, we are pretending that the screen is a desktop upon which windows reside. But, of course, the screen really isn't a desktop. Similarly when we engage in scenario- or persona-based design we are pretending about the settings, narrative, contexts and agents involved. Although there are exceptions, the overwhelming majority of the contents of these different kinds of stories are not the case. We also often pretend when we engage in the evaluation of these technologies (e.g. in the Wizard of Oz technique we "ignore the man behind the curtain"). We are pretending when we ascribe human-like qualities to digital technology. In each we temporarily believe something to be the case which is not. If we add the experience of tele- and social-presence to this, and the diverse experiences which can arise from using digital technology which too are predicted on pretending, then we are prompted to propose that human computer interaction and cognitive ergonomics are largely built on pretending and make believe. If this premise is accepted (and if not, please pretend for a moment), there are a number of interesting consequences.

Enactive appropriation.

The appropriation of digital artefacts involves their use, which has changed, evolved or developed beyond their original design. Thus, to understand appropriation, we must understand use. We define use as the active, purposive exploitation of the affordances offered by the technology and from this perspective; appropriation emerges as a natural consequence of this enactive use. Enaction tells us that perception is an active process. It is something we do, and not something that happens to us. From this reading, use then becomes the active exploitation of the affordances offered us by the artefact, system or service. In turn, we define appropriation as the engagement with these actively disclosed affordances—disclosed as a consequence of, not just, seeing but of seeing as. We present a small case study that highlights instances of perception as an actively engaged skill. We conclude that appropriation is a simple consequence of enactive perception.

Dialogue for bass clarinet and bassoon

This work specifically focuses on the lower register of both instruments, an area I've been led to explore as a result of my profound high frequency hearing loss. It was selected for performance following an international competitive call for scores and premiered at the 16th London New Wind Festival, 22nd November 2013. It was performed by Phil Edwards (bass clarinet) and Glyn Williams (bassoon).