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This study examined the intercultural communication apprehension of university students in Japan and China, and its relationship with language competence, and self-regulation, comparing the two to those in America. A total of 614 students from Japan (N=216), China (N=215), and America (N=183) completed the questionnaire online. Our findings demonstrated that Japanese and Chinese students were higher in intercultural communication apprehension and prevention focus, while Americans were higher in promotion focus. As predicted, apart from the English language ability, self-regulatory focus explained the intercultural communication anxiety of Japanese and Chinese students. The impact of language competence on intercultural communication apprehension was mediated by promotion focus. The findings uncovered some important motivational factors with potential for mitigating the intercultural communication apprehension of students in East Asian cultures. [ABSTRACT FROM AUTHOR]

Residual limb volume fluctuation and the resulting contact pressures are some of the key factors leading to skin ulcerations, suboptimal prosthetic functioning, pain, and diminishing quality of life of transtibial amputees. Self-management of socket fit is complicated by peripheral neuropathy, reducing the perception of pressure and pain in the residual limb. We introduce a novel proof-of-concept for a transtibial prosthetic socket liner with the potential to dynamically adjust the fit between the limb and socket. The core of the technology is a small air microfluidic chip (10 cm3 and 10 g) with 10 on-chip valves that enable sequential pressurizing of 10 actuators in custom sizes to match the pressures required by the residual limb's unique anatomy. The microfluidic chip largely reduced the number of electromechanical solenoid valves needed for sequential control of 10 actuators (2 instead of 10 valves), resulting in the reduction of the required power, size, mass, and cost of the control box toward an affordable and wearable prosthetic socket. Proof-of-concept testing demonstrated that the applied pressures can be varied in the desired sequence and to redistribute pressure. Future work will focus on integrating the system with biofidelic prosthetic sockets and residual limb models to investigate the ability to redistribute pressure away from pressure-sensitive regions (e.g., fibular head) to pressure tolerant areas. Overall, the dynamic prosthesis socket liner is very encouraging for creating a dynamic socket fit system that can be seamlessly integrated with existing socket fabrication methods for managing residual limb volume fluctuations and contact pressure. [ABSTRACT FROM AUTHOR]

Many viral surface glycoproteins and cell surface receptors are homo-oligomers, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites. In the first step, a small protein is designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza. [ABSTRACT FROM AUTHOR]

Broadly neutralizing antibodies targeting a highly conserved region in the hemagglutinin (HA) stem protect against influenza infection. Here, we investigate the protective efficacy of a protein (HB36.6) computationally designed to bind with high affinity to the same region in the HA stem. We show that intranasal delivery of HB36.6 affords protection in mice lethally challenged with diverse strains of influenza independent of Fc-mediated effector functions or a host antiviral immune response. This designed protein prevents infection when given as a single dose of 6.0 mg/kg up to 48 hours before viral challenge and significantly reduces disease when administered as a daily therapeutic after challenge. A single dose of 10.0 mg/kg HB36.6 administered 1-day post-challenge resulted in substantially better protection than 10 doses of oseltamivir administered twice daily for 5 days. Thus, binding of HB36.6 to the influenza HA stem region alone, independent of a host response, is sufficient to reduce viral infection and replication in vivo. These studies demonstrate the potential of computationally designed binding proteins as a new class of antivirals for influenza. [ABSTRACT FROM AUTHOR]

We engineered a disulfide-stabilized influenza virus hemagglutinin (HA) trimer, termed HA3-SS, by introducing cysteine residues into the HA stem to covalently bridge the three protomers. HA3-SS has increased thermostability compared to wild-type HA, and binding of head- and stem-targeted antibodies (Abs) is preserved; only minor structural changes are found in the vicinity of the additional disulfide. This platform has been applied to H1 and H3 HAs and provides prospects for design of intact, stabilized influenza virus HA immunogens. [ABSTRACT FROM AUTHOR]

Influenza viruses remain a persistent challenge to human health owing to their inherent ability to evade the immune response by antigenic drift. However, the discovery of broadly neutralizing antibodies (bnAbs) against divergent viruses has sparked renewed interest in a universal influenza vaccine and novel therapeutic opportunities. Here, a crystal structure at 1.70 Å resolution is presented of the Fab of the human antibody CH65, which has broad neutralizing activity against a range of seasonal H1 isolates. Previous studies proposed that affinity maturation of this antibody lineage pre-organizes the complementarity-determining region (CDR) loops into an energetically favorable HA-bound conformation. Indeed, from the structural comparisons of free and HA-bound CH65 presented here, the CDR loops, and in particular the heavy-chain CDR3, adopt the same conformations in the free and bound forms. Thus, these findings support the notion that affinity maturation of the CH65 lineage favorably preconfigures the CDR loops for high-affinity binding to influenza hemagglutinin. [ABSTRACT FROM AUTHOR]

Due to continuous changes to its antigenic regions, influenza viruses can evade immune detection and cause a significant amount of morbidity and mortality around the world. Influenza vaccinations can protect against disease but must be annually reformulated to match the current circulating strains. In the development of a broad-spectrum influenza vaccine, the elucidation of conserved epitopes is paramount. To this end, we designed an immunization strategy in mice to boost the humoral response against conserved regions of the hemagglutinin (HA) glycoprotein. Of note, generation and identification of broadly neutralizing antibodies that target group 2 HAs are rare and thus far have yielded only a few monoclonal antibodies (MAbs). Here, we demonstrate that mouse MAb 9H10 has broad and potent in vitro neutralizing activity against H3 and H10 group 2 influenza A subtypes. In the mouse model, MAb 9H10 protects mice against two divergent mouse-adapted H3N2 strains, in both pre- and postexposure administration regimens. In vitro and cell-free assays suggest that MAb 9H10 inhibits viral replication by blocking HA-dependent fusion of the viral and endosomal membranes early in the replication cycle and by disrupting viral particle egress in the late stage of infection. Interestingly, electron microscopy reconstructions of MAb 9H10 bound to the HA reveal that it binds a similar binding footprint to MAbs CR8020 and CR8043. [ABSTRACT FROM AUTHOR]

Influenza virus is a global health concern due to its unpredictable pandemic potential. This potential threat was realized in 2009 when an H1N1 virus emerged that resembled the 1918 virus in antigenicity but fortunately was not nearly as deadly. 5J8 is a human antibody that potently neutralizes a broad spectrum of H1N1 viruses, including the 1918 and 2009 pandemic viruses. Here, we present the crystal structure of 5 J8 Fab in complex with a bacterially expressed and refolded globular head domain from the hemagglutinin (HA) of the A/California/07/2009 (H1N1) pandemic virus. 5J8 recognizes a conserved epitope in and around the receptor binding site (RBS), and its HCDR3 closely mimics interactions of the sialic acid receptor. Electron microscopy (EM) reconstructions of 5J8 Fab in complex with an HA trimer from a 1986 H1 strain and with an engineered stabilized HA trimer from the 2009 H1 pandemic virus showed a similar mode of binding. As for other characterized RBS-targeted antibodies, 5J8 uses avidity to extend its breadth and affinity against divergent H1 strains. 5J8 selectively interacts with HA insertion residue 133a, which is conserved in pandemic H1 strains and has precluded binding of other RBS-targeted antibodies. Thus, the RBS of divergent HAs is targeted by 5J8 and adds to the growing arsenal of common recognition motifs for design of therapeutics and vaccines. Moreover, consistent with previous studies, the bacterially expressed H1 HA properly refolds, retaining its antigenic structure, and presents a low-cost and rapid alternative for engineering and manufacturing candidate flu vaccines. [ABSTRACT FROM AUTHOR]

Abstract: The σ subunits of bacterial RNA polymerase occur in many variant forms and confer promoter specificity to the holopolymerase. Members of the σ54 family of σ subunits require the action of a ‘transcriptional activator’ protein to open the promoter and initiate transcription. The activator proteins undergo regulated assembly from inactive dimers to hexamers that are active ATPases. These contact σ54 directly and, through ATP hydrolysis, drive a conformational change that enables promoter opening. σ54 activators use several different kinds of regulatory domains to respond to a wide variety of intracellular signals. One common regulatory module, the GAF domain, is used by σ54 activators to sense small-molecule ligands. The structural basis for GAF domain regulation in σ54 activators has not previously been reported. Here, we present crystal structures of GAF regulatory domains for Aquifex aeolicus σ54 activators NifA-like homolog (Nlh)2 and Nlh1 in three functional states—an ‘open’, ATPase-inactive state; a ‘closed’, ATPase-inactive state; and a ‘closed’, ligand-bound, ATPase-active state. We also present small-angle X-ray scattering data for Nlh2-linked GAF-ATPase domains in the inactive state. These GAF domain dimers regulate σ54 activator proteins by holding the ATPase domains in an inactive dimer conformation. Ligand binding of Nlh1 dramatically remodels the GAF domain dimer interface, disrupting the contacts with the ATPase domains. This mechanism has strong parallels to the response to phosphorylation in some two-component regulated σ54 activators. We describe a structural mechanism of GAF-mediated enzyme regulation that appears to be conserved among humans, plants, and bacteria. [Copyright &y& Elsevier]

The Great Western Woodlands in S.W. Australia is the largest remaining expanse of temperate woodland on the continent and globally, providing habitat for a significance number of bird species. Conservation planning needs information about bird distributions and habitat resource requirements. Using published information, bird habitat functional groups were identified based upon species that use similar vegetation-based resources. Data from four satellite-borne sensors were analysed to model the distribution of a subset of the key vegetation variables. These results were then used to predict the potential distribution of the functional groups. Field validation suggests ongoing advances in satellite data will enhance the model's accuracy. [ABSTRACT FROM PUBLISHER]

The article discusses the study of growth, feed conversion ratio (FCR), and faecal discharge of yellowtail kingfish in New Zealand. It notes the feeding of three commercial diets for the studied yellowtail kingfish species. It mentions the culture of the fishes in tanks over spring and summer seasons. Furthermore, it also discovers that yellowtail kingfishes grow rapidly during the warm and summer temperatures.

Since the mid-1970s the Limulus Amebocyte Lysate (LAL) assay has been used to test medical devices for bacterial endotoxins. The Association for the Advancement of Medical Instrumentation (AAMI) recently published a standard designated ANSI/AAMI ST 72: 2002, Bacterial Endotoxins--Test methodologies, routine monitoring, and alternatives to batch testing, which addresses LAL testing and associated issues. In order to perform the bacterial endotoxins test (BET), the test article must be extracted in an aqueous medium, with the extract being used as the test solution. In the early years of testing, and periodically throughout LAL test history, questions have arisen about validation of the extraction efficiency of endotoxins from medical devices. The AAMI Microbiological Methods Committee appointed a Task Group to thoroughly research the issue of extraction efficiency and to recommend whether validation of extraction efficiency is necessary for LAL testing of medical devices. [ABSTRACT FROM AUTHOR]

Pulmonary Retention of Inhaled Diesel Particles after Prolonged Exposures to Diesel Exhaust CHAN, T. L., LEE, P. S., AND HERING, W. E. (1984). . 4, 624–631. The effect of continuous exposure to diluted diesel exhaust on the pulmonary retention of inhaled diesel particles was studied in male Fischer 344 rats. Test animals were first exposed to clean air or diluted diesel exhaust in exposure chambers at nominal particulate concentrations of 250 μg/m or 6 mg/m for 20 hr/day, 7 days/week, for periods lasting from 7 to 112 days, followed by a nose-only exposure to C-tagged diesel particles for 45 min. At preselected time intervals after the radioactive exposure, the C-activities in the lungs of groups of four animals were measured to determine the clearance of the C-diesel particles up to 1 year. The pulmonary retention of the radioactive diesel particles was greater in animals which had been preexposed to diesel exhaust The slower alveolar clearance of particle-laden macrophages and leukocytes can be described by a normal Diphasic clearance model. Since some of the macrophages were found sequestered as aggregates in the pulmonary region, a slow-clearing residual component was included in a modified lung retention model. When these residual fractions were determined and excluded from the active particulate transport within the lungs, normal alveolar clearance rates were calculated for the animals with a preexposure diesel particulate dose less than 0.8 mg. Slower clearance was observed at a dose of 6.5 mg and no clearance was evident at a dose of 11.8 mg in their lungs. In effect, the greater retention of inhaled particles can be interpreted as-a sign of impaired lung clearance attributable to the prolonged exposures to high concentrations of diesel exhaust gases and/or the presence of accumulated carbonaceous particles residing in sequestered macrophage aggregates in the lungs. [ABSTRACT FROM PUBLISHER]