Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin

Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01) and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The beta-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus

Solid State NMR Characterization of Complex Metal Hydrides systems for Hydrogen Storage Applications

Solid state NMR is widely applied in studies of solid state chemistries for hydrogen storage reactions. Use of ^(11)B MAS NMR in studies of metal borohydrides (BH_4) is mainly focused, revisiting the issue of dodecaborane formation and observation of ^(11)B{^1H} Nuclear Overhauser Effect

C57BL/6 life span study: age-related declines in muscle power production and contractile velocity

Quantification of key outcome measures in animal models of aging is an important step preceding intervention testing. One such measurement, skeletal muscle power generation (force * velocity), is critical for dynamic movement. Prior research focused on maximum power (P max), which occurs around 30-40 % of maximum load. However, movement occurs over the entire load range. Thus, the primary purpose of this study was to determine the effect of age on power generation during concentric contractions in the extensor digitorum longus (EDL) and soleus muscles over the load range from 10 to 90 % of peak isometric tetanic force (P 0). Adult, old, and elderly male C57BL/6 mice were examined for contractile function (6-7 months old, 100 % survival; ~24 months, 75 %; and ~28 months, 50 % P 0). The shape of the force-velocity curve also changed with age (a/P 0 increased). In addition, there were prolonged contraction times to maximum force and shifts in the distribution of the myosin light and heavy chain isoforms in the EDL. The results demonstrate that age-associated difficulty in movement during challenging tasks is likely due, in addition to overall reduced force output, to an accelerated deterioration of power production and contractile velocity under heavily loaded conditions.R01 AG017768 - NIA NIH HHS; F31 AG044108 - NIA NIH HHS; T32 AG029796 - NIA NIH HHS; R01 EY15313 - NEI NIH HHS; R01 EY015313 - NEI NIH HH

Towards using a physio-cognitive model in tutoring for psychomotor tasks.

We report our exploratory research of psychomotor task training in intelligent tutoring systems (ITSs) that are generally limited to tutoring in the desktop learning environment where the learner acquires cognitively oriented knowledge and skills. It is necessary to support computer-guided training in a psychomotor task domain that is beyond the desktop environment. In this study, we seek to extend the current capability of GIFT (Generalized Intelligent Frame-work for Tutoring) to address these psychomotor task training needs. Our ap-proach is to utilize heterogeneous sensor data to identify physical motions through acceleration data from a smartphone and to monitor respiratory activity through a BioHarness, while interacting with GIFT simultaneously. We also uti-lize a computational model to better understand the learner and domain. We focus on a precision-required psychomotor task (i.e., golf putting) and create a series of courses in GIFT that instruct how to do putting with tactical breathing. We report our implementation of a physio-cognitive model that can account for the process of psychomotor skill development, the GIFT extension, and a pilot study that uses the extension. The physio-cognitive model is based on the ACT-R/Φ architecture to model and predict the process of learning, and how it can be used for improving the fundamental understanding of the domain and learner model. Our study contributes to the use of cognitive modeling with physiological con-straints to support adaptive training of psychomotor tasks in ITSs

Resilient High Catalytic Performance of Platinum Nanocatalysts with Porous Graphene Envelope.

Despite the innumerable developments of nanosized and well dispersed noble metal catalysts, the degradation of metal nanoparticle catalysts has proven to be a significant obstacle for the commercialization of the hydrogen fuel cell. Here, the formation of Pt nanoparticle catalysts with a porous graphene envelope has been achieved using a single step low temperature vaporization process. While these Pt-Gr core-shell nanoparticles possess superior resilience to degradation, it comes at the cost of degraded overall catalyst efficacy. However, it is possible to combat this lower overall performance through inclusion of low concentrations of nitrogen precursor in the initial stage of single-step synthesis, inhibiting the formation of complete graphene shells, as verified by atomic resolution aberration-corrected transmission electron microscopy (AC-TEM) imaging. The resultant porous graphene encapsulated Pt catalysts are found to have both the high peak performance of the bare Pt nanoparticle catalysts and the increased resilience of the fully shielded Pt-Gr core-shells, with the optimal N-doped Pt-Gr yielding a peak efficiency of 87% compared to bare Pt, and maintaining 90% of its catalytic activity after extended potential cycling. The nitrogen treated Pt-Gr core-shells thus act as an effective substitute catalyst for conventional bare Pt nanoparticles, maintaining their catalytic performance over prolonged use

A Most Unusual Zeolite Templating: Cage to Cage Connection of One Guest Molecule

An unusual case of a diquaternary ammonium dication, with large bulky end groups built from the tropane moiety and connected by a C4 methylene chain, is found to reside in zeolite SSZ-35 (STF). The structure of the guest/host product is such that the tropane bicylic entities reside in the shallow cavities of the cages of the STF structure and the C4 methylene chain runs through the 10-ring (~5.5 Å) window that connects the cages. This is a most unusual (and energy-intensive) templating of a zeolite structure with the guest molecule spanning two unit cells. The unusual result was found by single crystal studies with the addition of the use of the SQUEEZE program to show a consistent fit for the guest molecule following from measured electron densities in the crystal structure work. These analyses were followed with MAS NMR studies to confirm the integrity of the diquaternary guest molecule in the host sieve. A few comparative diquaternary guest molecules in MFI zeolite are also studied

Hydrogenation of Magnesium Nickel Boride for Reversible Hydrogen Storage

We report that a ternary magnesium nickel boride (MgNi_(2.5)B_2) mixed with LiH and MgH_2 can be hydrogenated reversibly forming LiBH_4 and Mg_2NiH_4 at temperatures below 300 °C. The ternary boride was prepared by sintering a mechanically milled mixture of MgB_2 and Ni precursors at 975 °C under inert atmosphere. Hydrogenation of the ternary, milled with LiH and MgH_2, was performed under 100 to 160 bar H_2 at temperatures up to 350 °C. Analysis using X-ray diffraction, Fourier transform infrared, and ^(11)B magic angle spinning NMR confirmed that the ternary boride was hydrogenated forming borohydride anions. The reaction was reversible with hydrogenation kinetics that improved over three cycles. This work suggests that there may be other ternary or higher order boride phases useful for reversible hydrogen storage

Human CD57(+ )germinal center-T cells are the major helpers for GC-B cells and induce class switch recombination

BACKGROUND: The function of CD57(+ )CD4(+ )T cells, constituting a major subset of germinal center T (GC-Th) cells in human lymphoid tissues, has been unclear. There have been contradictory reports regarding the B cell helping function of CD57(+ )GC-Th cells in production of immunoglobulin (Ig). Furthermore, the cytokine and co-stimulation requirement for their helper activity remains largely unknown. To clarify and gain more insight into their function in helping B cells, we systematically investigated the capacity of human tonsil CD57(+ )GC-Th cells in inducing B cell Ig synthesis. RESULTS: We demonstrated that CD57(+ )GC-Th cells are highly efficient in helping B cell production of all four subsets of Ig (IgM, IgG, IgA and IgE) compared to other T-helper cells located in germinal centers or interfollicular areas. CD57(+ )GC-Th cells were particularly more efficient than other T cells in helping GC-B cells but not naïve B cells. CD57(+ )GC-Th cells induced the expression of activation-induced cytosine deaminase (AID) and class switch recombination in developing B cells. IgG1-3 and IgA1 were the major Ig isotypes induced by CD57(+ )GC-Th cells. CD40L, but not IL-4, IL-10 and IFN-γ, was critical in CD57(+ )GC-Th cell-driven B cell production of Ig. However, IL-10, when added exogenously, significantly enhanced the helper activity of CD57(+ )GC-Th cells, while TGF-β1 completely and IFN-γ partially suppressed the CD57(+ )GC-Th cell-driven Ig production. CONCLUSIONS: CD57(+)CD4(+ )T cells in the germinal centers of human lymphoid tissues are the major T helper cell subset for GC-B cells in Ig synthesis. Their helper activity is consistent with their capacity to induce AID and class switch recombination, and can be regulated by CD40L, IL-4, IL-10 and TGF-β