Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost.

An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce protective antibody responses, as well as CD4(+) and CD8(+) T cell responses, that can be effective despite extraordinary diversity of HIV-1. The consensus and mosaic immunogens are complete but artificial proteins, computationally designed to elicit immune responses with improved cross-reactive breadth, to attempt to overcome the challenge of global HIV diversity. In this study, we have compared the immunogenicity of a transmitted-founder (T/F) B clade Env (B.1059), a global group M consensus Env (Con-S), and a global trivalent mosaic Env protein in rhesus macaques. These antigens were delivered using a DNA prime-recombinant NYVAC (rNYVAC) vector and Env protein boost vaccination strategy. While Con-S Env was a single sequence, mosaic immunogens were a set of three Envs optimized to include the most common forms of potential T cell epitopes. Both Con-S and mosaic sequences retained common amino acids encompassed by both antibody and T cell epitopes and were central to globally circulating strains. Mosaics and Con-S Envs expressed as full-length proteins bound well to a number of neutralizing antibodies with discontinuous epitopes. Also, both consensus and mosaic immunogens induced significantly higher gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) responses than B.1059 immunogen. Immunization with these proteins, particularly Con-S, also induced significantly higher neutralizing antibodies to viruses than B.1059 Env, primarily to tier 1 viruses. Both Con-S and mosaics stimulated more potent CD8-T cell responses against heterologous Envs than did B.1059. Both antibody and cellular data from this study strengthen the concept of using in silico-designed centralized immunogens for global HIV-1 vaccine development strategies. IMPORTANCE: There is an increasing appreciation for the importance of vaccine-induced anti-Env antibody responses for preventing HIV-1 acquisition. This nonhuman primate study demonstrates that in silico-designed global HIV-1 immunogens, designed for a human clinical trial, are capable of eliciting not only T lymphocyte responses but also potent anti-Env antibody responses.

Head-to-Head Comparison of Poxvirus NYVAC and ALVAC Vectors Expressing Identical HIV-1 Clade C Immunogens in Prime-Boost Combination with Env Protein in Nonhuman Primates.

UNLABELLED: We compared the HIV-1-specific cellular and humoral immune responses elicited in rhesus macaques immunized with two poxvirus vectors (NYVAC and ALVAC) expressing the same HIV-1 antigens from clade C, Env gp140 as a trimeric cell-released protein and a Gag-Pol-Nef polyprotein as Gag-induced virus-like particles (VLPs) (referred to as NYVAC-C and ALVAC-C). The immunization protocol consisted of two doses of the corresponding poxvirus vector plus two doses of a combination of the poxvirus vector and a purified HIV-1 gp120 protein from clade C. This immunogenicity profile was also compared to that elicited by vaccine regimens consisting of two doses of the ALVAC vector expressing HIV-1 antigens from clades B/E (ALVAC-vCP1521) plus two doses of a combination of ALVAC-vCP1521 and HIV-1 gp120 protein from clades B/E (similar to the RV144 trial regimen) or clade C. The results showed that immunization of macaques with NYVAC-C stimulated at different times more potent HIV-1-specific CD4(+) T-cell responses and induced a trend toward higher-magnitude HIV-1-specific CD8(+) T-cell immune responses than did ALVAC-C. Furthermore, NYVAC-C induced a trend toward higher levels of binding IgG antibodies against clade C HIV-1 gp140, gp120, or murine leukemia virus (MuLV) gp70-scaffolded V1/V2 and toward best cross-clade-binding IgG responses against HIV-1 gp140 from clades A, B, and group M consensus, than did ALVAC-C. Of the linear binding IgG responses, most were directed against the V3 loop in all immunization groups. Additionally, NYVAC-C and ALVAC-C also induced similar levels of HIV-1-neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC) responses. Interestingly, binding IgA antibody levels against HIV-1 gp120 or MuLV gp70-scaffolded V1/V2 were absent or very low in all immunization groups. Overall, these results provide a comprehensive survey of the immunogenicity of NYVAC versus ALVAC expressing HIV-1 antigens in nonhuman primates and indicate that NYVAC may represent an alternative candidate to ALVAC in the development of a future HIV-1 vaccine. IMPORTANCE: The finding of a safe and effective HIV/AIDS vaccine immunogen is one of the main research priorities. Here, we generated two poxvirus-based HIV vaccine candidates (NYVAC and ALVAC vectors) expressing the same clade C HIV-1 antigens in separate vectors, and we analyzed in nonhuman primates their immunogenicity profiles. The results showed that immunization with NYVAC-C induced a trend toward higher HIV-1-specific cellular and humoral immune responses than did ALVAC-C, indicating that this new NYVAC vector could be a novel optimized HIV/AIDS vaccine candidate for human clinical trials.

La retorica delle sarabandes : ricerca retorica nelle prime tre sarabandes delle Sechs Partiten für klavier di J. S. Bach

La presente tesi di ricerca si propone di studiare la danza della sarabanda come capolavoro di musica, retorica e poesia in tre delle Sechs Partiten für klavier di J. S. Bach (BWV 825-830). Lo studio svolto è fondamentalmente di tipo retorico: permette di individuare e interpretare la struttura oratorialepoetica del discorso letterario-musicale nelle tre danze scelte e di imarcarne i suoi aspetti più salienti di ritmica e ornatus. L’approccio permette di osservare, con uno sguardo di comparazione, la presenza di un percorso retorico comune alle tre sarabande, che evolve con gradualità, differenziandole nettamente: ciò riesce a valorizzare a pieno la danza nella sua forza ed efficacia espressiva, che la rende di fatto il movimento di massima commozione di ogni Partita.

Astrological prognostications in MS Beinecke 558: "Sonday prime drye wether"

Tutkimukseni käsittelee 1500-luvun keskivaiheilla kirjoitettua englanninkielistä käsikirjoitusta (New Haven, Yale University, Beinecke Rare Book and ManuscriptLibrary MS 558). Olen työssäni laatinut käsikirjoituksesta kuvauksen, joka sisältääesimerkiksi listan käsikirjoituksen sisältämistä teksteistä sekä käsikirjoituksen pääkirjurin käsialan paleografisen analyysin. Tarkastelemani käsikirjoitus sisältää paljon astronomista ja astrologista materiaalia. Keskityn erityisesti käsikirjoituksen sisältämiin astrologisiin ennustusteksteihin, jotkaolen jakanut kuuteen kategoriaan. Luokitteluni perustuu osittain Laurel Meansin ja Irma Taavitsaisen tutkimuksiin, jotka koskevat keskienglanninkielistä astrologista materiaalia.Työssäni olen soveltanut näitä tutkimuksia uuden ajan alun materiaaliin. Olen myös tarkastellut käsikirjoituskulttuurin ja kirjapainokulttuurin vuorovaikutusta viideneditoimani esimerkkitekstin kautta. Tutkimustulosteni perusteella käsikirjoituskulttuuria ja kirjapainokulttuuria ei tulisi nähdä vastakohtina. Niiden välistä vuorovaikutusta tulisi jatkossa tutkia tarkemmin, sillä näin voitaisiin saada uutta tietoa tekstien levittämisestä ja leviämisestä sekä Englannissa että koko Euroopassa kirjapainotaidon yleistymisen ensimmäisinä vuosisatoina. Tällaisessa tutkimuksessa tulisi käyttää niin määrällisiä kuin laadullisiakin menetelmiä ja ottaa huomioon kirjojen luonne sekä henkisinä ja taiteellisina tuotoksina että fyysisinä esineinä.

Open Access at the Nordic Council of Ministers

Presentation at the Nordic Perspectives on Open Access and Open Science seminar, Helsinki, October 15, 2013

The early facilitatory effect of a peripheral spatially noninformative prime stimulus depends on target stimulus features

We investigated the dependency of the early facilitatory effect of a prime stimulus (S1) on the physical characteristics of the target stimulus (S2). A go-no go reaction time paradigm was used. The S1 was a gray ring and the S2s were a white vertical line, a white horizontal line, a white cross and a white small ring, all inside a white ring with the same dimensions as the S1. S1 onset-S2 onset asynchrony was 100 ms. The stimuli appeared randomly in any one of the quadrants of a monitor screen. The S2 could occur at the same position as the S1 or at a different one. We observed a strong facilitatory effect when the vertical line or the horizontal line was the go stimulus and no effect when the cross was the go stimulus. These results show that the features of the target stimulus can be decisive for the appearance of the facilitatory effect of a peripheral spatially noninformative prime stimulus.

Message from the President of the United States, transmitting copies of the instructions given to the ministers of the United States appointed to negotiate a peace with Great Britain. --

13th Congress, 3d session. House. Doc. no. 8.

Message from the President of the United States, transmitting copies of the instructions given to the ministers of the United States appointed to negotiate a peace with Great Britain

13th Congress, 3d session. House. Doc. no. 8. -------------------------------------------------------------------------------- October 14, 1814. Read and referred to the Committee of Foreign Relations. Printed by Roger C. Weightman