2,469 research outputs found
Femtosecond laser nanostructuring of transparent materials: from bulk to fiber lasers
Progress in high power ultra-short pulse lasers has opened new frontiers in the physics of light-matter interactions and laser material processing. Recently there has been considerable interest in the application of femtosecond lasers to writing inside transparent materials and in particular to fabrication of three-dimensional microstructures
Nonlinear resonance interaction of ultrasonic waves under applied stress
Copyright 1984 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Journal of Applied Physics, 56(1), 235-237, 1984 and may be found at http://dx.doi.org/10.1063/1.33375
Embolism development observed with a compact MRI in Japanese black pine clones resistant to pine wilt disease
HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection.
Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV) infection and viral evasion by utilizing human CD4+ T cell cultures in vitro and a simian immunodeficiency virus (SIV) model of AIDS in vivo Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa. Suppression of protein synthesis and induction of protein kinase GCN2-ATF4 signaling were detected in the gut during acute SIV infection. These changes diminished during chronic viral infection. HIV replication induced by serum deprivation in CD4+ T cells was linked to the induction of ATF4 that was recruited to the HIV long terminal repeat (LTR) to promote viral transcription. Experimental inhibition of GCN2-ATF4 signaling either by a specific inhibitor or by amino acid supplementation suppressed the induction of HIV expression. Enhancing ATF4 expression through selenium administration resulted in reactivation of latent HIV in vitro as well as ex vivo in the primary CD4+ T cells isolated from patients receiving suppressive antiretroviral therapy (ART). In summary, HIV/SIV exploits the early host antiviral response through GCN2-ATF4 signaling by utilizing ATF4 for activating the viral LTR transcription to establish initial viral replication and is a potential target for HIV prevention and therapy.IMPORTANCE Understanding how HIV overcomes host antiviral innate defense response in order to establish infection and dissemination is critical for developing prevention and treatment strategies. Most investigations focused on the viral pathogenic mechanisms leading to immune dysfunction following robust viral infection and dissemination. Less is known about mechanisms that enable HIV to establish its presence despite rapid onset of host antiviral innate response. Our novel findings provide insights into the viral strategy that hijacks the host innate response of the suppression of protein biosynthesis to restrict the virus production. The virus leverages transcription factor ATF4 expression during the GCN2-ATF4 signaling response and utilizes it to activate viral transcription through the LTR to support viral transcription and production in both HIV and SIV infections. This unique viral strategy is exploiting the innate response and is distinct from the mechanisms of immune dysfunction after the critical mass of viral loads is generated
Designing movement into automotive seating - does it improve comfort?
Comfort is important for a good driving experience and automotive seat technology is an important enabler of this. Movement through frequent changes in posture is beneficial for reducing fixed postures. This paper reports on a laboratory study to investigate a novel automotive seat movement concept aiming to delay the onset of driving-related musculoskeletal fatigue and improve feelings of comfort and wellbeing, making the driver feel refreshed and ultimately improving driver performance. The research involved comparison of three seat conditions while driving - no seat movement, fore-aft movement, cushion and backrest angle movement. The movement was designed to be at a fixed speed, slow, smooth and only slightly perceptible
while driving. A sample of 10 participants was recruited to take part in a 60 minute drive for each condition-single blind, repeated measures, balanced order and sessions at a similar time of day. Discomfort and wellbeing questionnaires, driver Seat Fidgets and Movements (SFMs), posture capture and a de-brief were used as data collection methods. Results indicate that the two seat movement concepts were positively received. Statistically significant differences were found at minute 60 for buttock area discomfort, with less reported discomfort for the two movement conditions. As expected, overall discomfort ratings and SFMs frequency increased with time spent driving for all trials. Posture scores verified that driver posture was within comfortable ranges and as expected fairly static while driving
Discovery of coesite and stishovite in HED meteorite
第3回極域科学シンポジウム/第35回南極隕石シンポジウム 11月29日(木) 国立国語研究所 2階講
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PPARα-targeted mitochondrial bioenergetics mediate repair of intestinal barriers at the host-microbe intersection during SIV infection.
Chronic gut inflammatory diseases are associated with disruption of intestinal epithelial barriers and impaired mucosal immunity. HIV-1 (HIV) causes depletion of mucosal CD4+ T cells early in infection and disruption of gut epithelium, resulting in chronic inflammation and immunodeficiency. Although antiretroviral therapy (ART) is effective in suppressing viral replication, it is incapable of restoring the "leaky gut," which poses an impediment for HIV cure efforts. Strategies are needed for rapid repair of the epithelium to protect intestinal microenvironments and immunity in inflamed gut. Using an in vivo nonhuman primate intestinal loop model of HIV/AIDS, we identified the pathogenic mechanism underlying sustained disruption of gut epithelium and explored rapid repair of gut epithelium at the intersection of microbial metabolism. Molecular, immunological, and metabolomic analyses revealed marked loss of peroxisomal proliferator-activated receptor-α (PPARα) signaling, predominant impairment of mitochondrial function, and epithelial disruption both in vivo and in vitro. To elucidate pathways regulating intestinal epithelial integrity, we introduced probiotic Lactobacillus plantarum into Simian immunodeficiency virus (SIV)-inflamed intestinal lumen. Rapid recovery of the epithelium occurred within 5 h of L. plantarum administration, independent of mucosal CD4+ T cell recovery, and in the absence of ART. This intestinal barrier repair was driven by L. plantarum-induced PPARα activation and restoration of mitochondrial structure and fatty acid β-oxidation. Our data highlight the critical role of PPARα at the intersection between microbial metabolism and epithelial repair in virally inflamed gut and as a potential mitochondrial target for restoring gut barriers in other infectious or gut inflammatory diseases
Immune Modulation through 4-1BB Enhances SIV Vaccine Protection in Non-Human Primates against SIVmac251 Challenge
Costimulatory molecules play a central role in the development of cellular immunity. Understanding how costimulatory pathways can be directed to positively influence the immune response may be critical for the generation of an effective HIV vaccine. Here, we evaluated the ability of intravenous administration of a blocking monoclonal antibody (mAb) directed against the negative costimulatory molecule CTLA-4, and an agonist mAb directed against the positive costimulatory molecule 4-1BB, either alone or in combination, to augment intramuscular SIV DNA immunizations. We then tested the ability these of these responses to impact a high-dose SIVmac251 challenge. Following immunization, the groups infused with the anti-4-1BB mAb exhibited enhanced IFN-γ responses compared to the DNA vaccine only group. Interestingly, although CTLA-4 blockade alone did not enhance IFN-γ responses it did increase the proliferative capacity of the CD4+ and CD8+ T cells. The combination of both mAbs enhanced the magnitude of the polyfunctional CD8+ T cell response. Following challenge, the group that received both mAbs exhibited a significant, ∼2.0 log, decrease in plasma viral load compared to the naïve group the included complete suppression of viral load in some animals. Furthermore, the use of the CTLA-4 blocking antibody resulted in significantly higher viral loads during chronic infection compared to animals that received the 4-1BB mAb, likely due to the higher CD4+ T cell proliferative responses which were driven by this adjuvant following immunization. These novel studies show that these adjuvants induce differential modulation of immune responses, which have dramatically different consequences for control of SIV replication, suggesting important implications for HIV vaccine development
O PATRIMÔNIO ARQUITETÔNICO E URBANÍSTICO DE PRESIDENTE PRUDENTE: O POSSÍVEL PRESERVADO
O trabalho trata do processo de preservação do patrimônio arquitetônico e Urbanístico de Presidente Prudente, SP. Faz um resgate das atuações das instuições civis públicas e da participação dos autores no esforço para salvaguarda dos registros materiais históricos e culturais de Presidente Prudente. Subsidiado na pouca documentação existente, na memória oral e no relato de vivências, mesmo com lacunas e dúvidas, acumula informações para contribuir no debate dessa temática. A cidade apresenta um histórico de descaso em relação ao seu patrimônio cultural, especialmente o seu patrimônio material edificado. Os atores políticos e as instituições questionam o valor histórico e cultural de seu patrimônio histórico. A história da cidade é esquecida numa atitude de negar o passado em nome de um falso “progresso” ficando sujeita ao interesse do capital imobiliário. A atuação das instituições de preservação do patrimônio cultural é intermitente, dependem dos interesses relacionados aos poder político local. Apenas três bens patrimoniais são tombados, o Museu e Arquivo Histórico, o Centro Cultural Matarazzo e o Bebedouro de Animais. Essa investigação verifica possíveis diretrizes de políticas públicas que busquem encaminhamentos de ações para garantir a salvaguarda e a preservação dos diversos momentos da paisagem cultural da cidade. Palavras-chave: patrimônio cultural, Presidente Prudente, salvaguarda, políticas de preservação. Abstract This paper discusses the process of preserving the architectural heritage and Townscape of Presidente Prudente, SP. It recounts the actions of public civil institutions and the participation of the authors in the effort to safeguard the records of historical and cultural materials from Presidente Prudente. Subsidized in little existent documentation, in oral memory and in reporting of experiences, even with gaps and questions, collects information to contribute to the discussion of this theme. The city has a history of neglect in relation to its cultural heritage, particularly its material heritage buildings. Political actors and institutions question the value of their historical and cultural heritage. The city's history is forgotten in an attitude of denying the past in the name of a false "progress" being subject to the interest of real estate capital. The performance of the institutions of cultural heritage preservation is intermittent, depend on the interests related to local political power. Only three capital assets are tumbled, the Museum and Historical Archive, Cultural Centre Matarazzo and Animal Trough. This research finds possible guidelines for public policies that seek referrals of actions to ensure the safeguarding and preservation of the various moments of the cultural landscape of the city. Keywords: cultural heritage, Presidente Prudente, safeguarding, preservation policies
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