34 research outputs found
In-Space Propulsion Technology Products Ready for Infusion on NASA's Future Science Missions
Since 2001, the In-Space Propulsion Technology (ISPT) program has been developing and delivering in-space propulsion technologies that will enable or enhance NASA robotic science missions. These in-space propulsion technologies are applicable, and potentially enabling, for future NASA flagship and sample return missions currently being considered. They have a broad applicability to future competed mission solicitations. The high-temperature Advanced Material Bipropellant Rocket (AMBR) engine, providing higher performance for lower cost, was completed in 2009. Two other ISPT technologies are nearing completion of their technology development phase: 1) NASA s Evolutionary Xenon Thruster (NEXT) ion propulsion system, a 0.6-7 kW throttle-able gridded ion system; and 2) Aerocapture technology development with investments in a family of thermal protection system (TPS) materials and structures; guidance, navigation, and control (GN&C) models of blunt-body rigid aeroshells; aerothermal effect models; and atmospheric models for Earth, Titan, Mars and Venus. This paper provides status of the technology development, applicability, and availability of in-space propulsion technologies that have recently completed their technology development and will be ready for infusion into NASA s Discovery, New Frontiers, SMD Flagship, or technology demonstration missions
Carbon nanotubes applied in neuroscience: prospects and challenges
INTRODUÇÃO: Os nanotubos de carbono (NTCs) são os nanomateriais mais promissores para aplicação terapêutica em doenças neurodegenerativas. Aplicações potenciais incluem sistemas de liberação controlada de fármacos, interfaces elétricas e substratos para crescimento celular. OBJETIVO: Descrever o estado da arte e as perspectivas e desafios da aplicação dos NTCs nas neurociências. MÉTODO: Procedeu-se a uma busca sistemática nos indexadores Medline, Lilacs e SciELO, utilizando os descritores "carbon nanotubes", "drug delivery", "electrical interface", "tissue regeneration", "neuroscience", "biocompatibility" e "nanotechnology", devidamente agrupados. RESULTADOS: A revisão da literatura evidenciou controvérsias nos estudos relativos à biocompatibilidade dos NTCs, embora tenha ratificado o seu potencial para a neuromedicina e neurociências. CONCLUSÃO: Os dados obtidos apontam a necessidade de estudos padronizados sobre as aplicações e interações dessas nanoestruturas com os sistemas biológicos.BACKGROUND: Carbon nanotubes (CNTs) are the most promising nanomaterials for therapeutic application in neurodegenerative diseases. Potential applications include systems for controlled drug delivery, electrical interfaces and substrates for cell growth. OBJECTIVE: To describe the state of art, prospects and challenges of applying CNTs in neuroscience. METHODS: There has been systematic search in Medline, Lilacs and SciELO, using the keywords "carbon nanotubes", "drug delivery", "electrical interface", "tissue regeneration", "neuroscience", "nanotechnology" and "biocompatibility", properly grouped. RESULTS: The literature review showed controversies in studies on the biocompatibility of CNTs, although it has ratified its potential for neuromedicine and neuroscience. DISCUSSION: These results highlight the need for modeling studies on the applications and interactions of nanostructures with biological systems
Nanotubos de carbono aplicados às neurociências: perspectivas e desafios
BACKGROUND: Carbon nanotubes (CNTs) are the most promising nanomaterials for therapeutic application in neurodegenerative diseases. Potential applications include systems for controlled drug delivery, electrical interfaces and substrates for cell growth. OBJECTIVE: To describe the state of art, prospects and challenges of applying CNTs in neuroscience. METHODS: There has been systematic search in Medline, Lilacs and SciELO, using the keywords "carbon nanotubes", "drug delivery", "electrical interface", "tissue regeneration", "neuroscience", "nanotechnology" and "biocompatibility", properly grouped. RESULTS: The literature review showed controversies in studies on the biocompatibility of CNTs, although it has ratified its potential for neuromedicine and neuroscience. DISCUSSION: These results highlight the need for modeling studies on the applications and interactions of nanostructures with biological systems.INTRODUÇÃO: Os nanotubos de carbono (NTCs) são os nanomateriais mais promissores para aplicação terapêutica em doenças neurodegenerativas. Aplicações potenciais incluem sistemas de liberação controlada de fármacos, interfaces elétricas e substratos para crescimento celular. OBJETIVO: Descrever o estado da arte e as perspectivas e desafios da aplicação dos NTCs nas neurociências. MÉTODO: Procedeu-se a uma busca sistemática nos indexadores Medline, Lilacs e SciELO, utilizando os descritores "carbon nanotubes", "drug delivery", "electrical interface", "tissue regeneration", "neuroscience", "biocompatibility" e "nanotechnology", devidamente agrupados. RESULTADOS: A revisão da literatura evidenciou controvérsias nos estudos relativos à biocompatibilidade dos NTCs, embora tenha ratificado o seu potencial para a neuromedicina e neurociências. CONCLUSÃO: Os dados obtidos apontam a necessidade de estudos padronizados sobre as aplicações e interações dessas nanoestruturas com os sistemas biológicos
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Efeitos de diferentes sistemas de maturação in vitro no potencial de desenvolvimento de oócitos bovinos
In vitro maturation is an important step for in vitro embryo production. The objective of the present study was to investigate the effect of the interaction of serum and oxygen tension during in vitro maturation on nuclear maturation, viability of cumulus cells, oocyte transcript amount, preimplantation development and blastocyst apoptosis. Four experimental groups were designed: G1 (10% estrus cow serum [ECS] with 20% O2); G2 (0.1% polyvinyl alcohol [PVA] with 20% O2), G3 (10% ECS with 5% O2) e G4 (0.1% PVA with 5% O2). Proportion of metaphase II oocytes, viability of cumulus cells, blastocyst rates and the total cell number were not affected (P>0.05) when the ECS was replaced by PVA under 5% O2, whereas higher (P0.05) were found in nuclear maturation, viability of cumulus cells and blastocyst rate. Differences (P0,05) quando o soro foi substituÃdo por PVA em 5% de O2, enquanto a taxa de blastocistos e número total de células foi maior (P0,05) na taxa de maturação, viabilidade das células do cumulus e de blastocistos. Foram encontradas diferenças (P<0,05) na quantidade de transcritos especÃficos em oócitos maturados sobre as diferentes condições. Conclui-se que a presença de soro durante a maturação é importante para o desenvolvimento embrionário em tensão de 20% de O2, e a suplementação com PVA em 5% de O2 fornece o melhor ambiente de maturação para os oócitos, resultando em blastocistos com baixo Ãndice apoptótico.CAPES - Coordenação de Aperfeiçoamento de Pessoal de NÃvel Superio
Avaliação da toxicidade de nanomateriais em diferentes modelos biológicos e aplicações na transfecção gênica
Multi-walled carbon nanotubes (MWCNTs) and cotton cellulose nanofibers (CNFs) are
interesting nanomaterials (NMs) which possess great potential for applications in various
fields such as in water treatment, reinforcement materials, tissue engineering and therapeutic
molecule delivery. In particular, MWCNT have emerged as a new method for gene delivery
and they can be an alternative for cell and embryos transfection. However, while engineered
NMs provide great benefits, we know very little about the potential effects on human health
and the environment. Thus, the objectives of this study were to evaluate the potential toxicity
of MWCNT and CNF in various biological model organisms (bovine fibroblast and embryo,
and green microalgaes) and whether MWCNT is able to deliver exogenous DNA molecules
into bovine fibroblast and embryos. In experiment 1, we evaluated in vitro the effects of NMs
on bovine fibroblast viability and morphology. The results showed that low concentrations of
CNF (0.02-100μg ml-1) did not cause viability loss (P>0.05) or change in cell morphology.
However, at concentrations above 200μg ml-1, NFC significantly decreased cell viability
(P<0.05) and changes in cell shape. Fibroblasts exposed at concentrations above 100μg ml-1
MWCNT-COOH exhibited a reduced cell viability (P<0.05) and their cell morphology was
altered. In experiment 2, we examined gene expression, apoptosis response and
developmental rates of in vitro produced bovine embryos that were exposed to NMs. There
was no difference (P > 0.05) in the hatching, degeneration and apoptosis rate among the
control, MWCNT-COOH or cotton CNF- exposed embryos. In contrast, in embryos exposed
at 0.2 μg ml-1 MWCNT-COOH showed relatively higher levels (P<0.05) of the genes
associated with totipotency, differentiation and response to stress. In experiment 3, we
analyzed the cytotoxic response of C. vulgaris and K. flaccidum cells (green microalgae) to
NMs by investigating the zeta potential, trypan blue exclusion assay, photosynthetic activity,
superoxide dismutase activity, quantification of ATP levels and microscopic investigations.
NMs decreased viability, photosynthetic activity and ATP levels of microalgaes cells,
depending on concentration and time. Addition of NMs further induced an increase of
superoxide dismutase activity and ultrastructural damage cell. In experiment 4, we have used
plasmid DNA of green fluorescent protein (pGFP) in combination with MWCNT-COOH to
transfect bovine fibroblast and embryos. Detection of GFP accumulation by fluorescence
microscopy examination revealed that this gene was expressed in the fibroblast and the
embryo (2 to 8-cell stage). However, the expression GFP was not observed in blastocyst
stage. The PCR result confirmed the presence of the pGFP gene in the transfected cells
(3.30% GFP+) and embryos of 2-8–cell stage (46.67% GFP+). In conclusion, under the
conditions tested, the exposures to MWCNTs or CNFs in low concentrations are not toxic to
bovine fibroblast cells. However, these NMs have toxic effects in green microalgaes.
Especially, this work showed that MWCNT-COOH-transfection of embryo could be a simple
and suitable method to introduce foreign genes in embryos and perhaps could be also useful to
generate transgenic animals.Os nanotubos de carbono multicamadas (MWCNT) e as nanofibras de celulose (NFCs) são
interessantes nanomateriais (NMs) que possuem grande potencial de aplicação em áreas como
tratamento de água, reforço de materiais, engenharia tecidual e entrega de moléculas
terapêuticas. Em especial, os MWCNT são promissores vetores de DNA em células e
embriões de mamÃferos. Porém, o desenvolvimento desta área está relacionado à padronização
de sistemas para avaliar o potencial impacto dos NMs na saúde humana e ambiental. O
objetivo geral deste estudo foi avaliar a toxicidade de MWCNT e NFC em diferentes modelos
biológicos (fibroblastos e embriões bovinos; microalgas) e o potencial de carreamento gênico
de MWCNT-COOH em fibroblastos e embriões bovinos. No experimento 1, foi avaliada a
viabilidade e a morfologia dos fibroblastos cultivados in vitro expostos às NFCs e aos
MWCNT-COOHs. Os resultados deste experimento revelaram que em baixas concentrações
(0,02-100μg ml-1) as NFC não foram citotóxicas (P = 0,06). Porém, concentrações acima de
200 μg ml-1 NFC diminuÃram a viabilidade celular e causaram mudanças na morfologia das
células. Para os MWCNT-COOH, a exposição dos fibroblastos a 100μg ml-1 reduziram a
viabilidade (P= 0,001) e alteram a morfologia celular. No experimento 2, foram analisados os
efeitos desses NMs no desenvolvimento, expressão gênica e apoptose in situ de embriões
bovinos produzidos in vitro. Neste ensaio, os NMs não influenciaram o desenvolvimento
(P=0,24) e o Ãndice de apoptose embrionária (P=0,82). Contudo, os MWCNT-COOH
alteraram a expressão de genes (P=0,02) relacionados à totipotência, diferenciação e estresse
celular de forma mais acentuada quando comparada às NFCs. No experimento 3, o potencial
ecotóxico das NFCs e dos MWCNTs foi estudado em microalgas Chlorella vulgaris e
Klebsormidium flaccidum mediante análise de Potencial Zeta, viabilidade celular, atividade
fotossintética e de enzimas antioxidativas, quantificação dos nÃveis de ATP e microscopia
eletrônica. Os resultados revelaram que os MWCNTs e as NFCs afetaram a viabilidade
(P<0,001), a fotossÃntese (P<0,05), a atividade de enzimas antioxidativas (P<0,05), os nÃveis
de ATP (P<0,05) e a morfologia celular das microalgas em concentrações, tempos e sistemas
de cultura especÃficos. No experimento 4, os fibroblastos e embriões bovinos foram
transfectados com MWCNT-COOH complexados ao plasmÃdeo contendo o gene que codifica
a proteÃna verde fluorescente (pGFP). As análises de microscopia de fluorescência detectaram
que o gene GFP foi expresso nas células e nos embriões no estágio inicial de desenvolvimento
(2 a 8 células). Entretanto, a expressão de GFP não foi observada no estágio de blastocisto. A
análise por PCR confirmou a presença do gene GFP nos fibroblastos (3,30% GFP+) e
embriões de 2-8–células (46,67% GFP+). Em conclusão, nas condições testadas, a exposição
de fibroblastos a baixas concentrações de MWCNT-COOH ou NFC não causaram impacto na
viabilidade e morfologia celular. Entretanto, os MWCNTs e as NFCs foram citotóxicas para
as microalgas estudadas. O uso de MWCNT-COOH como vetor de DNA em embriões
bovinos mostrou-se promissora, o que abre possibilidades de geração de animais transgênicos
por este método.CAPES - Coordenação de Aperfeiçoamento de Pessoal de NÃvel Superio