801 research outputs found

    Design of a minimalist autonomous robotic vehicle

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    Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.Includes bibliographical references (leaf 18).The purpose of this thesis is to investigate design alternatives for the creation of a minimalist autonomous robotic vehicle, based on the Ford Escape. The work builds on prior work performed by the MIT DARPA Urban Challenge team, which competed in the national DARPA Urban Challenge NQE and UCE events in October and November 2007. The MIT team pursued an ambitious design that was rich in both sensors and computation. The excessive amount of equipment and computing power throughout the current vehicle make it too expensive and unreasonable to go into actual production. The goal for this work is to revisit the design approach of the MIT team, and from a Mechanical Engineering perspective, to perform a new conceptual design that would bridge the gap between the current vehicle and present in production technologies. By developing a minimalist sensor/processor configuration, the Ford Escape can more closely reflect a present day vehicle, in both appearance and cost, and be more viable for future production. Using the Ford Escape rapid prototype vehicle, the previous installation was stripped out in order to design, re-engineer, and implement a configuration that will allow new research in affordable autonomy and active safety for in-production vehicles.by Mark Spadafora.S.B

    Multi-Omics and Genome Editing Studies on Plant Cell Walls to Improve Biomass Quality

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    Biomass is one of the most important sources of renewable energy and plays an important role in reducing our reliance on fossil fuels. Efficient biomass production is essential to obtain large amounts of sustainable energy with minimal environmental cost. However, the biochemical and molecular processes behind the synthesis of the main components of biomass are still not fully understood. This review provides a comprehensive summary of the most relevant studies on cell wall biosynthesis and degradation mechanisms, focusing on the lignocellulosic component, in which the conversion process to fermentable sugars is expensive, due to its recalcitrant nature. A focus is placed on multi-omics research involving genomics, transcriptomics, proteomics, metabolomics, and phenomics, since multi-omics approaches offer a unique opportunity to investigate the biological pathways underlying the genotype traits characterizing cell wall energy crops. Furthermore, our study highlights the advances in genome editing approaches and proposes the modification of the genes that are involved in the complex cell wall structure as a feasible solution to an efficient biomass production. Several key points for future research activities based on these emerging technologies are also discussed, focusing on the combination of multi-omics and gene editing approaches, which offer potential for improved biomass valorization and the development of tangible bioproducts

    Plasmodium falciparum field isolates use complement receptor 1 (CR1) as a receptor for invasion of erythrocytes

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    AmajorityofPlasmodiumfalciparumstrainsinvadeerythrocytesthroughinteractionswithsialicacid(SA) on glycophorins. However, we recently reported that complement receptor 1 (CR1) is a SA-independent invasionreceptorofmanylaboratorystrainsofP.falciparum.TodeterminetheroleofCR1inerythrocyte invasion among P. falciparum field isolates, we tested eight isolates obtained from children in Kenya. All the parasites examined were capable of invading in a SA-independent manner, and invasion of neuraminidase-treatederythrocyteswasnearlycompletelyblockedbyanti-CR1andsolubleCR1(sCR1). Inaddition,anti-CR1andsCR1partiallyinhibitedinvasionofintacterythrocytesinamajorityofisolates tested. Sequencing of the hypervariable region of P. falciparum AMA-1 showed considerable diversity among all the isolates. These data demonstrate that CR1 mediates SA-independent erythrocyte invasion in P. falciparum field isolates.AmajorityofPlasmodiumfalciparumstrainsinvadeerythrocytesthroughinteractionswithsialicacid(SA) on glycophorins. However, we recently reported that complement receptor 1 (CR1) is a SA-independent invasionreceptorofmanylaboratorystrainsofP.falciparum.TodeterminetheroleofCR1inerythrocyte invasion among P. falciparum field isolates, we tested eight isolates obtained from children in Kenya. All the parasites examined were capable of invading in a SA-independent manner, and invasion of neuraminidase-treatederythrocyteswasnearlycompletelyblockedbyanti-CR1andsolubleCR1(sCR1). Inaddition,anti-CR1andsCR1partiallyinhibitedinvasionofintacterythrocytesinamajorityofisolates tested. Sequencing of the hypervariable region of P. falciparum AMA-1 showed considerable diversity among all the isolates. These data demonstrate that CR1 mediates SA-independent erythrocyte invasion in P. falciparum field isolates

    19-Hydroxy-bufalin, a major bufadienolide isolated from the parotoid gland secretions of the Panamanian endemic toad Rhinella centralis (Bufonidae), inhibits the growth of Trypanosoma cruzi

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    American trypanosomiasis is a parasitic neglected disease, responsible for the death of approximately 10,000 people every year. Amphibians are recognized for producing in their cutaneous glands substances with pharmacological potential against a variety of pathologies. Here we investigated the antiprotozoal activity against Trypanosoma cruzi of bufadienolides isolated from the parotoid glands secretions of the toad Rhinella centralis from Panama. NMR and mass spectrometry analysis led to the identification of the active compound 19-hydroxybufalin, for which its antitrypanosomal activity and occurrence in the genus Rhinella are reported for the first time. This compound showed low cytotoxicity and significant selectivity which confers to it a potential role for the treatment of Chagas diseaseAmerican trypanosomiasis is a parasitic neglected disease, responsible for the death of approximately 10,000 people every year. Amphibians are recognized for producing in their cutaneous glands substances with pharmacological potential against a variety of pathologies. Here we investigated the antiprotozoal activity against Trypanosoma cruzi of bufadienolides isolated from the parotoid glands secretions of the toad Rhinella centralis from Panama. NMR and mass spectrometry analysis led to the identification of the active compound 19-hydroxybufalin, for which its antitrypanosomal activity and occurrence in the genus Rhinella are reported for the first time. This compound showed low cytotoxicity and significant selectivity which confers to it a potential role for the treatment of Chagas diseas

    Effects of β2-receptor stimulation by indacaterol in chronic heart failure treated with selective or non-selective β-blockers: a randomized trial

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    Alveolar \u3b22-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar \u3b22-receptors. We investigated the safety and the effects of indacaterol on lung diffusion, lung mechanics, sleep respiratory behavior, cardiac rhythm, welfare, and exercise performance in HF patients treated with a selective (bisoprolol) or a non-selective (carvedilol) \u3b2-blocker. Study procedures were performed before and after indacaterol and placebo treatments according to a cross-over, randomized, double-blind protocol in forty-four patients (27 on bisoprolol and 17 on carvedilol). No differences between indacaterol and placebo were observed in the whole population except for a significantly higher VE/VCO2 slope and lower maximal PETCO2 during exercise with indacaterol, entirely due to the difference in the bisoprolol group (VE/VCO2 31.8\u2009\ub1\u20095.9 vs. 28.5\u2009\ub1\u20095.6, p\u2009<\u20090.0001 and maximal PETCO2 36.7\u2009\ub1\u20095.5 vs. 37.7\u2009\ub1\u20095.8\u2009mmHg, p\u2009<\u20090.02 with indacaterol and placebo, respectively). In carvedilol, indacaterol was associated with a higher peak heart rate (119\u2009\ub1\u200934 vs. 113\u2009\ub1\u200930 bpm, with indacaterol and placebo) and a lower prevalence of hypopnea during sleep (3.8 [0.0;6.3] vs. 5.8 [2.9;10.5] events/hour, with indacaterol and placebo). Inhaled indacaterol is well tolerated in HF patients, it does not influence lung diffusion, and, in bisoprolol, it increases ventilation response to exercise

    Chemical Constituents of the New Endophytic Fungus Mycosphaerella sp. nov. and Their Anti-Parasitic Activity

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    Chemical investigation of a new endophytic fungus, Mycosphaerella sp. nov. strain F2140 associated with the foliage of the plant Psychotria horizontalis (Rubiaceae) in Panama, resulted in the isolation of cercosporin (1) and a new cercosporin analogue (3) as the major components. The structures of minor compounds in the extract were elucidated by detailed spectroscopic analysis as 2-(2-butyl)-3-hydroxy-6-ethyl-6-methylcyclohex-2-ene-1,5-dione (4), 3-(2-butyl)-6-ethyl-6methyl-5-hydroxy-2-methoxy-cyclohex-2-eneone (5), and an isomer of 5 (6). To study the influence of the hydroxy groups on the anti-parasitic activity of cercosporin, compound 1 was acetylated to obtain derivative 2. The isolated compounds 1–6 were tested in vitro to determine their anti-parasitic activity against the causal agents of malaria ( Plasmodium falciparum ), leishmaniasis ( Leishmania donovani ), and Chagas disease ( Trypanosoma cruzi ). Also, the cytotoxicity and potential anticancer activity of these compounds were evaluated using mammalian Vero cells and MCF7 cancer cell lines, respectively. Compounds 1 and 2 displayed high potency against L. donovani (IC50 0.46 and 0.64 μM), T. cruzi (IC50 1.08 and 0.78 μM), P. falciparum (IC50 1.03 and 2.99 μM), and MCF7 cancer cell lines (IC50 4.68 and 3.56 μM). Compounds 3–6 were not active in these assays at a concentration of 10 μg/mL.Chemical investigation of a new endophytic fungus, Mycosphaerella sp. nov. strain F2140 associated with the foliage of the plant Psychotria horizontalis (Rubiaceae) in Panama, resulted in the isolation of cercosporin (1) and a new cercosporin analogue (3) as the major components. The structures of minor compounds in the extract were elucidated by detailed spectroscopic analysis as 2-(2-butyl)-3-hydroxy-6-ethyl-6-methylcyclohex-2-ene-1,5-dione (4), 3-(2-butyl)-6-ethyl-6methyl-5-hydroxy-2-methoxy-cyclohex-2-eneone (5), and an isomer of 5 (6). To study the influence of the hydroxy groups on the anti-parasitic activity of cercosporin, compound 1 was acetylated to obtain derivative 2. The isolated compounds 1–6 were tested in vitro to determine their anti-parasitic activity against the causal agents of malaria ( Plasmodium falciparum ), leishmaniasis ( Leishmania donovani ), and Chagas disease ( Trypanosoma cruzi ). Also, the cytotoxicity and potential anticancer activity of these compounds were evaluated using mammalian Vero cells and MCF7 cancer cell lines, respectively. Compounds 1 and 2 displayed high potency against L. donovani (IC50 0.46 and 0.64 μM), T. cruzi (IC50 1.08 and 0.78 μM), P. falciparum (IC50 1.03 and 2.99 μM), and MCF7 cancer cell lines (IC50 4.68 and 3.56 μM). Compounds 3–6 were not active in these assays at a concentration of 10 μg/mL

    N-terminal probrain natriuretic peptide is a stronger predictor of cardiovascular mortality than C-reactive protein and albumin excretion rate in elderly patients with type 2 diabetes: the Casale Monferrato population-based study.

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    OBJECTIVE: To study whether N-terminal probrain natriuretic peptide (NT-proBNP) is a short-term independent predictor of both all-cause and cardiovascular (CV) mortality in type 2 diabetic patients and to establish whether albuminuria and C-reactive protein (CRP) affect this relationship. RESEARCH DESIGN AND METHODS: The prospective study included 1,825 type 2 diabetic patients from the population-based cohort of the Casale Monferrato study. CV risk factors, preexisting CVD, and NT-proBNP levels were evaluated at baseline. All-cause and CV mortality were assessed 5.5 years after baseline examination. Multivariate Cox proportional hazards modeling was used to estimate mortality hazard ratios (HRs). RESULTS: During the follow-up period, 390 people died (175 for CVD) out of 9,101 person-years of observations. A significantly increased mortality risk by quartiles of NT-proBNP was observed (test for trend, P < 0.001). NT-proBN P values >91 pg/mL conferred HRs of 2.05 (95% CI 1.47–2.86) for all-cause and 4.47 (2.38–8.39) for CV mortality, independently of CV risk factors, including CRP and albumin excretion rate (AER). The association was also significant for modest rises in NT-proBNP levels and in patients without microalbuminuria and CVD at baseline (upper quartiles HRs 3.82 [95% CI 1.24–13.75]) and 3.14 [1.00–9.94]). Albuminuria and NT-proBNP had an additive effect on mortality, though the association was stronger for NT-proBNP. CONCLUSIONS: NT-proBNP is a strong independent predictor of short-term CV mortality risk in elderly people with type 2 diabetes, including those without preexisting CVD. This association is evident even in people with slightly increased values, is not modified by CRP, and is additive to that provided by AER

    A Calibration of NICMOS Camera 2 for Low Count-Rates

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    NICMOS 2 observations are crucial for constraining distances to most of the existing sample of z > 1 SNe Ia. Unlike the conventional calibration programs, these observations involve long exposure times and low count rates. Reciprocity failure is known to exist in HgCdTe devices and a correction for this effect has already been implemented for high and medium count-rates. However observations at faint count-rates rely on extrapolations. Here instead, we provide a new zeropoint calibration directly applicable to faint sources. This is obtained via inter-calibration of NIC2 F110W/F160W with WFC3 in the low count-rate regime using z ~ 1 elliptical galaxies as tertiary calibrators. These objects have relatively simple near-IR SEDs, uniform colors, and their extended nature gives superior signal-to-noise at the same count rate than would stars. The use of extended objects also allows greater tolerances on PSF profiles. We find ST magnitude zeropoints (after the installation of the NICMOS cooling system, NCS) of 25.296 +- 0.022 for F110W and 25.803 +- 0.023 for F160W, both in agreement with the calibration extrapolated from count-rates 1,000 times larger (25.262 and 25.799). Before the installation of the NCS, we find 24.843 +- 0.025 for F110W and 25.498 +- 0.021 for F160W, also in agreement with the high-count-rate calibration (24.815 and 25.470). We also check the standard bandpasses of WFC3 and NICMOS 2 using a range of stars and galaxies at different colors and find mild tension for WFC3, limiting the accuracy of the zeropoints. To avoid human bias, our cross-calibration was "blinded" in that the fitted zeropoint differences were hidden until the analysis was finalized.Comment: Accepted for Publication in the Astronomical Journal. New version contains added referenc

    Multi-omics approaches to study molecular mechanisms in Cannabis sativa

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    Cannabis (Cannabis sativa L.), also known as hemp, is one of the oldest cultivated crops, grown for both its use in textile and cordage production, and its unique chemical properties. However, due to the legislation regulating cannabis cultivation, it is not a well characterized crop, especially regarding molecular and genetic pathways. Only recently have regulations begun to ease enough to allow more widespread cannabis research, which, coupled with the availability of cannabis genome sequences, is fuelling the interest of the scientific community. In this review, we provide a summary of cannabis molecular resources focusing on the most recent and relevant genomics, transcriptomics and metabolomics approaches and investigations. Multi-omics methods are discussed, with this combined approach being a powerful tool to identify correlations between biological processes and metabolic pathways across diverse omics layers, and to better elucidate the relationships between cannabis sub-species. The correlations between genotypes and phenotypes, as well as novel metabolites with therapeutic potential are also explored in the context of cannabis breeding programs. However, further studies are needed to fully elucidate the complex metabolomic matrix of this crop. For this reason, some key points for future research activities are discussed, relying on multi-omics approaches
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