PJ.M. Otero, G. Panagiotou, L. Olsson: Fueling Industrial Biotechnology Growth with Bioethanol.- M. Galbe, G. Zacchi: Pretreatment of Lignocellulosic Materials for Efficient Bioethanol Production.- ...R.P. Chandra, R. Bura, W.E. Mabee, A. Berlin, X. Pan, J.N. Saddler: Substrate Pretreatment: The Key to Effective Enzymatic Hydrolysis of Lignocellulosics?- S.T. Merino, J. Cherry: Progress and Challenges in Enzyme Development of Biomass Utilization.- L. Viikari, M. Alapuranen, T. Puranen, J. Vehmaanper¿M. Siika-aho: Thermostable Enzymes in Lignocellulose Hydrolysis.- B. Hahn-H¿rdal, K. Karhumaa, M. Jeppsson, M.F. Gorwa-Grauslund: Metabolic Engineering for Pentose Utilization in Saccharomyces cerevisiae.- A.J.A. van Maris, A.A. Winkler, M. Kuyper, W.T.A.M. de Laat, J.P. van Dijken, J.T. Pronk: Development of Efficient Xylose Fermentation in Saccharomyces cerevisiae: Xylose Isomerase as a Key Component.- W.H. van Zyl, L.R. Lynd, R.den Haan, J.E. McBride: Consolidated Bioprocessing for Bioethanol Production Using Saccharomyces cerevisiae.- L.R. Jarboe, T.B. Grabar, L.P. Yomano, K.T. Shammugan, L.O. Ingram: Development of Ethanologenic Bacteria.- P.L. Rogers, Y.J. Jeon, K.J. Lee, G.G. Lawford: Zymomonas mobilis for Fuel Ethanol and Higher Value Products.- B.K. Ahring, P. Westermann: Coproduction of Bioethanol with Other Biofuels.- M. Galbe, P. Sassner, A. Wingren, G. Zacchi: Process Engineering Economics of Bioethanol Production.- W.E. Mabee: Policy Options to Support Biofuel Production./P
Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide ...drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein.
We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis.
In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants 41% vs. 0 of 27 0%, P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants 51% vs. 0 of 37 0%), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P=0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P=0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups.
Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074 .).
We report the detection of the cool, Jovian-mass planet MOA-2007-BLG-400Lb. The planet was detected in a high-magnification microlensing event (with peak magnification A max = 628) in which the ...primary lens transited the source, resulting in a dramatic smoothing of the peak of the event. The angular extent of the region of perturbation due to the planet is significantly smaller than the angular size of the source, and as a result the planetary signature is also smoothed out by the finite source size. Thus, the deviation from a single-lens fit is broad and relatively weak (approximately few percent). Nevertheless, we demonstrate that the planetary nature of the deviation can be unambiguously ascertained from the gross features of the residuals, and detailed analysis yields a fairly precise planet/star mass ratio of , in accord with the large significance () of the detection. The planet/star projected separation is subject to a strong close/wide degeneracy, leading to two indistinguishable solutions that differ in separation by a factor of ~8.5. Upper limits on flux from the lens constrain its mass to be M < 0.75 M (assuming that it is a main-sequence star). A Bayesian analysis that includes all available observational constraints indicates a primary in the Galactic bulge with a mass of ~0.2-0.5 M and thus a planet mass of ~0.5-1.3 M Jup. The separation and equilibrium temperature are ~5.3-9.7 AU (~0.6-1.1 AU) and ~34 K (~103 K) for the wide (close) solution. If the primary is a main-sequence star, follow-up observations would enable the detection of its light and so a measurement of its mass and distance.
Carbonaceous chondrites are considered to have originated from C-type asteroids and represent some of the most primitive material in our solar system. Furthermore, since carbonaceous chondrites can ...contain significant quantities of volatile elements, they may have played a crucial role in supplying volatiles and organic material to Earth and other inner solar system bodies. However, a major challenge of unravelling the volatile composition of chondritic meteorites is distinguishing between which features were inherited from the parent body, and what may be a secondary feature attributable to terrestrial weathering. In December 2020, the Hayabusa2 mission of the Japan Aerospace Exploration Agency (JAXA) successfully returned surface material from the C-type asteroid (162173) Ryugu to Earth. This material has now been classified as closely resembling CI-type chondrites, which are the most chemically pristine meteorites. The analysis of material from the surface of Ryugu therefore provides a unique opportunity to analyse the volatile composition of material that originated from a CI-type asteroid without the complications arising from terrestrial contamination. Given their highly volatile nature, the noble gas and nitrogen inventories of chondrites are highly sensitive to different alteration processes on the asteroid parent body, and to terrestrial contamination. Here, we investigate the nitrogen and noble gas signature of two pelletized grains collected from the first and second touchdown sites (Okazaki et al., 2022a), to provide an insight into the formation and alteration history of Ryugu. The concentration of trapped noble gas in the Ryugu samples is greater than the average composition of previously measured CI chondrites and are primarily derived from phase Q, although a significant contribution of presolar nanodiamond Xe-HL is noted. The large noble gas concentrations coupled with a significant contribution of presolar nanodiamonds suggests that the Ryugu samples may represent some of the most primitive unprocessed material from the early solar system. In contrast to the noble gases, the abundance of nitrogen and δ15N composition of the two Ryugu pellets are lower than the average CI chondrite value. We attribute the lower nitrogen abundances and δ15N measured in this study to the preferential loss of a 15N-rich phase from our samples during aqueous alteration on the parent planetesimal. The analyses of other grains returned from Ryugu have shown large variations in nitrogen concentrations and δ15N indicating that alteration fluids heterogeneously interacted with material now present on the surface of Ryugu. Finally, the ratio of trapped noble gases to nitrogen is higher than CI chondrites, and is closer to refractory phase Q and nanodiamonds. This indicates that Ryugu experienced aqueous alteration that led to the significant and variable loss of nitrogen, likely from soluble organic matter, without modification of the noble gas budget, which is primarily hosted in insoluble organic matter and presolar diamonds and is therefore more resistant to aqueous alteration.
Resistance to triazoles was recently reported in Aspergillus fumigatus isolates cultured from patients with invasive aspergillosis. The prevalence of azole resistance in A. fumigatus is unknown. We ...investigated the prevalence and spread of azole resistance using our culture collection that contained A. fumigatus isolates collected between 1994 and 2007.
We investigated the prevalence of itraconazole (ITZ) resistance in 1,912 clinical A. fumigatus isolates collected from 1,219 patients in our University Medical Centre over a 14-y period. The spread of resistance was investigated by analyzing 147 A. fumigatus isolates from 101 patients, from 28 other medical centres in The Netherlands and 317 isolates from six other countries. The isolates were characterized using phenotypic and molecular methods. The electronic patient files were used to determine the underlying conditions of the patients and the presence of invasive aspergillosis. ITZ-resistant isolates were found in 32 of 1,219 patients. All cases were observed after 1999 with an annual prevalence of 1.7% to 6%. The ITZ-resistant isolates also showed elevated minimum inhibitory concentrations of voriconazole, ravuconazole, and posaconazole. A substitution of leucine 98 for histidine in the cyp51A gene, together with two copies of a 34-bp sequence in tandem in the gene promoter (TR/L98H), was found to be the dominant resistance mechanism. Microsatellite analysis indicated that the ITZ-resistant isolates were genetically distinct but clustered. The ITZ-sensitive isolates were not more likely to be responsible for invasive aspergillosis than the ITZ-resistant isolates. ITZ resistance was found in isolates from 13 patients (12.8%) from nine other medical centres in The Netherlands, of which 69% harboured the TR/L98H substitution, and in six isolates originating from four other countries.
Azole resistance has emerged in A. fumigatus and might be more prevalent than currently acknowledged. The presence of a dominant resistance mechanism in clinical isolates suggests that isolates with this mechanism are spreading in our environment.
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