•Carbohydrate binding modules (CBMs) disrupt insoluble polysaccharide structures.•CBMs enhance cellulase-promoted lignocellulosic biomass hydrolysis.•CBM addition promotes generation of additional ...insoluble reducing ends.•Bovine serum albumin (BSA) causes an increase in soluble reducing ends.•Binding of CBMs to cellulose is irreversible and leads to its amorphisation.
Plant biomass is a low-cost and abundant source of carbohydrates for production of fuels, “green” chemicals and materials. Currently, biochemical conversion of the biomass into sugars via enzymatic hydrolysis is the most viable technology. Here, the role of carbohydrate binding modules (CBMs) in the disruption of insoluble polysaccharide structures and their capacity to enhance cellulase-promoted lignocellulosic biomass hydrolysis was investigated. We show that CBM addition promotes generation of additional reducing ends in the insoluble substrate by cellulases. On the contrary, bovine serum albumin (BSA), widely used in prevention of a non-specific protein binding, causes an increase in soluble reducing-end production, when applied jointly with cellulases. We demonstrate that binding of CBMs to cellulose is non-homogeneous, irreversible and leads to its amorphisation. Our results also reveal effects of CBM-promoted amorphogenesis on cellulose hydrolysis by cellulases.
Constraining the thermal and compositional state of the mantle is crucial for deciphering the formation and evolution of Mars. Mineral physics predicts that Mars’ deep mantle is demarcated by a ...seismic discontinuity arising from the pressure-induced phase transformation of the mineral olivine to its higher-pressure polymorphs, making the depth of this boundary sensitive to both mantle temperature and composition. Here, we report on the seismic detection of a midmantle discontinuity using the data collected by NASA’s InSight Mission to Mars that matches the expected depth and sharpness of the postolivine transition. In five teleseismic events, we observed triplicated P and S waves and constrained the depth of this discontinuity to be 1,006
±
40 km by modeling the triplicated waveforms. From this depth range, we infer a mantle potential temperature of 1,605
±
100 K, a result consistent with a crust that is 10 to 15 times more enriched in heat-producing elements than the underlying mantle. Our waveform fits to the data indicate a broad gradient across the boundary, implying that the Martian mantle is more enriched in iron compared to Earth. Through modeling of thermochemical evolution of Mars, we observe that only two out of the five proposed composition models are compatible with the observed boundary depth. Our geodynamic simulations suggest that the Martian mantle was relatively cold 4.5 Gyr ago (1,720 to 1,860 K) and are consistent with a present-day surface heat flow of 21 to 24 mW/m
2
.
Abstract Musculoskeletal models are increasingly used to estimate medial and lateral knee contact forces, which are difficult to measure in vivo. The sensitivity of contact force predictions to ...modeling parameters is important to the interpretation and implication of results generated by the model. The purpose of this study was to quantify the sensitivity of knee contact force predictions to simultaneous errors in frontal plane knee alignment and contact locations under different dynamic conditions. We scaled a generic musculoskeletal model for N=23 subjects’ stature and radiographic knee alignment, then perturbed frontal plane alignment and mediolateral contact locations within experimentally-possible ranges of 10 to -10 degrees and 10 to -10 mm, respectively. The sensitivity of first peak, second peak, and mean medial and lateral knee contact forces to knee adduction angle and contact locations was modeled using linear regression. Medial loads increased, and lateral loads decreased, by between 3 and 6 percent bodyweight for each degree of varus perturbation. Shifting the medial contact point medially increased medial loads and decreased lateral loads by between 1 and 4 percent bodyweight per millimeter. This study demonstrates that realistic measurement errors of 5 mm (contact distance) or 5 degrees (frontal plane alignment) could result in a combined 50% BW error in subject specific contact force estimates. We also show that model sensitivity varies between subjects as a result of differences in gait dynamics. These results demonstrate that predicted knee joint contact forces should be considered as a range of possible values determined by model uncertainty.
We report improved measurements of elemental abundances and spectra for galactic cosmic-ray (GCR) nuclei obtained by the Cosmic Ray Isotope Spectrometer on board NASA's Advanced Composition Explorer ...(ACE) spacecraft during the minimum and maximum phases of solar cycle 23. We discuss results for particles with nuclear charge 5 <= Z <= 28 and typical energies between 50 and 500 MeV nucleon-1. We demonstrate that a detailed 'leaky box' Galactic propagation model combined with a spherically symmetric solar modulation model gives a good (but not perfect) fit to the observed spectra by using a solar modulation parameter of = 325 MV at solar minimum and = 900 MV at solar maximum. Although our results are generally consistent with previous measurements from space-based and balloon-based missions, there are significant differences. The large geometrical acceptance and excellent charge resolution of the instrument result in the most detailed and statistically significant record of GCR composition to date in this energy range. The measurements reported here serve as a high-precision baseline for continued studies of GCR composition, solar modulation over the solar cycle, space radiation hazards, and other applications.
Peak knee joint contact forces ("loads") in running are much higher than they are in walking, where the peak load has been associated with the initiation and progression of knee osteoarthritis. ...However, runners do not have an especially high risk of osteoarthritis compared with nonrunners. This paradox suggests that running somehow blunts the effect of very high peak joint contact forces, perhaps to provide a load per unit distance (PUD) traveled that is relatively low.
This study aimed to compare peak and PUD knee joint loads between human walking and running.
Fourteen healthy adults walked and ran at self-selected speeds. Ground reaction force and motion capture data were measured and combined with inverse dynamics and musculoskeletal modeling to estimate the peak knee joint loads, PUD knee joint loads, and the impulse of the knee joint contact force for each gait with a matched-pair (within-subject) design.
The peak load was three times higher in running (8.02 vs 2.72 body weight, P < 0.001), but the PUD load did not differ between running and walking (0.80 vs 0.75 body weight per meter, P = 0.098). The impulse of the joint contact force was greater for running than for walking (1.30 vs 1.04 body weight per second, P < 0.001). The peak load increased with increasing running speed, whereas the PUD load decreased with increasing speed.
Compared with walking, the relatively short duration of ground contact and relatively long length of strides in running seem to blunt the effect of high peak joint loads, such that the PUD loads are no higher than that in walking. Waveform features other than or in addition to the peak value should be considered when studying joint loading and injuries.
Advancement of in silico tools would be enabled by the availability of data for metabolic reaction rates and intrinsic clearance (CLint) of a diverse compound structure data set by specific metabolic ...enzymes. Our goal is to measure CLint for a large set of compounds with each major human cytochrome P450 (P450) isozyme. To achieve our goal, it is of utmost importance to develop an automated, robust, sensitive, high-throughput metabolic stability assay that can efficiently handle a large volume of compound sets. The substrate depletion method in vitro half-life (t1/2) method was chosen to determine CLint The assay (384-well format) consisted of three parts: 1) a robotic system for incubation and sample cleanup; 2) two different integrated, ultraperformance liquid chromatography/mass spectrometry (UPLC/MS) platforms to determine the percent remaining of parent compound, and 3) an automated data analysis system. The CYP3A4 assay was evaluated using two long t1/2 compounds, carbamazepine and antipyrine (t1/2 > 30 minutes); one moderate t1/2 compound, ketoconazole (10 < t1/2 < 30 minutes); and two short t1/2 compounds, loperamide and buspirone (t½ < 10 minutes). Interday and intraday precision and accuracy of the assay were within acceptable range (∼12%) for the linear range observed. Using this assay, CYP3A4 CLint and t1/2 values for more than 3000 compounds were measured. This high-throughput, automated, and robust assay allows for rapid metabolic stability screening of large compound sets and enables advanced computational modeling for individual human P450 isozymes.
Summary
This review examined evidence of the association between maternal pre‐pregnancy overweight/obesity status and child neurodevelopmental outcomes. PubMed and PsycINFO databases were ...systematically searched for empirical studies published before April 2017 using keywords related to prenatal obesity and children's neurodevelopment. Of 1483 identified papers, 41 were included in the systematic review, and 32 articles representing 36 cohorts were included in the meta‐analysis. Findings indicated that compared with children of normal weight mothers, children whose mothers were overweight or obese prior to pregnancy were at increased risk for compromised neurodevelopmental outcomes (overweight: OR = 1.17, 95% CI 1.11, 1.24, I2 = 65.51; obese: OR = 1.51; 95% CI 1.35, 1.69, I2 = 79.63). Pre‐pregnancy obesity increased the risk of attention deficit–hyperactivity disorder (OR = 1.62; 95% CI 1.23, 2.14, I2 = 70.15), autism spectrum disorder (OR = 1.36; 95% CI 1.08, 1.70, I2 = 60.52), developmental delay (OR = 1.58; 95% CI 1.39, 1.79, I2 = 75.77) and emotional/behavioural problems (OR = 1.42; 95% CI 1.26, 1.59, I2 = 87.74). Given the current obesity prevalence among young adults and women of childbearing age, this association between maternal obesity during pregnancy and atypical child neurodevelopment represents a potentially high public health burden.
Uncertainty in pre-industrial natural aerosol emissions is a major component of the overall uncertainty in the radiative forcing of climate. Improved characterisation of natural emissions and their ...radiative effects can therefore increase the accuracy of global climate model projections. Here we show that revised assumptions about pre-industrial fire activity result in significantly increased aerosol concentrations in the pre-industrial atmosphere. Revised global model simulations predict a 35% reduction in the calculated global mean cloud albedo forcing over the Industrial Era (1750-2000 CE) compared to estimates using emissions data from the Sixth Coupled Model Intercomparison Project. An estimated upper limit to pre-industrial fire emissions results in a much greater (91%) reduction in forcing. When compared to 26 other uncertain parameters or inputs in our model, pre-industrial fire emissions are by far the single largest source of uncertainty in pre-industrial aerosol concentrations, and hence in our understanding of the magnitude of the historical radiative forcing due to anthropogenic aerosol emissions.
PDF
