An experimental determination of the thermodynamic stabilities of a series of amyloid fibrils reveals that this structural form is likely to be the most stable one that protein molecules can adopt ...even under physiological conditions. This result challenges the conventional assumption that functional forms of proteins correspond to the global minima in their free energy surfaces and suggests that living systems are conformationally as well as chemically metastable.
This study presents a method based on retrofitted low-cost and easy to implement tracking devices, used to monitor the whole harvesting process in viticulture, to map yield andharvest quality ...parameters in viticulture. The method consists of recording the geolocation of all the machines (harvest trailers and grape harvester) during the harvest to spatially reallocate production parameters measured at the winery. The method was tested on a vineyard of 30 ha during the whole 2022 harvest season. It has identified harvest sectors (HS) associated with measured production parameters (grape mass and harvest quality parameters: sugar content, total acidity, pH, yeast assimilable nitrogen, organic nitrogen) and calculated production parameters (potential alcohol of grapes, yield, yield per plant) over the entire vineyard. The grape mass was measured at the vineyard cellar or at the winegrowing cooperative by calibrated scales. The harvest quality parameters were measured on grape must samples in a commercial laboratory specialized in oenological analysis and using standardized protocols. Results validate the possibility of making production parameters maps automatically solely from the time and location records of the vehicles. They also highlight the limitations in terms of spatial resolution (the mean area of the HS is 0.3 ha) of the resulting maps which depends on the actual yield and size of harvest trailers. Yield per plant and yeast assimilable nitrogen maps have been used, in collaboration with the vineyard manager, to analyze and reconsider the fertilization process at the vineyardscale, showing the relevance of the information.
Biomass burning (BB) plumes were measured at the Cape Grim Baseline Air Pollution Station during the 2006 Precursors to Particles campaign, when emissions from a fire on nearby Robbins Island ...impacted the station. Measurements made included non-methane organic compounds (NMOCs) (PTR-MS), particle number size distribution, condensation nuclei (CN) > 3 nm, black carbon (BC) concentration, cloud condensation nuclei (CCN) number, ozone (O3), methane (CH4), carbon monoxide (CO), hydrogen (H2), carbon dioxide (CO2), nitrous oxide (N2O), halocarbons and meteorology. During the first plume strike event (BB1), a 4 h enhancement of CO (max ~ 2100 ppb), BC (~ 1400 ng m-3) and particles > 3 nm (~ 13 000 cm-3) with dominant particle mode of 120 nm were observed overnight. A wind direction change lead to a dramatic reduction in BB tracers and a drop in the dominant particle mode to 50 nm. The dominant mode increased in size to 80 nm over 5 h in calm sunny conditions, accompanied by an increase in ozone. Due to an enhancement in BC but not CO during particle growth, the presence of BB emissions during this period could not be confirmed. The ability of particles > 80 nm (CN80) to act as CCN at 0.5 % supersaturation was investigated. The ΔCCN / ΔCN80 ratio was lowest during the fresh BB plume (56 ± 8 %), higher during the particle growth period (77 ± 4 %) and higher still (104 ± 3 %) in background marine air. Particle size distributions indicate that changes to particle chemical composition, rather than particle size, are driving these changes. Hourly average CCN during both BB events were between 2000 and 5000 CCN cm-3, which were enhanced above typical background levels by a factor of 6–34, highlighting the dramatic impact BB plumes can have on CCN number in clean marine regions. During the 29 h of the second plume strike event (BB2) CO, BC and a range of NMOCs including acetonitrile and hydrogen cyanide (HCN) were clearly enhanced and some enhancements in O3 were observed (ΔO3 / ΔCO 0.001–0.074). A short-lived increase in NMOCs by a factor of 10 corresponded with a large CO enhancement, an increase of the NMOC / CO emission ratio (ER) by a factor of 2–4 and a halving of the BC / CO ratio. Rainfall on Robbins Island was observed by radar during this period which likely resulted in a lower fire combustion efficiency, and higher emission of compounds associated with smouldering. This highlights the importance of relatively minor meteorological events on BB emission ratios. Emission factors (EFs) were derived for a range of trace gases, some never before reported for Australian fires, (including hydrogen, phenol and toluene) using the carbon mass balance method. This provides a unique set of EFs for Australian coastal heathland fires. Methyl halide EFs were higher than EFs reported from other studies in Australia and the Northern Hemisphere which is likely due to high halogen content in vegetation on Robbins Island. This work demonstrates the substantial impact that BB plumes can have on the composition of marine air, and the significant changes that can occur as the plume interacts with terrestrial, aged urban and marine emission sources.
Constitutive models for soft soils require a large number of parameters to model the complex material response. One set of parameters should capture the soil response for various laboratory & in situ ...stress paths. This requires a new method to calibrate a consistent set of model parameters using test data from different load paths of classic geomechanical tests. The feasibility of the proposed method is demonstrated with the recently developed CREEP-SCLAY1S model. After a sensitivity analysis that highlights the model parameters for optimisation, an optimisation process for two different configurations is designed. The latter is successfully verified against artificially generated laboratory data.
This paper presents a three-dimensional constitutive model for natural clay that includes creep, anisotropy and structure, as well as a theoretical means to estimate the range for anisotropy- and ...structure-related parameters, as needed for parameter optimisation. Creep-SCLAY1S is an extension of the Creep-SCLAY1 model proposed by Sivasithamparam et al. (Comput Geotech 69:46–57,
2015
) which includes the effects of bonding and destructuration. The model needs 14 model parameters, of which five are similar to those used in the modified Cam–Clay model. A method is developed to quantify the range for the three parameters related to structure and anisotropy that cannot be derived directly from experimental data. The theoretically derived range compares favourably with the values found in the literature. As a result, the model now can be used with more confidence, enabling sensitivity analysis and systematic parameter derivation with optimisation techniques.
Parallel transmission (pTX) is a versatile solution to enable UHF MRI of the human body, where radiofrequency (RF) field inhomogeneity appears very challenging. Today, state of the art monitoring of ...the local SAR in pTX consists in evaluating the RF power deposition on specific SAR matrices called Virtual Observation Points (VOPs). It essentially relies on accurate electromagnetic simulations able to return the local SAR distribution inside the body in response to any applied pTX RF waveform. In order to reduce the number of SAR matrices to a value compatible with real time SAR monitoring <inline-formula> <tex-math notation="LaTeX">(\boldsymbol {\ll 1}{\boldsymbol {0}^{\boldsymbol {3}}}) </tex-math></inline-formula>, a VOP set is obtained by partitioning the SAR model into clusters, and associating a so- called dominant SAR matrix to every cluster. More recently, a clustering-free compression method was proposed, allowing for a significant reduction in the number of SAR matrices. The concept and derivation however assumed static RF shims and their extension to dynamic pTX is not straightforward, thereby casting doubt on the strict validity of the compression approach for these more complicated RF waveforms. In this work, we provide the mathematical framework to tackle this problem and find a rigorous justification of this criterion in the light of convex optimization theory. Our analysis led us to a variant of the clustering-free compression approach exploiting convex optimization. This new compression algorithm offers computational gains for large SAR models and for high-channel count pTX RF coils.
EHT0202 (etazolate hydrochloride) is a new compound exhibiting both potential disease-modifying and symptomatic treatment properties in Alzheimer's Disease increasing alpha-secretase activity and ...sAPP alpha secretion, as well as acting as a GABA-A receptor modulator and as a PDE-4 inhibitor.
This pilot, randomized, double-blind, placebo-controlled, parallel group, multicentre, Phase IIA study was conducted in 159 randomized patients suffering from mild to moderate Alzheimer's Disease. EHT0202 (40 or 80 mg bid) or placebo was administered as adjunctive therapy to one acetylcholinesterase inhibitor over a 3-month period. This study was designed to assess the clinical safety and tolerability of EHT0202 as a primary objective, with secondary endpoints (cognitive function, daily living activities, behaviour, caregiver burden and global functioning) included to explore clinical efficacy of EHT0202 versus placebo.
EHT0202 was shown to be safe and generally well tolerated. Dose-dependent numbers of early withdrawal and central nervous system related adverse events were observed. As expected, since the study was not powered and not designed to show drug efficacy, and except for ratings on the ADCS-ADL scale, no significant differences were seen between treatment groups.
These first encouraging safety results do support further development of EHT0202 in order to assess its clinical efficacy and to confirm its tolerability in a larger cohort of Alzheimer patients and for a longer period.
Summary
Background
Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to ...subclinical injuries. Cardiac troponin‐I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value.
Objectives
To assess the predictive value of cTnI in patients with TTP for death or refractoriness.
Patients/Methods
The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS‐13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission.
Results
Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty‐two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 μg L−1) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 μg L−1 was the only independent factor in predicting death (odds ratio OR 2.87; 95% confidence interval CI 1.13–7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27–7.3; P = 0.01).
Conclusions
A CTnI level of > 0.25 μg L−1 at presentation in patients with TTP appears to be an independent factor associated with a three‐fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP.
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