Measurement of Microstructure of Snow from Surface Sections

A new approach to modelling the microstructure of snow is presented. The features involved in this formulation include skeletonising of the granular material and the modelling of the necks as a system of truncated cones. The skeletonising involves the process of representing the granular structure by a series of lines describing the grains and the necks and bonds. The value associated with any point on the skeleton is determined by the closest distance from the point to a grain boundary or neck boundary, whichever is smaller. This approach allows for easy visualisation of the material and efficient data storage. The use truncated cone model for the necked regions represents a more accurate physical description of the necks and should provide for a better relationship between microstructure and material properties. Preliminary results of one case study are presente

Atomic force microscopy studies on two-step nucleation and epitaxial growth

Continues advancement and rapid development of techniques operating at the nanoscale open new opportunities to revise and question commonly accepted nucleation and crystal growth theories. Atomic Force Microscopy (AFM) has been successfully involved in various aspects of active pharmaceutical ingredient (API) characterisation including crystal growth, stability of solid dispersions, surface morphology, phase changes and dissolution [1]. Recent studies conducted on proteins crystallisation at nanoscale show new evidence disproving generally accepted Classical Nuclea/on Theory (CNT)[2]. Currently, ‘dense liquid droplets’ seen in protein crystallisation and ‘pre-nucleation clusters’ [3] seen mostly in inorganic salt crystallisation, are two main concepts of non-classical nucleation theory, although no significant progress has been made towards better understanding of mechanisms controlling heterogeneous nucleation in small organic molecules systems, what is in particular interest, as an epitaxial ordering phenomenon is frequently used to enhance nucleation rates and control properties of materials. Our studies present a new light on heteronucleation and the epitaxial growth mechanisms based epitaxial growth of olanzapine dihydrate D on the surface of olanzapine form I (OZPN I) both in high humidity conditions and water solu*on. Results obtained from Peak Force Quan/ta/ve Nanomechanical Mapping Atomic Force Microscopy (PF- QNM-AFM) [4] indicate the presence of intermediate dense liquid-like phase in process of dihydrate D nucleation

Molecular mechanisms and animal models of spinal muscular atrophy

AbstractSpinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is characterized by the degeneration of spinal motor neurons and muscle atrophy. Although the genetic cause of SMA has been mapped to the Survival Motor Neuron1 (SMN1) gene, mechanisms underlying selective motor neuron degeneration in SMA remain largely unknown. Here we review the latest developments and our current understanding of the molecular mechanisms underlying SMA pathogenesis, focusing on the animal model systems that have been developed, as well as new diagnostic and treatment strategies that have been identified using these model systems. This article is part of a special issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis

Spall And Dynamic Yielding Of Aluminum And Aluminum Alloys At Strain Rates Of 3X10(6) S(-1)

We have explored the role that grain size, impurity particles and alloying in aluminum play in dynamic yielding and spall fracture at tensile strain rates of similar to 3x10(6) We achieved these strain rates shocking the aluminum specimens via laser ablation using the Z-Beamlet Laser at Sandia National Laboratories. The high purity aluminum and 1100 series aluminum alloy produced very different spall strengths and nearly the same yield strengths. In contrast, various grain-sized Al + 3 wt. % Mg specimens presented the lowest spall strength, but the greatest dynamic yield strength. Fracture morphology results and particle analysis are presented along with hydrodynamic simulations to put these results in context. Impurity particles appeared to play a vital role in spall fracture at these fast strain rates. Alloying elements such as Mg seem to be the dominant factor in the dynamic yield results.Mechanical Engineerin

Laser-Induced Spall Of Aluminum And Aluminum Alloys At High Strain Rates

We conducted laser-induced spall experiments aimed at studying how a material's microstructure affects the tensile fracture characteristics at high strain rates (> 10(6) s(-1)). We used the Z-Beamlet Laser at Sandia National Laboratory to drive shocks and to measure the spall strength of aluminum targets with various microstructures. The targets were recrystallized, high-purity aluminum (Al-HP RX), recrystallized aluminum + 3 wt.% magnesium (Al-3Mg RX), and cold-worked aluminum + 3 wt.% magnesium (Al-3Mg CW). The Al-3Mg RX and Al-3Mg CW are used to explore the roles that solid-solution alloying and cold-work strengthening play in the spall process. Using a line-VISAR (Velocity Interferometer System for Any Reflector) and analysis of recovered samples, we were able to measure spall strength and determine failure morphology in these targets. We find that the spall strength is highest for Al-HP RX. Analysis reveals that material grain size plays a vital role in the fracture morphology and spall strength results.Mechanical Engineerin

Comparison of Accu Chek Inform II point-of-care test blood glucose meter with Hexokinase Plasma method for a diabetes mellitus population during surgery under general anesthesia

Purpose Blood glucose (BG) concentrations of patients with diabetes mellitus (DM) are monitored during surgery to prevent hypo- and hyperglycemia. Access to point-of-care test (POCT) glucose meters at an operating room will usually provide monitoring at shorter intervals and may improve glycemic control. However, these meters are not validated for patients under general anesthesia. Methods This cross-sectional study included 75 arterial BG measurements from 75 patients (71 with DM, mostly insulin dependent) who underwent elective non-cardiac surgery under general anesthesia. Arterial blood samples were taken at least 60 minutes after induction. One drop of blood was used for Accu Chek Inform II (ACI II) POCT BG meter and the residual blood was sent to the clinical laboratory for a Hexokinase Plasma reference method. A Bland-Altman plot was used to visualize the differences between both methods, and correlation was assessed using the intra-class correlation coefficient (ICC). Results The results showed an estimated mean difference of 0.8 mmol/L between ACI II and the reference method, with limits of agreement equal to -0.6 and 2.2 mmol/L. In general, the reference method produced higher values than ACI II. ICC was 0.955 (95% CI 0.634-0.986), P &lt; 0.001, and concordance correlation coefficient (CCC) was 0.955 (95% CI 0.933-0.970). Conclusion Arterial BG measurements during surgery in patients with DM under general anesthesia using POCT BG meter are in general lower than laboratory measurements, but the ICC and CCC show a clinically acceptable correlation. We conclude that POCT measurements conducted on arterial specimens using the ACI II provide sufficiently accurate results for glucose measurement during surgery under general anesthesia.</p

Performance of continuous glucose monitoring devices during intensive exercise conditions in people with diabetes:the Mont Blanc experience

With increasing use of both flash glucose monitoring and real-time continuous glucose monitoring and the reliance of users on these readings, accuracy is important, in particular during intensive exercise. We investigated the performance of the FreeStyle Libre 1 flash glucose monitor and the Guardian Connect EnliteTM real-time continuous glucose monitor by comparing readings with self-monitored blood glucose values during intensive exercise.</p

Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox

High molecular weight homologues of gp91phox, the superoxide-generating subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, have been identified in human (h) and Caenorhabditis elegans (Ce), and are termed Duox for “dual oxidase” because they have both a peroxidase homology domain and a gp91phox domain. A topology model predicts that the enzyme will utilize cytosolic NADPH to generate reactive oxygen, but the function of the ecto peroxidase domain was unknown. Ce-Duox1 is expressed in hypodermal cells underlying the cuticle of larval animals. To investigate function, RNA interference (RNAi) was carried out in C. elegans. RNAi animals showed complex phenotypes similar to those described previously in mutations in collagen biosynthesis that are known to affect the cuticle, an extracellular matrix. Electron micrographs showed gross abnormalities in the cuticle of RNAi animals. In cuticle, collagen and other proteins are cross-linked via di- and trityrosine linkages, and these linkages were absent in RNAi animals. The expressed peroxidase domains of both Ce-Duox1 and h-Duox showed peroxidase activity and catalyzed cross-linking of free tyrosine ethyl ester. Thus, Ce-Duox catalyzes the cross-linking of tyrosine residues involved in the stabilization of cuticular extracellular matrix

Do metastable polymorphs always grow faster? Measuring and comparing growth kinetics of three polymorphs of tolfenamic acid

The phenomenon of molecular crystal polymorphism is of central importance for all those industries that rely on crystallisation for the manufacturing of their products. Computational methods for the evaluation of thermodynamic properties of polymorphs have become incredibly accurate and a priori prediction of crystal structures is becoming routine. The computational study and prediction of the kinetics of crystallisation impacting polymorphism, however, have received considerably less attention despite their crucial role in directing crystallisation outcomes. This is mainly due to the lack of available experimental data, as nucleation and growth kinetics of polymorphs are generally difficult to measure. On the one hand, the determination of overall nucleation and growth kinetics through batch experiments suffers from unwanted polymorphic transformations or the absence of experimental conditions under which several polymorphs can be nucleated. On the other hand, growth rates of polymorphs obtained from measurements of single crystals are often only recorded along a few specific crystal dimensions, thus lacking information about overall growth and rendering an incomplete picture of the problem. In this work, we measure the crystal growth kinetics of three polymorphs (I, II and IX) of tolfenamic acid (TFA) in isopropanol solutions, with the intention of providing a meaningful comparison of their growth rates. First, we analyse the relation between the measured growth rates and the crystal structures of the TFA polymorphs. We then explore ways to compare their relative growth rates and discuss their significance when trying to determine which polymorph grows faster. Using approximations for describing the volume of TFA crystals, we show that while crystals of the metastable TFA-II grow the fastest at all solution concentrations, crystals of the metastable TFA-IX become kinetically competitive as the driving force for crystallisation increases. Overall, both metastable forms TFA-II and TFA-IX grow faster than the stable TFA-I

Increased glycation and oxidative damage to apolipoprotein B100 of LDL cholesterol in patients with type 2 diabetes and effect of metformin

OBJECTIVE The aim of this study was to investigate whether apolipoprotein B100 of LDL suffers increased damage by glycation, oxidation, and nitration in patients with type 2 diabetes, including patients receiving metformin therapy. RESEARCH DESIGN AND METHODS For this study, 32 type 2 diabetic patients and 21 healthy control subjects were recruited; 13 diabetic patients were receiving metformin therapy (median dose: 1.50 g/day). LDL was isolated from venous plasma by ultracentrifugation, delipidated, digested, and analyzed for protein glycation, oxidation, and nitration adducts by stable isotopic dilution analysis tandem mass spectrometry. RESULTS Advanced glycation end product (AGE) content of apolipoprotein B100 of LDL from type 2 diabetic patients was higher than from healthy subjects: arginine-derived AGE, 15.8 vs. 5.3 mol% (P < 0.001); and lysine-derived AGE, 2.5 vs. 1.5 mol% (P < 0.05). Oxidative damage, mainly methionine sulfoxide residues, was also increased: 2.5 vs. 1.1 molar equivalents (P < 0.001). 3-Nitrotyrosine content was decreased: 0.04 vs. 0.12 mol% (P < 0.05). In diabetic patients receiving metformin therapy, arginine-derived AGE and methionine sulfoxide were lower than in patients not receiving metformin: 19.3 vs. 8.9 mol% (P < 0.01) and 2.9 vs. 1.9 mol% (P < 0.05), respectively; 3-nitrotyrosine content was higher: 0.10 vs. 0.03 mol% (P < 0.05). Fructosyl-lysine residue content correlated positively with fasting plasma glucose. Arginine-derived AGE residue contents were intercorrelated and also correlated positively with methionine sulfoxide. CONCLUSIONS Patients with type 2 diabetes had increased arginine-derived AGEs and oxidative damage in apolipoprotein B100 of LDL. This was lower in patients receiving metformin therapy, which may contribute to decreased oxidative damage, atherogenicity, and cardiovascular disease