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Long-range HNCO NMR spectra for proteins show crosspeaks due to 1JNC', 2JNC', 3JNCγ, and h3JNC' couplings. The h3JNC' couplings are transmitted through hydrogen bonds and their sizes are correlated to hydrogen bond lengths. We collected long-range HNCO data at a series of temperatures for four protein structures. P22i and CUS-3i are six-stranded beta-barrel I-domains from phages P22 and CUS-3 that share less than 40% sequence identity. The cis and trans states of the C-terminal domain from pore-forming toxin hemolysin ΙΙ (HlyIIC) arise from the isomerization of a single G404-P405 peptide bond. For P22i and CUS-3i, hydrogen bonds detected by NMR agree with those observed in the corresponding domains from cryoEM structures of the two phages. Hydrogen bond lengths derived from the h3JNC' couplings, however, are poorly conserved between the distantly related CUS-3i and P22i domains and show differences even between the closely related cis and trans state structures of HlyIIC. This is consistent with hydrogen bond lengths being determined by local differences in structure rather than the overall folding topology. With increasing temperature, hydrogen bonds typically show an apparent increase in length that has been attributed to protein thermal expansion. Some hydrogen bonds are invariant with temperature, however, while others show apparent decreases in length, suggesting they become stabilized with increasing temperature. Considering the data for the three proteins in this study and previously published data for ubiquitin and GB3, lowered protein folding stability and cooperativity corresponds with a larger range of temperature responses for hydrogen bonds. This suggests a partial uncoupling of hydrogen bond energetics from global unfolding cooperativity as protein stability decreases. [ABSTRACT FROM AUTHOR]

Long-range HNCO NMR spectra for proteins show crosspeaks due to 1JNC′, 2JNC′, 3JNCγ, and h3JNC′ couplings. The h3JNC′ couplings are transmitted through hydrogen bonds and their sizes are correlated to hydrogen bond lengths. We collected long-range HNCO data at a series of temperatures for four protein structures. P22i and CUS-3i are six-stranded beta-barrel I-domains from phages P22 and CUS-3 that share less than 40% sequence identity. The cis and trans states of the C-terminal domain from pore-forming toxin hemolysin ΙΙ (HlyIIC) arise from the isomerization of a single G404-P405 peptide bond. For P22i and CUS-3i, hydrogen bonds detected by NMR agree with those observed in the corresponding domains from cryoEM structures of the two phages. Hydrogen bond lengths derived from the h3JNC′ couplings, however, are poorly conserved between the distantly related CUS-3i and P22i domains and show differences even between the closely related cis and trans state structures of HlyIIC. This is consistent with hydrogen bond lengths being determined by local differences in structure rather than the overall folding topology. With increasing temperature, hydrogen bonds typically show an apparent increase in length that has been attributed to protein thermal expansion. Some hydrogen bonds are invariant with temperature, however, while others show apparent decreases in length, suggesting they become stabilized with increasing temperature. Considering the data for the three proteins in this study and previously published data for ubiquitin and GB3, lowered protein folding stability and cooperativity corresponds with a larger range of temperature responses for hydrogen bonds. This suggests a partial uncoupling of hydrogen bond energetics from global unfolding cooperativity as protein stability decreases.

The BBR test has received growing concerns regarding its applicability to field studies and special materials due to the large amount of long-term aged asphalt binder used in preparing asphalt binder beams and the time-consuming beam preparation and testing process. In recent years, the application of a dynamic shear rheometer (DSR) to investigate the low-temperature performance of asphalt binder has attracted widespread attention because it uses significantly less asphalt binder for testing and allows for easy specimen preparation. The objective of this study was to develop an efficient and robust method to evaluate the low-temperature performance of asphalt binder based on DSR testing. Frequency sweep tests were performed on twelve asphalt binders at temperatures ranging from 0 to 25 °C using the 8-mm parallel plate geometry. Two conversions were applied to frequency sweep test data in order to predict the flexural creep stiffness and m -value of asphalt binder, namely the conversion from frequency domain to time domain and the conversion from shear loading to bending loading. The 1S2P1D model was employed to construct the master curves of storage modulus and loss modulus. Afterwards, the flexural creep stiffness was predicted using the shear creep compliance master curve model, which was derived from the 1S2P1D model using the inverse Laplace transform, and the Poisson's ratio, which was assumed to be constant. It was found that the predicted values of S (60) and m (60) were comparable to the counterparts measured by the BBR, which well demonstrated the feasibility of the proposed DSR-BBR conversion method. In comparison to existing analysis methods, the proposed conversion method strictly complied with the linear viscoelastic theory, and it enabled efficient and robust predictions because the prediction model of flexural creep stiffness had the same parameters as those of the 1S2P1D model, thus avoiding multiple data fittings. • Prediction of flexural creep stiffness and m -value based on DSR frequency sweep tests. • Conversion of DSR test data from frequency to time domain and from shear to bending loading. • Derivation of shear creep compliance master curve model from 1S2P1D model using inverse Laplace transform. • Verified feasibility of proposed conversion method by comparing predicted and measured values. [ABSTRACT FROM AUTHOR]

While it is widely appreciated that the denatured state of a protein is a heterogeneous conformational ensemble, there is still debate over how this ensemble changes with environmental conditions. Here, we use single-molecule chemo-mechanical unfolding, which combines force and urea using the optical tweezers, together with traditional protein unfolding studies to explore how perturbants commonly used to unfold proteins (urea, force, and temperature) affect the denatured-state ensemble. We compare the urea m-values, which report on the change in solvent accessible surface area for unfolding, to probe the denatured state as a function of force, temperature, and urea. We find that while the urea- and force-induced denatured states expose similar amounts of surface area, the denatured state at high temperature and low urea concentration is more compact. To disentangle these two effects, we use destabilizing mutations that shift the Tm and Cm. We find that the compaction of the denatured state is related to changing temperature as the different variants of acyl-coenzyme A binding protein have similar m-values when they are at the same temperature but different urea concentration. These results have important implications for protein folding and stability under different environmental conditions.

While there is a significant body of research on the dynamics of chromophoric dissolved organic matter (CDOM) in coastal and offshore waters, our understanding of CDOM dynamics in tropical inland water bodies remains limited. To bridge this knowledge gap, a monthly in-situ investigation was carried out at 33 stations along a monsoon driven lagoon, Chilika, on the southeast coast of India for one year i.e., from July 2018 to June 2019. CDOM absorption at 440 nm [aCDOM(440)] data were analyzed as a proxy for CDOM concentration which varied between a range of 0.04–65.14 m−1 with an average value of 2.77 ± 5.23 m−1. A gradient in aCDOM(440) was observed from the river discharge dominated shallower northern sector (4.91 ± 8.32) m−1 to the more isolated and less fresh water influenced deeper southern sector (1.21 ± 1.55) m−1. Spectral slope (S), spectral slope ratio (S R), and molecular weight proxy (M) were computed to understand the possible source and fate of CDOM in the lagoon. The average spectral slope of S 280–500 and S 350–500 vary between 0.002 and 0.096 nm−1 and 0.001–0.095 nm−1, respectively. The (S R) and (M) values ranged between of 0.01–6.81 and 0.31–52.28. It was observed that large-sized, high molecular weight CDOM from terrestrial origin was prevalent during monsoon with lower (S 280–500), (S R), and (M)values. In contrast, lower molecular weight CDOM fractions were prevalent during pre- and post-monsoon which were mainly of autochthonous origin with higher (S 350–500), (S R), and (M) values. Our findings indicate significant spatio-temporal variations of CDOM in Chilika Lagoon, influenced by the monsoon-driven influx of freshwater and the mixing of fresh and marine water. In-situ changes in CDOM are likely shaped by microbial breakdown and photodegradation. [Display omitted] • Monthly CDOM study in Chilika Lagoon from July 2018 to June 2019. • CDOM concentration varied widely, averaging 2.77 ± 5.23 m-1. • North sector had higher CDOM, south sector had lower. • Monsoon brought large, heavy CDOM; other seasons had lighter forms. • Spatial and temporal CDOM variations driven by monsoon and water mixing. [ABSTRACT FROM AUTHOR]

Abstract Background High-throughput technologies enable the cost-effective collection and analysis of DNA methylation data throughout the human genome. This naturally entails missing values management that can complicate the analysis of the data. Several general and specific imputation methods are suitable for DNA methylation data. However, there are no detailed studies of their performances under different missing data mechanisms –(completely) at random or not- and different representations of DNA methylation levels (β and M-value). Results We make an extensive analysis of the imputation performances of seven imputation methods on simulated missing completely at random (MCAR), missing at random (MAR) and missing not at random (MNAR) methylation data. We further consider imputation performances on the popular β- and M-value representations of methylation levels. Overall, β-values enable better imputation performances than M-values. Imputation accuracy is lower for mid-range β-values, while it is generally more accurate for values at the extremes of the β-value range. The MAR values distribution is on the average more dense in the mid-range in comparison to the expected β-value distribution. As a consequence, MAR values are on average harder to impute. Conclusions The results of the analysis provide guidelines for the most suitable imputation approaches for DNA methylation data under different representations of DNA methylation levels and different missing data mechanisms.

An asphalt-binder is one of the key constituent elements that significantly influences and controls the fracture behavior and cracking performance of hot-mix asphalt (HMA). In particular, the low-temperature rheological properties of asphalt-binders are critical in terms of improving the HMA fracture properties in the laboratory and ultimately mitigating cracking in the field. The bending beam rheometer (BBR) is one of the most widely used laboratory test methods for evaluating and quantifying the asphalt-binder behavior at low temperatures, mostly using the stiffness (S) and m-value parameters. Using the Texas flexible pavements and overlays database, namely, the Texas data storage system (DSS), as the primary data source, this study was conducted to correlate the asphalt-binder low-temperature rheological properties (measured using the BBR) to the HMA fracture properties. The HMA fracture properties were measured in the laboratory using the monotonic-loading overlay tester (ML-OT). In general, the asphalt-binder low-temperature rheological properties [particularly the stiffness (S)] exhibited promising potential to predict the HMA fracture properties, namely, the tensile strain (εt) and fracture energy index (FE Index), with a coefficient of determination (R2) greater than 60%. [ABSTRACT FROM AUTHOR]

Temperature and loading time influence the viscoelastic behavior of bitumen. The present study aimed to compare the results of some analyses including Burger model, relaxation modulus, dissipation energy ratio, statistical analysis of ANOVA and artificial neural networks (ANN) and to investigate the viscoelastic behavior of bitumen modified with nano-CaCO3 (NCCO) and ethylene-vinyl acetate (EVA). To this end, the Bending Beam Rheometer (BBR) tests were conducted on NCCO- and EVA-modified bitumen at various temperatures. According to the previous studies, NCCO was utilized for 4% and 6% weight of neat bitumen and the BBR test was conducted at low temperatures of -6 and -12°C. In addition, EVA was utilized for 6% weight of neat bitumen and the BBR test was conducted at low temperatures of -6, -12 and -18°C. Hence, results of four models showed that EVA-modified bitumen could improve the viscoelastic behavior of bitumen in low temperatures and NCCO had a negligible effect on improving bitumen. Finally, results of the Burger model, relaxation modulus, and dissipation energy ratio were compared and based on these results, the relaxation modulus and dissipation energy ratio were more accurate than the Burger model. Additionally, results of the statistical analysis of ANOVA were weaker than the artificial neural networks (ANN) method. [ABSTRACT FROM AUTHOR]

Long-range HNCO NMR spectra for proteins show crosspeaks due to 1 J NC' , 2 J NC' , 3 J NCγ , and h3 J NC' couplings. The h3 J NC' couplings are transmitted through hydrogen bonds and their sizes are correlated to hydrogen bond lengths. We collected long-range HNCO data at a series of temperatures for four protein structures. P22i and CUS-3i are six-stranded beta-barrel I-domains from phages P22 and CUS-3 that share less than 40% sequence identity. The cis and trans states of the C-terminal domain from pore-forming toxin hemolysin ΙΙ (HlyIIC) arise from the isomerization of a single G404-P405 peptide bond. For P22i and CUS-3i, hydrogen bonds detected by NMR agree with those observed in the corresponding domains from cryoEM structures of the two phages. Hydrogen bond lengths derived from the h3 J NC' couplings, however, are poorly conserved between the distantly related CUS-3i and P22i domains and show differences even between the closely related cis and trans state structures of HlyIIC. This is consistent with hydrogen bond lengths being determined by local differences in structure rather than the overall folding topology. With increasing temperature, hydrogen bonds typically show an apparent increase in length that has been attributed to protein thermal expansion. Some hydrogen bonds are invariant with temperature, however, while others show apparent decreases in length, suggesting they become stabilized with increasing temperature. Considering the data for the three proteins in this study and previously published data for ubiquitin and GB3, lowered protein folding stability and cooperativity corresponds with a larger range of temperature responses for hydrogen bonds. This suggests a partial uncoupling of hydrogen bond energetics from global unfolding cooperativity as protein stability decreases.

The Illumina Infinium HumanMethylation450 Beadchips have been widely utilized in epigenome-wide association studies (EWAS). However, the existing two types of probes (type I and type II), with the distribution of measurements of probes and dynamic range different, may bias downstream analyses. Here, we propose a method, MGMIN (M-values Gaussian-MIxture Normalization), to correct the probe designs based on M-values of DNA methylation. Our strategy includes fitting Gaussian mixture distributions to type I and type II probes separately, a transformation of M-values into quantiles and finally a dilation transformation based on M-values of DNA methylation to maintain the continuity of the data. Our method is validated on several public datasets on reducing probe design bias, reducing the technical variation and improving the ability to find biologically differential methylation signals. The results show that MGMIN achieves competitive performances compared to BMIQ which is a well-known normalization method on β-values of DNA methylation.

The Illumina Infinium HumanMethylation450 Beadchips have been widely utilized in epigenome-wide association studies (EWAS). However, the existing two types of probes (type I and type II), with the distribution of measurements of probes and dynamic range different, may bias downstream analyses. Here, we propose a method, MGMIN (M -values Gaussian-MIxture Normalization), to correct the probe designs based on M -values of DNA methylation. Our strategy includes fitting Gaussian mixture distributions to type I and type II probes separately, a transformation of M -values into quantiles and finally a dilation transformation based on M -values of DNA methylation to maintain the continuity of the data. Our method is validated on several public datasets on reducing probe design bias, reducing the technical variation and improving the ability to find biologically differential methylation signals. The results show that MGMIN achieves competitive performances compared to BMIQ which is a well-known normalization method on β-values of DNA methylation. [ABSTRACT FROM AUTHOR]

The predictability of strain distributions and the related prediction of hardening and failure plays a central role in tool and process design for any metal forming process. Studying yielding behaviour, it was discovered that for various well established yield loci no satisfying agreement between DIC (digital image correlation) measurement of strain distribution and simulation result could be obtained, even after optimization of parameters based on associated flow assumption. In parallel, crystal plasticity simulations were investigated with the objective to predict the relation between stress and strain ratios for a large number of load cases based on texture measurement. To include macroscopic data, a secondary strategy uses cruciform tension specimen as defined in ISO16842 to obtain strain and stress ratios. The resulting relations were then applied separately as input parameters for the plastic yield description. Both approaches reach high agreement between forming experiment and simulation. Against the previous assumption, the output can be obtained with either anisotropic or free shape yield loci and associated flow description. The methodology discussed provides an alternative and challenges to rethink the definition of yielding for aluminium alloys on the example of an AA6014-T4 aluminium alloy. [ABSTRACT FROM AUTHOR]

Background: High-throughput technologies enable the cost-effective collection and analysis of DNA methylation data throughout the human genome. This naturally entails missing values management that can complicate the analysis of the data. Several general and specific imputation methods are suitable for DNA methylation data. However, there are no detailed studies of their performances under different missing data mechanisms –(completely) at random or not- and different representations of DNA methylation levels (β and M-value). Results: We make an extensive analysis of the imputation performances of seven imputation methods on simulated missing completely at random (MCAR), missing at random (MAR) and missing not at random (MNAR) methylation data. We further consider imputation performances on the popular β- and M-value representations of methylation levels. Overall, β-values enable better imputation performances than M-values. Imputation accuracy is lower for mid-range β-values, while it is generally more accurate for values at the extremes of the β-value range. The MAR values distribution is on the average more dense in the mid-range in comparison to the expected β-value distribution. As a consequence, MAR values are on average harder to impute. Conclusions: The results of the analysis provide guidelines for the most suitable imputation approaches for DNA methylation data under different representations of DNA methylation levels and different missing data mechanisms. [ABSTRACT FROM AUTHOR]

In this study, we investigate the thermodynamic mechanisms by which electron transfer proteins adapt to environmental temperature by directly comparing the redox properties and folding stability of a psychrophilic cytochrome c and a mesophilic homolog. Our model system consists of two cytochrome c6 proteins from diatoms: one adapted specifically to polar environments, the other adapted generally to surface ocean environments. Direct electrochemistry shows that the midpoint potential for the mesophilic homolog is slightly higher at all temperatures measured. Cytochrome c6 from the psychrophilic diatom unfolds with a melting temperature 10.4 °C lower than the homologous mesophilic cytochrome c6. Changes in free energy upon unfolding are identical, within error, for the psychrophilic and mesophilic protein; however, the chemical unfolding transition of the psychrophilic cytochrome c6 is more cooperative than for the mesophilic cytochrome c6. Substituting alanine residues found in the mesophile with serine found in corresponding positions of the psychrophile demonstrates that burial of the polar serine both decreases the thermal stability and decreases the midpoint potential. The mutagenesis data, combined with differences in the m-value of chemical denaturation, suggest that differences in solvent accessibility of the hydrophobic core underlie the adaptation of cytochrome c6 to differing environmental temperature. [ABSTRACT FROM AUTHOR]

This paper presents a new phenomenological model for describing the main features of the viscoplastic behavior of superplastic sheet metals, namely, strain hardening, softening, and damage. The proposed model is based on a variable strain rate sensitivity index (m-value) measured from uniaxial tensile tests at different strain rates under constant temperature. In this study, the uniaxial tensile tests were carried out at three strain rates (i.e., 10−3, 10−2, and 10−1 s−1) on a superplastic grade AA5083 aluminum sheet alloy. In addition, the volume fractions of cavities at different plastic strain levels were assessed using X-ray microtomography. The performance of the model was investigated by comparing its predictions with the experimental data. In addition, the model was validated with two sets of reference data for AA5083 aluminum alloy and AZ31 magnesium alloy. In particular, it was observed that the new model could predict the flow behavior of these metals more successfully compared with two reference models; nevertheless, it requires minimal experimentation and calculation efforts. [ABSTRACT FROM AUTHOR]

The present article investigates in laboratory conditions the effect of cyclic freezing and thawing (CFT) on characteristics of the neat bitumen and bitumens modified with different polymers, as well as stone mastic asphalt concretes prepared with the use of the neat and the modified bitumens. Maximal and minimal temperature in cycles of freezing and thawing (FT) is accepted equal to +20 °C and −18 ± 2 °C respectively. Characteristics of low temperature resistance of bitumens (stiffness S and m-value) have been determined on bending beam rheometer at the temperatures of −24 °C, −30 °C, and −36 °C. Strength at direct tension of the stone mastic asphalt concretes has been evaluated in the device TRAVIS (Infratest Ltd., Brackenheim, Germany) at the temperatures of 0 °C, −10 °C, −20 °C, and −30 °C. Resistance of stone mastic asphalt concretes to rutting has been determined on a Hamburg wheel tracking machine. The characteristics of the bitumens have been determined in the initial condition and after 25 and 50 cycles of FT, and the characteristics of stone mastic asphalt concretes, in the initial condition and after 50 cycles of FT. The results obtained experimentally have shown that CFT impacts essentially on the investigated characteristics of bitumens and stone mastic asphalt concretes. Modification with polymers improves the mechanical characteristics of the bitumens and decreases the effect of CFT. It is also found out that when selecting a bitumen for specific climatic conditions it is necessary to take into account both the number of cycles of FT and the characteristic low temperature. [ABSTRACT FROM AUTHOR]

Highlights • RTOT aged samples of sixteen polymer modified asphalt were produced. • Rheological properties of PPA modified binders under RTFO aging state was studied. • The effect on road properties of PPA modified binder were evaluated. • 0.5% PPA could improve the aging resistance of polymer modified asphalt. Abstract High viscosity is an important feature of SBS modified asphalt, but it is not always favorable because it need more energy to achieve the same viscosity for mixing and construction. Therefore, there are many attempts to improve rheological properties, and on the other hand maintain excellent high-temperature and low-temperature properties of SBS asphalt. Some researchers found that the polyphosphoric acid (PPA) can change the road performance and rheological properties (such as viscosity) of the modified asphalt effectively. The objective of this study is to investigate the high-temperature rheological properties and short-term aging resistance of SBS and three alternative polymer modified binders with/without PPA under Rolling Thin-Film Oven (RTFO) aging process. The rheological properties of these modified binders were tested by DSR and BBR under RTFO short-term aging. The test results indicated that some physical properties such as failure temperature, complex modulus were changed while SBS was replaced partially by PPA, and some properties such as zero shear viscosity, relaxation stress were not influenced regardless of RTFO short-term aging. Therefore it shows that PPA could improve the short-term aging resistance of modified binders. [ABSTRACT FROM AUTHOR]

The present article investigates in laboratory conditions the effect of cyclic freezing and thawing (CFT) on characteristics of the neat bitumen and bitumens modified with different polymers, as well as stone mastic asphalt concretes prepared with the use of the neat and the modified bitumens. Maximal and minimal temperature in cycles of freezing and thawing (FT) is accepted equal to +20 °C and −18 ± 2 °C respectively. Characteristics of low temperature resistance of bitumens (stiffness S and m-value) have been determined on bending beam rheometer at the temperatures of −24 °C, −30 °C, and −36 °C. Strength at direct tension of the stone mastic asphalt concretes has been evaluated in the device TRAVIS (Infratest Ltd., Brackenheim, Germany) at the temperatures of 0 °C, −10 °C, −20 °C, and −30 °C. Resistance of stone mastic asphalt concretes to rutting has been determined on a Hamburg wheel tracking machine. The characteristics of the bitumens have been determined in the initial condition and after 25 and 50 cycles of FT, and the characteristics of stone mastic asphalt concretes, in the initial condition and after 50 cycles of FT. The results obtained experimentally have shown that CFT impacts essentially on the investigated characteristics of bitumens and stone mastic asphalt concretes. Modification with polymers improves the mechanical characteristics of the bitumens and decreases the effect of CFT. It is also found out that when selecting a bitumen for specific climatic conditions it is necessary to take into account both the number of cycles of FT and the characteristic low temperature.

Reclaimed asphalt pavement (RAP) has many advantages and is utilized to improve the high temperature properties of asphalt mixtures. Low temperature cracking is a predominant distress in asphalt pavements containing RAP materials. Thus, the evaluation of fracture resistance for asphalt mixtures containing RAP is of interest. The objective of this research is to explore the low temperature performance characteristics of RAP mortars containing sieved RAP and soft binders at three aged states. The stiffness values and m-values from bending beam rheometer (BBR) tests at three test temperatures of -18 °C, -12 °C and -6 °C were obtained to conduct the minimum low temperature grades. RAP mortar with a higher aged binder content had a higher minimum low temperature regardless of RAP source. In addition, RAP mortars with virgin soft binder had the best low temperature resistance followed by the RAP mortars with rolling thin film oven (RTFO) and pressure-aged vessel (PAV) binders. [ABSTRACT FROM AUTHOR]

This article contains protocols for determining the conformational stability of a globular protein from either urea or thermal unfolding curves. Circular dichroism is the optical spectroscopic technique most commonly used to monitor protein unfolding. These protocols describe how to analyze data from an unfolding curve to obtain the thermodynamic parameters necessary to calculate conformational stability, and how to determine differences in stability between protein variants. Curr. Protoc. Protein Sci. 71:28.4.1-28.4.14. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Determining protein conformational stability from urea-induced unfolding curves Support Protocol 1: Preparing a urea stock solution Support Protocol 2: Analyzing urea unfolding curves Basic Protocol 2: Determining the conformational stability of a protein from thermal unfolding curves Support Protocol 3: Analyzing thermal unfolding curves Support Protocol 4: Determining differences in conformational stability for protein variants., (© 2023 Wiley Periodicals LLC.)

ABSTRACT Small and large PEGs greatly increase chemical potentials of globular proteins (μ2), thereby favoring precipitation, crystallization, and protein-protein interactions that reduce water-accessible protein surface and/or protein-PEG excluded volume. To determine individual contributions of PEG-protein chemical and excluded volume interactions to μ2 as functions of PEG molality m3, we analyze published chemical potential increments μ23 = dμ2/dm3 quantifying unfavorable interactions of PEG (PEG200-PEG6000) with BSA and lysozyme. For both proteins, μ23 increases approximately linearly with the number of PEG residues (N3). A 1 molal increase in concentration of PEG -CH2OCH2- groups, for any chain-length PEG, increases μBSA by ∼2.7 kcal/mol and μlysozyme by ∼1.0 kcal/mol. These values are similar to predicted chemical interactions of PEG -CH2OCH2- groups with these protein components (BSA ∼3.3 kcal/mol, lysozyme ∼0.7 kcal/mol), dominated by unfavorable interactions with amide and carboxylate oxygens and counterions. While these chemical effects should be dominant for small PEGs, larger PEGS are expected to exhibit unfavorable excluded volume interactions and reduced chemical interactions because of shielding of PEG residues in PEG flexible coils. We deduce that these excluded volume and chemical shielding contributions largely compensate, explaining why the dependence of μ23 on N3 is similar for both small and large PEGs. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 517-527, 2015. [ABSTRACT FROM AUTHOR]

Background Patients with psoriasis have increased risk of type 2 diabetes. The pathophysiology is largely unknown, but it is hypothesized that systemic inflammation causes insulin resistance. Insulin sensitivity has only been sparsely investigated in patients with psoriasis, and previous studies have used suboptimal methodology. The hyperinsulinemic euglycemic clamp remains the gold standard for quantifying whole-body insulin sensitivity. Objective We sought to investigate if normal glucose-tolerant patients with psoriasis exhibit impaired insulin sensitivity. Methods Three-hour hyperinsulinemic euglycemic clamps were performed in 16 patients with moderate to severe, untreated psoriasis and 16 matched control subjects. Results The 2 groups were similar with regard to age, gender, body mass index, body composition, physical activity, fasting plasma glucose, and glycosylated hemoglobin. Mean ± SEM psoriasis duration was 23 ± 3 years and Psoriasis Area and Severity Index score was 12.7 ± 1.4. Patients with psoriasis exhibited reduced insulin sensitivity compared with control subjects (median M-value 4.5 [range 1.6-14.0] vs 7.4 [range 2.1-10.8] mg/kg/min, P = .046). There were no differences between groups in plasma glucose, insulin, C-peptide, and glucagon during the clamp. Limitations The classic hyperinsulinemic euglycemic clamp technique does not allow assessment of endogenous glucose production. Conclusion Patients with psoriasis were more insulin resistant compared with healthy control subjects. This supports that psoriasis may be a prediabetic condition. [ABSTRACT FROM AUTHOR]

Low temperature cracking is a very serious distress for asphalt pavements built in Northern U.S. and Canada. As temperature rapidly decreases, thermal stresses develop in the restrained asphalt surface layer and, when the temperature reaches a critical value, cracking occurs. A 'simple' solution to overcome this problem is to use a very soft asphalt binder with high relaxation properties, which limits the accumulation of high stress and the formation of cracks. However, these types of binder may lead to significant permanent deformation at high temperature (e.g., rutting) and, therefore, cannot be used for real pavement constructions. In this research, the possibility of obtaining stiffer asphalt binders by adding fine taconite filler available in Minnesota was investigated. Two different types of asphalt binders were selected and from each binder, three different types of asphalt mastics were prepared based on the amount (i.e., level) of taconite particles used as filler: 5%, 10% and 25%. Bending Beam Rheometer (BBR) and Dynamic Shear Rheometer (DSR) tests were performed to evaluate the low and high temperature properties of asphalt binder and corresponding mastics. From these experimental works, creep stiffness, m-value, thermal stress and shear complex modulus were calculated and then graphically and statistically compared. It was observed that asphalt mastic containing 5% taconite filler presents similar properties at low temperature and better performances at high temperature compared to the corresponding asphalt binder. On the other hand, asphalt mastics containing higher amount of taconite fines (10% and 25%) are much more brittle compared to the original binder at low temperature, even though higher rutting resistance was observed at high temperature. [ABSTRACT FROM AUTHOR]

Abstract: Thermal unfolding of ribonuclease A (RNase) was analyzed in various osmolyte solutions of glycine, proline, sarcosine, N,N-dimethylglycine, betaine, myo-inositol, taurine, and trimethylamine-N-oxide (TMAO). All the osmolytes tested stabilized the protein. The thermal unfolding curve was described well by the van't Hoff equation and the melting temperature and the enthalpy of protein unfolding were obtained. The Wyman–Tanford equation, which describes the unfolded-to-folded protein ratio as a function of water activity, was successfully applied to obtain a linear plot. In consideration of this experimentally obtained linearity, the Wyman–Tanford plot could be integrated to calculate the stabilization free energy of the protein (∆∆G) in the solution. The ∆∆G was proved to be described by the property of the microstructure around the protein surface, which is composed of the protein hydration, the cosolute-binding, and the preferential exclusion, and the property of the bulk solution; water activity. The m-values of osmolytes for protein unfolding were obtained from ∆∆G calculated. Among the osmolytes tested, myo-inositol showed the highest m-value. [Copyright &y& Elsevier]

This paper investigates the possibility of developing low temperature limit criteria for asphalt mixtures, similarly to what is currently available in the standard specification for asphalt binder. The investigation is based on extensive experimental work that includes Bending Beam Rheometer (BBR) creep tests on asphalt binders and asphalt mixtures at low temperature and on semi-empirical Hirsch model, and on the rheological model proposed by Christensen, Anderson and Marasteanu (CAM). Limiting asphalt mixture creep stiffness values are predicted from Pressure Aging Vessel (PAV; Long term aging) binder creep stiffness data and are next compared with results available in literature. Then, BBR creep data for Rolling Thin-Film Oven Test (RTFOT; Short term aging) asphalt binder are used to predict creep stiffness of the corresponding short term aged asphalt mixtures. Based on these results, a range of limiting stiffness values is obtained. Due to large variations in the calculated slopes of the mixture creep stiffness curves, a limiting value for the relaxation parameter m-value could not be recommended. [ABSTRACT FROM AUTHOR]

Using recycled materials in pavement applications is a viable option to reduce costs and limit the environmental impact of road construction. During the past decades, many agencies in the U.S. have investigated the effect on pavement performance of adding Reclaimed Asphalt Pavement (RAP), and, more recently, Recycled Asphalt Shingles (RAS) to asphalt mixtures, and limits were proposed on the amount of recycled materials which can be used. This paper investigates the effect of adding both RAP and RAS to virgin asphalt mixtures by means of a simple low temperature creep test performed on asphalt mixture beams. From the experimental work, creep stiffness, m-value, thermal stress and critical cracking temperature are calculated and compared statistically and graphically. Based on the results, it is concluded that most of the mixtures prepared with combinations of RAP and RAS perform similarly to standard mixtures at low temperature. For a limited number of mixtures, a negative effect is observed. [ABSTRACT FROM AUTHOR]

To determine the effects of alcohols on the low-frequency local motions that control slow changes in structural dynamics of native-like compact states of proteins, we have studied the effects of alcohols on structural fluctuation of M80-containing Ω-loop by measuring the rate of thermally driven CO dissociation from a natively folded carbonmonoxycytochrome c under varying concentrations of alcohols (methanol, ethanol, 1-propanol, 2-propanol, 3°-butanol, 2,2,2-trifluoroethanol). As alcohol is increased, the rate coefficient of CO dissociation (kdiss) first decreases in subdenaturing region and then increases on going from subdenaturing to denaturing milieu. This decrease in kdiss is more for 2,2,2-trifluroethanol and 1-propanol and least for methanol, indicating that the first phase of motional constraint is due to the hydrophobicity of alcohols and intramolecular protein cross-linking effect of alcohols, which results in conformational entropy loss of protein. The thermal denaturation midpoint for ferrocytochrome c decreases with increase in alcohol, indicating that alcohol decrease the global stability of protein. The stabilization free energy (ΔΔG) in alcohols’ solution was calculated from the slope of the Wyman–Tanford plot and water activity. The m-values obtained from the slope of ΔΔG versus alcohols plot were found to be more negative for longer and linear chain alcohols, indicating destabilization of proteins by alcohols through disturbance of hydrophobic interactions and hydrogen bonding. [ABSTRACT FROM AUTHOR]

This work identifies the influence of strain rate, temperature, plastic strain, and microstructure on the strain rate sensitivity of automotive sheet steel grades in crash conditions. The strain rate sensitivity m has been determined by means of dynamic tensile tests in the strain rate range 10−3-200 s−1 and in the temperature range 233-373 K. The dynamic flow curves have been tested by means of servohydraulic tensile testing. The strain rate sensitivity decreases with increasing plastic strain due to a gradual exhausting of work hardening potential combined with adiabatic softening effects. The strain rate sensitivity is improved with decreasing temperature and increasing strain rate, according to the thermally activated deformation mechanism. The m-value is reduced with increasing strength level, this decrease being most pronounced for steels with a yield strength below 400 MPa. Solid solution alloying with manganese, silicon, and especially phosphorous elements lowers the strain rate sensitivity significantly. Second phase hardening with bainite and martensite as the second constituent in a ferritic matrix reduces the strain rate sensitivity of automotive sheet steels. A statistical modeling is proposed to correlate the m-value with the corresponding quasistatic tensile flow stress. [ABSTRACT FROM AUTHOR]

Asphalt emulsions are a key material used for pavement preservation. Over time, asphalt concrete pavements become oxidized, which can lead to cracking and other surface deterioration. The addition of pavement maintenance treatments, such as scrub seals, chip seals, or fog seals, can rejuvenate the pavement surface as the asphalt emulsion penetrates the oxidized layer of pavement. However, most existing test methods for asphalt emulsions are empirical in nature and do not directly address field performance. With the aim of improving material characterization and testing so as to better capture field properties, this research explored using a bending beam rheometer (BBR) to measure the stiffness and rate of change of the stiffness (or m-value) of asphalt concrete mixture beams treated with asphalt emulsions. There were three components of this study. First, procedures for fabricating BBR beams from field asphalt concrete samples were developed, as the top portion of pavement is often brittle after field aging and oxidation. It was determined that beams could be successfully fabricated with reasonable geometric variability. Second, asphalt concrete BBR specimens compacted and fabricated in the laboratory were sawn and tested, with and without asphalt emulsion, to determine whether the addition of emulsion could he detected. Third, the same emulsion applied to the laboratory fabricated specimens was applied to field mixes to determine the influence of asphalt emulsion on candidate materials for pavement preservation. Overall, beam fabrication was repeatable, and coefficient of variation values for test results were lower for the laboratory compacted plant mix (10 % to 25 %) than for the field mixtures (9 % to 57 %). Emulsion addition increased the m-value and decreased the stiffness of all pavements, which indicates rejuvenation of the asphalt concrete. BBR mixture beams appear to be able to capture the effect of adding emulsion to both lab produced and field specimens, but more types of emulsions, a more comprehensive conditioning regime, and more asphalt concrete mixtures should be examined in order to determine the effectiveness of the measured performance properties of asphalt concrete with the addition of asphalt emulsion. [ABSTRACT FROM AUTHOR]

Abstract: Artificial neural networks (ANNs) are useful in place of conventional physical models for analyzing complex relationship involving multiple variables and have been successfully used in civil engineering applications. The objective of this study was to develop a series of ANN models to simulate the long-term aging of three asphalt binders (PG 64-22, crumb rubberized asphalt modifier, PG 76-22) regarding seven aging variables such as aging temperature and duration, m-value, mass loss of pressurized aging vessel (PAV) samples, percentages of large and small molecular sizes of high pressure-gel permeation chromatographic (GPC) testing, and binder stiffness. The results indicated that ANN-based models are more effective than the regression models and can easily be implemented in a spreadsheet, thus making it easy to apply. The results also show that the aging temperature, aging duration, percentage of large and small molecular sizes, and binder stiffness are the most important factors in the developed ANN models for prediction of penetration index after a long-term aging process. [Copyright &y& Elsevier]

Abstract: In adaptation biology the discovery of intracellular osmolyte molecules that in some cases reach molar levels, raises questions of how they influence protein thermodynamics. We''ve addressed such questions using the premise that from atomic coordinates, the transfer free energy of a native protein (ΔG tr, N ) can be predicted by summing measured water-to-osmolyte transfer free energies of the protein''s solvent exposed side chain and backbone component parts. ΔG tr, D is predicted using a self avoiding random coil model for the protein, and ΔG tr, D − ΔG tr, N , predicts the m-value, a quantity that measures the osmolyte effect on the N ⇌ D transition. Using literature and newly measured m-values we show 1:1 correspondence between predicted and measured m-values covering a range of 12kcal/mol/M in protein stability for 46 proteins and 9 different osmolytes. Osmolytes present a range of side chain and backbone effects on N and D solubility and protein stability key to their biological roles. [Copyright &y& Elsevier]

Abstract: GuHCl-induced denaturation of human plasma apoA-I, apoA-II, apoA-IV, apoE3 and three recombinant apoE isoforms in solution and discoidal complexes with phosphatidylcholine (only plasma proteins) was studied. The protein conformational stability (ΔG(H2O)) and a slope of linear dependence of free energy of unfolding on GuHCl concentration (m-value) were estimated with the three equilibrium schemes. The data for all proteins, except apoA-II, fit with the three-state model, thus evidencing two-domain structure. The predicted folding rate of the four apoE in solution correlated with conformational stability. The dependence disappeared at the inclusion of apoA-I and apoA-IV into analysis and the m-values, adjusted for residue number in helices (m rh), differed between those for apoE and apoA-I/apoA-IV. However, the m rh-values for six proteins correlated positively with the fractional change in accessible surface area at unfolding for Phe, Lys and Asn, while negatively for Arg, Ala and Gly residues. The difference between the adjusted ΔG rh(H2O) values for apolipoproteins in complexes and in solution decreased at the increase of reduced temperature (T obs − T t)/T t. The induction of intrinsic disorder by arginine residues may be of primary importance in metabolism and function of exchangeable apolipoproteins, while their stability in nascent discoidal HDL is controlled by the physical state of phosphatidylcholine. [Copyright &y& Elsevier]

Small solutes affect protein and nucleic acid processes because of favorable or unfavorable chemical interactions of the solute with the biopolymer surface exposed or buried in the process. Large solutes also exclude volume and affect processes where biopolymer molecularity and/or shape changes. Here, we develop an analysis to separate and interpret or predict excluded volume and chemical effects of a flexible coil polymer on a process. We report a study of the concentration-dependent effects of the full series from monomeric to polymeric PEG on intramolecular hairpin and intermolecular duplex formation by 12-nucleotide DNA strands. We find that chemical effects of PEG on these processes increase in proportion to the product of the amount of DNA surface exposed on melting and the amount of PEG surface that is accessible to this DNA, and these effects are completely described by two interaction terms that quantify the interactions between this DNA surface and PEG end and interior groups. We find that excluded volume effects, once separated from these chemical effects, are quantitatively described by the analytical theory of Hermans, which predicts the excluded volume between a flexible polymer and a rigid molecule. From this analysis, we show that at constant concentration of PEG monomer, increasing PEG size increases the excluded volume effect but decreases the chemical interaction effect, because in a large PEG coil a smaller fraction of the monomers are accessible to the DNA. Volume exclusion by PEG has a much larger effect on intermolecular duplex formation than on intramolecular hairpin formation. [ABSTRACT FROM AUTHOR]

The present investigation deals with the influence of pre-straining with or without bake hardening on the strain rate sensitivity of automotive sheet steels in typical crash conditions. The strain rate sensitivity m has been determined by means of dynamic tensile tests in the strain rate range 0.005-1000 s and in the temperature range 233-373K. A bake hardening heat treatment at 170 °C for 20 min without pre-straining does not influence the m-value in comparison to the base material condition. A small pre-straining near plane strain condition, as commonly found in outer door panels, or a 10% uniaxial, plane strain and biaxial pre-straining, as typically used in formed automotive crash components, without bake hardening does not affect the m-value of sheet steels in comparison to the base material condition. Uniaxial 2% to 10% pre-straining, longitudinal or transverse to rolling direction with subsequent bake hardening, does not clearly change the m-value in comparison to the base material condition either. Small differences in the strain rate sensitivity behaviour are rather attributed to experimental scattering without real physical background. [ABSTRACT FROM AUTHOR]

Abstract: Thermal unfolding of ribonuclease A and α-chymotrypsinogen A was analyzed in various alcohol solutions of methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, tert-butanol, trifluoroethanol, and glycerol. The change in thermal unfolding ratio with temperature was described well by the van''t Hoff equation and the melting temperature and the enthalpy of protein unfolding were obtained. The reciprocal form of the Wyman–Tanford equation, which describes the unfolded-to-folded protein ratio as a function of water activity, was applied to obtain a linear plot. From the slope of this plot and water activity, the stabilization free energy (ΔΔG) in a solution was calculated. This shows an important role of water activity in protein stability. ΔΔG was linearly dependent on alcohol concentration and m-values of alcohols for protein unfolding were obtained. This provides a theoretical basis for the linear extrapolation model (LEM). The m-values for alcohols were negative except for glycerol. The negative higher m-value for longer and linear chain alcohols suggested the important role of the disturbance of hydrophobic interactions as well as the hydrogen-bonding in the mechanism of protein destabilization by alcohols. The number of change in bound-alcohol molecules upon protein unfolding was also obtained. [Copyright &y& Elsevier]

ABSTRACT: Rubberized asphalt has been used to improve the mechanical characteristics (e.g., rutting resistance, fatigue life, friction, and skid resistance) of hot mix asphalt mixtures. The objective of this research was to investigate the rheological characteristics of the rubberized asphalt binders after various long-term aging procedures, using the penetration index, the dynamic shear rheometer, the bending beam rheometer, and high pressure-gel permeation chromatographic testing. The experimental design included the use of three binder sources, three binder grades (PG 64-22, PG 64-22+10 %-40 ambient rubber, and PG 76-22) and three aging states, i.e., virgin, rolling thin film oven, and pressurized aged vessel [four test temperatures (65, 80, 100, and 110°AC) and five aging durations ( 15, 20, 40, 80, and 144 h) under the pressure of 2070 kPa]. The test results show that, as expected, the use of crumb rubber can effectively improve the PG grade and aging resistance of the virgin asphalt binder. A series of rheological properties (e.g., penetration, stiffness, m-value, and percentages of large and small molecular sizes) illustrate that the PG 64-22 binder, mixed with 10 %-40 ambient rubber, yields similar or improved theological properties in comparison with PG 76-22 using 3 % styrene-butadiene-styrene polymer after various long-term aging procedures. [ABSTRACT FROM AUTHOR]

Abstract: An especially fine-grained structure d <10μm is necessary for superplastic forming. Conventional magnesium alloys in cast condition show only a very coarse-grained structure with an average grain size of d >100μm. Yet through overageing and successive warm extrusion moulding a sufficient number of recrystallization nuclei are formed in the magnesium alloys so that during the final recrystallization treatment a very fine microstructure results. It has been shown that the optimal temperature for overageing lies in the range from 300 to 350°C for the magnesium alloys AE42, AZ91, ZRE1 and QE22. Using this temperature range we obtained an average grain size of 6.2μm in the AE42 alloy and 6.4μm in the AZ91 alloy. In the ZRE1 magnesium alloy a grain size of 1.2μm and in the QE22 a grain size of 0.7μm were obtained. The heat-treated magnesium alloys QE22 and ZRE1 investigated here elongate up to 750% and have an m value of 0.75 under a constant strain rate of 3×10−4 s−1 and a deformation temperature of 420°C. Under the same conditions AZ91 und AE42 elongate up to 260% and have m-values of 0.45. [Copyright &y& Elsevier]

Aim As the practice of multiple assessments of glucose concentration throughout the day increases for people with diabetes, there is a need for an assessment of glycaemic control weighted for the clinical risks of both hypoglycaemia and hyperglycaemia. Methods We have developed a methodology to report the degree of risk which a glycaemic profile represents. Fifty diabetes professionals assigned risk values to a range of 40 blood glucose concentrations. Their responses were summarised and a generic function of glycaemic risk was derived. This function was applied to patient glucose profiles to generate an integrated risk score termed the Glycaemic Risk Assessment Diabetes Equation (GRADE). The GRADE score was then reported by use of the mean value and the relative percent contribution to the weighted risk score from the hypoglycaemic, euglycaemic, hyperglycaemic range, respectively, e.g. GRADE (hypoglycaemia%, euglycaemia%, hyperglycaemia%). Results The GRADE scores of indicative glucose profiles were as follows: continuous glucose monitoring profile non-diabetic subjects GRADE = 1.1, Type 1 diabetes continuous glucose monitoring GRADE = 8.09 (20%, 8%, 72%), Type 2 diabetes home blood glucose monitoring GRADE = 9.97 (2%, 7%, 91%). Conclusions The GRADE score of a glucose profile summarises the degree of risk associated with a glucose profile. Values < 5 correspond to euglycaemia. The GRADE score is simple to generate from any blood glucose profile and can be used as an adjunct to HbA1c to report the degree of risk associated with glycaemic variability. [ABSTRACT FROM AUTHOR]

Objective. Semicarbazide‐sensitive amine oxidase (SSAO) is widely expressed in adipose tissue, where it may contribute to stimulation of glucose transport via GLUT4 recruitment. We tested the relationships of soluble SSAO, as reflected by its plasma activity, with insulin sensitivity and indices of body fat, and determined whether insulin is involved in regulating plasma SSAO activity. Material and methods. In 24 non‐diabetic subjects, the relationships of plasma SSAO activity with insulin sensitivity (M‐value and free fatty acid (FFA) suppression during a 3‐h hyperinsulinemic (8.3 µU kg-1 s-1), euglycemic clamp), body mass index (BMI 25.5±3.1 kg m-2), waist‐hip ratio and fat mass were assessed. In 16 subjects, the effect of insulin infusion, administered at a rate of 8.3 µU kg-1 s-1 during 3 h, followed by 3‐h insulin infusion at a high rate of 41.7 µU kg-1 s-1 on plasma SSAO activity was determined. In the other 8 subjects, the response of plasma SSAO activity to 24‐h insulin infused at 8.3 µU kg-1 s-1 was assessed. Results. There were no relationships (all p >0.10) of plasma SSAO activity (215±60 mU L-1) with the M‐value or with any indices of body fat and FFA before and after insulin suppression. Plasma SSAO activity changed by -7.2 (95% CI, -14.5 to +0.2)% after 3 h (NS) and decreased by 10.1 (95% CI, 19.2 to 1)% after 6 h of insulin infusion (p <0.05). Plasma SSAO activity did not significantly change after 8 h (change 0.4 (95% CI, -15.3 to +16.2)%, NS) and after 24 h (change -8.8 (95% CI, -27.4 to +9.7)%, NS) of insulin infusion. Conclusions. It is unlikely that circulating SSAO is a clinically important marker of insulin sensitivity on glucose and fatty acid metabolism. The reduction in plasma SSAO activity in response to pronounced hyperinsulinemia suggests that insulin is involved in the regulation of the soluble form of this enzyme. [ABSTRACT FROM AUTHOR]

Most protein domains are found in multi-domain proteins, yet most studies of protein folding have concentrated on small, single-domain proteins or on isolated domains from larger proteins. Spectrin domains are small (106 amino acid residues), independently folding domains consisting of three long α-helices. They are found in multi-domain proteins with a number of spectrin domains in tandem array. Structural studies have shown that in these arrays the last helix of one domain forms a continuous helix with the first helix of the following domain. It has been demonstrated that a number of spectrin domains are stabilised by their neighbours. Here we investigate the molecular basis for cooperativity between adjacent spectrin domains 16 and 17 from chicken brain α-spectrin (R16 and R17). We show that whereas the proteins unfold as a single cooperative unit at 25°C, cooperativity is lost at higher temperatures and in the presence of stabilising salts. Mutations in the linker region also cause the cooperativity to be lost. However, the cooperativity does not rely on specific interactions in the linker region alone. Most mutations in the R17 domain cause a decrease in cooperativity, whereas proteins with mutations in the R16 domain still fold cooperatively. We propose a mechanism for this behaviour. [Copyright &y& Elsevier]

Analyzing the stability of a multimeric protein is challenging because of the intrinsic difficulty in handling the mathematical model for the folded multimer-unfolded monomer equilibrium. To circumvent this problem, we introduce the concept of effective stability, Δ Geff (= − RTln Keff), where Keff is the equilibrium constant expressed in monomer units. Analysis of the denaturant effect on Δ Geff gives new insight into the stability of multimeric proteins. When a multimeric protein is mostly folded, the dependence of effective stability on denaturant concentration (effective m-value) is simply the m-value of its monomeric unit. However, when the protein is mostly unfolded, its stability depends on denaturant concentration with the m-value of its multimeric form. We also find that the effective m-value at the C m is a good approximation of the apparent m-value determined by fitting the equilibrium unfolding data from multimeric proteins with a two-state monomer model. Moreover, when the m-value of a monomeric unit is estimated from its size, the effective stability of a multimeric protein can be determined simply from C m and this estimated m-value. These simple and intuitive approaches will allow a facile analysis of the stability of multimeric proteins. These analyses are also applicable for high-throughput analysis of protein stability on a proteomic scale. [ABSTRACT FROM AUTHOR]

Three hundred and twenty eight serial measurements of blood glucose (SMBG) performed in a Department of Medicine were rated by 7 experienced diabetes specialists. A statistical study showed considerable variation among the raters. Similarly, the ratings of the 7 physicians relative to the mean rating showed a great deal of individual variation. A highly satisfactory correlation was found between the mean rating of the 7 physicians and the M-value of Schlichtkrull as computed from 7 or 8 samples collected during the day. On the basis of these findings the degree of diabetes control for this population can be judged satisfactory, good or very good when the M-value is ⩽ 10. If the M-value is ⩾ 22, control is poor or very poor and major changes in the treatment program are indicated. Intermediate values, seen in one out of five cases, indicate the need for systematic consultation with a diabetes specialist. [ABSTRACT FROM AUTHOR]