A study of the molecular sources of nonideal osmotic pressure of bovine serum albumin solutions as a function of pH

The nonideal osmotic pressure of bovine serum albumin (BSA) solutions was studied extensively by Scatchard and colleagues. The extent of pH- and salt-dependent nonideality changes are large and unexplained. In 1992, Fullerton et al. derived new empirical expressions to describe solution nonideal colligative properties including osmotic pressure (Fullerton et al. 1992. Biochem. Cell Biol. 70:1325–1331). These expressions are based on the concepts of volume occupancy and hydration force. Nonideality is accurately described by a solute/solvent interaction parameter I and an "effective" osmotic molecular weight Ae. This paper uses the interaction-corrected nonideal expressions for osmotic pressure to calculate the hydration I values and "effective" osmotic molecular weight of BSA, Ae, as a function of pH. Both factors vary in a predictable manner due to denaturing of the BSA molecule. Both contribute to an increase in osmotic pressure for the same protein concentration as the solution pH moves away from the isoelectric point. Increased nonideality is caused by larger hydration resulting from larger solvent-accessible surface areas and by the decrease in "effective" osmotic molecular weight, Ae, due to segmental motion of denatured (filamentous) molecules

Targeted protein delivery: carbodiimide crosslinking influences protein release from microparticles incorporated within collagen scaffolds

open access articleTissue engineering response may be tailored via controlled, sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional (3D) ice-templated collagen scaffolds. However, the effects of covalent crosslinking during scaffold preparation on the availability and release of protein from the incorporated microparticles have not been explored. Here, we load 3D ice-templated collagen scaffolds with controlled additions of poly-(DL-lactide-co-glycolide) microparticles. We probe the effects of subsequent N-(3-dimethylaminopropyl)- N0-ethylcarbodiimide hydrochloride crosslinking on protein release, using microparticles with different internal protein distributions. Fluorescein isothiocyanate labelled bovine serum albumin is used as a model protein drug. The scaffolds display a homogeneous microparticle distribution, and a reduction in pore size and percolation diameter with increased microparticle addition, although these values did not fall below those reported as necessary for cell invasion. The protein distribution within the microparticles, near the surface or more deeply located within the microparticles, was important in determining the release profile and effect of crosslinking, as the surface was affected by the carbodiimide crosslinking reaction applied to the scaffold. Crosslinking of microparticles with a high proportion of protein at the surface caused both a reduction and delay in protein release. Protein located within the bulk of the microparticles, was protected from the crosslinking reaction and no delay in the overall release profile was seen

A structural decomposition-based diagnosis method for dynamic process systems using HAZID information

A novel diagnosis method is proposed in this paper that uses the results of the blended HAZID analysis extended to the dynamic case of process systems controlled by operational procedures. The algorithm is capable of finding fault root causes in process systems using nominal and observed possible faulty operational procedure execution traces. The algorithm uses the structural decomposition of the process system and its component-level dynamic HAZID (P-HAZID) tables and executes the diagnosis component-wise by first decomposing the observed execution traces, and then assembling the diagnosis results. The exact structure of the algorithm is also discussed, followed by two case studies on which its operation is demonstrated. © 2014 Elsevier Ltd

Risk-based systems analysis for emerging technologies: Applications of a technology risk assessment model to public decision making

The risk-based systems analysis model was designed to establish funding priorities among competing technologies for tank waste remediation. The model addresses a gap in the Department of Energy`s (DOE`s) ``toolkit`` for establishing funding priorities among emerging technologies by providing disciplined risk and cost assessments of candidate technologies within the context of a complete remediation system. The model is comprised of a risk and cost assessment and a decision interface. The former assesses the potential reductions in risk and cost offered by new technology relative to the baseline risk and cost of an entire system. The latter places this critical information in context of other values articulated by decision makers and stakeholders in the DOE system. The risk assessment portion of the model is demonstrated for two candidate technologies for tank waste retrieval (arm-based mechanical retrieval -- the ``long reach arm``) and subsurface barriers (close-coupled chemical barriers). Relative changes from the base case in cost and risk are presented for these two technologies to illustrate how the model works. The model and associated software build on previous work performed for DOE`s Office of Technology Development and the former Underground Storage Tank Integrated Demonstration, and complement a decision making tool presented at Waste Management 1994 for integrating technical judgements and non-technical (stakeholder) values when making technology funding decisions

Cartilage-specific ablation of XBP1 signaling in mouse results in a chondrodysplasia characterized by reduced chondrocyte proliferation and delayed cartilage maturation and mineralization

SummaryObjectiveTo investigate the in vivo role of the IRE1/XBP1 unfolded protein response (UPR) signaling pathway in cartilage.DesignXbp1flox/flox.Col2a1-Cre mice (Xbp1CartΔEx2), in which XBP1 activity is ablated specifically from cartilage, were analyzed histomorphometrically by Alizarin red/Alcian blue skeletal preparations and X-rays to examine overall bone growth, histological stains to measure growth plate zone length, chondrocyte organization, and mineralization, and immunofluorescence for collagen II, collagen X, and IHH. Bromodeoxyuridine (BrdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses were used to measure chondrocyte proliferation and cell death, respectively. Chondrocyte cultures and microdissected growth plate zones were analyzed for expression profiling of chondrocyte proliferation or endoplasmic reticulum (ER) stress markers by Quantitative PCR (qPCR), and of Xbp1 mRNA splicing by RT-PCR to monitor IRE1 activation.ResultsXbp1CartΔEx2 displayed a chondrodysplasia involving dysregulated chondrocyte proliferation, growth plate hypertrophic zone shortening, and IRE1 hyperactivation in chondrocytes. Deposition of collagens II and X in the Xbp1CartΔEx2 growth plate cartilage indicated that XBP1 is not required for matrix protein deposition or chondrocyte hypertrophy. Analyses of mid-gestation long bones revealed delayed ossification in Xbp1CartΔEx2 embryos. The rate of chondrocyte cell death was not significantly altered, and only minimal alterations in the expression of key markers of chondrocyte proliferation were observed in the Xbp1CartΔEx2 growth plate. IRE1 hyperactivation occurred in Xbp1CartΔEx2 chondrocytes but was not sufficient to induce regulated IRE1-dependent decay (RIDD) or a classical UPR.ConclusionOur work suggests roles for XBP1 in regulating chondrocyte proliferation and the timing of mineralization during endochondral ossification, findings which have implications for both skeletal development and disease

School-level determinants of incidence of sports-related concussion: Findings from the CARE Consortium

OBJECTIVE: Epidemiologic research on sports-related concussion (SRC) has focused on individual risk factors, with limited research on institutional risk factors and variability in concussion rates. METHODS: This study used data from 53,822 athletes-seasons collected at 30 United States sites (26 civilian institutions and 4 military service academies), from 2014/15 to 2018/19 academic years, by the Concussion Assessment, Research, and Education Consortium. School-level risk factors included competitive division (DI, DII, DIII), school type (military/civilian) and a Sport Risk Index (SRI; Low, Medium, High). For comparability between civilian institutions and military academies, only NCAA athletes and concussions in sports games and practices were included. Random intercepts log-binomial regression was used to estimate Risk Ratios (RRs) and model variability in SRC risk. RESULTS: A total of 2,503 SRCs were observed during the study period, including 829 competition SRCs (33%) and 1,674 practice SRCs (67%). Most variability in SRC risk was at the level of athlete or team (within-school), rather than at the school-level. Specifically, across the three SRC outcomes (all [competition and practice combined], competition-only, and practice-only), within-school variability was 5 to 7 times greater than between-school variability. Three school-level risk factors (Division, School Type, and SRI) accounted for over one-third (36%) of between-school variability. SRI was the strongest school-level predictor of SRC risk (RR = 5.7; 95%CI: 4.2, 7.6 for High vs. Low). SRC risk was higher for Division I compared to Divisions II/III (RR = 1.6; 95%CI: 0.9, 2.9 for DI vs. DIII), and military academies had a moderately elevated risk of SRC (RR = 1.4; 95%CI: 0.7, 2.7). CONCLUSION: A large portion of the apparent variability between schools was attributable to structural factors (sport risk and competitive level), suggesting that there were minimal systemic differences in concussion identification between schools. While most variability is within-school, understanding school-level determinants of concussion risk may still be important in providing the implementation science context for individual-level interventions

Cash by any other name? Evidence on labeling from the UK Winter Fuel Payment

Government transfers to individuals are often given labels indicating that they are designed to support the consumption of particular goods. Standard economic theory implies that the labeling of cash transfers or cash-equivalents should have no effect on spending patterns. We study the UK Winter Fuel Payment, a cash transfer to older households. Our empirical strategy nests a regression discontinuity design within an Engel curve framework. We find robust evidence of a behavioral effect of labeling. On average households spend 47% of the WFP on fuel. If the payment were treated as cash, we would expect households to spend 3% of the payment on fuel. © 2014 Elsevier B.V

Predicting the Amplitude of a Solar Cycle Using the North-South Asymmetry in the Previous Cycle: II. An Improved Prediction for Solar Cycle~24

Recently, using Greenwich and Solar Optical Observing Network sunspot group data during the period 1874-2006, (Javaraiah, MNRAS, 377, L34, 2007: Paper I), has found that: (1) the sum of the areas of the sunspot groups in 0-10 deg latitude interval of the Sun's northern hemisphere and in the time-interval of -1.35 year to +2.15 year from the time of the preceding minimum of a solar cycle n correlates well (corr. coeff. r=0.947) with the amplitude (maximum of the smoothed monthly sunspot number) of the next cycle n+1. (2) The sum of the areas of the spot groups in 0-10 deg latitude interval of the southern hemisphere and in the time-interval of 1.0 year to 1.75 year just after the time of the maximum of the cycle n correlates very well (r=0.966) with the amplitude of cycle n+1. Using these relations, (1) and (2), the values 112 + or - 13 and 74 + or -10, respectively, were predicted in Paper I for the amplitude of the upcoming cycle 24. Here we found that in case of (1), the north-south asymmetry in the area sum of a cycle n also has a relationship, say (3), with the amplitude of cycle n+1, which is similar to (1) but more statistically significant (r=0.968) like (2). By using (3) it is possible to predict the amplitude of a cycle with a better accuracy by about 13 years in advance, and we get 103 + or -10 for the amplitude of the upcoming cycle 24. However, we found a similar but a more statistically significant (r=0.983) relationship, say (4), by using the sum of the area sum used in (2) and the north-south difference used in (3). By using (4) it is possible to predict the amplitude of a cycle by about 9 years in advance with a high accuracy and we get 87 + or - 7 for the amplitude of cycle 24.Comment: 21 pages, 7 figures, Published in Solar Physics 252, 419-439 (2008

Low-value clinical practices in injury care: a scoping review and expert consultation survey

BACKGROUND: Tests and treatments that are not supported by evidence and could expose patients to unnecessary harm, referred to here as low-value clinical practices, consume up to 30% of healthcare resources. Choosing Wisely and other organisations have published lists of clinical practices to be avoided. However, few apply to injury and most are based uniquely on expert consensus. We aimed to identify low-value clinical practices in acute injury care. METHODS: We conducted a scoping review targeting articles, reviews and guidelines that identified low-value clinical practices specific to injury populations. Thirty-six experts rated clinical practices on a 5-point Likert scale from clearly low-value to clearly beneficial. Clinical practices reported as low-value by at least one level I, II or III study and considered clearly or potentially low-value by at least 75% of experts were retained as candidates for low-value injury care. RESULTS: Of 50,695 citations, 815 studies were included and led to the identification of 150 clinical practices. Of these 63 were considered candidates for low-value injury care; 33 in the emergency room, 9 in trauma surgery, 15 in the intensive care unit and 5 in orthopaedics. We also identified 87 'grey zone' practices, which did not meet our criteria for low-value care. CONCLUSIONS: We identified 63 low-value clinical practices in acute injury care that are supported by empirical evidence and expert opinion. Conditional on future research, they represent potential targets for guidelines, overuse metrics and de-implementation interventions. We also identified 87 'grey zone' practices, which may be interesting targets for value-based decision-making. Our study represents an important step towards the de-implementation of low-value clinical practices in injury care. LEVEL OF EVIDENCE: III