Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.     

Power-dependent dispersion in far-off-resonant raman scattering

We investigate the saturation effects of power broadening, Stark shifting, and population transfer on Stokes conversion in stimulated Raman scattering. We do not make the usual rotating wave approximation because the detuning from the next electronic state is assumed to be in the optical regime. Retaining the counter-rotating terms allows an exact determination of the pump and Stokes indexes of refraction. Steady-state solutions for the Stokes intensity and phase are obtained and the effects of making the rotating wave approximation (RWA) are discussed. Finally, we examine the behavior of these solutions for Stokes conversion in hydrogen gas when geometric propagation is appropriate.     

Integrating trust into the CyberCraft Initiative via the Trust Vectors model [Application Notes]

This research supports the hypothesis that the Trust Vector model can be modified to fit the CyberCraft Initiative, and that there are limits to the utility of historical data. This research proposed some modifications and expansions to the Trust Model Vector, and identified areas for future research.     

Evaluation of the antireflux mechanism following laparoscopic fundoplication

BACKGROUND: Laparoscopic Nissen fundoplication is an effective procedure for the treatment of gastro-oesophageal reflux disease (GORD), but the underlying motility mechanisms that explain the success of this operation remain unclear. METHODS: Twenty patients with a history of GORD underwent stationary oesophageal manometry and prolonged ambulatory pH monitoring, both before and 3 months after fundoplication. RESULTS: Eighteen patients were completely cured of reflux symptoms and stopped all antireflux medication after operation. After fundoplication there was a significant increase (P < 0.01) in median resting lower oesophageal sphincter (LOS) pressure and length. Median residual LOS pressure during swallow-induced LOS relaxation also increased significantly after operation (P < 0.01). The number of reflux episodes decreased from a median of 48 to 3 after fundoplication (P < 0.01). The time at pH less than 4 decreased from 5.7 to 0 per cent in the supine position (P < 0.01), and from 9.8 to 0.2 per cent while upright (P < 0.001). CONCLUSION: Early subjective results at 3 months following laparoscopic antireflux surgery show improved symptoms. One of the mechanisms underlying the antireflux action of fundoplication is an increase in median residual LOS pressure at the gastro-oesophageal junction. This may be a purely mechanical effect of the fundic wrap extrinsic to the LOS.     

Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia

Infants with congenital diaphragmatic hernia (DH) and profound pulmonary hypoplasia are currently unsalvageable. The authors previously demonstrated that tracheal ligation (TL) accelerates fetal lung growth and reverses the pulmonary hypoplasia of fetal nephrectomy. The purpose of this study was to determine if the pulmonary hypoplasia of experimental DH could be similarly reversed and, if so, whether the resulting lungs would show better function than those of their DH counterparts. Eighteen fetal lambs were divided into three experimental groups of six animals each. In group 1, DH was created at 90 days' gestation. In group 2, DH was created at 90 days' gestation and TL performed during the same operation. Group 3 consisted of sham-operated controls. These animals were delivered near full-term, and their lungs analyzed by standard morphometric techniques. Ten additional fetal lambs were divided into two experimental groups of five animals each. In group 4, DH was created at 90 days' gestation. In group 5, DH was created at 90 days' gestation and TL performed 20 days later, at 110 days' gestation. These animals were pressure-ventilated via tracheostomy over a 2-hour period in which PaO2, PaCO2, and compliance were measured. Intratracheal pressure (ITP) was measured at the time of delivery in all groups. Upon retrieval, DH animals had abdominal viscera in the chest and small lungs; in contrast, DH/TL animals had the herniated viscera reduced from the chest by enlarged lungs. DH/TL lungs showed markedly increased growth, with significant increases in lung volume:body weight ratio (LV:BW; P = .0001), alveolar surface area (ALV.SA; P = .0001), and alveolar number (ALV#) (P = .0001) when compared with those of the DH or control group. This growth was associated with a normal maturation pattern based on histological appearance, normal airspace fraction, and normal alveolar numerical density. ITP in the DH/TL group was increased when compared with that of DH and control animals (P = .0001). Total lung DNA and protein were both elevated in the DH/TL animals (P = .0001). However, the DNA:protein ratio remained normal, suggesting lung growth had occurred through cell proliferation, not by hypertrophy. When ventilated over a range of settings, DH/TL lungs were more compliant (P = .0001) and achieved higher PaO2s (P < .003) and lower PaCO2s (P = .0001) than their DH counterparts. From these data, the authors conclude: (1) Experimental fetal DH produces hypoplastic lungs that are not capable of adequate gas exchange with conventional ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Generativity and social motives in young adults.

Different forms of generativity in the writings of E. H. Erikson (1950/1963) and J. Kotre (1984) were related to agentic and communal motives in a sample of young adults (M?=?28 yrs old). For women, the power motive related to parenting, whereas the achievement motive was associated with forms of generative expression outside of the household. The opposite pattern of achievement and power motive relationships was found for men, although in a weaker form. The affiliation–intimacy motive, on the other hand, related both to women's parenting and societal concerns. Differences in expectations and opportunities for young men and women may account for these gender differences. The results for women support D. P. McAdams's (1988) suggestions that agency and communion are important for understanding generativity. In addition, the results provide evidence that people begin to grapple with generative issues as young adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Two-dimensional singular vector elements for finite-elementanalysis

The finite-element method (FEM) exhibits a reduced convergence rate when used for the analysis of geometries containing sharp edges where the electromagnetic field is singular. The convergence of the method can be-improved by introducing singular elements that model analytically predicted singular behavior. A number of authors have developed singular elements that are compatible with the scalar FEM. In this paper, we propose a new singular element that is compatible with edge-based vector finite elements and can cope with any order of singularity while preserving the sparsity of the FEM equations. Edge-based singular elements more correctly model singular fields and thus require fewer unknowns, while avoiding the introduction of spurious modes in the numerical solution. Numerical results verify that the convergence of the FEM is significantly improved     

Experimental evaluation of velocity and power estimation forultrasound blood flow imaging, by means of a two-dimensionalautocorrelation approach

This paper evaluates experimentally the performance of a novel axial velocity estimator, the 2D autocorrelator, and its Doppler power estimation counterpart, the 2D zero-lag autocorrelator, in the context of ultrasound color flow mapping. The evaluation also encompasses the well-established 1D autocorrelation technique for velocity estimation and its corresponding power estimator (1D zero-lag autocorrelator), to allow performance comparisons under identical conditions. Clutter-suppressed in vitro data sets from a steady-flow system are used to document the effect of the range gate and ensemble length, noise level and angle of insonation on the precision of the velocity estimates. The same data sets are used to examine issues related to the estimation of the Doppler signal's power. The first-order statistics of power estimates from regions corresponding to flow and noise are determined experimentally and the ability of power-based thresholding to separate flow signals from noise is characterized by means of ROC analysis. In summary, the results of the in vitro evaluation show that the proposed 2D-autocorrelation form of processing is consistently better than the corresponding 1D-autocorrelation techniques, in terms of both velocity and power estimation. Therefore, given their relatively modest implementation requirements, the 2D-autocorrelation algorithms for velocity and power estimation appear to represent a superior, yet realistic, alternative to conventional Doppler processing for color flow mapping