A diminished role for hydrogen bonds in antifreeze protein binding to ice

The most abundant isoform (HPLC-6) of type I antifreeze protein (AFP1) in winter flounder is a 37-amino-acid-long, alanine-rich, alpha-helical peptide, containing four Thr spaced 11 amino acids apart. It is generally assumed that HPLC-6 binds ice through a hydrogen-bonding match between the Thr and neighboring Asx residues to oxygens atoms on the {2021} plane of the ice lattice. The result is a lowering of the nonequilibrium freezing point below the melting point (thermal hysteresis). HPLC-6, and two variants in which the central two Thr were replaced with either Ser or Val, were synthesized. The Ser variant was virtually inactive, while only a minor loss of activity was observed in the Val variant. CD, ultracentrifugation, and NMR studies indicated no significant structural changes or aggregation of the variants compared to HPLC-6. These results call into question the role of hydrogen bonds and suggest a much more significant role for entropic effects and van der Waals interactions in binding AFP to ice.     

The Role of Adsorbate–Adsorbate Interactions in the Rate Controlling Step and the Most Abundant Reaction Intermediate of NH3 Decomposition on Ru

N–N adsorbate–adsorbate interactions on a Ru(0001) surface are first estimated using quantum mechanical density functional theory (DFT) calculations, and subsequently incorporated, for the first time, in a detailed microkinetic model for NH₃ decomposition on Ru using the unity bond index-quadratic exponential potential (UBI–QEP) method. DFT simulations indicate that the cross N–H interactions are relatively small. Microkinetic model predictions are compared to ultra-high vacuum temperature programmed desorption and atmospheric fixed bed reactor data. The microkinetic model with N–N interactions captures the experimental features quantitatively. It is shown that the N–N interactions significantly alter the rate determining step, the most abundant reaction intermediate, and the maximum N*-coverage, compared to mechanisms that ignore adsorbate–adsorbate interactions.     

Measurement and analysis of unbound drug concentrations

The plasma protein binding of drugs has been shown to have significant effects on numerous aspects of clinical pharmacokinetics and pharmacodynamics. In many clinical situations, measurement of the total drug concentration does not provide the needed information concerning the unbound fraction of drug in plasma which is available for distribution, elimination, and pharmacodynamic action. Thus, accurate determination of unbound plasma drug concentrations is essential in the therapeutic monitoring of drugs. Many methodologies are available for determining the extent of plasma protein binding of drugs, however, in the clinical evaluation of drug therapy, equilibrium dialysis and ultrafiltration are the most routinely utilised methods. Both of these methods have been proven to be experimentally sound and to yield adequate protein binding data. Furthermore, the characterisation of the interactions between drug and protein molecules is essential for the assessment of the pharmacokinetic implications of drug-protein binding. Protein binding parameters which characterise the affinity of the drug-protein association, the number of classes of binding sites, the number of binding sites per class or protein and the binding capacity are useful for predicting unbound drug concentrations. Simple graphical methods have often been used to obtain protein binding parameters, but these methods have limitations and are not useful for drugs with more than 1 class of binding site. Therefore, the fitting of protein binding models which characterise the drug-protein binding interaction for experimental data is the preferred method of calculating binding parameters. Using the appropriate model, values for binding parameters are typically estimated by using nonlinear least-squares regression analysis.     

Methane output and lactation response in Holstein cattle with monensin or unsaturated fat added to the diet

We measured effects of continuous vs twice-daily feeding, the addition of unsaturated fat to the diet, and monensin on milk production, milk composition, feed intake, and CO2-methane production in four experiments in a herd of 88 to 109 milking Holsteins. Methane and CO2 production increased with twice-daily feeding, but the CO2:CH4 ratio remained unchanged. Soybean oil did not affect the milkfat percentages, but fatty acid composition was changed. All saturated fatty acids up to and including 16:0 decreased (P < .01), whereas 18:0 and trans 18:1 increased (P < .001). The 18:2 conjugated dienes also increased (P < .01) when the cows were fed soybean oil. Monensin addition to the diet at 24 ppm decreased methane production (P < .01); the CO2:CH4 ratios reached 15, milk production increased (P < .01), and milkfat percentage and total milkfat output decreased (P < .01), as did feed consumption, compared with cows fed diets without monensin (P < .05). Milk fatty acid composition showed evidence of depressed ruminal biohydrogenation: saturated fatty acids (P < .05) decreased and 18:1 increased (P < .001); most of the increase was seen in the trans 18:1 isomer. As with soybean oil feeding, addition of monensin also increased (P < .05) the concentration of conjugated dienes. The monensin feeding trial was repeated 161 d later with 88 cows, of which 67 received monensin in the diet in the first trial and 21 cows were newly freshened and had never received monensin. Methane production again decreased (P < .05), but this time the CO2:CH4 ratio did not change and all other monensin-related effects were absent. The ruminal microflora in the cows that had previously received monensin seemed to have undergone some adaptive changes and no longer responded as before.     

Long-term outcomes in open pelvic fractures

BACKGROUND: Open pelvic fractures represent one of the most devastating injuries in orthopedic trauma. The purpose of this study was to document the injury characteristics, complications, mortality, and long-term, health-related quality of life outcomes in patients with open pelvic fractures. METHODS: The trauma registry at an adult trauma center was used to identify all multiple system blunt trauma patients with a pelvic fracture from January of 1987 to August of 1995 (n = 1,179). Demographic data, mechanism of injury, and fracture type were determined from hospital records. Short-term outcome measures included infectious complications, mortality, and length of stay in hospital. Long-term outcomes of survivors were obtained by telephone interview using the SF-36 Health Survey and the Functional Independence Measure. RESULTS: Open pelvic fractures were uncommon, occurring in 44 patients (4%). Patients with open fractures were about 9 years younger, on average, than patients with closed fractures (30 vs. 39, p < 0.001). Similarly, patients with open fractures were more likely to be male (75 vs. 57%, p < 0.02), more likely to have been involved in a motorcycle crash (27 vs. 6%, p < 0.001), and more likely to have an unstable pelvic ring disruption (45 vs. 25%, p < 0.001). Open pelvic fracture patients required more blood than closed pelvic fracture patients, both in the first day (16 vs. 4 units, p < 0.001) and during the total hospital admission (29 vs. 9 units, p < 0.001). Five patients with perineal wounds did not receive a diverting colostomy; in turn, these individuals had a total of six pelvic infectious complications (one abscess, two with osteomyelitis, and three perineal wound infections). Overall, 11 patients died, six patients were lost to follow-up, and 27 were long-term survivors (mean duration of 4 years). Chronic disability was common after a pelvic fracture, with problems related to physical role performance and physical functioning, and was particularly severe after an open pelvic fracture (p < 0.05 for both as measured by the SF-36). CONCLUSIONS: Patients with open pelvic fractures often survive, need to be treated with massive blood transfusions, and often require a colostomy. They are frequently left with chronic pain and residual disabilities in physical functioning and physical roles, and many remain unemployed years after injury.     

用输入滤波器防止仪表放大器射频整流误差

仪表放大器用于需要从大共模噪声或干扰中提取微弱差分信号的各种设备.但是,设计师常常会忽视仪表放大器内存在的潜在射频整流问题.放大器的共模抑制通常能大大减小仪表放大器输入端的共模噪声.但遗憾的是,射频整流仍然会发生,这是因为即使最好的仪表放大器在频率高于20kHz时实际上也不能抑制共模噪声.放大器的输入级可能会对强信号进行整流,然后以直流偏移误差的形式出现.     

Outcomes of hand surgery. British Society for Surgery of the Hand

The findings are presented of a conference on Outcomes of Hand Surgery organized by the audit committee of British Society for Surgery of the Hand in 1993. Measures of outcome in terms of movement, power, sensibility, pain, activities of daily living, complications and patient satisfaction are considered, and an example of a patient evaluation measure given as an appendix.     

A cone-and-plate device for the investigation of platelet biomaterial interactions

As part of a class action suit, the author was asked to assess the quality of mental health services in eight prisons in Georgia. This paper describes the background to the suit, reviews selected literature on assessing quality of correctional mental health care, and describes methods used to survey prison mental health services. A standardized survey instrument was developed with probe questions to assess the quality of services. Individual cases were reviewed, inmates were interviewed, and the quality of mental health structures, processes, and outcomes were assessed. Key findings from the survey are summarized. The author concluded that the quality of mental health services in the prisons surveyed was so low overall as to constitute a pattern of deliberate indifference, and that the services were constitutionally inadequate.