A fast and inexpensive method for N-terminal fluorescein-labeling of peptides

AIMS: The pharmacokinetics of intramuscular artemether and its major plasma metabolite-dihydroartemisinin, were investigated in patients with severe manifestations of falciparum malaria. METHODS: Six severe falciparum malaria patients with acute renal failure (ARF) and 11 without ARF were recruited into the study. They were treated with intramuscular artemether at a loading dose of 160 mg, followed by daily doses of 80 mg for another 6 days (total dose 640 mg). RESULTS: Patients with and without ARF showed a good initial response to treatment; the parasite and fever clearance times were 66(30-164) and 76(36-140) h [median(range)], respectively. None had reappearance of parasitaemia in their peripheral blood smear within 7 days of initiation of treatment. In comatose patients, the time to recovery of consciousness was 51.6(22-144) h. Artemether was detected in plasma as early as 1 h after a 160 mg dose, and declined to undetectable levels within 24 h in most cases. Patients with ARF had significantly higher Cmax [2.38(1.89-3.95) vs 1.56(1.05-3.38) ng ml(-1) mg(-1) dose], AUC [35.4(22-52.9) vs 25.2(13.4-52.9) ng ml(-1) h mg(-1) dose], and lower Vz/F [5.45(3.2-6.9) vs 8.6(4.2-12.3) l kg(-1)] and CL/F [7.4(5.4-13.8) vs 19.1(8.5-25.1) ml min(-1) kg(-1)] when compared with those without ARF. In addition, t1/2,z was significantly longer in ARF patients [7.0(5.5-10.0) vs 5.7(4.2-6.6) h]. The pharmacokinetics of dihydroartemisinin in the two groups of patients were comparable. CONCLUSIONS: ARF significantly modified the pharmacokinetics of intramuscular artemether. The changes could be attributed to either improved absorption/bioavailability, a reduction of systemic clearance, or a change in plasma protein binding of the drug.     

Shrinkage and splitting of microcracks under pressure simulated by the finite-element method

The two-dimensional finite-element method is applied to analyze the shrinkage and splitting of microcracks regularly arranged on or perpendicular to a grain boundary under pressure. Grain-boundary and surface diffusions are coupled by the boundary conditions at the triple point of the microcrack surface and the grain boundary. The shrinkage and splitting processes for the two kinds of microcracks are revealed by detailed finite-element analyses. For the microcrack lying on a grain boundary, it first shrinks to a small void shape, then the void is split by the grain boundary and the two split voids assume a cylindrical shape under the capillary force of the surface. For the microcrack perpendicular to the grain boundary, it is split into two segments by the grain boundary during the early stage of shrinkage. Then, the split microcracks stop shrinking and evolve into two cylindrical channels with a circular section by the capillary force of the surface. These evolution processes are controlled by the applied pressure, microcrack spacing, ratio of grain-boundary diffusion to surface diffusion, and equilibrium dihedral angle, defined by surface and grain-boundary tensions. The influences of these controlled parameters on the evolution processes are numerically clarified based on a great number of finite-element analyses.     

Modification of method for determination of medium-molecular peptides and its application in pediatric surgery

Taking into account clinical significance of determination of medium-molecular peptides' concentration in various surgical diseases and limitation of blood sampling in children, modification of the method for determination of medium-molecular peptides in blood serum is proposed, which requires 0.1 ml of serum and is based on deproteinization of cooled ethanol followed by spectrophotometry of peptide solution at 210 nm. Comparison study of the results of examination by this method and routine one was carried out. Specificity and advantages of the suggested modification are discussed.     

Thiazolidine formation as a general and site-specific conjugation method for synthetic peptides and proteins

Interleukin-6 is a multifunctional cytokine important for host defense. Macrophages are potent producers of interleukin-6. Conversely, interleukin-6 acts on monocytes to induce their differentiation to macrophages. This paper reviews the in vivo roles of interleukin-6 and nuclear factor for interleukin-6 expression that have been revealed by gene targeting as well as recent progress in understanding the interleukin-6 gene regulation and signaling pathway in macrophages.     

异原子配位结构碳基单原子电催化剂结构与性能相关性的研究进展

单原子催化剂（SACs）由于其原子利用率高、活性中心明确、比活性高和稳定性强等优点,在催化电解水领域具有独特的优势. 然而,材料中的金属−载体相互作用对催化过程具有重大影响. 首先,本文明确了单原子催化剂的特点并研究了其电子结构和构效关系方面独特优势. 其次综述了氧化物载体在稳定金属单原子、分散活性物种、调节中心电子结构、吸附和活化反应物等方面的重要作用;并详细分析了载体如何通过结构缺陷、表面基团、空间限域和晶格作用等实现对金属原子的负载和稳定. 然后,通过实例对比了单原子在不同氧化物载体上配位结合方式,以及在析氢、析氧和全水解反应中的性能差异. 最后,对利用载体与单原子相互作用调节催化剂性能的机遇和挑战、关键问题和可能的解决方案进行了展望.

     

Use of a fluorescent method for detection of lymphocyte Fc-receptors]

Studies in both the human and ovine near-term fetus have identified the clustering of physiologic and behavioral parameters into states. In a recent study in the human fetus a considerable decrease was found in fetal urine production during non-rapid eye movement (non-REM) compared with REM sleep. Whether this decrease was caused by decreased renal blood flow or changes in urine concentration is not known. This prompted us to investigate the relation between fetal urine production rate and electrocortical activity in the near-term ovine fetus. We hypothesized that in the ovine fetus urine production and renal blood flow during REM [comparable to low voltage electrocortical activity (LV ECoG)] would be lower than during non-REM [(high voltage (HV) ECoG)]. In eight fetal sheep between 123 and 127 d of gestation (term 147 d), ECoG, renal blood flow, urine flow, and urine osmolality were measured continuously for 6 h on 2 consecutive days. Data were analyzed into HV ECoG and LV ECoG whereafter urine flow, urine osmolality, and renal blood flow data were averaged per state. We found no significant differences in urine flow, urine osmolality, or renal blood flow between the two behavioral states in the ovine fetus. Because these data are in sharp contrast to those found in the human fetus, we conclude that the observed dissimilarities in renal responses between the human and sheep fetus add to the already known differences in behavioral states between the two species.     

Quantitation of methionyl peptides in nanomole quantities by a fluorometric method

A quantitative and highly specific method to determine low concentrations of methionyl peptides, which do not contain tryptophan or cysteine residues, has been developed. The method is based on the stoichiometry and selectivity of N-chlorosuccinimide (NCS) towards methionine and N-acetyltryptophan. N-Chlorosuccinimide reacts with N-acetyltryptophan in a 1:1 ratio to produce the N-acetyl-2-oxindolealanine--a derivative essentially devoid of fluorescence. The decrease in fluorescence intensity is approximately linear with respect to the NCS concentration. Preincubation of NCS with methionine or methionyl peptide consumes a stoichiometric amount of the reagent and the unreacted NCS is quantitated by the decrease in fluorescence intensity resulting upon incubation of the mixture with 1 eq of N-acetyltryptophan. Less than 1 nmol of methionyl peptide can be accurately quantitated by this method.     

Use of conformationally constrained peptides for a topographical analysis of the combing site of a monoclonal anti-substance P antibody

We studied the trends from 1969 to the mid-1980s in the incidence and mortality of acute myocardial infarction and stroke in Swedish women residing in the Uppsala Health Care Region. We used data from the Inpatient Care and Causes of Death registers to obtain total first event incidence and mortality rates. In our population, there were 20,182 acute myocardial infarctions and 30,462 stroke events, and 17,359 and 21,336 deaths, respectively. We found an average overall annual increase of 1.3% in the age-standardized incidence of acute myocardial infarction during the 1970s, followed by decreasing rates during the early 1980s. Mortality was virtually unchanged. Notably, among women 45-49 years of age, we observed a rising trend during the whole period, whereas in the oldest age groups, the increase slowed and reversed in the latter years. Both the incidence and mortality for stroke declined steadily: the age-standardized incidence fell by an average of 2.1% per year for all stroke and 7.8% for intracerebral hemorrhage. The falling rate of stroke was best explained by birth cohort effects, with a 30% reduction in women born in 1920 and later as compared with those born in 1890. We conclude that important changes in Swedish women's cardiovascular health have taken place and that increasing cigarette smoking and hypertensive treatment are major determinants.     

Use of conductivity method for online measurement of alkalinity of caustic washing liquid

In this paper,the online measurement of the alkalinity of caustic washing liquid by the conductivity method was discussed,and a working curve of the conductivity vs.alkalinity was established,for which the correlation coefficient is 0.9979 (n=7 ).The influence of the temperature of the caustic washing liquid and the presence of coexisting ions,such as iron and oil,on the accuracy of the conductivity method was discussed.The temperature is compensated for by establishing the correlation between conductivity and temperature.When the iron concentration is≤1000 mg/L,and the oil concentration is ≤1000 mg/L,the deviation in the results obtained using the conductivity and titration methods is≤2.5 g/L.The t-test results show that there is no systematic devia-tion between the conductivity and titration methods.The conductivity method has the advantages of a fast response and good real-time performance,which meet the requirements for the online determination of the alkalinity of caustic washing liquid.     

Use of a finite element method to calculate roll profiles for broad-strip mills

A model is proposed to calculate the polishing profiling of rolls in broad-strip mills using a finite element method, and it is applied to develop new roll profiles. The finite element method is used to determine the polishing profiling of a roll with a complex shape, which substantially decreases the nonuniformity of reduction and drawing over the strip width. This profiling can be executed on numerical control roll grinders.     

Use of capillary electrophoresis as a method development tool for classical gel electrophoresis

Capillary electrophoresis (CE) was used to optimize the buffer pH, ionic strength and sulfated cyclodextrin concentrations for enantiomeric separation of piperoxan. These enantioseparation conditions were then applied to a classical gel electrophoresis system. Binding constants of the sulfated beta-cyclodextrin-piperoxan couple were approximated using CE and the effects of organic solvents on the system were also investigated.     

Use of a correlational method to estimate a listener's weighting function for speech

The purpose of this study was to determine if it is feasible to use the correlational method (Lutfi, 1995; Richards and Zhu, 1994) to estimate how listeners use or weight the information contained within various frequency bands of speech. Three naturally spoken vowel-consonant-vowel (VCV) syllables (/aba/, /aga/, and /ada/) were presented monaurally to listeners. Each of the VCV waveforms were filtered into three separate frequency bands (i.e., low, mid, and high). Each band was then independently and randomly degraded at various signal-to-noise (S/N) levels (-7, -5, -3, -1, or +1). On each trial, listeners were asked to identify the VCV that was presented to them. For each trial, the S/N level of each frequency band, the stimulus that was presented, and the listener's responses were all recorded and stored in a file. From this trial-by-trial data, a point biserial correlation was computed between the listener's response (correct or incorrect identification) and the degradation within each frequency band. The stronger the correlation, the greater influence that given frequency band had on the listener's performance on the task. From these relations it was shown that it is possible to obtain a listener's weighting function for speech. Results showed that although most listeners weighted the mid-frequency band the greatest, several of the listeners used different weighting strategies to perform the task. Several methodological issues are discussed in regard to improving the future application of the correlational method to speech.     

Recent advances in molecular recognition and signal transduction of active peptides: receptors for opioid peptides

1. Opioid peptides are a family of structurally related neuromodulators which play a major role in the control of nociceptive pathways. These peptides act through membrane receptors of the nervous system, defined as mu, delta and kappa and endowed with overlapping but distinct pharmacological, anatomical and functional properties. 2. Recent cloning of an opioid receptor gene family has opened the way to the use of recombinant DNA technology at the receptor level. 3. This review focuses on the molecular cloning and functional characterization of opioid receptors and provides first insights into molecular aspects of opioid peptide recognition and signal transduction mechanisms, using the cloned receptors as investigation tools.     

Use of an on-line computer for psychophysical testing with the up-and-down method.

Employed an IBM 1620, Model 1 computer associated with a 1710 control system for psychophysical testing. The test operations are divided into (a) acceptance of test parameters, (b) test programing, (c) stimulus presentation, (d) record keeping, (e) rest scheduling, (f) calculation, and (g) test termination. The computer was found to be versatile and flexible. "In the case of the up-and-down method with complementary concurrent series a good estimate exists for the standard error of the estimate of P.50. The on-line computer can use intertrial or interblock times to keep estimates of P.50 and its standard error up to date and terminate testing when the desired level of precision of measurement" is reached. (19 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthetic peptides for diagnostic use

Interdisciplinary teaching rounds were initiated on a general surgery service at a university teaching hospital. These rounds were designed to promote more efficient patient care by providing an opportunity for enhanced communication among health-care professionals. Improved collaboration is a prerequisite for implementation of critical paths and case management. The authors describe their methods of rounds development and the impact of the rounds on patient outcomes.     

A novel derivatization method with 5-bromonicotinic acid N-hydroxysuccinimide for determination of the amino acid sequences of peptides

We have developed a novel method that effectively identifies the N-terminal product ions produced in the tandem mass spectrometry (MS/MS) analysis of peptides done in conjunction with the specific derivatization of the N-terminal amino group using 5-bromonicotinic acid N-hydroxysuccinimide ester (BrNA-NHS). Electrospray ionization with low-energy collision-induced dissociation (CID) MS/MS clearly differentiated the N-terminal product ions labeled with the 5-bromonicotinyl group from other ions, on the basis of the appearance of CID peaks with a doublet pattern characteristically separated by 2 mass units produced by the equal natural abundances of 79Br and 81Br. The tracing of a series of these bromine-containing product ions allows the easy amino acid sequencing of peptides. Using Gln-Arg-Leu-Gln-Ser-Asn-Gln-Leu-Lys as the test peptide, we found that within 30 minutes at pH 6.5 and 37 degrees C its alpha-amino group was completely acylated with BrNA-NHS (peptide: BrNA-NHS = 1:40; mol/mol). The epsilon-amino group of the C-terminal lysine residue was less likely to be acylated under these conditions, being only partly modified (about 20%). This suggests the possibility of keeping the epsilon-amino group free from acylation. The method was successfully applied to the determination of the amino acid sequences of peptides from porcine kidney aminoacylase I produced by digestion with lysyl endopeptidase and with Staphylococus aureus V8 protease.