Protein modification by a Maillard reaction intermediate methylglyoxal. Immunochemical detection of fluorescent 5-methylimidazolone derivatives in vivo

Methylglyoxal (MG), an endogenous metabolite that increases in diabetes, is a common intermediate in nonenzymatic glycation (Maillard reaction) in vivo. Here we describe the immunochemical approach to the detection of MG adducts in proteins in vitro and in atherosclerotic lesions of human aorta in vivo. The reaction of protein (bovine serum albumin) with MG led to selective loss of arginine and lysine residues, accompanied by the formation of 5-methylimidazolone (N delta-(5-methylimidazolon-2-yl)ornithine) and imidazolysine (1,3-di-lysino-4-methylimidazole) derivatives, respectively. The anti-5-methylimidazolone antibody was prepared by immunizing rabbits with a MG-keyhole limpet hemocyanin conjugate and purifying the serum on an affinity gel prepared by covalent attachment of the 5-methylimidazolone derivative. The antibody cross-reacted with the proteins treated with not only MG but trioses, such as hydroxyacetone, dihydroxyacetone, and glyceraldehyde. The immunohistochemical analysis revealed that atherosclerotic lesions of human aorta contained 5-methylimidazolone derivatives whose distributions were identical to those of advanced glycation end products (AGEs) detected by the anti-AGE antibody.     

Maximum likelihood analysis of algorithms and data structures

We present a new approach for an average-case analysis of algorithms and data structures that supports a non-uniform distribution of the inputs and is based on the maximum likelihood training of stochastic grammars. The approach is exemplified by an analysis of the expected size of binary tries as well as by three sorting algorithms and it is compared to the known results that were obtained by traditional techniques. Investigating traditional settings like the random permutation model, we rediscover well-known results formerly derived by pure analytic methods; changing to biased data yields original results. All but one step of our analysis can be automated on top of a computer-algebra system. Thus our new approach can reduce the effort required for an average-case analysis, allowing for the consideration of realistic input distributions with unknown distribution functions at the same time. As a by-product, our approach yields an easy way to generate random combinatorial objects according to various probability distributions.     

System specification experiments on a common benchmark

To contribute to the current effort toward the definition of a system-level design language, this article proposes a benchmark for system specification. The authors analyze the results of experiments using the benchmark with several languages     

Influence on Diamonds During the Spraying of Diamond-Bronze Abrasive Coatings

Detonation spraying provides the opportunity to produce diamond grinding tools for the machining of stone, cement, and concrete. Especially the atmospheric conditions of the spraying process yield in a high production flexibility. However, during detonation spraying, the oxygenic atmosphere as well as the thermal and kinetic energy have an impact on the processed diamond. Despite its importance for the tools’ performance, the influence of the spraying process on the superabrasive diamond is predominantly unknown. The potential decrease of the diamond durability and strength due to degradation effects during the production of sprayed diamond-CuSn 85/15 composites has not yet been determined. X-ray diffraction and Raman spectroscopy were used to verify thermally initiated surface reactions of the sprayed diamonds after exposure to the spraying process. Additionally, reference measurements on the degradation of diamonds in oxidizing and inert conditions were carried out to compare the spraying results. Differential thermal and thermogravimetric analyses were employed. To validate the mechanical properties of the diamond superabrasives, friability tests and fracture force tests were performed. It was found that under optimized detonation spraying conditions the thermal and mechanical impact remains low enough to ensure a good reliability of the processed diamonds. The diamond crystal structure endured the spraying process without detectable graphitization or oxidation. Deterioration indicators were not observed in SEM micrographs, x-ray diffraction patterns or Raman spectra. Furthermore, a high durability and strength of the sprayed diamonds were confirmed by mechanical testing.     

Effect of sex-sorted sperm dosage on conception rates in Holstein heifers and lactating cows

Ejaculates were collected by artificial vagina from 3 Holstein sires and sorted to 90% purity for X-chromosome-bearing spermatozoa (range 88 to 93%) using flow cytometry. Sorted sperm were diluted to 2.1, 3.5, or 5.0 × 10⁶ sperm per dose in an egg yolk (20%), Tris, glycerol (7%) extender. Collections were repeated until >600 straws per sperm dose per sire were obtained. Each sperm dose was loaded into color-coded 0.25-mL French straws, with alternate colors used to define treatments across sires. Within sires, straws were packaged at 9 per cane (3 of each color) and strategically allocated to 75 Holstein herds with targets for 50% use in heifers and 50% in lactating cows. Straw color was recorded in the on-farm record-keeping system at the time of insemination. Data were analyzed separately for cows and heifers. Among heifers, a total of 2,125 usable records were retrieved from 51 herds (238 ± 5.5 services/ sperm dose per sire, range: 218 to 263). Conception rates in heifers were influenced by the sire × sperm dosage interaction. Within sire A, conception rates of heifers were greater for the 5 × 10⁶ (59.5%) than for the 2.1 × 10⁶ (46.4%) sperm dose and intermediate for the 3.5 × 10⁶ sperm dose (52.2%). However, across sires, sperm dosage had no effect on heifer conception rates (46.7, 51.2, and 52.5% for the 2.1, 3.5, and 5.0 × 10⁶ sperm dosages, respectively). Among cows, a total of 2,369 services were retrieved from 56 herds (263 ± 8.8 services/sperm dose per sire, range: 233 to 303). Conception rates of cows (29.4%) were not affected by sire or sperm dosage (27.0, 29.1, and 30.3% for the 2.1, 3.5, and 5.0 × 10⁶ sperm dosages, respectively). In conclusion, these data indicate that an increased sperm dosage may enhance virgin heifer conception rates for some (but not all) sires, whereas neither sire nor sexed-sperm dosage affected conception rates of lactating cows. Additional studies of sexed-sperm dosage across a larger sampling of bulls are warranted to determine whether and how such a practice can be implemented cost effectively for the benefit of the dairy industry.     

Expert system for evaluation of reproductive performance and management.

A microcomputer expert system for dairy herd reproductive management was developed using an expert system shell and Turbo Pascal. The expert system initially examines the broad areas of days open, days to first breeding, detection of estrus, and conception rate to determine whether a problem exists. Interpretations ranging from "excellent" to "severe" were established for each trait. The system then selects an area for evaluation that has the largest negative influence on days open. Once an area has been selected for further evaluation, the expert system utilizes information from the user and DHI reports developed by the Dairy Records Processing Center in Raleigh, NC. These reports identify problems with conception categorized by production, parity, service number, days in milk, breed, and service sire. In addition, questions are presented by the expert system to isolate problems of accuracy of data, use of natural service, semen handling, AI technique, detection of estrus, signs of estrus, and other management areas. Recommendations and suggestions are given. Ten commercial herds having a conception rate less than 40% were evaluated by the expert system and by an extension reproduction specialist who supplied information for the system. Of 100 areas investigated, the expert system and extension specialist identified 47 as potential problem areas, agreeing on 85% of them. Most discrepancies resulted from the specialist applying a less restrictive standard when values were close to a preselected threshold.     

Percutaneous bile duct drainage; experiences with a new type of endoprosthesis]

Self expandable stents were placed percutaneously in 105 patients with malignant biliary obstruction. Stent diameter was 1 cm; length, 3.5-10.5 cm. Of the 60 patients with common bile duct obstruction, 50 died 0.2-12 months (median 3 months) after stent insertion. Two patients developed recurrent jaundice and cholangitis after 6 and 12 months, respectively. One patient underwent reintervention. Ten patients, one after a successful reintervention, were alive without jaundice 1-8 months (median 5 months) after stent placement. Of the 45 patients with hilar lesions, 26 died 0.7-18 months (median 5 months) after stent placement, five of them with signs of cholangitis. Nineteen are alive 1-21 months (median 7 months) afterwards. Reinterventions were carried out in 13 patients (29%). The most common cause of stent malfunction was tumour overgrowth. Stent-related complications were seen in three patients.     

Primary lung cancer in patients under 40 years of age

There seems to be a resistance of patients and physicians towards aggressive diagnostic evaluation of the symptoms of lung cancer in young people. We here review nine series of young patients with primary lung cancer. Patients below 40 years of age represent between 1.2 and 5% of the total lung cancer population. The distribution of sex and histopathologic findings is different, there being more women, fewer cases of squamous cell and more cases of small anaplastic and adenocarcinoma in the young group. Between 87 and 96% are smokers. There is a delay from the debut of symptoms to the first contact with a general physician of 2.4 to 10.8 months. There is a wide variation concerning tendency to operate with a frequency of curative resection of between 15 and 57%. Based on the survival of young patients who are treated by curative surgical resection, the outcome of surgical treatment for young patients does not differ from the general experience concerning resection in patients of all ages. Young patients who are found inoperable have worse survival than the older patients. Seventy to 90%, more than in the group of patients of all ages, have stadium II or III at the time of diagnosis. In conclusion, physicians should be aggressive with respect to the diagnostic evaluation even of young patients with symptoms suggestive of lung cancer.     

Pregnancy rates after timed AI of heifers following removal of intravaginal progesterone inserts

Reproductive performance of dairy heifers was compared for each of 2 synchronization protocols: The first group of 54 heifers was synchronized using intravaginal progesterone inserts (CIDR) plus estradiol cypionate (ECP) on d 0, PGF(2alpha) on d 7, and ECP again on d 8 (CIDR-ECP); a second group of 56 heifers was synchronized using CIDR and ECP on d 0, PGF(2alpha) on d 7, and GnRH on d 9 (CIDR-GnRH). All heifers received timed artificial insemination (TAI) at 48, 56, or 72 h after CIDR removal on d 7. Pregnancy diagnosis was conducted by ultrasonography 32 +/- 1 d post AI to confirm pregnancy and at 60 +/- 1 d post AI to determine embryo survival. Ovaries were monitored by ultrasonography daily from d 0 to 7 and twice daily from d 8 to ovulation to examine emergence of a new wave of follicles, size of the ovulatory follicle, and timing of ovulation on 15 heifers per protocol. New follicular development was detected 3.7 +/- 0.2 d after CIDR insertion. Heifers receiving CIDR-ECP had a shorter interval from CIDR removal to ovulation than heifers receiving CIDR-GnRH (63.8 +/- 3.0 vs. 71.6 +/- 2.3 h, respectively); however, ovulation occurred 39.8 +/- 3.0 h after ECP or 23.6 +/- 2.3 h after GnRH. Diameters of ovulatory follicles did not differ between treatments. Overall pregnancy rate for synchronized heifers was 60.1%, and embryo survival was 98%. Pregnancy rate for heifers synchronized with CIDR-ECP was 63.0% and similar to that in heifers synchronized with CIDR-GnRH (57.1%). Pregnancy rate was affected by time of AI for heifers synchronized using CIDR-ECP but not for those synchronized with CIDR-GnRH. Heifers in the CIDR-ECP group that were inseminated 56 h after CIDR removal had a higher pregnancy rate (81.0%) compared with heifers inseminated 48 (66.7%) or 72 h (50.0%) after CIDR removal. Either ECP or GnRH used in a CIDR-based TAI program in dairy heifers can achieve acceptable reproductive performance.