A self-adaptive mesh refinement technique for boundary element solution of the Laplace equation.

A self-adaptive mesh refinement technique is developed for boundary element solutions of the two-dimensional Laplace equation. The method is based on error reduction and applied on the element and global level to estimate the error associated with each mesh. This adaptive technique is then utilized to analyze problems with and without singularities. Results employing constant two-dimensional boundary elements are presented.     

Ultrafine particle concentrations and exposures in seven residences in northern California

Human exposures to ultrafine particles (UFP) are poorly characterized given the potential associated health risks. Residences are important sites of exposure. To characterize residential exposures to UFP in some circumstances and to investigate governing factors, seven single-family houses in California were studied during 2007-2009. During multiday periods, time-resolved particle number concentrations were monitored indoors and outdoors and information was acquired concerning occupancy, source-related activities, and building operation. On average, occupants were home for 70% of their time. The geometric mean time-average residential exposure concentration for 21 study subjects was 14,500 particles per cm(3) (GSD = 1.8; arithmetic mean ± standard deviation = 17,000 ± 10,300 particles per cm(3)). The average contribution to residential exposures from indoor episodic sources was 150% of the contribution from particles of outdoor origin. Unvented natural-gas pilot lights contributed up to 19% to exposure for the two households where present. Episodic indoor source activities, most notably cooking, caused the highest peak exposures and most of the variation in exposure among houses. Owing to the importance of indoor sources and variations in the infiltration factor, residential exposure to UFP cannot be characterized by ambient measurements alone. PRACTICAL IMPLICATIONS: Indoor and outdoor sources each contribute to residential ultrafine particle (UFP) concentrations and exposures. Under the conditions investigated, peak exposure concentrations indoors were associated with cooking, using candles, or the use of a furnace. Active particle removal systems can mitigate exposure by reducing the persistence of particles indoors. Eliminating the use of unvented gas pilot lights on cooking appliances could also be beneficial. The study results indicate that characterization of human exposure to UFP, an air pollutant of emerging public health concern, cannot be accomplished without a good understanding of conditions inside residences.     

A multiplicative model of software defect repair times

We hypothesize that software defect repair times can be characterized by the Laplace Transform of the Lognormal (LTLN) distribution. This hypothesis is rooted in the observation that software defect repair times are influenced by the multiplicative interplay of several factors, and the lognormal distribution is a natural choice to model rates of occurrence of such phenomenon. Conversion of the lognormal rate distribution to an occurrence time distribution yields the LTLN. We analyzed a total of more than 10,000 software defect repair times collected over nine products at Cisco Systems to confirm our LTLN hypothesis. Our results also demonstrate that the LTLN distribution provides a statistically better fit to the observed repair times than either of the two most widely used repair time distributions, namely, the lognormal and the exponential. Moreover, we show that the repair times of subsets of defects, partitioned according to the Orthogonal Defect Classification (ODC) scheme also follow the LTLN distribution. Finally, we describe how the insights that lead to the LTLN repair time model allow us to consider and evaluate alternative process improvement strategies.     

Evaluation of rib steak colour from Friesian, Hereford and Charolais heifers pastured or overwintered prior to slaughter

Heifers (n=10) were randomly selected from the slaughter line of a local factory each month for a period of 21 months. Rib steak (sampled at the 10th rib) from the left side of each carcass was taken for analysis. The cattle breeds selected during this study were Friesian, Hereford and Charolais. The mean weight of the left side for all carcasses was 146.6 (S.E.M.= 1.0kg). Graded carcasses selected for sampling during this trial were classified using the EUROP scale and the specific heifer grades chosen were factory grades EO4L and EO4H. Initial Hunter 'a' values (on the day of arrival in the laboratory) of rib steak from heifers finished between November and March (overwintered) were significantly (P<0.001) higher than Hunter 'a' values from heifers finished between April and October (pastured). After storage at 4?°C under simulated retail display conditions for 6 days, the Hunter 'a' values for overwintered samples were also significantly (P<0.001) greater than those for pastured samples. Breed also had an effect on the colour of the meat. After storage for 6 days, Hunter 'a' values of rib steak from Charolais were significantly (P<0.05) higher than either Friesian or Hereford. Pastured heifers had significantly (P<0.05) higher levels of the monounsaturated fatty acid C16.1 in the total lipid fraction of rib steak (neutral and polar) than samples taken from overwintered heifers. Pastured heifers had significantly (P<0.01) higher levels of the polyunsaturated fatty acid (PUFA) C18.3 in the phospholipid fraction than those from overwintered cattle. However, Hereford had significantly (P<0.05) higher levels of C14.0, C16.1 and C18.0 in the phospholipid fraction than those found in Friesian and Charolais. The level of α-tocopherol in the muscle was not affected by either pasturing/overwintering or breed. However, Continental breeds had significantly (P<0.05) higher levels of α-tocopherol in adipose tissue than Friesian.     

Effects of LHRH-analogues on mitogenic signal transduction in cancer cells

The expression of luteinizing hormone-releasing hormone (LHRH) and its receptors has been demonstrated in a number of human malignant tumors, including cancers of the breast, ovary, endometrium and prostate. These findings suggest the presence of an autocrine regulatory system based on LHRH. Recent studies in our laboratory have demonstrated that the function of LHRH produced by ovarian cancer cells is the inhibition of their proliferation. Dose-dependent antiproliferative effects of LHRH-agonists have been observed by several laboratories in cell lines derived from the above cancers. Interestingly, also LHRH-antagonists have marked antiproliferative activity in most of the ovarian, breast and endometrial cancer cell lines tested so far, indicating that the dichotomy of LHRH-agonists/LHRH-antagonists is not valid for the LHRH-system in cancer cells. In addition, our data suggest that the classical LHRH receptor signal transduction mechanisms known from the pituitary (phospholipase-C, protein kinase C, adenylyl cyclase) are not involved in the mediation of LHRH effects in cancer cells. Data obtained by several groups, including ours, rather suggest that LHRH analogs interfere with the signal transduction of growth-factor receptors and related oncogene products associated with tyrosine-kinase activity. The mechanism of action is probably an LHRH-induced activation of a phosphotyrosine phosphatase, counteracting the effects of receptor associated tyrosine kinase. In our hands, LHRH analogs virtually blocked the EGF-induced MAP-kinase activity of ovarian and endometrial cancer cells. The pharmacological exploitation of this mechanism might provide promising new therapies for these cancers.     

Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentrations: a randomized controlled trial in humans

Isoflavonoids are a class of flavonoids that are derived in the human diet mainly from soybean-based foods. The major dietary isoflavonoids, genistein and daidzein, have estrogen-like activity and are classed as phytoestrogens. Because estrogens can lower serum LDL cholesterol and raise HDL cholesterol, the objective of this study was to determine if isoflavonoids could improve serum lipids in healthy subjects. Forty-six men and 13 postmenopausal women not receiving hormone replacement therapy completed a randomized, double-blind, placebo-controlled trial of two-way parallel design and 8 wk duration. One tablet containing 55 mg of isoflavonoids (predominantly in the form of genistein) or one placebo tablet was taken daily with the evening meal. Subjects maintained their usual diet and physical activity, which were unchanged throughout the intervention. Measurement of isoflavonoids and their metabolites in 24-h urine samples provided an assessment of compliance and of isoflavonoid metabolism. Serum total, LDL, HDL and HDL subclass cholesterol, triglycerides and lipoprotein (a) were assessed at baseline and during the last week of intervention. After adjustment for baseline values, no significant differences in postintervention serum lipid and lipoprotein (a) concentrations between groups were identified. Further adjustment for age, gender and weight change did not alter the results. In addition, changes in urinary isoflavonoids were not significantly correlated with changes in serum lipids and lipoprotein (a). Therefore, this study does not support the hypothesis that isoflavonoid phytoestrogens can improve the serum lipids, at least in subjects with average serum cholesterol concentrations.     

DNA polymerase fidelity: from genetics toward a biochemical understanding

This review summarizes mutagenesis studies, emphasizing the use of bacteriophage T4 mutator and antimutator strains. Early genetic studies on T4 identified mutator and antimutator variants of DNA polymerase that, in turn, stimulated the development of model systems for the study of DNA polymerase fidelity in vitro. Later enzymatic studies using purified T4 mutator and antimutator polymerases were essential in elucidating mechanisms of base selection and exonuclease proofreading. In both cases, the base analogue 2-aminopurine (2AP) proved tremendously useful-first as a mutagen in vivo and then as a probe of DNA polymerase fidelity in vitro. Investigations into mechanisms of DNA polymerase fidelity inspired theoretical models that, in turn, called for kinetic and thermodynamic analyses. Thus, the field of DNA synthesis fidelity has grown from many directions: genetics, enzymology, kinetics, physical biochemistry, and thermodynamics, and today the interplay continues. The relative contributions of hydrogen bonding and base stacking to the accuracy of DNA synthesis are beginning to be deciphered. For the future, the main challenges lie in understanding the origins of mutational hot and cold spots.     

Relative resistance of striatal neurons containing calbindin or parvalbumin to quinolinic acid-mediated excitotoxicity compared to other striatal neuron types

To evaluate the relative ability of those striatal neuron types containing calbindin or parvalbumin to withstand a Ca(2+)-mediated excitotoxic insult, we injected the NMDA receptor-specific excitotoxin quinolinic acid (QA) into the striatum in mature adult rats and 2 months later examined the relative survival of striatal interneurons rich in parvalbumin and striatal projection neurons rich in calbindin. To provide standardization to the survival of striatal neuron types thought to be poor in Ca2+ buffering proteins, the survival was compared to that of somatostatin-neuropeptide Y (SS/NPY)-containing interneurons and enkephalinergic projection neurons, which are devoid of or relatively poorer in such proteins. The various neuron types were identified by immunohistochemical labeling for these type-specific markers and their relative survival was compared at each of a series of increasing distances from the injection center. In brief, we found that parvalbuminergic, calbindinergic, and enkephalinergic neurons all showed a generally comparable gradient of neuronal loss, except just outside the lesion center, where calbindin-rich neurons showed significantly enhanced survival. In contrast, striatal SS/NPY interneurons were more vulnerable to QA than any of these three other types. These observed patterns of survival following intrastriatal QA injection suggest that calbindin and parvalbumin content does not by itself determine the vulnerability of striatal neurons to QA-mediated excitotoxicity in mature adult rats. For example, parvalbuminergic striatal interneurons were not impervious to QA, while cholinergic striatal interneurons are highly resistant and SS/NPY+ striatal interneurons are highly vulnerable. Both cholinergic and SS/NPY+ interneurons are devoid of any known calcium buffering protein. Similarly, calbindin does not prevent striatal projection neuron vulnerability to QA excitotoxicity. Nonetheless, our data do suggest that calbindin may offer striatal neurons some protection against moderate excitotoxic insults, and this may explain the reportedly slightly greater vulnerability of striatal neurons that are poor in calbindin to ischemia and Huntington's disease.