cssi/SciSciGPT-SciSciNet huggingface dataset:
The in vivo pharmacological profile of eletriptan (UK-116,044): a potent and novel 5-HT1B/1D receptor agonist

The anti-migraine drug, eletriptan [(R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]-1 H-indole; UK-116,044], is a novel 5-HT(1B/1D) receptor agonist. In this paper, the regional vasoconstrictor profile of eletriptan, in comparison with sumatriptan, was examined in the anaesthetised dog. The inhibitory actions of eletriptan on neurogenic inflammation in rat dura mater were also assessed. In the anaesthetised dog, eletriptan (1-1000 microg kg(-1) i.v.) produced a dose-dependent reduction of carotid arterial blood flow with a similar potency and maximum effect to sumatriptan (ED(50) values: eletriptan and sumatriptan, 12 and 9 microg kg(-1), i.v., respectively). However, eletriptan exhibited a significantly lower potency than sumatriptan in reducing coronary artery diameter (ED(50) values: 63 and 19 microg kg(-1), i.v., respectively, P<0.05). In the femoral circulation, sumatriptan caused a significant reduction in arterial blood flow (ED(50) 35 microg kg(-1) i.v.) whereas eletriptan (1-1000 microg kg(-1) i.v.) had no significant effect upon femoral arterial blood flow when compared to vehicle-treated animals. In rats, eletriptan (30-300 microg kg(-1) i.v.) administered prior to electrical stimulation of the trigeminal ganglion produced a dose-related and complete inhibition of plasma protein extravasation in the dura mater (mean extravasation ratio: control 1.9; eletriptan 1.0, minimum effective dose 100 microg kg(-1), P<0.05). The potency and maximum effect of eletriptan was identical to that of sumatriptan in this model. When administered during a period of continual stimulation of the trigeminal nerve, eletriptan (100 microg kg(-1) i.v.) produced a complete inhibition of plasma protein extravasation. The ability to reduce canine carotid arterial blood flow and inhibit neurogenic inflammation in rat dura mater suggests that vascular and neurogenic mechanisms may contribute to eletriptan's clinical efficacy in migraine patients. In addition, eletriptan exhibits some selectivity for reducing carotid arterial blood flow when compared with femoral arterial blood flow and coronary artery diameter, in the anaesthetised dog.
β-Aspartylhydroxamic acid: Its action as a feedback inhibitor and a represser of asparagine synthetase in Lactobacillus arabinosus

Abstract β-Aspartylhydroxamic acid (BAH) has been found to mimic asparagine in cells of Lactobacillus arabinosus 17-5 by inhibiting asparagine synthetase activity and repressing the formation of the same enzyme. The action of BAH is apparently specific, since the compound does not inhibit the formation of the repressible glutamine synthetase of L. arabinosus . Further, extracts of the organism catalyze a BAH-dependent and an asparagine-dependent ATP-PP i exchange, and evidence is given which indicates that only one enzyme activity is involved with both the BAH and asparagine activations. This latter finding is in agreement with the hypothesis that certain amino acids which repress biosynthetic enzyme formation must be capable of being activated and transferred to an appropriate tRNA molecule. However, enzymatic transfer of BAH to tRNA has not been demonstrated in this study.
Estimate of fusion through bose degeneracy

An estimate is made of the fusion probability for an aggregate of D2 molecules that have suffered bose degeneracy. A WKB analysis for the tunneling of deuterons through the electron intermolecular barrier gives the penetration rate $$R = (2E/h)\exp \left[ { - \frac{8}{3}\sqrt {\frac{{2mV_0 x_0^2 }}{\hbar }} \left( {1 - \frac{E}{{V_0 }}} \right)^{3/2} } \right]$$ In this expression,V0 andx0 are the potential barrier height and width, respectively, andE is the zero point energy of a deuteron in its ground molecular state. With molecules assumed effectively to be adjacent in the bose condensate, the number of fusion events per mole is found to be vanishingly small.
Lactosylceramidase assays for diagnosis of globoid cell leukodystrophy and Gmi-gangliosidosis

Abstract An assay procedure was developed for accurate estimation of lactosylceramidase II in the presence of relatively high activity of lactosylceramidase I. The procedure involves determination of lactosylceramide-cleaving activities under two different assay conditions, and lactosylceramidase II activity is calculated by the difference. Applicability of the procedure was evaluated with separated soluble fractions of the two β-galactosidases from normal human brains, and with whole homogenates of gray and white matter, liver and cultured fibroblasts from control individuals and from patients with globoid cell leukodystrophy or G M1 -gangliosidosis. The use of the lactosylceramidase I assay procedure developed by Wenger, D.A., Sattler, M., Clark, C. and McKelvey, H. ((1974) Clin. Chim. Acta 56, 199–206) and of the present procedure permits accurate diagnosis of both globoid cell leukodystrophy and G M1 -gangliosidosis with one natural substrate, lactosylceramide, irrespective of the relative proportion of the two β-galactosidases in the tissue.
Blind study on the relations between the extent of coronary arteriosclerosis and the strength of the myocardial contraction as measured by invasive and noninvasive tests

Abstract Invasive tests based on cardiac catheterization, and noninvasive tests based on the ballistocardiogram (Bcg) and pulse derivative (PD), were performed within a few days of each other on 76 cardiac patients. To eliminate those who reacted emotionally to the invasive test, only those whose pulse rates and systolic blood pressures were reasonably similar in the two tests were admitted to this study. Two methods of detecting excitement during catheterization were devised and tried, the first more rigorous than the second. The first method identified over one half of our subjects as excited during catheterization; after these had been eliminated, 29 stable subjects remained who had withstood the rigors of catheterization without excitement detectable by our methods. In these 29 stable patients, each of 13 items of physiological interest measured during the noninvasive test, and each of 14 measured during the invasive test, were correlated with all the others by means of a computer, a total of 351 correlations. In these stable subjects, four items measured at the noninvasive test correlated significantly with the amount of coronary sclerosis rated by angiogram: and pulse pressure × mean pressure. In four other items significance was missed by a narrow margin. Correlations between the coronary rating and physiological measurements made at the invasive test, such as stroke volume, cardiac output, ejection fraction, ejection velocity, and LV enddiastolic pressure, were very poor and did not approach significance. In cases of coronary heart disease the cardiac strength/coronary sclerosis relationship is strong in both the stable group and in those excited during catheterization. But the same relation does not hold in cases of valvular heart disease. Mathematically, the product Bcg amp/ BSA × mean blood pressure is proportionally related to the first time derivative of cardiac power. Using data secured several years ago, 10 when systoles differing in strength were simulated in cadaver experiments, the formula's product was also found to be strongly correlated with both cardiac work and power. So, our data indicate that, as coronary obstruction increases, the strength of the resting cardiac contraction diminishes. Our data have important diagnostic implications; if the heart of any patient is beating strongly , the presence of severe coronary heart disease can be ruled out. But if the heart is beating weakly , the presence of significant coronary heart disease cannot be safely inferred, for coronary heart disease is only one of many causes of cardiac weakness.
Should I Stay or Should I Go? Examining the Career Choices of Alternatively Licensed Teachers in Urban Schools

In order to address the issue of persistent teacher shortages, urban districts increasingly rely on alternatively licensed teachers who are often viewed as well-suited to work in urban areas because of their greater age, life and work experiences, and understanding of diverse communities. Yet, research on the retention of these teachers remains inconclusive, with some notable studies suggesting that alternatively licensed teachers are as likely as their traditionally prepared counterparts to quit teaching or migrate out of urban school settings. In this study, we explore the process and salient considerations of five alternatively licensed math and science teachers deciding whether or not to continue teaching in a Midwestern, urban school district. Whereas previous studies typically examine teacher recruitment and retention issues through a narrow analysis of labor market incentives and other external inducements, our study situates teachers’ career decisions within a more holistic narrative that illustrates how individual actions are never determined by any single factor, but rather a web of simultaneous and sometimes contradictory forces generated by prior expectations and immediate realities that are professional as well as personal in nature.
MicroRNAs Both Promote and Antagonize Longevity in C. elegans

Summary Background Aging is under genetic control in C. elegans , but the mechanisms of life-span regulation are not completely known. MicroRNAs (miRNAs) regulate various aspects of development and metabolism, and one miRNA has been previously implicated in life span. Results Here we show that multiple miRNAs change expression in C. elegans aging, including novel miRNAs, and that mutations in several of the most upregulated miRNAs lead to life-span defects. Some act to promote normal life span and stress resistance, whereas others inhibit these phenomena. We find that these miRNAs genetically interact with genes in the DNA damage checkpoint response pathway and in the insulin signaling pathway. Conclusions Our findings reveal that miRNAs both positively and negatively influence life span. Because several miRNAs upregulated during aging regulate genes in conserved pathways of aging and thereby influence life span in C. elegans , we propose that miRNAs may play important roles in stress response and aging of more complex organisms.
Wideband optical propagation measurement system for characterization of indoor optical wireless channels

The main objective of the presented research is to characterize an indoor wireless optical communication channel. Until recently, there have not been any comprehensive published measurements results presenting characteristics of this channel for high data rates, e. g. 1Gbit/s. To this end, a measurement setup is implemented, with a high-power laser diode acting as the optical transmitter and an avalanche photodiode acting as the receiver. Using a network analyzer, the laser is modulated by CW frequencies up to 1 GHz, which is the bandwidth of the receiver, as limited by the intrinsic capacitance and the response-time of the avalanche photodiode. A single collimated optical spot with a small elliptical shape on the ceiling is tested. The impacts of receiver orientation and configuration on the channel frequency response are investigated. These measurements will enable us to explore the possibility of higher data transmission rates, potentially beyond 1 Gbps, on indoor optical wireless channels. These channels can be a viable alternative to inherently insecure and interference-prone RF wireless channels, and therefore, could be the basis of next-generation high data rate wireless local area networks.
Why did the chicken cross the road? … To get the antibiotics*

Abstract [Talan DA, Moran GJ. Why did the chicken cross the road? … to get the antibiotics. Ann Emerg Med. October 2000;36:353-355.]
The ritual of corruption

J. McIver Weatherford. Tribes on the Hill. Rawson, Wade Publishers, Inc. 1981. xii + 300 pp. $12.95
The Influence of Communal vs. Individual Learning Context on the Academic Performance in Social Studies of Grade 4-5 African-Americans.

Empirical research utilizing the communal learning construct suggests that culturally-informed pedagogy enhances academic performance for African-American children. The present investigation examined the effect of culturally-informed learning contexts on recall performance in geography lessons. The sample consisted of 69 African-American Grade 4–5 public school students. Weeks 1 and 2 consisted of both learning and testing phases. Week 3 consisted only of a testing phase. Analyses of variance techniques revealed that, overall, subjects in the communal learning context performed significantly better on each of the two weekly quizzes and on the comprehensive examination than those in the individual learning context. Limitations of the findings and future research directions are discussed.
Cadherin-mediated cellular signaling

Recent cadherin studies focusing on cellular signaling have shown that several pathways are activated by cadherin-mediated cell-cell contact. Cadherin-mediated contacts activate Rho family GTPases, regulate the availability of beta-catenin to participate in Wnt signaling, and function in receptor tyrosine kinase signaling. Although different classical cadherins bind to the same cytosolic proteins via their cytoplasmic tails, one message that is clear from the recent literature is that downstream signals emanating from cadherin-mediated contacts are both cadherin-specific and cell-context-specific.
CLAY MINERALS IN ROCKS OF THE LOWER PART OF THE OQUIRRH FORMATION, UTAH1

ABSTRACT An association between clay minerals and rock type is recognized in the rocks of an inter-layered sequence of fossiliferous shaly, sandy bioclastic, and cherty limestone, dolomitic limestone, calcareous and dolomitic quartzite, and quartzite that form a portion of the lower part (Pennsylvanian age) of the Oquirrh formation in the northern Oquirrh Range, Utah. These sedimentary rocks are largely of clastic origin and range from fine- to coarsegrained. In part they are cross-bedded, and fossils are locally abundant. Calcite-rich rocks predominate (78 percent) over dolomite-and quartz-rich rocks (17 and 5 percent, respectively). Clay minerals constitute less than one percent in quartzite and range from one to five percent in some limestones. Clay minerals and rock types are commonly observed in the following associations: Illite and chlorite occur in limestone; illite, chlorite, and mixed-layer clay occur in cherty, bioclastic, and sandy limestone and in calcareous quartzite; chlorite and illite commonly are present in dolomitic quartzite; chlorite, illite, and mixed-layer clay are found in dolomitic limestone; and kaolinite, illite and chlorite are typically present in quartzite. The mixed-layer clay has a lattice spacing of 29.4 A that expands to 31.0 A when glycolated and contracts irregularly to 13.2 A when heated to 500 °C; the clay is assumed to consist of 14 A chloritic and 15 A montmorillonitic material. Chlorite or mixed-layer clay, or both, generally are associated with rocks containing dolomite.
An Approach for Structural-Acoustic Optimization of Ribbed Panels Using Component Mode Synthesis

Component mode synthesis (CMS) is an approach used to couple dynamics of complex structures using modes of individual components. A CMS approach is developed to determine the response of a ribbed panel based on the individual rib and plate modes. The CMS method allows for rapid evaluation of noise-control designs as component modes need to be solved only once. Since efficient evaluation is required for global design optimization procedures, the CMS approach can be well suited in optimization problems. A simple structural-acoustic optimization problem was created to demonstrate the utility of the formulation by finding the optimal rib location and material to reduce sound radiation for a point-driven plate. Several parameters of the optimization algorithm are varied to test convergence speed and accuracy.Copyright © 2012 by ASME
Behavioral and histopathological consequences of paraquat intoxication in mice: Effects of α‐synuclein over‐expression

Genetic variability in the alpha-synuclein gene and long-term exposure to the pesticide paraquat constitute possible risk factors for sporadic Parkinson's disease. The goal of the present study was to further characterize the effects of paraquat in mice as a model of Parkinson's disease and to determine whether it acted synergistically with alpha-synuclein over-expression to cause nigrostriatal cell death or dysfunction. Paraquat (10 mg/kg i.p.) was administered once a week for 3 weeks to mice over-expressing human alpha-synuclein under the Thy1 promoter and their wild-type littermates. The effect of paraquat on catecholaminergic neurons was reminiscent of that of Parkinson's disease, with preferential loss of dopaminergic neurons in the ventral tier of the substantia nigra pars compacta and loss of tyrosine hydroxylase staining in the locus coeruleus. alpha-Synuclein over-expression did not increase paraquat-induced cell loss, and paraquat did not worsen the behavioral deficits observed in the transgenic mice. However, paraquat markedly increased proteinase-K-resistant alpha-synuclein aggregates in substantia nigra of the transgenic mice. The data further validate the use of paraquat to model Parkinson's disease in mice and show that although paraquat and alpha-synuclein over-expression act synergistically to increase protein aggregation in vivo, this interaction does not result in short-term neuroprotection or increased vulnerability of nigrostriatal neurons.
A structural model of parent and teacher influences on science attitudes of eighth graders: Evidence from NELS: 88

Research on science attitudes has focused mostly on teacher variables and learning environment variables. Furthermore, in the parent involvement literature, the outcome variable of interest has been mostly science achievement rather than science attitudes. Limited research is available on the joint influence of teacher and parent variables on science attitudes. This article proposes a model of parent and teacher influences on the science attitudes of eighth graders using data from the base year survey of the National Educational Longitudinal Study of 1988. The data were analyzed using structural equation modeling methodology for categorical data. The results show that the availability of science facilities has a significant direct effect on science experiments. Parental involvement has significant direct as well as indirect effects on science attitudes mediated through science activities and library/museum visits. Science activities have a significant direct effect on science attitudes. This study suggests that improving the quality of science instruction and science activities in schools will have implications for science education in schools and this will, in turn, indirectly affect the science attitudes of students. More importantly, the findings of this study provide concrete empirical evidence that parents play a very important role in the development of science attitudes of students. © 1998 John Wiley & Sons, Inc. Sci Ed82:93–109, 1998.
One-electron oxidation is not a major route of metabolic activation and DNA binding for the carcinogen 7H-dibenzo[c,g]carbazole in vitro and in mouse liver and lung

7H-Dibenzo[c,g]carbazole (DBC) is a potent multi-site, multi-species carcinogen present in a variety of complex mixtures derived from the incomplete combustion of organic matter. Like many carcinogens, DBC requires metabolic activation to an electrophilic species to exert its mutagenic and carcinogenic effects. One-electron oxidation, leading to the formation of radical cation intermediates, has been proposed as a mechanism of metabolic activation for DBC in vitro resulting in unstable DNA adducts. The purpose of this research was to determine whether one-electron oxidation is a mechanism of activation and DNA binding for DBC in vivo. Specific depurinating DBC-DNA adducts formed by one-electron oxidation were analyzed in mouse liver at 4 h following a single i.p. dose of 40 mg/kg of 11 microCi [(14)C]DBC. In addition to five previously published adduct standards, two newly identified adduct standards were characterized by mass spectrometry and NMR, namely DBC-6-N7-Ade and DBC-6-N1-Ade; however, neither was observed in mouse liver. Only the DBC-5-N7-Gua adduct was observed in mouse liver extracts at a level of 6.5 +/- 1. 8 adducts/10(6) nucleotides. In addition, the formation of AP sites and stable DBC-DNA adducts was analyzed in mouse liver and lung at 4, 12 and 24 h following a single i.p. dose of 0.4, 4 or 40 mg/kg DBC (n = 3/group). There was a distinct time- and dose-response of stable DBC-DNA adducts detected by (32)P-post-labeling. There was not a clear dose-response for formation of AP sites; however, a significant increase over control levels was observed at the 4 and 40 mg/kg dose groups at 4 and 12 h post dosing, respectively. Quantitative comparisons indicate that the depurinating DBC-5-N7-Gua adduct constitutes approximately 0.4% of total adducts measured whereas the stable adducts detected by (32)P-post-labeling constitute 99.6% of total adducts measured following a 40 mg/kg dose and a 4 h time-point. The data indicate that one-electron oxidation does occur in mouse liver in vivo. However, one-electron oxidation is a minor mechanism of activation in that the percentage of total adducts formed through this route constitutes a minor percentage of the total adducts formed.
Congenital Heart Disease, HLA Sensitization, and Heart Transplantation

Purpose Children after operative interventions for congenital heart disease (CHD-O) are frequently sensitized to HLA types from exposure to blood transfusions and cadaver tissue used for reconstructions. However, these anti-HLA antibody levels may fall with increasing time from surgery. It is possible that some CHD-O with a negative pre-transplant (Tx) PRA have been sensitized but are relatively quiescent at the time it is drawn. We hypothesized that a negative pre-Tx PRA might be falsely reassuring and that this group might be at increased risk for an early and marked rise in HLA antibodies with antigen re-exposure at implantation compared to children with cardiomyopathy (CM) or congenital heart disease with no prior cardiac surgery (CHD-N), both less likely to have had prior non-self exposure. Methods and Materials A retrospective chart review was done for all children undergoing heart Tx at our center to identify those with at least 6 mn post-Tx follow-up and at least 1 post-Tx PRA. Results The 123 children meeting criteria were divided into groups based on pre-Tx diagnosis: CM (N=50; AgeTx=5.2 y; FU=6.8y), CHD-N (N=21; AgeTx=0.28y; FU=11.8y) and CHD-O (N=52; AgeTx=6.6y; FU=7.3y). As age at Tx was much lower in the CHD-N group, subsequent analysis compared only CM and CHD-O which did not differ significantly for AgeTx or FU. A positive pre-Tx PRA (>10%) was present in 3.6% (CM) vs. 29% (CHD-O). If the pre-Tx PRA was negative, a positive post-Tx PRA was observed in 22% (CM) vs. 17% (CHD-O) (NS); and the median time post-Tx to positive PRA was 3.3 y; range 0.19-19 y (CM) vs. 2.2 y; range 0.019-12 y (CHD-O) (NS, p=0.40). Regardless of the pre-Tx PRA, donor specific antibody was seen in 18% (CM) and 19% (CHD-O) (NS) following Tx. Conclusions As long as the pre-Tx PRA is negative, prior congenital heart surgery does not appear to increase the likelihood of a positive post-Tx PRA or lead to an earlier appearance of positive PRA. Although some CHD-O with negative pre-Tx PRA develop anti-HLA antibody early post-Tx, it occurred no more often than in those transplanted for CM.
Nuclear energy: health impact of carbon-14.

Estimates are presented on the carbon-14 generation rates in several reactor types and in peaceful nuclear explosions. If the carbon-14 generated in light water reactors is released, the population radiationdose rate it causes initially will be comparable to that resulting from the krypton-85 and tritium generated in these reactors. Because of the long half-life, the radiationdose commitment and thedose rate resulting from the environmental build-up of carbon-14 are considerably larger than those of the two other radionuclides.
Functional interactions between calmodulin and estrogen receptor-α

Abstract The effects of estrogen in breast epithelial cells are mediated primarily via estrogen receptor α and estrogen receptor β (ERα and ERβ). Accumulating evidence implicates a role for Ca2+ and calmodulin in breast carcinoma, as well as in the function of ERα. Calmodulin contributes to the regulation of both ERα degradation and ERα-mediated transcriptional activation. Recent data will be summarized in this review. Models to explain the molecular mechanisms by which calmodulin modulates ERα function are proposed.
Is peroxisome proliferator-activated receptor gamma (PPARγ) a therapeutic target for the treatment of pulmonary hypertension?

AbstractPulmonary hypertension (PH), a progressive disorder associated with significant morbidity and mortality, is caused by complex pathways that culminate in structural and functional alterations of the pulmonary circulation and increases in pulmonary vascular resistance and pressure. Diverse genetic, pathological, or environmental triggers stimulate PH pathogenesis culminating in vasoconstriction, cell proliferation, vascular remodeling, and thrombosis. We conducted a thorough literature review by performing MEDLINE searches via PubMed to identify articles pertaining to PPARγ as a therapeutic target for the treatment of PH. This review examines basic and preclinical studies that explore PPARγ and its ability to regulate PH pathogenesis. Despite the current therapies that target specific pathways in PH pathogenesis, including prostacyclin derivatives, endothelin-receptor antagonists, and phosphodiesterase type 5 inhibitors, morbidity and mortality related to PH remain unacceptably high, indicating the ...
A follow-up study of the characteristics of dean's letters.

PURPOSE To assess the content and quality of dean's letters since the publication of guidelines recommended by the Association of American Medical Colleges (AAMC) in 1989. METHOD In 1998, the dean's letter writers at all 124 U.S. medical schools were surveyed. The questionnaire incorporated items from two previous surveys (1981 and 1992). In addition, samples of dean's letters (n = 451) from all U.S. medical schools for the graduating class of 1998 were rated based on the AAMC's guidelines. RESULTS The response rate of the 1998 survey (66%) was lower than those of the two previous surveys (87% for 1992 and 85% for 1981). Schools that prepared letters that followed the AAMC's guidelines were somewhat more likely to have responded. According to the letter writers in 1998, close to 300,000 letters (approximately 1,050,000 pages total) were sent to residency directors, at an estimated cost of $26,000 per school. A total of 65% of schools produced adequate dean's letters based on the 1989 AAMC's guidelines, compared with 55% in 1992. Many schools were organizing the dean's letter in more readable formats, and more schools provided information that allowed for a comparison of students within the same school. CONCLUSION The improvements in dean's letters are encouraging, but ten years after the AAMC's guidelines, 35% of U.S. schools still produce unacceptable letters. With the addition of the electronic submission of information, it is time to review further improvements to the dean's letter.
Genes Don't Count

It is the regulation of gene expression that determines phenotype and cellular response. Several families of proteins control gene expression in cells and influence the pathogenesis of multiple organ failure, the acute phase response, atherosclerosis, and graft-vs-host disease. Understanding the basics of the regulation of gene transcription will allow the knowledgeable surgeon to target gene expression as a therapeutic modality in multiple diseases. We examine nuclear factor kappa B as an example of a transcription factor that is involved in multiple surgical diseases and has pharmacological inhibitors available to knowledgeable surgeons.
How moral agents became ghosts or why the history of ethics diverged from that of the philosophy of mind

At the very beginning of modern moral philosophy which for reasons that will become clear, I date in the 1780s the moral agent as traditionally understood almost, if not quite, disappeared from view. The moral agent's character, the structure of his desires and dispositions, became at best a peripheral rather than a central topic for moral philosophy, thus losing the place assigned to it by the vast majority of moral philosophers from Plato to Hume. And with this displacement the history of moral philosophy was divorced to a large and quite new extent from the philosophy of mind and action. The implications for the philosophy of mind are not inconsiderable, for it is in part at least because of this divorce, and not only because of Cartesian influences upon epistemology, that that part of philosophy became merely the philosophy of mind rather than the philosophy of mind-and-action. But the alterations in the preoccupations of moral philosophy itself were even more drastic. What replaced and still too often replaces the concept of moral character at the core of philosophical thinking about morality was and is a conception of choice of a particular kind as central to moral agency. Originally in the writings of Reid and Kant this choice was conceived of as that which individuals make between the promptings of desire and the requirements of morality; much later in the writings of Sartre it has become the individual's choice of those principles obedience to whose prescriptions constitutes morality. In both earlier and later writers it is common to find this notion of choice closely connected with the praise of individual autonomy as a defining property of morality. A. N. Prior summarised Reid's view of the matter accurately: "In
Cardiac Sodium-Calcium Exchanger Is Regulated by Allosteric Calcium and Exchanger Inhibitory Peptide at Distinct Sites

The sarcolemmal Na+-Ca2+ exchanger (NCX) is the main Ca2+ extrusion mechanism in cardiac myocytes and is thus essential for the regulation of Ca2+ homeostasis and contractile function. A cytosolic region (f-loop) of the protein mediates regulation of NCX function by intracellular factors including inhibition by exchanger inhibitory peptide (XIP), a 20 amino acid peptide matching the sequence of an autoinhibitory region involved in allosteric regulation of NCX by intracellular Na+, Ca2+, and phosphatidylinositol-4,5-biphosphate (PIP2). Previous evidence indicates that the XIP interaction domain can be eliminated by large deletions of the f-loop that also remove activation of NCX by intracellular Ca2+. By whole-cell voltage clamping experiments, we demonstrate that deletion of residues 562-679, but not 440- 456, 498-510, or 680-685 of the f-loop selectively eliminates XIP-mediated inhibition of NCX expressed either heterologously (HEK293 and A549 cells) or in guinea pig cardiac myocytes. In contrast, by plotting I(NCX) against reverse-mode NCX-mediated Ca2+ transients in myocytes, we demonstrate that Ca2+-dependent regulation of NCX is preserved in Delta562-679, but significantly reduced in the other three deletion mutants. The findings indicate that f-loop residues 562-679 may contain the regulatory site for endogenous XIP, but this site is distinct from the Ca2+-regulatory domains of the NCX. Because regulation of the NCX by Na+ and PIP2 involves the endogenous XIP region, the Delta562-679 mutant NCX may be a useful tool to investigate this regulation in the context of the whole cardiac myocyte.
Macrophage Apolipoprotein E Reduces Atherosclerosis and Prevents Premature Death in Apolipoprotein E and Scavenger Receptor–Class BI Double-Knockout Mice

Objective— Mice null for both apolipoprotein (apo)E and scavenger receptor (SR)-BI (DKO) develop severe hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarction, and premature death. The current study examines the ability of macrophage apoE to improve the dyslipidemia, reduce atherosclerosis, and rescue the lethal phenotype of DKO mice. Methods and Results— Initially, bone marrow transplantation (BMT) was unsuccessful, because the DKO mice died from a rapidly fatal anemia 3 to 5 days after lethal irradiation. Therefore, probucol was used to rescue the DKO mice during BMT and was discontinued 2-weeks after BMT, allowing successful reconstitution with donor marrow. Twelve male apoE −/− SR-BI −/− mice fed 0.5% probucol in a chow diet were lethally irradiated and transplanted with either wild-type (WT) or DKO bone marrow. Two-weeks after BMT, apoE was detected in serum in WT→DKO mice, and mean serum cholesterol levels were reduced by 70% versus DKO→DKO mice. Lipoprotein profiles and HDL subpopulations in WT→DKO mice were similar to apoE +/+ SR-BI −/− →DKO mice and resembled those of SR-BI −/− mice. In WT→DKO mice, aortic atherosclerosis was reduced by 88% to 90% versus DKO→DKO mice. Furthermore, the DKO→DKO mice died &8 weeks after BMT, whereas WT→DKO mice exhibited a life span >40 weeks after BMT. Conclusions— Macrophage apoE is able to rescue the lethal phenotype of apoE −/− SR-BI −/− mice by improving the dyslipidemia and dramatically reducing atherosclerotic lesion development.
Extracting novel information from gene expression data

Data from high throughput technologies, such as DNA microarrays, necessitated the development of new computational methodologies for analyzing the high dimensional information contained within the gene expression data. Liao's group suggested the use of network component analysis to predict transcription factor activities by integrating gene expression data from Escherichia coli with known connectivity information between their genes and transcription factors. This introduces an approach for obtaining novel information from gene expression data.
Mucosectomy vs. stapled ileal pouch-anal anastomosis in patients with familial adenomatous polyposis: functional outcome and neoplasia control.

PURPOSE: The tradeoff of neoplasia control for better function represented by a stapled ileal pouch-anal anastomosis is still controversial in patients with familial adenomatous polyposis. We compared outcomes after mucosectomy and hand-sewn ileal pouch-anal anastomosis with those after stapled ileal pouch-anal anastomosis in 119 patients with familial adenomatous polyposis who underwent surgery since 1983. METHODS: Age, gender, length of follow-up, complications, quality of life, incontinence, urgency, nighttime and daytime seepage, pad usage, necessity of ileostomy, and incidence of adenomas developing in pouch and anal transitional zone were recorded. RESULTS: There were 42 mucosectomy and 77 stapled patients who were followed up for an average of 5.8 and 3.6 years, respectively, with endoscopic surveillance. There was one postoperative death in the stapled group that prohibited long-term follow-up. Nine of 42 mucosectomy patients developed pouch adenomasvs. 8 of 76 in the stapled group. Six of 42 patients developed adenomas in the mucosectomized anal transitional zone in the mucosectomy group. Twenty-one of 76 patients developed adenomas in the anal transitional zone in the stapled group. All were managed with local procedures or further surveillance. One of 76 patients developed cancer in the residual low rectum; this required further resection. Patients with stapled anastomosis had better outcomes in every category. Differences in incontinence, daytime and nighttime seepage, pad usage, and avoidance of ileostomy were statistically significant. All patients with mucosectomy required ileostomyvs. only 40 of 77 patients with stapled anastomosis. CONCLUSION: Familial adenomatous polyposis patients with stapled ileal pouch-anal anastomosis have better functional outcome and can avoid temporary diversion. This should be balanced against a 28 percent incidence of adenomas in the anal transitional zone.
Scientists map out research plans for Lake Vostok

About 100 lakes lie under the approximately 4-km-thick ice sheet covering Antarctica. John Priscu, a microbial biologist with Montana State University, said that Lake Vostok, the largest of the known sub-glacial lakes on the continent, will provide the greatest scientific return from research efforts. He made his remarks at a 28 May briefing held at the AGU 2002 Spring Meeting in Washington, D.C.
Alkylation of rat lens crystallins with iodoacetamide

Abstract Alkylation of rat lens proteins with iodoacetamide during homogenization had no effect on protein disulfide content or on the proportions of soluble and insoluble lens protein. These results were similar for lenses, from young or older animals. With the exceptin of the β H -crystallin fraction. alkylation yielded a normal crystallin population as determined by gel-permeation chromatography. Although each crystallin fraction reacted with iodoacetamide in proportion to its free sulfhydryl content, only the alkylated β H -crystallin demonstrated an apparent reduction in molecular size so that it co-chromatographed with β L -crystallin. Molecular weights of subunits for both β H - and β L -crystallin were modified by alkylation. Isoelectric focusing further revealed bands of higher isoelectric pH after alkylation. We conclude that subunit interactions which result in the protein assemblies, characterized as crystallins, do not depend on disulfide formation during isolation, and that β H -crystallin has unique conformational or subunit properties which are sensitive to modification of the free-sulfhydryl group.
Self-control program in the treatment of obesity

In a pilot study utilizing self-control techniques for the purpose of modifying the cue-reactive eating habits of obese patients, three subjects maintained a continuous weight loss throughout the first year of treatment. Techniques included goal setting, self-monitoring, brief delay and self-confrontation prior to eating unauthorized food and direct observation of oneself in a mirror when eating unauthorized food. All patients are expected to remain in treatment for the foreseeable future with no termination of the program despite apparent success with regard to control of their feeding disturbance. The rationale for this approach is discussed.
Enabling high-speed, high-resolution ADCs using signal conditioning algorithms

Time-interleaving several identical A/D converters enhances the overall conversion speed in a power-economical way. However, mismatches between individual channels in such schemes degrade the overall dynamic range of the converter. Several algorithms to mitigate such effects are discussed with special emphasis on an adaptive signal-conditioning algorithm. The algorithm is further extended towards a hardware-friendly implementation using interpolation filters. Behavioral simulations corroborating the same are presented.
Surface reconstruction with discontinuities

Thin-plate spline fitting is often applied to fitting smooth surfaces to a collection of data. However, discontinuities in the data are smoothed by this technique. This occurs because of several underlying assumptions of spline fitting that do not hold when discontinuities are present. The theory of robust statistics can be used to deal with these outliers. In this paper, we present one way to apply the theory of robust statistics to the problem of discontinuous surface fitting.
Invasive skin carcinoma--Ras and alpha6beta4 integrin lead the way.

Abstract Although the genesis of invasive squamous cell carcinoma (SCC) from stratified epithelia of the skin is considered to be a complex, multistage process, recent work on human epidermis reveals that sustained Ras signaling coupled with suppression of Ras-induced growth arrest is sufficient to drive the entire process and that the α6β4 integrin and its laminin 5 ligand are essential components of this process.
THE DEVELOPMENT AND EVALUATION OF ALTERNATIVE GENERALIZED M-ESTIMATION TECHNIQUES

Least squares estimation is a widely used regression technique. The presence of outliers in data can have an adverse effect on least squares estimates, resulting in a model that does not adequately fit the bulk of the data. Robust regression techniques have been proposed as an alternative to least squares when outliers are present. We develop and evaluate new robust regression procedures and compare their performance to the best alternatives currently available in terms of efficiency, breakdown, and bounded influence. We offer the better performing alternatives as possible methods for use in a robust regression scenario.
Ex vivo evaluation of a Taylor-Couette flow, immobilized heparinase I device for clinical application

Efficient and safe heparin anticoagulation has remained a problem for continuous renal replacement therapies and intermittent hemodialysis for patients with acute renal failure. To make heparin therapy safer for the patient with acute renal failure at high risk of bleeding, we have proposed regional heparinization of the circuit via an immobilized heparinase I filter. This study tested a device based on Taylor-Couette flow and simultaneous separation/reaction for efficacy and safety of heparin removal in a sheep model. Heparinase I was immobilized onto agarose beads via cyanogen bromide activation. The device, referred to as a vortex flow plasmapheretic reactor, consisted of two concentric cylinders, a priming volume of 45 ml, a microporous membrane for plasma separation, and an outer compartment where the immobilized heparinase I was fluidized separately from the blood cells. Manual white cell and platelet counts, hematocrit, total protein, and fibrinogen assays were performed. Heparin levels were indirectly measured via whole-blood recalcification times (WBRTs). The vortex flow plasmapheretic reactor maintained significantly higher heparin levels in the extracorporeal circuit than in the sheep (device inlet WBRTs were 1.5 times the device outlet WBRTs) with no hemolysis. The reactor treatment did not effect any physiologically significant changes in complete blood cell counts, platelets, and protein levels for up to 2 hr of operation. Furthermore, gross necropsy and histopathology did not show any significant abnormalities in the kidney, liver, heart, brain, and spleen.
Vibrational circular dichroism in the mid-infrared

Abstract Vibrational circular dichroism (VCD) has been measured for the First tune in the CH 2 bending region down to 1250 cm −1 . This advance in technique was facilitated by the addition of a carbon-rod light source, a cooled HgCdTe detector, and signal averaging to our instrument.
Raman Spectroscopic Analysis of Fertilizers and Plant Tissue for Perchlorate

Raman spectroscopy, without the need for prior chromatographic separation, was used for qualitative and quantitative analysis of 59 samples of fertilizers for perchlorate (ClO4-). These primarily lawn and garden products had no known link to Chile saltpeter, which is known to contain perchlorate. Perchlorate contamination is emerging as an important environmental issue since its discovery in water resources that are widely used for drinking, crop irrigation, and recreation in the Western U.S. Approximately 90% of the 32 fertilizer samples acquired between November 1998 and January 1999 contained perchlorate, and of these, the level was typically high (500-8000 mg/kg). However, only two of the 27 fertilizer samples acquired from June 1999 to May 2000 contained perchlorate and at a lower level than previously observed (i.e., ~250-350 mg/kg). Raman spectroscopy was also applied to the qualitative identification of perchlorate in extracts of lettuce that had been grown in a greenhouse using irrigation water spiked (at 10 ppm) with perchlorate. Generally, with a fertilizer extract, detection limits were ~50 ppm for perchlorate with short spectral acquisition times (~5 min). Quantitation was typically accurate to within 2 to 14%, with an average %CV (coefficient of variation) of 6.3 among replicate runs. We compare Raman spectroscopy to ion chromatography, which is the currently recommended method for perchlorate analysis.
ARE ACUTE DECOMPENSATED VOLUME OVERLOADED HEART FAILURE PATIENTS BEING DIURESED AS RECOMMENDED BY ACCF/AHA HEART FAILURE GUIDELINES?

Acute decompensated volume overloaded heart failure (ADVOHF) is a common presentation to the emergency department (ED) that leads to hospitalization. Updated guidelines from the ACCF/AHA on Heart Failure (JACC, 2009) make Class I recommendations in terms of initial management of volume overloaded
Optimization of layer-by-layer electrostatic self-assembly processing parameters for optical biosensing

The effect of layer-by-layer electrostatic self-assembly processing parameters on resulting thin-film characteristics was determined in order to optimize the thin-film structure for optical biosensing. The use of long-period fiber gratings (LPFGs) requires careful control of the refractive index of the surrounding medium, which can be achieved by tuning the refractive index and thickness of an optical thin film deposited directly on the optical fiber surface. The high-sensitivity LPFG refractometry range falls in a window just below the effective index of the relevant cladding mode. We investigated five factors at two levels using variable-angle spectroscopic ellipsometry and analysis of variance. Salt concentration and pH were found to be critical parameters for refractive index control.
Effect of Insulin Treatment on the Susceptibility of the Diabetic Rat to Escherichia coli-Induced Pyelonephritis

Escherichia coli-induced pyelonephritis was studied in untreated alloxan-diabetic rats, insulin-treated diabetic rats, glucose water-drinking (diuresing) nondiabetic rats, and tap water-drinking (nondiuresing) nondiabetic rats following injection of E. coli either into the emptied urinary bladder, into the left kidney, or intravenously. For prevention of an ascending infection in the right kidney, the right ureter was ligated and transected immediately prior to bladder or intrarenal inoculation. These experiments established that in normal rats ascending renal infection alone occurred following introduction of small inocula into the bladder--and then only when facilitated by diuresis. In diabetic rats both ascending and hematogenous renal infection occurred following introduction of small inocula into the bladder. Insulin treatment that reduced hyperglycemia also reduced glycosuria and restored urinary antibacterial activity against small inocula of E. coli but only partially reduced polyuria and prevented hematogenous but not ascending infection. Thus, hyperglycemia was probably the major factor promoting hematogenous renal infection, whereas polyuria--and therefore vesicoureteral reflux--was the major factor promoting ascending infection.