cssi/SciSciGPT-SciSciNet huggingface dataset:
Transgenic Expression of a Soluble Complement Inhibitor Protects Against Renal Disease and Promotes Survival in MRL/lpr Mice

To investigate the role of complement in lupus nephritis, we used MRL/ lpr mice and a transgene overexpressing a soluble complement regulator, soluble CR1-related gene/protein y (sCrry), both systemically and in kidney. Production of sCrry in sera led to significant complement inhibition in Crry-transgenic mice relative to littermate transgene negative controls. This complement inhibition with sCrry conferred a survival advantage to MRL/ lpr mice. In a total of 154 animals, 42.5% transgene-negative animals had impaired renal function (blood urea nitrogen > 50 mg/dl) compared with 16.4% mice with the sCrry-producing transgene ( p < 0.001). In those animals that died spontaneously, MRL /lpr mice with the sCrry-producing transgene did not die of renal failure, while those without the transgene did (blood urea nitrogen values of 46.6 ± 9 and 122 ± 29 mg/dl in transgene-positive and transgene-negative animals, respectively; p < 0.001). Albuminuria was reduced in those transgenic animals in which sCrry expression was maximally stimulated (urinary albumin/creatinine = 12.4 ± 4.3 and 36.9 ± 7.7 in transgene-positive and transgene-negative animals, respectively; p < 0.001). As expected in the setting of chronic complement inhibition, there was less C3 deposition in glomeruli of sCrry-producing transgenic mice compared with transgene-negative animals. In contrast, there was no effect on glomerular IgG deposition, levels of anti-dsDNA Ab and rheumatoid factor, or spleen weights between the two groups. Thus, long-term complement inhibition reduces renal disease in MRL/ lpr mice, which translates into improved survival. MRL/ lpr mice in which complement is inhibited still have spontaneous mortality, yet this is not from renal disease.
On Liberty: Positive and Negative

One century after the publication of On Liberty, Sir Isaiah Berlin delivered his celebrated Inaugural Lecture before the University of Oxford entitled “Two Concepts of Liberty.”1 Berlin’s lecture is described by Ronald Dworkin as “the most famous modern essay on liberty” and praised by John Gray as developing “an argument of unsurpassed perspicuity.”2 It is therefore understandable that scholars would consider it alongside the famous nineteenth-century essay On Liberty and apply Berlin’s ideas to those of John Stuart Mill. Unfortunately, imposing Berlin’s two concepts on Mill’s theory has been a source of confusion and has added to the misunderstanding that surrounds Mill. The goal of this chapter will be to clear up this confusion and thereby regain a better understanding of Mill’s theory of liberty.
How “Organization” Can Weaken the Norm of Reciprocity: The Effects of Attributions for Favors and a Calculative Mindset

Why are employee loyalty and effort sometimes not reciprocated by employers? Five experimental studies tested the hypothesis that people feel less obligated to reciprocate in an organizational as c...
Chapter 6 – Stem Cell Niches

The ability of adult stem cells to both self-renew and produce daughter cells that initiate differentiation is the key to tissue homeostasis. The decision between self-renewal and differentiation must be tightly controlled. Too many daughter cells and the stem cell population might become depleted; too many self-renewal divisions could facilitate tumorigenesis. A detailed understanding of how this choice is determined is a critical first step toward harnessing the potential of adult stem cells for tissue replacement and gene therapy.
Influence of the relA gene on ribosome frameshifting.

We have examined the influence of genotype at the relA locus on the kinetics of leftward (or –1) frameshifting at a variety of codons calling for a limiting aminoacyl-tRNA species. We used lacZ left-frameshift reporter constructs carrying the sequence U UUC xyz, where xyz was each of three triplets coding for three different amino acids; we slowed the ribosomes at each of these by limiting for the amino acid or for the aminoacyl-tRNA. In all cases, limitation stimulated leftward frameshifting. In all cases, the stimulation was greater in relA mutant cells than in their wild-type relA + counterparts. In the latter genotype, the increased frameshifting was constant from the start of the limitation regime. This was also true of the relA mutant strain during limitation for lysine-tRNA or for leucine; however, during limitation for isoleucine-tRNA (or for isoleucine) the mutant showed a gradual, progressive increase in frameshifting, suggesting an indirect effect. We suggest that gradual accumulation of undermodified tRNAs, which is characteristic of the relA response, is involved. However, the specific modification involved is unknown. It is not queosine: analysis of a tgt mutant that is completely defective in queosine modification showed no increase in leftward frameshifting on the reporter which showed the larger, gradual increase during the relA response to isoleucine-tRNA limitation.
Introduction of restriction enzyme sites in protein-coding DNA sequences by site-specific mutagenesis not affecting the amino acid sequence: a computer program.

Abstract Structure/function relationship studies of proteins are greatly facilitated by recombinant DNA technology which allows specific amino acid mutations to be made at the DNA sequence level by site-specific mutagenesis employing synthetic oligonucleotides. This technique has been successfully used to alter one or two amino acids in a protein. Replacement of existing DNA sequence coding for several amino acids with new synthetic DNA fragments would be facilitated by the presence of unique restriction enzyme sites in the region of interest. This computer program provides a means of searching the DNA sequence of interest for restriction enzyme sites that could be introduced by site-specific mutagenesis not affecting the amino acid sequence of the protein. Alternately, the program will also allow single amino acid changes to be made.
Stochastic Properties of Conflict Frequency at Multiple Connected Air Route Intersections

Previous results regarding the stochastic properties of the frequency of conflict situations at a single intersection of two air routes have been extended to the case of multiple connected intersections. Such a situation occurs when more than one aircraft stream intersects with another aircraft stream. Examples include multiple discrete velocity groups of vehicles on routes, intersections in the horizontal plan involving more than two routes, and routes transitioning through altitude strata or flight levels. It is determined that the conflict frequency at multiple intersections connected with a common vehicle stream are correlated, and the expression for the covariance is derived. With these results, not only the mean, but the variance of conflict frequency for an ATC sector may be predicted from traffic-flow and route-geometry information, both of which are important parameters for sector capacity analyses.
Interrelationship of breath components in neighboring breaths of normal eupneic subjects.

To determine the fraction of variational activity that is correlated on a breath-to-breath basis from uncorrelated random fluctuations, we performed autocorrelation analysis in 33 normal subjects during resting breathing. A calibrated inductive plethysmograph was used to nonobtrusively record 700 breaths in each subject. The group mean autocorrelation coefficients at a lag of 1 breath for each of the three primary breath components, tidal volume (VT), inspiratory time (TI), and expiratory time (TE), were significantly different from zero (p < 0.001). The autocorrelation coefficients for VT, 0.295 +/- 0.148 (SD), and TE, 0.259 +/- 0.121, were greater than that for TI, 0.201 +/- 0.135 (p < 0.001 and p < 0.01, respectively). The autocorrelation coefficients for each breath component remained significant for approximately 3 consecutive breaths (p < 0.001), indicating the presence of "short-term memory." Cross-correlation analysis revealed significant interrelationships (p < 0.001) for all component irrespecti...
Prioritizing investments in innovations to protect women from the leading causes of maternal death

PATH, an international nonprofit organization, assessed nearly 40 technologies for their potential to reduce maternal mortality from postpartum hemorrhage and preeclampsia and eclampsia in low-resource settings. The evaluation used a new Excel-based prioritization tool covering 22 criteria developed by PATH, the Maternal and Neonatal Directed Assessment of Technology (MANDATE) model, and consultations with experts. It identified five innovations with especially high potential: technologies to improve use of oxytocin, a uterine balloon tamponade, simplified dosing of magnesium sulfate, an improved proteinuria test, and better blood pressure measurement devices. Investments are needed to realize the potential of these technologies to reduce mortality.
Comparative localization of endothelial and inducible nitric oxide synthase isoforms in haemochorial and epitheliochorial placentae

The presence and immunolocalization of type II (inducible or macrophage) and type III (endothelial) nitric oxide synthase (NOS) isoforms were compared in the term placentae of humans, rhesus monkeys, baboons, guinea-pigs, rats and sheep using isoform specific antibodies. In the human placenta, intense immunohistochemical staining for type III NOS was seen in syncytiotrophoblast with weaker staining in vascular endothelial cells. Only vascular endothelial cells showed positive type III NOS staining in rhesus monkey, baboon, guinea-pig, rat and sheep placentae. No positive type III NOS immunostaining was seen in trophoblast from any non-human placentae. Western blotting revealed a 135-kDa type III NOS species in placental homogenates, semi-purified by ADP-sepharose affinity chromatography, from all the species tested confirming antibody specificity. Type II NOS immunostaining was localized to certain villous stromal cells which also stained for CD14 (a monocyte/macrophage marker) in the placenta of humans, rhesus monkeys, baboons and sheep. No specific immunohistochemical staining for type II NOS or CD14 was noted in the two rodent species, guinea-pig and rat. On Western blots, a 130-kDa type II NOS species was identified in semi-purified placental homogenates of every species except guinea-pig, although weak bands were seen for rhesus monkey and baboon. The failure of the antibodies to show type II NOS in the rat placenta by immunohistochemistry may be due to a difference in antigen conformation from Western blots. As only human placental syncytiotrophoblast expresses type III NOS, the putative functions ascribed to this isoform in syncytiotrophoblast, i.e. to prevent platelet and leucocyte aggregation in the intervillous space and adhesion to the trophoblast surface or to mediate peptide hormone release from trophoblast, may be unique to humans. Alternatively, syncytiotrophoblast-derived NO may fulfil some other unknown function. The similar pattern of expression of type II NOS in those species with villous fetomaternal interdigitation and multivillous fetomaternal blood flow interrelations may represent a more universal role in surveillance and/or protection against maternal insults or pathogens by immunologic activation and subsequent synthesis of nitric oxide which exerts a cytostatic/cytotoxic response.
Trapping of hydrated electrons by cetyl pyridinium chloride micelles

Abstract Using a surfactant (cetyl pyridinium chloride) whose head group itself rapidly reacts with e aq − , the rate of hydrated electron trapping in the positively charged micelle surface has been measured. From the high rate constant obtained (≈ 5 × 10 12 M −1 s −1 ) and its very marked dependence on ionic strength, double layer theory may be evoked to explain the trapping mechanism.
ON ESTIMATING THE PARAMETER OF A TRUNCATED GEOMETRIC DISTRIBUTION.

Abstract : The paper is concerned with the problem of maximum likelihood estimation for the parameter, of the geometric distribution, from samples which are truncated at arbitrary points in either or both tails of the distribution. It is shown that the maximum likelihood estimator is the solution of a polynomial of high degree, and a table is given for solving the maximum likelihood estimating equation. The derivation of the asymptotic variance of the estimator is presented and the result is used in the study of the asymptotic efficiency of the estimation in truncated sampling. The efficiency of the maximum likelihood estimator for complete samples is derived and it is shown that the estimator based on truncated samples always provide less information about the parameter than that based on complete sample of the same size. (Author)
Gene expression profiling of the aging mouse cardiac myocytes

Heart disease remains the most frequent cause of death in the general population with increasing incidence in the elderly population. The pathologic failure of the aging heart may be related to structural and functional alterations in cardiac muscle cells. However, the molecular mechanisms underlying the aging-related decline in cardiac muscle function are largely unknown. To provide the first analysis of cardiac aging at the level of gene expression, we established and compared cDNA libraries from apparently healthy young and aged mouse ventricular cardiac muscle cells. We report the identification of genes that exhibit aging-related changes of mRNA levels. Aging expression profiles in aged hearts indicate decreased cellular adaptation and protection against stress-induced injury together with the development of contractile dysfunction. The data suggest reduced activity of the mitochondrial electron transport system and reduced levels of cardiac-specific transcription regulators. The cardiomyocyte aging profile of gene expression displays similarities with known heart disorders. Genes whose mRNA levels change with aging in cardiomyocytes might profoundly affect pathological changes in the heart.
Confidence interval estimation of a common correlation coefficient

This paper presents a generalized variable approach for confidence interval estimation of a common correlation coefficient from several independent samples drawn from bivariate normal populations. This approach can provide one-sided bounds and two-sided confidence intervals with satisfying coverage probabilities regardless of the number of samples, sample sizes and magnitude of the common correlation coefficient while the large sample approach can be very liberal for one-sided bounds. The large sample approach generally performs well for two-sided confidence interval estimation.
Prostaglandins and the pulmonary circulation

Abstract Prostaglandins (PG) E 1 , E 2 , F 2 α , and A 1 were infused into 15 normal mongrel dogs at doses varying from .04 – 6.0 μg/kg/min. Pressures were recorded from the pulmonary artery, left atrium and femoral artery; pulmonary blood volume and cardiac output were determined using sequential indicator dilution curves from injections into the pulmonary artery and left atrium. PGE 1 caused mild active vasodilatation while PGF 2 α resulted in milactive vasoconstriction in the lung. PGE 2 and PGA 1 caused passive shrinkage of the pulmonary vascular bed secondary to a shift of blood to the peripheral circulation.
Maximally fast and arbitrarily fast implementation of linear computations

Linear systems are the most often used type of systems in many engineering and scientific areas. By estab- lishing a relationship between the basic properties of linear computations and several optimizing transformations, it is possible to optimally speed-up linear computations with respect to those transformations while keeping the latency fixed. Furthermore, arbitrarily fast, asymptotically optimal implementations can be obtained by adding retiming and loop unrolling to the transformations set and trading latency for throughput. The proposed techniques have yielded results superior to the best published previously on ail benchmark examples. Finally, the presented approach is also applicable to general (non-linear) computations. 1.0 Motivation and Prior Art The major goal of this paper is to demonstrate how for the large class of linear computations the maximally fast imple- mentation with respect to five important and powerful trans- formations (associativity, distributivity, commutativity, common subexpression and constant propagation) can be efficiently derived and to show how an arbitrarily fast, asymptotically optimal (with respect to the hardware cost) implementation of a general linear computation can be pro- duced combining those five transformations with retiming and loop unfolding. Transformations alter the organization of a computation in a such a way that the user specified input/output relationship is maintained. They are often used as an effective approach for the improvement of the implementation of computations. Their use in compilers (1,5), theoretical computer science (2) and high level synthesis (3,7,9, 111 is surveyed in (lo).
Transcription and hybridization of 125I-cRNA from flow sorted chromosomes.

Metaphase chromosomes from the Chinese hamster cell line M3-1 were separated by means of a flow sorter. Two chromosome fractions were used for this study: A, which consisted of 95% pure chromosome no. 1, and B, which was 90% pure chromosome no. 2. The DNA of 106 chromosomes of each type was purified, and a 125I-cRNA transcript was synthesized in a reaction containing E. coli RNA polymerase and carrier-free 125I-CTP (1.7 Ci/μmole). The cRNA product synthesized with template DNA from 105 sorted chromosomes contained more than 106 dpm. The electrophoretic mobility profiles of the cRNAs on 7.5% SDS acrylamide gels demonstrated that more than 50% of the ribo-polymers were equal to or longer than marker E. coli met-tRNAf. In hybridization reactions 21% and 17% of the transcripts from Chinese hamster whole cell and sorted chromosome DNA hybridized to Chinese hamster DNA and did not hybridize significantly over background in reactions containing calf DNA at Crt values of 1.3 and 1.9×102 mole sec/l. Labelled cRNAs transcribed from the DNA of sorted chromosomes hybridized with the DNA of each sorted chromosome fractions at a Crt of 0.6 mole sec/l. This study demonstrated that the DNA can be (1) recovered from small numbers of highly purified flow sorted chromosomes, (2) used as template by E. coli RNA polymerase and (3) used to prepare a cRNA in reactions containing polymerase and carrier-free 125I-CTP to yield a product which can be employed for hybridization analysis.
Grundlagen, Section 64: Frege's Discussion of Definitions by Abstraction in Historical Context

I offer in this paper a contextual analysis of Frege's Grundlagen, section 64. It is surprising that with so much ink spilled on that section, the sources of Frege's discussion of definitions by abstraction have remained elusive. I hope to have filled this gap by providing textual evidence coming from, among other sources, Grassmann, Schlomilch, and the tradition of textbooks in geometry for secondary schools (including a textbook Frege had used when teaching in a Privatschule in Jena in 1882–1884). In addition, I put Frege's considerations in the context of a widespread debate in Germany on ‘directions’ as a central notion in the theory of parallels.
Effects of mercuric chloride on synchronized Chinese hamster ovary cells: survival and DNA replication.

Abstract Chinese hamster ovary (CHO) cells in vitro were treated with HgCl2 at various stages in the cell cycle and the effects of this chemical on cell survival, DNA replication, and cell division were observed. In terms of survival the early G1 cells were the most sensitive to treatment, followed by late G1 and early S, while mid S and late S-G2 treated cells were the least sensitive. Treatment with HgCl2 also resulted in reduced rates of DNA replication and delays in cell division. The early G1 treated cells showed substantially reduced rates of DNA replication followed by a 4–5 h division delay. The early S and late S-G2 treated cells had some reduction in their rates of DNA replication followed by corresponding division delay of 2.5 h in the early S treated cells and 1 h in the late S-G2 treated cells.
Female genital anomalies affecting reproduction

Abstract Objective: A multitude of female congenital anomalies are uncommon. However, their impact on reproduction can be profound. The aim of this review is to remind the practicing physician of the clinically relevant embryology and summarize the studies that look at the impact of such various anomalies on a woman's fecundity. We review particular surgical therapies that possibly may improve fertility in such women. Design: Review and critique of available studies in which particular surgical therapies were done and whether they truly improved fertility in these women with congenital reproductive anomalies. Results: Clear evidence demonstrates that uterine septum resection is effective in women with demonstrated recurrent pregnancy losses. Arcuate uterus has little impact on reproduction. Other studies fail to definitively show that surgical correction will improve pregnancy retention or fertility except for specifically indicated clinical scenarios. Conclusions: The practicing reproductive specialist should have working knowledge of evidence-based therapeutic options for women with reproductive congenital anomalies. A summary chart has been devised to clearly associate embryologic structures with normal adult derivative as well as anomalous structures.
Pseudoplastic flow: Viscometry, correlations of shear stress vs. shear rate, and prediction of laminar flow in tubes

Abstract The relations of shear stress τ to shear rate D for low molecular weight polyisobutylenes dissolved in cyclohexane were studied in a coaxial cylinder viscometer. Flow curves of τ vs. D were found invariably to be typical of pseudoplastic fluids, without dependency on time of shear, and were well correlated by empirical equations of the form: τ = bD8, wherein b and s are experimental constants depending on concentration C and temperature T. It is shown that In b is linear in √C and in 1 T . The correspondence of b as a measure of anomalous flow with viscosity ν (defined as τ = ηD) for Newtonian flow is suggested. For a pseudoplastic fluid whose shear stress-shear rate relation can be described mathematically as τ = bD2, an equation is derived to relate volumetric flow rate through a straight tube to pressure gradient, for conditions of laminar flow. This equation is similar in form to the Hagen-Poiseuille formula for flow of Newtonian fluids. Tube-flow experiments with pseudoplastic fluids in tubes are described which confirm the validity of the equation.
Hepatitis-Associated Markers in the American Red Cross Blood Donor Population

. A total of 20,643 samples of blood donated to three American Red Cross Blood Service regions were tested for antibodies to hepatitis B core antigen (anti-HBc) in order to evaluate and understand its significance and implications. All 20,643 samples were non-reactive for hepatitis B surface antigen (HBsAg) when screened at the regions. Overall, 2.2% of all samples were found to have anti-HBc, and a total of 16 had anti-HBc in the absence of antibodies to surface antigen (anti-HBs) activity. 1 of the 16 samples with anti-HBc in the absence of anti-HBs was found to have HBsAg when tested by a sensitive procedural modification of the Ausria II test. Samples with low levels of anti-HBc activity were significantly more likely to be negative for anti-HBs.
Control of Apolipoprotein B mRNA Editing: Implications of mRNA Dynamics at Various Maturation Stages

Apolipoprotein (apo) B mRNA editing is a genetic regulatory mechanism whereby nucleotide 6666 in apo-B-100 mRNA is converted from a C to a U. The end result of this change is the creation of a premature stop codon so that the translation product of the edited (apoB-48) mRNA contains 2152 amino acids residues instead of 4536 residues in the product (apoB-100) encoded by the unedited mRNA. ApoB mRNA editing is a post-transcriptional process that is expressed in a tissue-specific manner. Here we present a model for the control of apoB mRNA editing. The three variables in the model include editing activity, apoB mRNA transcription rate and mRNA degradation rate at various maturation stages for the mRNA, and a simple formula can be used to quantify the degree of apoB mRNA editing with respect to these variables at different apoB mRNA maturation stages. Time-dependent equations were solved numerically. Using this model, it can be shown that, in addition to editing activity, the degradation kinetics of apoB mRNA can also serve as an efficient modulator of the degree of editing. The rate of apoB mRNA transcription has a transient effect on the degree of editing; varying the apoB mRNA degradation constant tends to change the degree of editing only at the specific maturation stage. This model can render some previously proposed hypothesis (e.g. coupling of mRNA editing to splicing/polyadenylation) unnecessary and provides a rational basis for the design of experiments on specific aspects of apoB mRNA editing in the future; it may also be applicable to other types of RNA editing.
A revision of the Oligocene apes of the Fayum Province, Egypt

Paleontology, Hominoidea, apes, Propliopithecus, Aegyptopi- ABSTRACT Three years of field excavations in the Oligocene strata of the Fayum Province, Egypt, have yielded more than two dozen new jaws and teeth of fossil apes. This material contributes significantly to our understanding of catarrhine systematics and phylogeny. Here we present a systematic revision of the earliest apes and discuss their relationship with Miocene forms. Two ape species have been recovered from Quarries I and M in the Upper Fossil Wood zone of the Jebel el Qatrani Formation, Aegyptopithecus zewcis and Pro- pliopithecus (= Aeolopithecus) chirobates. Female Propliopithecus chirobates have small canines which somewhat resemble those of the enigmatic Propliopithecus haeckeli, but have a longer, narrower P3 than the latter. No specimens of either P. haeckeli or Moeripithecus markgrafi have been found in the Upper Fossil Wood zone after ten field seasons, suggesting that these species may occur only lower in the section. Aegyptopithecus and Propliopithecus have no shared derived features that ex- clude them from the ancestry either of Old World monkeys or apes. Thus, Ae- gyptopithecus, the better known form, is suitably primitive to have been the ancestor of all later Old World monkeys and apes (and hominids). The possibility of a separate gibbon or hominid lineage going back to the Oligocene is unlikely on present evidence. Ape-like fossil anthropoids have been known from Oligocene sediments of the Fayum prov- ince of Egypt since the early part of this cen- tury. On the basis of two specimens collected by Richard Markgraf in 1907, Schlosser (1911) diagnosed two species of Oligocene hominoid- Propliopithecus hueckeli and Moeripithecus markgrafi. After fifty years, expeditions or- ganized by one of us (E.L.S.) renewed palaeon- tological work in this area. Simons (1962) de- scribed first a possible ape, Oligopithecus sauugei, and then (1965) two additional taxa of early apes Aegyptopithecus zeuxis, and Aeo- lopithecus chirobates. In contrast with the pre- viously described materials, which are from unknown parts of the area, the fossils de- scribed by Simons come from documented stra- tigraphic levels in the Jebel el Qatrani For- mation (Simons 1968). In 1968, paleontological collecting in this area ceased because access to it was halted for security reasons. At that time, Oligocene fossil apes were known only from a series of isolated teeth and less than a dozen specimens preserving significant por- tions of either the upper or lower dental arcade. Three recent paleontological expeditions (1977, 1978, 1979) in the Egyptian Oligocene carried out by the Geological Survey of Egypt in cooperation with the Duke University Pri- mate Center have greatly increased the fossil sample of these early hominoids. These finds provide new information on many aspects of dental and gnathic morphology in earliest apes. The purpose of this paper is to bring up to date knowledge (through 1979) of dental and cranial morphology in Oligocene hominoids, to set all the fossils in a revised taxomonic frame-
Bryophyte community response to silvicultural opening size in a managed northern hardwood forest

Abstract We examined the influence of group-selection opening size on the structure and composition of bryophyte communities in a managed northern hardwood forest. We quantified bryophyte communities in 49 group-selection openings, ranging in size from 200 to 1460 m2, 2 years following overstory removal. Bryophyte communities in forest openings were compared to those observed on 20 closed canopy reference plots in the surrounding forest matrix. Both the overall importance ([relative percent cover + frequency]/2) of bryophytes as a group and total percent cover of bryophytes were significantly lower (P
Metabolism of nalidixic acid in the calf: the effect of age

Abstract The metabolism of nalidixic acid (NA) has been studied in Holstein calves following the administration of a single dose of the 14C-labeled sodium salt, or of multiple doses of the unlabeled salt. In immature calves (30–45 kg) the disposition of the drug proved to be very slow (a half-life of about 24 hours) as compared to the only existing norm (a half-life of 1–1.5 hours in adult humans). The label derived from a single 2.3-g dose of the 14C-labeled sodium salt, for example, was not completely cleared from the tissues and excreta within 15 days. The plasma and urine of calves receiving 0.25-g doses of sodium NA twice daily for 4 days appeared to be drug free within 48 hours after the last dose, but those receiving 1.25-g doses twice daily for the same period were still excreting traces of the drug 6 days after the last dose. On the basis of tissue analyses, 30–45-kg calves receiving 0.25-g doses of the sodium salt twice daily for 5 days were essentially, but not completely, drug free 4 days after the administration of the last dose. The metabolic pattern of NA in these immature calves differed from that in man in the high level of fecal excretion, the comparatively low extent of conjugation of the drug excreted in the urine, and in the failure (or inability) to excrete the free drug in the urine in a concentration much exceeding that in the plasma. At 7 months of age the metabolic pattern of NA in the calf was quite different. The plasma half-life was now about 1.5 hours, the animals excreted the free drug in the urine in a concentration at least 10–15 times that in the plasma, and the extent of conjugation for equivalent doses per kilogram was slightly increased (from 37%–50%). The incomplete development of metabolic and excretory mechanisms is considered, therefore, to account for the slow disposition of NA in the immature calf.
Evaluating Supply Chain Energy Use in a Smart Grid Paradigm

A key paradigm shift resulting from the intersection of the information technology (IT) and utility sectors is the availability of real-time data regarding energy use across different industries. Historically, ascertaining the energy costs across the value chain of a given product or service was a laborious and expensive task, requiring many months of data collection; several proxies or approximations for cases where measured data might not be cost-effectively available; and even then, the resulting energy footprint could have significant uncertainty based on time-of-measurement, geographic diversity of manufacturing sites, etc. As dynamic energy pricing begins to take hold and environmental externalities begin to be priced into existing cost structures, the ability to optimize a given value chain for minimal energy use becomes increasingly attractive. In this paper, we discuss an approach for leveraging dynamically available data alongside historical n-tier supply chain models to avail the ability for such optimization. The approach is illustrated for the case study of a computer manufacturer, where we find that metering electricity use at a small subset of sites can allow for a reasonable estimate of the total energy use across the supply chain.Copyright © 2011 by ASME
Termination and hydration of forsteritic olivine (0 1 0) surface

Abstract Termination and hydration of the forsteritic (Fo90Fa10) olivine (0 1 0) surface have been investigated with high-resolution specular X-ray reflectivity and Atomic Force Microscopy. The surface was prepared by polishing a naturally grown {0 1 0} face, from which we found the polished surface in acidic (pH 3.5) alumina suspension exhibits regular steps while the basic (pH 9.5) silica polished surface is irregularly roughened, indicating there are two distinguishable mechanochemical processes for the surface dissolution. The quantitative interpretation of the regular steps from the alumina-polished surface suggests that the observed step heights correspond to multiples of crystallographic unit cell. Only this atomically terraced surface is investigated with the high-resolution X-ray reflectivity (HRXR) to determine the surface termination and hydration. The basic silica paste polished surface turned out too rough to measure with X-ray reflectivity. HRXR reveals that the alumina polished olivine (0 1 0) surface in pure water is terminated at a plane including half-occupied metal ion sites (M1), an oxygen vacancy site, and a silicate tetrahedral unit with one of its apices pointing outward with respect to the surface. An ideal termination with the oxygen vacancy would fulfill the stoichiometry of the formula unit; however, in the observation, the vacancy site is filled by an adsorbed water species and about a quarter of the remaining metal ions are further depleted. The terminating plane generates two distinct atomic layers in the laterally averaged electron density profile, on which two highly ordered adsorbed water layers are formed. The first layer formation is likely through the direct interaction with the M1 plane and the second layer is likely through the hydrogen bonding interaction with the first water layer. With this multilayered adsorbed water structure, the surface metal ion is partially hydrated by the vacancy-filling water species and adsorbed water molecules. The bulk water links to these distinct adsorbed water layers, with weak density oscillations that almost completely damp out after the first bulk water layer. The total thickness of the layered water structure including the two distinct adsorbed layers and the first layer of bulk water is slightly less than 1 nm, which corresponds to roughly three molecular layers of water. These results describe the steric constraints of the surface metal ion hydration and the iron redox environment during water–olivine interactions in this particular crystallographic orientation.
Spin-orbit-interaction-induced surface resonance on W(011).

A surface resonance has been observed on the (011) surface of tungsten using angle-resolved photoemission. The resonance is located near the center of the surface Brillouin zone in a pseudogap opened by the spin-orbit interaction. It is degenerate with a bulk band, which in the absence of the spin-orbit interaction would have a different symmetry than a state in the gap. The resultant weak coupling leads to the formation of a well-defined resonance. These conclusions are supported by polarization- and photon-energy-dependent studies. The generality of our observations is discussed.
A partially-averaged Navier–Stokes model for the simulation of turbulent swirling flow with vortex breakdown

Abstract This paper presents the development and validation of a new partially-averaged Navier–Stokes (PANS) model which can successfully predict turbulent swirling flow with vortex breakdown. The proposed PANS model uses an extended low Reynolds number k–e model as the baseline model. Furthermore, a new formulation for the unresolved-to-total turbulent kinetic energy ratio fk is developed using partial integration of the complete turbulence energy spectrum. Therefore, the present formulation of fk is believed to be superior to the previously used constant or computed values. The newly developed PANS model is used in unsteady numerical simulations of two turbulent swirling flows containing vortex breakdown, namely swirling flow through an abrupt expansion and flow in a draft tube of a hydraulic turbine operating under partial load. The present PANS model accurately predicts time-averaged and root-mean-square (rms) velocities in the case of the abrupt expansion, while it is shown to be superior to the Delayed Detached Eddy Simulation (DDES) and Shear Stress Transport (SST) k–ω models. Predictions of the reattachment length using the present model shows at least 14% and 23% improvements compared to the DDES and the SST k–ω models respectively. Also, transient features of the flow, e.g. vortex rope formation and precession, is well captured in the case of the complex draft tube flow. The frequency of the vortex rope precession, which causes severe fluctuations and vibrations, is well predicted by only 7% deviations from the experimental data.
Design and synthesis of a novel series of [1-(4-hydroxy-benzyl)-1H-indol-5-yloxy]-acetic acid compounds as potent, selective, thyroid hormone receptor β agonists

The design, synthesis, and structure activity relationships for a novel series of indoles as potent, selective, thyroid hormone receptor β (TRβ) agonists is described. Compounds with >50× binding selectivity for TRβ over TRα were generated and evaluation of compound 1c from this series in a model of dyslipidemia demonstrated positive effects on plasma lipid endpoints in vivo.
Sequence Dependent Exposure of Mammary Carcinoma Cells to Taxotere® and the MEK1/2 Inhibitor U0126 Causes Enhanced Cell Killing In Vitro

Taxol (paclitaxel) and Taxotere (docetaxel) are considered as two of the most important anti-cancer chemotherapy drugs. The cytotoxic action of these drugs has been linked to their ability to inhibit microtubule depolymerization, causing growth arrest and subsequent cell death. Studies by a number of laboratories have also linked suppression of mitogen activated protein kinase (MAPK) signaling to enhanced Taxol toxicity. The present study examined the interactions of the semi-synthetic taxane Taxotere with MEK1/2 inhibitors in epithelial tumor cells. Concurrent treatment of MDA-MB-231 mammary and DU145 prostate carcinoma cells with Taxotere and MEK1/2 inhibitor resulted in protection from the anti-proliferative effects of Taxotere in MTT assays. In contrast, in MCF-7 mammary cells, concurrent Taxotere and MEK1/2 inhibitor treatment weakly enhanced the anti-proliferative effects of the taxane. Sequential treatment of MDA-MB-231 and MCF-7 cells with Taxotere followed by MEK1/2 inhibitor also enhanced the anti-proliferative effects of the taxane in MTT assays. However, no enhancement was observed in DU145 or PC-3 cells. Colony formation assays, including isobologram analyses, provided a more definitive demonstration that MCF-7 and MDA-MB-231 cells were sensitized to the toxic effects of Taxotere by U0126. Similar data were observed using Laulimalide, which binds to tubulin at a different site to Taxotere. The enhancement in Taxotere anti-proliferative effects by U0126 correlated with increased cell killing, 48-72h after treatment of cells that was blocked by inhibition of caspase 9, but not caspase 8, function. This observation was associated with prolonged suppression of ERK1/2 and AKT activity, without alteration in either p38 or JNK1/2 activity. Collectively these findings demonstrate that sequential administration of Taxotere followed by MEK1/2 inhibition can lead to increased cell death and loss of reproductive capacity in some, but not all, human tumor cells.
Gastrointestinal motor effects of corticotropin-releasing factor in mice

The present investigation examined the effects of centrally and peripherally administered corticotropin-releasing factor on gastric emptying and gastrointestinal transit in mice. Corticotropin-releasing factor, given either intracerebroventricularly or intrathecally, caused a dose-dependent inhibition of gastric emptyping and gastrointestinal transit. Intravenous or intraperitoneal administration of corticotropin-releasing factor, while 5- to 7-fold less potent than after central injection, produced an equivalent level of effect. alpha-Helical corticotropin-releasing factor, a corticotropin-releasing factor receptor antagonist, blocked the effects of intracerebroventricularly administered corticotropin-releasing factor when the antagonist was given concurrently by the intracerebroventricular, but not by the intraperitoneal, route. Conversely, corticotropin-releasing factor, when given peripherally, was antagonized equally well by intracerebroventricular or intraperitoneal administration of the antagonist. The inhibition of gastric emptying induced by corticotropin-releasing factor was reduced by pretreatment with the ganglionic blocking agent, chlorisondamine, and in adrenalectomized mice, but this effect was not antagonized by naloxone. These findings provide evidence for an action of corticotropin-releasing factor within the central nervous system, as well as a peripheral site of action, to inhibit gastric emptying in the mouse. The gastrointestinal motor effects of corticotropin-releasing factor are not mediated through opioid mechanisms although their full expression may require intact autonomic innervation and adrenal function.
Contingency management for alcohol use reduction: a pilot study using a transdermal alcohol sensor.

Abstract Background Contingency management (CM) has not been thoroughly evaluated as a treatment for alcohol abuse or dependence, in part because verification of alcohol use reduction requires frequent in-person breath tests. Transdermal alcohol sensors detect alcohol regularly throughout the day, providing remote monitoring and allowing for rapid reinforcement of reductions in use. Methods The purpose of this study was to evaluate the efficacy of CM for reduction in alcohol use, using a transdermal alcohol sensor to provide a continuous measure of alcohol use. Participants were 13 heavy drinking adults who wore the Secure Continuous Remote Alcohol Monitoring (SCRAM) bracelet for three weeks and provided reports of alcohol and drug use using daily web-based surveys. In Week 1, participants were asked to drink as usual; in Weeks 2 and 3, they were reinforced on an escalating schedule with values ranging from $5 to $17 per day on days when alcohol use was not reported or detected by the SCRAM. Results Self-reports of percent days abstinent and drinks per week, and transdermal measures of average and peak transdermal alcohol concentration and area under the curve declined significantly in Weeks 2–3. A nonsignificant but large effect size for reduction in days of tobacco use also was found. An adjustment to the SCRAM criteria for detecting alcohol use provided an accurate but less conservative method for use with non-mandated clients. Conclusion Results support the efficacy of CM for alcohol use reductions and the feasibility of using transdermal monitoring of alcohol use for clinical purposes.
Street addiction: A proposed theoretical model for understanding the draw of street life and gang activity

Through qualitative analysis of interviews conducted with men who have histories of gang affiliation and street crime, this article posits understanding these behaviors through the framework of addictions. The participants in this study describe themselves as being addicted to the action of the streets and their narratives fit with the evolving framework of a behavioral addiction. There is currently no formal diagnosis for understanding the draw of action to street crime and gang association as addiction. Through semi-structured interviews we examine the key constructs of cognition and behaviors relevant to understanding the cycle of gang involvement, crime, and violence under the rubric of behavioral addictions. Thematic elements of significance emerged which parallel the analytic framework of addictions and delineate ways that being addicted to the “action of the streets” is a substantive factor in recidivism with the criminal justice system. The construct of “street addiction” articulated by those who ...
Middle LPC leaders and the contingency model of leadership effectiveness.

Abstract The present study examines the performance of middle least preferred co-worker (LPC) leaders in relation to the performance of high and low LPC leaders and tests Fiedler's contingency model of leadership effectiveness directly in an analysis of variance design. The results indicate that the performance of the middle LPC leaders is generally superior to that of the high and low LPC leaders in the situations that can be described by the model. In addition, the interaction between LPC and situational control predicted by the contingency model is found to be significant. The contribution of these findings to the contingency model and their theoretical implications are discussed.
Quantitative analysis of depolarization of backscattered light by stochastically inhomogeneous dielectric particles.

We determine the relationship between the depolarization properties of inhomogeneous particles and the statistical parameters of their internal refractive-index distributions. Our analysis demonstrates that the linear depolarization ratio of backscattered light by an inhomogeneous particle is approximately proportional to both the squared standard deviation and the squared correlation length of the particle’s internal refractive-index distribution. We verify this result by conducting rigorous numerical studies using the finite-difference time-domain method. This improved understanding of light depolarization by inhomogeneous structures may enhance polarization-based biomedical optical imaging techniques.
Some Estimates of Integrals with a Composition Operator

We give some estimates of integrals with a composition operator, namely, composition of homotopy, differential, and Green's operators , with the Lipschitz and norms. We also have estimates of those integrals with a singular factor.
Mechanisms of Abnormal Renal Sodium Handling in Obesity Hypertension

Obesity-induced hypertension, like all forms of experimental and human hypertension studied thus far, is associated with renal dysfunction characterized by the resetting of pressure natriuresis. In obese subjects, this resetting is primarily a result of increased renal tubular reabsorption as glomerular filtration rate and renal blood flow are markedly elevated. Obesity activates the sympathetic nervous and renin-angiotensin systems, and causes insulin resistance and hyperinsulinemia, all of which have been postulated to increase tubular reabsorption and raise blood pressure. In humans and dogs, chronic hyperinsulinemia, comparable to that found in obesity, does not cause hypertension even in the presence of insulin resistance. Activation of the sympathetic nervous system appears to be important in obesity, as chronic adrenergic blockade or renal denervation greatly ameliorates the hypertension associated with weight gain. Resetting of pressure natriuresis in obesity may also be attributable to altered intrarenal forces caused by histologic changes in the renal medulla that may compress the loops of Henle and vasa recta, increase tubular sodium reabsorption, and activate the renin-angiotensin system. The quantitative importance of these intrarenal changes and their interrelationship with neurohumoral activation in obesity is an important area for further investigation.
Conservative motion of discrete, tetrahedral tops and gyroscopes

Abstract Tetrahedral tops and gyroscopes are simulated as discrete, rigid bodies in rotation by introducing a molecular mechanics formulation. The model uses the popular engineering lumped mass technique, so that molecules are aggregated into particles at the vertices. The conservative, dynamical differential equations are solved numerically in such a fashion that all the system invariants are preserved. Examples which include precession and nutation are described and discussed.