cssi/SciSciGPT-SciSciNet huggingface dataset:
The INTERSALT Study: background, methods, findings, and implications.

The INTERSALT Study is a standardized, worldwide epidemiologic study of large sample size (n = 10079 men and women aged 20-59 y from 32 countries) that tested both within- and cross-population prior hypotheses on 24-h sodium excretion and blood pressure. For individuals, a significant, positive, independent linear relation between 24-h sodium excretion and systolic blood pressure (SBP) was found. With multivariate adjustment for underestimation, the estimated effect of a sodium intake higher by 100 mmol/d was higher SBP/DBP (diastolic blood pressure) by approximately 3-6/0-3 mm Hg. This relation prevailed for both men and women, for younger and older people, and for 8344 people without hypertension. In tests of prior cross-population hypotheses (n = 52), significant, independent relations were found between sample 24-h median urinary sodium excretion and sample median SBP and DBP, prevalence rate of hypertension, and slope of SBP and DBP from age 20 to 59 y (median sodium intake greater by 100 mmol/d was associated with a 30-y increase in SBP/DBP, i.e., at the age of 55 y compared with 25 y, of 10-11/6 mm Hg. The INTERSALT results, which agree with findings from other diverse studies, including data from clinical observations, therapeutic interventions, randomized controlled trials, animal experiments, physiologic investigations, evolutionary biology research, anthropologic research, and epidemiologic studies, support the judgment that habitual high salt intake is one of the quantitatively important, preventable mass exposures causing the unfavorable population-wide blood pressure pattern that is a major risk factor for epidemic cardiovascular disease.
Asian linkages in children's writing and writing for children

: Reflecting on the influence of English nursery rhyme poems on one individual Asian child's language development, the paper reviews current studies on the socio-cultural dynamics of creativity, to examine how these theoretical and empirical investigations may help shape specific pedagogical practices in the expressive language arts in a Hong Kong context where English is not the first language, with particular reference to some Hong Kong young students’ responses to these creative writing classroom strategies.
Conserved enhancer and silencer elements responsible for differential Adh transcription in Drosophila cell lines.

Abstract The distal promoter of Adh is differentially expressed in Drosophila tissue culture cell lines. After transfection with an exogenous Adh gene, there was a specific increase in distal alcohol dehydrogenase (ADH) transcripts in ADH-expressing (ADH+) cells above the levels observed in transfected ADH-nonexpressing (ADH-) cells. We used deletion mutations and a comparative transient-expression assay to identify the cis-acting elements responsible for enhanced Adh distal transcription in ADH+ cells. DNA sequences controlling high levels of distal transcription were localized to a 15-base-pair (bp) region nearly 500 bp upstream of the distal RNA start site. In addition, a 61-bp negative cis-acting element was found upstream from and adjacent to the enhancer. When this silencer element was deleted, distal transcription increased only in the ADH+ cell line. These distant upstream elements must interact with the promoter elements, the Adf-1-binding site and the TATA box, as they only influenced transcription when at least one of these two positive distal promoter elements was present. Internal deletions targeted to the Adf-1-binding site or the TATA box reduced transcription in both cell types but did not affect the transcription initiation site. Distal transcription in transfected ADH- cells appears to be controlled primarily through these promoter elements and does not involve the upstream regulatory elements. Evolutionary conservation in distantly related Drosophila species suggests the importance of these upstream elements in correct developmental and tissue-specific expression of ADH.
The elderly, disabled and handicapped adult burned through abuse and neglect

A retrospective review of 1152 acute burns treated at the University of Michigan Burn Center during the past 5.5 years identified 26 adult patients in whom abuse and neglect was suspected. These patients, 12 females and 14 males, had an average age of 42 years and average total body area burn (TBA) of 18 per cent. Eight of these cases were in situations in which the question of inflicted injury was raised and 18 were in situations of neglect and/or improper supervision. Seven (27 per cent) died from their injury. All of these adults were either very old, mentally impaired, and/or physically handicapped. Twenty-three were burned in health care facilities or institutions. Adult abuse in the elderly, handicapped and disabled population is similar to that found in child abuse and includes characteristic burn patterns, a story that does not fit the injury, and a delay in seeking medical care. An increased awareness of the problem is necessary for improved diagnosis and management of these patients. Language: en
Endogenously Expressed Muscarinic Receptors in HEK293 Cells Augment Up-regulation of Stably Expressed α4β2 Nicotinic Receptors

Nicotine-induced up-regulation of neuronal nicotinic receptors (nAChRs) has been known and studied for more than 25 years. Other nAChR ligands can also up-regulate nAChRs, but it is not known if these ligands induce up-regulation by mechanisms similar to that of nicotine. In this study, we compared up-regulation by three different nicotinic agonists and a competitive antagonist of several different nAChR subtypes expressed in HEK293 cells. Nicotine markedly increased α4β2 nAChR binding site density and β2 subunit protein. Carbachol, a known nAChR and muscarinic receptor agonist, up-regulated both α4β2 nAChR binding sites and subunit protein 2-fold more than did nicotine. This increased up-regulation was shown pharmacologically to involve endogenously expressed muscarinic receptors, and stimulation of these muscarinic receptors also correlated with a 2-fold increase in α4 and β2 mRNA. Muscarinic receptor activation in these cells appears to affect CMV promoter activity only minimally (∼1.2 fold), suggesting that the increase in α4 and β2 nAChR mRNA may not be dependent on enhanced transcription. Instead, other mechanisms may contribute to the increase in mRNA and a consequent increase in receptor subunits and binding site density. These studies demonstrate the possibility of augmenting nAChR expression in a cell model through mechanisms and targets other than the nAChR receptor itself.
QCD tests with Kaons

Final results from an analysis of about 400 K± → π±γγ rare decay candidates collected by the NA48/2 and NA62 experiments at CERN are presented. The results include a model-independent decay rate measurement and fits to Chiral Perturbation Theory (ChPT) description. The data support the ChPT prediction for a cusp in the di-photon invariant mass spectrum at the two pion threshold. The NA48/2 Collaboration at CERN has accumulated unprecedented statistics of rare kaon decays in the Ke4 modes K±e4 → π+π− eν and K00e4 → π0π0eν with one percent background contamination. The detailed study of the form factors brings new inputs to low energy QCD description and crucial tests of predictions from ChPT and lattice QCD calculations.
Jet subdivision schemes on the k-regular complex

We introduce a new family of subdivision schemes called jet subdivision schemes. Jet subdivision schemes are a natural generalization of the commonly used subdivision schemes for free-form surface modeling. In an order r jet subdivision scheme, rth order Taylor expansions, or r-jets, of functions are the essential objects being generated in a coarse-to-fine fashion. Standard subdivision surface methods correspond to the case r=0. Just as the standard free-form subdivision surface schemes, jet subdivision schemes are based on combining (i) a symmetric subdivision scheme in the shift-invariant setting with (ii) an extraordinary vertex rule. We formulate the notions of stationarity, symmetry, and smoothness for jet subdivision schemes. We then extend some well-known results in the theory of subdivision surfaces to the setting of jet subdivision schemes.By incorporating high order data into the subdivision rules, jet subdivision schemes offer more degrees of freedom for the design of extraordinary vertex rules than do standard subdivision schemes. Using a simple 2-point stencil, we construct an order 1 jet subdivision scheme, which is interpolatory, C1 everywhere, and free from polar artifacts at extraordinary vertices of any valence. It is similar to the popular butterfly scheme, but unlike the butterfly scheme, it produces surfaces that can be explicitly parameterized by spline functions. In addition, our jet subdivision scheme allows for explicit control of gradient information on the resulting surface.We address the problem of constructing curvature continuous subdivision schemes at extraordinary vertices by giving an example of a 'flexible C2 scheme' for extraordinary vertex of valence k = 3. The stencils for this subdivision scheme coincide with those of the popular Loop scheme. We discuss the mathematical structure of this example of a C2 scheme.
Near-infrared spectroscopy: a potential method for continuous, transcutaneous monitoring for compartmental syndrome in critically injured patients.

Background: Near-infrared spectroscopy (NIRS) noninvasively measures tissue O 2 saturation (Sto 2 ), and has been proposed as a means of monitoring for compartmental syndrome (CS). However, its specificity in hypoxemic, hypotensive patients with severely reduced systemic oxygen delivery has not been tested. We hypothesized that NIRS can differentiate muscle ischemia caused by shock from ischemia caused by CS. Methods: Nine swine were anesthetized and an NIRS probe placed over the anterolateral compartment of the hind leg. Compartment pressure was also measured. A nerve stimulator was placed over the peroneal nerve, and CS was defined as loss of dorsiflexion twitch. At 30-minute sequential intervals, mean arterial blood pressure was reduced to 60% of baseline (phlebotomy), fraction of inspired oxygen was reduced to 0.15, and compartment pressure was increased in one limb by interstitial albumin infusion until CS occurred. Results: Hypotension combined with hypoxemia reduced Sto 2 from 82 ± 4% to 66 ± 10%. CS further reduced Sto 2 to 16 ± 12% (p < 0.0001). During hypotension + hypoxemia + CS, control limb Sto 2 was 70 ± 15% (p = 0.0002 vs. experimental limb). Conclusion: NIRS detects muscle ischemia caused by CS despite severe hypotension and hypoxemia, making it potentially useful in critically injured, unstable patients.
Spectral theory of two-point differential operators determined by −D2. I. Spectral properties

Abstract The necessary tools for the complete resolution of the spectral theory for all linear two-point differential operators L in L2[0, 1] determined by τ = −D2 and by boundary values B1, B2 are developed. All work is based on six numerical parameters defined in terms of the coefficients of B1, B2. These quantities are utilized in the development of the characteristic determinant of L and the Green's function of λI − L, and in the development of the projections of L2[0, 1] onto the generalized eigenspaces of L; they are used in the study of the decay rates of the resolvent operator R λ (L) as ¦λ¦ → ∞ ; and they are used to identify the 13 cases treated in developing the spectral theory for τ = −D2. All results pertaining to the spectrum σ(L) of L, to the algebraic multiplicities of the eigenvalues λ ϵ σ(L), to the ascents of the operators λI − L, to the boundedness of the family of all finite sums of the projections associated with L, to the denseness of the generalized eigenfunctions, and to bases consisting of generalized eigenfunctions are summarized in a table. The proofs of these results are the subject of the sequel (Part II).
Systems design engineering

Design is the creative process by which our understanding of logic and science is joined with our understanding of human needs and wants to conceive and refine artifacts that serve specific human purposes. Design is central to the practice of systems engineering and systems engineers understand that design is a creative, iterative, decision-making process. In this paper, we provide an overview of design from the perspective of the systems engineer. We review the steps in the design process and consider the characteristic activities, techniques, and tools of systems engineering in terms of how these activities support the central mission of systems design. We briefly discuss some of the major influences on current design research. Of particular interest is the axiomatic theory of design developed from the perspective of manufacturing engineering, which ultimately leads to a set of design principles, rules, and practices which are embodied in Design for Manufacture (DFM). DFM is a systems approach to improving the competitiveness of a manufacturing enterprise by developing products that are easier, faster, and less expensive to make, while maintaining required standards of functionality, quality, and marketability. We review the systems engineering philosophy underlying DFM—and its broader interpretation as concurrent or simultaneous engineering, or integrated product development—and define some of the strategies, techniques, and tools currently used to implement this philosophy in industry. © 1999 John Wiley & Sons, Inc. Syst Eng 1: 285–302, 1998
NURSHING BOTTLE WEANING: MATERNAL PERSPECTIVES

Numerous studies have documented the deleterious effects of prolonged bottle feeding in children. Little information exists regarding the optimal age for terminating bottle feedings, what advice pediatricians provide to parents, and what methods parents employ for bottle weaning. Information about bottle weaning practices was gathered from 172 mothers with bottle-fed children between the ages of 2 and 5 years (x = 42 mos.) scheduled for pediatric clinic visits. SES ranged from lower to upper middle, with 75% falling in the lower middle and lower categories. Forty percent of mothers reported pediatricians as the primary care provider. Although the mean recommended age for weaning was 7 months, the average age for attainment of daytime bottle weaning was 14 months. Seventy-one percent of mothers reported that bedtime bottle feeding practices were not discussed by their physicians. Forty-five percent of children were allowed to sleep with the bottle, which contained milk in 27% of the cases. Two weaning methods were commonly reported: (1) gradual reduction of the number of bottles (42%) and (2) abrupt termination (38%). Only 11% of mothers cited physicians as the primary source of information on nursing bottle weaning, with 36% relying on instinctual judgement. Data suggest pediatricians need to include explicit information on the timing of and methods for cessation of bottle feeding as part of anticipatory guidance interventions.
Quantitative description of mixture toxicity: Effect of level of response on interactions

The simultaneous exposure of a biological system to a mixture of toxic substances may result in an ideal or nonideal combination of effects. In an extension of linear isobole theory, models are quantitatively developed to describe these combinations, in which the nature of the nonideal effect combination may or may not be a function of the magnitude of predicted response (as opposed to only the proportions of the substances in a mixture). The approach is tested using data on rat carcinogenesis, drug action, and aquatic toxicity of pesticides. In the cases examined, the models predict substantial deviation from ideal behavior even under low doses.
New insights into the cellular mechanisms of vasospas

Previous attempts to define the etiology of coronary artery spasm have focused on such mechanisms as autonomic nervous system dysfunction or enhanced platelet activation leading to high levels of circulating vasoconstrictors. More recent evidence, however, suggests that the basic abnormality may be hypercontractility of the arterial wall associated with the atherosclerotic process itself. Results of both animal experiments and clinical studies support a role for certain cellular events in atherogenesis, including endothelial injury, presence of mitogenic factors and leukotrienes generated by platelets and macrophages, changes in histamine and serotonin receptor density of vascular smooth muscle and neovascularization of atherosclerotic plaque. The mechanisms postulated to underlie coronary vasospasm are discussed, relative to the clinical characteristics of vasospastic angina and the possible therapeutic implications.
Situating the concern for information privacy through an empirical study of responses to video recording

In this paper, we present the results of an empirical study of perceptions towards pervasive video recording. We describe a commonly used model for understanding information privacy, the Concern for Information Privacy (CFIP) model, and present the ways that this model and its associated questionnaire can shed light on information privacy concerns about pervasive and ubiquitous computing technologies. Specifically, the CFIP model encourages analysis of data across four facets of experience: the collection of personal data, the risk of improper access, the potential for unauthorized secondary use, and the challenge of preventing or correcting errors in the data. We further identify areas not well handled by this model of information privacy and suggest avenues for future work, including research on how and when to notify people about recording technologies, awareness of data provenance and leakage, and understanding of and access to the data assemblage being created about individuals.
acLDL Binding and Endocytosis by Macrophages and Macrophage Foam Cells in Situ

The direct binding and internalization of acLDL by monocyte-derived macrophages associated with atherosclerotic lesions in the White Carneau pigeon were observed. Using an organ culture labeling protocol, pigeon thoracic aortae containing atherosclerotic lesions were incubated with colloidal gold-acLDL conjugates. When analyzed by electron microscopy acLDL-gold was bound and internalized by monocyte-derived macrophages residing on the lumenal surface of the endothelium. Macrophage foam cells located within the intima and projecting from the lesion into the arterial lumen also bound and internalized acLDL. In contrast, acLDL was not observed in spherical (nonactivated) monocytes adherent to the lesion surface. Colabeling experiments with acLDL in combination with beta VLDL resulted in the preferential (> 90%) binding and internalization of acLDL by macrophages and macrophage foam cells. The results of this study indicated that macrophages located on the endothelial surface were able to bind and internalize lipoprotein, although this binding and internalization was enhanced in foam cells spanning the endothelium to the subendothelial intima. Acetyl-LDL binding and internalization was effectively inhibited through competition studies using an excess of unconjugated acLDL. Through the direct observation of lipoprotein binding by macrophages and foam cells, we have demonstrated the expression of a functional receptor for modified lipoprotein on monocyte-derived macrophages during different stages of association with foam cell lesions.
PREDICTING SOFTWARE QUALITY, DURING TESTING, USING NEURAL NETWORK MODELS: A COMPARATIVE STUDY

The application of statistical modeling techniques has been an intensely pursued area of research in the field of software engineering. The goal has been to model software quality and use that information to better understand the software development process. Neural network modeling methods have recently been applied to this field. The results reported indicate that neural network models have better predictive quality than some statistical models when predicting reliability and the number of faults. In this paper, we will investigate the application of principal components analysis to neural network modeling as a way of improving the predictive quality of neural network quality models. Using data we collected from a large commercial software system, we developed a multiple regression model using the principal components. Then, we trained two neural nets, one with raw data, and one with principal components. Then, we compare the predictive quality of the three competing models for a variety of quality measures.
A sulfhydryl group of the canine cardiac beta-adrenergic receptor observed in the absence of hormone.

Canine cardiac beta-adrenergic receptors contain a free sulfhydryl group in the adrenergic ligand binding site. (/sup 125/I)-Iodohydroxybenzylpindolol ((/sup 125/I)-IHYP) binding to cardiac beta-receptors was inhibitied 80% by treatment with 1 mM p-chloromercuribenzoic acid (pCMB). Occupation of the beta-receptors by an antagonist prior to treatment with pCMB prevented this effect suggesting that a sulfhydryl group is present in or near the ligand binding site of the cardiac beta-receptor. In the presence of agonists, the sensitivity of cardiac beta-receptors to pCMB was increased. Incubation of isoproterenol-occupied cardiac beta-receptors with 0.25 mM pCMB, which had no effect on the unoccupied receptors, resulted in a 57% inhibition of (/sup 125/I)-IHYP binding measured after extensive washing to remove bound agonist. The ability of isoproterenol to increase the reactivity of cardiac beta-adrenergic receptors supports the hypothesis that agonists produce a conformational change upon binding. 13 references, 4 figures, 1 table.
BOLD responses to visual stimulation in survivors of childhood cancer

Children surviving certain cancers have a high incidence of cognitive deficits caused by central nervous system (CNS) disease or treatments directed at the CNS. To establish the feasibility of using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study cognitive deficits in survivors of childhood cancer, we tested the hypothesis that this population has the same BOLD response to visual stimulation as healthy subjects. We used BOLD fMRI to measure spatial and temporal patterns of brain activity after brief visual stimulation in 16 survivors of childhood cancer, 11 age-similar healthy siblings of survivors, and 16 healthy adults. Functional data for the survivors were analyzed with two general linear models, one used a canonical hemodynamic response function (HRF) and the other used a Fourier set as basis functions. The measured BOLD signal and brain activation patterns were similar in the survivors with both models. The BOLD signal for survivors was qualitatively similar in timing and shape, but there were significant quantitative differences as compared with healthy subjects. The activation was normally located in the primary visual cortex in 13 survivors, but the activation volume was significantly smaller in brain tumor survivors than in other groups. These findings demonstrate the feasibility of using BOLD fMRI to investigate brain function in survivors of childhood cancer. However, fMRI studies in this population must take into account effects of quantitative differences in their BOLD responses as compared to healthy subjects.
RDIS: A recursively defined invertible set scheme to tolerate multiple stuck-at faults in resistive memory

With their potential for high scalability and density, resistive memories are foreseen as a promising technology that overcomes the physical limitations confronted by charge-based DRAM and flash memory. Yet, a main burden towards the successful adoption and commercialization of resistive memories is their low cell reliability caused by process variation and limited write endurance. Typically, faulty and worn-out cells are permanently stuck at either ‘0’ or ‘1’. To overcome the challenge, a robust error correction scheme that can recover from many hard faults is required. In this paper, we propose and evaluate RDIS, a novel scheme to efficiently tolerate memory stuck-at faults. RDIS allows for the correct retrieval of data by recursively determining and efficiently keeping track of the positions of the bits that are stuck at a value different from the ones that are written, and then, at read time, by inverting the values read from those positions. RDIS is characterized by a very low probability of failure that increases slowly with the relative increase in the number of faults. Moreover, RDIS tolerates many more faults than the best existing scheme-by up to 95% on average at the same overhead level.
Synthesis and structure of diamine bis(phenolate) complexes containing the Ti(OEt)–O–Ti(OEt) function

Abstract Reaction of diamine-bis(phenol) ligands containing a mixture of N-methyl and N,N′-dimethyl-N,N-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine, H2L1 and H2L3, with [Ti(OCHMe2)4 in absolute ethanol under reflux without exclusion of air and moisture gives [(L1)Ti (OEt–O–Ti(OEt)(L1)] (1). [(L3)Ti(OEt)–O–Ti(OEt)(L3)] (2) forms when the remaining solution containing [(L3)Ti(OEt)2] (3) (characterised by X-ray crystallography) is hydrolysed with H2O. For the N-methyl and N,N′-dimethyl ligand mixture H2L2 and H2L4, which contain tert-butyl groups on the ortho-positions of the aryl rings, [(L2)Ti(OEt)–O–Ti(OEt)(L2)] (4) forms much more slowly and [(L4)Ti(OEt)2] (5) does not hydrolyse when H2O is added. When the N-protonated ligand N,N-bis(2-hydroxy-3-methyl-5-tert-butylbenzyl)ethylenediamine, H2L5, is used, rapid hydrolysis to two isomers of [(L5)Ti(OEt–O–Ti(OEt)(L5)] (6) occurs without addition of water. For N,N-bis(2-hydroxy-3,5-di-tert-butylbenzyl)ethylenediamine, H2L6, hydrolysis to [(L6)Ti(OEt)–O–Ti(OEt)(L6)] (7) occurs slowly when H2O is added. For pendant NMe2 ligand N,N-dimethyl-N′,N′-bis(2-hydroxy-3-methyl-5-tert-butylbenzyl)ethylenediamine, H2L7, the hydrolysis reaction readily gives [(L7)Ti(OEt)–O–Ti(OEt)(L7)] (8) for which an X-ray crystal structure was obtained. The ortho-tert-butyl ligand derivative H2L8 formed a complex analysing as [(L8)Ti(OEt)–O–Ti(OEt)(L8)] (9) which could not be studied further due to insolubility. Pendant pyridine ligand N-(2-pyridylmethyl)-N,N-bis(2′-hydroxy-3′-methyl-5′-tert-butylbenzyl)amine, H2L9, apparently forms isomers of [(L9)Ti(OEt)–O–Ti(OEt)(L9)] and possibly [{(L9)Ti(O)}2] from [(L9)Ti(OEt)2] (10). The ortho-tert-butyl ligand derivative H2L10 formed [(L10)Ti(OEt)–O–Ti(OEt)(L10)] (11) for which an X-ray crystal structure was obtained.
Reconnaissance and Chemistry of the Lakes and Bogs of the Galapagos Islands

In the summer of 1966 Dr Colinvaux led an expedition to the Galapagos Islands with the aim of constructing an environmental history of the archipelago from the evidence in lacustrine deposits. This article describes the first results on the lakes and their chemistry.
Clinical use of a new pH 4.25 intravenous immunoglobulin preparation (gamimune-N).

Summary A multicentre, randomised, double-blinded, cross-over study was done to evaluate the clinical use and safety of a new immunoglobulin preparation for intravenous use (IVIgG). This reagent, IVIgG pH 4·25, was compared to a standard commercially available preparation IVIgG pH 6·8. Thirty-nine patients with primary immunodeficiency disease received a total of 232 infusions at a dose of 400 mg/kg every 4 weeks. Adverse effects from such infusions were transient and minimal. Clinically significant abnormalities did not occur. There were no statistically significant differences between the results for IVIgG pH 6·8 and for the new IVIgG pH 4·25 preparation. It was possible to infuse the new IVIgG pH 4·25 reagent at rates of 0·1 ml (5·0 mg)/kg/min without inducing vasomotor adverse effects.
Cyclophilin C-associated protein is a mediator for fibronectin fragment-induced matrix metalloproteinase-13 expression.

The function of cyclophilin C-associated protein (CyC-AP) on expression of extracellular matrix and matrix metalloproteinases (MMPs) was studied in CyC-AP-null mice. Fibronectin showed increased expression of the 53- and 29-kDa fragments in skin and wounds from CyC-AP-null mice. Type I collagen had an initial degraded pattern in the skin of CyC-AP-null mice, which did not occur in wild-type mice. MMP-3, MMP-13, MMP-14, and tumor necrosis factor-α (TNFα) had a higher expression in CyC-AP-null skin. During wound healing, MMP-13 and TNFα were stimulated to an even higher level, suggesting they are regulated by multiple factors. To understand the regulatory mechanisms of the up-regulated MMPs, the direct effects of TNFα, IL-1β, 45-kDa fibronectin fragment (FN-45), and the 70-kDa fibronectin fragments (FN-70) on the expression of MMPs were studied. MMP-13 expression increased significantly in both CyC-AP-null and wild-type dermal fibroblasts after treatment with IL-1β or with TNFα. However, MMP-13 expression did not increase in CyC-AP-null fibroblasts but did increase only in wild-type fibroblasts after FN-45 and FN-70 treatment. MMP-3 activation was induced by FN-45 and did not show a difference between CyC-AP-null and wild-type fibroblasts, suggesting different regulatory pathways for FN-45 on MMP-13 and MMP-3 expression. Our data are the first to demonstrate that deletion of CyC-AP can abolish fibronectin fragment-induced MMP-13 expression through an unknown mechanism. CyC-AP is an important factor for the regulation of MMP-13 expression.
Neurosecretion. XII. The formation of neurosecretory granules in the earthworm, Lumbricus terrestris L.

The granules of neurosecretory cells in the supraesophageal ganglion of the earthworm, Lumbricus terrestris L., are formed by the Golgi apparatus. The process of neurosecretion is discussed in relation to this observation.
Shifting ditypic site analysis: heuristics for expanding the phylogenetic range of nucleotide sequences in Sankoff analyses.

We describe and illustrate a simple heuristic approach to the Sankoff methods for construction of parsimonious evolutionary trees from nucleotide sequence data. The procedure is intended to permit more valid inferences, particularly from relatively short sequences, concerning relationships among taxa separated for long time intervals. The procedure is based on the freat variability of evolutionary plasticity among sites in the molecules and removes from consideration the more highly variable sites. Editing is accomplished after classifying sites in carefully aligned arrays of sequences. Only “ditypic sites,” i.e., sites observed in only two evolutionary states within the array, are used in making phylogenetic inferences. This strategy makes possible the construction of good approximations to the most parsimonious Steiner strees, by means of efficient programs that require “dense species arrays,” i.e., species sets that differ from each other by relatively small numbers of differences in conservative sites. The technique is illustrated with 5S and 5.8S rRNA sequence data from published catalogs.
Telehealth: An Assessment of Growth and Distribution

Telemedicine uses telecommunications technologies to deliver health care to populations located at some distance from health care providers. Telehealth is a somewhat broader term that includes non-clinical applications (such as education). This article draws on data from a nationwide survey of telehealth networks that assesses the extent and character of telemedicine activity. Although statistics point to increased utilization, the distribution of growth has been skewed toward a few applications and it is not clear that rural areas would derive substantial benefit in the absence of federal subsidy. Reported barriers to building sustainable programs often seem to reflect concerns of large hospitals and health care systems rather than constraints faced by rural organizational and individual network members. The potential role of government in addressing barriers is discussed.
Hydrodynamic plasmid DNA gene therapy model in liver transplantation.

Background There is great interest in the field of transplantation to genetically modify grafts to decrease preservation injury or allograft rejection. Although adenoviral gene transfer has been effective in experimental liver transplantation, viral toxicity and safety concerns limit potential use in clinical trials. Therefore, the purpose of this study was to develop a model of nonviral gene transfer in the liver transplant setting, allowing for efficient transgene expression. Materials and methods Orthotopic syngeneic rat liver transplantation was performed with 3 h cold ischemia using University of Wisconsin (UW) preservation. A hydrodynamic gene transfer technique was developed where plasmid DNA was delivered to the liver graft by ex vivo rapid infusion of DNA in UW via the IVC with other vessels clamped. Expression plasmids for the marker genes luciferase and secreted human α1-antitrypsin (α1-AT) were used. Hepatic injury was assessed by graft histology and liver transaminases. Transgene expression was determined by hepatic luciferase relative light units activity (RLU) and serum α1-AT protein levels. Variables examined included the effect of (a) volume injected on the intravenous pressure in the liver graft; (b) injury to the liver, as measured by hepatic enzymes and histopathology; (c) variable expression between lobes; (d) volume of UW that the plasmid is administered in; (e) amount of DNA plasmid; (f) type of the promoter used; (g) clamp time; as well as (h) the time course of the marker gene expression. Results Control rats underwent standard orthotopic syngeneic rat liver transplantation and had no detectable hepatic luciferase activity or serum human α1-AT. The optimal DNA plasmid dose was found to be 400 μg/liver graft, as there was no increase in the luciferase expression by increasing the dose. Furthermore, cytomegalovirus promoter yielded greater expression than Rous sarcoma virus. A high injection pressure gradient allowed for more efficient transgene expression, but produced greater liver injury shown by elevated transaminases and centrilobular necrosis. Lowering injection volume from 75 to 50% of graft weight decreased liver injury by 4.5-fold. Although higher UW injection volumes were associated with increased expression, volumes of only 50% led to luciferase expression up to 10,000,000 RLU/mg; this expression was homogeneous between the different liver lobes. Human α1-AT was detected in recipient blood as early as 6 h, peaked at 24 h, and remained high for 5 days. Conclusions We have developed a nonviral gene transfer technique where hydrostatic pressure across the cold-preserved liver vascular bed allows for efficient plasmid DNA delivery. This simple strategy should prove useful to genetically modify liver grafts in the transplantation setting.
The effects of caffeine on plasma MHPG, subjective anxiety, autonomic symptoms and blood pressure in healthy humans

The effects of oral administration of caffeine (10 mg/kg) on plasma free 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels, behavioral ratings, blood pressure, and autonomic symptoms was determined in eleven healthy subjects. Caffeine produced robust increases in subject rated anxiety and nervousness and small elevations in blood pressure and a decrease in heart rate. Caffeine did not alter plasma MHPG in a consistent fashion and there was no correlation between changes in plasma MHPG and changes in anxiety or other ratings. Caffeine may produce symptoms of anxiety-nervousness without increasing central norepinephrine turnover.
Correlation of peripheral venous pressure and central venous pressure in surgical patients.

Abstract Objective: To determine the degree of agreement between central venous pressure (CVP) and peripheral venous pressure (PVP) in surgical patients. Design: Prospective study. Setting: University hospital. Participants: Patients without cardiac dysfunction undergoing major elective noncardiac surgery (n = 150). Measurements and Main Results: Simultaneous CVP and PVP measurements were obtained at random points in mechanically ventilated patients during surgery (n = 100) and in spontaneously ventilating patients in the postanesthesia care unit (n = 50). In a subset of 10 intraoperative patients, measurements were made before and after a 2-L fluid challenge. During surgery, PVP correlated highly to CVP ( r = 0.86), and the bias (mean difference between CVP and PVP) was −1.6 ± 1.7 mmHg (mean ± SD). In the postanesthesia care unit, PVP also correlated highly to CVP ( r = 0.88), and the bias was −2.2 ± 1.9 (mean ± SD). When adjusted by the average bias of −2, PVP predicted the observed CVP to within ±3 mmHg in both populations of patients with 95% probability. In patients receiving a fluid challenge, PVP and CVP increased similarly from 6 ± 2 to 11 ± 2 mmHg and 4 ± 2 to 9 ± 2 mmHg. Conclusion: Under the conditions of this study, PVP showed a consistent and high degree of agreement with CVP in the perioperative period in patients without significant cardiac dysfunction. PVP −2 was useful in predicting CVP over common clinical ranges of CVP. PVP is a rapid noninvasive tool to estimate volume status in surgical patients. Copyright © 2001 by W.B. Saunders Company
Thermal transport properties of MgO and Nd2Zr2O7 pyrochlore by molecular dynamics simulation

Abstract Atomic level simulation methods are used to determine the thermal conductivity of magnesium oxide, MgO, and pyrochlore structured neodymium zirconate, Nd 2 Zr 2 O 7 , (NDZ), two potential constituents of inert-matrix fuel systems. A simple anharmonicity analysis correctly predicts that the simulated and experimental values of the thermal conductivity of MgO should be in good agreement, as we explicitly demonstrate. Likewise, they correctly predict significantly that a large correction is needed to bring consistency between the experimental and simulated thermal conductivities for NDZ. Simulations of the thermal conductivity of fine-grained polycrystals of both materials yield estimates of the temperature dependence of the interfacial conductance and of the grain-size dependence of the thermal conductivity.
Oxygen precipitate precursors and size thresholds for the preferential nucleation for copper and nickel precipitation in silicon: the detection of copper and nickel contamination by minority carrier lifetime methods

The precipitation of Cu and Ni at very small oxygen clusters has been investigated by an Elymat-based photocurrent technique. The technique has been demonstrated to be capable of revealing the point at which the precipitation at oxygen cluster sites becomes predominant over surface precipitation, even for very small amounts of metal contaminants. This corresponds to the threshold for effective gettering. Conversely the technique may also be useful as a simple and convenient method for detecting small amounts of Cu or Ni contamination by electrical means.
Effects of TNF-α neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome

In a prior study, we have shown that tumor necrosis factor (TNF)-α neutralization improves inflammatory markers and total adiponectin in patients with the metabolic syndrome, without improving insu...
Bedside twist drill craniostomy for chronic subdural hematoma: a comparative study.

Abstract Background Although the bedside twist drill craniostomy is used to treat chronic subdural hematomas, the efficacy of this technique has not been compared with that of standard treatments (operative bur hole or craniotomy). Methods Twist drill craniostomy was compared with operative bur hole or craniotomy in a prospective nonrandomized trial. The inclusion criteria were computed tomographic evidence of chronic subdural hematoma (isodense or hypodense compared with brain) and symptoms indicating the need for drainage. Selection of the procedure depended on the on-call surgeon's preference. Clinical success of the procedure, recurrence, length of hospitalization, complications, and neurologic outcome were compared. Results Between August 2001 and October 2002, 79 consecutive patients with 91 chronic subdural hematomas were treated (67 unilateral and 12 bilateral) at our institution. Fifty-five patients were treated with twist drill craniostomy and 24 with bur hole or craniotomy. There were no differences in the mean age of presentation, thickness of hematoma, length of hospitalization, reoperation rate, mortality rates, or ability to be discharged to home between the 2 groups. There was no difference in the neurologic outcomes in the 57 of the 79 patients available for follow-up. Conclusions Twist drill craniostomy performed at the bedside is just as effective in treating chronic subdural hematomas as bur holes or craniotomy in the operating room. This procedure can most often be the first line of treatment in patients with symptomatic chronic subdural hematomas.
An efficient enzymatic preparation of rhinovirus protease inhibitor intermediates

Abstract The development of an efficient route for the preparation of (2S)-2-[3-{[(5-methylisoxazol-3-yl)carbonyl]amino}-2-oxopyridin-1(2H)-yl]pent-4-ynoic acid ( 4 ), a key intermediate in the synthesis of a human rhinovirus (HRV) protease inhibitor, is presented. In the presence of 40% acetonitrile, the alkaline protease from Bacillus lentus can catalyze the kinetic resolution of racemic ester 7 to afford (S)-acid 4 in 49% chemical yield/per cycle with 98% ee and >98% HPLC purity. The (R)-ester can then be readily recycled via a DBU catalyzed epimerization. The enzymatic preparation described here is superior to the existing chemical resolution route, exhibiting lower costs as well as higher yields, enantioselectivity, and substrate loads. In addition, this protease displays broad substrate specificity toward this class of compounds and can be easily extended to the preparation of other tripeptide mimetics of rhinovirus protease inhibitors.
Colorectal carcinoma and brain metastasis: distribution, treatment, and survival.

Background: Brain metastasis from colorectal cancer is rare. The present study reports the nature of this disease and analyzes factors correlated with survival in patients harboring such disease. Patients and Methods: One hundred patients diagnosed between 1980 and 1994 with metastatic brain tumors secondary to colorectal adenocarcinoma were retrospectively reviewed. Of these patients, 36 underwent surgery, 57 underwent radiotherapy alone, and the remaining seven received steroids. Results: The most common primary sites were the sigmoid colon and rectum (65%). Brain metastases with concomitant liver and/or lung metastases were seen more frequently than brain metastases alone. The median interval between the diagnosis of primary cancer and the diagnosis of brain metastasis was 26 months (95% confidence interval =22–30). The median survival time after the diagnosis of brain metastasis was 1 month for patients who received only steroids, 3 months for those who received radiotherapy (p=0.1), and 9 months for those who underwent surgery (p 0.05), but early onset of brain metastasis was significantly associated with poor prognosis (p=0.04). Conclusion: Surgical removal of colorectal metastatic brain lesions results in significantly increased survival time, regardless of the status of the noncerebral systemic disease.
THERMAL STRESSES OF ROTATING ROLLS IN ROLLING PROCESSING

In a modern rolling mill, proper roll cooling has been identified as a critical factor in the problems of excessive roll wear and poor surface finish of rolled product. In this paper, an analytical solution to determine the cyclic stresses produced in the roll is developed. An understanding of the cyclic stresses can be utilized to evaluate roll wear and leads to proper cooling practices for increasing roll life and better product surface quality. In the present analysis, a rotating roll subjected to surface heat fluxes and convective cooling is considered under the assumption that it rotates at high speeds. The methods of the thermoelastic displacement potential and the general stress function are used to solve the governing partial differential equations in order to calculate the thermal stresses. Examples of typical rolling conditions are given to demonstrate the feasibility and applicability of the model developed
Use and Misuse of Motor Vehicle Crash Death Rates in Assessing Highway Safety Performance

Objectives. The objectives of the article are to assess the extent to which comparisons of motor-vehicle crash death rates can be used to determine the effectiveness of highway-safety policies over time in a country or to compare policy effectiveness across countries. Methods. Motor-vehicle crash death rates per mile traveled in the 50 U.S. states from 1980 to 2003 are used to show the influence on these rates of factors independent of highway-safety interventions. Multiple regression models relating state death rates to various measures related to urbanization and demographics are used. Results. The analyses demonstrate strong relationships between state death rates and urbanization and demographics. Almost 60% of the variability among the state death rates can be explained by the independent variables in the multiple regression models. When the death rates for passenger vehicle occupants (i.e., excluding motorcycle, pedestrian, and other deaths) are used in the regression models, almost 70% of the varia...
Feasibility of Converting Two-Way Left-Turn Lane into Bus Rapid Transit Lane

Although past research and experience have demonstrated the benefits of bus rapid transit (BRT) to the transportation system, implementation of BRT on congested local arterials having minimal or no rights-of-way remains a challenge. A feasible solution is to use the two-way left-turn lane (TWLTL) in the center of local streets for the purpose of BRT during peak hours. However, a TWLTL can be used in two ways for this purpose: directly as a median BRT lane and as a reversible general traffic lane (so that the curb lane is reserved for BRT). Without a clear understanding of the impacts of traffic characteristics, intersection layouts, and traffic signal control types on each of the alternatives, transit agencies usually have difficulty in determining the option that best serves transit vehicles and simultaneously minimizes impacts to the general traffic. This study evaluates the performance of a median BRT lane and a curb BRT lane and considers varying traffic conditions and physical configurations of the street and the intersections. The pros and cons of each alternative are also specified, in accordance with the simulation analysis.
Ageing of Neurospora crassa. II. Organic hydroperoxide toxicity and the protective role of antioxidant and the antioxygenic enzymes.

Abstract Cumene hydroperoxide and tert. -butyl hydroperoxide at sublethal concentrations initially prevent growth of mycelia of wild-type Neurospora crassa , but after a time the cells grow at a subnormal steady-state rate. The antioxidant nordihydroguaiaretic acid protects unadapted cells from hydroperoxide inhibition, leading to a decrease in the time before growth begins, an increase in steady-state growth rate and an increase in biomass production. The results of growth transfer experiments and enzyme measurements indicated that the acquired resistance to the hydroperoxides is physiological and most likely involves the induction of the synthesis of the antioxygenic enzymes superoxide dismutase, glutathione peroxidase and glutathione reductase. Nordihydroguaiaretic acid normalizes the levels of activities of glutathione peroxidase and glutathione reductase during culture with hydroperoxide. Molecular-induced homolysis of the hydroperoxides, a process that is induced by unsaturated fatty acids of membrane lipids, leads to lipid autoxidation in a chain reaction which produces lipid hydroperoxides, which in turn decomposes to form more free radicals. Nordihydroguaiaretic acid, a well-known free radical scavenger, probably serves to minimize hydroperoxide decomposition, lipid autoxidation and molecular damage from free radicals, whereas the coupled enzyme system glutathione peroxidase and glutathione reductase minimizes these processes by decomposing the hydroperoxides to harmless alcohols. We suggest that either free radicals derived from these processes or some consequent non-radical products may serve as the inducers of this enzyme system, rather than the hydroperoxide substrates.