cssi/SciSciGPT-SciSciNet huggingface dataset:
Risk extrapolation for chlorinated methanes as promoters vs initiators of multistage carcinogenesis

"Cell-kinetic multistage" (CKM) models account for clonal growth of intermediate, premalignant cell populations and thus distinguish somatic mutations and cell proliferation as separate processes that may influence observed rates of tumor formation. This paper illustrates the application of two versions of a two-stage CKM model (one assuming exponential and the other geometric proliferation of intermediate cells) for extrapolating cancer risk potentially associated with exposure to carbon tetrachloride, chloroform, and dichloromethane, three suspect human carcinogens commonly present in trace amounts in groundwater supplies used for domestic consumption. For each compound, the models were used to calculate a daily oral "virtually safe dose" (VSD) to humans associated with a cancer risk of 10(-6), extrapolated from bioassay data on increased hepatocellular tumor incidence in B6C3F1 mice. Exposure-induced bioassay tumor responses were assumed first to be due solely to "promotion" (enhanced proliferation of premalignant cells, here associated with cytotoxicity), in accordance with the majority of available data on in vivo genotoxicity for these compounds. Available data were used to model dose response for induced hepatocellular proliferation in mice for each compound. Physiologically based pharmacokinetic models were used to predict the hepatotoxic effect (metabolized) dose as a function of parent compound administered dose in mice and in humans. Resulting calculated VSDs are shown to be from three to five orders of magnitude greater than corresponding values obtained assuming each of the compounds is carcinogenic only through induced somatic mutations within the CKM framework. Key issues and uncertainties in applying CKM models to risk assessment for cancer promoters are discussed.
Clinical trials for polyneuropathy: the role of nerve conduction studies, quantitative sensory testing, and autonomic function testing.

Summary:Clinical trials to assess the treatment of diabetic and other forms of polyneuropathy are becoming increasingly common. Nerve conduction studies, quantitative sensory testing, and autonomic function testing are often used in these trials. This article reviews the sensitivity and reproducibil
Ethical Decision Making in Turkish Sales Management

Both scholars and practitioners in the various business professions are becoming increasingly interested in knowing what determines managers to judge subordinates' behaviors as ethical or unethical, and what prompts them to either choose certain rewards or certain punishments to encourage or discourage, respectively, behaviors that are judged ethical or unethical. Traditionally, the study of organizational consequences of employees' behaviro has gained importance in view of the fact the managerial decisions aimed at influencing subordinates' ethical conduct seem to be affected by the consideration of the consequences of such behavior for the company (utilitarian ethics). More recently, the perception that people act morally because of a prevailing moreal commitment (deontological ethics) has gained some ground. Moreoever, recent research findings show that deotological (moral) considerations prevail over teleological (consequential) considerations. Our study replicates this research in a different setting...
Review and management of side effects associated with antiplatelet therapy for prevention of recurrent cerebrovascular events.

The risk of secondary events following noncardioembolic ischemic stroke or transient ischemic attack (TIA) is high and especially pronounced in the first days and weeks following the initial event; to reduce this risk, it is recommended that antiplatelet therapy be initiated immediately. Although the risk and impact of antiplatelet-associated side effects are generally far less substantial than those of secondary events, some (especially bleeding) can be severe and even life-threatening, and others may reduce adherence to antiplatelet regimens. Therefore, clinicians should implement strategies to reduce the risk of side effects and to manage those that occur. Three antiplatelet regimens have demonstrated substantial reductions in secondary event risk and are currently recommended by consensus panels: aspirin monotherapy at 50–325 mg/day; the combination of aspirin plus extended-release dipyridamole (ER-DP); and clopidogrel monotherapy. Bleeding is potentially the most significant antiplatelet-associated side effect. As bleeding risk with aspirin monotherapy is dose dependent, while preventive efficacy appears similar at all doses above 50 mg/day, aspirin doses should be kept as low as possible. Clopidogrel bleeding risk is similar to aspirin, although a reduced incidence of gastrointestinal bleeding events suggests lower gastrotoxicity. Clopidogrel should not be combined with aspirin after stroke or TIA, as the combination increases bleeding risk without improving antiplatelet efficacy. Patients should be assessed for bleeding risk (especially gastrointestinal bleeding) before initiating antiplatelet therapy; those at elevated risk should be made aware of the signs and symptoms of bleeding events to facilitate prompt treatment. The addition of ER-DP to aspirin does not increase bleeding risk, although ER-DP is associated with risk of headache, which may be severe. The prevalence of headache drops rapidly following initiation of ER-DP, suggesting most patients are able to “push through” this side effect; for those who find headache intolerable, short-term use of a reduced-dose regimen may be helpful.
AIDS virus seeks refuge in B cell follicles.

A study of SIV-infected rhesus macaques suggests that T follicular helper (TFH) cells, a specialized CD4+ T cell subset within the B cell follicles, are a sanctuary for SIV that is largely inaccessible to CD8+ T cells. These findings may open new avenues for research aimed at eradicating HIV.
Macrocyclic oligoimides. I. Preparation of macrocyclic oligoetherimides via Kricheldorf substitution polymerization

Macrocyclic oligoetherimides were synthesized by means of Kricheldorf's nucleophilic aromatic substitution polycondensation. A solution containing equimolar quantities of bis (trimethylsilyl ether) of bisphenol and arylenebis (fluorophthalimide) was continuously added into a high boiling solvent containing CsF catalyst under a pseudo-high dilution condition. The resulting reaction mixture contained a high yield of cyclic oligomers which could be isolated by solvent extraction.
Synthesis of Progesterone and Estradiol by Monkey Luteal Cells in Culture: Effects of Insulin, Thyroxine, Cortisol, and Cholesterol With and Without hCG

The objective of the present work was to define further the hormonal factor or factors which participate in the maintenance of primate luteal cells in culture, including both luteotropic and luteolytic processes. Corpora lutea (CL) were obtained from rhesus monkeys during midluteal phase (17-19 days after onset of menses) of the menstrual cycle and were dissociated with collagenase. In the first experiment the basic culture medium (FlO + 10% fetal calf serum) was supplemented by the nongonadotropin hormones insulin (I), thyroxin (T4), and cortisol (C), and/or cholesterol (Ch), in the presence or absence of human chorinoic gonadotropin (hCG). Concentrations of progesterone (P) and estradiol (E2) were determined by radioimmunoassay of unextracted samples. P synthesis by luteal cells in the basic medium progressively declined throughout the 10-day culture period. Although we were unable to stabilize P production under any condition, with the addition of I-T4 -C and in the presence of hCG, P synthesis was significantly higher (P <0.05) throughout the 10-day incubation period. E2 production showed a similar declining pattern, regardless of the composition of the culture medium. Ch alone had no beneficial effects on maintenance of high levels of P secretion, whereas in the presence of hCG production of P was enhanced (P<0.01) for the first 2 days of culture. In the second experiment the combination of any two nongonadotropin hormones with hCG appeared equally beneficial during the first 2 days of culture, after which P secretion declined rapidly. In an additional experiment, luteal cells were initially cultured with I-T4-C for 2, 4, 6 or 8 days, at which times hCG was added for the remaining days of culture. When hCG was initially added on Days 2 or 4, P production was significantly elevated on Days 4 and 6, and on Day 6, respectively, followed by a gradual decline. The results demonstrate that the combination of nongonadotropin hormones, when in concert with hCG, is beneficial in maintaining P synthesis at higher levels for longer intervals. Addition of hCG slowed the declining pattern of P production when introduced on culture Days 2 or 4; nevertheless, the declining pattern of P output continued. The current state of this culture system does not permit in vitro imitation of chorionic gonadotropin-induced “rescue” of CL, as it occurs in the fertile menstrual cycle.
Plasma gelsolin accumulates in macrophage nodules in brains of simian immunodeficiency virus infected rhesus macaques

Plasma gelsolin (pGSN), an isoform 1, is secreted by various types of cells in the central nervous system (CNS) and periphery, but not by the liver. pGSN circulates in blood and cerebrospinal fluid (CSF); however, its concentration in CSF is approximately twenty times lower than in plasma. It has been shown that several types of cells such as oligodendrocytes, neurons, and/or astrocytes contribute to the overall pool of pGSN in the CNS. Further, it has been postulated that pGSN plays multiple roles during microbial infection and modulates inflammatory responses; however, the exact mechanism of regulation is not known. We previously showed that levels of pGSN in CSF of individuals with advanced neurocognitive impairment due to HIV infection of the brain are decreased. Here, we show that macrophages express significant amounts of pGSN in response to HIV infection in vitro. Using immunohistochemistry of simian immunodeficiency virus infected rhesus monkey brains, we show that increased levels of pGSN are present in macrophage nodules creating locally a high level of this protein within the brain. This may not be reflected by the overall decreased level in the distinct CSF compartment.
Catecholamine regulation of the prefrontal cortex

The catecholamines dopamine (DA) and norepinephrine provide an essential modulatory influence on the working memory and attentional functions of the prefrontal cortex (PFC). The following critique reviews evidence that (1) either insufficient or excessive DA D1 receptor stimulation is detrimental to PFC function, while DA stimulation of the D2 family of receptors may contribute to detrimental actions in PFC and (2) that norepinephrine has an important beneficial influence on PFC function through its actions at post-synaptic, alpha 2A adrenergic receptors, but impairs PFC function through actions at alpha 1 adrenergic receptors. Critical levels of catecholamine stimulation may be needed to optimize PFC cognitive function; high levels of catecholamine release during stress may serve to take the PFC 'off-line' to allow faster, more habitual responses mediated by the posterior and/or subcortical structures to regulate behavior. These studies have relevance to our understanding and treatment of disorders with prominent symptoms of PFC dysfunction.
A large displacement, high frequency, underwater microelectromechanical systems actuator

Here, we demonstrate an in situ electrostatic actuator that can operate underwater across a wide range of displacements and frequencies, achieving a displacement of approximately 10 μm at 500 Hz and 1 μm at 5 kHz; this performance surpasses that of existing underwater physical actuators. To attain these large displacements at such high speeds, we optimized critical design parameters using a computationally efficient description of the physics of low quality (Q) factor underwater electrostatic actuators. Our theoretical model accurately predicts actuator motion profiles as well as limits of bandwidth and displacement.
The locus coeruleus in behavior regulation: evidence for behavior-specific versus general involvement.

Brief reviews of current catecholamine research techniques, the comparative anatomy of the nucleus locus coeruleus, and the role of noradrenaline in the brain are followed by an examination of the literature dealing with the effects of direct intervention in the locus coeruleus and its dorsal noradrenergic bundle upon learning and ingestion as representative behaviors. The evidence for a connection between behavior and structure points away from a behavior-specific relationship. Possible reinforcement and arousal functions are considered briefly. Morphological and physiological hints from the literature suggest a supportive or modulatory role for the locus coeruleus.
HIV disease: fallout from a mucosal catastrophe?

The pathogenesis of human immunodeficiency virus has long been thought to center on a gradual depletion of CD4+ T cells, with an average of 100 cells lost per microliter of blood per year. However, studies of macaques infected with simian immunodeficiency virus and humans infected with human immunodeficiency virus have shown that the infection rapidly kills most CD4+ T cells at mucosal surfaces. Although most CD4+ T cells reside at these sites, the magnitude of this assault on the immune system is not reflected in the peripheral blood. Here we consider models of human immunodeficiency virus disease pathogenesis given those findings and propose a hypothesis to account for particular aspects of the disease during the chronic phase of infection that can be directly attributed to early depletion of mucosal CD4+ T cells.
How Do High-Risk Youth Use the Internet? Characteristics and Implications for Prevention:

Using data from the Second Youth Internet Safety Survey, a nationally representative telephone survey of 1,500 youth Internet users (ages 10 to 17), this study explores differences in Internet use characteristics between high risk youth and other Internet users. Those youth who engaged in aggressive behavior online and those who used the Internet on a cell phone were about twice as likely to be classified as high risk (having experienced high parent conflict or child maltreatment) as compared to other Internet users. Those youth who talked with known friends online were significantly less likely to be included in the high risk group. Controlling for demographic and Internet use characteristics, youth who received an aggressive sexual solicitation were almost 2.5 times as likely to report experiencing physical abuse, sexual abuse or high parent conflict. Implications for prevention are discussed, including avenues for reaching high risk populations of youth.
Regulating Glut4 vesicle dynamics by phosphoinositide kinases and phosphoinositide phosphatases.

Abstract Phosphorylated derivatives of phosphatydylinositol (PtdIns), collectively called phosphoinositides (PIs), have been recognized as versatile second messengers and modulators of lipid membrane composition in all eukaryotes. Over the last several years, PIs emerged as key membrane-localized signals for regulating a myriad of cellular processes, including insulin-induced membrane receptor signaling, GLUT4 membrane trafficking and the accompanying actin cytoskeletal rearrangement. PIs are synthesized from PtdIns by the action of kinases, specific for one of the 3 hydroxyls at positions D-3, D-4 and D-5 in the inositol head group and are degraded/turned over by the also position-specific action of phosphoinositide phosphatases. Work over the last several years has clearly implicated the products of PI 3-kinase activity, PtdIns 3,4,5-P3 and PtdIns 3,4-P2, as key elements in the proximal insulin receptor signaling circuit that regulates GLUT4 membrane dynamics. Emerging evidence has accumulated to suggest the role for the products of PI 4-kinases and PI 5-kinases in this process, likely at more distal steps. Here I review our current understanding of the role for PIs and the enzymes involved in their turnover in the regulation of GLUT4 membrane dynamics in response to insulin, endothelin-1 and hyperosmotic shock.
Transgendered Prisoners in the United States: A Progression of Laws

In 1976, prisoners acquired the right to medical treatment from the U.S. Supreme Court through the Eighth Amendment to the United States Constitution, which forbade, in part, cruel and unusual punishment. The following year, a Fourth Circuit Court of Appeals ruled that medical treatment included psychiatric or mental health treatment. These rulings applied to general prisoners, but not initially prisoners who suffered from gender identity disorder. Courts ruled then that gender identity disorder was not a serious mental disorder—a critical component of the right to medical care and mental health treatment. Later, a few appeals courts ruled that gender identity disorder was a serious mental disorder, triggering a prisoner’s right to medical care and mental health treatment for this disorder. Prisoners with gender identity disorder have litigated for sex realignment surgery as part of their treatment, which prison administrators have balked. The latest ruling unequivocally ordered the Massachusetts Department of Corrections to give a prisoner suffering from gender identity disorder sex reassignment surgery, but the prison system has appealed. This ruling, and previous rulings, has furthered policy towards transsexual prisoners.
Antioxidant function of a novel selenoprotein in Drosophila melanogaster

Background : Insects appear to have diverged from both higher and lower organisms in their defense mechanisms against oxidative damage. They do not encode glutathione peroxidases or glutathione reductases, and their thioredoxin reductases exhibit distinct properties from those of higher and lower species. Nonetheless, appropriate balance of antioxidants and pro-oxidants, and protection from damaging reactive oxygen species are clearly crucial in insects for viability, normal functioning of signalling pathways and morphogenesis, and have been implicated in studies on longevity in flies and other organisms. We have used RNAi in D. melanogaster embryos and in Schneider S2 cells to inhibit expression of these proteins. We report that inhibition of either dselH or dselK expression significantly reduces viability in embryos. We further show that dselH silencing decreases total anti-oxidant capacity in embryos and Schneider cells, and increases lipid peroxidation in cells. Conversely, transient expression of dselH in the cell line decreases lipid peroxidation, and reverses the toxic effects of a glutathione-depleting drug. The latter correlates with sparing of glutathione levels.
A BIBLIOGRAPHY OF VETERINARY RADIOTHERAPY

A review of the veterinary radiotherapy literature from 1939 through June of 1989 is presented. Subject material includes: radiation effects/injury, radiation oncology, hyperthermia, phototherapy, and various combination treatment protocols. Species covered are divided into small animal (canine, feline), large animal (equine, bovine, caprine, ovine) and miscellaneous species.
Specific binding of CAP factor to lac promoter DNA.

CATABOLITE repression in Escherichia coli is mediated by the cyclic AMP dependent catabolite activator protein (CAP). Growth conditions where the induced catabolism of certain sugars is energetically favourable, primarily in the absence of glucose, promote the intracellular induction of a high cyclic AMP concentration; CAP binds cyclic AMP, is activated, and stimulates mRNA synthesis from promoters of catabolite repressible operons1–4. The mechanism by which CAP influences the interaction between RNA polymerase and promoter DNA in unknown. Purified CAP preparations exhibit a cyclic AMP-dependent DNA binding activity, but efforts to detect specific binding to promoters of catabolite repressible genes have been unsuccessful; all DNAs tested have shown similar binding affinities5,6. The only evidence for a specific interaction between CAP and promoter DNA is a fluorescent probe study which showed that a lac transducing phage DNA molecule induces a conformational change in CAP that is not seen with the wild-type phage molecule7; but no effort was made to correlate this difference with in vivo CAP behaviour. Here I report experiments which demonstrate that the CAP factor binds specifically to a site within the lac promoter. This binding is sensitive to mutations which affect the ability of CAP to stimulate in vivo and in vitro lac gene expression.
On the discontinuity of lyapunov exponents of an almost periodic linear differential system affinely depending on a parameter

We construct a linear differential system \( \dot x \) = (A(t) + μB(t))x, x ∈ ℝ2, t ≥ 0, with almost periodic coefficients which is almost reducible for all μ ∈ ℝ except for an at most countable set and whose singular and higher characteristic exponents treated as functions of the parameter μ are discontinuous at some point.
STATistical power of clonal analysis: differential STAT1 pathway activation downstream of the JAK2V617F mutation.

The biological basis of the phenotypic diversity observed in JAK2V617F -positive myeloproliferative neoplasms is poorly understood. In this issue of Cancer Cell , Chen et al. show that interferon and STAT1 signaling are activated in essential thrombocythemia but not in polycythemia vera. STAT1 promotes megakaryopoiesis and thus contributes to an essential thrombocythemia phenotype.
Reflections on the memory wall

This paper looks at the evolution of the "Memory Wall" problem over the past decade. It begins by reviewing the short Computer Architecture News note that coined the phrase, including the motivation behind the note, the context in which it was written, and the controversy it sparked. What has changed over the years? Are we hitting the Memory Wall? And if so, for what types of applications?
Self-Configuring Applications for Heterogeneous Systems: Program Composition and Optimization Using Cognitive Techniques

This paper describes several challenges facing programmers of future edge computing systems, the diverse many-core devices that will soon exemplify commodity mainstream systems. To call attention to programming challenges ahead, this paper focuses on the most complex of such architectures: integrated, power-conserving systems, inherently parallel and heterogeneous, with distributed address spaces. When programming such complex systems, new concerns arise: computation partitioning across functional units, data movement and synchronization, managing a diversity of programming models for different devices, and reusing existing legacy and library software. We observe that many of these challenges are also faced in programming applications for large-scale heterogeneous distributed computing environments, and current solutions as well as future research directions in distributed computing can be adapted to commodity computing environments. Optimization decisions are inherently complex due to large search spaces of possible solutions and the difficulty of predicting performance on increasingly complex architectures. Cognitive techniques are well suited for managing systems of such complexity, citing recent trends of using cognitive techniques for code mapping and optimization support. Combining these, we describe a fundamentally new programming paradigm for complex heterogeneous systems, where programmers design self-configuring applications and the system automates optimization decisions and manages the allocation of heterogeneous resources.
Comparison of conformal and nonconformal meshes in the electromagnetic simulation of atherosclerotic lesions

The complex impedance that would be measured by a four-point electrode on the intimal surface of type Va and Vb atherosclerotic lesions was simulated using two different electromagnetic software programs. One program used a nonconformal hexahedral mesh of 2.5 million elements to describe the lesion morphology, whereas the second program used a Conformal mesh of 320,000 elements. Even though the nonconformal mesh used more elements, the geometry of the lesion and electrodes was more accurately described by the Conformal mesh. The impedance of the lesions was calculated for the frequencies of 10/sup 5/,10/sup 6/,10/sup 7/, and 10/sup 8/ Hz. The simulated resistance and phase of the lesion for both the nonconformal and conformal mesh were very similar. The small difference in the results can be attributed to the more accurate modeling of the interface between the electrodes and the underlying layer.
In situ nucleic acid hybridization of pyruvate dehydrogenase complex-E2 in primary biliary cirrhosis: pyruvate dehydrogenase complex-E2 messenger RNA is expressed in hepatocytes but not in biliary epithelium.

Abstract Pyruvate dehydrogenase-E2, or a cross-reactive molecule, has been shown by a variety of immunohistochemical methods to be present in increased amounts in biliary epithelial cells (BEC) in primary biliary cirrhosis (PBC). In this study, to further understand the nature of the immunoreactive molecule in BEC, we examined the expression of pyruvate dehydrogenase complex-E2 (PDC-E2) messenger RNA (mRNA) and PDC-E2 protein in sections of livers from patients and controls to help identify the molecule found in BEC. We performed in situ hybridization using an antisense probe against the major epitope of PDC-E2. The data were very striking and suggested that there was no increased production of PDC-E2 in BEC. For example, in livers from patients with PBC, PDC-E2 mRNA was found in periportal hepatocytes in 16 of 17 cases (94%). In contrast, interlobular bile ducts and septal bile ducts had detectable levels of PDC-E2 mRNA in only 1 of 17 (6%) and 3 of 8 (38%) cases, respectively. Interestingly, proliferating bile ductules contained detectable levels of mRNA in 12 of 15 cases (80%). In control liver, periportal hepatocytes were positive in 15 of 17 cases (88%). Interlobular bile ducts, septal bile ducts, and proliferating bile ductules expressed mRNA signals in 4 of 17 (24%), 2 of 10 (20%), and 14 of 16 (88%), respectively. When formalin-fixed, paraffin-embedded sections were examined by immunohistochemical staining with anti-PDC-E2 monoclonal antibody (mAb) C355.1, the interlobular bile ducts showed typical aberrant apical staining in all 10 PBC cases, but 0 of 9 liver controls. Periportal hepatocytes, proliferating bile ductules and infiltrating mononuclear cells stained with C355.1 but in a characteristic mitochondrial staining pattern. The presence of a PDC-E2-like molecule recognized by C355.1 is not reflected by the expression levels of PDC-E2 mRNA in the BEC of patients with PBC. (Hepatology 1997 Jan;25(1):27-32)
Object Recognition by Computer: The Role of Geometric Constraints

With contributions from Tomas LozanoPerez and Daniel P. Huttenlocher.An intelligent system must know "what "the objects are and "where "they are in its environment. Examples of this ubiquitous problem in computer vision arise in tasks involving hand-eye coordination (such as assembling or sorting), inspection tasks, gauging operations, and in navigation and localization of mobile robots. This book describes an extended series of experiments into the role of geometry in the critical area of object recognition. It provides precise definitions of the recognition and localization problems, describes the methods used to address them, analyzes the solutions to these problems, and addresses the implications of this analysis.The solution to problems of object recognition are of fundamental importance in many real applications and versions of the techniques described here are already being used in industrial settings. Although a number of questions remain to be solved, the authors provide a valuable framework for understanding both the strengths and limitations of using object shape to guide recognition.W. Eric L. Grimson is Matsushita Associate Professor in the Department of Electrical Engineering and Computer Science at MIT.Contents: Introduction. Recognition as a Search Problem. Searching for Correspondences. Two-Dimensional Constraints. Three-Dimensional Constraints. Verifying Hypotheses. Controlling the Search Explosion. Selecting Subspaces of the Search Space. Empirical Testing. The Combinatorics of the Matching Process. The Combinatorics of Hough Transforms. The Combinatorics of Verification. The Combinatorics of Indexing. Evaluating the Methods. Recognition from Libraries. Parameterized Objects. The Role of Grouping. Sensing Strategies. Applications. The Next Steps.
Smoothing-based Optimization

We propose an efficient method for complex optimization problems that often arise in computer vision. While our method is general and could be applied to various tasks, it was mainly inspired from problems in computer vision, and it borrows ideas from scale space theory. One of the main motivations for our approach is that searching for the global maximum through the scale space of a function is equivalent to looking for the maximum of the original function, with the advantage of having to handle fewer local optima. Our method works with any non-negative, possibly non-smooth function, and requires only the ability of evaluating the function at any specific point. The algorithm is based on a growth transformation, which is guaranteed to increase the value of the scale space function at every step, unlike gradient methods. To demonstrate its effectiveness we present its performance on a few computer vision applications, and show that in our experiments it is more effective than some well established methods such as MCMC, Simulated Annealing and the more local Nelder-Mead optimization method.
Automatic implantable cardioverter defibrillator implantation for malignant ventricular arrhythmias associated with congential heart disease

The prognosis for patients with congenital cardiac abnormalities can be improved by surgical correction of hemodynamics. With1 or without2 surgery, sudden death from malignant ventricular arrhythmias is an important potential problem in congenital heart disease. Pharmacologic arrhythmia control may be limited by side effects, noncompliance or unreliable indexes predictive of drug efficacy. The automatic implantable cardioverter difibrillator (AICD) is a potential alternative. The incidence of arrhythmic death is <2% per year following AICD implant3 in adults with ventricular arrhythmias refractory to medical management. This success rate favors AICD therapy in selected patients with congenital heart disease. We present 4 such cases (Table I) and discuss their management.
Active transport of proline in membrane preparations from Mycobacterium phlei.

Abstract Active transport of proline was observed in both electron transport particles and cell membrane ghosts from Mycobacterium phlei. The transport of proline was dependent upon substrate oxidation and the presence of Li+ or Na+, but not upon the formation of a high energy phosphorylated intermediate. The requirement for Na+ was different from Na+ coupled transport systems which have been described; as the concentration of Na+ was increased, the Vmax of proline transport increased while the Km remained constant. Sonication of the membrane ghost preparations resulted in membrane vesicles which were equivalent to electron transport particles with respect to membrane orientation, and which were able to actively transport proline. The transport of proline by either of the two membrane preparations was dependent upon the nature of the substrate used as electron donor. Ascorbate-tetramethyl-p-phenylenediamine or succinate supported the transport of proline equally well in the membrane ghost preparations. In contrast, the transport of proline with electron transport particles was 10-fold greater with ascorbate-tetramethyl-p-phenylenediamine than with succinate. Furthermore, succinate induced proline efflux with the electron transport particles, but not with the membrane ghost preparations. Evidence is presented that succinic dehydrogenase is located on the cytoplasmic side of the membrane.
Heritability of oral microbial species in caries-active and caries-free twins

Oral microbes that colonize in the mouths of humans contribute to disease susceptibility, but it is unclear if host genetic factors mediate colonization. We therefore tested the hypothesis that the levels at which oral microbes colonize in the mouth are heritable. Dental plaque biofilms were sampled from intact tooth surfaces of 118 caries-free twins. An additional 86 caries-active twins were sampled for plaque from carious lesions and intact tooth surfaces. Using a reverse capture checkerboard assay the relative abundance of 82 bacterial species was determined. An integrative computational predictive model determined microbial abundance patterns of microbial species in caries-free twins as compared to caries-active twins. Heritability estimates were calculated for the relative microbial abundance levels of the microbial species in both groups. The levels of 10 species were significantly different in healthy individuals than in caries-active individuals, including, A. defectiva, S. parasanguinis, S. mitis/oralis, S. sanguinis, S. cristatus, S. salivarius, Streptococcus sp. clone CH016, G. morbillorum and G. haemolysans. Moderate to high heritability estimates were found for these species (h(2) = 56%-80%, p < .0001). Similarity of the overall oral microbial flora was also evident in caries-free twins from multivariate distance matrix regression analysis. It appears that genetic and/or familial factors significantly contribute to the colonization of oral beneficial species in twins.
Chiral discrimination in dispersion interactions and sum frequency generation

It is shown that the orientation averaged dispersion interaction which exhibits chiral discrimination is proportional to a double frequency integral of the product of two complex sum frequency generation responses.
The effect of percutaneous dimethyl sulfoxide on cutaneous manifestations of systemic sclerosis

DMSO exerts a palliative, therapeutic effect on healing of cutaneous ulcers in systemic sclerosis. The therapeutic response was variable and, therefore, the concentration of DMSO, as well as frequency and duration of treatments, should be individualized to obtain maximum healing effect with a minimum of adverse reactions. There was no evidence of ocular toxicity or other serious toxicity manifestations in this group of patients treated with topical DMSO for one year or longer. Delayed improvement was observed in the untreated extremity in the majority of patients studied. In no instance did improvement in the untreated extremities exceed improvement in the treated, bilateral counterpart. It is believed this resulted from a systemic, carry-over effect of DMSO rather than spontaneous improvement in the disease course. DMSO is a worthwhile, supplemental, therapeutic agent providing the limitations of therapy are understood.
Use of DNA Ladders for Reproducible Protein Fractionation by Sodium Dodecyl Sulfate−Polyacrylamide Gel Electrophoresis (SDS−PAGE) for Quantitative Proteomics

In proteomics, one-dimensional (1D) sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) is widely used for protein fractionation prior to mass spectrometric analysis to enhance the dynamic range of analysis and to improve the identification of low-abundance proteins. Such protein prefractionation works well for quantitation strategies if the proteins are labeled prior to separation. However, because of the poor reproducibility of cutting gel slices, especially when small amounts of samples are analyzed, its application in label-free and peptide-labeling quantitative proteomics methods has been greatly limited. To overcome this limitation, we developed a new strategy in which a DNA ladder is mixed with the protein sample before PAGE separation. After PAGE separation, the DNA ladder is stained to allow for easy, precise, and reproducible gel cutting. To this end, a novel visible DNA-staining method was developed. This staining method is fast, sensitive, and compatible with mass spectrometry. To evaluate the reproducibility of DNA-ladder-assisted gel cutting for quantitative protein fractionation, we used stable isotope labeling with amino acids in cell culture (SILAC). Our results show that the quantitative error associated with fractionation can be minimized using the DNA-assisted fractionation and multiple replicates of gel cutting. In conclusion, 1D PAGE fractionation in combination with DNA ladders can be used for label-free comparative proteomics without compromising quantitation.
Detection of internal insects in wheat using a conductive roller mill and estimation of insect fragments in the resulting flour

A laboratory roller mill that monitors the conductance of kernels that pass through it was tested for its ability to estimate the number of insect fragments in flour after milling. This system can test a kilogram of whole wheat in approximately 1 min and requires little sample preparation. Hard red winter wheat samples were infested with lesser grain borers and stored at 24 � C. Infestations ranged from 12 to over 2000 infested kernels per 1 kg or per 30,000 kernels. After crushing of samples in the conductance instrument, the samples were milled into flour and sub-samples were sent to two laboratories for insect fragment analysis. The insect fragments were proportional to the number of detection incidences obtained using the conductance instrument and X-ray images. Insect fragment counts per 50 g of flour ranged from 0 to over 5000. For insect fragment counts from 0 to 250, correlations between fragment counts and conductance mill detection were 0.75 and 0.80 from two separate cereal chemistry laboratories. Therefore, the conductance mill is potentially a good method for testing incoming grain for live internally infesting insects; it is able to test 1 kg of grain in about 1 min and can detect low levels (as low as three insects) of live internal infestations in a 1- or 2-kg sample. Published by Elsevier Ltd.
Developmental Programming of Branching Morphogenesis in the Kidney

The kidney developmental program encodes the intricate branching and organization of approximately 1 million functional units (nephrons). Branching regulation is poorly understood, as is the source of a 10-fold variation in nephron number. Notably, low nephron count increases the risk for developing hypertension and renal failure. To better understand the source of this variation, we analyzed the complete gestational trajectory of mouse kidney development. We constructed a computerized architectural map of the branching process throughout fetal life and found that organogenesis is composed of two distinct developmental phases, each with stage-specific rate and morphologic parameters. The early phase is characterized by a rapid acceleration in branching rate and by branching divisions that repeat with relatively reproducible morphology. The latter phase, however, is notable for a significantly decreased yet constant branching rate and the presence of nonstereotyped branching events that generate progressive variability in tree morphology until birth. Our map identifies and quantitates the contribution of four developmental mechanisms that guide organogenesis: growth, patterning, branching rate, and nephron induction. When applied to organs that developed under conditions of malnutrition or in the setting of growth factor mutation, our normative map provided an essential link between kidney architecture and the fundamental morphogenetic mechanisms that guide development. This morphogenetic map is expected to find widespread applications and help identify modifiable targets to prevent developmental programming of common diseases.
At the Crossroads: The Intersection of Private Spirituality in the Public Workplace

Spirituality as an aspect of human work appears in religions, belief systems, and secular actions. Catholic Social Thought, expressed in John Paul II’s (1981) encyclical Laborem Exercens, serves as...
Simplified Expression for Seismic Fragility Estimation of Sliding-Dominated Equipment and Contents

Abstract Damage to small equipment and contents during seismic events has gained considerable attention following recent earthquakes, largely due to the potential for operational downtime, which results in significant economic losses. The estimation of losses from this interior building damage is a daunting task, due to the complexity of types of equipment and the randomness of their location within the structure. Nonetheless, a precursor to calculating such losses is a reasonable association between structural and nonstructural (equipment or contents) demands. Cast in a probabilistic framework, such an association is best represented through the use of seismic fragility curves, where the probabilities of exceeding a given damage state is correlated with an input parameter. In this paper, analytically developed seismic fragility curves for various unattached equipment and contents are calculated and presented. The emphasis of the study is on rigid scientific equipment and contents, which are often placed ...
A computerized diet history questionnaire for epidemiologic studies

Abstract Objective To describe methods used to computerized the diet history questionnaire developed for the Coronary Artery Risk Factor Development in Young Adult (CARDIA) study and to describe quality-control procedures used in conjunction with dietary assessment. Design The computerized diet history is being used in a case-control study. Because of the computerized nature of the questionnaire, we developed quality-control procedures that incorporate listening to an audiotape of the interview while visually reviewing recorded data. Setting Three centers involved in a population-based epidemiologic study of colon cancer. Subjects Men and women between the ages of 30 and 79 years. Results Quality-control results showed that 100% of the computerized forms would be free of errors if the data were subjected to visual review only. Probing errors, which accounted for 47.3% of all errors, were the most commonly encountered errors. In probing errors the interviewer did not probe in a nondirective manner, or the interviewer failed to verify responses that might be considered questionable. Applications The CARDIA diet history was computerized for use in epidemiologic studies of the association between diet and disease. Review of the audiotapes of the interviews showed that most errors made in obtaining a dietary assessment were not detectable from visual review of the data. Although the quality-control procedures were developed for a computerized diet history questionnaire, they are applicable to other dietary assessment methods.
Integrated CT-SPECT system for small animal imaging

We are developing a scanner for simultaneous acquisition of x-ray computed tomography (CT) and single photon emission tomography (SPECT) images of small animals such as mice and rats. The scanner uses a cone beam geometry for both the x- ray transmission and gamma emission projections by using an area x-ray detector and pinhole collimator, respectively. The CT and SPECT data set are overlaid to form a coregistered structural-functional 3D image. The CT system includes a single CCD-based x-ray detector and a microfocus x-ray source. The SPECT scanner utilizes tungsten pinhole collimators and arrays of CsI(Tl) scintillation detectors. We describe considerations and the early performance of a prototype scanner.
The Black-Litterman Model for Structured Equity Portfolios

The Black-Litterman model enables the development of sound inputs for portfolio optimization. Before Black-Litterman, investors were often frustrated by the seemingly unreasonable solutions that portfolio optimization techniques would produce. Many either abandoned the technology or relinquished most of its benefits by applying so many constraints that the solution was largely predetermined. In fact, any “unreasonable” solutions have been not so much a problem with optimization per se, but rather the result of feeding inconsistent risk and return forecasts into an optimizer. To be effective in optimization, risk and return forecasts must be consistent with one another. When structured equity portfolio managers who develop views based on factors (like value or momentum) want to use the Black-Litterman model to construct equity portfolios, they generally focus on returns relative to a benchmark. The basic Black-Litterman approach is robust in this case and easily adaptable to the problem at hand.
Healthcare Marketing On The Internet: A Review Of On-Going Concerns

There is no doubt that the Internet has proven itself to be the most powerful vehicle for distributing information to millions of individuals. After all, it is interactive, user-controlled, and provides a means for communication detailed information across a vast spectrum of topics. When the topic is healthcare marketing, its popularity becomes even more eminent. There are over 25,000 Internet health sites and this number is climbing rapidly. On the other hand, there are many who are concerned about the healthcare marketing practices on the Internet. One of the basic premises of these concerns is based on the questionable accuracy of the information on the Internet and the crucial impact of this lack of accuracy when the information is about healthcare. This paper proposes various research propositions to understand the nature of these concerns and the potential future of healthcare marketing efforts on the Internet. It is hoped that future inquiries of these propositions and the ones alike provide a better understanding of the required components of the upcoming healthcare marketing strategies.
Proteinuria and the Nephrotic Syndrome

Richard Bright drew attention to the association between renal disease and protein in the urine in 1827. Since that time proteinuria has become one of the major screening tests for pathology in the genitourinary tract. Recent work has greatly expanded our knowledge of the kidney’s role in the metabolism of many proteins. It is now recognized that, in contrast to the larger plasma proteins, many smaller proteins in the plasma are readily filtered, that there are well-developed tubular mechanisms for reabsorption of proteins, that the kidney plays a major role in the elimination or catabolism of many proteins, and that proteins may be added to the urine as it traverses the renal tubules and lower urine tracts. Thus the amount and types of protein appearing in the urine represent the sum of the amounts filtered through the glomeruli and the amounts reabsorbed and added to the urine in the tubules and lower urinary tract.