cssi/SciSciGPT-SciSciNet huggingface dataset:
Vitamin D, DNA methylation, and breast cancer

Vitamin D has anticarcinogenic and immune-related properties and may protect against some diseases, including breast cancer. Vitamin D affects gene transcription and may influence DNA methylation. We studied the relationships between serum vitamin D, DNA methylation, and breast cancer using a case-cohort sample (1070 cases, 1277 in subcohort) of non-Hispanic white women. For our primary analysis, we used robust linear regression to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and methylation within a random sample of the cohort (“subcohort”). We focused on 198 CpGs in or near seven vitamin D-related genes. For these 198 candidate CpG loci, we also examined how multiplicative interactions between methylation and 25(OH)D were associated with breast cancer risk. This was done using Cox proportional hazards models and the full case-cohort sample. We additionally conducted an exploratory epigenome-wide association study (EWAS) of the association between 25(OH)D and DNA methylation in the subcohort. Of the CpGs in vitamin D-related genes, cg21201924 (RXRA) had the lowest p value for association with 25(OH)D (p = 0.0004). Twenty-two other candidate CpGs were associated with 25(OH)D (p < 0.05; RXRA, NADSYN1/DHCR7, GC, or CYP27B1). We observed an interaction between 25(OH)D and methylation at cg21201924 in relation to breast cancer risk (ratio of hazard ratios = 1.22, 95% confidence interval 1.10–1.34; p = 7 × 10−5), indicating a larger methylation-breast cancer hazard ratio in those with high serum 25(OH)D concentrations. We also observed statistically significant (p < 0.05) interactions for six other RXRA CpGs and CpGs in CYP24A1, CYP27B1, NADSYN1/DHCR7, and VDR. In the EWAS of the subcohort, 25(OH)D was associated (q < 0.05) with methylation at cg24350360 (EPHX1; p = 3.4 × 10−8), cg06177555 (SPN; p = 9.8 × 10−8), and cg13243168 (SMARCD2; p = 2.9 × 10−7). 25(OH)D concentrations were associated with DNA methylation of CpGs in several vitamin D-related genes, with potential links to immune function-related genes. Methylation of CpGs in vitamin D-related genes may interact with 25(OH)D to affect the risk of breast cancer.
Arrhythmias in Pregnancy and Postpartum

The significant physiologic adaptations of pregnancy predispose to arrhythmias, while concurrent changes in pharmacokinetics and concerns for fetal health and well-being complicate management. An increased incidence of both atrial and ventricular arrhythmias has been reported in population-based Holter studies, yet most incident pregnancy-related arrhythmias are benign and do not require intervention. Pharmacologic absorption, distribution, metabolism, and elimination are altered, as are gut absorption, protein binding, and hepatic and renal blood flow. This chapter will review antiarrhythmic drug therapy by Vaughn Williams classification, nonpharmacologic arrhythmia therapy (cardiovascular implanted electronic devices and ablation), as well as management of specific cardiovascular conditions during pregnancy, labor, and postpartum.
Abstract 493: Serum Leptin and TNFa Levels in Relation to Systolic and Diastolic Heart Function in Obese and Normal-overweight Pregnant. First Trimester Data

Introduction: Maternal obesity (MO) defined as pre-pregnancy body-mass index (BMI) >30kg/m2, is the strongest risk factors for preeclampsia (PE). Information regarding cardiac changes in MO as well...
Label free detection of pre-cancerous cells in vivo with a/LCI (Conference Presentation)

Detection of pre-cancerous (dysplastic) tissues in the clinic remains an ongoing challenge. Current methods often rely on systematic biopsies with no visual cues to guide the physician to areas likely to harbor dysplasia. We have developed novel spectroscopic techniques for assessing cell structure and diagnosing disease based on combining interferometry with light scattering. Angle-resolved low coherence interferometry (a/LCI) combines the depth gating of coherence imaging, as used in optical coherence tomography, with the high resolution structural information that can be obtained with light scattering spectroscopy. The a/LCI approach has been validated with in vitro measurements of phantoms and in vitro cells to recover sub-cellular structure with sub-wavelength accuracy and precision. Discrimination of pre-cancerous tissue states was initially demonstrated using animal models and ex vivo human tissues, by using light scattering and interferometry to measure the size of cell nuclei in selected tissue layers. We will discuss various light scattering models used in a/LCI, including Mie theory, T-matrix, and analysis methods based on wavelet transforms and machine learning, as they relate to their application to this clinical problem. To implement a/LCI for detection of pre-cancerous tissues in patients, we have developed a clinical a/LCI system, including a portable optical engine, and an endoscope compatible fiber probe for in vivo measurements. The capabilities of a/LCI will be shown with results from clinical studies to detect precancerous cells in both the esophagus and cervix during routine clinical examination. Further directions to enhance clinical utility and ergonomic ease of use will also be discussed.
Di-ionizable p-tert-butylcalix[4]arene-1,3-crown-4 ligands: synthesis and alkaline earth metal cation extraction

Abstract A series of di-ionizable calix[4]arene-1,3-crown-4 compounds has been synthesized. The ionizable groups are oxyacetic acid and N -(X)sulfonyl oxyacetamide groups with X=methyl, phenyl, 4-nitrophenyl and trifluoromethyl, which ‘tunes’ the acidity of the latter. The efficiency and selectivity of these novel ligands are assessed with competitive solvent extractions of alkaline earth metal cations from aqueous solutions into chloroform. The results are compared with those reported previously for calix[4]arene-crown analogues with crown-6 and crown-5 rings.
A positive emotion regulation intervention for bipolar I disorder: Treatment development and initial outcomes

Abstract Objective: Dysfunction in positive affect is a defining symptom of bipolar I disorder (BD), both during and between mood episodes. We hypothesize that helping people with BD learn skills to create balance in their affective experiences by engaging in strategies that increase low activation positive emotion (LAP; e.g., relaxation) could help to improve well-being during periods of symptom remission. We discuss the development and preliminary outcomes of a positive emotion regulation (PER) group treatment for people with BD, designed as a supplement to pharmacological treatment. Method: The Learning Affective Understanding for a Rich Emotional Life (LAUREL) intervention is a group-based intervention covering 10 empirically supported skills designed to increase LAP. Sixteen people with BD enrolled in the LAUREL intervention and twelve completed baseline and post-intervention assessments. Results: Participants who completed the study (n = 12) attended the majority of groups (87.96%) and reported practicing skills, on average, 16 times a week. We were unable to detect significant differences in mania symptoms following engagement in this PER intervention. Finally, participants reported increases in several areas associated with well-being post-intervention, including mindfulness, reappraisal, and self-compassion. Conclusion: This study provides a theoretical framework and preliminary support for a PER intervention for BD.
Continuous Flow Synthesis of ACE Inhibitors From N-Substituted l-Alanine Derivatives

A strategy for the continuous flow synthesis of angiotensin converting enzyme (ACE) inhibitors is described. An optimization effort guided by in situ IR analysis resulted in a general amide coupling approach facilitated by N-carboxyanhydride (NCA) activation that was further characterized by reaction kinetics analysis in batch. The three-step continuous process was demonstrated by synthesizing 8 different ACE inhibitors in up to 88 % yield with throughputs in the range of ≈0.5 g h-1 , all while avoiding both isolation of reactive intermediates and process intensive reaction conditions. The process was further developed by preparing enalapril, a World Health Organization (WHO) essential medicine, in an industrially relevant flow platform that scaled throughput to ≈1 g h-1 .
Predictors of Late Mortality in D‐Transposition of the Great Arteries After Atrial Switch Repair: Systematic Review and Meta‐Analysis

Background Existing data on predictors of late mortality and prevention of sudden cardiac death after atrial switch repair surgery for D‐transposition of the great arteries (D‐TGA) are heterogeneou...
Responding to Unprofessional Behavior by Trainees — A “Just Culture” Framework

Responding to Unprofessional Behavior by Trainees Professionalism lapses by trainees can be addressed productively if viewed through a lens of medical error, drawing on “just culture” principles. W...
Community-acquired pneumonia: Strategies for triage and treatment

Community-acquired pneumonia significantly contributes to patient morbidity and healthcare costs. As our understanding of this common infection grows, collaborative efforts among researchers and clinical societies provide new literature and updated guidelines informing its management. This review discusses diagnostic methods, empiric treatment, and infection prevention strategies for patients with suspected community-acquired pneumonia.
Therapeutic Approaches for NF1

Although there is not, as yet, a definitive treatment for NF1, many of the manifestations are amenable to various forms of treatment. Until recently, treatment options were focused mainly on surgical treatment of tumors or other lesions, such as skeletal dysplasias, and chemotherapy and/or radiation therapy for malignancies. Insights into the pathogenesis of NF1 has paved the way towards new therapeutics that target the underlying disease mechanisms. There are many ongoing clinical trials and some significant successes to date. Prospects for further development of targeted therapeutics for NF1 are bright, offering hope for effective treatments for many of the manifestations in the near future.
Examining International Students’ Holistic Wellness

This quantitative study examines differences between the holistic wellness of international students in the United States (n = 244) and a random sub-sample of their domestic U.S. peers (n = 244) us...
Benchtop plasma treatment of titanium surfaces enhances cell response.

Abstract Objective Modifications to implant surface properties, including topography, chemistry, and wettability, alter immune response, osteoblast differentiation of bone marrow stromal cells (MSCs), and implant integration in vivo. Dielectric barrier discharge (DBD) plasma treatment has been used to sterilize surfaces and remove adsorbed carbon, improving wettability. However, unless it is used immediately prior to placement, ambient atmospheric hydrocarbons rapidly adhere to the surface, thereby reducing its hydrophilicity. Moreover, this method is not practical in many clinical settings. The aim of this study was to evaluate the effectiveness of an on-site benchtop modification technique for implants at time of placement, consisting of a DBD plasma that is used to sterilize implants that are pre-packaged in a vacuum. Effects of the plasma-treatment on implant surface properties and cellular response of MSCs and osteoblasts were assessed in vitro. Methods Titanium-aluminum-vanadium implant surfaces were grit-blasted (GB) or grit-blasted and acid-etched (AE), and packaged under vacuum. AE surfaces were also plasma-treated using the benchtop device (GB + AE) and then removed from the vacuum. GB surface morphology was altered with AE but AE microroughness was not changed with the plasma-treatment. Plasma-treatment increased the surface wettability, but did not alter surface atomic concentrations of titanium, oxygen, or carbon. Results MSCs and osteoblast-like cells (MG63 s) produced increased concentrations of osteocalcin, osteopontin, and osteoprotegerin after plasma-treatment of AE surfaces compared to non-plasma-treated AE surfaces; production of IL6 was reduced and IL10 was. Aging GB + AE surfaces for 7 days after plasma-treatment but still in the vacuum environment reduced the effectiveness of plasma on cellular response. Significance Overall, these data suggest that application of benchtop plasma at the time of implant placement can alter the surface free energy of an implant surface without modifying surface chemical composition and enhance the differentiation and activity of MSCs and osteoblasts that are in contact with these implant surfaces.
Pipeline Construction Cost Forecasting Using Multivariate Time Series Methods

AbstractPipe material and labor costs constitute about 70% of pipeline construction costs. Pipe and labor costs are subject to considerable fluctuations over time. These fluctuations are problemati...
Stable finite difference methods for Kirchhoff-Love plates on overlapping grids.

In this work, we propose and develop efficient and accurate numerical methods for solving the Kirchhoff-Love plate model in domains with complex geometries. The algorithms proposed here employ curvilinear finite-difference methods for spatial discretization of the governing PDEs on general composite overlapping grids. The coupling of different components of the composite overlapping grid is through numerical interpolations. However, interpolations introduce perturbation to the finite-difference discretization, which causes numerical instability for time-stepping schemes used to advance the resulted semi-discrete system. To address the instability, we propose to add a fourth-order hyper-dissipation to the spatially discretized system to stabilize its time integration; this additional dissipation term captures the essential upwinding effect of the original upwind scheme. The investigation of strategies for incorporating the upwind dissipation term into several time-stepping schemes (both explicit and implicit) leads to the development of four novel algorithms. For each algorithm, formulas for determining a stable time step and a sufficient dissipation coefficient on curvilinear grids are derived by performing a local Fourier analysis. Quadratic eigenvalue problems for a simplified model plate in 1D domain are considered to reveal the weak instability due to the presence of interpolating equations in the spatial discretization. This model problem is further investigated for the stabilization effects of the proposed algorithms. Carefully designed numerical experiments are carried out to validate the accuracy and stability of the proposed algorithms, followed by two benchmark problems to demonstrate the capability and efficiency of our approach for solving realistic applications. Results that concern the performance of the proposed algorithms are also presented.
Draft Genome Sequences of Two Bacteria from the Roseobacter Group

Here, we report the draft genome sequences of strains HS012 and HS039, which were isolated from cnidarian polyps that had recently undergone metamorphosis. Genomic analyses place these strains within the Phaeobacter and Leisingera genera, members of the Roseobacter group.
Development of a PLGA Nanoparticle Drug Delivery System Containing Imaging/Hyperthermia and Chemotherapy Agents

Nanoparticulate drug delivery systems have the potential to allow delivery of diagnostic and therapeutic agents to tumor sites in a targeted manner. The objective of this study was to develop biodegradable poly(DL-lactide-co-glycolic acid) (PLGA) nanoparticles loaded with an imaging/hyperthermia agent and a chemotherapy agent to allow for simultaneous diagnostics and treatment. Indocyanine Green (ICG) was selected as the imaging/hyperthermia agent, and doxorubicin (DOX) as the chemotherapy agent. The modified oil in water emulsion solvent evaporation method was used for PLGA nanoparticle preparation. To achieve an optimal degree of incorporation and particle size, we systematically assessed four independent processing variables including amount of PLGA, initial ICG amount, initial DOX amount, and PVA concentration. For every combination, we measured the nanoparticle size and the percent entrapment of ICG and DOX into the PLGA nanoparticles. The nanoparticles produced by optimal formulation had sizes of 171± 2 nm, (n=3) with a low polydispersity index (0.040 ± 0.014, n=3). We determined the entrapment efficiency (by fluorescence measurements using DMSO burst release) as 44.4 ± 1.6 % for ICG and 74.3 ± 1.9 % for DOX. Drug loading was 0.015 ± 0.001 % w/w for ICG and 0.022 ± 0.001% w/w for DOX (n=3). The release pattern was biphasic.
Participatory Practice: Community-Based Action for Transformative Change by Ledwith, M., & Springett, J.

Participatory Practice: Community-Based Action for Transformative Change by Margaret Ledwith and Jane Springett is appropriately titled. The authors present a strong rationale for authentic partici...
Processing of Survey Data

Upon completion of data collection, the survey data must be converted from its raw and unedited state to a verified and corrected state that is ready for analysis and/or dissemination to the users. These steps may include questionnaire inspection, data entry, editing, coding, data preparation, documentation, and data analysis. This chapter discusses these steps as well as their potential effect on data quality. Keywords: coding; data cleaning; documentation; editing; data quality assurance; outliers; grouping/recoding variables; checking for nonresponse bias; weighting of data; missing data
Gene therapy for human SCID: Dreams become reality

After a decade of unsuccessful attempts to correct one form of severe combined immunodeficiency using gene therapy, success has finally been achieved in another genetic type. Whether this success is due to the type of defect or to other factors, such as improved retroviral vectors or stem cell growth conditions, is not yet apparent.
Diet alters probiotic Lactobacillus persistence and function in the intestine

Summary We investigated the effects of host diet on the intestinal persistence and gene expression of Lactobacillus plantarum WCFS1 in healthy and health-compromised, 2,4,6-trinitrobenzene sulfonic acid (TNBS)-treated mice. Mice fed either a low-fat chow diet (CD) or high fat and sucrose Western diet (WD) received 109 L. plantarum WCFS1 cells for five consecutive days. Lactobacillus plantarum persistence was 10- to 100-fold greater in the intestines of WD-fed compared with CD-fed mice. TNBS, an intestinal irritant that induces the development of inflammatory bowel disease-like symptoms, resulted in up to a 104-fold increase in L. plantarum survival in the digestive tract relative to healthy animals. Expression levels of 12 metabolic and gut-inducible L. plantarum genes were differentially affected by diet and TNBS administration. Pyrosequencing of 16S rRNA transcripts from the indigenous intestinal microbiota showed that WD resulted in significant reductions in proportions of metabolically active indigenous Lactobacillus species and increases in the Desulfovibrionaceae family. Feeding L. plantarum WCFS1 resulted in lower levels of colitis and higher concentrations of colonic IL-10 and IL-12 in WD and not CD-fed mice. Interactions between probiotics, nutritional components and the intestinal bacteria should be considered when examining for probiotic-mediated effects and elucidating mechanisms of probiotic function in the mammalian gut.
Microfabrication of transformers and inductors for high frequency power conversion

Transformers and inductors fabricated with micron-scale magnetic-alloy and copper thin films are proposed for high-frequency power conversion applications. Fine patterning produced by photolithography reduces eddy current losses, resulting in very high power densities. Calculated design graphs and design examples for 10 MHz transformers are presented. >
All-Inside Posterior Cruciate Ligament Reconstruction

Posterior cruciate ligament injuries can occur in isolation or in combination with other knee ligament injuries. In the setting of a multiligament injury, posterior cruciate ligament reconstruction enhances patient function. Several techniques and graft options exist; however, the optimal treatment strategy has yet to be elucidated. This article describes a safe, effective, and reliable all-inside, arthroscopic approach using a quadrupled tibialis anterior or peroneus longus allograft secured with both tibial and femoral suspensory fixation.
Myoglobin oxygen affinity in aquatic and terrestrial birds and mammals

ABSTRACT Myoglobin (Mb) is an oxygen binding protein found in vertebrate skeletal muscle, where it facilitates intracellular transport and storage of oxygen. This protein has evolved to suit unique physiological needs in the muscle of diving vertebrates that express Mb at much greater concentrations than their terrestrial counterparts. In this study, we characterized Mb oxygen affinity ( P 50 ) from 25 species of aquatic and terrestrial birds and mammals. Among diving species, we tested for correlations between Mb P 50 and routine dive duration. Across all species examined, Mb P 50 ranged from 2.40 to 4.85 mmHg. The mean P 50 of Mb from terrestrial ungulates was 3.72±0.15 mmHg (range 3.70–3.74 mmHg). The P 50 of cetaceans was similar to terrestrial ungulates ranging from 3.54 to 3.82 mmHg, with the exception of the melon-headed whale, which had a significantly higher P 50 of 4.85 mmHg. Among pinnipeds, the P 50 ranged from 3.23 to 3.81 mmHg and showed a trend for higher oxygen affinity in species with longer dive durations. Among diving birds, the P 50 ranged from 2.40 to 3.36 mmHg and also showed a trend of higher affinities in species with longer dive durations. In pinnipeds and birds, low Mb P 50 was associated with species whose muscles are metabolically active under hypoxic conditions associated with aerobic dives. Given the broad range of potential globin oxygen affinities, Mb P 50 from diverse vertebrate species appears constrained within a relatively narrow range. High Mb oxygen affinity within this range may be adaptive for some vertebrates that make prolonged dives.
Coupling supercritical CO2 and subcritical (hot) water for the determination of Dacthal and its acid metabolites in soil

Dacthal and its mono- and diacid metabolites were sequentially extracted from soils by first performing a supercritical carbon dioxide extraction to recover Dacthal, followed by a subcritical (hot) water extraction step to recover metabolites. Dacthal was recovered from soil in 15 min by supercritical carbon dioxide at 150 °C and 400 bar. The mono- and diacid metabolites were extracted from soil in 10 min under the subcritical water conditions of 50 °C and 200 bar. The metabolites were trapped in situ on a strong anion-exchange disk placed over the exit frit of the extraction cell. Metabolites are combined with Dacthal by placing the disk into the GC autosampler vial containing the SFE extract. The metabolites then are simultaneously eluted from the disk and derivatized to their ethyl esters by adding 100 μL of ethyl iodide and heating the vial at 100 °C for 1 h. Using this approach, only a single sample is analyzed, and because the disk-catalyzed alkylation reaction does not transesterify Dacthal, the sp...
Enhancement of leukemia rejection by mice successfully treated for L1210 leukemia due to low dose compared to high dose VP-16

We have earlier shown that VP-16 combined with Cyclosporin A (CsA) produces tumor specific immunity to L1210 leukemia in BDF/1 mice [Slater LM, Sweet P, Stupecky M, Reynolds JT. Cyclosporin A/VP-16 produced immunity to L1210 leukemia: the participation of cytotoxic CD(8) T-lymphocytes, Clin Immunol Immunopathol 1995;75:239-45]. Our current studies, designed to determine the role of VP-16 independently of CsA in this effect show that increased dose intensity of VP-16, in the absence of CsA, improves the frequency of 60 day survival of treated mice but impairs the ability of 60 day surviving mice to reject L1210 leukemia challenge. This impairment is associated with progressive diminution of mitogen responses by spleen cells harvested from tumor free VP-16 treated mice.
Torsion in the Nottingham group

From local class-field theory and higher ramification theory one gets a classification up to conjugacy of the torsion elements of arbitrary order in the Nottingham group over a finite field, in terms of continuous characters on the multiplicative group of principal units in the ring of formal power series over the field. An essential part of this classification is to partition the torsion elements according to the depths of their successive p-power iterates. The classification described here is good enough to permit an independent proof of Klopsch’s theorem on torsion elements of order p, but not good enough to give a full description of the finite set of classes of torsion elements with a given depth-sequence. The final section exhibits an efficient method of calculating the first few hundred terms of a series of order p, limited only by the capabilities of the computation package used, but gives no idea of any formula for describing the coefficients.
Can human embryonic stem cells contribute to the discovery of safer and more effective drugs

Few scientific achievements have received such irresistible attention from scientists, clinicians, and the general public as the ability of human embryonic stem (hES) cells to differentiate into functional cell types for regenerative medicine. The most immediate benefit of neurons, cardiomyocytes, and insulin-secreting cells derived from hES cells, however, may reside in their application in drug discovery and toxicology. The availability of renewable human cells with functional similarities to their in vivo counterparts is the first landmark for a new generation of cell-based assays. The development of cell-based assays using human cells that are physiological targets of drug activity will increase the robustness of target validation and efficacy, high-throughput screening (HTS), structure–activity relationship (SAR), and should introduce safer drugs into clinical trials and the marketplace. The pluripotency of embryonic stem cells, that is, the capacity to generate multiple cell types, is a novel path for the discovery of ‘regenerative drugs’, the pursuit of small molecules that promote tissue repair (neurogenesis, cardiogenesis) or proliferation of resident stem cells in different organs, thus creating drugs that work by a novel mechanism.
Mean first passage times in fluid queues

A stochastic fluid queueing system describes the input-output flow of a fluid in a storage device, called a buffer. The rates at which the fluid enters and leaves the buffer depend on a random environment process. The external governing process is an irreducible CTMC and the fluid from the buffer is emptied at a constant rate @m. Let X(t) denote the buffer content at time t and I(t) denote the state of the random environment at time t. In this paper we present a method for computing the mean first passage times in the {X(t),t>=0} process, as well as in the bivariate {(X(t),I(t)),t>=0} process. We derive a system of first-order non-homogeneous linear differential equations for the mean first passage times which can easily be solved using well-known techniques. The method developed here can be readily implemented for computational purposes. We present two examples illustrating how to find explicitly the analytical solution to a small two-state problem and how to obtain numerical solutions to a multistate problem.
Modulation of O-LinkedN-Acetylglucosamine Levels on Nuclear and Cytoplasmic Proteins in Vivo Using the PeptideO-GlcNAc-β-N-acetylglucosaminidase InhibitorO-(2-Acetamido-2-deoxy-dglucopyranosylidene)amino-N-phenylcarbamate

O-Linked N-acetylglucosamine (O-GlcNAc) is a ubiquitous and abundant post-translational modification found on nuclear and cytoplasmic proteins and is thought to be a dynamically regulated modification much like phosphorylation. In this study we have demonstrated that O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbama te (PUGNAc), a potent in vitro inhibitor of the enzyme responsible for the removal of O-GlcNAc from proteins (peptide O-GlcNAc-beta-N-acetylglucosaminidase), can be used to increase O-GlcNAc levels on nuclear and cytoplasmic proteins in vivo. Overall, PUGNAc caused approximately a 2-fold increase in O-GlcNAc levels in the human colon cancer cells, HT29, although the effects on individual proteins varied. The increase appeared to be the result of the direct inhibition of the peptide O-GlcNAc-beta-N-acetylglucosaminidase since neither the O-GlcNAc transferase nor UDP-GlcNAc levels were affected by the treatment. O-GlcNAc levels in other cell lines tested (NIH 3T3, CV-1, and HeLa) were also affected by PUGNAc, although the effects on HeLa cells were minimal. At the concentrations tested, PUGNAc was non-toxic and had no affect on the growth rate of any of the cell lines examined. Interestingly, we demonstrated that an increase in O-GlcNAc levels on the transcription factor Sp1 resulted in a reciprocal decrease in its level of phosphorylation, supporting the hypothesis that O-GlcNAc competes with phosphate on some proteins. These studies demonstrate that PUGNAc is an effective inhibitor of O-GlcNAc turnover within cells and can be used to selectively alter the extent of O-GlcNAc on cellular proteins.
Iron uptake and Nramp2/DMT1/DCT1 in human bronchial epithelial cells.

The capacity of natural resistance-associated macrophage protein-2 [Nramp2; also called divalent metal transporter-1 (DMT1) and divalent cation transporter-1 (DCT1)] to transport iron and its ubiqu...
Chemical Structure- and Time-Dependent Effects of Polycyclic Aromatic Hydrocarbon-Type Inducers on Rat Liver Cytochrome P450, DNA Adducts, and I-Compounds

Abstract Chemical Structure- and Time-Dependent Effects of Polycyclic Aromatic Hydrocarbon-Type Inducers on Rat Liver Cytochrome P450, DNA Adducts, and I-Compounds. Moorthy, B., Sriram, P., and Randerath, K. (1994). Fundam. Appl. Toxicol. 22, 549-560. It is well documented that cytochrome P450IA1 (CYP1A1) plays an important role in carcinogen activation. CYP1A1/1A2 induction may serve as a biomarker of exposure to environmental toxins. In order to explore a specific role of CYP1A1 in metabolism of I-compounds (age-dependent indigenous DNA modifications), 2-month-old female Sprague-Dawley rats were treated ip with corn oil (2 ml/kg) or with one of several CYP1A1 inducers, i.e., dibenz[a,c]anthracene (DBA) (93 μmol/kg), benzo[a]pyrene (BP) (93 μmol/kg), naphthacene (NAP) (93 μmol/kg), or β-naphthoflavone (BNF) (140 μmol/kg), once daily for 4 days. Levels of total cytochrome P450 and activities of CYP1A1-associated enzymes, i.e., ethoxycoumarin O -deethylase (ECD) and ethoxyresorufin O-deethylase (EROD), were determined in liver microsomes at 1, 8, or 15 days after the last treatment. DNA adducts and I-compounds were analyzed by nuclease P1-enhanced 32 P-postlabeling. DNA synthesis rate was determined by measuring [3H]methylthymidine incorporation into DNA. Each inducer significantly elevated the total P450 level at 1 day. The enzyme levels in BP-, NAP-, and BNF-treated animals gradually returned to control by 8 and 15 days, but elevated levels persisted in DBA-treated rats. Similar trends were observed for ECD and EROD activities. DBA and BP, but not NAP and BNF, gave rise to several measurable DNA adducts, which persisted throughout the period of study. All P450 inducers, irrespective of adduct formation, strongly depleted both nonpolar and polar I-compounds, the effects being most pronounced at 1 and 8 days. These results imply a specific role for CYP1A1 in the regulation of I-compound metabolism, in addition to PAH activation.
Spectrally resolved comparison of TOMS estimates of surface UV irradiances with those of ground-based measurements at time of overpass

Most comparisons of TOMS estimates of surface UV irradiation with measured values from ground-based instruments have indicated a bias of the TOMS estimates toward larger values. A portion of this bias results from absolute uncertainties in the ground-based instruments. The comparison reported here is based on ground-based data from four sites in the UGA/EPA Brewer network. The raw data from the ground-based instruments has been corrected for (1) stray light rejection, (2) the cosine errors associated with the full sky diffuser, (3) the temperature dependence of the response of the instruments and (4) the temporal variation in the instrument response reducing the estimated errors of the absolute irradiance values of each spectral measurement to < ±7%. Comparisons of TOMS with the surface measurements are performed both at spectrally resolved wavelengths at the time of overpass and for erythemally-weighted daily-integrated doses. These comparisons are made for all days and for clear-sky days only. The comparisons are carried out using both linear regressions of scatter plots of the two sets of data and for mean differences with respect to both TOMS and the Brewer measurements. It is found that spectrally resolved comparisons suffer from inconsistencies at some of the sites that are believed to result from wavelength uncertainties in the Brewer; they are therefore of more limited use than wavelength integrated data. A comparison based on daily-integrated doses shows only a small positive TOMS bias (4%) for clear-sky days with a somewhat larger bias (8%) for data taken from all days.
Charm Production in e + e - Annihilation

The cross sections for charm production in continuum e+e- annihilation near 10 GeV and near 30 GeV are presented. With the latest values for the D-meson decay branching ratios, about 70% of the charm quarks end up in the D° or D± mesons. There is no evidence for a charm deficit. The relative production of the vector and pseudoscalar mesons is in accord with the expectations of spin counting. Measurements of the D decay angular distribution show that the vector mesons are primarily produced with equal populations in all helicity states, although there is some evidence for D alignment for the highest D* momenta in the 10 GeV data.
Ultrastructural localization of enkephalin and μ-opioid receptors in the rat ventral tegmental area

Abstract Enkephalins are endogenous ligands for opioid receptors whose activation potently modulates the output of mesocorticolimbic dopaminergic neurons within the ventral tegmental area. Many of the reinforcing effects of enkephalins in the mesocorticolimbic system are mediated by μ-opioid receptors. To determine the sites for Leu 5 -enkephalin activation of μ-opioid receptors in the ventral tegmental area, we examined the dual electron microscopic immunocytochemical localization of their respective antigens in this region of rat brain. Enkephalin immunoperoxidase reaction product and μ-opioid receptor immunogold–silver labeling showed similar cellular and subcellular distribution in both the paranigral and parabrachial subdivisions of the ventral tegmental area. Enkephalin immunoreactivity was mainly localized in small unmyelinated axons (50.4%) and in axon terminals (40.4%). The majority of these terminals formed symmetric, inhibitory-type synapses, many of which were on dendrites expressing plasmalemmal μ-opioid receptors. Appositional contacts were also often seen between axons or terminals that were differentially labeled for the two antigens. In addition, some of the enkephalin-labeled terminals and a few somatodendritic profiles showed a plasmalemmal or vesicular localization of μ-opioid receptors. Our results indicate that dendritic targets of inhibitory terminals, as well as nearby axon terminals, are potential sites for enkephalin activation of μ-opioid receptors throughout the ventral tegmental area. Moreover, co-localization of enkephalin and μ-opioid receptors in selective neuronal profiles may indicate an autoregulatory role for these receptors or their internalization along with the bound ligand in this brain region.
The Smooth Monostratified Ganglion Cell: Evidence for Spatial Diversity in the Y-Cell Pathway to the Lateral Geniculate Nucleus and Superior Colliculus in the Macaque Monkey

In the primate visual system approximately 20 morphologically distinct pathways originate from retinal ganglion cells and project in parallel to the lateral geniculate nucleus (LGN) and/or the superior colliculus. Understanding of the properties of these pathways and the significance of such extreme early pathway diversity for later visual processing is limited. In a companion study we found that the magnocellular LGN-projecting parasol ganglion cells also projected to the superior colliculus and showed Y-cell receptive field structure supporting the hypothesis that the parasol cells are analogous to the well studied alpha-Y cell of the cat's retina. We here identify a novel ganglion cell class, the smooth monostratified cells, that share many properties with the parasol cells. Smooth cells were retrogradely stained from tracer injections made into either the LGN or superior colliculus and formed inner-ON and outer-OFF populations with narrowly monostratified dendritic trees that surprisingly appeared to perfectly costratify with the dendrites of parasol cells. Also like parasol cells, smooth cells summed input from L- and M-cones, lacked measurable S-cone input, showed high spike discharge rates, high contrast and temporal sensitivity, and a Y-cell type nonlinear spatial summation. Smooth cells were distinguished from parasol cells however by smaller cell body and axon diameters but ∼2 times larger dendritic tree and receptive field diameters that formed a regular but lower density mosaic organization. We suggest that the smooth and parasol populations may sample a common presynaptic circuitry but give rise to distinct, parallel achromatic spatial channels in the primate retinogeniculate pathway.
ON THE THEORY OF THE GEODYNAMO

Abstract I trace the development of geodynamo theory leading from Larmor's original hypothesis (Larmor, 1919, Rep. Br. Assoc. Adv. Sci., A, 159–160) to the present. I consider a number of kinematic results, from Cowling's proof (Cowling, 1934, Mon. Not. R. Astron. Soc., 94: 39–48) that two-dimensional dynamo action is not possible, to the proofs by Backus (1958, Ann. Phys., 4: 372–447) and Herzenberg (1958, Philos. Trans. R. Soc. London, Ser. A, 250: 543–585) that three-dimensional dynamo action is possible. I next turn to various mean-field and convective models in which the fluid flow is no longer kinematically prescribed, but is itself dynamically determined. In these dynamical models, I describe the distinction between weak and strong field regimes that comes about owing to the effect of the field on the pattern of convection in a rapidly rotating system. I consider the dynamics of Taylor's constraint (Taylor, 1963, Proc. R. Soc. London, Ser. A, 274: 274–283), and demonstrate how it makes the analysis of the geophysically appropriate strong field regime particularly difficult.
Adjuvant brachytherapy for primary high-grade soft tissue sarcoma of the extremity.

Background: We reviewed single-institution experience using brachytherapy alone for primary high-grade soft tissue sarcoma of the extremity. Methods: Between July 1982 and September 1997, 202 adult patients with primary high-grade soft tissue sarcoma of the extremity were treated with limb-sparing surgery and adjuvant brachy-therapy. All patients underwent complete gross resection, but the margin of resection was micro-scopically positive in 18% of patients. The median dose of brachytherapy was 45 Gy delivered over 5 days. Tumors located in the shoulder or groin were defined as central location. Complications were assessed in terms of wound complications, bone fracture, and peripheral nerve damage. Results: With a median follow-up of 61 months, the 5-year local control, distant relapse-free survival, and overall survival rates were 84%, 63%, and 70%, respectively. On multivariate analysis, poor local control correlated with shoulder location, positive microscopic margins of resection, and nonshoulder upper extremity site. The 5-year actuarial rates of wound complications requiring reoperation, bone fracture, and grade ≥3 nerve damage were 12%, 3%, and 5%, respectively. Conclusions: Adjuvant brachytherapy provides adequate local control and acceptable morbidity that compares favorably with data reported for external beam radiation. Shoulder tumor location was identified as an independent prognostic factor for poor local control, mandating further improvement in the local management of these tumors.
Organizational goals and values: A socialization model

Abstract Research on the content of socialization has incorporated multiple content areas into one general framework. However, it has been suggested that the organizational content areas actually assess different constructs, thus, researchers should examine the content areas independently. The purpose of this article is to present a model of socialization that focuses on the antecedents and outcomes of socialization in one specific content area: organizational goals and values. The model suggests that an individual's agreement with the organization's values (work value congruence) and the importance of the individual's own work values interact to determine the outcomes of socialization to the organizational goals and values. When there is low work value congruence, the individual may engage in detrimental behaviors if the individual has a strong belief in his/her own values.
Purpose of Quality Standards for Infectious Diseases

Peter A. Gross, Trisha L. Barrett, E. Patchen Dellinger, From Hackensack Medical Center, Hackensack. and New Jersey Medical Peter J. Krause, William J. Martone, School, Newark. New Jersey; Alta Bates Medical Center, Berkeley, John E. McGowan, Jr., Richard L, Sweet, California; University of Washington Medical Center, Seattle, Joh~and Richard P. Wenzel .Rchar .Sweet,Washington; Hartford Hospital, Hartford, Connecticut; Hospital ~~~and Richard r~P~~. Wenzel ~Infections Program, Centers for Disease Control and Prevention, and Em1ory University School of Medicine, Atlanta, Georgia; Magee Wonmen's Hospital, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and University of Iowa Hospitals and Clinics, Iowa City, Iowa
The potential influence of cell protectors for dose escalation in cancer therapy: an analysis of amifostine

The attempt to increase the therapeutic ratio in an effort to improve survival or quality of life is the goal of modern cancer therapy. It is commonly accepted that local and systemic tumor control would increase if the dose intensity of antineoplastic drugs, radiation therapy, or the combination were increased. Radiation dose escalation using intensity-modulated radiation therapy (IMRT), accelerated or hypofractionated radiation schemes, and multidrug chemotherapy regimens are being used to try to increase tumor kill while inflicting minimal injury to normal tissue. Modern chemoradiation techniques have led to improved local regional control and increased cure rates, but the potentially severe and debilitating adverse effects of the therapies prevent them from reaching the ultimate goal of curing the disease while leaving the patient with a good quality of life. Cell protectants such as amifostine function by reducing the effects of therapy on normal cells while maintaining tumor sensitivity to the therapy. In various studies, amifostine has been analyzed and appears to be a potentially powerful adjuvant to current cancer therapy. Administering amifostine may allow dose escalation with less or equal risk to surrounding normal tissues. This could improve therapeutic efficacy, survival, and quality of life for cancer patients.
A ligand column for the purification of steroid-binding proteins

Abstract Isolation of steroid-binding proteins has been a formidable task because only trace amounts of these materials are normally present. We have developed a specific method based on attachment of the 21 position of cortisol to an insoluble matrix. The steroid derivative used has structural features designed to produce stability to severe elution conditions and to serum and tissue enzymes. Agarose gel was found to be extremely stable to a variety of organic solvents. CBG was purified 20 to 40 fold at a single step. Albumin was the major contaminant but traces of β and γ globulin were also eluted from the column by cortisol.
Infiltration and Solidification/Remelting of a Pure Metal in a Two-Dimensional Porous Preform

Infiltration and solidification/remelting of a pure metal in a two-dimensional porous preform are modeled numerically. It is assumed that under the action of constant applied pressure, the flow of liquid metal through the preform is within the range of the validity of Darcy's Law. The distinguishing feature of this flow and heat transfer problem is the existence of two moving fronts : the infiltration front and the remelting front. The governing momentum and energy equations are nondimensionalized and cast into a Body-Fitted Coordinates (BFC) system to deal with the transient and irregular physical domains. The dimensionless groups that govern the infiltration and remelting processes are : the dimensionless pressure difference, the dimensionless melting temperature, the preform permeability ratio, porosity, and the geometric parameters (inlet gate size, and the preform aspect ratio). A computational code has been developed to solve the problem and is verified by using the available published results. The key parameters describing the physical phenomena, i.e., the infiltration front and remelting front evolution, the total infiltration time, and the remelting region size, are presented as a function of the operating variables for two different aspect ratios. The results can be used to optimize the infiltration processing of Metal-Matrix Composites and other related manufacturing processes.
An alternation characterization of best uniform approximations on noncompact intervals

Abstract We present a characterization for a best uniform approximation to a given bounded continuous function f defined on the real but not necessarily compact interval T from an n -dimensional subspace S of the bounded continuous functions on T . When S is a Haar subspace and each element of S satisfies an additional endpoint regularity condition, such a best approximation may be characterized by an appropriate generalization of the familiar alternation criterion which holds for compact T . One such best approximation that has an alternating error curve may be obtained as the uniform limit of a sequence whose v th term is the unique best uniform approximation to f on the v th member of a suitably chosen expanding sequence of compact subintervals of T . The results apply in the special case where T = [0, + ∞) and S is a family of exponential sums with real exponents.
Evaluating point concentrations on a map: Earthquakes in the Colorado Lineament

A common problem in geology is the objective evaluation of points that are suspected to concentrate nonrandomly in a specified part of a map area. Evaluation can be rigorous with the binomial test, but results often are distorted by prior inspection of the only available group of points. Such distortion can be hard to avoid because concentration may not be suspected until the sample is inspected. Distortion can be evaluated by analyzing overlapping subsamples, mapping independent cells that are significantly overpopulated by points, and arguing that the sample is representative of the population from which it was drawn. Such distortion occurs in evaluation of earthquake hazard. For example, visual inspection of epicenters in the west-central United States suggests that they have been concentrated in the Colorado Lineament for the past century. Results of distortion evaluation support that suggestion: concentration is strongly indicated, although it cannot be evaluated rigorously.
Fairness and Tax Policy: A Response to Mankiw's Proposed “Just Deserts”

I further pursue the proposal of Mankiw to consider fairness or “Just Deserts” as the main guide to tax policy. I suggest very different policy conclusions. In particular, I point out some key assumptions that were left implicit in Mankiw's analysis, and question whether these hold in practice. I then suggest a different formal approach to determining a fair policy.