bluuebunny/crossref_metadata_2025 huggingface dataset:
MECHANISMS OF DIGESTION AND ABSORPTION OF DIETARY VITAMIN A
Authors: Harrison Earl H.
Published: March 2005

▪ Abstract  Mechanisms involved in the digestion and absorption of dietary vitamin A require the participation of several proteins. Dietary retinyl esters are hydrolyzed in the intestine by the pancreatic enzyme, pancreatic triglyceride lipase, and intestinal brush border enzyme, phospholipase B. Unesterified retinol taken up by the enterocyte is complexed with cellular retinol-binding protein type 2 and the complex serves as a substrate for reesterification of the retinol by the enzyme lecithin:retinol acyltransferase (LRAT). The retinyl esters are then incorporated into chylomicrons, intestinal lipoproteins containing other dietary lipids, such as triglycerides, phospholipids, and free and esterified cholesterol, and apolipoprotein B. Chylomicrons containing newly absorbed retinyl esters are then secreted into the lymph. Although under normal dietary conditions much of the dietary vitamin A is absorbed via the chylomicron/lymphatic route, it is also clear that under some circumstances there is substantial absorption of unesterified retinol via the portal route. Evidence supports the idea that the cellular uptake and efflux of unesterified retinol by enterocytes is mediated by lipid transporters, but the exact number, identity, and role of these proteins is not known and is an active area of research.
Modulation of endothelial cell migration by extracellular nucleotides
Authors: Erb Laurie , Koziak Katarzyna , Jarzyna Robert , Wink Marcia R. , Guckelberger Olaf , Blusztajn Krzysztof J. , Trinkaus-Randall Vickery , Weisman Gary A. , Robson Simon C. , Kaczmarek Elzbieta
Published: March 2005

Extracellular nucleotides bind to type-2 purinergic/pyrimidinergic (P2) receptors that mediate various responses, such as cell activation, proliferation and apoptosis, implicated in inflammatory processes. The role of P2 receptors and their associated signal transduction pathways in endothelial cell responses has not been fully investigated. Here, it is shown that stimulation of human umbilical vein endothelial cells (HUVEC) with extracellular ATP or UTP increased intracellular free calcium ion concentrations ([Ca2+]i), induced phosphorylation of focal adhesion kinase (FAK), p130cas and paxillin, and caused cytoskeletal rearrangements with consequent cell migration. Furthermore, UTP increased migration of HUVEC in a phosphatidylinositol 3-kinase (PI3-K)-dependent manner. BAPTA or thapsigargin inhibited the extracellular nucleotide-induced increase in [Ca2+]i, a response crucial for both FAK phosphorylation and cell migration. Furthermore, long-term exposure of HUVEC to ATP and UTP, agonists of the G protein-coupled P2Y2 and P2Y4 receptor subtypes, caused upregulation of αv integrin expression, a cell adhesion molecule known to directly interact with P2Y2 receptors. Our results suggest that extracellular nucleotides modulate signaling pathways in HUVEC influencing cell functions, such as cytoskeletal changes, cellular adhesion and motility, typically associated with integrin-activation and the action of growth factors. We propose that P2Y2 and possibly P2Y4 receptors mediate those responses that are important in vascular inflammation, atherosclerosis and angiogenesis.
Transcriptional control of cell density dependent regulation of matrix metalloproteinase and TIMP expression in breast cancer cell lines
Authors: Vené Roberta , Iancu Cristina M. , Pfeffer Ulrich , Mayer Barbara , Noonan Douglas , Albini Adriana , Jochum Marianne , Nerlich Andreas G. , Bachmeier Beatrice E.
Published: March 2005

Our recent studies on breast carcinoma cell lines with differing tumorigenicity / invasiveness (MCF-7< MDA-MB-468< MDAMB-231< MDA-MB-435) had shown significantly decreasing expression levels of MMPs-1,-2,-3,-8,-9,-10,-11 and –13 with increasing cell density while the levels of TIMP-1 and –2 increased. This correlated well with a lower invasiveness of confluent cells. In the present study, we extend our in vitro studies on three-dimensional cultures of breast cancer cell lines MCF-7 and MDAMB-435 and the transcriptional control of MMP and TIMP-expression in two-dimensional cultures of MDA-MB-231 and –435 cells. The tumor spheroid model showed that MMP expression and proteolytic activity were considerably higher in loosely structured tumor groups as compared to densely growing “compact” cell complexes. These data suggested that cell density regulates MMP and TIMP transcription and therefore, we tested whether AP-1, NFκB and CRE are involved in this process. Gene silencing of c-jun in sparse cultures had an inhibitory effect on MMP-3,–9 and –13 expression, on proteolytic activity as well as on the invasive potential of the cells, thus confirming a role for AP-1. TIMP-1, and –2 expression was up-regulated as compared to control cells. Consistent with this, overexpression of c-jun and c-fos in confluent breast cancer cell lines leads to up-regulation of MMP expression, proteolytic activity and invasion as well as down-regulation of TIMP-1. In summary, we provide evidence that cell density influences the invasive potential of tumor cells via regulation of MMPs and TIMPs by AP-1, NFκB and CRE transcription factors. Overexpression of MMPs in sparse cultures could help explain early dissemination of potentially metastatic cells.
Thrombolytic agents
Authors: Lijnen Roger H. , Collen Désiré
Published: March 2005

Thrombolytic agents are plasminogen activators that convert the zymogen plasminogen to the active enzyme plasmin, which degrades fibrin. Elucidation of the molecular mechanism of physiological fibrinolysis opened up a new era of fibrin-specific thrombolysis. Fibrin-specific plasminogen activators, including tissue-type plasminogen activator (t-PA), single-chain urokinase-type plasminogen activator (scu-PA) and staphylokinase (Sak), preferentially activate fibrin-associated plasminogen. Generated plasmin remains associated with fibrin, where it is protected from rapid inhibition and can efficiently degrade fibrin, avoiding systemic activation of the fibrinolytic system. Following a decade of clinical investigation t-PA and variants thereof are routinely used for treatment of patients with thromboembolic disease.
Transcriptional and posttranscriptional regulation of the plasminogen activator system
Authors: Medcalf Robert L. , Muñoz-Cánoves Pura , Nagamine Yoshikuni
Published: March 2005

The core protein components of the plasminogen activator (PA) system are two plasminogen activators, two plasminogen activator inhibitors and a urokinase type plasminogen activator-specific cell surface receptor. Various types of biological regulation are exerted through the interplay of these components mutually and with extracellular matrix proteins and cell membrane proteins, with or without involving proteolytic activity. Reflecting these diverse biological roles, the level and activity of each component of the PA system is under the control of a variety of regulatory mechanisms. The expression level of a protein reflects the level of the corresponding mRNA, which is essentially the net result of de novo synthesis, i.e. transcription, and degradation. Many recent studies have shown that the regulation of mRNA stability is dynamic and cell specific. Accordingly, we are learning that the mRNAs of the PA system are also the subject of diverse regulatory mechanisms. In this short review, we summarize current understanding of the transcriptional and mRNA-stability regulation of the PA system.
Structure and function of the plasminogen/plasmin system
Authors: Ploplis Victoria A. , Castellino Francis J.
Published: March 2005

Activation of the fibrinolytic system is dependent on the conversion of the plasma zymogen, plasminogen (Pg), to the serine protease plasmin (Pm) by the physiological activators urokinase-type Pg activator (uPA) or tissue-type plasminogen activator (tPA). The primary in vivo function of Pm is to regulate vascular patency by degrading fibrin-containing thrombi. However, the identification of Pg/Pm receptors and the ability of Pm to degrade other matrix proteins have implicated Pm in other functions involving degradation of protein barriers, thereby mediating cell migration, an important event in a number of normal e.g., embryogenesis, wound healing, angiogenesis, and pathological, e.g., tumor growth and dissemination, processes. Prior to the development of Pg-deficient mice, much of the evidence for its role in other biological events was based on indirect studies. With the development and characterization of these mice, and ability to apply challenges utilizing a number of animal models that mimic the human condition, a clearer delineation of Pg/Pm function has evolved and has contributed to an understanding of mechanisms associated with a number of pathophysiological events.
Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease
Authors: Dellas Claudia , Loskutoff David J.
Published: March 2005

Although plasminogen activator inhibitor 1 (PAI-1) is one of the primary regulators of the fibrinolytic system, it also has dramatic effects on cell adhesion, detachment and migration. PAI-1 also differs from other serine protease inhibitors (serpins) in that it is a trace protein in plasma, it has a short half-life in vivo, its synthesis is highly regulated, and it binds to the adhesive glycoprotein vitronectin (VN) with high affinity and specificity. These unique and diverse properties of PAI-1 probably account for the many observations in the literature that correlate abnormalities in PAI-1 gene expression with a variety of pathological conditions. In this review, we discuss the discovery, origin, properties and regulation of PAI-1, and then speculate about its potential role in vascular disease, fibrosis, obesity and the metabolic syndrome, and cancer.
Cytokine Preconditioning Promotes Codifferentiation of Human Fetal Liver CD133
+
Stem Cells Into Angiomyogenic Tissue
Authors: Shmelkov Sergey V. , Meeus Sarah , Moussazadeh Nelson , Kermani Pouneh , Rashbaum William K. , Rabbany Sina Y. , Hanson Marilee A. , Lane William J. , St. Clair Ryan , Walsh Kathryn A. , Dias Sergio , Jacobson Jason T. , Hempstead Barbara L. , Edelberg Jay M. , Rafii Shahin
Published: March 2005

Background—

CD133 (AC133) is a surface antigen that defines a broad population of stem cells, including myogenic and endothelial progenitors. CD133
+
cells are rare in adult tissues, and the factors that support their differentiation into mature angiomyogenic cells are not known. These hurdles have hampered the use of CD133
+
cells for therapeutic purposes. Because human fetal liver is a rich source of CD133
+
cells, we sought to identify the growth factors that promote codifferentiation of these cells into angiogenic and myogenic cells.

Methods and Results—

Human fetal liver CD133
+
and CD133
−
cell subpopulations were cultured with 5′-azacytidine or vascular endothelial growth factor (VEGF
165
) and/or brain-derived nerve growth factor (BDNF). CD133
+
but not CD133
−
cells from human fetal liver codifferentiated into spindle-shaped cells, as well as flat adherent multinucleated cells capable of spontaneous contractions in culture. The resulting spindle-shaped cells were confirmed to be endothelial cells by immunohistochemistry analysis for von Willebrand factor and by acetylated LDL uptake. Multinucleated cells were characterized as striated muscles by electron microscopy and immunohistochemistry analysis for myosin heavy chain. Presence of VEGF
165
and BDNF significantly enhanced angiomyogenesis in vitro. Inoculation of cells derived from CD133
+
cells, but not CD133
−
cells, into the ear pinna of NOD/SCID mice resulted in the formation of cardiomyocytes, as identified by immunostaining with cardiac troponin-T antibody. These cells generated electrical action potentials, detectable by ECG tracing.

Conclusions—

CD133 defines a population of human fetal liver cells capable of differentiating into both angiogenic and myogenic cells. Preconditioning of these CD133
+
cells with VEGF
165
and BDNF enhances the angiomyogenesis. CD133
+
fetal liver cells ultimately may be used for therapeutic angiomyogenesis.
p38 Mitogen-Activated Protein Kinase Downregulates Endothelial Progenitor Cells
Authors: Seeger Florian H. , Haendeler Judith , Walter Dirk H. , Rochwalsky Ulrich , Reinhold Johannes , Urbich Carmen , Rössig Lothar , Corbaz Anne , Chvatchko Yolande , Zeiher Andreas M. , Dimmeler Stefanie
Published: March 2005

Background—

Transplantation of endothelial progenitor cells (EPCs) improves neovascularization after ischemia, but patients with coronary artery disease (CAD) or diabetes mellitus show a reduced number of EPCs and impaired functional activity. Therefore, we investigated the effects of risk factors, such as glucose and TNF-α, on the number of EPCs in vitro to elucidate the underlying mechanisms.

Methods and Results—

EPCs of patients or healthy subjects were isolated from peripheral blood. Incubation with glucose or TNF-α dose-dependently reduced the number of EPCs (79.9±1.3% and 74.3±8.1% of control;
P
<0.05, respectively). This reduction was not caused by apoptosis. TNF-α and glucose induced a dose- and time-dependent activation of the p38 MAP kinase, the downstream kinase mitogen- and stress-activated kinase 1, and the transcription factor cAMP-responsive element–binding protein (CREB), in EPCs. Moreover, EPCs from CAD patients had significantly higher basal p38-phosphorylation levels (1.83±0.2-fold increase;
P
<0.05) compared with healthy subjects. The inhibition of the p38-kinase by SB203580 or infection with a dominant negative p38 kinase adenovirus significantly increased basal number of EPCs (136.7±6.3% and 142.9±18% versus control, respectively). Likewise, ex vivo cultivation of EPCs from patients with CAD with SB203580 significantly increased the number of EPCs and partially reversed the impaired capacity for neovascularization of EPCs in vivo (relative blood flow: 0.40±0.03 versus 0.64±0.08,
P
<0.05). The increased numbers of EPCs by SB203580 were associated with an augmentation of EPC proliferation and a reduction of cells expressing the monocytic marker proteins CD14 and CD64, suggesting that p38 regulates proliferation and differentiation events.

Conclusions—

These results demonstrate that p38 MAP kinase plays a pivotal role in the signal transduction pathways regulating the number of EPCs ex vivo. SB203580 can prevent the negative effects of TNF-α and glucose on the number of EPCs and may be useful to improve the number of EPCs for potential cell therapy.
The Scaling and Structure of the Estuarine Bottom Boundary Layer
Authors: Stacey Mark T. , Ralston David K.
Published: March 2005

A two-week dataset from a partially and periodically stratified estuary quantifies variability in the turbulence across the tidal and spring–neap time scales. These observations have been fit with a two-parameter model of the Reynolds stress profile, which produces estimates of the time variation of the bottom boundary layer height and the friction velocity. Conditions at the top of the bottom boundary layer indicate that the dynamics governing the development of the estuarine bottom boundary layer are different on ebb tides than on flood tides. The asymmetry in the flow is explained by consideration of the strain-induced buoyancy flux, which is stabilizing on ebb tides and destabilizing on flood tides. Based on these observations, a scaling approach to estimating estuarine bottom boundary layer parameters (height and friction velocity) is presented, which includes a modified Monin–Obukhov length scale to account for the horizontal buoyancy flux created by the sheared advection. Comparison with the observations of boundary layer height and friction velocity suggests that this approach may be successful in predicting bottom boundary layer parameters in estuaries and coastal regions with significant horizontal buoyancy fluxes. Comparison between the strain-induced buoyancy flux and shear production indicates that the straining of the density field is an important contributor to the turbulent kinetic energy budget and creates an asymmetry in turbulent energy between ebb and flood tides. It appears that the structure of the turbulence, specifically the ratio of the Reynolds stress to the turbulent energy, is also modified by tidal straining, further accentuating the ebb–flood asymmetries.
High Temporal Resolution Path-Average Rain Gauge with 50-GHz Band Microwave
Authors: Minda Haruya , Nakamura Kenji
Published: March 2005

Rain radar measures instantaneous spatial-average rainfall, while conventional rain gauges directly measure point rainfall with low temporal resolution. Thus differences in the resolution of the sensors create difficulties for rain radar validation, especially for spaceborne rain radar. Accordingly, rainfall measurement by microwave link has been proposed for several decades, as it estimates instantaneous path-average rainfall. Thus it is expected that the microwave link rain gauge will overcome, at least partly, the problems in the rain radar validation, toward which a 50-GHz band microwave link [the path-averaged rain gauge (PRG)] was developed that has been in operation since September 2000. In this paper, the authors show the potential of the PRG system by a simple model and rainfall comparison with a disdrometer and a tipping-bucket rain gauge. Differences observed by the instruments were within 15% (within 10% in half of the cases) during actual rain events in 2003. This confirmed that the PRG system displayed good performance as a rain gauge. Finally, the possibility of the PRG system being applied for spaceborne rain radar validation is considered.
The West Texas Mesonet: A Technical Overview
Authors: Schroeder J. L. , Burgett W. S. , Haynie K. B. , Sonmez I. , Skwira G. D. , Doggett A. L. , Lipe J. W.
Published: March 2005

The West Texas Mesonet originated in 1999 as a project of Texas Tech University. The mesonet consists of 40 automated surface meteorological stations, two atmospheric profilers, and one upper-air sounding system. Each surface station measures up to 15 meteorological and 10 agricultural parameters over an observation period of 5 and 15 min, respectively. The mesonet uses a combination of radio, cell phone, landline phone, and serial server (Internet) communication systems to relay data back to the base station at Reese Technology Center (formerly Reese Air Force Base), Texas. Data are transmitted through the radio network every 5 min for most meteorological data and every 15 min for agricultural data. For stations located outside of the radio network, phone systems transmit data every 30–60 min. The archive includes data received through the various communication systems, as well as data downloaded in the field from each station during regularly scheduled maintenance visits. Quality assurance/control (QA/QC) tests effectively flag data for manual review from a decision maker. The QA/QC flags and review decisions are then added to the database. All data are available free of charge; real-time data are available on the West Texas Mesonet Web page, and an interface to access the data archive is currently being developed.
Comparison of Near–Real Time Estimates of Integrated Water Vapor Derived with GPS, Radiosondes, and Microwave Radiometer
Authors: Van Baelen Joël , Aubagnac Jean-Pierre , Dabas Alain
Published: March 2005

In this study, the authors compare the integrated water vapor (IWV) retrieved with a global positioning system (GPS) receiver, radiosondes (RS), and a microwave radiometer (MWR) using data collected simultaneously during a 3-month campaign in the fall of 2002 in Toulouse, France. In particular for this study, the GPS analysis was performed in near–real time to provide estimates of the IWV in order to evaluate the potential of GPS observations for operational meteorological purposes. Although the three instrument estimates agree quite well together, the IWV estimates retrieved by GPS are generally larger than those of RS, while evidence is shown of a marked diurnal cycle: the differences are larger during the day (up to 2 mm) than at night (less than 0.5 mm). This can be explained by a daytime dry bias of the RS. Regarding the MWR, similar findings but to a lesser extent (differences between 0 and 1 mm) are reported. Furthermore, it has been established that the GPS estimates exhibit a strong dependency upon the IWV values resulting in a 15% faster variation when compared to the other means of IWV estimation in this study.
Occurrence of Summertime Convective Precipitation and Mesoscale Convective Systems in Finland during 2000–01
Authors: Punkka Ari-Juhani , Bister Marja
Published: March 2005

There are few if any studies of statistics of deep convection occurring in high-latitude regions. In this study, the basic characteristics of convective precipitation and mesoscale convective systems (MCSs) in Finland and nearby regions have been investigated by using composite reflectivity data from seven operational C-band weather radars. The period of study covered summers 2000 and 2001 from the beginning of April to the end of September. During the study period, the fraction of days with convective precipitation (with reflectivity exceeding 40 dBZ) occurring anywhere in the study region was 88%, and the fraction of days with heavy convective precipitation (with reflectivity exceeding 50 dBZ) was 61%.

An MCS was defined by means of radar reflectivity as follows: a continuous area of stratiform precipitation (18–40 dBZ), with a long axis of 100 km or more in at least one direction, must exist for at least 4 h, and during the lifetime of the system the maximum reflectivity must exceed 40 dBZ during at least two consecutive hours. All precipitation features that met these criteria were considered MCSs whether they occurred in extratropical cyclones or not. An MCS was qualified as intense if the maximum reflectivity exceeded 50 dBZ during at least two consecutive hours. The total amount of MCSs observed in the study region was 341, out of which 32% were intense. Over 50% of all intense MCSs occurred in July when the majority of systems traveled along south–north- or southeast–northwest-oriented paths. For instance, in July 2001, 34 intense MCSs developed in the study region. The majority of intense systems arrived in the region of study from a channel outlined by the Sarema and the Karelian Isthmus.

The average duration of all MCSs was 11.1 h with a monthly minimum of 9 h occurring in July. Generally, the intense and midsummer MCSs were clearly modulated by the diurnal heating–cooling cycle whereas the nonintense and springtime systems were less dependent on the time of the day.
A Systematic Economic Approach to Evaluating Public Investment in Observations for Weather Forecasting
Authors: Morss Rebecca E. , Miller Kathleen A. , Vasil Maxine S.
Published: March 2005

Observations of the current state of the atmosphere are a major input to production of modern weather forecasts. As a result, investments in observations are a major component of public expenditures related to weather forecasting. Consequently, from both a meteorological and societal perspective, it is desirable to select an appropriate level of public investment in observations. Although the meteorological community has discussed optimal investment in observations for more than three decades, it still lacks a practical, systematic framework for analyzing this issue. This paper presents the basic elements of such a framework, using an economic approach. The framework is then demonstrated using an example for radiosonde observations and numerical weather forecasts. In presenting and demonstrating the framework, the paper also identifies gaps in existing knowledge that must be addressed before a more complete economic evaluation of investment in observations can be implemented.
Scatterometer-Based Assessment of 10-m Wind Analyses from the Operational ECMWF and NCEP Numerical Weather Prediction Models
Authors: Chelton Dudley B. , Freilich Michael H.
Published: March 2005

Wind measurements by the National Aeronautics and Space Administration (NASA) scatterometer (NSCAT) and the SeaWinds scatterometer on the NASA QuikSCAT satellite are compared with buoy observations to establish that the accuracies of both scatterometers are essentially the same. The scatterometer measurement errors are best characterized in terms of random component errors, which are about 0.75 and 1.5 m s−1 for the along-wind and crosswind components, respectively.

The NSCAT and QuikSCAT datasets provide a consistent baseline from which recent changes in the accuracies of 10-m wind analyses from the European Centre for Medium-Range Weather Forecasts (ECMWF) and the U.S. National Centers for Environmental Prediction (NCEP) operational numerical weather prediction (NWP) models are assessed from consideration of three time periods: September 1996–June 1997, August 1999–July 2000, and February 2002–January 2003. These correspond, respectively, to the 9.5-month duration of the NSCAT mission, the first 12 months of the QuikSCAT mission, and the first year after both ECMWF and NCEP began assimilating QuikSCAT observations. There were large improvements in the accuracies of both NWP models between the 1997 and 2000 time periods. Though modest in comparison, there were further improvements in 2002, at least partly attributable to the assimilation of QuikSCAT observations in both models.

There is no evidence of bias in the 10-m wind speeds in the NCEP model. The 10-m wind speeds in the ECMWF model, however, are shown to be biased low by about 0.4 m s−1. While it is difficult to eliminate systematic errors this small, a bias of 0.4 m s−1 corresponds to a typical wind stress bias of more than 10%. This wind stress bias increases to nearly 20% if atmospheric stability effects are not taken into account. Biases of these magnitudes will result in significant systematic errors in ocean general circulation models that are forced by ECMWF winds.
A Bayesian Approach for the Spatiotemporal Interpolation of Environmental Data
Authors: Riccio Angelo
Published: March 2005

Numerically based models are extensively used for many environmental applications, as for example, to assist in the prediction of weather phenomena (numerical weather prediction models), in risk assessment, or in pollutant emission control (air-quality models). These models often produce predictions for grid points over some temporal window, while observations are usually available as a set of spatially scattered values at individual locations (not coincident with the model grid points), so that the model assessment procedure, that is, the statistical evaluation of how well model output compares with observed data, should address the issue of comparing the grid-based model results with interpolated values estimated from observed data at a different spatial resolution.

In this paper, a Bayesian inference procedure for the spatiotemporal interpolation of environmental data from irregularly spaced monitoring sites is presented. The spatial interpolation is based on the use of the predictive posterior distribution. It is shown how this procedure can be exploited to obtain statistically consistent interpolated values (at the same spatial resolution as that of model results) and valid standard errors for these estimates.

Comparisons of the wind speed fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) results against grid-cell values estimated from observed data are presented.
Surface Observations of Landfalling Hurricane Rainbands
Authors: Skwira G. D. , Schroeder J. L. , Peterson R. E.
Published: March 2005

This study examines the rainband-scale fluctuations of various meteorological parameters for Hurricanes Bonnie (1998) and Dennis (1999). Hurricane rainbands, identified by Next Generation Weather Surveillance Radar-1988 Doppler (NEXRAD WSR-88D) data, are examined shortly after making landfall on the North Carolina coastline. Additionally, Wind Engineering Mobile Instrumented Tower Experiment (WEMITE) data are exploited to provide a unique look into the surface structure of the captured rainbands. The observed meteorological data suggest equivalent potential temperature minima and decreasing hurricane-relative inflow to be commonly associated with intensifying or mature landfalling hurricane rainbands. Available vertical thermodynamic profiles suggest the source of the lower equivalent potential temperature air to range anywhere from 750 to 869 m above the surface, assuming no entrainment. Additionally, no discernable trend in wind speed is found to accompany the rainband’s passage.
Long-Term Disability Protection for Executives
Authors: Karp Stephen , O’Brien Heidi
Published: March 2005

Employer-provided group long-term disability insurance typically falls short in covering higher paid executives for several reasons. First, although group plans cover a percentage of salary, they often exclude bonus and other nonsalary compensation. Second, group plans impose maximum benefit limits. Sadly, employers and employees often fail to realize how devastatingly inadequate executive coverage is until disability strikes. Employers can help executives close this gap by sponsoring an optional supplemental long-term disability insurance plan. Under these plans, executives pay for individual supplemental policies that cover nonsalary compensation and have higher dollar limits. The individual policies are noncancelable, include premium discounts unavailable outside of the plan and are portable. Sponsoring a supplemental plan is an increasingly popular way for employers to provide a crucial executive benefit at little or no cost to companies and with little continuing effort required by HR departments.
Preventive Services: Improving the Bottom Line for Employers and Employees
Authors: Finch Ron
Published: March 2005

Many studies have shown that health promotion and disease prevention programs improve employee health and productivity and reduce longterm health care costs. For every $100 spent on health promotion, employers could see a $300 return on investment. Screenings for health conditions such as hypertension and colorectal cancer can save lives and reduce costs by catching diseases at an earlier, more manageable stage. The Agency for Healthcare Research and Quality, the leading federal health agency charged with improving quality, safety and effectiveness within the U.S. health care system, regularly convenes an independent panel of experts in prevention called the U.S. Preventive Services Task Force (USPSTF). The USPSTF systematically reviews clinical evidence and provides preventive health care recommendations for specific populations. The National Business Group on Health recently translated the USPSTF recommendations into accessible language in their Employer’s Guide to Health Improvement and Preventive Services, an employer resource to help benefits professionals build an appropriate prevention benefits package for their workforce.
Retiree Medical Benefit Developments in the Courts, Congress and EEOC
Authors: McElligott James P.
Published: March 2005

Recent legal developments will affect the design of retiree medical plans. By rejecting a reverse age discrimination claim, the Supreme Court’s General Dynamics decision clarifies the right to use design options that provide additional retiree medical rights to employees close to retirement, such as the “grandfathering” provision used by General Dynamics. In another age discrimination development, the Equal Employment Opportunity Commission (EEOC) has approved rules permitting employers to coordinate retiree health benefit plans with eligibility for Medicare. This administrative rejection of the infamous Erie County case provides important legal support for a common retiree medical plan design. Changes to retiree medical benefit plans continue to be hotly litigated across the country. Recent decisions emphasize the need for plan documents and labor agreements to reserve the plan sponsor’s rights to modify future retiree medical benefits. Finally, the Medicare Modernization Act dramatically affects retiree medical plan design by authorizing subsidies for employers who provide qualified retiree prescription drug coverage and by creating health savings accounts to provide an important new retirement medical benefits tool for employers and employees.
Neuroimaging Studies of Aggressive and Violent Behavior
Authors: Bufkin Jana L. , Luttrell Vickie R.
Published: March 2005

With the availability of new functional and structural neuroimaging techniques, researchers have begun to localize brain areas that may be dysfunctional in offenders who are aggressive and violent. Our review of 17 neuroimaging studies reveals that the areas associated with aggressive and/or violent behavioral histories, particularly impulsive acts, are located in the prefrontal cortex and the medial temporal regions. These findings are explained in the context of negative emotion regulation, and suggestions are provided concerning how such findings may affect future theoretical frameworks in criminology, crime prevention efforts, and the functioning of the criminal justice system.
Transforming Selves
Authors: Tennant Mark
Published: March 2005

Transformative education is aimed at promoting awareness and fundamental change at the personal, relational, institutional, and global levels. In doing so, it deploys a range of techniques, processes, and practices aimed at assisting learners to “work on themselves.” Such practices, or technologies of the self, contain within them assumptions about self and identity and the relevance of society to personal formation and change. The purpose of this article is to examine the various conceptions of self and identity apparent in the language of transformative learning designs and subsequently, the various technologies of the self deployed for the purpose of transformative change. Four broad categories of technologies of the self are identified: knowing oneself, controlling oneself, caring for oneself, and recreating oneself. These categories cut across the various conceptions of self and society, but they can be usefully used in conjunction with them to critically analyse different designs for transformative learning.
The Effect of Age on Vitamin E Status, Metabolism, and Function: Metabolism as Assessed by Labeled Tocopherols
Authors: BRIGELIUS‐FLOHÉ REGINA , ROOB JOHANNES M. , TIRAN BEATE , WUGA SANDRA , RIBALTA JOSEP , ROCK EDMOND , WINKLHOFER‐ROOB BRIGITTE M.
Published: March 2005

Abstract: The effects of age on vitamin E metabolism were studied in 97 healthy 20‐75‐year‐old male nonsmoking Austrian volunteers of the VITAGE project. After a single oral intake of 30 mg d6‐RRR‐α‐ and d2‐RRR‐γ‐tocopheryl acetate, blood and 24‐hour urine was collected. Deuterated tocopherols in plasma and deuterated urinary metabolites were analyzed by GC‐MS. A first evaluation revealed a similar uptake of d6‐α‐ and d2‐γ‐tocopherol during the first 6 hours, and then d2‐γ‐tocopherol started to decrease. Urinary d2‐γ‐ carboxyethyl hydroxychroman metabolites (CEHCs) exceeded those of d6‐α‐CEHCs by about 10 times. There was no effect of age. Thus, there might be no need for a higher vitamin E intake for healthy elderly nonsmoking men.
Vitamin E and Gene Expression in Immune Cells
Authors: HAN SUNG NIM , ADOLFSSON OSKAR , LEE CHEOL‐KOO , PROLLA TOMAS A. , ORDOVAS JOSE , MEYDANI SIMIN NIKBIN
Published: March 2005

Abstract: Aging is associated with dysregulation of immune cells, particularly T cells. Previous studies indicated that vitamin E improves T cell function, in part by a direct effect on T cells. We studied gene expression profile of T cells to better understand the underlying mechanisms of aging‐ and vitamin E‐induced changes in T cell function. Young and old C57BL mice were fed diets containing 30 (control) or 500 (E) ppm of vitamin E for 4 weeks. T cells were purified from splenocytes by negative selection using magnetic beads (anti‐Mac‐1 and anti‐MHC class II), then cultured with media or stimulated with anti‐CD3 and anti‐CD28. Gene expression profile was assessed using microarray analysis. Genes showing more than two‐fold changes, P < 0.05 by ANOVA, and with at least one present call were selected. Aging had significant effects on genes involved in signal transduction, transcriptional regulation, and apoptosis pathways in T cells, while vitamin E had a significant effect on genes associated with the regulation of cell cycle.
Tocotrienol: The Natural Vitamin E to Defend the Nervous System?
Authors: SEN CHANDAN K. , KHANNA SAVITA , ROY SASHWATI
Published: March 2005

Abstract: Vitamin E is essential for normal neurological function. It is the major lipid‐soluble, chain‐breaking antioxidant in the body, protecting the integrity of membranes by inhibiting lipid peroxidation. Mostly on the basis of symptoms of primary vitamin E deficiency, it has been demonstrated that vitamin E has a central role in maintaining neurological structure and function. Orally supplemented vitamin E reaches the cerebrospinal fluid and brain. Vitamin E is a generic term for all tocopherols and their derivatives having the biological activity of RRR‐α‐tocopherol, the naturally occurring stereoisomer compounds with vitamin E activity. In nature, eight substances have been found to have vitamin E activity: α‐, β‐, γ‐ and δ‐tocopherol; and α‐, β‐, γ‐ and δ‐tocotrienol. Often, the term vitamin E is synonymously used with α‐tocopherol. Tocotrienols, formerly known as ζ, ε, or η‐tocopherols, are similar to tocopherols except that they have an isoprenoid tail with three unsaturation points instead of a saturated phytyl tail. Although tocopherols are predominantly found in corn, soybean, and olive oils, tocotrienols are particularly rich in palm, rice bran, and barley oils. Tocotrienols possess powerful antioxidant, anticancer, and cholesterol‐lowering properties. Recently, we have observed that α‐tocotrienol is multi‐fold more potent than α‐tocopherol in protecting HT4 and primary neuronal cells against toxicity induced by glutamate as well as by a number of other toxins. At nanomolar concentration, tocotrienol, but not tocopherol, completely protected neurons by an antioxidant‐independent mechanism. Our current work identifies two major targets of tocotrienol in the neuron: c‐Src kinase and 12‐lipoxygenase. Dietary supplementation studies have established that tocotrienol, fed orally, does reach the brain. The current findings point towards tocotrienol as a potent neuroprotective form of natural vitamin E.
Oral Supplementation with All‐Rac‐ and RRR‐α‐Tocopherol Increases Vitamin E Levels in Human Sebum after a Latency Period of 14‐21 Days
Authors: EKANAYAKE‐MUDIYANSELAGE SWARNA , KRAEMER KLAUS , THIELE JENS J.
Published: March 2005

Abstract: In human skin, highest α‐tocopherol levels are found in facial sebum. We hypothesized that the bioavailability of vitamin E in human skin is, at least in part, dependent on sebaceous gland secretion. To test this, 24 volunteers were subjected to a randomized daily supplementation with either 400 mg RRR‐α‐tocopheryl acetate (RRR‐α‐toc) or 400 mg all‐rac‐α‐tocopheryl acetate (all‐rac‐α‐toc) for 14 days. Fasting blood samples, facial sebum samples, and lower‐arm skin‐surface lipids (SSL) were taken at time‐points between 0‐21 days. Samples were analyzed by HPLC for α‐tocopherol and squalene concentrations. Increased serum α‐tocopherol levels were detectable as early as 12 h after supplementation of RRR‐α‐toc or all‐rac‐α‐toc and peaked on day 7. No significant changes were observed in lower‐arm SSL. Remarkably, while unchanged until day 14, α‐tocopherol sebum levels were increased on day 21 in both the RRR‐α‐toc and the all‐rac‐α‐toc group by 87% and 92%, respectively. With respect to dietary supplementation of vitamin E and its bioavailability in human skin, these results suggest that (1) sebaceous gland secretion is a relevant delivery mechanism; (2) the bioavailabilities of RRR‐α‐toc and the all‐rac‐α‐toc are similar; and (3) significant accumulation requires a daily supplementation period of at least 2‐3 weeks.
Vitamin E and Respiratory Infection in the Elderly
Authors: MEYDANI SIMIN NIKBIN , HAN SUNG NIM , HAMER DAVIDSON H.
Published: March 2005

Abstract: Respiratory infections are prevalent in the elderly, resulting in increased morbidity, mortality, and utilization of health care services. Contributing to the increased incidence of infection with age is the well‐described decline in immune response, which has been correlated with patterns of illness in the elderly. For example, there are higher morbidity and mortality from cancer, pneumonia, and post‐operative complications in those who have diminished, delayed‐type hypersensitivity skin test responses. Nutritional status is an important determinant of immune function. We have shown in double‐blind, placebo‐controlled trials that vitamin E supplementation significantly improved immune response, including DTH and response to vaccines. Furthermore, subjects receiving vitamin E in the 6‐month trial had a 30% lower incidence of infectious diseases. That study, however, was not powered to demonstrate statistical significance, and the infections were self‐reported. To overcome these limitations, we conducted a double‐blind, placebo‐controlled trial to determine the effect of one‐year supplementation with 200 IU/day vitamin E on the incidence and duration of respiratory infections in 617 elderly nursing home residents. The results of this clinical trial show that vitamin E supplementation significantly reduces the incidence rate of common colds and the number of subjects who acquire a cold among elderly nursing home residents. A nonsignificant reduction in the duration of colds was also observed. Because of the high rate and more severe morbidity associated with common colds in this age group, these findings have important implications for the well being of the elderly as well as for the economic burden associated with their care.
Vitamin E in Preeclampsia
Authors: POSTON LUCILLA , RAIJMAKERS MAARTEN , KELLY FRANK
Published: March 2005

Abstract: Preeclampsia is the disorder of pregnancy with the highest rate of both maternal and neonatal morbidity and mortality. The maternal syndrome is characterized by oxidative stress and activation of the vascular endothelium that may originate from placental release of lipid peroxidation products, cytokines, and microparticles leading to an acute inflammatory response. The current understanding of the etiology has allowed the improvement of predictive tests, tests that could make intervention possible from early pregnancy onwards. Although the large secondary intervention antioxidant trials in cardiovascular diseases did not show any beneficial effect of vitamin E and vitamin C, either alone or in combination, knowledge of the nature of the pathogenesis of preeclampsia offers hope for the beneficial use of antioxidants in the prevention of the disorder. Not only has our previous small trial shown that antioxidant prophylactics in high‐risk women lowered the prevalence of preeclampsia, but also new evidence has demonstrated multiple other actions of α‐tocopherol (such as anti‐inflammation and inhibition of NAD(P)H oxidase activation) besides its antioxidant properties that could be advantageous in the prevention of the disorder. Several larger trials are under way to investigate the precise role that vitamins C and E can play in the prevention of preeclampsia.
Vitamin E for the Treatment of Cardiovascular Disease: Is There a Future?
Authors: VIOLI FRANCESCO , CANGEMI ROBERTO , SABATINO GIUSEPPE , PIGNATELLI PASQUALE
Published: March 2005

Abstract: Oxidative stress seems to play a key role in the pathogenesis of atherosclerosis. Agents that protect low‐density lipoprotein from oxidation have been shown in a range of in vitro and animal models to reduce the development and progression of atherosclerosis. These agents include antioxidant micronutrients such as vitamin E. They have gained wide interest because of the potential for prevention of atherosclerotic vascular disease in humans. In the last decade, many trials with antioxidants have been carried out in patients with cardiovascular disease, but the results are equivocal. The reason for the disappointing findings is unclear, but one possible explanation is the lack of identification criteria of patients who are potential candidates for antioxidant treatment. This review analyses the data reported so far to determine whether they clearly support the premise that patients at risk of cardiovascular disease may be candidates for antioxidant treatment.
Fluorescent Tocopherols as Probes of Inter‐Vesicular Transfer Catalyzed by the α‐Tocopherol Transfer Protein
Authors: ATKINSON JEFFREY K. , NAVA PHILLIP , FRAHM GRANT , CURTIS VALERIE , MANOR DANNY
Published: March 2005

Abstract: Novel fluorescent analogues of α‐tocopherol have been prepared that incorporate the useful fluorophores nitrobenoxadiazyl (NBD) and anthroyloxy (AO). Both fluorescent tocopherol analogues bind specifically to recombinant human tocopherol transfer protein (hTTP). The NBD‐α‐tocopherol is particularly useful for protein‐binding assays, whereas the AO‐α‐tocopherol was designed to be one of a pair of chromophores for a fluorescence resonance energy transfer (FRET) assay of intervesicular tocopherol transfer. It is now possible to follow AO‐α‐tocopherol transfer from donor lipid vesicles composed of predominantly phosphatidylcholine (PC) to acceptor lipid vesicles containing PC and a quenching lipid NBD‐PE (2‐dipalmitoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[7‐nitro‐2‐1,3‐benzoxadiazol‐4‐yl]). The presence of hTTP substantially increases the rate of AO‐α‐tolcopherol transfer over the uncatalyzed spontaneous rate.
Intracellular Localization of α‐Tocopherol Transfer Protein and α‐Tocopherol
Authors: QIAN JINGHUI , WILSON KATHLEEN , NAVA PHIL , MORLEY SAMANTHA , ATKINSON JEFFREY , MANOR DANNY
Published: March 2005

Abstract: The mechanism of action of tocopherol transfer protein (TTP) and its role in the intracellular processing of vitamin E were investigated using confocal fluorescence microscopy. The results from this work suggest that TTP functions by transporting vitamin E from endocytic organelles to other locations in the cell.
Structure‐Function Relationship in the Tocopherol Transfer Protein
Authors: MORLEY S , PANAGABKO C , STOCKER A , ATKINSON J , MANOR D
Published: March 2005

Abstract: The role of specific amino acid residues in mediating the biochemical functions of tocopherol transfer protein (TTP) was investigated using site‐directed mutagenesis and functional assays. These findings further current understanding of TTP mechanism of action and its role in human health.
Vitamin E in Uremia and Dialysis Patients
Authors: GALLI FRANCESCO , BUONCRISTIANI UMBERTO , CONTE CARMELA , AISA CRISTINA , FLORIDI ARDESIO
Published: March 2005

Abstract: Vitamin E therapy (based either on oral supplements or new dialysis methods such as vitamin E‐coated hemodialysers) has been suggested to yield a better clinical outcome in hemodialysis (HD) patients than in other populations of patients. Among other factors, the presence of a modified vitamin E status might help to explain this apparently paradoxical response to vitamin E. In this study we investigated 104 regular HD patients. The results indicate that, besides having a low dietary intake, these subjects show some abnormalities in the levels and metabolism of vitamin E, such as a disproportion between plasma tocopherols and lipids, low levels of γ‐T, and CEHC accumulation. Although further studies are needed to confirm the clinical relevance of vitamin E therapy in HD, these findings might lead to recommending a higher vitamin E intake in these patients.