bluuebunny/crossref_metadata_2025 huggingface dataset:
A bioactive withanolide Tubocapsanolide A inhibits proliferation of human lung cancer cells via repressing Skp2 expression
Authors: Chang Hui-Chiu , Chang Fang-Rong , Wang Yu-Chu , Pan Mei-Ren , Hung Wen-Chun , Wu Yang-Chang
Published: May 2007

Withanolides are generally defined as C28 steroidal lactones built on an intact or rearranged ergostane skeleton and have been shown to exhibit antiproliferative activity on various types of cancer cells. In this study, we investigated the effect of a new withanolide Tubocapsanolide A isolated from Tubocapsicum anomalum and addressed its molecular action. Tubocapsanolide A inhibited proliferation of A549, H358, and H226 human lung cancer cells via induction of G1 growth arrest. We found that Tubocapsanolide A treatment led to up-regulation of cyclin E, p21, and p27, whereas other cyclins and cyclin-dependent kinases were not affected in A549 cells. Conversely, Skp2, the F-box protein that is implicated in the mediation of degradation of p21 and p27, was significantly down-regulated. Chromatin immunoprecipitation assay suggested that Tubocapsanolide A suppressed Skp2 expression by inhibiting the binding of Rel A to the nuclear factor-κB site of Skp2 gene promoter. In addition, we showed that inhibition of Skp2 is a critical step for the suppression of cell proliferation by Tubocapsanolide A because ectoexpression of Skp2 effectively reversed Tubocapsanolide A–induced p27 up-regulation and growth inhibition in human lung cancer cells. Collectively, we have identified Skp2 as a molecular target for Tubocapsanolide A and suggest that this withanolide may be useful for the prevention or treatment of cancer cells with Skp2 overexpression. [Mol Cancer Ther 2007;6(5):1572–8]
Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator–activated receptor γ agonists in colon cancer cells
Authors: Chintharlapalli Sudhakar , Papineni Sabitha , Jutooru Indira , McAlees Alan , Safe Stephen
Published: May 2007

Glycyrrhizin, a pentacyclic triterpene glycoside, is the major phytochemical in licorice. This compound and its hydrolysis product glycyrrhetinic acid have been associated with the multiple therapeutic properties of licorice extracts. We have investigated the effects of 2-cyano substituted analogues of glycyrrhetinic acid on their cytotoxicities and activity as selective peroxisome proliferator–activated receptor γ (PPARγ) agonists. Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (β-CDODA-Me) and methyl 2-cyano-3,11-dioxo-18α-olean-1,12-dien-30-oate (α-CDODA-Me) were more cytotoxic to colon cancer cells than their des-cyano analogues and introduction of the 2-cyano group into the pentacyclic ring system was necessary for the PPARγ agonist activity of α-CDODA-Me and β-CDODA-Me isomers. However, in mammalian two-hybrid assays, both compounds differentially induced interactions of PPARγ with coactivators, suggesting that these isomers, which differ only in the stereochemistry at C18 which affects conformation of the E-ring, are selective receptor modulators. This selectivity in colon cancer cells was shown for the induction of two proapoptotic proteins, namely caveolin-1 and the tumor-suppressor gene Krüppel-like factor-4 (KLF-4). β-CDODA-Me but not α-CDODA-Me induced caveolin-1 in SW480 colon cancer cells, whereas caveolin-1 was induced by both compounds in HT-29 and HCT-15 colon cancer cells. The CDODA-Me isomers induced KLF-4 mRNA levels in HT-29 and SW480 cells but had minimal effects on KLF-4 expression in HCT-15 cells. These induced responses were inhibited by cotreatment with a PPARγ antagonist. This shows for the first time that PPARγ agonists derived from glycyrrhetinic acid induced cell-dependent caveolin-1 and KLF-4 expression through receptor-dependent pathways. [Mol Cancer Ther 2007;6(5):1588–98]
Four-Dimensional Dynamic Radar Mosaic
Authors: Langston Carrie , Zhang Jian , Howard Kenneth
Published: May 2007

Communities and many industries are affected by severe weather and have a need for real-time accurate Weather Surveillance Radar-1988 Doppler (WSR-88D) data spanning several regions. To fulfill this need the National Severe Storms Laboratory has developed a Four-Dimensional Dynamic Grid (4DDG) to accurately represent discontinuous radar reflectivity data over a continuous 4D domain. The objective is to create a seamless, rapidly updating radar mosaic that is well suited for use by forecasters in addition to advance radar applications such as qualitative precipitation estimates. Several challenges are associated with creating a 3D radar mosaic given the nature of radar data and the spherical coordinates of radar observations. The 4DDG uses spatial and temporal weighting schemes to overcome these challenges, with the intention of applying minimal smoothing to the radar data. Previous multiple radar mosaics functioned in two or three dimensions using a variety of established weighting schemes. The 4DDG has the advantage of temporal weighting to smooth radar observations over time. Using an exponentially decaying weighting scheme, this paper will examine different weather scenarios and show the effects of temporal smoothing using different time scales. Specifically, case examples of the 4DDG approach involving a rapidly evolving convective event and a slowly developing stratiform weather regime are considered.
Spaced-Antenna Interferometry to Measure Crossbeam Wind, Shear, and Turbulence: Theory and Formulation
Authors: Zhang Guifu , Doviak Richard J.
Published: May 2007

The theory of measuring crossbeam wind, shear, and turbulence within the radar’s resolution volume V6 is described. Spaced-antenna weather radar interferometry is formulated for such measurements using phased-array weather radar. The formulation for a spaced-antenna interferometer (SAI) includes shear of the mean wind, allows turbulence to be anisotropic, and allows receiving beams to have elliptical cross sections. Auto- and cross-correlation functions are derived based on wave scattering by randomly distributed particles. Antenna separation, mean wind, shear, and turbulence all contribute to signal decorrelation. Crossbeam wind cannot be separated from shear, and thus crossbeam wind measurements are biased by shear. It is shown that SAI measures an apparent crossbeam wind (i.e., the angular shear of the radial wind component). Whereas the apparent crossbeam wind and turbulence within V6 cannot be separated using monostatic Doppler techniques, angular shear and turbulence can be separated using the SAI.
Advancements in Techniques for Calibration and Characterization of In Situ Optical Particle Measuring Probes, and Applications to the FSSP-100 Probe
Authors: Nagel Dagmar , Maixner Uwe , Strapp Walter , Wasey Mohammed
Published: May 2007

Advancements in techniques for the operational calibration and characterization of instrument performance of the Particle Measuring Systems, Inc. (PMS), forward scattering spectrometer probe (FSSP) and optical array probes (OAPs) are presented, which also can be used for most in situ particle-measuring optical probes on the market. These techniques include the determination of a distortion matrix to correct for instrumental broadening of the measured particle size distribution. A new version of a monodisperse droplet generator is introduced for absolute calibration in the size range between 10 and 100 μm. In addition, a high-speed technique was employed for the determination of airspeed influence on the sample volume and the sizing of particles.

The calibration of a PMS FSSP with real water droplets may be significantly different from the usual calibration with glass beads. High-speed measurements simulate particles at speeds of up to about 250 m s−1. Particle undersizing and the decrease of the sample volume with increasing airspeed are described. The use of the modular tools, built for this work, is discussed for probe alignment, functionality checks, and general characterization and diagnostics both in laboratory and field environments.
Analyzing Monthly Extreme Sea Levels with a Time-Dependent GEV Model
Authors: Méndez Fernando J. , Menéndez Melisa , Luceño Alberto , Losada Inigo J.
Published: May 2007

A statistical model to analyze different time scales of the variability of extreme high sea levels is presented. This model uses a time-dependent generalized extreme value (GEV) distribution to fit monthly maxima series and is applied to a large historical tidal gauge record (San Francisco, California). The model allows the identification and estimation of the effects of several time scales—such as seasonality, interdecadal variability, and secular trends—in the location, scale, and shape parameters of the probability distribution of extreme sea levels. The inclusion of seasonal effects explains a large amount of data variability, thereby allowing a more efficient estimation of the processes involved. Significant correlation with the Southern Oscillation index and the nodal cycle, as well as an increase of about 20% for the secular variability of the scale parameter have been detected for the particular dataset analyzed. Results show that the model is adequate for a complete analysis of seasonal-to-interannual sea level extremes providing time-dependent quantiles and confidence intervals.
Examination of the μ–Λ Relation Suggested for Drop Size Distribution Parameters
Authors: Moisseev Dmitri N. , Chandrasekar V.
Published: May 2007

Raindrop size distributions are often assumed to follow a three-parameter gamma distribution. Since rain intensity retrieval from radar observations is an underdetermined problem, there is great interest in finding physical correlations between the parameters of the gamma distribution. One of the more common approaches is to measure naturally occurring drop size distributions (DSDs) using a disdrometer and to find DSD parameters by fitting a gamma distribution to these observations. Often the method of moments is used to retrieve the parameters of a gamma distribution from disdrometer observations.

In this work the effect of the method of moments and data filtering on the relation between the parameters of the DSD is investigated, namely, the shape μ and the slope Λ parameters. For this study the disdrometer observations were simulated. In these simulations the gamma distribution parameters Nw, D0, and μ were randomly selected from a wide range of values that are found in rainfall. Then, using simulated disdrometer measurements, DSD parameters were estimated using the method of moments. It is shown that the statistical errors associated with data filtering of disdrometer measurements might produce a spurious relation between μ and Λ parameters. It is also shown that three independent disdrometer measurements can be used to verify the existence of such a relation.
International Region-Building
Authors: Keskitalo Carina
Published: May 2007

The Arctic has emerged as a region in international cooperation during the past 20—30 years, as manifest in the creation of the Arctic Council and its predecessor, the Arctic Environmental Protection Strategy, and in the incidence of a host of scientific and political cooperation projects. The region now includes eight states over the circumpolar area; namely, the United States, Russia, Canada and the Nordic countries. How this international region has developed over time is investigated with reference to the conception of regions as understood in region-building discourse. Accordingly, the Arctic as a region that is not natural or given but as constructed by and for particular actors and interests is studied. It is concluded that the regional superstructure includes conceptions of the North that draw on images developed in historical exploration and research, shaped by a discourse of the Arctic representing North American more than Nordic understandings.
Mercosur and the European Union
Authors: Mukhametdinov Mikhail
Published: May 2007

The European Union (EU) and the Common Market of the South (Mercosur) are very different regions that have come to seemingly analogous compromises as far as the operation of their common markets is concerned. Like the EU, Mercosur seems to confirm the textbook logic of integration development from a free trade area to a customs union and then to a common market. Does this mean that well-developed theories of European integration that emphasize certain properties of the European region are useless in explaining and predicting the Mercosur process? This article proposes a framework for comparison of the two blocs that uses selected theories of European integration: neofunctionalism, liberal inter-governmentalism, social constructivism and neo-realism. The framework is applied to the examination of intra-regional cohesion of the two interstate cooperative groups. Comparison of the two unions demonstrates that, despite similar institutional structures and partial set-ups of the common markets, they are qualitatively different processes that are highly conditioned by their unique regional properties. There is therefore no contradiction between Mercosur and the predictions of the Mercosur integration based on the theories of European integration. At the same time, Mercosur is strongly affected by the passive and active influence of the EU. However, the one-size-fits-all prescriptions for regionalism in the global south should be critically reevaluated. Mercosur and other regions have to optimize their development looking for solutions to specific regional problems rather than trying to adapt textbook models of integration derived from integration experience of the EU or NAFTA. The study emphasizes the importance of non-economic factors of integration and the necessity to evaluate the success of integration associations outside Europe in the context of local social realities rather than against the EU criteria.
Dynamics-based Damage Detection of Composite Laminated Beams using Contact and Noncontact Measurement Systems
Authors: Qiao Pizhong , Lestari Wahyu , Shah Mitali G. , Wang Jialai
Published: May 2007

A reliable and effective damage detection technique is one of the significant tools to maintain the safety and integrity of structures. A dynamic response offers viable information for the identification of damage in the structures. However, the performance of such dynamics-based damage detection depends on the quality of measured data and the effectiveness of data processing algorithms. In this article, the experimentally measured data of two sensor systems, i.e., a surface-bonded piezoelectric sensor system and a noncontact scanning laser vibrometer (SLV) system, are studied, and their effectiveness in damage identification of composite laminated beams is compared. Three dynamics-based damage detection algorithms are evaluated using the data acquired from these two measurement systems. The curvature mode shape is selected as a parameter to locate damage due to its sensitivity. The piezoelectric sensors directly acquire the curvature mode shapes of the structures, while the SLV measures the displacement mode shapes. The difference in the measurement characteristics of these systems and their influence in the damage identification performance are addressed. The beam specimens are made of E-glass/epoxy composites, and several different types of damages are introduced in the beams (i.e., delaminations, and impact and saw-cut damages). This study provides a thorough assessment of the two sensor systems in damage detection of composite laminated beams and verifies the validity of dynamics-based damage detection methodology in locating the local defects in composite structures.
Romantic Anarchism and Pedestrian Liberalism
Authors: Herzog Don
Published: May 2007

Emma Goldman's stance toward anarchism was oddly mystified, even loving. Precisely this enchantment led her to see clearly the deep vices of Soviet Russia, when so many on the sane and sober Left were blind to them. So pedestrian liberals ought to relish having the extreme likes of Goldman in their midst. They—we—can faithfully recite their lessons from Mill about free speech, eccentrics, and the proliferation of viewpoints. But more recent liberals and deliberative democrats, insisting on the political centrality of reasonableness, would have problems embracing her. That should give us pause at the politics of reasonableness. And Goldman's infatuation with her own politics offers a tweak on Aristotle: a bad person can make a good citizen.
Making Meaning of Educational Leadership: The Principalship in Metaphor
Authors: Linn Genie B. , Sherman Ross , Gill Peggy B.
Published: May 2007

This article explores how future educational leaders make meaning of the principalship through metaphor. At the conclusion of a university principal preparation program, principal interns were asked to use figurative language to represent the principalship. The metaphors identified four distinct themes: (a) protection and nurturing; (b) skill, adventure, or problem solving; (c) challenge, risk, and threat; and (d) chance and luck. Their responses provide a glimpse into their perceptions and mental models that shape their understanding and influence leadership behaviors.
IDEA 2004 and Disciplining Students With Disabilities
Authors: Ryan Joseph B. , Katsiyannis Antonis , Peterson Reece , Chmelar Rebecca
Published: May 2007

Individuals with Disabilities Education Improvement Act (IDEA) included substantive changes in the area of disciplining students with disabilities. Historically, discipline has been a divisive issue within the field of special education. Many administrators and teachers believe differential treatment has been afforded to this population, fostering a system that promotes separatism and inequality. The authors provide an overview of IDEA 2004 provisions on discipline and outline practical recommendations that will aid school personnel maintain a safe environment for all students. Areas of discussion include suspension procedures, functional behavioral assessments, manifestation determination meetings, and interim alternative educational settings. The authors also provide a list of potential alternatives to disciplinary exclusions.
Sin Papeles
Authors: Hancock Tina U.
Published: May 2007

Drawing on structural and life-cycle perspectives and a limited body of literature, this article explores the obstacle of illegal status to expanding views of self, the more equitable gender roles in marriage, and the mothering responsibilities for young working-class women from rural Mexico who have settled in rural communities and small towns in the United States. Strengths related to the Mexican culture and risks and opportunities accompanying migration in young adulthood are examined within this framework.
Reclaiming Their Lives and Breaking Free
Authors: Valandra
Published: May 2007

Little research has examined the specific healing needs of prostituted African American women. In this qualitative research study, eight African American women who were receiving culturally specific services at an Afrocentric agency participated in a focus group and in-depth semistructured interviews.. The analysis revealed seven categories of experience: (1) a legacy of violence and underreporting, (2) family and self-preservation, (3) kinship support and spirituality, (4) hitting rock bottom, (5) barriers to recovery, (6) helpful and harmful services, and (7) a prism of oppression. Implications for social workers, policy makers, advocates, and further research are discussed.
Making a Wish in Rwanda
Authors: Wood Starr A.
Published: May 2007

Though the genocide in Rwanda occurred in 1994, its debilitating effects on the survivors persist, and probably will continue to persist for many years, if not generations. This paper explores the question of why a simple Western tradition may have helped a Rwandan woman to emerge from a 13-year-old state of grief. The key elements involved in her transformation were: resilience, timing, connection, and creativity. Additionally, positive regard and sincere respect can promote healing and can transcend language and culture. Parallels between self-in-relation theory and trauma recovery work are discussed. Social workers must strive to be culturally competent, but should not underestimate the effectiveness of their essential social work training and practical experience.
Schema Model of the Self-Concept to Examine the Role of the Self-Concept in Alcohol Dependence and Recovery
Authors: Corte Colleen
Published: May 2007

In this article, we review the existing research on the self-concept in alcohol dependence and recovery and describe a theoretical model of the self-concept, called the schema model, that can be used to interpret the findings from the existing literature and serve as a framework for further research studies. Next, we provide some empirical evidence from a recent study based on the schema model that demonstrates that specific content and structural properties of the self-concept are associated with alcohol dependence and recovery. We then discuss implications for nursing research and practice. J Am Psychiatr Nurses Assoc, 2007; 13(1), 31-41.
Cost-Benefit Analysis of Tacoma's Assigned Vehicle Program
Authors: Lauria Donald T.
Published: May 2007

The Police Department's Assigned Vehicle Program (AVP) in Tacoma was adopted in 1999. In 2004, the city decided to make an economic evaluation of it. Focus groups preceded development of a questionnaire about current and changed usage of police vehicles since inception of the AVP. A second questionnaire explored citizen attitudes toward the AVP. The evaluation addressed two questions: (a) Is the present AVP better than using pool vehicles? and (b) Is it better to let officers take vehicles home when off duty or should they be kept in the city? The analysis found that the benefits of assigning vehicles and allowing them to be taken home far outweigh costs; police productivity is significantly enhanced, and free parking at officers' homes is much less expensive than parking provided by the city. The study methodology is a prototype for similar benefit-cost evaluations.
Drug Law Enforcement
Authors: Mazerolle Lorraine , Soole David , Rombouts Sacha
Published: May 2007

This article describes the results of a systematic review of drug law enforcement evaluations. The authors describe the search procedures and document the results in five main categories: international/national interventions (e.g., interdiction and drug seizure), reactive/ directed interventions (e.g., crackdowns, raids, buy-busts, saturation patrol, etc.), proactive/ partnership interventions (e.g., third-party policing, problem-oriented policing, community policing, drug nuisance abatement, etc.), individualized interventions (e.g., arrest referral and diversion), or interventions that used a combination of reactive/directed and proactive/ partnership strategies. Results indicate that proactive interventions involving partnerships between the police and third parties and/or community entities appear to be more effective at reducing both drug and nondrug problems in drug problem places than are reactive/ directed approaches. But the general quality of research in drug law enforcement is poor, the range of interventions that have been evaluated is limited, and more high-quality research is needed across a greater variety of drug interventions.
The interaction of PP1 with BRCA1 and analysis of their expression in breast tumors
Authors: Winter Sherry L , Bosnoyan-Collins Lucine , Pinnaduwage Dushanthi , Andrulis Irene L
Published: May 2007

Background

The breast cancer susceptibility gene,BRCA1, is implicated in multiple cellular processes including DNA repair, the transactivation of genes, and the ubiquitination of proteins; however its precise functions remain to be fully understood. Identification and characterization of BRCA1 protein interactions may help to further elucidate the function and regulation of BRCA1. Additionally, detection of changes in the expression levels ofBRCA1and its interacting proteins in primary human breast tumors may further illuminate their role in the development of breast cancer.

Methods

We performed a yeast two-hybrid study to identify proteins that interact with exon11 of BRCA1 and identified Protein Phosphatase 1β (PP1β), an isoform of the serine threonine phosphatase, PP1. GST-pull down and co-immunoprecipitation assays were performed to further characterize this interaction. Additionally, Real-Time PCR was utilized to determine the expression ofBRCA1,PP1α, β and γ in primary human breast tumors and normal breast tissue to identify alterations in the expression of these genes in breast cancer.

Results

PP1 and BRCA1 co-immunoprecipitate and the region within BRCA1 as well as the specific PP1 interacting domain mediating this interaction were identified. Following mRNA expression analysis, we identified low levels ofBRCA1and variable levels ofPP1α and β in primary sporadic human breast tumors. Furthermore, BRCA1,PP1β and PP1γ were significantly higher in normal tissue specimens (BRCA1 p = 0.01,PP1β: p = 0.03,PP1γ, p = 1.9 × 10-6) compared to sporadic breast tumor samples. Interestingly, we also identified that ER negative tumors are associated with low levels ofPP1α expression.

Conclusion

The identification and characterization of the interaction of BRCA1 with PP1 and detection of changes in the expression ofPP1and genes encoding other BRCA1 associated proteins identifies important genetic pathways that may be significant to breast tumorigenesis. Alterations in the expression of genes, particularly phosphatases that operate in association with BRCA1, could negatively affect the function of BRCA1 or BRCA1 associated proteins, contributing to the development of breast cancer.
Costs of a successful public-private partnership for TB control in an urban setting in Nepal
Authors: Karki Deepak K , Mirzoev Tolib N , Green Andrew T , Newell James N , Baral Sushil C
Published: May 2007

Background

In South Asia a large number of patients seek treatment for TB from private practitioners (PPs), and there is increasing international interest in involving PPs in TB control. To evaluate the feasibility, effectiveness and costs of public-private partnerships (PPPs) for TB control, a PPP was developed in Lalitpur municipality, Nepal, where it is estimated that 50% of patients with TB are managed in the private sector. From the clinical perspective the PPP was shown to be effective. The aim of this paper is to assess and report on the costs involved in the PPP scheme.

Methods

The approach to costing took a comprehensive view, with inclusion of costs not only incurred by health facilities but also social costs borne by patients and their escorts. Semi-structured questionnaires and guided interviews were used to collect start-up and recurrent costs for the scheme.

Results

Overall costs for treating a TB patient under the PPP scheme averaged US$89.60. Start-up costs per patient represented 12% of the total budget. Half of recurrent costs were incurred by patients and their escorts, with institutional costs representing most of the rest. Female patients tended to spend more and patients referred from the private sector had the highest reported costs.

Conclusion

Treating TB patients in the PPP scheme had a low additional cost, while doubling the case notification rate and maintaining a high success rate. Costs incurred by patients and their escorts were the largest contributors to the overall total. This suggests a focus for follow-up studies and for cost-minimisation strategies.
Inhibition of indoleamine 2,3-dioxygenase-mediated tryptophan catabolism accelerates collagen-induced arthritis in mice
Authors: Szántó Sándor , Koreny Tamás , Mikecz Katalin , Glant Tibor T , Szekanecz Zoltán , Varga John
Published: May 2007

Indoleamine 2,3-dioxygenase (IDO) is one of the initial and rate-limiting enzymes involved in the catabolism of the essential amino acid tryptophan. In cultured cells, the induction of IDO leads to depletion of tryptophan and tryptophan starvation. Recent studies suggest that modulation of tryptophan concentration via IDO plays a fundamental role in innate immune responses. Induction of IDO by interferon-γ in macrophages and dendritic cells results in tryptophan depletion and suppresses the immune-mediated activation of fibroblasts and T, B, and natural killer cells. To assess the role of IDO in collagen-induced arthritis (CIA), a model of rheumatoid arthritis characterized by a primarily Th1-like immune response, activity of IDO was inhibited by 1-methyl-tryptophan (1-MT) in vivo. The results showed significantly increased incidence and severity of CIA in mice treated with 1-MT. Activity of IDO, as determined by measuring the levels of kynurenine/tryptophan ratio in the sera, was increased in the acute phase of arthritis and was higher in collagen-immunized mice that did not develop arthritis. Treatment with 1-MT resulted in an enhanced cellular and humoral immune response and a more dominant polarization to Th1 in mice with arthritis compared with vehicle-treated arthritic mice. The results demonstrated that development of CIA was associated with increased IDO activity and enhanced tryptophan catabolism in mice. Blocking IDO with 1-MT aggravated the severity of arthritis and enhanced the immune responses. These findings suggest that IDO may play an important and novel role in the negative feedback of CIA and possibly in the pathogenesis of rheumatoid arthritis.
IL-4-stimulated NF-κB activity is required for Stat6 DNA binding
Authors: Thieu Vivian T , Nguyen Evelyn T , McCarthy Brian P , Bruns Heather A , Kapur Reuben , Chang Cheong-Hee , Kaplan Mark H
Published: May 2007

IL-4 is a critical cytokine in the regulation of immune responses. In B lymphocytes, IL-4 signaling promotes the Stat6-dependent cell surface expression of several proteins including MHC Class II and CD86. However, the requirement for other transcription factors in IL-4-induced B cell gene expression has not been studied extensively. Here, we show that IL-4 induces NF-κB p100 processing to NF-κB p52 in B cells but not in T cells or macrophages. IL-4 induced NF-κB p52 production requires PI-3K activity and correlates with IκB kinase phosphorylation and TNF receptor-associated factor 3 degradation. Blocking NF-κB activity eliminates IL-4-stimulated gene expression in B cells by reducing IL-4-induced DNA binding but not phosphorylation or nuclear localization of Stat6. These results describe a novel role for NF-κB in IL-4-induced signaling and gene expression.
Phase I Trial of Histone Deacetylase Inhibition by Valproic Acid Followed by the Topoisomerase II Inhibitor Epirubicin in Advanced Solid Tumors: A Clinical and Translational Study
Authors: Münster Pamela , Marchion Douglas , Bicaku Elona , Schmitt Morgen , Lee Ji Hyun , DeConti Ronald , Simon George , Fishman Mayer , Minton Susan , Garrett Chris , Chiappori Alberto , Lush Richard , Sullivan Daniel , Daud Adil
Published: May 2007

Purpose

To determine the safety, toxicity, and maximum-tolerated dose of a sequence-specific combination of the histone deacetylase inhibitor (HDACi), valproic acid (VPA), and epirubicin in solid tumor malignancies and to define the clinical feasibility of VPA as an HDACi.

Patients and Methods

Patients were treated with increasing doses of VPA (days 1 through 3) followed by epirubicin (day 3) in 3-week cycles. The study evaluated pharmacokinetic and pharmacodynamic end points, toxicities, and tumor response.

Results

Forty-eight patients were enrolled, and 44 received at least one cycle of therapy. Patients (median age, 54 years; range, 39 to 78 years) received the following doses of VPA: 15, 30, 45, 60, 75, 90, 100, 120, 140, and 160 mg/kg/d. Dose-limiting toxicities were somnolence (n = 1), confusion (n = 3), and febrile neutropenia (n = 1). No exacerbation of epirubicin-related toxicities was observed. Partial responses were seen across different tumor types in nine patients (22%), and stable disease/minor responses were seen in 16 patients (39%), despite a median number of three prior regimens (range, zero to 10 prior regimens). Patients received a median number of four treatment cycles (range, one to 10 cycles), and treatment was stopped after reaching maximal epirubicin doses rather than progression in 13 (32%) of 41 patients patients. Total and free VPA plasma concentrations increased linearly with dose and correlated with histone acetylation in peripheral-blood mononuclear cells.

Conclusion

The maximum-tolerated dose and recommended phase II dose was VPA 140 mg/kg/d for 48 hours followed by epirubicin 100 mg/m2. Sustained plasma concentrations of VPA exceeding those required for in vitro synergy were achieved with acceptable toxicity. Noteworthy antitumor activity was observed in heavily pretreated patients and historically anthracycline-resistant tumors.
The NS3 protein of Rice hoja blanca tenuivirus suppresses RNA silencing in plant and insect hosts by efficiently binding both siRNAs and miRNAs
Authors: Hemmes Hans , Lakatos Lóránt , Goldbach Rob , Burgyán József , Prins Marcel
Published: May 2007

RNA silencing plays a key role in antiviral defense as well as in developmental processes in plants and insects. Negative strand RNA viruses such as the plant virus Rice hoja blanca tenuivirus (RHBV) replicate in plants and in their insect transmission vector. Like most plant-infecting viruses, RHBV encodes an RNA silencing suppressor, the NS3 protein, and here it is demonstrated that this protein is capable of suppressing RNA silencing in both plants and insect cells. Biochemical analyses showed that NS3 efficiently binds siRNA as well as miRNA molecules. Binding of NS3 is greatly influenced by the size of small RNA molecules, as 21 nucleotide (nt) siRNA molecules are bound > 100 times more efficiently than 26 nt species. Competition assays suggest that the activity of NS3 is based on binding to siRNAs prior to strand separation during the assembly of the RNA-induced silencing complex. In addition, NS3 has a high affinity for miRNA/miRNA* duplexes, indicating that its activity might also interfere with miRNA-regulated gene expression in both insects and plants.
Evolution of the iron-responsive element
Authors: Piccinelli Paul , Samuelsson Tore
Published: May 2007

An RNA hairpin structure referred to as the iron-responsive element (IRE) and iron regulatory proteins (IRPs) are key players in the control of iron metabolism in animal cells. They regulate translation initiation or mRNA stability, and the IRE is found in a variety of mRNAs, such as those encoding ferritin, transferrin receptor (Tfr), erythroid aminolevulinic acid synthase (eALAS), mitochondrial aconitase (mACO), ferroportin, and divalent metal transporter 1 (DMT1). We have studied the evolution of the IRE by considering all mRNAs previously known to be associated with this structure and by computationally examining its occurrence in a large variety of eukaryotic organisms. More than 100 novel sequences together with ∼50 IREs that were previously reported resulted in a comprehensive view of the phylogenetic distribution of this element. A comparison of the different mRNAs shows that the IREs of eALAS and mACO are found in chordates, those of ferroportin and Tfr1 are found in vertebrates, and the IRE of DMT1 is confined to mammals. In contrast, the IRE of ferritin occurs in a majority of metazoa including lower metazoa such as sponges and Nematostella (sea anemone). These findings suggest that the ferritin IRE represents the ancestral version of this type of translational control and that during the evolution of higher animals the IRE structure was adopted by other genes. On the basis of primary sequence comparison between different organisms, we suggest that some of these IREs developed by “convergent evolution” through stepwise changes in sequence, rather than by recombination events.
Book Reviews
Authors: Gallucci Marcello
Published: May 2007

Effect sizes for research: A broad practical approach Grissom Robert J Kim John J New Jersey: Erlbaum, 2005, Hardback £43.95 ISBN 0805850147
Book Reviews
Authors: Smillie Luke D.
Published: May 2007

The essence of multivariate thinking Harlow Lisa L. London: Lawrence Erlbaum Associates 240, £57.65 ISBN: 0‐8058‐3730‐2
Solubility of salts in water: Key issue for crystal growth and dissolution processes
Authors: Koutsoukos Petros G. , Kofina Aikaterini N. , Kanellopoulou Dimitra G.
Published: May 2007

The formation of sparingly soluble salts from aqueous solutions and their dissolution has attracted broad research interest. Of particular importance is the formation and transformation of minerals exhibiting polymorphism or encountered in more than one crystalline phase as, for example, in the case of calcium phosphates, formed in biological mineralization and in industrial-scale deposits. Understanding of these processes depends primarily on the equilibrium between the mineral phases considered and the aqueous medium in contact. Precipitation takes place in supersaturated solutions with rates depending on the solution supersaturation. The experimental investigation may reveal mechanistic details if done at sustained supersaturation. The kinetics of crystal growth depends either on surface diffusion or on bulk diffusion, which in turn is controlled by the medium fluid dynamics. In the case of magnesium ammonium phosphate (struvite), the presence of water-soluble organic compounds is responsible for the retardation both of the time needed for the onset of precipitation and for the kinetics of growth of the supercritical nuclei. Dissolution processes are controlled by the same mechanisms. In the case of calcitic marble, the dissolution in alkaline solutions is controlled by surface diffusion. Compounds active at the marble/water interface may in this case be used as protective agents.
Li-air batteries: A classic example of limitations owing to solubilities
Authors: Kowalczk Ian , Read Jeffery , Salomon Mark
Published: May 2007

A review is presented of the present state-of-the-art of Li-air cells and batteries. We examine the properties of this unique system in terms of the effects of solubilities of reactants and products in both nonaqueous (aprotic) and aqueous electrolyte solutions. Definite trends are observed, such as increasing cell-specific energy and capacity as both the oxygen solubility increases and viscosity decreases in organic solvents, but quantitative analyses are limited owing to the complex relations between solubility, solution viscosity, oxygen diffusion, and electrolytic conductivity. Adding to this complex relation is the dependence of the nature of the carbon-based air cathode (surface area and pore volume) upon practical specific capacities, which can be realized with Li-air cells that far exceed the specific energies and capacities of all present commercial metal-air and Li-ion cells and batteries.
Feature Construction Can Improve Diagnostic Criteria for High-Dimensional Metabolic Data in Newborn Screening for Medium-Chain Acyl-CoA Dehydrogenase Deficiency
Authors: Ho Sirikit , Lukacs Zoltan , Hoffmann Georg F , Lindner Martin , Wetter Thomas
Published: May 2007

Background: In newborn screening with tandem mass spectrometry, multiple intermediary metabolites are quantified in a single analytical run for the diagnosis of fatty-acid oxidation disorders, organic acidurias, and aminoacidurias. Published diagnostic criteria for these disorders normally incorporate a primary metabolic marker combined with secondary markers, often analyte ratios, for which the markers have been chosen to reflect metabolic pathway deviations.

Methods: We applied a procedure to extract new markers and diagnostic criteria for newborn screening to the data of newborns with confirmed medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and a control group from the newborn screening program, Heidelberg, Germany. We validated the results with external data of the screening center in Hamburg, Germany. We extracted new markers by performing a systematic search for analyte combinations (features) with high discriminatory performance for MCADD. To select feature thresholds, we applied automated procedures to separate controls and cases on the basis of the feature values. Finally, we built classifiers from these new markers to serve as diagnostic criteria in screening for MCADD.

Results: On the basis of χ2 scores, we identified ∼800 of >628 000 new analyte combinations with superior discriminatory performance compared with the best published combinations. Classifiers built with the new features achieved diagnostic sensitivities and specificities approaching 100%.

Conclusion: Feature construction methods provide ways to disclose information hidden in the set of measured analytes. Other diagnostic tasks based on high-dimensional metabolic data might also profit from this approach.
Development and implementation of water safety plans for small water supplies in Bangladesh: benefits and lessons learned
Authors: Mahmud S. G. , Shamsuddin Sk. Abu Jafar , Ahmed M. Feroze , Davison Annette , Deere Dan , Howard Guy
Published: May 2007

Water safety plans (WSPs) are promoted by the WHO as the most effective means of securing drinking water safety. To date most experience with WSPs has been within utility supplies, primarily in developed countries. There has been little documented experience of applying WSPs to small community-managed systems, particularly in developing countries. This paper presents a case study from Bangladesh describing how WSPs can be developed and implemented for small systems. Model WSPs were developed through consultation with key water sector practitioners in the country. Simplified tools were developed to translate the formal WSPs into a format that was meaningful and accessible for communities to use. A series of pilot projects were implemented by Non-Governmental Organisations (NGOs) across the country covering all major water supplies. The results show that WSPs can be developed and implemented for small community managed water supplies and improve the sanitary condition and water quality of water sources. Hygiene behaviour improved and household water quality showed a significant reduction in contamination. Chlorination was found to be important for some technologies, thus increasing the costs of water supply and raising important problems with respect to transfer to the communities. Simple tools for community monitoring were found to be effective in supporting better water safety management.
Multipathway risk assessment of trihalomethane exposure in drinking water of Lebanon
Authors: Semerjian Lucy , Dennis John
Published: May 2007

The toxicological risks and lifetime cancer risks of trihalomethanes through oral ingestion, dermal absorption, and inhalation exposure from tap water in selected regions in Lebanon are estimated. Existing trihalomethane concentrations do not pose any non-carcinogenic and developmental risks in the exposed population via oral ingestion. Among the three pathways, residents have a higher risk of cancer through oral ingestion than through the other two pathways. The lifetime cancer risk through oral ingestion for dibromochloromethane makes the highest contribution to total risks, followed by bromodichloromethane, bromoform, and chloroform. The total multipathway cancer risk analysis suggests that no cancer risks exist during the summer and winter seasons; however, in the spring the total cancer risks exceeds the USEPA acceptable level of 10−6 by a factor of 10.7.
Determinants of water pricing – a regression analysis with cross-country data
Authors: Min Byung S.
Published: May 2007

As water has become a scarce resource, international organisations predict that the problem of water scarcity will become acute. This study investigates the role of socio-political factors such as the forward-looking water pricing hypothesis and the impact of globalisation as determinants of water pricing in 22 selected countries. Our statistical estimation results have two important policy implications. First, the statistical significance of the variable for the forward-looking water pricing hypothesis indicates the need for further debate and discussion about current and predicted water shortage problems at an international level. Second, the estimation results also indicate that globalisation via membership of international environmental organisations and promoting the activities of multinational companies should be encouraged, so that countries can enjoy positive information spill-overs and mutual knowledge acquisition through their interaction with the rest of the world.
The Importance of Resubmitting Rejected Papers
Authors: Donovan Stephen K.
Published: May 2007

If your research paper is rejected for publication by a peer-reviewed journal, what do you do next? Some editors would suggest that it should not be sent to another journal, yet there are contributors who would just put a ‘failed’ paper straight back in the mail to another journal and trust to luck. I argue that rejection should be a time for reassessment, when the input of the editor(s) and reviewers(s), all experts in their field, should be considered and acted upon as necessary. The revitalized and improved contribution can then be sent to a new journal with confidence.
Carbonated Beverages
Authors: Morrow R. Steve , Quinn Christine M. ,   Updated by Staff
Published: May 2007

Carbonated beverages were first introduced in the late 1880s. The annual per capita consumption of soft drinks in the United States has steadily risen from 16 oz (<0.5 L) in 1860 to nearly 192 gallons today.

The ingredients used to produce soft drinks include water, nutritive or nonnutritive sweeteners, acidulants, preservatives, carbon dioxide, colorants, and flavoring ingredients. Manufacturing of soft drinks generally includes preparing syrup from ingredients and then mixing with carbon dioxide and water. Quality control programs for ingredients, syrups, beverages, and packaging materials are conducted to ensure the integrity of the beverage.

Beverages are packaged in steel or aluminum cans, returnable and nonreturnable glass, and plastic bottles. Recycling and source reduction are important issues to the soft drink industry. New packaging utilizing recycled materials, market growth, and development of new nonnutritive sweeteners are important areas for future development health and safety issues are discussed.
Dietary Fiber
Authors: Lewis B. A. ,   Updated by Staff
Published: May 2007

Dietary fiber is a complex mixture of nondigestible polysaccharides and lignin, the exact composition depends on the plant or other food source, maturity, growing conditions, and processing. Plant cell wall polysaccharides are extensively fermented by the microbial enzymes in the lower digestive tract. The particle size and shape, density, crystallinity, water‐holding capacity, and the level and type of dietary fiber affect the rate of passage of the digests through the digestive tract. Dietary fiber itself and the microbial fermentation in the colon give rise to various beneficial physiological effects. Dietary sources of soluble and insoluble fiber and their properties and methods for analysis are summarized. Specific food sources of dietary fiber are given. Fiber supplements are discussed.
Syrups
Authors: Hebeda Ronald E. ,   Updated by Staff
Published: May 2007

Corn sweeteners, maple syrup, and molasses, all commercially available syrups, are concentrated solutions of carbohydrate. These products, produced for a variety of food and nonfood applications, are in some cases also available in a dry form. Corn sweeteners are prepared from hydrolyzed starch and include dextrose, high fructose corn syrup, regular corn syrup, and maltodextrin, which all have in common the raw material source, general methods of preparation, and many properties and applications. Dextrose, the common or commercial name forD‐glucose, is available as a syrup or as a pure crystalline solid. High fructose corn syrup is produced by the partial enzymatic isomerization of dextrose. Corn syrups and maltodextrins are clear, colorless, viscous liquids prepared by hydrolysis of starch to solutions of dextrose, maltose, and higher molecular weight saccharides. Maple syrup, like corn syrup, is a nutritive sweetener produced as a concentrated carbohydrate (sucrose) solution. Molasses is a syrup produced as a by‐product of sugar manufacture.