bluuebunny/crossref_metadata_2025 huggingface dataset:
Letter to the Next President
Authors: Rotherham Andrew J. , Mikuta Julie , Freeland Julia
Published: April 2008

This article takes the form of a letter to the 44th president of the United States, urging the president to pursue an aggressive agenda to improve teacher quality. The authors assert that because teacher quality is the single most important factor shown to impact student outcomes, the next administration must dedicate resources to human capital reform and entrepreneurial efforts to better recruit, train, and support teachers. The recommendation includes five areas where the federal government can leverage its power to encourage innovations that bolster teacher effectiveness and improve outcomes for all students. These include (a) filling the teacher pipeline with better qualified teacher candidates, (b) creating more and better pathways to the teaching profession, (c) improving the supply of and demand for better induction and professional development, (d) developing data systems to measure teacher effectiveness by student outcomes, and (e) promoting and funding research and development in the field of teacher quality.
Letter to the President
Authors: Berliner David C.
Published: April 2008

Six suggestions for improving education in the country are offered. The case is made first that unless children's health care is improved, educational achievement among the poor will not improve. The second point is that poverty limits school achievement as well. Without work on these two issues, neither the nation nor the nation's schools will be in better places at the end of the next president's term in office. The third and fourth suggestions for improvement are inside the school factors that the president can influence. It is argued that higher-quality teachers are required than the nation now has and that school accountability systems now in use undermine the professionalism of the teaching force. The fifth and sixth suggestions are about how to improve the funding of educational research, suggestions easily implemented by the next president.
Rasch Analysis as a Technique to Examine the Psychometric Properties of a Career Ability Placement Survey Subtest
Authors: Pomeranz Jamie L. , Byers Katherine L. , Moorhouse Michael D. , Velozo Craig A. , Spitznagel Ronald J.
Published: April 2008

Rasch analysis offers researchers an innovative method for developing and validating rehabilitation instruments. Despite the increased use of Rasch analysis by allied health researchers, this method continues to be underutilized by rehabilitation counseling professionals. In the rehabilitation counseling profession, vocational evaluators use various instruments, such as the Career Ability Placement Survey (CAPS), to determine client aptitudes and justify job placement recommendations. The purpose of this article is to introduce Rasch analysis as a method for analyzing vocational assessments by examining the psychometric properties of the Word Knowledge (WK) subtest of the CAPS. University undergraduate and graduate students ( n = 227) completed the WK subtest as part of a classroom exercise. The analysis determined item hierarchy, item gaps and redundancies, item-fit statistics (unidimensionality), and person reliability and separation statistics. Although the WK construct demonstrates good psychometric characteristics relating to unidimensionality and to person reliability and separation statistics, several items deviated from the expected ordering pattern. The reordering of items revealed potential item gaps and redundancies as well as poor person—instrument match. Adding and removing items will improve the validity and reliability of the WK subtest psychometrics.
The Multi-Item Randomized Response Technique
Authors: Himmelfarb Samuel
Published: April 2008

The randomized response technique (RRT) attempts to reduce social desirability bias in self-reports by creating a probabilistic relationship between the response given and the question posed. The multi-item RRT extends the RRT procedure to scales composed of multiple items. The multi-item RRT reduces the added variability contributed by the procedure and affords more accurate estimates of parameters than does a single-item RRT. Formulas are presented for correcting the mean, standard deviation, and correlation coefficient for the procedure. Data are presented from a study (Jarman 1996) of male date rape to illustrate the application of the multi-item RRT. Those data show higher reports of rape-supportive attitudes, beliefs, and sexual aggression under RRT conditions.
Pharmacokinetics of Mycophenolic Acid in Live Donor Liver Transplant Patients vs Deceased Donor Liver Transplant Patients
Authors: Jain Ashok , Venkataramanan Raman , Sharma Rajeev , Kwong Tai , Abt Peter , Orloff Mark , Kashyap Randeep , Tsoulfas Georgious , Bozorgzadeh Adel
Published: April 2008

The exposure of mycophenolic acid in live donor liver transplant patients (those receiving a partial hepatic volume) in comparison to deceased donor liver transplant patients (those receiving the whole hepatic volume) after administration of mycophenolate mofetil has not been reported earlier. The aim of the present study is to compare the pharmacokinetics parameters of mycophenolic acid and mycophenolic acid glucuronide in live donor liver transplant patients versus deceased donor liver transplant patients. Twelve live donor liver transplant and 12 deceased donor liver transplant recipients were studied over a dosing interval after intravenous administration of mycophenolate mofetil. The maximum concentration (Cmax) and the area under the plasma concentration versus time curve (AUC) for mycophenolic acid in live donor liver transplant patients were significantly higher than in deceased donor liver transplant patients (Cmax/AUC: live donor liver transplant patients: 16.1 ± 6.6 μg/mL/43.9 ± 12.6 μg/mLṁh vs deceased donor liver transplant patients: 10.7 ± 2.0 μg/mL/28.9 ± 7.1 μg/mLṁh; P = .046/.002). The volume of distribution was higher in the deceased donor liver transplant patients compared with live donor liver transplant patients. However, the mean plasma concentration at 12 hours (Clast), drug disposition rate constant, half‐life (t1/2), and mean residence time were similar in both groups. The mean plasma concentration of mycophenolic acid glucuronide was 1.4 to 2.0 times higher in deceased donor liver transplant patients compared with live donor liver transplant patients. These observations point to the need to use a lower dosage (approximately 30%) of mycophenolate mofetil in live donor liver transplant patients compared with deceased donor liver transplant patients.
Pharmacometrics: A Multidisciplinary Field to Facilitate Critical Thinking in Drug Development and Translational Research Settings
Authors: Barrett Jeffrey S. , Fossler Michael J. , Cadieu K. David , Gastonguay Marc R.
Published: April 2008

Pharmacometrics has evolved beyond quantitative analysis methods used to facilitate decision making in drug development, although the application of the discipline in this arena continues to represent the primary emphasis of scientists calling themselves pharmacometricians. While related fields populate and interface with pharmacometrics, there is a natural synergy with clinical pharmacology due to common areas of research and the decision‐making expectation with respect to evolving conventional and translational research paradigms. Innovative and adaptable training programs and resources are essential in this regard as both disciplines promise to be key elements of the clinical research workplace of the future. The demand for scientists with pharmacometrics skills has risen substantially. Likewise, the salary garnered by those with these skills appears to be surpassing their counterparts without such backgrounds. Given the paucity of existing training programs, available training materials, and academic champions, a virtual faculty and online curriculum would allow students to matriculate into one of several programs associated with their advisor but take instruction from faculty at multiple institutions, including instructors in both industrial and regulatory settings. Flexibility in both the curriculum and the governance of the degree would provide the greatest hope of addressing the short supply of trained pharmacometricians.
Comparative Inhibitory Activity of Etoricoxib, Celecoxib, and Diclofenac on COX‐2 Versus COX‐1 in Healthy Subjects
Authors: Schwartz Jules I. , Dallob Aimee L. , Larson Patrick J. , Laterza Omar F. , Miller Jutta , Royalty Jane , Snyder Karen M. , Chappell Derek L. , Hilliard Deborah A. , Flynn Mary E. , Cavanaugh Paul F. , Wagner John A.
Published: April 2008

We determined cyclo‐oxygenase‐1 and cyclo‐oxygenase‐2 inhibition in healthy middle‐aged subjects (41–65 years) randomly assigned to four 7‐day treatment sequences of etoricoxib 90 mg every day, celecoxib 200 mg twice a day, diclofenac 75 mg twice a day, or placebo in a double‐blind, randomized, 4‐period crossover study. Maximum inhibition of thromboxane B2(cyclo‐oxygenase‐1 activity) in clotting whole blood on day 7 (0–24 hours postdose) was the primary endpoint. Inhibition of lipopolysaccharide‐induced prostaglandin E2in whole blood (cyclo‐oxygenase‐2 activity) was assessed on day 7 (0–24 hours postdose) as a secondary endpoint. Diclofenac had significantly greater maximum inhibition of thromboxane B2versus each comparator (P< .001); placebo 2.4% (95% confidence interval: −8.7% to 12.3%), diclofenac 92.2% (91.4% to 92.9%), etoricoxib 15.5% (6.6% to 23.5%), and celecoxib 20.2% (11.5% to 28.1%). Prostaglandin E2synthesis was inhibited with a rank order of potency of diclofenac > etoricoxib > celecoxib. In summary, at doses commonly used in rheumatoid arthritis, diclofenac significantly inhibits both cyclo‐oxygenase‐1 and cyclo‐oxygenase‐2, whereas etoricoxib and celecoxib significantly inhibit cyclo‐oxygenase‐2 and do not substantially inhibit cyclo‐oxygenase‐1.
Two Worlds Apart
Authors: Poppelaars Caelesta , Scholten Peter
Published: April 2008

Immigrant integration has become an intractable policy controversy in the Netherlands. One facet of this controversy involves the different ways in which immigrant integration has been framed by national and local governments. National government has formulated a “citizenship approach” to immigrant integration, whereas local governments often chose a more accommodative approach to migrant groups. In this article, the authors argue that this discrepancy originates from the divergent institutional logic of national and local integration policies. National integration policies have resulted from belief in strong central policy coordination, a sharp turn from depoliticization to politicization, responsiveness to a series of focus events, and mood swings during the past decades. Local integration policies, in contrast, are characterized by a considerable degree of pragmatic problem coping, in particular, the instrumental use of migrant organizations. As such, the divergent logics of national and local integration policies seem to represent two different worlds of problem framing.
The Association Between an Electric Pump Loan Program and the Timing of Requests for Formula by Working Mothers in WIC
Authors: Meehan Karen , Harrison Gail G. , Afifi Abdelmonem A. , Nickel Nathan , Jenks Eloise , Ramirez Anthony
Published: April 2008

An electric pump loan program designed to facilitate breastfeeding for low-income mothers returning to full-time work was evaluated. All mothers were WIC participants in the Los Angeles area. Electric pump loans were made until the infant's first birthday or until the mother requested formula from WIC. Information was provided to employers on supporting breastfeeding in the workplace. A subsample of mothers who received an electric pump on return to full-time work was compared with counterparts in a wait list control group. Mothers who received an electric pump as soon as requested did not request formula until 8.8 months on average, whereas those who did not receive an electric pump requested formula on average at 4.8 months ( P < .0001). Mothers who received an electric pump when requested were 5.5 (95% CI 2.0-15.1) times as likely as mothers who did not receive an electric pump to not request formula at 6 months. J Hum Lact. 24(2):150-158.
Nutrient Composition of Hindmilk Produced by Mothers of Very Low Birth Weight Infants Born at Less Than 28 Weeks' Gestation
Authors: Bishara Rosine , Dunn Michael S. , Merko Susan E. , Darling Pauline
Published: April 2008

The objectives of this study were to describe and compare retinol, α-tocopherol and γ-tocopherol, fat, energy, and nitrogen concentrations between the foremilk and hindmilk fractions of 24-hour milk collected by 24 mothers of very preterm (< 28 weeks' gestation) infants and to relate milk vitamins A and E content to maternal vitamin intake. Concentrations of retinol were significantly higher in hindmilk than in foremilk (1.6-fold), as were concentrations of α-tocopherol (1.6-fold), γ-tocopherol (1.5-fold), fat (1.7-fold), energy (1.3-fold), and nitrogen (1.05-fold). Retinol, α-tocopherol, and γ-tocopherol were positively related ( P < .05) to milk fat and energy but not to maternal intake. Estimates of vitamins A and E intakes of infants fed hindmilk with added human milk fortifier surpassed current recommended upper level of intakes. The higher fat-soluble vitamin content of hindmilk produced by mothers of very low birth weight infants needs to be considered in the design and recommendations for use of human milk fortifier. J Hum Lact . 24(2):159-167.
Is the Glass Half-Empty or Half-Full? A Feminist Assessment of Buddhism at the Beginning of the Twenty-First Century
Authors: Gross Rita M.
Published: April 2008

Doctrinally, Buddhism is free of the myths and symbols that make some other religions so intractable to feminist reforms. In its philosophical views and its meditation practices, Buddhism has tremendous potential for deconstructing gender. In less than thirty years, we have gone from a situation in which almost nothing had been written about Buddhist women to a situation in which books and articles appear regularly. There is now a worldwide Buddhist women's movement, many women Buddhist teachers—at least in North America—and a growing consensus that the traditional male dominance of Buddhism is a problem. Yet, despite the advances made in the last thirty years, Buddhism still privileges men above women. So is the glass half full? Are we well on the way to recasting Buddhism in ways that make it more adequate for its female followers? Or is the glass half empty? Is Buddhism still a religion that works better for men than for women, despite the changes of the past thirty years? In looking at the half-full, half-empty glass, I will consider three topics: first, Buddhism's potential for deconstructing gender, second, some reasons why this potential did not come to fruition historically, and third, some of the changing situations in the contemporary Buddhist world, both Asian and Western.
In Exile from No Homeland: Or, Being at Home in the Middle of Time
Authors: Tatman Lucy
Published: April 2008

Abrasive, harsh, uncompromising, blunt, uncomfortable. Lyrical, haunting, evocative, pleasure-full, drenching, soaring. All of this, all at once, now, not later. No postponing, no deferring to an endlessly deferred not yet, not yet, not yet.
Re-Imagining Theological Reflection on God from the Context of Korean Women
Authors: Choi Hee An
Published: April 2008

When Western Christianity came to Asia, it merged with Eastern religions and histories and developed very differently in different places. Today Asian women in each country build up very unique images of God. They practice Eastern forms of worship and liturgical rites, and do indigenized theologies. They simultaneously try to find their own ways of naming, imaging, believing in and communicating with their own God.

Korean Christianity has inherited many images of God from Western Christian doctrines and theologies. However, when it meets and merges with Koreanized Buddhism, Confucianism, and Shamanism, some of the images of God in Christianity are transformed and re-imagined in Korean women's social cultural and religious contexts. As an Asian woman, especially a Korean woman, I would like to introduce one of the many Asian women's theologies, Korean women's images of God. It cannot represent all Asian women's ways of doing theologies, but it will give some clues to show how Asian women do theologies in their own context. In particular, I will examine three images of God that demonstrate how Western Christianity and Eastern religions meet and are transformed in Korean Christian women's living contexts.
“Interest” Is a Verb
Authors: Mathiowetz Dean
Published: April 2008

The hundredth anniversary of Arthur Bentley's The Process of Government is an occasion to recover his distinctive but forgotten view of interest, namely, that an appeal to “interest” is an activity of provoking political identity and agency—an activity exemplified by the “group process” of politics. Bentley's insight has been lost as students of politics, as diversely inclined as David Truman, Bill Connolly, and many others, approach interests instead as a psychological bulwark and expression of sovereign agency. Reading Bentley prompts us to see how the language of “interest” undercuts such a picture, encouraging instead a critical theory of interests—and of politics more generally—that is sensitive to the active provocation of identity at sites of contestation.
The Knowledge Organization
Authors: Meerwarth Tracy L. , Trotter Robert T. , Briody Elizabeth K.
Published: April 2008

General Motors Research and Development (R&D) management is planning to renovate portions of the Warren, Michigan, research facility. The study's goal was to help organizational leaders and planners understand culturally endorsed workspace architecture and design elements. Researchers used a rapid ethnographic assessment research design grounded in cognitive anthropology and methods to capture impressions and cultural requirements for workspace. This study adds to the existing body of knowledge at the intersection of workspace, culture, and user-oriented design by analyzing employee comments and research observations to construct a cultural model of R&D workspace. All model components underscore the cultural values of productivity and pragmatism. The authors examine features associated with the workspace productivity model, behaviors associated with the workspace, and differences in workspace perceptions and behaviors by organizational role. Findings refine the definition of knowledge worker culture and suggest that an orientation to productivity reflects broader American cultural values including pragmatism, individualism, and effectiveness.
Jewish Interpretation of Paul in the Last Thirty Years
Authors: Bird Michael F. , Sprinkle Preston M.
Published: April 2008

This essay offers a sampling of recent Jewish interpretations of the Apostle Paul in the last thirty years. Attention is given to the works of Pinchas Lapide, Hyam Maccoby, Alan F. Segal, Daniel Boyarin, Mark D. Nanos and Pamela M. Eisenbaum including a survey of their scholarship and an assessment of their contribution and significance for Pauline studies. This study concludes that Jewish interpretation of Paul remains highly diverse and there is not likely to be a Jewish `reclamation' of Paul in the foreseeable future.
Discovering biclusters in gene expression data based on high-dimensional linear geometries
Authors: Gan Xiangchao , Liew Alan Wee-Chung , Yan Hong
Published: April 2008

Background

In DNA microarray experiments, discovering groups of genes that share similar transcriptional characteristics is instrumental in functional annotation, tissue classification and motif identification. However, in many situations a subset of genes only exhibits consistent pattern over a subset of conditions. Conventional clustering algorithms that deal with the entire row or column in an expression matrix would therefore fail to detect these useful patterns in the data. Recently, biclustering has been proposed to detect a subset of genes exhibiting consistent pattern over a subset of conditions. However, most existing biclustering algorithms are based on searching for sub-matrices within a data matrix by optimizing certain heuristically defined merit functions. Moreover, most of these algorithms can only detect a restricted set of bicluster patterns.

Results

In this paper, we present a novel geometric perspective for the biclustering problem. The biclustering process is interpreted as the detection of linear geometries in a high dimensional data space. Such a new perspective views biclusters with different patterns as hyperplanes in a high dimensional space, and allows us to handle different types of linear patterns simultaneously by matching a specific set of linear geometries. This geometric viewpoint also inspires us to propose a generic bicluster pattern, i.e. the linear coherent model that unifies the seemingly incompatible additive and multiplicative bicluster models. As a particular realization of our framework, we have implemented a Hough transform-based hyperplane detection algorithm. The experimental results on human lymphoma gene expression dataset show that our algorithm can find biologically significant subsets of genes.

Conclusion

We have proposed a novel geometric interpretation of the biclustering problem. We have shown that many common types of bicluster are just different spatial arrangements of hyperplanes in a high dimensional data space. An implementation of the geometric framework using the Fast Hough transform for hyperplane detection can be used to discover biologically significant subsets of genes under subsets of conditions for microarray data analysis.
Identification of coherent patterns in gene expression data using an efficient biclustering algorithm and parallel coordinate visualization
Authors: Cheng Kin-On , Law Ngai-Fong , Siu Wan-Chi , Liew Alan Wee-Chung
Published: April 2008

Background

The DNA microarray technology allows the measurement of expression levels of thousands of genes under tens/hundreds of different conditions. In microarray data, genes with similar functions usually co-express under certain conditions only [1]. Thus, biclustering which clusters genes and conditions simultaneously is preferred over the traditional clustering technique in discovering these coherent genes. Various biclustering algorithms have been developed using different bicluster formulations. Unfortunately, many useful formulations result in NP-complete problems. In this article, we investigate an efficient method for identifying a popular type of biclusters called additive model. Furthermore, parallel coordinate (PC) plots are used for bicluster visualization and analysis.

Results

We develop a novel and efficient biclustering algorithm which can be regarded as a greedy version of an existing algorithm known as pCluster algorithm. By relaxing the constraint in homogeneity, the proposed algorithm has polynomial-time complexity in the worst case instead of exponential-time complexity as in the pCluster algorithm. Experiments on artificial datasets verify that our algorithm can identify both additive-related and multiplicative-related biclusters in the presence of overlap and noise. Biologically significant biclusters have been validated on the yeast cell-cycle expression dataset using Gene Ontology annotations. Comparative study shows that the proposed approach outperforms several existing biclustering algorithms. We also provide an interactive exploratory tool based on PC plot visualization for determining the parameters of our biclustering algorithm.

Conclusion

We have proposed a novel biclustering algorithm which works with PC plots for an interactive exploratory analysis of gene expression data. Experiments show that the biclustering algorithm is efficient and is capable of detecting co-regulated genes. The interactive analysis enables an optimum parameter determination in the biclustering algorithm so as to achieve the best result. In future, we will modify the proposed algorithm for other bicluster models such as the coherent evolution model.
Inverse association between gastroesophageal reflux and blood pressure: Results of a large community based study
Authors: Murray Liam J , McCarron Peter , McCorry Roger B , Anderson Lesley A , Lane Athene J , Johnston Brian T , Smith George Davey , Harvey Richard F
Published: April 2008

Background

In a cross-sectional community based study, as part of a randomised controlled trial of eradication of Helicobacter pylori infection, the association between blood pressure and symptoms of gastro-oesophageal reflux was examined.

Methods

Linear regression was used to examine the association between systolic and diastolic blood pressure and the frequency of heartburn and acid regurgitation in 4,902 of 10,537 participants aged 20–59 years.

Results

In multivariable analyses, adjusted mean systolic blood pressure was 4.2 (95% confidence interval 1.5 to 7.0) mm Hg lower in participants with daily acid regurgitation compared to those with less frequent symptoms. Similarly, for diastolic blood pressure, a reduction of 2.1 (0.0 to 4.3) mm Hg wasobserved.

Conclusion

People who experience daily symptoms of gastro-oesophageal reflux have lower blood pressure than people with less frequent or no symptoms. It is possible that factors influencing nitric oxide concentrations both at the lower oesophageal sphincter and within the vasculature may be involved. This hypothesis requires confirmation.

Trials registration number

ISRCTN44816925
Association of common ATMvariants with familial breast cancer in a South American population
Authors: González-Hormazábal Patricio , Bravo Teresa , Blanco Rafael , Valenzuela Carlos Y , Gómez Fernando , Waugh Enrique , Peralta Octavio , Ortuzar Waldo , Reyes Jose M , Jara Lilian
Published: April 2008

Background

The ATM gene has been frequently involved in hereditary breast cancer as a low-penetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory.

Methods

In this study, a full mutation analysis of the ATM gene was carried out in patients from 137 Chilean breast cancer families, of which 126 were BRCA1/2 negatives and 11 BRCA1/2 positives. We further perform a case-control study between the subgroup of 126 cases BRCA1/2 negatives and 200 controls for the 5557G>A missense variant and the IVS38-8T>C and the IVS24-9delT polymorphisms.

Results

In the full mutation analysis we detected two missense variants and eight intronic polymorphisms. Carriers of the variant IVS24-9delT, or IVS38-8T>C, or 5557G>A showed an increase in breast cancer risk. The higher significance was observed in the carriers of IVS38-8T>C (OR = 3.09 [95%CI 1.11–8.59], p = 0.024). The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype confered a 3.19 fold increase in breast cancer risk (OR = 3.19 [95%CI 1.16–8.89], p = 0.021). The haplotype estimation suggested a strong linkage disequilibrium between the three markers (D' = 1). We detected only three haplotypes in the cases and control samples, some of these may be founder haplotypes in the Chilean population.

Conclusion

The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype alone or in combination with certain genetic background and/or environmental factors, could modify the cancer risk by increasing genetic inestability or by altering the effect of the normal DNA damage response.
CD24 cross-linking induces apoptosis in, and inhibits migration of, MCF-7 breast cancer cells
Authors: Kim Jong Bin , Ko Eunyoung , Han Wonshik , Lee Jeong Eon , Lee Kyung-Min , Shin Incheol , Kim Sangmin , Lee Jong Won , Cho Jihyoung , Bae Ji-Yeon , Jee Hyeon-Gun , Noh Dong-Young
Published: April 2008

Background

The biological effects of CD24 (FL-80) cross-linking on breast cancer cells have not yet been established. We examined the impact of CD24 cross-linking on human breast cancer cell line MCF-7.

Methods

MCF-7 and MDA-MB-231 cells were treated with anti-rabbit polyclonal IgG or anti-human CD24 rabbit polyclonal antibodies to induce cross-linking, and then growth was studied. Changes in cell characteristics such as cell cycle modulation, cell death, survival in three-dimensional cultures, adhesion, and migration ability were assayed after CD24 cross-linking in MCF-7.

Results

Expression of CD24 was analyzed by flow cytometry in MDA-MB-231 and MCF-7 cells where 2% and 66% expression frequencies were observed, respectively. CD24 cross-linking resulted in time-dependent proliferation reduction in MCF-7 cells, but no reduction in MDA-MB-231 cells. MCF-7 cell survival was reduced by 15% in three-dimensional culture after CD24 cross-linking. Increased MCF-7 cell apoptosis was observed after CD24 cross-linking, but no cell cycle arrest was observed in that condition. The migration capacity of MCF-7 cells was diminished by 30% after CD24 cross-linking.

Conclusion

Our results showed that CD24 cross-linking induced apoptosis and inhibited migration in MCF-7 breast cancer cells. We conclude that CD24 may be considered as a novel therapeutic target for breast cancer.
Application of microarray outlier detection methodology to psychiatric research
Authors: Ernst Carl , Bureau Alexandre , Turecki Gustavo
Published: April 2008

Background

Most microarray data processing methods negate extreme expression values or alter them so that they do not lie outside the mean level of variation of the system. While microarrays generate a substantial amount of false positive and spurious results, some of the extreme expression values may be valid and could represent true biological findings.

Methods

We propose a simple method to screen brain microarray data to detect individual differences across a psychiatric sample set. We demonstrate in two different samples how this method can be applied.

Results

This method targets high-throughput technology to psychiatric research on a subject-specific basis.

Conclusion

Assessing microarray data for both mean group effects and individual effects can lead to more robust findings in psychiatric genetics.
Evaluation of behavioural and antioxidant activity of Cytisus scoparius Link in rats exposed to chronic unpredictable mild stress
Authors: Nirmal Jayabalan , Babu Chidambaram Saravana , Harisudhan Thanukrishnan , Ramanathan Muthiah
Published: April 2008

Background

Various human diseases have oxidative stress as one of their component. Many herbs have been reported to exhibit properties that combat oxidative stress through their active constituents such as flavonoids, tannins, phenolic compounds etc. Cytisus scoparius (CS) Link, (Family: Leguminosae), also called Sarothamnus scoparius, has been shown in invitro experiments to be endowed with anti-diabetic, hypnotic and sedative and antioxidant activity. Therefore this study was carried out to evaluate CS for its anxiolytic, antidepressant and anti-oxidant activity in stressed rats.

Methods

60% methanolic extract of CS was quantified for phenolic content by Folin-Ciocalteau's method. Chronic unpredictable mild stress (CMS) was employed to induce stress in rats. CS (125 and 250 mg/kg, p.o) and diazepam (DZM) (2 mg/kg, p.o) was administered during the 21 day stress exposure period. Anxiolytic and antidepressant activities of CS were assessed in open field exploratory and behavioural despair paradigms, respectively. Plasma glucose and total lipids; endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT); non-enzymic-ascorbic acid and thiobarbituric acid reactive substances (TBARS) levels were measured in brain, kidneys and adrenals using standard protocols to assess the effect of CS.

Results

Total phenolic content of CS was found to be 8.54 ± 0.16% w/w. CMS produced anxiogenic and depressive behaviour in experimental rats with metabolic disturbance. Significant decrease in SOD, CAT levels and increase in lipid peroxidation level was observed in stressed rats. CS administration for 21 days during stress exposure significantly increased the ambulatory behaviour and decreased the freezing time in open field behaviour. In behavioural despair test no significant alteration in the immobility period was observed. CS also improved SOD, CAT, and ascorbic acid level and controlled the lipid peroxidation in different tissues.

Conclusion

CS possesses anti-stress and moderate anxiolytic activity which may be due, in part, to its antioxidant effect that might warrant further studies.
Systemic TNF blockade does not modulate synovial expression of the pro-inflammatory mediator HMGB1 in rheumatoid arthritis patients – a prospective clinical study
Authors: Sundberg Erik , Grundtman Cecilia , af Klint Erik , Lindberg Johan , Ernestam Sofia , Ulfgren Ann-Kristin , Harris Helena Erlandsson , Andersson Ulf
Published: April 2008

Introduction

High-mobility group box chromosomal protein 1 (HMGB1) has recently been identified as an endogenous mediator of arthritis. TNF and IL-1β, pivotal cytokines in arthritis pathogenesis, both have the ability to induce the release of HMGB1 from myeloid and dendritic cells. It was, therefore, decided to investigate whether treatment based on TNF blockade in rheumatoid arthritis (RA) affects the expression of synovial HMGB1.

Methods

Repeated arthroscopy-guided sampling of synovial tissue was performed in nine patients with RA before and nine weeks after initiation of anti-TNF mAb (infliximab) therapy. Synovial biopsy specimens were analysed for HMGB1 protein by immunohistochemical staining and for HMGB1 mRNA expression by real-time reverse transcriptase PCR (RT-PCR). Statistical evaluations were based on Wilcoxon's signed rank tests or Spearman rank sum tests.

Results

Aberrant, extranuclear HMGB1 and constitutive nuclear HMGB1 expression, with histological signs of inflammation, were evident in all biopsies obtained before infliximab therapy. Signs of inflammation were still evident in the second biopsies obtained nine weeks after initiation of infliximab therapy. The cytoplasmic and extracellular expression of HMGB1 decreased in five patients, remained unchanged in one patient and increased in three patients, making the overall change in HMGB1 protein expression not significant. No correlation between the clinical response, as measured by disease activity score calculated for 28 joints (DAS28) or the American College of Rheumatology response criteria (ACR 20, 50, and 70), and the direction of change of HMGB1 expression in individual patients could be discerned. In addition, infliximab therapy did not alter HMGB1 mRNA synthesis.

Conclusion

Pro-inflammatory HMGB1 expression during rheumatoid synovitis was not consistently influenced by TNF-blocking therapy with infliximab. This suggests that TNF is not the main inducer of extranuclear HMGB1 during synovitis and that HMGB1 may represent a TNF-independent molecule that could be considered as a possible target for future therapeutic intervention in RA.
Action of fibroblast growth factor-2 on the intervertebral disc
Authors: Li Xin , An Howard S , Ellman Michael , Phillips Frank , Thonar Eugene J , Park Daniel K , Udayakumar Ranjith K , Im Hee-Jeong
Published: April 2008

Introduction

Fibroblast growth factor 2 (FGF2) is a growth factor that is immediately released after cartilage injury and plays a pivotal role in cartilage homeostasis. In human adult articular cartilage, FGF2 mediates anti-anabolic and potentially catabolic effects via the suppression of proteoglycan (PG) production along with the upregulation of matrix-degrading enzyme activity. The aim of the present study was to determine the biological effects of FGF2 in spine disc cells and to elucidate the complex biochemical pathways utilized by FGF2 in bovine intervertebral disc (IVD) cells in an attempt to further understand the pathophysiologic processes involved in disc degeneration.

Methods

We studied the effect of FGF2 on IVD tissue homeostasis by assessing MMP-13 expression (potent matrix-degrading enzyme), PG accumulation, and PG synthesis in the bovine spine IVD, as well as evaluating whether FGF2 counteracts known anabolic factors such as BMP7. To understand the molecular mechanisms by which FGF2 antagonizes BMP7 activity, we also investigated the signaling pathways utilized by FGF2 in bovine disc tissue.

Results

The primary receptor expressed in bovine nucleus pulposus cartilage is FGFR1, and this receptor is upregulated in degenerative human IVD tissue compared with normal IVD tissue. Stimulation of bovine nucleus pulposus cells cultured in monolayer with FGF2 augmented the production of MMP-13 at the transcriptional and translational level in a dose-dependent manner. Stimulation of bovine nucleus pulposus cells cultured in alginate beads for 21 days with FGF2 resulted in a dose-dependent decrease in PG accumulation, due at least in part to the inhibition of PG synthesis. Further studies demonstrate that FGF2 (10 ng/ml) antagonizes BMP7-mediated acceleration of PG production in bovine nucleus pulposus cells via the upregulation of noggin, an inhibitor of the transforming growth factor beta/bone morphogenetic protein signaling pathway. Chemical inhibitor studies showed that FGF2 utilizes the mitogen-activated protein kinase and NF-κB pathways to upregulate noggin, serving as one potential mechanism for its anti-anabolic effects.

Conclusion

FGF2 is anti-anabolic in bovine spine disc cells, revealing the potential of FGF2 antagonists as unique biologic treatments for both prevention and reversal of IVD degeneration.
ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells
Authors: Pan Ling , Deng Min , Xie Xiaoling , Gan Lin
Published: April 2008

LIM-homeodomain (HD) and POU-HD transcription factors play crucial roles in neurogenesis. However, it remains largely unknown how they cooperate in this process and what downstream target genes they regulate. Here, we show that ISL1, a LIM-HD protein, is co-expressed with BRN3B, a POU-HD factor, in nascent post-mitotic retinal ganglion cells (RGCs). Similar to the Brn3b-null retinas, retina-specific deletion of Isl1 results in the apoptosis of a majority of RGCs and in RGC axon guidance defects. The Isl1 and Brn3b double null mice display more severe retinal abnormalities with a near complete loss of RGCs, indicating the synergistic functions of these two factors. Furthermore, we show that both Isl1and Brn3b function downstream of Math5 to regulate the expression of a common set of RGC-specific genes. Whole-retina chromatin immunoprecipitation and in vitro transactivation assays reveal that ISL1 and BRN3B concurrently bind to and synergistically regulate the expression of a common set of RGC-specific genes. Thus, our results uncover a novel regulatory mechanism of BRN3B and ISL1 in RGC differentiation.
Myopic acts in the endocytic pathway to enhance signaling by theDrosophilaEGF receptor
Authors: Miura Grant I. , Roignant Jean-Yves , Wassef Michel , Treisman Jessica E.
Published: April 2008

Endocytosis of activated receptors can control signaling levels by exposing the receptors to novel downstream molecules or by instigating their degradation. Epidermal growth factor receptor (EGFR) signaling has crucial roles in development and is misregulated in many cancers. We report here that Myopic, the Drosophila homolog of the Bro1-domain tyrosine phosphatase HD-PTP, promotes EGFR signaling in vivo and in cultured cells. myopic is not required in the presence of activated Ras or in the absence of the ubiquitin ligase Cbl, indicating that it acts on internalized EGFR, and its overexpression enhances the activity of an activated form of EGFR. Myopic is localized to intracellular vesicles adjacent to Rab5-containing early endosomes, and its absence results in the enlargement of endosomal compartments. Loss of Myopic prevents cleavage of the EGFR cytoplasmic domain, a process controlled by the endocytic regulators Cbl and Sprouty. We suggest that Myopic promotes EGFR signaling by mediating its progression through the endocytic pathway.
Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy
Authors: Mak Kinglun Kingston , Kronenberg Henry M. , Chuang Pao-Tien , Mackem Susan , Yang Yingzi
Published: April 2008

Chondrocyte hypertrophy is an essential process required for endochondral bone formation. Proper regulation of chondrocyte hypertrophy is also required in postnatal cartilage homeostasis. Indian hedgehog (Ihh) and PTHrP signaling play crucial roles in regulating the onset of chondrocyte hypertrophy by forming a negative feedback loop, in which Ihh signaling regulates chondrocyte hypertrophy by controlling PTHrP expression. To understand whether there is a PTHrP-independent role of Ihh signaling in regulating chondrocyte hypertrophy, we have both activated and inactivated Ihh signaling in the absence of PTHrP during endochondral skeletal development. We found that upregulating Ihh signaling in the developing cartilage by treating PTHrP-/- limb explants with sonic hedgehog (Shh) protein in vitro, or overexpressing Ihh in the cartilage of PTHrP-/- embryos or inactivating patched 1(Ptch1), a negative regulator of hedgehog (Hh) signaling, accelerated chondrocyte hypertrophy in the PTHrP-/- embryos. Conversely, when Hh signaling was blocked by cyclopamine or by removing Smoothened (Smo), a positive regulator of Hh signaling,chondrocyte hypertrophy was delayed in the PTHrP-/-embryo. Furthermore, we show that upregulated Hh signaling in the postnatal cartilage led to accelerated chondrocyte hypertrophy during secondary ossification, which in turn caused reduction of joint cartilage. Our results revealed a novel role of Ihh signaling in promoting chondrocyte hypertrophy independently of PTHrP, which is particularly important in postnatal cartilage development and homeostasis. In addition, we found that bone morphogenetic protein (Bmp) and Wnt/β-catenin signaling in the cartilage may both mediate the effect of upregulated Ihh signaling in promoting chondrocyte hypertrophy.
Hyaluronan fragments generated by sperm-secreted hyaluronidase stimulate cytokine/chemokine production via the TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization
Authors: Shimada Masayuki , Yanai Yoshiari , Okazaki Tetsuji , Noma Noritaka , Kawashima Ikkou , Mori Takahide , Richards JoAnne S.
Published: April 2008

The toll-like receptor (TLR) system is expressed in cumulus cells of ovulated cumulus-oocyte complexes (COCs) and is activated by bacterial lipopolysaccharides (LPS). However, the endogenous ligand(s) for the TLRs and the physiological role(s) in ovulated COCs remain to be defined. Based on reports that hyaluronan fragments can activate TLR2 and TLR4 in macrophages,and that ovulated COCs are characterized by a hyaluronan-rich matrix, we cultured ovulated mouse COCs with purified hyaluronan fragments, treated them with purified hyaluronidase or exposed them to sperm as a physiologically relevant source of hyaluronidase. Hyaluronan fragments or hyaluronidase activated the NFκB pathway and induced Il6, Ccl4 and Ccl5 mRNA expression within 2 hours. Anti-TLR2 and anti-TLR4 neutralizing antibodies significantly suppressed hyaluronan fragment- and hyaluronidase-induced activation of the NFκB pathway and the expression of these genes. When ovulated COCs were cultured with sperm, the expression and secretion of cytokine/chemokine family members were induced in a time-dependent manner that could be blocked by TLR2/TLR4 antibodies or by a hyaluronan-blocking peptide (Pep-1). The chemokines secreted from TLR2/TLR4-stimulated COCs activated cognate chemokine receptors (CCRs)localized on sperm and induced sperm protein tyrosine phosphorylation, which was used as an index of capacitation. Significantly, in vitro fertilization of COC-enclosed oocytes was reduced by the TLR2/TLR4 neutralizing antibodies or by Pep-1. From these results, we propose that TLR2 and TLR4 present on cumulus cells were activated by the co-culture with sperm in a hyaluronan fragment-dependent manner, and that chemokines secreted from COCs induced sperm capacitation and enhanced fertilization, providing evidence for a regulatory loop between sperm and COCs during fertilization.
Dynamic thermo-elastic response of a discrete multi-layered cylindrical shell subjected to transient thermal loading
Authors: Zheng J Y , Wu X D , Chen Y J , Deng G D , Li Q M , Sun G Y
Published: April 2008

Explosion containment vessels (ECVs) are used to fully contain the effects of explosion events. A discrete multi-layered cylindrical shell (DMC) consisting of a thin inner cylindrical shell and helically cross-winding flat steel ribbons has been proposed, which has obvious advantages of fabrication convenience and low costs. The applications of ECVs are closely associated with blast and thermal loads, and thus, it is important to understand the response of a DMC under transient thermal load in order to develop a design code and operation procedures for the use of DMC as ECV. In this paper, a mathematical model for the elastic response of a DMC subjected to thermal loading due to rapid heating is proposed. Based on the axisymmetric plane strain assumption, the displacement solution of the dynamic equilibrium equations of both inner shell and outer ribbon layer are decomposed into two parts, i.e. a thermo-elastic part satisfying inhomogeneous stress boundary conditions and a dynamic part for homogeneous stress boundary conditions. The thermo-elastic part is solved by a linear method and the dynamic part is determined by means of finite Hankel transform and Laplace transform. The thermo-elastic solution of a DMC is compared with the solution of a monobloc cylindrical shell, and numerical results are presented and discussed in terms of winding angle and material parameters.
Evolution of constrained layer damping using a cellular automaton algorithm
Authors: Chia C M , Rongong J A , Worden K
Published: April 2008

Constrained layer damping (CLD) is a highly effective passive vibration control strategy if optimized adequately. Factors controlling CLD performance are well documented for the flexural modes of beams but not for more complicated mode shapes or structures. The current paper introduces an approach that is suitable for locating CLD on any type of structure. It follows the cellular automaton (CA) principle and relies on the use of finite element models to describe the vibration properties of the structure. The ability of the algorithm to reach the best solution is demonstrated by applying it to the bending and torsion modes of a plate. Configurations that give the most weight-efficient coverage for each type of mode are first obtained by adapting the existing ‘optimum length’ principle used for treated beams. Next, a CA algorithm is developed, which grows CLD patches one at a time on the surface of the plate according to a simple set of rules. The effectiveness of the algorithm is then assessed by comparing the generated configurations with the known optimum ones.