bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing Disagreement and Discomfort through Auto-ethnography and Personal Narrative
Authors: Trotter Joy , Brogatzki Lee , Duggan Lesley , Foster Emma , Levie Jo
Published: August 2006

Social worker educators in the UK are familiar with social issues of exclusion and marginalization, and are used to teaching about sexual abuse or sexual exploitation. However, many are less informed about work with gay people or with broader issues of sexuality. Adopting an auto-ethnographical perspective and using semi-structured discussion groups (which were audio taped, transcribed and analysed), this small group of gay and ‘straight’ practitioners and academics explored current social work practice and culture in the North East of England and reflected on their own learning and teaching experiences. They identified three key themes: differing opinions about what is regarded as an acceptable level of disclosure about personal information, disagreement about the use and meaning of key terms, and discomfort and defensiveness among social work educators, practitioners and students when addressing these issues. These findings are presented alongside some of the literature in this area, highlighting the links with professionals’ exclusion of gay people and the marginalization of gay and ‘straight’ issues in education and practice.
Humoral immune response against 38-kDa and 16-kDa mycobacterial antigens in tuberculosis
Authors: Senol G. , Erer O. F. , Yalcin Y. A. , Coskun M. , Gündüz A. T. , Biçmen C. , Ertas M. , Özkan S. A.
Published: August 2006

Several ELISA tests based on mycobacterial antigens have been used for the rapid diagnosis of tuberculosis (TB), although demonstration ofMycobacterium tuberculosisin a smear or culture is the most reliable method. In the present study, the diagnostic value of 16-kDa and 38-kDa mycobacterial antigens was investigated in patients who were diagnosed with tuberculosis by clinical and/or bacteriological findings in Turkey.

The PATHOZYME-TB Complex Plus commercial ELISA kit was used for measuring immunoglobulin G against 38-kDa and 16-kDa recombinant antigens. Humoral immune response was analysed in a group of 179 TB patients (143 smear-positive, 19 smear-negative, eight lymphadenitis and nine pleuritis), 15 inactive TB cases and in control groups consisting of 40 healthy volunteers and 20 subjects with pulmonary diseases other than TB.

The sensitivity, specifity, positive predictive value and negative predictive value of the test were determined at 52.5%, 93.3%, 95.9% and 39.7%, respectively in TB cases. Antibodies were detected at above cut-off level in three (20%) out of 15 subjects with inactive TB.

In conclusion, the ELISA test has a very good specifity and an acceptable sensitivity and positive predictive value. It is thought that it could be used in combination with other methods to increase diagnostic accuracy, especially for culture-negative tuberculosis cases, which are difficult to diagnose.
Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil
Authors: Barst R. J. , Galie N. , Naeije R. , Simonneau G. , Jeffs R. , Arneson C. , Rubin L. J.
Published: August 2006

Pulmonary arterial hypertension (PAH) is fatal if untreated. Intravenous epoprostenol improves exercise capacity and haemodynamics in PAH, and increases survival in idiopathic PAH (IPAH). To evaluate the effects of subcutaneous (SC) treprostinil, a longer-acting prostacyclin analogue, followed by the addition of other PAH therapies if needed, 860 PAH patients treated with SC treprostinil for up to 4 yrs were followed.

Survival is reported as Kaplan–Meier estimates. For 332 IPAH patients with baseline haemodynamics, observed survival is also compared with predicted survival using the National Institute of Health formula.

Out of the 860 patients, 199 (23%) discontinued due to adverse events, 136 (16%) died, 117 (14%) discontinued due to deterioration, 29 (3%) withdrew consent and 11 (1%) underwent transplantation. In total, 97 patients (11%) switched from SC treprostinil to an alternative prostacyclin analogue; bosentan was added in 105 patients (12%) and sildenafil in 25 (3%).

In conclusion, survival was 87–68% over 1–4 yrs for all 860 patients and 88–70% over 1–4 yrs with subcutaneous treprostinil monotherapy. For the idiopathic pulmonary arterial hypertension subset with baseline haemodynamics (n = 332), survival was 91–72% over 1–4 yrs. In contrast, predicted survival was 69–38% over 1–4 yrs. The safety profile for long-term subcutaneous treprostinil was consistent with previous short-term trials with no unexpected adverse events.
Identification of differentially expressed proteins in human malignant pleural effusions
Authors: Hsieh W-Y. , Chen M-W. , Ho H-T. , You T-M. , Lu Y-T.
Published: August 2006

A high protein concentration in a pleural effusion makes it more likely to be a malignant than a transudative effusion. However, the variability in protein composition between these two forms of pleural effusion is not well understood.

In order to compare their protein compositions, the proteomic profiles of 14 malignant and 13 transudative pleural effusions were studied using two-dimensional gel electrophoresis. Protein spots with differential expression were identified by matrix-assisted laser desorption/ionisation quadrupole time-of-flight mass spectrometry and liquid chromatography/tandem mass spectrometry. Targeted proteins were further examined by ELISA and Western immunoassay in all samples.

Two-dimensional gel electrophoresis revealed seven spots whose expression was reduced in malignant pleural effusions. Four of the abnormal spots were identified as fibrinogen γ-chain precursor, two as fibrinogen β-chain precursor and one as pigment epithelium-derived factor. ELISA and Western immunoassay showed that pigment epithelium-derived factor levels were significantly lower in malignant than in transudative pleural effusions.

It has been demonstrated that proteomic technologies may help in the elucidation of variable expression of proteins with particular functions. By applying these technologies, the level of pigment epithelium-derived factor, a potent anti-angiogenic factor, was found to be significantly lower in malignant than in transudative pleural effusions. This finding allows for further exploration regarding how underexpression of pigment epithelium-derived factor may relate to the pathogenesis of malignant pleural effusions.
A methodology for global validation of microarray experiments
Authors: Miron Mathieu , Woody Owen Z , Marcil Alexandre , Murie Carl , Sladek Robert , Nadon Robert
Published: August 2006

Background

DNA microarrays are popular tools for measuring gene expression of biological samples. This ever increasing popularity is ensuring that a large number of microarray studies are conducted, many of which with data publicly available for mining by other investigators. Under most circumstances, validation of differential expression of genes is performed on a gene to gene basis. Thus, it is not possible to generalize validation results to the remaining majority of non-validated genes or to evaluate theoverallquality of these studies.

Results

We present an approach for the global validation of DNA microarray experiments that will allow researchers to evaluate the general quality of their experiment and to extrapolate validation results of a subset of genes to the remaining non-validated genes. We illustrate why the popular strategy of selecting only the most differentially expressed genes for validation generally fails as a global validation strategy and propose random-stratified sampling as a better gene selection method. We also illustrate shortcomings of often-used validation indices such as overlap of significant effects and the correlation coefficient and recommend the concordance correlation coefficient (CCC) as an alternative.

Conclusion

We provide recommendations that will enhance validity checks of microarray experiments while minimizing the need to run a large number of labour-intensive individual validation assays.
Automatic document classification of biological literature
Authors: Chen David , Müller Hans-Michael , Sternberg Paul W
Published: August 2006

Background

Document classification is a wide-spread problem with many applications, from organizing search engine snippets to spam filtering. We previously described Textpresso, a text-mining system for biological literature, which marks up full text according to a shallow ontology that includes terms of biological interest. This project investigates document classification in the context of biological literature, making use of the Textpresso markup of a corpus of Caenorhabditis elegans literature.

Results

We present a two-step text categorization algorithm to classify a corpus of C. elegans papers. Our classification method first uses a support vector machine-trained classifier, followed by a novel, phrase-based clustering algorithm. This clustering step autonomously creates cluster labels that are descriptive and understandable by humans. This clustering engine performed better on a standard test-set (Reuters 21578) compared to previously published results (F-value of 0.55 vs. 0.49), while producing cluster descriptions that appear more useful. A web interface allows researchers to quickly navigate through the hierarchy and look for documents that belong to a specific concept.

Conclusion

We have demonstrated a simple method to classify biological documents that embodies an improvement over current methods. While the classification results are currently optimized for Caenorhabditis elegans papers by human-created rules, the classification engine can be adapted to different types of documents. We have demonstrated this by presenting a web interface that allows researchers to quickly navigate through the hierarchy and look for documents that belong to a specific concept.
Validating MOSPA questionnaire for measuring physical activity in Pakistani women
Authors: Iqbal Romaina , Rafique Ghazala , Badruddin Salma , Qureshi Rahat , Gray-Donald Katherine
Published: August 2006

Background

Precise measurements of activity at a population level are important for monitoring trends and evaluating health promotion strategies. Few studies have assessed the measurement of physical activity in developing countries. The aim of this study was to validate the MOSPA (Monica Optional Study of Physical Activity) questionnaire which was developed for the WHO-Monitoring trends and determinants of cardiovasculr disease (MONICA) study sites.

Methods

The MOSPA questionnaire assesses energy expendtiture (EE) related to physical activity (employment, household work, transportation, and leisure time) over a one year period. This questionnaire has been described in the manuscript as the long term (LT) questionnaire. An adapted short term (ST) 5 day questionnaire was developed to assess convergent validity. Questionnaire data were compared with physical activity EE estimates from a Caltrac accelerometer and with body composition measures (height, weight and bioelectrical impedance) in 50 women from the Aga Khan University (AKU) hospital antenatal clinics, Pakistan. Other forms of EE i.e. resting EE and thermic effect of food were not assessd in this study.

Results

Subjects were aged 26 ± 3.8 years and were 16.1 ± 6.7 weeks pregnant. Their average weight was 58.8 ± 10.7 Kg. The average EE/day assessed by the Caltrac accelerometer, was 224 kcal and by MOSPA LT questionnaire it was 404 kcal. The questionnaires and Caltrac data were reasonably well correlated: r = 0.51 and r = 0.60 (P < 0.01) for LT and ST questionnaires respectively. Energy expenditure from questionnaire data was not correlated with body composition measures.

Conclusion

The MOSPA questionnaire is useful in assessing physical activity levels in a sedentary population over a one year period.
Demographic and biologic influences on survival in whites and blacks: 40 years of follow-up in the Charleston heart study
Authors: Nietert Paul J , Sutherland Susan E , Keil Julian E , Bachman David L
Published: August 2006

Background

In the United States, life expectancy is significantly lower among blacks than whites. We examined whether socioeconomic status (SES) and cardiovascular disease (CVD) risk factors may help explain this disparity.

Methods

Forty years (1961 through 2000) of all-cause mortality data were obtained on a population-based cohort of 2,283 subjects in the Charleston Heart Study (CHS). We examined the influence of SES and CVD risk factors on all-cause mortality.

Results

Complete data were available on 98% of the original sample (647 white men, 728 white women, 423 black men, and 443 black women). After adjusting for SES and CVD risk factors, the hazard ratios (HRs) for white ethnicity were 1.14 (0.98 to 1.32) among men and 0.90 (0.75 to 1.08) among women, indicating that the mortality risk was 14% greater for white men and 10% lower for white women compared to their black counterparts. However the differences were not statistically significant.

Conclusion

While there are marked contrasts in mortality among blacks and whites in the CHS, the differences can be largely explained by SES and CVD risk factors. Continued focus on improving and controlling cardiovascular disease risk factors may reduce ethnic disparities in survival.
Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine
Authors: Segura-Pacheco Blanca , Perez-Cardenas Enrique , Taja-Chayeb Lucia , Chavez-Blanco Alma , Revilla-Vazquez Alma , Benitez-Bribiesca Luis , Duenas-González Alfonso
Published: August 2006

Background

The development of resistance to cytotoxic chemotherapy continues to be a major obstacle for successful anticancer therapy. It has been shown that cells exposed to toxic concentrations of commonly used cancer chemotherapy agents develop DNA hypermetylation. Hence, demethylating agents could play a role in overcoming drug resistance.

Methods

MCF-7 cells were rendered adriamycin-resistant by weekly treatment with adriamycin. Wild-type and the resulting MCF-7/Adr cells were analyzed for global DNA methylation. DNA methyltransferase activity and DNA methyltransferase (dnmt) gene expression were also determined. MCF-7/Adr cells were then subjected to antisense targeting of dnmt1, -3a, and -b genes and to treatment with the DNA methylation inhibitor hydralazine to investigate whether DNA demethylation restores sensitivity to adriamycin.

Results

MCF-7/Adr cells exhibited the multi-drug resistant phenotype as demonstrated by adriamycin resistance, mdr1 gene over-expression, decreased intracellular accumulation of adriamycin, and cross-resistance to paclitaxel. The mdr phenotype was accompanied by global DNA hypermetylation, over-expression of dnmt genes, and increased DNA methyltransferase activity as compared with wild-type MCF-7 cells. DNA demethylation through antisense targeting of dnmts or hydralazine restored adriamycin sensitivity of MCF-7/Adr cells to a greater extent than verapamil, a known inhibitor of mdr protein, suggesting that DNA demethylation interferes with the epigenetic reprogramming that participates in the drug-resistant phenotype.

Conclusion

We provide evidence that DNA hypermethylation is at least partly responsible for development of the multidrug-resistant phenotype in the MCF-7/Adr model and that hydralazine, a known DNA demethylating agent, can revert the resistant phenotype.
AICAR inhibits adipocyte differentiation in 3T3L1 and restores metabolic alterations in diet-induced obesity mice model
Authors: Giri Shailendra , Rattan Ramandeep , Haq Ehtishamul , Khan Mushfiquddin , Yasmin Rifat , Won Je-song , Key Lyndon , Singh Avtar K , Singh Inderjit
Published: August 2006

Background

Obesity is one of the principal causative factors involved in the development of metabolic syndrome. AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. The role of AMP-activated protein kinase in adipocyte differentiation is not completely understood, therefore, we examined the effect of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK) on adipocyte differentiation in 3T3L1 cells and in a mouse D iet i nduced o besity (DIO) model.

Methods

To examine the effect of AICAR on adipocyte differentiation in 3T3L1 cells and in a mouse D iet i nduced o besity (DIO) model, 3T3L1 cells were differentiatied in the presence or absence of different concentration of AICAR and neutral lipid content and expression of various adipocyte-specific transcription factors were examined. In vivo study, treated and untreated mice with AICAR (0.1–0.5 mg/g body weight) were fed high-fat diet (60% kcal% fat) to induce DIO and several parameters were studied.

Results

AICAR blocked adipogenic conversion in 3T3L1 cells along with significant decrease in the neutral lipid content by downregulating several adipocyte-specific transcription factors including peroxisome proliferators-activated receptor γ (PPARγ), C/EBPα and ADD1/SREBP1, which are critical for adipogenesis in vitro. Moreover, intraperitoneal administration of AICAR (0.5 mg g/body weight) to mice fed with high-fat diet (60% kcal% fat) to induce DIO, significantly blocked the body weight gain and total content of epididymal fat in these mice over a period of 6 weeks. AICAR treatment also restored normal adipokine levels and resulted in significant improvement in glucose tolerance and insulin sensitivity. The reduction in adipose tissue content in AICAR treated DIO mice was due to reduction in lipid accumulation in the pre-existing adipocytes. However, no change was observed in the expression of PPARγ, C/EBPα and ADD1/SREBP1 transcription factors in vivo though PGC1α expression was significantly induced.

Conclusion

This study suggests that AICAR inhibits adipocyte differentiation via downregulation of expression of adipogenic factors in vitro and reduces adipose tissue content in DIO mice by activating expression of PGC1α without inhibiting adipocyte-specific transcription factors in DIO mice.
The relationship between reproductive outcome measures in DDT exposed malaria vector control workers: a cross-sectional study
Authors: Dalvie Mohamed A , Myers Jonathan E
Published: August 2006

Background

The utility of blood reproductive endocrine biomarkers for assessing or estimating semen quality was explored.

Methods

A cross-sectional study of 47 DDT exposed malaria vector control workers was performed. Tests included blood basal and post gonadotrophin releasing hormone (GnRH), lutenizing hormone (LH), follicle stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG), estradiol (E2) and inhibin; a questionnaire (demographics and general medical history); a physical examination and semen analysis. Semen parameters were determined using either/or or both WHO or the strict Tygerberg criteria. Relationships between semen parameters and endocrine measures were adjusted for age, duration of abstinence before sampling, presence of physical abnormalities and fever in the last two months. All relationships between specific endocrine hormones were adjusted for age and basal SHBG.

Results

Multiple logistic regression showed a consistent positive relationship (prevalence odds ratio (POR) = 8.2, CI:1.4–49.2) between low basal inhibin (<100 pg/ml) and low semen count (< 40 million) and density (< 20 million/ml); consistent positive, but weaker relationships (1> POR < 2) between abnormally low semen count as well as density and baseline and post GnRH FSH; and positive relationships (POR = 37, CI:2–655) between the prevalence of high basal estradiol (> 50 pg/ml) and abnormal morphology (proportion < 5%) and low motility (proportion <50%). Most of the expected physiological relationships between specific endocrines were significant.

Conclusion

The study has demonstrated that low basal inhibin, elevated basal FSH and high basal E2 can serve as markers of impaired semen quality.
AceView: a comprehensive cDNA-supported gene and transcripts annotation
Authors: Thierry-Mieg Danielle , Thierry-Mieg Jean
Published: August 2006

Background

Regions covering one percent of the genome, selected by ENCODE for extensive analysis, were annotated by the HAVANA/Gencode group with high quality transcripts, thus defining a benchmark. The ENCODE Genome Annotation Assessment Project (EGASP) competition aimed at reproducing Gencode and finding new genes. The organizers evaluated the protein predictions in depth. We present a complementary analysis of the mRNAs, including alternative transcript variants.

Results

We evaluate 25 gene tracks from the University of California Santa Cruz (UCSC) genome browser. We either distinguish or collapse the alternative splice variants, and compare the genomic coordinates of exons, introns and nucleotides. Whole mRNA models, seen as chains of introns, are sorted to find the best matching pairs, and compared so that each mRNA is used only once. At the mRNA level, AceView is by far the closest to Gencode: the vast majority of transcripts of the two methods, including alternative variants, are identical. At the protein level, however, due to a lack of experimental data, our predictions differ: Gencode annotates proteins in only 41% of the mRNAs whereas AceView does so in virtually all. We describe the driving principles of AceView, and how, by performing hand-supervised automatic annotation, we solve the combinatorial splicing problem and summarize all of GenBank, dbEST and RefSeq into a genome-wide non-redundant but comprehensive cDNA-supported transcriptome. AceView accuracy is now validated by Gencode.

Conclusion

Relative to a consensus mRNA catalog constructed from all evidence-based annotations, Gencode and AceView have 81% and 84% sensitivity, and 74% and 73% specificity, respectively. This close agreement validates a richer view of the human transcriptome, with three to five times more transcripts than in UCSC Known Genes (sensitivity 28%), RefSeq (sensitivity 21%) or Ensembl (sensitivity 19%).
Vertebrate gene finding from multiple-species alignments using a two-level strategy
Authors: Carter David , Durbin Richard
Published: August 2006

Background

One way in which the accuracy of gene structure prediction in vertebrate DNA sequences can be improved is by analyzing alignments with multiple related species, since functional regions of genes tend to be more conserved.

Results

We describe DOGFISH, a vertebrate gene finder consisting of a cleanly separated site classifier and structure predictor. The classifier scores potential splice sites and other features, using sequence alignments between multiple vertebrate species, while the structure predictor hypothesizes coding transcripts by combining these scores using a simple model of gene structure. This also identifies and assigns confidence scores to possible additional exons. Performance is assessed on the ENCODE regions. We predict transcripts and exons across the whole human genome, and identify over 10,000 high confidence new coding exons not in the Ensembl gene set.

Conclusion

We present a practical multiple species gene prediction method. Accuracy improves as additional species, up to at least eight, are introduced. The novel predictions of the whole-genome scan should support efficient experimental verification.
JIGSAW, GeneZilla, and GlimmerHMM: puzzling out the features of human genes in the ENCODE regions
Authors: Allen Jonathan E , Majoros William H , Pertea Mihaela , Salzberg Steven L
Published: August 2006

Background

Predicting complete protein-coding genes in human DNA remains a significant challenge. Though a number of promising approaches have been investigated, an ideal suite of tools has yet to emerge that can provide near perfect levels of sensitivity and specificity at the level of whole genes. As an incremental step in this direction, it is hoped that controlled gene finding experiments in the ENCODE regions will provide a more accurate view of the relative benefits of different strategies for modeling and predicting gene structures.

Results

Here we describe our general-purpose eukaryotic gene finding pipeline and its major components, as well as the methodological adaptations that we found necessary in accommodating human DNA in our pipeline, noting that a similar level of effort may be necessary by ourselves and others with similar pipelines whenever a new class of genomes is presented to the community for analysis. We also describe a number of controlled experiments involving the differential inclusion of various types of evidence and feature states into our models and the resulting impact these variations have had on predictive accuracy.

Conclusion

While in the case of the non-comparative gene finders we found that adding model states to represent specific biological features did little to enhance predictive accuracy, for our evidence-based 'combiner' program the incorporation of additional evidence tracks tended to produce significant gains in accuracy for most evidence types, suggesting that improved modeling efforts at the hidden Markov model level are of relatively little value. We relate these findings to our current plans for future research.
An Agarose Matrix Facilitates Sectioning of Tissue Microarray Blocks
Authors: Yan Pu , Seelentag Walter , Bachmann Astrid , Bosman Fred T.
Published: August 2006

Tissue microarray (TMA) is a powerful, high-throughput technique for in situ investigation of biomarkers in many tissue samples in a paraffin block by immunohistochemistry or fluorescence in situ hybridization (FISH), and has rapidly become the standard in marker studies. One of the difficult steps in the procedure is the sectioning of array blocks and mounting of sections using special slides and/or adhesive-coated tape, which demands specific experience and is time-consuming. We report an arraying method that allows melting of the receiving paraffin block and subsequent sectioning like any ordinary paraffin-embedded tissue block. The major difference from the standard microarray technique is the use of an agarose matrix in the recipient block. The agarose matrix allows melting of the paraffin without disturbing the array, resulting in perfect integration of the tissue cores. The agarose-paraffin TMA blocks limit tissue core loss during cutting, mounting, or immunohistochemical or FISH staining and better maintains the array.
Prolonged Exposure to Hyperoxia Increases Perivascular Mast Cells in Rat Lungs
Authors: Brock Thomas G. , Giulio Camillo Di
Published: August 2006

Prolonged hyperoxia, as may be used to treat patients with severe hypoxemia, can lead to lung injury, respiratory failure, and death. Resident mast cells play important roles in regulating the lung response to changing environmental conditions, as evidenced by their roles in asthma and airway hyperresponsiveness. In this study we evaluated the effect of prolonged hyperoxia on the number and distribution of mast cells in the rat lung. In rats maintained in normoxia, mast cells were distributed primarily in the loose connective tissue surrounding large bronchioles and vessels of the lung. In rats exposed to normobaric hyperoxia for 72 hr, mast cell number in lung sections increased significantly, and mast cells were found preferentially accumulated around vessels throughout the lung. Notably, mast cells around smaller vessels were abundant in hyperoxic lungs but rare in normoxic lungs. Also, mast cells were increased in the pleura of lungs exposed to hyperoxia. These changes in mast cell number and distribution in response to hyperoxia were evident in aged (22-month-old) rats as well as young (3-month-old) rats. As mast cell-derived mediators have many effects, e.g., on vascular leak and vascular tone, positioning of increased mast cell numbers throughout the lung vasculature may be an important contributor to changes in lung function subsequent to persistent hyperoxia.
Cytoglobin Is a Stress-responsive Hemoprotein Expressed in the Developing and Adult Brain
Authors: Mammen Pradeep P.A. , Shelton John M. , Ye Qiu , Kanatous Shane B. , McGrath Amanda J. , Richardson James A. , Garry Daniel J.
Published: August 2006

Cytoglobin (Cygb) is a novel tissue hemoprotein relatively similar to myoglobin (Mb). Because Cygb shares several structural features with Mb, we hypothesized that Cygb functions in the modulation of oxygen and nitric oxide metabolism or in scavenging free radicals within a cell. In the present study we examined the spatial and temporal expression pattern of Cygb during murine embryogenesis. Using in situ hybridization, RT-PCR, and Northern blot analyses, limited Cygb expression was observed during embryogenesis compared with Mb expression. Cygb expression was primarily restricted to the central nervous system and neural crest derivatives during the latter stages of development. In the adult mouse, Cygb is expressed in distinct regions of the brain as compared with neuroglobin (Ngb), another globin protein, and these regions are responsive to oxidative stress (i.e., hippo-campus, thalamus, and hypothalamus). In contrast to Ngb, Cygb expression in the brain is induced in response to chronic hypoxia (10% oxygen). These results support the hypothesis that Cygb is an oxygen-responsive tissue hemoglobin expressed in distinct regions of the normoxic and hypoxic brain and may play a key role in the response of the brain to a hypoxic insult.
A Novel Method for Multiple Labeling Combining In Situ Hybridization With Immunofluorescence
Authors: Pineau Isabelle , Barrette Benoit , Vallières Nicolas , Lacroix Steve
Published: August 2006

In situ hybridization (ISH) is a particularly useful method to investigate de novo mRNA expression in tissue sections. High specificity and sensitivity of this technique combined with the great preservation of tissue and cellular morphology conferred by fixatives such as 4% paraformaldehyde, pH 9.5, make ISH a tool of choice for detecting genes of interest in individual cells in the central nervous system (CNS). Here we describe a novel method that combines radioactive ISH with immunofluorescence on the same tissue section to identify cell populations expressing selected mRNA transcripts. This novel method has several major advantages over previously described double-labeling light microscopic methods combining enzymatic immunohistochemistry and ISH including (1) complete protection against loss of hybridization signal that normally occurs during the immunoenzymatic reaction, (2) improved immunolabeling sensitivity due to the proteinase K digestion step during ISH, (3) detection of several proteins specific for different cell populations on the same tissue section, and (4) counterstaining of tissue sections without affecting visualization of immunolabeling. This new method will be particularly useful for investigators looking to identify cell populations producing mRNAs expressed in low abundance such as cytokines, chemokines, and growth factors in the intact and/or injured mammalian CNS.
On Euclidean designs
Authors: Bajnok Béla
Published: August 2006

A Euclidean t-design, as introduced by Neumaier and Seidel (1988), is a finite set 𝒳 ⊂ ℝ
n
with a weight function w : 𝒳 → ℝ+ for which

holds for every polynomial ƒ of total degree at most t; here R is the set of norms of the points in 𝒳, Wr
is the total weight of all elements of 𝒳 with norm r, Sr
is the n-dimensional sphere of radius r centered at the origin, and

is the average of ƒ over Sr
. Neumaier and Seidel (1988), as well as Delsarte and Seidel (1989), also proved a Fisher-type inequality |𝒳| ≥ N(n, |R|, t) (assuming that the design is antipodal if t is odd). For fixed n and |R| we have N(n, |R|, t) = O(t

n−1).

This paper contains two main results. First, we provide a recursive construction for Euclidean t-designs in ℝ
n
. Namely, we show how to use certain Gauss–Jacobi quadrature formulae to ‘lift’ a Euclidean t-design in ℝ
n−1 to a Euclidean t-design in ℝ
n
, preserving both the norm spectrum R and the weight sum Wr
for each r ∈ R. For fixed n and |R| this construction yields a design of size O(t

n−1); however, the coefficient of t

n−1 here is significantly greater than it is in N(n, |R|, t).

A Euclidean design with exactly N(n, |R|, t) points is called tight; in both of the above mentioned papers it was conjectured that a tight Euclidean design with t ≥ 4 must be a spherical design, that is, |R| = 1 and w is constant on 𝒳. Bannai and Bannai (2003) disproved this conjecture by exhibiting an example for the parameters, (n, |R|, t) = (2,2,4). Here we construct tight Euclidean designs for n = 2 and every t and |R| with |R| ≤

.
Carnot spaces and the k-stein condition
Authors: Druetta María J
Published: August 2006

A riemannian manifold M with associated Jacobi operators R
X
(R
X

Y = R(Y, X) X), X in TM, is said to be k-stein, k ≥ 1, if there exists a function μk
on M such that tr(R
k

X
) = μk
|X|2k
for all X in TM. We study the k-stein condition on Lie groups of Iwasawa type and in particular in those which are Carnot spaces. We show that a Carnot space which is k-stein for some k > 1 is necessarily a Damek–Ricci space; Damek–Ricci spaces are Einstein and 2-stein and they are not k-stein for any k ≥ 3, unless they are symmetric. Moreover, we show that a harmonic Lie group of Iwasawa type which is 3-stein is a symmetric space of noncompact type and rank one.
Entropy of the geodesic flow for metric spaces and Bruhat–Tits buildings
Authors: Leuzinger Enrico
Published: August 2006

Let (X, dX
) be a geodesically complete Hadamard space endowed with a Borel-measure μ. Assume that there exists a group Γ of isometries of X which acts totally discontinuously and cocompactly on X and preserves μ. We show that the topological entropy of the geodesic flow on the space of (parametrized) geodesics of the compact quotient Γ\X is equal to the volume entropy of μ (if X satisfies a certain local uniformity condition). This extends a result of Manning for riemannian manifolds of nonpositive curvature to the singular case. The result in particular holds for Bruhat–Tits buildings, for which we also compute the entropy explicitly.
Briggs–Rauscher Reaction with 1,4-Cyclohexanedione Substrate
Authors: Keresztúri Klára , Szalai István
Published: August 2006

A new organic substrate has been used to promote oscillations under batch conditions in the Briggs–Rauscher oscillating system. The new substrate, 1,4-cyclohexanedione (CHD), reacts with aqueous iodine via an enol mechanism. We discuss the effect of the initial concentrations, the temperature and chemical perturbations. In a definite range of concentrations long-lived oscillations with two significantly different frequency periods were observed. The low frequency parts are temperature-dependent while the high frequency oscillations do not show temperature dependence. The inhibitory effects of 1,4-hydroquinone and 1,4-benzoquinone on the oscillations and the kinetics of some important component reactions were studied to develop a model for the simulation of the observed oscillations.
Estrogen receptor-related receptors in the killifish Fundulus heteroclitus: diversity, expression, and estrogen responsiveness
Authors: Tarrant A M , Greytak S R , Callard G V , Hahn M E
Published: August 2006

The estrogen receptor-related receptors (ERRs) are a group of nuclear receptors that were originally identified on the basis of sequence similarity to the estrogen receptors. The three mammalian ERR genes have been implicated in diverse physiological processes ranging from placental development to maintenance of bone density, but the diversity, function, and regulation of ERRs in non-mammalian species are not well understood. In this study, we report the cloning of four ERR cDNAs from the Atlantic killifish, Fundulus heteroclitus, along with adult tissue expression and estrogen responsiveness. Phylogenetic analysis indicates that F. heteroclitus (Fh)ERRα is an ortholog of the single ERRα identified in mammals, pufferfish, and zebrafish. FhERRβa and FhERRβb are co-orthologs of the mammalian ERRβ. Phylogenetic placement of the fourth killifish ERR gene, tentatively identified as FhERRγb, is less clear. The four ERRs showed distinct, partially overlapping mRNA expression patterns in adult tissues. FhERRα was broadly expressed. FhERRβa was expressed at apparently low levels in eye, brain, and ovary. FhERRβb was expressed more broadly in liver, gonad, eye, brain, and kidney. FhERRγb was expressed in multiple tissues including gill, heart, kidney, and eye. Distinct expression patterns of FhERRβa and FhERRβb are consistent with subfunctionalization of the ERRβ paralogs. Induction of ERRα mRNA by exogenous estrogen exposure has been reported in some mammalian tissues. In adult male killifish, ERR expression did not significantly change following estradiol injection, but showed a trend toward a slight induction (three- to five-fold) of ERRα expression in heart. In a second, more targeted experiment, expression of ERRα in adult female killifish was downregulated 2.5-fold in the heart following estradiol injection. In summary, our results indicate that killifish contain additional ERR genes relative to mammals, including ERRβ paralogs. In addition, regulation of ERRα expression in killifish apparently differs from regulation in mammals. Together, these features may facilitate determination of both conserved and specialized ERR gene functions.
Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF–VEGF receptor 2 binding in diabetic retinopathy
Authors: Zhang Sarah X , Wang Joshua J , Gao Guoquan , Parke Kyoungmin , Ma Jian-xing
Published: August 2006

It has been shown that the balance between vascular endothelial growth factor (VEGF), a major angiogenic stimulator, and pigment epithelium-derived factor (PEDF), a potent angiogenic inhibitor, is critical for the regulation of vascular permeability and angiogenesis. However, the regulation of the balance is largely unclear. The present study demonstrated that there is a reciprocal interaction between VEGF and PEDF in the retina. PEDF significantly decreased VEGF expression in both retinal capillary endothelial cells (RCEC) and Müller cells. This PEDF effect was confirmed in the retina of rats with oxygen-induced retinopathy. Silencing of the PEDF gene by siRNA in Müller cells resulted in a significant upregulation of VEGF expression at both the RNA and protein levels, suggesting that PEDF is an endogenous negative regulator of VEGF. The further study of the mechanism showed that PEDF inhibited hypoxia-induced increases in VEGF promoter activity, HIF-1 nuclear translocation and mitogen activated protein kinase phosphorylation. These results suggest that PEDF inhibits VEGF expression at the transcriptional level. In addition, PEDF effectively inhibited VEGF binding to RCEC. Moreover, in vitro receptor-binding assay demonstrated that PEDF competed with VEGF for binding to VEGF receptor 2, which may represent a new mechanism for PEDF activity. On the other hand, VEGF significantly downregulated PEDF expression in RCEC, but not in retinal Müller cells, suggesting a VEGF receptor-mediated process. These results suggest that the reciprocal regulation between VEGF and PEDF may play a role in angiogenic control. The decrease in PEDF levels in the retina is at least partially responsible for the increase in VEGF expression and subsequent vascular leakage and neovascularization in diabetes.
cAMP-independent signaling regulates steroidogenesis in mouse Leydig cells in the absence of StAR phosphorylation
Authors: Manna Pulak R , Chandrala Syam P , Jo Youngah , Stocco Douglas M
Published: August 2006

In the regulation of steroid biosynthesis, a process mediated by the steroidogenic acute regulatory (StAR) protein, both cAMP-dependent and -independent pathways are involved. While the cAMP-dependent regulatory events represent, by far, the most robust increase in steroid synthesis and are well established, the knowledge regarding cAMP-independent mechanisms is lacking. The present investigation was designed to elucidate the potential involvement of the latter in regulating StAR expression and steroidogenesis in mouse Leydig tumor cells (mLTC-1 cells). Treatment of mLTC-1 cells with a number of factors including insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), fibroblast growth factor, transforming growth factor (TGF)α, interleukin-1 (IL-1), and colony-stimulating factor-1, increased the levels of StAR mRNA, StAR protein, and progesterone to varying degrees and utilized signaling pathways that are not associated with elevations in intracellular cAMP levels. Importantly, phosphorylation of StAR in response to these stimuli was undetectable, which is in marked contrast to observations with human chorionic gonadotropin (hCG), indicating factors that do not alter intracellular cAMP, regulate the steroid biosynthesis in a StAR phosphorylation-independent manner. In addition, the roles for factors involved in cross-talk between the protein kinase pathways, PKA and PKC, were demonstrated. Further characterization of signaling by one such cAMP-independent factor, TGFα, demonstrated that the mechanism, whereby it increased StAR expression and steroid synthesis, was dependent on de novo protein synthesis and mediated via activation of the EGF receptor. TGFα was also able to augment hCG-stimulated cAMP synthesis, StAR protein and StAR phosphorylation, and influence hCG binding and LH receptor mRNA expression. Furthermore, TGFα increased phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and cAMP-response element-binding protein (CREB), processes inhibited by the mitogen-activated protein kinase/ERK inhibitor U0126 and by expression of non-phosphorylatable CREB-M1 respectively. Inhibition of ERK activity enhanced TGFα-mediated StAR protein expression (but not its phosphorylation) and decreased progesterone synthesis, events correlated with the expression of dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene 1 (DAX-1) and scavenger receptor class B type 1 (SR-B1). Collectively, these findings demonstrate that, in mouse Leydig cells, cAMP-independent signaling events regulate steroidogenesis in a StAR phosphorylation-independent manner.
Physicochemical and Mineralogical Characterization of Soil–Saprolite Cores from a Field Research Site, Tennessee
Authors: Moon Ji‐Won , Roh Yul , Phelps Tommy J. , Phillips Debra H. , Watson David B. , Kim Young‐Jin , Brooks Scott C.
Published: August 2006

Site characterization is an essential initial step in determining the feasibility of remedial alternatives at hazardous waste sites. Physicochemical and mineralogical characterization of U‐contaminated soils in deeply weathered saprolite at Area 2 of the DOE Field Research Center (FRC) site, Oak Ridge, TN, was accomplished to examine the feasibility of bioremediation. Concentrations of U in soil–saprolite (up to 291 mg kg−1in oxalate‐extractable Uo) were closely related to low pH (ca. 4–5), high effective cation exchange capacity without Ca (64.7–83.2 cmolckg−1), amorphous Mn content (up to 9910 mg kg−1), and the decreased presence of relative clay mineral contents in the bulk samples (i.e., illite 2.5–12 wt. %, average 32 wt. %). The pH of the fill material ranged from 7.0 to 10.5, whereas the pH of the saprolite ranged from 4.5 to 8. Uranium concentration was highest (about 300 mg kg−1) at around 6 m below land surface near the saprolite–fill interface. The pH of ground water at Area 2 tended to be between 6 and 7 with U concentrations of about 0.9 to 1.7 mg L−1These site specific characteristics of Area 2, which has lower U and nitrate contamination levels and more neutral ground water pH compared with FRC Areas 1 and 3 (ca. 5.5 and <4, respectively), indicate that with appropriate addition of electron donors and nutrients bioremediation of U by metal reducing microorganisms may be possible.
Distribution of Uranium Contamination in Weathered Fractured Saprolite/Shale and Ground Water
Authors: Phillips D. H. , Watson D. B. , Roh Y. , Mehlhorn T. L. , Moon J.‐W. , Jardine P. M.
Published: August 2006

The objective of this study was to determine how structure, stratigraphy, and weathering influence fate and transport of contaminants (particularly U) in the ground water and geologic material at the Department of Energy (DOE) Environmental Remediation Sciences Department (ERSD) Field Research Center (FRC). Several cores were collected near four former unlined adjoining waste disposal ponds. The cores were collected, described, analyzed for U, and compared with ground water geochemistry from surrounding multilevel wells. At some locations, acidic U‐contaminated ground water was found to preferentially flow in small remnant fractures weathering the surrounding shale (nitric acid extractable U [UNA] usually < 50 mg kg−1) into thin (<25 cm) Fe oxide‐rich clayey seams that retain U (UNA 239 to 375 mg kg−1). However, greatest contaminant transport occurs in a 2 to 3 m thick more permeable stratigraphic transition zone located between two less permeable, and generally less contaminated zones consisting of (i) overlying unconsolidated saprolite (UNA < 0.01 to 200 mg kg−1) and (ii) underlying less‐weathered bedrock (UNA generally < 0.01 to 7 mg kg−1). In this transition zone, acidic (pH < 4) U‐enriched ground water (U of 38 mg L−1) has weathered away calcite veins resulting in greater porosity, higher hydraulic conductivity, and higher U contamination (UNA 106 to 745 mg kg−1) of the weathered interbedded shale and sandstone. These characteristics of the transition zone produce an interval with a high flux of contaminants that could be targeted for remediation.
Sorption–Desorption of Carbamazepine from Irrigated Soils
Authors: Williams C. F. , Williams C. F. , Adamsen F. J.
Published: August 2006

Th anti‐seizure medication carbamazepine is often found in treated sewage effluent and environmental samples. Carbamazepine has been shown to be very persistent in sewage treatment, as well as ground water. Due to environmental persistence, irrigation with sewage effluent could result in carbamazepine contamination of surface and ground water. To determine the potential for leaching of carbamazepine, a series of adsorption and desorption batch equilibrium experiments were conducted on irrigated soils. It was found that carbamazepine adsorption to biosolid‐amended (T) soils had aKDof 19.8 vs. 12.6 for unamended soil. Based on adsorption, carbamazepine leaching potential would be categorized as low. During desorption significant hysteresis was observed andKDincreased for both soils. Desorption isotherms also indicate a potential for irreversibly bound carbamazepine in the T soil. Results indicate that initial removal of carbamazepine via adsorption from irrigation water is significant and that desorption characteristics would further limit the mobility of carbamazepine through the soil profile indicating that carbamazepine found in sewage effluent used for irrigation has a low leaching potential.