bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Intercollegiate Athletics on Employment in the Restaurant and Accommodations Industries
Authors: Lentz Bernard F. , Laband David N.
Published: February 2009

In this article, we analyze metropolitan and micropolitan statistical area (MSA) level data in the United States to examine the economic impact of college athletics. Specifically, we examine the relationship between total athletics revenues (aggregated across all colleges in an MSA) and MSA level employment in the accommodations and food services industries. Controlling for a variety of other factors that might influence hotel/restaurant employment within an MSA, we find a statistically significant, positive relationship between college athletics revenues and MSA employment in the food services and accommodations industries.
Exploring the Role of Leader—Subordinate Interactions in the Construction of Organizational Positivity
Authors: Pina e Cunha Miguel , Campos e Cunha Rita , Rego Arménio
Published: February 2009

In this article we discuss individual implicit theories of how positive and negative organizing unfold. The discussion is grounded in data collected from 89 individuals working in different organizational contexts. An inductive logic was followed, based on critical incidents of positive and negative processes and outcomes presented by participants, according to how they viewed their professional situation. Through a dialectical process of analysis, we extracted six dimensions that were present in different combinations among narratives provided by the participants: recognition/indifference, communication/silence, interaction/separation, confidence/ distrust, loyalty/betrayal, and organizational transparency/organizational secrecy. We then analysed how these dimensions fit together and discovered that they could be organized around four major patterns combining the clarity/secrecy of organizational rules and the considerate/detached behavior of leaders. We assert that positive leaders are essential in the creation of patterns of organizing, regardless of the features of the external context.
From Ineffectiveness to Destruction: A Qualitative Study on the Meaning of Negative Leadership
Authors: Schilling Jan
Published: February 2009

This article aims at analyzing the content and structure of managers' conceptions of negative leadership. Using semi-structured interviews, 42 managers were asked about their conceptions of negative leadership, its antecedents and consequences. Results show that the concept of negative leadership is associated with eight behavioural categories: insincere, despotic, exploitative, restrictive, failed, laissez-faire, and active- and passive-avoiding leadership. Negative leadership was causally attributed to the environment of the leader, especially the followers, the immediate working field, as well as organizational processes, structures, and resources were seen as potential sources for negative leadership. The main factors regarded as its consequences included negative follower feelings and attitudes, destructive follower behaviour, and devastating organizational results. An analysis of the relationship between the leadership categories revealed two underlying dimensions of human- versus task-orientation and passive versus active behaviour. Limitations of the present approach, implications for future research and organizational practice are discussed.
Therapeutic jurisprudence and procedural justice in Scottish Drug Courts
Authors: McIvor Gill
Published: February 2009

Scotland, like other western jurisdictions, has recently witnessed the development of problem-solving courts aimed at responding more effectively to issues that underlie certain types of offending behaviour. The first to be established were two pilot Drug Courts, which drew upon experience of Scottish Drug Treatment and Testing Orders. In common with Drug Courts elsewhere, the Scottish pilots combined treatment, drug testing, supervision and judicial oversight. This article focuses upon the role of judicial involvement in the ongoing review of Drug Court participants' progress, drawing upon court observation and interviews with offenders and Drug Court professionals. Drug Court dialogues were typically encouraging on the part of sheriffs, aimed at recognizing and reinforcing the progress made by participants and motivating them to maintain and build upon their achievements to date, while participants were generally responsive to the positive feedback they received from the sheriffs as their orders progressed. Interactions within the Scottish Drug Courts reflect key features of procedural justice, including ethicality, efforts to be fair and representation. By contributing to enhanced perceptions of procedural justice, Drug Court dialogues may, it is argued, increase the perceived legitimacy of the court and by so doing encourage increased compliance with treatment and desistance from crime.
A HaemAtlas: characterizing gene expression in differentiated human blood cells
Authors: Watkins Nicholas A. , Gusnanto Arief , de Bono Bernard , De Subhajyoti , Miranda-Saavedra Diego , Hardie Debbie L. , Angenent Will G. J. , Attwood Antony P. , Ellis Peter D. , Erber Wendy , Foad Nicola S. , Garner Stephen F. , Isacke Clare M. , Jolley Jennifer , Koch Kerstin , Macaulay Iain C. , Morley Sarah L. , Rendon Augusto , Rice Kate M. , Taylor Niall , Thijssen-Timmer Daphne C. , Tijssen Marloes R. , van der Schoot C. Ellen , Wernisch Lorenz , Winzer Thilo , Dudbridge Frank , Buckley Christopher D. , Langford Cordelia F. , Teichmann Sarah , Göttgens Berthold , Ouwehand Willem H.
Published: February 2009

Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and helper T cells, natural killer cells, granulocytes, and monocytes using whole genome microarrays. A bioinformatics analysis of these data was performed focusing on transcription factors, immunoglobulin superfamily members, and lineage-specific transcripts. We observed that the numbers of lineage-specific genes varies by 2 orders of magnitude, ranging from 5 for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel coexpression patterns for key transcription factors involved in hematopoiesis (eg, GATA3-GFI1 and GATA2-KLF1). This study represents the most comprehensive analysis of gene expression in hematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which are freely accessible, will be invaluable for future studies on hematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.
Mantle cell lymphoma cells express high levels of CXCR4, CXCR5, and VLA-4 (CD49d): importance for interactions with the stromal microenvironment and specific targeting
Authors: Kurtova Antonina V. , Tamayo Archito T. , Ford Richard J. , Burger Jan A.
Published: February 2009

Mantle cell lymphoma (MCL) is characterized by an early, widespread dissemination and residual disease after conventional treatment, but the mechanisms responsible for lymphoma cell motility and drug resistance are largely unknown. There is growing evidence suggesting that chemokine receptors and adhesion molecules are critical for malignant B-cell trafficking and homing to supportive tissue microenvironments, where they receive survival and drug resistance signals. Therefore, we examined chemokine receptor and adhesion molecule expression and function in MCL cells and their importance for migration and adhesion to marrow stromal cells (MSCs). We found that MCL cells display high levels of functional CXCR4 and CXCR5 chemokine receptors and VLA-4 adhesion molecules. We also report that MCL cells adhere and spontaneously migrate beneath MSCs in a CXCR4- and VLA-4–dependent fashion (pseudoemperipolesis). Moreover, we demonstrate that MSCs confer drug resistance to MCL cells, particularly to MCL cells that migrate beneath MSC. To target MCL-MSC interactions, we tested Plerixafor, a CXCR4 antagonist, and natalizumab, a VLA-4 antibody. Both agents blocked functional responses to the respective ligands and inhibited adhesive interactions between MCL cells and MSCs. These findings provide a rationale to further investigate the therapeutic potential of these drugs in MCL.
Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia
Authors: Chen Rong , Wierda William G. , Chubb Sherri , Hawtin Rachael E. , Fox Judith A. , Keating Michael J. , Gandhi Varsha , Plunkett William
Published: February 2009

Inhibitors of cyclin-dependent kinases (Cdks) have been reported to have activities in chronic lymphocytic leukemia cells by inhibiting Cdk7 and Cdk9, which control transcription. Here we studied the novel Cdk inhibitor SNS-032, which exhibits potent and selective inhibitory activity against Cdk2, Cdk7, and Cdk9. We hypothesized that transient inhibition of transcription by SNS-032 would decrease antiapoptotic proteins, resulting in cell death. SNS-032 effectively killed chronic lymphocytic leukemia cells in vitro regardless of prognostic indicators and treatment history. This was associated with inhibition of phosphorylation of RNA polymerase II and inhibition of RNA synthesis. Consistent with the intrinsic turnover rates of their transcripts and proteins, antiapoptotic proteins, such as Mcl-1 and X-linked inhibitor of apoptosis protein (XIAP), were rapidly reduced on exposure to SNS-032, whereas Bcl-2 protein was not affected. The initial decrease of Mcl-1 protein was the result of transcriptional inhibition rather than cleavage by caspase. Compared with flavopiridol and roscovitine, SNS-032 was more potent, both in inhibition of RNA synthesis and at induction of apoptosis. SNS-032 activity was readily reversible; removal of SNS-032 reactivated RNA polymerase II, which led to resynthesis of Mcl-1 and cell survival. Thus, these data support the clinical development of SNS-032 in diseases that require short-lived oncoproteins for survival.
DNA phosphorothioation in Streptomyces lividans: mutational analysis of the dnd locus
Authors: Xu Tiegang , Liang Jingdan , Chen Shi , Wang Lianrong , He Xinyi , You Delin , Wang Zhijun , Li Aiying , Xu Zhongli , Zhou Xiufen , Deng Zixin
Published: February 2009

Background

A novel DNA phosphorothioate modification (DNA sulfur modification), in which one of the non-bridging oxygen atoms in the phosphodiester bond linking DNA nucleotides is exchanged by sulphur, was found to be genetically determined by dnd or dnd-counterpart loci in a wide spectrum of bacteria from diverse habitats. A detailed mutational analysis of the individual genes within the dnd locus in Streptomyces lividans responsible for DNA phosphorothioation was performed and is described here. It should be of great help for the mechanistic study of this intriguing system.

Results

A 6,665-bp DNA region carrying just five ORFs (dndA-E) was defined as the sole determinant for modification of the DNA backbone in S. lividans to form phosphorothioate. This provides a diagnostically reliable and easily assayable Dnd (DNA degradation) phenotype. While dndA is clearly transcribed independently, dndB-E constitute an operon, as revealed by RT-PCR analysis. An efficient mutation-integration-complementation system was developed to allow for detailed functional analysis of these dnd genes. The Dnd- phenotype caused by specific in-frame deletion of the dndA, C, D, and E genes or the enhanced Dnd phenotype resulting from in-frame deletion of dndB could be restored by expression vectors carrying the corresponding dnd genes. Interestingly, overdosage of DndC or DndD, but not other Dnd proteins, in vivo was found to be detrimental to cell viability.

Conclusion

DNA phosphorothioation is a multi-enzymatic and highly coordinated process controlled by five dnd genes. Overexpression of some proteins in vivo prevented growth of host strain, suggesting that expression of the gene cluster is strictly regulated in the native host.
Identification and validation of reference genes for quantitative RT-PCR normalization in wheat
Authors: Paolacci Anna R , Tanzarella Oronzo A , Porceddu Enrico , Ciaffi Mario
Published: February 2009

Background

Usually the reference genes used in gene expression analysis have been chosen for their known or suspected housekeeping roles, however the variation observed in most of them hinders their effective use. The assessed lack of validated reference genes emphasizes the importance of a systematic study for their identification. For selecting candidate reference genes we have developed a simple in silico method based on the data publicly available in the wheat databases Unigene and TIGR.

Results

The expression stability of 32 genes was assessed by qRT-PCR using a set of cDNAs from 24 different plant samples, which included different tissues, developmental stages and temperature stresses. The selected sequences included 12 well-known HKGs representing different functional classes and 20 genes novel with reference to the normalization issue. The expression stability of the 32 candidate genes was tested by the computer programs geNorm and NormFinder using five different data-sets. Some discrepancies were detected in the ranking of the candidate reference genes, but there was substantial agreement between the groups of genes with the most and least stable expression. Three new identified reference genes appear more effective than the well-known and frequently used HKGs to normalize gene expression in wheat. Finally, the expression study of a gene encoding a PDI-like protein showed that its correct evaluation relies on the adoption of suitable normalization genes and can be negatively affected by the use of traditional HKGs with unstable expression, such as actin and α-tubulin.

Conclusion

The present research represents the first wide screening aimed to the identification of reference genes and of the corresponding primer pairs specifically designed for gene expression studies in wheat, in particular for qRT-PCR analyses. Several of the new identified reference genes outperformed the traditional HKGs in terms of expression stability under all the tested conditions. The new reference genes will enable more accurate normalization and quantification of gene expression in wheat and will be helpful for designing primer pairs targeting orthologous genes in other plant species.
Phenotypic instability and epigenetic variability in a diploid potato of hybrid origin, Solanum ruiz-lealii
Authors: Marfil Carlos F , Camadro Elsa L , Masuelli Ricardo W
Published: February 2009

Background

The wild potato Solanum ruiz-lealii Brüch. (2n = 2x = 24), a species of hybrid origin, is endemic to Mendoza province, Argentina. Recurrent flower malformations, which varied among inflorescences of the same plant, were observed in a natural population. These abnormalities could be the result of genomic instabilities, nucleus-cytoplasmic incompatibility or epigenetic changes. To shed some light on their origin, nuclear and mitochondrial DNA of plants with normal and plants with both normal and malformed flowers (from here on designated as plants with normal and plants with abnormal flower phenotypes, respectively) were analyzed by AFLP and restriction analyses, respectively. Also, the wide genome methylation status and the level of methylation of a repetitive sequence were studied by MSAP and Southern blots analyses, respectively.

Results

AFLP markers and restriction patterns of mitochondrial DNA did not allow the differentiation of normal from abnormal flower phenotypes. However, methylation patterns of nuclear DNA discriminated normal and abnormal flower phenotypes into two different groups, indicating that abnormal phenotypes have a similar methylation status which, in turn, was different from the methylation patterns of normal phenotypes. The abnormal flower phenotype was obtained by treating a normal plant with 5-Azacytidine, a demethylating agent, giving support to the idea of the role of DNA methylation in the origin of flower abnormalities. In addition, the variability detected for DNA methylation was greater than the detected for nucleotide sequence.

Conclusion

The epigenetic nature of the observed flower abnormalities is consistent with the results and indicates that in the diploid hybrid studied, natural variation in methylation profiles of anonymous DNA sequences could be of biological significance.
Moderate alcohol consumption is associated with better endothelial function: a cross sectional study
Authors: Suzuki Keiko , Elkind Mitchell SV , Boden-Albala Bernadette , Jin Zhezhen , Berry Grace , Di Tullio Marco R , Sacco Ralph L , Homma Shunichi
Published: February 2009

Background

Moderate alcohol consumption is protective against coronary artery disease. Endothelial dysfunction contributes to atherosclerosis and the pathogenesis of cardiovascular disease. The effects of alcohol consumption on endothelial function may be relevant to these cardiovascular outcomes, but very few studies have examined the effect of alcohol consumption on endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery in humans.

Methods

In the population-based Northern Manhattan Study (NOMAS), we performed a cross-sectional analysis of lifetime alcohol intake and brachial artery FMD during reactive hyperemia using high-resolution B-mode ultrasound images among 884 stroke-free participants (mean age 66.8 years, women 56.6%, Hispanic 67.4%, black 17.4%, and white 15.2%).

Results

The mean brachial FMD was 5.7% and the median was 5.5%. Compared to non-drinkers, those who drank >1 drink/month to 2 drinks/day were more likely to have FMD above the median FMD (5.5%) (unadjusted OR 1.7, 95% CI 1.2–2.4, p = 0.005). In multivariate analysis, the relationship between moderate alcohol consumption and FMD remained significant after adjusting for multiple traditional cardiovascular risk factors, including sex, race-ethnicity, body mass index, diabetes mellitus, coronary artery disease, Framingham risk score, medication use (adjusted OR 1.8, 95%CI 1.1–3.0, p = 0.03). No beneficial effect on FMD was seen for those who drank more than 2 drinks/day.

Conclusion

In conclusion, consumption of up to 2 alcoholic beverages per day was independently associated with better FMD compared to no alcohol consumption in this multiethnic population. This effect on FMD may represent an important mechanism in explaining the protective effect of alcohol intake on cardiovascular disease.
ARC (NSC 188491) has identical activity to Sangivamycin (NSC 65346) including inhibition of both P-TEFb and PKC
Authors: Stockwin Luke H , Yu Sherry X , Stotler Howard , Hollingshead Melinda G , Newton Dianne L
Published: February 2009

Background

The nucleoside analog, ARC (NSC 188491) is a recently characterized transcriptional inhibitor that selectively kills cancer cells and has the ability to perturb angiogenesisin vitro. In this study, the mechanism of action of ARC was further investigated by comparingin vitroandin vivoactivity with other anti-neoplastic purines.

Methods

Structure-based homology searches were used to identify those compounds with similarity to ARC. Comparator compounds were then evaluated alongside ARC in the context of viability, cell cycle and apoptosis assays to establish any similarities. Following this, biological overlap was explored in detail using gene-expression analysis and kinase inhibition assays.

Results

Results demonstrated that sangivamycin, an extensively characterized pro-apoptotic nucleoside isolated fromStreptomyces, had identical activity to ARC in terms of 1) cytotoxicity assays, 2) ability to induce a G2/M block, 3) inhibitory effects on RNA/DNA/protein synthesis, 4) transcriptomic response to treatment, 5) inhibition of protein kinase C, 6) inhibition of positive transcription elongation factor b (P-TEFb), 7) inhibition of VEGF secretion, and 8) activity within hollow fiber assays. Extending ARC activity to PKC inhibition provides a molecular basis for ARC cancer selectivity and anti-angiogenic effects. Furthermore, functional overlap between ARC and sangivamycin suggests that development of ARC may benefit from a retrospective of previous sangivamycin clinical trials. However, ARC was found to be inactive in several xenograft models, likely a consequence of rapid serum clearance.

Conclusion

Overall, these data expand on the biological properties of ARC but suggest additional studies are required before it can be considered a clinical trials candidate.
Expression and biological significance of c-FLIP in human hepatocellular carcinomas
Authors: Du Xilin , Bao Guoqiang , He Xianli , Zhao Huadong , Yu Fang , Qiao Qing , Lu Jianguo , Ma Qingjiu
Published: February 2009

Background

c-FLIP can be considered as a tumor-progression factor in regard to its anti-apoptotic functions. In the present study, we intended to investigate the expression of c-FLIP in human HCC tissues, and its relation with drug-induced cell apoptosis through the specific inhibition of c-FLIP expression by siRNA in 7721 cells.

Methods

c-FLIP expression was quantified immunohistochemically in HCC tissues(eighty-six cases), and corresponding noncancerous tissues (fifty-seven cases). Patients with HCC were followed up for cancer recurrence. Then, the c-FLIP gene was silenced with specific siRNA in 7721 HCC cells. c-FLIP expression was detected by RT-PCR, Western Blot and immunocytochemical staining. The cellular viability and cell apoptosis were assayedin vitrowith cells treated with doxorubicin.

Results

Positive immunostaining was detected for c-FLIP in 83.72% (72/86) human HCC tissues, 14.81% (4/27) hepatic cirrhosis, 11.11% (2/18) hepatic hemangioma tissues, and absent in normal hepatic tissues. The overexpression(more than 50%) of c-FLIP in HCC adversely affected the recurrence-free survival. Through c-FLIP gene silencing with siRNA, the expressions of c-FLIP mRNA and protein were remarkably down-regulated in 7721 HCC cells. And doxorubicin showed apparent inhibition on cell proliferations, and induced more apoptosis.

Conclusion

These results indicate that c-FLIP is frequently expressed in human HCCs, and its overexpression implied a lesser probability of recurrence-free survival. The specific silencing of c-FLIP gene can apparently up-regulate drug-induced HCC cell apoptosis, and may have therapeutic potential for the treatment of human HCC.
Association between breast cancer susceptibility loci and mammographic density: the Multiethnic Cohort
Authors: Woolcott Christy G , Maskarinec Gertraud , Haiman Christopher A , Verheus Martijn , Pagano Ian S , Le Marchand Loïc , Henderson Brian E , Kolonel Laurence N
Published: February 2009

Introduction

Mammographic density is a strong risk factor for breast cancer. Our objective was to examine its association with polymorphisms identifying breast cancer susceptibility loci that were ascertained in recent genome-wide association studies.

Methods

Subjects were 825 women who participated in previous case–control studies of mammographic density and genetic factors nested within the Multiethnic Cohort study and were from three ethnic groups (White, Japanese American, Native Hawaiian). Eight polymorphisms (rs2981582 in FGFR2, rs3803662 and rs12443621in TOX3, rs3817198 in LSP1, rs981782 and rs10941679 near HCN1/MRPS30, rs889312 in MAP3K1, and rs13387042 at 2q) were examined. Mammographic density was quantified with a computer-assisted method as the percent dense area: the area of radiologically dense fibroglandular tissue relative to the total breast area that also includes radiologically lucent fatty tissue.

Results

The polymorphism rs12443621 in TOX3 was associated with percent dense area; women with at least one G allele (previously associated with increased breast cancer risk) had 3% to 4% higher densities than women with two A alleles. The polymorphism rs10941679 near HCN1/MRPS30 was also associated with percent dense area; women who were homozygous for the G allele (previously associated with increased breast cancer risk) had 4% to 5% lower densities than women with at least one A allele. The other polymorphisms were not associated with percent dense area.

Conclusions

The available data suggest that the effects of most of these polymorphisms on breast cancer are not mediated by mammographic density. Some effects may have been too small to be detected. The association with rs12443621 may provide clues as to how variation in TOX3 influences breast cancer risk.
Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis
Authors: Flierl Michael A , Stahel Philip F , Rittirsch Daniel , Huber-Lang Markus , Niederbichler Andreas D , Hoesel L Marco , Touban Basel M , Morgan Steven J , Smith Wade R , Ward Peter A , Ipaktchi Kyros
Published: February 2009

Introduction

Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis.

Methods

Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls.

Results

Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group.

Conclusions

Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis.
Contrast enhancement of stimulus intermittency in a primary olfactory network and its behavioral significance
Authors: Lei Hong , Riffell Jeffrey A , Gage Stephanie L , Hildebrand John G
Published: February 2009

Background

An animal navigating to an unseen odor source must accurately resolve the spatiotemporal distribution of that stimulus in order to express appropriate upwind flight behavior. Intermittency of natural odor plumes, caused by air turbulence, is critically important for many insects, including the hawkmoth, Manduca sexta, for odor-modulated search behavior to an odor source. When a moth's antennae receive intermittent odor stimulation, the projection neurons (PNs) in the primary olfactory centers (the antennal lobes), which are analogous to the olfactory bulbs of vertebrates, generate discrete bursts of action potentials separated by periods of inhibition, suggesting that the PNs may use the binary burst/non-burst neural patterns to resolve and enhance the intermittency of the stimulus encountered in the odor plume.

Results

We tested this hypothesis first by establishing that bicuculline methiodide reliably and reversibly disrupted the ability of PNs to produce bursting response patterns. Behavioral studies, in turn, demonstrated that after injecting this drug into the antennal lobe at the effective concentration used in the physiological experiments animals could no longer efficiently locate the odor source, even though they had detected the odor signal.

Conclusions

Our results establish a direct link between the bursting response pattern of PNs and the odor-tracking behavior of the moth, demonstrating the behavioral significance of resolving the dynamics of a natural odor stimulus in antennal lobe circuits.
M. bovisBCG induced expression of COX-2 involves nitric oxide-dependent and -independent signaling pathways
Authors: Bansal Kushagra , Narayana Yeddula , Patil Shripad A , Balaji Kithiganahalli N
Published: February 2009

In a multifaceted immunity to mycobacterial infection, induced expression of cyclooxygenase-2 (COX-2) by Mycobacterium bovis bacillus Calmette-Guerin (BCG) may act as an important influencing factor for the effective host immunity. We here demonstrate that M. bovis BCG-triggered TLR2-dependent signaling leads to COX-2 and PGE2 expression in vitro in macrophages and in vivo in mice. Further, the presence of PGE2 could be demonstrated in sera or cerebrospinal fluid of tuberculosis patients. The induced COX-2 expression in macrophages is dependent on NF-κB activation, which is mediated by inducible NO synthase (iNOS)/NO-dependent participation of the members of Notch1-PI-3K signaling cascades as well as iNOS-independent activation of ERK1/2 and p38 MAPKs. Inhibition of iNOS activity abrogated the M. bovis BCG ability to trigger the generation of Notch1 intracellular domain (NICD), a marker for Notch1 signaling activation, as well as activation of the PI-3K signaling cascade. On the contrary, treatment of macrophages with 3-morpholinosydnonimine, a NO donor, resulted in a rapid increase in generation of NICD, activation of PI-3K pathway, as well as the expression of COX-2. Stable expression of NICD in RAW 264.7 macrophages resulted in augmented expression of COX-2. Further, signaling perturbations suggested the involvement of the cross-talk of Notch1 with members with the PI-3K signaling cascade. These results implicate the dichotomous nature of TLR2 signaling during M. bovis BCG-triggered expression of COX-2. In this perspective, we propose the involvement of iNOS/NO as one of the obligatory, early, proximal signaling events during M. bovis BCG-induced COX-2 expression in macrophages.
The Xenoestrogen Bisphenol A Inhibits Postembryonic Vertebrate Development by Antagonizing Gene Regulation by Thyroid Hormone
Authors: Heimeier Rachel A. , Das Biswajit , Buchholz Daniel R. , Shi Yun-Bo
Published: February 2009

Bisphenol A (BPA), a chemical widely used to manufacture plastics, is estrogenic and capable of disrupting sex differentiation. However, recent in vitro studies have shown that BPA can also antagonize T3 activation of the T3 receptor. The difficulty in studying uterus-enclosed mammalian embryos has hampered the analysis on the direct effects of BPA during vertebrate development. This study proposed to identify critical T3 pathways that may be disrupted by BPA based on molecular analysis in vivo. Because amphibian metamorphosis requires T3 and encompasses the postembryonic period in mammals when T3 action is most critical, we used this unique model for studying the effect of BPA on T3-dependent vertebrate development at both the morphological and molecular levels. After 4 d of exposure, BPA inhibited T3-induced intestinal remodeling in premetamorphic Xenopus laevis tadpoles. Importantly, microarray analysis revealed that BPA antagonized the regulation of most T3-response genes, thereby explaining the inhibitory effect of BPA on metamorphosis. Surprisingly, most of the genes affected by BPA in the presence of T3 were T3-response genes, suggesting that BPA predominantly affected T3-signaling pathways during metamorphosis. Our finding that this endocrine disruptor, well known for its estrogenic activity in vitro, functions to inhibit T3 pathways to affect vertebrate development in vivo and thus not only provides a mechanism for the likely deleterious effects of BPA on human development but also demonstrates the importance of studying endocrine disruption in a developmental context in vivo.
Biological and Anatomical Evidence for Kisspeptin Regulation of the Hypothalamic-Pituitary-Gonadal Axis of Estrous Horse Mares
Authors: Magee Christianne , Foradori Chad D. , Bruemmer Jason E. , Arreguin-Arevalo Jesus A. , McCue Patrick M. , Handa Robert J. , Squires Edward L. , Clay Colin M.
Published: February 2009

The purpose of the present study was to evaluate the effects of kisspeptin (KiSS) on LH and FSH secretion in the seasonally estrous mare and to examine the distribution and connectivity of GnRH and KiSS neurons in the equine preoptic area (POA) and hypothalamus. The diestrous mare has a threshold serum gonadotropin response to iv rodent KiSS decapeptide (rKP-10) administration between 1.0 and 500 μg. Administration of 500 μg and 1.0 mg rKP-10 elicited peak, mean, and area under the curve LH and FSH responses indistinguishable to that of 25 μg GnRH iv, although a single iv injection of 1.0 mg rKP-10 was insufficient to induce ovulation in the estrous mare. GnRH and KiSS-immunoreactive (ir) cells were identified in the POA and hypothalamus of the diestrous mare. In addition, KiSS-ir fibers were identified in close association with 33.7% of GnRH-ir soma, suggesting a direct action of KiSS on GnRH neurons in the mare. In conclusion, we are the first to reveal a physiological role for KiSS in the diestrous mare with direct anatomic evidence by demonstrating a threshold-like gonadotropin response to KiSS administration and characterizing KiSS and GnRH-ir in the POA and hypothalamus of the diestrous horse mare.
Tax-Exempt Hospitals and Community Benefits: A Review of State Reporting Requirements
Authors: Hellinger Fred Joseph
Published: February 2009

In June 2007 the Internal Revenue Service proposed a major overhaul of its reporting requirements for tax-exempt hospitals and released draft Form 990 (the IRS form filed by tax-exempt organizations each year). In December 2007 the IRS promulgated the final Form 990 after incorporating some of the recommendations made in the almost seven hundred public comments on the discussion draft. One recommendation adopted in the final Form 990 is the postponement until tax year 2009 (returns filed in 2010) of the requirement for hospitals to submit detailed information on the percentage of total expenses attributable to charity care, unreimbursed Medicaid costs, and community-health improvement programs (the discussion draft required this information for tax year 2007). Although the IRS will not require tax-exempt hospitals to provide detailed information about community benefits until the 2009 tax year, sixteen states have laws requiring tax-exempt hospitals to enumerate the benefits that they provide to the community. Information about the impact of these laws on the provision of community benefits (e.g., charity and uncompensated care) is examined in this study whose primary purpose is to highlight information policy makers may glean from states that have adopted community-benefit reporting laws.
Effects of Regulation and Competition on Health Care Disparities: The Case of Cardiac Angiography in New Jersey
Authors: DeLia Derek , Cantor Joel C. , Tiedemann Amy , Huang Cecilia S.
Published: February 2009

This article evaluates a Certificate of Need (CON) reform in New Jersey that was designed to expand hospital capacity to provide cardiac angiography (CA) and reduce long-standing disparities in access to the procedure. Using data from 1995 to 2004, we find that expanded capacity increased CA utilization overall and did so more rapidly for blacks, leading to a large reduction in the disparity. However, this reduction was not attributable to services provided by new entrants to the CA market, since they were located in mostly white suburban areas. Instead, the new entrants cut into the incumbents' share of white CA patients who had previously traveled from the suburbs to receive the procedure at inner-city incumbent hospitals. As a result, it appears that incumbents were forced to serve more black patients in their local area to maintain their CA volume. These findings suggest that prior restrictions on CA capacity contributed to the historical disparity in access to the procedure.
Effective shock factors for the inelastic damage prediction of clamped plane plates subjected to non-contact underwater explosion
Authors: Rajendran R
Published: February 2009

Shock factors are conventionally used to designate the effect of an underwater explosion on a target. The concept of the effective shock factor was introduced by Rajendran and Narasimhan in a paper entitled ‘A shock factor based approach for the damage assessment of plane plates subjected to underwater explosion’, published in the Journal of Strain Analysis in 2006 (volume 41, issue 6, pages 417–425) for predicting the elastic and yield response of circular and rectangular plates; it was revealed that the coupling factor drastically influences the effect of shock factor on the response of plane plates. It will be of immense use to the designer if effective shock factors are introduced for predicting the inelastic damage of target plates, as shock factors notionally present a pessimistic picture about the damage scenario. The current investigation introduces the concept of effective shock factors to the existing prediction methodologies for estimating inelastic damage of plane plates. Water-backed plate is analysed along with air-backed plates to represent the water-filled side shell of a ship.
The complexity analysis of a machining error propagation network and its application
Authors: Liu D , Jiang P
Published: February 2009

There are some complicated interactions among different stages in multistage machining processes (MMPs), so it is important and necessary to explore the inherent mechanism of machining error propagation for improving product quality. With respect to this issue, a machining error propagation network (MEPN) of MMPs is proposed and its complexity is discussed. In order to establish this MEPN, the machining form feature (MFF) of the workpiece, machine tool, fixture, and cutting tool (i.e. machining element, ME) are defined as different network nodes. The associated relationship among different nodes is mapped by graph theory, according to the computer aided process planning (CAPP) information of the workpiece. Based on this, complex networks theory is introduced to analyse the characteristics of the established MEPN, and several measuring indices of error propagation at different nodes are proposed to quantify the interactions among different nodes. The synthesized propagation index (SPI) is then established to identify the key nodes and the SPI variation curve is used to quantify these key nodes' influences on the MEPN. Finally, a box part of a missile launcher is used to illustrate the proposed methods.
Simulation of shock wave interaction with porous compressible foam
Authors: Igra O , Jiang J P
Published: February 2009

A simple model is proposed for simulating the flow field developed in porous foam as a result of its head-on collision with a planar shock wave. In the model, the foam is simulated by a suspension composed of air and small, rigid spheres. The sphere's drag coefficient is increased beyond its regular level in order to account for the drag acting on the foam resulting from the air being forced to flow through the tortuous passages in the foam. The obtained numerical results are compared with appropriate experimental findings. Based on the obtained good agreement between experiments and simulations, a parametric study on the foam—shock-wave interaction process is conducted. It is shown that although the proposed dusty-gas model is very simple and might not simulate accurately all experimental findings, it certainly represents the main features and mechanism of the considered interaction process.
Satellite formation flying using variable structure model reference adaptive control
Authors: Shahid K , Kumar K D
Published: February 2009

In this paper a variable structure model reference adaptive control technique for spacecraft formation flying is proposed. The system consisting of a leader and a follower satellite is considered. The stability of the proposed controller is established using a Lyapunov function. Also, the robustness of the control law to non-linearities and external disturbances is presented. A reference model suitable for formation reconfiguration is then established. The performance of the proposed controller is tested through numerical simulation of the governing non-linear equations of motion and is applied for both formation keeping and formation reconfiguration. The effect of the control parameters on tracking performance and fuel consumption is examined. The effects of initial state errors, leader satellite eccentricity, constant perturbation, and differential J2 are also considered. The numerical results demonstrate the effectiveness of the proposed control technique for satellite formation flying. In the case of the formation reconfiguration, the proposed controller outperforms the adaptive sliding mode control.
A perturbation approach in determination of closed-loop optimal-fuzzy control policy for planetary landing mission
Authors: Afshari H H , Roshanian J , Novinzadeh A B
Published: February 2009

Development of time-optimal strategy for non-linear problem of planetary landing mission by using perturbation technique is investigated on two scenarios in this study. The first scenario includes finding an optimal control policy for descent in the variable gravitational field of the target planet analytically. In the second scenario, the optimal policy is derived by considering the effect of spacecraft mass variations in an analytic solution. To validate the accuracy of each generated policy, a numeric method such as steepest descent is employed. Afterwards, the fuzzy algorithm is followed to achieve the closed-loop guidance strategy for this non-linear system. The training process of the fuzzy system is based on the achieved perturbation solution of variable mass landing problem by utilizing a set of states-related non-dimensional variables for faster convergence rate. Finally, the lunar landing mission is demonstrated as a viable example of the non-linear planetary landing mission. Simulation results show that the presented optimal guidance laws are so effective which can be utilized in the real world spacecraft applications.
Flow over an aerofoil without and with a leading-edge slat at a transitional Reynolds number
Authors: Genç M S , Kaynak Ü , Lock G D
Published: February 2009

In this study, a multi-element aerofoil including NACA2415 aerofoil with NACA22 leading-edge slat is experimentally and computationally investigated at a transitional Reynolds number of 2×105. In the experiment, the single-element aerofoil experiences a laminar separation bubble, and a maximum lift coefficient of 1.3 at a stall angle of attack of 12° is obtained. This flow has been numerically simulated by FLUENT, employing the recently developed, k— kL—ω and k—ω shear—stress transport (SST) transition models. Both transition models are shown to accurately predict the location of the experimentally determined separation bubble. Experimental measurements also illustrate that the leading-edge slat significantly delays the stall up to an angle of attack of 20°, with a maximum lift coefficient of 1.9. The fluid dynamics governing this improvement is the elimination of the separation bubble by the injection of high momentum fluid through the slat over the main aerofoil — an efficient means of flow control. Numerical simulations using k— kL—ω are shown to accurately predict the lift curve, including stall, but not the complete elimination of the separation bubble. Conversely, the lift curve prediction using the k—ω SST transition model is less successful, but the separation bubble is shown to fully vanish in agreement with the experiment.
The influence of sea water in oil emulsion on bearing performance
Authors: Liu H , Xu H , Zhang Y , Ji H , Ge Y , Ellison P , Jin Z
Published: February 2009

The lubricant in the bearings of ships can be easily polluted by sea water. Too much sea water may deteriorate the bearing performance and result in catastrophic failure; therefore, the lubricant should be changed regularly to prevent this. It is important to investigate the effect of adding sea water to mineral oil on the tribological performance of these bearings. In the present study, different amounts of sea water of 1, 2, and 3 per cent (by mass) were mixed with a typical mineral oil with a viscosity of 46 mm2/s at 40 °C and tested in 12 identical journal bearings under different operation conditions of rotational speed and load. For each case, the temperature within the oil film, the loci of the shaft centre, the power consumption, and the viscosity of the emulsion were measured. In parallel to these measurements, a CFD simulation was performed for the test bearings to estimate the friction force and load capacity. The experimental measurements and the computational predictions were compared. A maximum amount of sea water that can be tole-rated in the mineral oil was established for the normal working conditions of the journal bearing.
The effect of load and viscosity on the minimum operating oil film thickness of piston-rings in internal combustion engines
Authors: Söchting S J , Sherrington I
Published: February 2009

Computer simulations are now routinely used in the design and analysis of ring packs for internal combustion engines. Commonly they predict that an increase in engine load decreases minimum operating film thickness because oil availability and oil transport through the ring pack are reduced under these conditions. To assess the reliability of new simulations, investigators compare the output of computer models with experimental measurements of parameters on operating engines. Contributing to this process this paper presents an experimental study of an investigation into the effect of load on the minimum oil film thickness between piston rings and cylinder liner in a fired compression ignition engine. Oil film thickness data were collected using capacitance-based transducers located near top dead centre and mid-stroke. Experiments were performed at 2000 r/min using two mono-grade oils (SAE 50 and SAE 20) and one multi-grade oil (SAE 5W50) under a range of fixed engine loads. The experimental data obtained are discussed in the context of experimental and theoretical work published by other investigators.
The influence of swing phase load on the electrochemical response, friction, and ion release of metal-on-metal hip prostheses in a friction simulator
Authors: Yan Y , Neville A , Dowson D , Williams S , Fisher J
Published: February 2009

Second-generation metal-on-metal (MoM) hip replacements have been considered as an alternative to commonly used polyethylene-on-metal joint prostheses due to polyethylene wear debris-induced osteolysis. However, the role of corrosion is still not fully understood. Bench tests have been carried out to characterize the relationship and interactions between electrochemical reactions ( corrosion), mechanical damage ( wear), and biological environments. An investigation of the corrosion response of MoM hip replacements has been conducted in a friction simulator in an initial attempt to reveal the tribocorrosion behaviour of clinically used metallic hip implants. These are the first reported results where electrochemical measurements have been made in-situ in a joint simulator.

A ProSim friction simulator was used with an integrated electrochemical cell in this study of biotribocorrosion. Peak loads of 2 kN with three different swing phase loads, 25, 100, and 300 N were used to determine the effect of different swing loads on the corrosion processes (through electrochemical measurements and the release of metal ions). The three lubricants, NaCl solution, 25 per cent serum, and bovine synovial fluid, were employed as lubricants in this study. All femoral heads of the tested hip implants were 36 mm in diameter and made from a CoCrMo alloy. The open circuit potential (OCP) was monitored while implants were subjected to dynamic loading cycles. The link between swing phase load, lubricant, and ion release is discussed in relation to corrosion processes occurring at the tribological interface.