bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of rat lung-specific microRNAs by microRNA microarray: valuable discoveries for the facilitation of lung research
Authors: Wang Yang , Weng Tingting , Gou Deming , Chen Zhongming , Chintagari Narendranath Reddy , Liu Lin 
Published: January 2007

Abstract

Background
An important mechanism for gene regulation utilizes small non-coding RNAs called microRNAs (miRNAs). These small RNAs play important roles in tissue development, cell differentiation and proliferation, lipid and fat metabolism, stem cells, exocytosis, diseases and cancers. To date, relatively little is known about functions of miRNAs in the lung except lung cancer.

Results
In this study, we utilized a rat miRNA microarray containing 216 miRNA probes, printed in-house, to detect the expression of miRNAs in the rat lung compared to the rat heart, brain, liver, kidney and spleen. Statistical analysis using Significant Analysis of Microarray (SAM) and Tukey Honestly Significant Difference (HSD) revealed 2 miRNAs (miR-195 and miR-200c) expressed specifically in the lung and 9 miRNAs co-expressed in the lung and another organ. 12 selected miRNAs were verified by Northern blot analysis.

Conclusion
The identified lung-specific miRNAs from this work will facilitate functional studies of miRNAs during normal physiological and pathophysiological processes of the lung.
A proteomic study of Corynebacterium glutamicumAAA+ protease FtsH
Authors: Lüdke Alja , Krämer Reinhard , Burkovski Andreas , Schluesener Daniela , Poetsch Ansgar 
Published: January 2007

Abstract

Background
The influence of the membrane-bound AAA+ protease FtsH on membrane and cytoplasmic proteins of Corynebacterium glutamicum was investigated in this study. For the analysis of the membrane fraction, anion exchange chromatography was combined with SDS-PAGE, while the cytoplasmic protein fraction was studied by conventional two-dimensional gel electrophoresis.

Results
In contrast to the situation in other bacteria, deletion of C. glutamicum ftsH has no significant effect on growth in standard minimal medium or response to heat or osmotic stress. On the proteome level, deletion of the ftsH gene resulted in a strong increase of ten cytoplasmic and membrane proteins, namely biotin carboxylase/biotin carboxyl carrier protein (accBC), glyceraldehyde-3-phosphate dehydrogenase (gap), homocysteine methyltransferase (metE), malate synthase (aceB), isocitrate lyase (aceA), a conserved hypothetical protein (NCgl1985), succinate dehydrogenase A (sdhA), succinate dehydrogenase B (sdhB), succinate dehydrogenase CD (sdhCD), and glutamate binding protein (gluB), while 38 cytoplasmic and membrane-associated proteins showed a decreased abundance. The decreasing amount of succinate dehydrogenase A (sdhA) in the cytoplasmic fraction of the ftsH mutant compared to the wild type and its increasing abundance in the membrane fraction indicates that FtsH might be involved in the cleavage of a membrane anchor of this membrane-associated protein and by this changes its localization.

Conclusion
The data obtained hint to an involvement of C. glutamicum FtsH protease mainly in regulation of energy and carbon metabolism, while the protease is not involved in stress response, as found in other bacteria.
Therapeutic effect of all-trans-retinoic acid (at-RA) on an autoimmune nephritis experimental model: role of the VLA-4 integrin
Authors: Escribese María M , Conde Elisa , Martín Ana , Sáenz-Morales David , Sancho David , de Lema Guillermo Pérez , Lucio-Cazaña Javier , Sánchez-Madrid Francisco , García-Bermejo María L , Mampaso Francisco M 
Published: January 2007

AbstractBackgroundMercuric chloride (HgCl2) induces an autoimmune nephritis in the Brown Norway (BN) rats characterized by anti-glomerular basement membrane antibodies (anti-GBM Ab) deposition, proteinuria and a severe interstitial nephritis, all evident at day 13 of the disease. We assessed the effects of all-trans retinoic acid (at-RA) in this experimental model. At-RA is a vitamin A metabolite which has shown beneficial effects on several nephropathies, even though no clear targets for at-RA were provided.MethodsWe separated animals in four different experimental groups (HgCl2, HgCl2+at-RA, at-RA and vehicle). From each animal we collected, at days 0 and 13, numerous biological samples: urine, to measure proteinuria by colorimetry; blood to determine VLA-4 expression by flow citometry; renal tissue to study the expression of VCAM-1 by Western blot, the presence of cellular infiltrates by immunohistochemistry, the IgG deposition by immunofluorescence, and the cytokines expression by RT-PCR. Additionally, adhesion assays to VCAM-1 were performed using K562 α4 transfectant cells. ANOVA tests were used for statistical significance estimation.ResultsWe found that at-RA significantly decreased the serum levels of anti-GBM and consequently its deposition along the glomerular membrane. At-RA markedly reduced proteinuria as well as the number of cellular infiltrates in the renal interstitium, the levels of TNF-α and IL-1β cytokines and VCAM-1 expression in renal tissue. Moreover, we reported here for the first time in anin vivomodel that at-RA reduced, to basal levels, the expression of VLA-4 (α4β1) integrin induced by mercury on peripheral blood leukocytes (PBLs). In addition, using K562 α4 stable transfectant cells, we found that at-RA inhibited VLA-4 dependent cell adhesion to VCAM-1.ConclusionHere we demonstrate a therapeutic effect of at-RA on an autoimmune experimental nephritis model in rats. We report a significant reduction of the VLA-4 integrin expression on PBLs as well as the inhibition of the VLA4/VCAM1-dependent leukocyte adhesion by at-RA treatment. Thereby we point out the VLA-4 integrin as a target for at-RAin vivo.
Primary sclerosing cholangitis – The arteriosclerosis of the bile duct?
Authors: Fickert Peter , Moustafa Tarek , Trauner Michael 
Published: January 2007

Abstract
Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of unknown aetiology affecting the large bile ducts and characterized by periductal fibrosis and stricture formation, which ultimately result in biliary cirrhosis and liver failure. Arteriosclerosis involves the accumulation of altered lipids and lipoproteins in large arteries; this drives inflammation and fibrosis and ultimately leads to narrowing of the arteries and hypoperfusion of dependent organs and tissues.
Knowledge of the causative factors is crucial to the understanding of disease mechanisms and the development of specific treatment. Based on pathogenetic similarities between PSC and arteriosclerosis, we hypothesize that PSC represents
"arteriosclerosis of the bile duct"
initiated by toxic biliary lipids. This hypothesis is based on common molecular, cellular, and morphological features providing the conceptual framework for a deeper understanding of their pathogenesis. This hypothesis should stimulate translational research to facilitate the search for novel treatment strategies for both diseases.
Overdose prevention for injection drug users: Lessons learned from naloxone training and distribution programs in New York City
Authors: Piper Tinka Markham , Rudenstine Sasha , Stancliff Sharon , Sherman Susan , Nandi Vijay , Clear Allan , Galea Sandro 
Published: January 2007

Abstract

Background
Fatal heroin overdose is a significant cause of mortality for injection drug users (IDUs). Many of these deaths are preventable because opiate overdoses can be quickly and safely reversed through the injection of Naloxone [brand name Narcan], a prescription drug used to revive persons who have overdosed on heroin or other opioids. Currently, in several cities in the United States, drug users are being trained in naloxone administration and given naloxone for immediate and successful reversals of opiate overdoses. There has been very little formal description of the challenges faced in the development and implementation of large-scale IDU naloxone administration training and distribution programs and the lessons learned during this process.

Methods
During a one year period, over 1,000 participants were trained in SKOOP (Skills and Knowledge on Opiate Prevention) and received a prescription for naloxone by a medical doctor on site at a syringe exchange program (SEP) in New York City. Participants in SKOOP were over the age of 18, current participants of SEPs, and current or former drug users. We present details about program design and lessons learned during the development and implementation of SKOOP. Lessons learned described in the manuscript are collectively articulated by the evaluators and implementers of the project.

Results
There were six primary challenges and lessons learned in developing, implementing, and evaluating SKOOP. These include a) political climate surrounding naloxone distribution; b) extant prescription drug laws; c) initial low levels of recruitment into the program; d) development of participant appropriate training methodology; e) challenges in the design of a suitable formal evaluation; and f) evolution of program response to naloxone.

Conclusion
Other naloxone distribution programs may anticipate similar challenges to SKOOP and we identify mechanisms to address them. Strategies include being flexible in program planning and implementation, developing evaluation instruments for feasibility and simplicity, and responding to and incorporating feedback from participants.
Resistance of the target islet tissue to autoimmune destruction contributes to genetic susceptibility in Type 1 diabetes
Authors: Hill Natasha J , Stotland Aleksandr , Solomon Michelle , Secrest Patrick , Getzoff Elizabeth , Sarvetnick Nora 
Published: January 2007

AbstractAbstractType 1 diabetes occurs when self-reactive T lymphocytes destroy the insulin-producing islet β cells of the pancreas. The defects causing this disease have often been assumed to occur exclusively in the immune system. We present evidence that genetic variation at theIdd9diabetes susceptibility locus determines the resilience of the targets of autoimmunity, the islets, to destruction. Susceptible islets exhibit hyper-responsiveness to inflammatory cytokines resulting in enhanced cell death and increased expression of the death receptor Fas. Fas upregulation in β cells is mediated by TNFR2, and colocalization of TNFR2 with the adaptor TRAF2 in NOD β cells is altered.TNFR2lies within the candidateIdd9interval and the diabetes-associated variant contains a mutation adjacent to the TRAF2 binding site. A component of diabetes susceptibility may therefore be determined by the target of the autoimmune response, and protective TNFR2 signaling in islets inhibit early cytokine-induced damage required for the development of destructive autoimmunity.ReviewersThis article was reviewed by Matthiasvon Herrath, HaraldVon Boehmer, and Ciriaco Piccirillo (nominated by Ethan Shevach).
Gene therapy with an improved doxycycline-regulated plasmid encoding a tumour necrosis factor-alpha inhibitor in experimental arthritis
Authors: Gould David , Yousaf Nasim , Fatah Rewas , Subang Maria Cristina , Chernajovsky Yuti 
Published: January 2007

Abstract
Inhibition of tumour necrosis factor (TNF)-alpha with biological molecules has proven an effective treatment for rheumatoid arthritis, achieving a 20% improvement in American College of Rheumatology score in up to 65% of patients. The main drawback to these and many other biological treatments has been their expense, which has precluded their widespread application. Biological molecules could alternatively be delivered by gene therapy as the encoding DNA. We have developed novel plasmid vectors termed pGTLMIK and pGTTMIK, from which luciferase and a dimeric TNF receptor II (dTNFR) are respectively expressed in a doxycycline (Dox)-regulated manner. Regulated expression of luciferase from the self-contained plasmid pGTLMIK was examined in vitro in a variety of cell lines and in vivo following intramuscular delivery with electroporation in DBA/1 mice. Dox-regulated expression of luciferase from pGTLMIK of approximately 1,000-fold was demonstrated in vitro, and efficient regulation was observed in vivo. The vector pGTTMIK encoding dTNFR was delivered by the same route with and without administration of Dox to mice with collagen-induced arthritis. When pGTTMIK was delivered after the onset of arthritis, progression of the disease in terms of both paw thickness and clinical score was inhibited when Dox was also administered. Vectors with similar regulation characteristics may be suitable for clinical application.
Diet and body constitution in relation to subgroups of breast cancer defined by tumour grade, proliferation and key cell cycle regulators
Authors: Borgquist Signe , Wirfält Elisabet , Jirström Karin , Anagnostaki Lola , Gullberg Bo , Berglund Göran , Manjer Jonas , Landberg Göran 
Published: January 2007

Abstract
Background
The general lack of clear associations between diet and breast cancer in epidemiological studies may partly be explained by the fact that breast cancer is a heterogeneous disease that may have disparate genetic associations and different aetiological bases.

Method
A total of 346 incident breast cancers in a prospective cohort of 17,035 women enrolled in the Malmö Diet and Cancer study (Sweden) were subcategorized according to conventional pathology parameters, proliferation and expression of key cell cycle regulators. Subcategories were compared with prediagnostic diet and body measurements using analysis of variance.

Results
A large hip circumference and high body mass index were associated with high grade tumours (P = 0.03 and 0.009, respectively), whereas low energy and unadjusted fat intakes were associated with high proliferation (P = 0.03 and 0.004, respectively). Low intakes of saturated, monounsaturated and polyunsaturated fatty acids were also associated with high proliferation (P = 0.02, 0.004 and 0.003, respectively). Low energy and unadjusted fat intakes were associated with cyclin D1 overexpression (P = 0.02 and 0.007, respectively), whereas cyclin E overexpression was positively correlated with fat intake. Oestrogen receptor status and expression of the tumour suppressor gene p27 were not associated with either diet or body constitution.

Conclusion
Low energy and low total fat (polyunsaturated fatty acids in particular) intakes, and high body mass index were associated with relatively more malignant breast tumours. Dietary behaviours and body constitution may be associated with specific types of breast cancer defined by conventional pathology parameters and cyclin D1 and cyclin E expression. Further studies including healthy control individuals are needed to confirm our results.
Outcomes of Patients with Prostate Cancer Receiving Zoledronic Acid or Pamidronate for Prevention of Skeletal‐Related Events
Authors: Sherer Jeffrey T. , Adamus Andrea T. 
Published: January 2007

Study Objective. To determine the relative effectiveness of two bisphosphonates—pamidronate and zoledronic acid—for preventing skeletal‐related events (SREs) in patients with prostate cancer metastatic to bone.Design. Retrospective cohort study.Setting. Large, tertiary care cancer center.Patients. One hundred thirty‐seven patients with a diagnosis of prostate cancer who received either pamidronate or zoledronic acid between January 1, 1998, and December 31, 2004, were identified in the electronic medical records; 24 of these patients met all prespecified eligibility criteria, and 105 patients met relaxed eligibility criteria.Measurements and Main Results. Using a binary logistic regression model, we explored the effect of the bisphosphonate received on development of an SRE. Whether the patient was receiving chemotherapy as of the date of first receipt of a study drug, the number of bisphosphonate doses received, time since the diagnosis of prostate cancer, and the number of previous SREs were included as covariates. The odds ratio for developing an SRE after receiving zoledronic acid was 0.80 (95% confidence interval 0.08–7.50) compared with the reference group that received pamidronate. This difference did not reach statistical significance (p=0.84). Because of the limited number of patients who met all prespecified eligibility criteria, various post hoc analyses were performed in the 105 patients with use of relaxed eligibility criteria. None provided definitive evidence of the superiority of one agent versus the other.Conclusion. No definitive evidence of a difference in the efficacy for preventing the development of an SRE was found between pamidronate and zoledronic acid, although a smaller‐than‐expected sample size impairs the interpretability of this finding. In the absence of additional research, it seems reasonable to assume that no clinically important difference exists between the two agents.
Extrapolation designs with constraints
Authors: Fang Zhide 
Published: January 2007

AbstractThe author considers (asymptotically) minimax extrapolation designs for an approximately multiple linear model with the model contaminant f being restricted only by its L2norm. He splits the integrated mean squared prediction error (IMSPE) of the fitted value over the extrapolation space into two parts, namely the integrated prediction variance (IPV) and the integrated prediction bias (IPB). For a spherical design space and an annular extrapolation space, he constructs the design that minimizes the maximum value, over f, of IPB subject to bounding IPV. He also constructs the design that minimizes IPV subject to bounding the maximum IPB.
On blest's measure of rank correlation
Authors: Genest Christian , Plante Jean‐François 
Published: January 2007

AbstractBlest (2000) proposed a new nonparametric measure of correlation between two random variables. His coefficient, which is dissymmetric in its arguments, emphasizes discrepancies observed among the first ranks in the orderings induced by the variables. The authors derive the limiting distribution of Blest's index and suggest symmetric variants whose merits as statistics for testing independence are explored using asymptotic relative efficiency calculations and Monte Carlo simulations.
Empirical likelihood confidence intervals for the mean of a population containing many zero values
Authors: Chen Jiahua , Chen Shun‐Yi , Rao J. N. K. 
Published: January 2007

AbstractIf a population contains many zero values and the sample size is not very large, the traditional normal approximation‐based confidence intervals for the population mean may have poor coverage probabilities. This problem is substantially reduced by constructing parametric likelihood ratio intervals when an appropriate mixture model can be found. In the context of survey sampling, however, there is a general preference for making minimal assumptions about the population under study. The authors have therefore investigated the coverage properties of nonparametric empirical likelihood confidence intervals for the population mean. They show that under a variety of hypothetical populations, these intervals often outperformed parametric likelihood intervals by having more balanced coverage rates and larger lower bounds. The authors illustrate their methodology using data from the Canadian Labour Force Survey for the year 2000.
The historical functional linear model
Authors: Malfait Nicole , Ramsay James O. 
Published: January 2007

AbstractThe authors develop a functional linear model in which the values at time t of a sample of curves yi (t) are explained in a feed‐forward sense by the values of covariate curves xi(s) observed at times s ±.t. They give special attention to the case s ± [t — δ, t], where the lag parameter δ is estimated from the data. They use the finite element method to estimate the bivariate parameter regression function β(s, t), which is defined on the triangular domain s ± t. They apply their model to the problem of predicting the acceleration of the lower lip during speech on the basis of electromyographical recordings from a muscle depressing the lip. They also provide simulation results to guide the calibration of the fitting process.
Adaptive tests of regression functions via multiscale generalized likelihood ratios
Authors: Zhang Chunming M. 
Published: January 2007

AbstractMany applications of nonparametric tests based on curve estimation involve selecting a smoothing parameter. The author proposes an adaptive test that combines several generalized likelihood ratio tests in order to get power performance nearly equal to whichever of the component tests is best. She derives the asymptotic joint distribution of the component tests and that of the proposed test under the null hypothesis. She also develops a simple method of selecting the smoothing parameters for the proposed test and presents two approximate methods for obtaining its P‐value. Finally, she evaluates the proposed test through simulations and illustrates its application to a set of real data.
Optimal design for the proportional odds model
Authors: Perevozskaya Inna , Rosenberger William F. , Haines Linda M. 
Published: January 2007

AbstractThe authors construct locally optimal designs for the proportional odds model for ordinal data. While they investigate the standard D‐optimal design, they also investigate optimality criteria for the simultaneous estimation of multiple quantiles, namely DA‐optimality and the omnibus criterion. The design of experiments for the simultaneous estimation of multiple quantiles is important in both toxic and effective dose studies in medicine. As with c‐optimality in the binary response problem, the authors find that there are distinct phase changes when exploring extreme quantiles that require additional design points. The authors also investigate relative efficiencies of the criteria.
A note on penalized minimum distance estimation in nonparametric regression
Authors: Bunea Florentina , Wegkamp Marten H. 
Published: January 2007

AbstractThe authors introduce a penalized minimum distance regression estimator. They show the estimator to balance, among a sequence of nested models of increasing complexity, the L1 ‐approximation error of each model class and a penalty term which reflects the richness of each model and serves as a upper bound for the estimation error.
On testing for multivariate ARCH effects in vector time series models
Authors: Duchesne Pierre , Lalancette Simon 
Published: January 2007

AbstractUsing a spectral approach, the authors propose tests to detect multivariate ARCH effects in the residuals from a multivariate regression model. The tests are based on a comparison, via a quadratic norm, between the uniform density and a kernel‐based spectral density estimator of the squared residuals and cross products of residuals. The proposed tests are consistent under an arbitrary fixed alternative. The authors present a new application of the test due to Hosking (1980) which is seen to be a special case of their approach involving the truncated uniform kernel. However, they typically obtain more powerful procedures when using a different weighting. The authors consider especially the procedure of Robinson (1991) for choosing the smoothing parameter of the spectral density estimator. They also introduce a generalized version of the test for ARCH effects due to Ling & Li (1997). They investigate the finite‐sample performance of their tests and compare them to existing tests including those of Ling & Li (1997) and the residual‐based diagnostics of Tse (2002).Finally, they present a financial application.
The analysis of unreplicated factorial experiments from a geometric perspective
Authors: Miller Arden E. 
Published: January 2007

AbstractThe author investigates the analysis of unreplicated factorial experiments from a geometric perspective. He considers more specifically a (k + 1)‐run experiment used to estimate k orthogonal contrasts. He observes that once centered and scaled to unit length, the response vector can be viewed as a point on the unit sphere in the vector space spanned by the contrasts. In this context, a model selection procedure is equivalent to a partition of the unit sphere into regions corresponding to the different models considered. The author exploits this approach to gain useful insights into the analysis of such experiments.