bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclostratigraphic record of the Triassic: a critical examination
Authors: Tanner Lawrence H. 
Published: June 2010

Abstract
High frequency (fourth- and fifth-order) cyclicity is a common feature of sedimentary sequences in all depositional settings. While tectonism and autocyclic processes are clearly responsible for this cyclicity in some instances, many cases are interpreted as resulting from orbitally forced variations in solar insolation at the Milankovitch frequencies, that is, the precession and short and long eccentricity cycles at scales of tens of thousands to hundreds of thousands of years. This forcing is presumed to have controlled sedimentation through periodic changes in climate or sea-level. Examples of interpreted Milankovitch-frequency cyclicity occur throughout the Triassic record, and include much of the German Triassic, the Alpine Triassic and the Newark Supergroup of North America. The cyclostratigraphy of these sections has been used as a tool for intrabasinal and interbasinal correlation, and for chronostratigraphy. These interpretations are not always without controversy, however, as conceptual arguments and radio–isotopic age data have called some of these conclusions into question.
CYP2D6 Polymorphisms as Predictors of Outcome in Breast Cancer Patients Treated with Tamoxifen: Expanded Polymorphism Coverage Improves Risk Stratification
Authors: Schroth Werner , Hamann Ute , Fasching Peter A. , Dauser Silke , Winter Stefan , Eichelbaum Michel , Schwab Matthias , Brauch Hiltrud 
Published: June 2010

Abstract
Purpose: This study aimed to validate matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS)/Taqman copy number assay (CNA) CYP2D6 genotyping by AmpliChip CYP450 Test for the prediction of tamoxifen metabolizer phenotypes in breast cancer, and to investigate the influence of CYP2D6 variant coverage on genotype-phenotype relationships and tamoxifen outcome.
Experimental Design: Hormone receptor–positive postmenopausal breast cancer patients (n = 492) treated with adjuvant tamoxifen, previously analyzed by MALDI-TOF MS/CNA, were reanalyzed by AmpliChip CYP450 Test and validated by independent methods. Cox proportional hazard ratios (HR) were calculated for recurrence of poor (PM) relative to extensive metabolizer (EM) phenotypes with increasing numbers of CYP2D6 variants. Kaplan-Meier distributions were calculated for different phenotype classifications.
Results: Concordance was 99.2% to 99.5% for CNA and 99.8% to 100% per CYP2D6 allele (*3, *4, *5, *9, *10, and *41). The prevalence of predicted phenotypes was 1.2% for ultrarapid metabolizer (UM), 37.2% for EM without variant, 43.5% for heterozygous EM, 9.7% for intermediate metabolizer (IM), and 8.3% for PM. Approximately, one third of patients were misclassified based on a *4 analysis only, but inclusion of all reduced-function alleles increased the PM-associated HR from 1.33 (P = 0.58) to 2.87 (P = 0.006). Kaplan-Meier analyses showed highest and lowest clinical benefit for UM and PM with respect to both the AmpliChip-based and a redefined phenotype assignment. The latter revealed significant allele–dose-dependent associations (P = 0.011) and largest effect size (HRPM_EM = 2.77; 95% confidence interval, 1.31-5.89).
Conclusions: MALDI-TOF MS/CNA is suitable for accurate CYP2D6 genotyping. For tamoxifen pharmacogenetics, broad CYP2D6 allele coverage is recommended to reduce phenotype misclassification. Classification based on refined EM and reduced-function metabolizers is advisable. Clin Cancer Res; 16(17); 4468–77. ©2010 AACR.
A Preclinical Study on the Rescue of Normal Tissue by Nicotinic Acid in High-Dose Treatment with APO866, a Specific Nicotinamide Phosphoribosyltransferase Inhibitor
Authors: Olesen Uffe Høgh , Thougaard Annemette V. , Jensen Peter Buhl , Sehested Maxwell 
Published: June 2010

Abstract
Inhibitor of nicotinamide phosphoribosyltransferase APO866 is a promising cancer drug currently in phase II clinical trials in oncology. Here, we present a strategy for increasing the therapeutic potential of APO866 through the rescue of normal tissues by coadministration of nicotinic acid (Vitamin B3). We examined the toxicity profile of APO866 in B6D2F1 mice and the effect of oral administration of nicotinic acid on tissue toxicity. Nicotinic acid (50 mg/kg) protects mice from death and severe toxicity from an APO866 dose (60 mg/kg) four times the monotherapy maximum tolerated dose (15 mg/kg). In a panel of six cancer cell lines, we find that three (including ML-2 cells) are protected by nicotinic acid in vitro, whereas the cytotoxicity of APO866 remains unaffected in the remaining three (including A2780 cells). A selective biomarker for the protection by nicotinic acid was subsequently identified by quantitative RT-PCR. The expression of nicotinic acid phosphoribosyltransferase is low in the cell lines not rescued from APO866 by nicotinic acid compared with protected cell lines. The findings in cell lines translated into xenograft models in which the combination of 50 mg/kg nicotinic acid and 50 mg/kg APO866 in mouse xenografts of A2780 cells increased life span by &gt;3-fold compared with standard treatment of 15 mg/kg, and the effect of APO866 was clearly decreased when using the same treatment paradigm in ML-2 xenografts. In conclusion, the combination of high doses of APO866 with rescue by nicotinic acid may significantly increase the therapeutic potential in a subset of cancers with low expression of nicotinic acid phosphoribosyltransferase. Mol Cancer Ther; 9(6); 1609–17. ©2010 AACR.
The NF-κB Inhibitor LC-1 Has Single Agent Activity in Multiple Myeloma Cells and Synergizes with Bortezomib
Authors: Walsby Elisabeth J. , Pratt Guy , Hewamana Saman , Crooks Peter A. , Burnett Alan K. , Fegan Chris , Pepper Chris 
Published: June 2010

AbstractMultiple myeloma remains incurable with conventional therapeutics. Thus, new treatments for this condition are clearly required. In this study we evaluated the novel NF-κB inhibitor LC-1 in multiple myeloma cell lines and plasma cells derived from multiple myeloma patients. LC-1 was cytotoxic to multiple myeloma cell lines H929, U266, and JJN3, and induced apoptosis in a dose-dependent manner with an overall LD50 of 3.6 μmol/L (±1.8) after 48 hours in culture. Primary multiple myeloma cells, identified by CD38 and CD138 positivity, had a mean LD50 for LC-1 of 4.9 μmol/L (±1.6); normal bone marrow cells were significantly less sensitive to the cytotoxic effects of LC-1 (P = 0.0002). Treatment of multiple myeloma cell lines with LC-1 resulted in decreased nuclear localization of the NF-κB subunit Rel A and the inhibition of NF-κB target genes. In addition, LC-1 showed synergy with melphalan, bortezomib, and doxorubicin (combination indices of 0.72, 0.61, and 0.78, respectively), and was more effective when cells were cultured on fibronectin. These data show that LC-1 has activity in multiple myeloma cell lines and primary multiple myeloma cells, and its ability to inhibit NF-κB seems important for its cytotoxic effects. Furthermore, LC-1–induced transcriptional suppression of survivin and MCL1 provides a potential explanation for its synergy with conventional agents. Mol Cancer Ther; 9(6); 1574–82. ©2010 AACR.
Age-related variation in threat-sensitive behavior exhibited by spotted hyenas: observational and experimental approaches
Authors: Pangle Wiline , Holekamp Kay 
Published: June 2010

AbstractWe examined ontogenetic variation in threat-sensitive behaviors exhibited by spotted hyenas (Crocuta crocuta). We documented naturally-occurring vigilance throughout ontogeny, and used playback experiments to evaluate age-related variation in hyenas' responses to control sounds or lion roars. We inquired whether juveniles respond to lions more cautiously than do adults. Naturalistic observations showed that juveniles are less vigilant than adults when no immediate threat is present, but more vigilant than adults when lions are present. Our playback experiments revealed that both adult and juvenile hyenas moved in response to lion roars but not to control sounds, and their reactions were stronger to roars emitted by male than female lions. However, juveniles showed a stronger response to lions than adults, as expressed by spending more time avoiding speakers after roar onset, and by having a shorter latency to first movement than adults. Like adults, juvenile hyenas, thus, appear to recognize certain signals as dangerous and respond accordingly. However, our data suggest that young hyenas may need experience with danger early in life to learn the environmental circumstances under which they ought to be vigilant when no threat is immediately apparent.
Truth, Reality and Temporality: Tractarian Visions
Authors: Bassols Alejandro Tomasini 
Published: June 2010

AbstractLudwig Wittgenstein's Tractatus Logico-Philosophicus sketches a formal view of language, reality and truth. On this account, the work only offers a purely abstract picture of the world. Wittgenstein makes clear that in order to explain the sense and the truth of our propositions we have to appeal to notions like ostension (showing) and verification. From this perspective, it turns out that everything we say is one way or another verified in the present. In particular, our past-tense propositions are verified now, i.e., in the present. Thus Wittgenstein links his formal ontology, his Picture Theory and what I refer to as his 'logical theory of truth' with an appealing solipsistic stance. From this perspective, temporality just vanishes as a feature of reality. It is always now that the world is the totality of facts.
School Counselors’ Perceptions and Experience With Acceleration as a Program Option for Gifted and Talented Students
Authors: Wood Susannah , Portman Tarrell Awe Agahe , Cigrand Dawnette L. , Colangelo Nicholas 
Published: June 2010

This article presents findings from a national survey of 149 practicing school counselors who are members of the American School Counselor Association. The survey gathered information on school counselors’ perceptions of and experiences with acceleration as a program option for gifted students. Results indicate that, although school counselors’ opinions are being solicited in decision making regarding acceleration, they do not possess training and accurate information regarding acceleration. Hence, training and professional development focusing on the research-based practices of acceleration are needed to ensure that school counselors give accurate advice and guidance concerning gifted students’ education. Future research is needed to compare and contrast the effectiveness of accelerative decision making between school counselors who are trained and untrained in acceleration programmatic options. Putting the Research to Use School counselors are ubiquitous to schools and it is expected that they will assume an important role in the academic planning of students. In addition, they are looked to for consultation on the social and emotional development of students and how these dimensions may help or hinder academic choices. This study indicates that school counselors are prominent in the academic and social issues of gifted students when it comes to the issue of acceleration. Parents and educators do look to counselors for information and perspective regarding acceleration and counselors do provide their perspective. Also, acceleration has become a more prominent option for gifted students in schools. Unfortunately, the information and perspectives of school counselors on acceleration is not based on formal training and familiarity with the research but on informal information and limited knowledge of the research. School counselors are not well prepared to fulfill their role in helping parents, educators and students make sound decisions regarding acceleration. This study makes it clear that there is need for formal training of school counselors in the research and practice of acceleration both at the preservice and inservice levels. School counselors should participate in acceleration decisions because they bring a general and comprehensive understanding of the student. However, they need a specific understanding of acceleration in order to be effective in such decisions.
Continuous Passive Motion, Early Weight Bearing, and Active Motion following Knee Articular Cartilage Repair
Authors: Howard Jennifer S. , Mattacola Carl G. , Romine Spencer E. , Lattermann Christian 
Published: June 2010

Objective: To systematically review the literature regarding postoperative rehabilitation for articular cartilage repair: (1) does the use of continuous passive motion (CPM) enhance healing, and if so, what parameters should be applied? (2) Can active range of motion (AROM) be used in place of or with CPM? (3) When can individuals safely resume weight bearing (WB) following repair? Data Sources: A search using Medline, SportsDiscus, and CINAHL databases was performed with the following keywords: articular cartilage, AROM, CPM, microfracture, osteochondral allograft, autologous chondrocyte implantation, rehabilitation, weight bearing, and knee. Study Selection: Basic science or clinical outcomes examining the effects of CPM, AROM, or WB on knee articular cartilage healing. Data Extraction: Selected articles were rated using the Strength of Recommendation Taxonomy (SORT) to determine evidence for clinical application. Data Synthesis: Sixteen articles met selection criteria: 12 were basic science studies; 4 were clinical studies. Basic science evidence supporting CPM exists. However, few patient-oriented outcomes have been documented resulting in a SORT rating of C. Early WB and AROM received a SORT rating of B based on limited clinical research and patient-oriented outcomes. Conclusions: Basic science evidence supports CPM to maintain ROM, reduce pain, and promote healing. Patient-oriented research is needed to strengthen CPM’s recommendation. Limited evidence exists regarding early WB and AROM post cartilage repair. There is insufficient evidence to confidently address when to begin WB for maximum healing. Appropriate basic science and patient-oriented research are needed for rehabilitation protocols to maximize benefits of cartilage repair procedures.
Mitochondrial cytochrome redox states and respiration in acute pulmonary oxygen sensing
Authors: Sommer N. , Pak O. , Schörner S. , Derfuss T. , Krug A. , Gnaiger E. , Ghofrani H.A. , Schermuly R.T. , Huckstorf C. , Seeger W. , Grimminger F. , Weissmann N. 
Published: June 2010

Hypoxic pulmonary vasoconstriction (HPV) is an essential mechanism to optimise lung gas exchange. We aimed to decipher the proposed oxygen sensing mechanism of mitochondria in HPV.Cytochrome redox state was assessed by remission spectrophotometry in intact lungs and isolated pulmonary artery smooth muscle cells (PASMC). Mitochondrial respiration was quantified by high-resolution respirometry. Alterations were compared with HPV and hypoxia-induced functional and molecular readouts on the cellular level. Aortic and renal arterial smooth muscle cells (ASMC and RASMC, respectively) served as controls.The hypoxia-induced decrease of mitochondrial respiration paralleled HPV in isolated lungs. In PASMC, reduction of respiration and mitochondrial cytochrome c and aa3 (complex IV), but not of cytochrome b (complex III) matched an increase in matrix superoxide levels as well as mitochondrial membrane hyperpolarisation with subsequent cytosolic calcium increase. In contrast to PASMC, RASMC displayed a lower decrease in respiration and no rise in superoxide, membrane potential or intracellular calcium. Pharmacological inhibition of mitochondria revealed analogous kinetics of cytochrome redox state and strength of HPV.Our data suggest inhibition of complex IV as an essential step in mitochondrial oxygen sensing of HPV. Concomitantly, increased superoxide release from complex III and mitochondrial membrane hyperpolarisation may initiate the cytosolic calcium increase underlying HPV.
Comparison of normalization methods for Illumina BeadChip HumanHT-12 v3
Authors: Schmid Ramona , Baum Patrick , Ittrich Carina , Fundel-Clemens Katrin , Huber Wolfgang , Brors Benedikt , Eils Roland , Weith Andreas , Mennerich Detlev , Quast Karsten 
Published: June 2010

AbstractBackgroundNormalization of microarrays is a standard practice to account for and minimize effects which are not due to the controlled factors in an experiment. There is an overwhelming number of different methods that can be applied, none of which is ideally suited for all experimental designs. Thus, it is important to identify a normalization method appropriate for the experimental setup under consideration that is neither too negligent nor too stringent. Major aim is to derive optimal results from the underlying experiment. Comparisons of different normalization methods have already been conducted, none of which, to our knowledge, comparing more than a handful of methods.ResultsIn the present study, 25 different ways of pre-processing Illumina Sentrix BeadChip array data are compared. Among others, methods provided by the BeadStudio software are taken into account. Looking at different statistical measures, we point out the ideal versus the actual observations. Additionally, we compare qRT-PCR measurements of transcripts from different ranges of expression intensities to the respective normalized values of the microarray data. Taking together all different kinds of measures, the ideal method for our dataset is identified.ConclusionsPre-processing of microarray gene expression experiments has been shown to influence further downstream analysis to a great extent and thus has to be carefully chosen based on the design of the experiment. This study provides a recommendation for deciding which normalization method is best suited for a particular experimental setup.
Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?
Authors: Hahntow Ines N , Mairuhu Gideon , van Valkengoed Irene GM , Koopmans Richard P , Michel Martin C 
Published: June 2010

Abstract

Background
Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may have stronger phenotype associations than those within a single gene. We have tested this hypothesis using genes encoding components of the renin-angiotensin-aldosterone system and the high blood pressure phenotype.

Methods
Our analysis is based on 1379 participants of the cross-sectional SUNSET study randomly selected from the population register of Amsterdam. Each subject was genotyped for the angiotensinogen M235T, the angiotensin-converting enzyme insertion/deletion and the angiotensin II type 1 receptor A1166C polymorphism. The phenotype high blood pressure was defined either as a categorical variable comparing hypertension versus normotension as in most previous studies or as a continuous variable using systolic, diastolic and mean blood pressure in a multiple regression analysis with gender, ethnicity, age, body-mass-index and antihypertensive medication as covariates.

Results
Genotype-phenotype relationships were explored for each polymorphism in isolation and for double and triple polymorphism combinations. At the single polymorphism level, only the A allele of the angiotensin II type 1 receptor was associated with a high blood pressure phenotype. Using combinations of polymorphisms of two or all three genes did not yield stronger/more consistent associations.

Conclusions
We conclude that combinations of physiologically related polymorphisms of multiple genes, at least with regard to the renin-angiotensin-aldosterone system and the hypertensive phenotype, do not necessarily offer additional benefit in analyzing genotype/phenotype associations.
Translating the Dutch Walking Stairs, Walking Ability and Rising and Sitting Questionnaires into German and assessing their concurrent validity with VAS measures of pain and activities in daily living
Authors: Heitz Carolin , Bachmann Lucas M , Leibfried Anne , Kissling Rudolf , Kessels Alfons GH , Perez Roberto SGM , Marinus Johan , Brunner Florian 
Published: June 2010

Abstract

Background
The Dutch Walking Stairs, Walking Ability and Rising and Sitting Questionnaires are three validated instruments to measure physical activity and limitations in daily living in patients with lower extremity disorders living at home of which no German equivalents are available. Our scope was to translate the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires into German and to verify its concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale.

Methods
We translated the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires according to published guidelines. Demographic data and validity were assessed in 52 consecutive patients with Complex Regional Pain Syndrome 1 of the lower extremity. Information on age, duration of symptoms, type of Complex Regional Pain Syndrome 1 and type of initiating event were obtained. We assessed the concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale.

Results
We found that variability in the German Walking Stairs, Walking Ability and Rising and Sitting Questionnaires was largely explained by measures of pain and activities in daily living on the Visual Analogue Scale.

Conclusion
Our study shows that the domains pain and activities in daily living are properly represented in the German versions of the Walking Stairs, Walking Ability and Raising and Sitting Questionnaires. We would like to propagate their use in clinical practice and research alike.
Microprocessor of microRNAs: regulation and potential for therapeutic intervention
Authors: Beezhold Kevin J , Castranova Vince , Chen Fei 
Published: June 2010

Abstract
MicroRNAs (miRNAs) are a class of small, noncoding RNAs critically involved in a wide spectrum of normal and pathological processes of cells or tissues by fine-tuning the signals important for stem cell development, cell differentiation, cell cycle regulation, apoptosis, and transformation. Considerable progress has been made in the past few years in understanding the transcription, biogenesis and functional regulation of miRNAs. Numerous studies have implicated altered expression of miRNAs in human cancers, suggesting that aberrant expression of miRNAs is one of the hallmarks for carcinogenesis. In this review, we briefly discuss most recent discoveries on the regulation of miRNAs at the level of microprocessor-mediated biogenesis of miRNAs.