bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in the homeostasis of phospholipids and cholesterol by antitumor alkylphospholipids
Authors: Jiménez-López José M , Ríos-Marco Pablo , Marco Carmen , Segovia Josefa L , Carrasco María P 
Published: April 2010

Abstract
The alkylphospholipid analog miltefosine (hexadecylphosphocholine) is a membrane-directed antitumoral and antileishmanial drug belonging to the alkylphosphocholines, a group of synthetic antiproliferative agents that are promising candidates in anticancer therapy. A variety of mechanisms have been suggested to explain the actions of these compounds, which can induce apoptosis and/or cell growth arrest. In this review, we focus on recent advances in our understanding of the actions of miltefosine and other alkylphospholipids on the human hepatoma HepG2 cell line, with a special emphasis on lipid metabolism. Results obtained in our laboratory indicate that miltefosine displays cytostatic activity and causes apoptosis in HepG2 cells. Likewise, treatment with miltefosine produces an interference with the biosynthesis of phosphatidylcholine via both CDP-choline and phosphatidylethanolamine methylation. With regard to sphingolipid metabolism, miltefosine hinders the formation of sphingomyelin, which promotes intracellular accumulation of ceramide. We have demonstrated for the first time that treatment with miltefosine strongly impedes the esterification of cholesterol and that this effect is accompanied by a considerable increase in the synthesis of cholesterol, which leads to higher levels of cholesterol in the cells. Indeed, miltefosine early impairs cholesterol transport from the plasma membrane to the endoplasmic reticulum, causing a deregulation of cholesterol homeostasis. Similar to miltefosine, other clinically-relevant synthetic alkylphospholipids such as edelfosine, erucylphosphocholine and perifosine show growth inhibitory effects on HepG2 cells. All the tested alkylphospholipids also inhibit the arrival of plasma-membrane cholesterol to the endoplasmic reticulum, which induces a significant cholesterogenic response in these cells, involving an increased gene expression and higher levels of several proteins related to the pathway of biosynthesis as well as the receptor-mediated uptake of cholesterol. Thus, membrane-targeted alkylphospholipids exhibit a common mechanism of action through disruption of cholesterol homeostasis. The accumulation of cholesterol within the cell and the reduction in phosphatidylcholine and sphingomyelin biosyntheses certainly alter the ratio of choline-bearing phospholipids to cholesterol, which is critical for the integrity and functionality of specific membrane microdomains such as lipid rafts. Alkylphospholipid-induced alterations in lipid homeostasis with probable disturbance of the native membrane structure could well affect signaling processes vital to cell survival and growth.
HP1γ function is required for male germ cell survival and spermatogenesis
Authors: Brown Jeremy P , Bullwinkel Jörn , Baron-Lühr Bettina , Billur Mustafa , Schneider Philipp , Winking Heinz , Singh Prim B 
Published: April 2010

AbstractBackgroundHP1 proteins are conserved components of eukaryotic constitutive heterochromatin. In mammals, there are three genes that encode HP1-like proteins, termed HP1α, HP1β and HP1γ, which have a high degree of homology This paper describes for the first time, to our knowledge, the physiological function of HP1γ using a gene-targeted mouse.ResultsWhile targeting theCbx3gene (encoding the HP1γ protein) with a conditional targeting vector, we generated a hypomorphic allele (Cbx3hypo), which resulted in much reduced (barely detectable) levels of HP1γ protein. Homozygotes for the hypomorphic allele (Cbx3hypo/hypo) are rare, with only 1% ofCbx3hypo/hypoanimals reaching adulthood. Adult males exhibit a severe hypogonadism that is associated with a loss of germ cells, with some seminiferous tubules retaining only the supporting Sertoli cells (Sertoli cell-only phenotype). The percentage of seminiferous tubules that are positive for L1 ORF1 protein (ORF1p) inCbx3hypo/hypotestes is greater than that for wild-type testes, indicating that L1 retrotransposon silencing is reversed, leading to ectopic expression of ORF1p inCbx3hypo/hypogerm cells.ConclusionsTheCbx3gene product (the HP1γ protein) has a non-redundant function during spermatogenesis that cannot be compensated for by the other two HP1 isotypes. TheCbx3hypo/hypospermatogenesis defect is similar to that found inMiwi2andDnmt3Lmutants. TheCbx3gene-targeted mice generated in this study provide an appropriate model for the study of HP1γ in transposon silencing and parental imprinting.
C-Reactive Protein and Risk of Lung Cancer
Authors: Chaturvedi Anil K. , Caporaso Neil E. , Katki Hormuzd A. , Wong Hui-Lee , Chatterjee Nilanjan , Pine Sharon R. , Chanock Stephen J. , Goedert James J. , Engels Eric A. 
Published: April 2010

Purpose Chronic inflammation could play a role in lung carcinogenesis, underscoring the potential for lung cancer prevention and screening. We investigated the association of circulating high-sensitivity C-reactive protein (CRP, an inflammation biomarker) and CRP single nucleotide polymorphisms (SNPs) with prospective lung cancer risk. Patients and Methods We conducted a nested case-control study of 592 lung cancer patients and 670 controls with available prediagnostic serum and 378 patients and 447 controls with DNA within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 77,464). Controls were matched to patients on age, sex, entry year, follow-up time, and smoking. We measured CRP levels in baseline serum samples and genotyped five common CRP SNPs. Results Elevated CRP levels were associated with increased lung cancer risk (odds ratio [OR], 1.98; 95% CI, 1.35 to 2.89; P-trend < .001 for fourth quartile [Q4, ≥ 5.6 mg/L] v Q1 [< 1.0 mg/L]). The CRP association did not differ significantly by histology, follow-up time, or smoking status, but was most apparent for squamous cell carcinomas (OR, 2.92; 95% CI, 1.30 to 6.54), 2 to 5 years before lung cancer diagnosis (OR, 2.33; 95% CI, 1.24 to 4.39), and among former smokers (OR, 2.48; 95% CI, 1.53 to 4.03) and current smokers (OR, 1.90; 95% CI, 1.06 to 3.41). Although CRP SNPs and haplotypes were associated with CRP levels, they were not associated with lung cancer risk. Ten-year standardized absolute risks of lung cancer were higher with elevated CRP levels among former smokers (Q4: 2.55%; 95% CI, 1.98% to 3.27% v Q1: 1.39%; 95% CI, 1.07% to 1.81%) and current smokers (Q4: 7.37%; 95% CI, 5.81% to 9.33% v Q1: 4.03%; 95% CI, 3.01% to 5.40%). Conclusion Elevated CRP levels are associated with subsequently increased lung cancer risk, suggesting an etiologic role for chronic pulmonary inflammation in lung carcinogenesis.
Complications of Chemonucleolysis for Lumbar Disc Disease
Authors: Watts Clark 
Published: April 2010

Abstract
In 13,700 patients who received one or more lumbar disc injections of chymopapain, 401 complications, adverse reactions, and delayed untoward events were recorded, including eight deaths. The deaths were secondary to anaphylaxis, pulmonary embolism, discitis with subacute bacterial endocarditis, ruptured abdominal aortic aneurysms (two patients), encephalitis (of unknown etiology), and myocardial infarction. Of these, the deaths secondary to anaphylaxis and discitis with subacute bacterial endocarditis can be attributed directly to the procedure of chemonucleolysis.
The Infratentorial-Supracerebellar Exposure of Tumors in the Pineal Area
Authors: Page Larry K. 
Published: April 2010

Abstract
Nine pineal area lesions were operated upon by the infratentorial-supracerebellar approach. There was one operative death and one death due to disseminated germinoma recurrence 2/12 years postoperatively. The remaining seven patients have shown no sign of recurrence and are neurologically normal. The surgical method that has evolved through these nine cases is discussed. The infratentorial-supracerebellar exposure is an excellent one for lesions in the region of the pineal gland, posterior 3rd ventricle, and superior cerebellar vermis. Access is less hampered by the major tributaries of the vein of Galen than with the supratentorial operations. This approach is also a useful extension of the standard posterior fossa exploration when dealing with primarily subtentorial lesions that involve the dorsal midbrain or herniate upward.
Eye-Movement Patterns of Readers With Down Syndrome During Sentence-Processing: An Exploratory Study
Authors: Frenck-Mestre Cheryl , Zardan Nathalie , Colas Annie , Ghio Alain 
Published: April 2010

AbstractEye movements were examined to determine how readers with Down syndrome process sentences online. Participants were 9 individuals with Down syndrome ranging in reading level from Grades 1 to 3 and a reading-level-matched control group. For syntactically simple sentences, the pattern of reading times was similar for the two groups, with longer reading times found at sentence end. This “wrap-up” effect was also found in the first reading of more complex sentences for the control group, whereas it only emerged later for the readers with Down syndrome. Our results provide evidence that eye movements can be used to investigate reading in individuals with Down syndrome and underline the need for future studies.
Crack-Closure Behavior of 7050 Aluminum Alloy near Threshold Conditions for Wide Range in Load Ratios and ConstantKmax Tests
Authors: Newman J. C. , Yamada Y. , Newman J. A. 
Published: April 2010

AbstractFatigue-crack-growth rate tests were conducted on compact specimens made of a 7050-T7451 aluminum alloy to study the behavior over a range in load ratios (0.1≤R≤0.9) and constant Kmax test conditions. Previous research had suggested that differences in the threshold regime at high load ratios were attributed to Kmax effects. But recent measurements of crack-closure behavior under high R and constant Kmax test conditions near threshold conditions on a variety of materials have indicated that these tests may not be crack-closure free as suspected. Strain gages were placed near and ahead of the crack tip to measure crack-opening loads from local strain records. In addition, a back-face strain (BFS) gage was used to monitor crack sizes and to measure crack-opening loads from remote strain records during the same tests. The 7050 alloy produced very rough crack-surface profiles. For R=0.1, the BFS and local gages indicated very similar high crack-opening loads. For R≥0.7 and Kmax test results in the threshold regime, the BFS gages indicated lower crack-opening loads than the local gages. Based on local measurements, crack-closure-free fatigue-crack-growth data (ΔKeff against rate) were calculated. These results indicated that the ΔKeff against rate relation is nearly a unique function over a wide range of R values even in the threshold regime, if crack-opening loads were measured from local strain gages. At low R, all three major shielding mechanisms (plasticity, roughness, and fretting debris) are suspected to cause crack closure. But for high R and Kmax tests, roughness and fretting debris are suspected to cause crack closure above the minimum load. A strip-yield model was also used to correlate the data over a wide range in load ratios and rates, but required a very low constraint factor (α=1.3), due to the high crack-opening loads.
Mek1 Suppression of Meiotic Double-Strand Break Repair Is Specific to Sister Chromatids, Chromosome Autonomous and Independent of Rec8 Cohesin Complexes
Authors: Callender Tracy L , Hollingsworth Nancy M 
Published: April 2010

AbstractDuring meiosis, recombination is directed to occur between homologous chromosomes to create connections necessary for proper segregation at meiosis I. Partner choice is determined at the time of strand invasion and is mediated by two recombinases: Rad51 and the meiosis-specific Dmc1. In budding yeast, interhomolog bias is created in part by the activity of a meiosis-specific kinase, Mek1, which is localized to the protein cores of condensed sister chromatids. Analysis of meiotic double-strand break (DSB) repair in haploid and disomic haploid strains reveals that Mek1 suppresses meiotic intersister DSB repair by working directly on sister chromatids. Rec8 cohesin complexes are not required, however, either for suppression of intersister DSB repair or for the repair itself. Regulation of DSB repair in meiosis is chromosome autonomous such that unrepaired breaks on haploid chromosomes do not prevent interhomolog repair between disomic homologs. The pattern of DSB repair in haploids containing Dmc1 and/or Rad51 indicates that Mek1 acts on Rad51-specific recombination processes.
Cost-Effectiveness Analysis of Recurrence Score-Guided Treatment Using a 21-Gene Assay in Early Breast Cancer
Authors: Tsoi Daphne T. , Inoue Miho , Kelly Catherine M. , Verma Sunil , Pritchard Kathleen I. 
Published: April 2010

Abstract

Purpose.
Most guidelines for hormone receptor (HR)–positive early breast cancer recommend addition of adjuvant chemotherapy for most women, leading to overtreatment, which causes considerable morbidity and cost. There has been recent incorporation of gene expression analysis in aiding decision making. We evaluated the cost-effectiveness of recurrence score (RS)–guided treatment using 21-gene assay as compared with treatment guided by the Adjuvant! Online program (AOL).

Patients and Methods.
A Markov model was developed to compare the cost-effectiveness of treatment guided either by 21-gene assay or by AOL in a 50-year-old woman with lymph node–negative HR-positive breast cancer over a lifetime horizon. We assumed that women classified to be at high risk all received chemotherapy followed by tamoxifen and those classified to be at low risk received tamoxifen only. The model took a health care payer's perspective with results reported in 2008 Canadian dollars ($). Event rates, costs, and utilities were derived from the literature. Both costs and benefits were discounted at 5%. Outcome measures were life years gained, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs).

Results.
For a 50-year-old woman, RS-guided treatment was associated with an incremental lifetime cost of $4,102 and a gain in 0.065 QALY, with an ICER of $63,064 per QALY compared with AOL-guided treatment. ICER increased with increasing cost of 21-gene assay and increasing age of patients. Results were most sensitive to probabilities relating to risk categorization and recurrence rate.

Conclusions.
The 21-gene assay appears cost-effective from a Canadian health care perspective.
New Data on Successful Invasion of Mediterranean Predatory Mite Typhlodromus Beglarovi (Parasitiformes, Phytoseiidae) into the Forest-Steppe of Ukraine
Authors: Kolodochka L. , Omeri I. 
Published: April 2010

New Data on Successful Invasion of Mediterranean Predatory MiteTyphlodromus Beglarovi(Parasitiformes, Phytoseiidae) into the Forest-Steppe of UkraineEvidences of more than 30 years (1975-2007) existence of the northern isolated population Forest-Steppe of Ukraine (near Kozyn Village, Obukhiv District, Kyiv Oblast, Ukraine) is given. It is considered as an example of unpremeditated introduction of a beneficial predating mite together with transported plants. This is the first registered and investigated case of invasion, acclimatization and inclusion biocoenosis as an equal right member for mites of the family Phytoseiidae.
The Kaali crater field and other geosites of Saaremaa Island (Estonia): the perspectives for a geopark
Authors: Raukas Anto , Stankowski Wojciech 
Published: April 2010

The Kaali crater field and other geosites of Saaremaa Island (Estonia): the perspectives for a geoparkThe Island of Saaremaa in Estonia offers highly spectacular geological features that belong to the most interesting in the Baltic Sea area. A unique geological monument on the island is the Kaali meteorite-crater field, formed by nine meteorite impacts. There are also attractive coastal cliffs, huge erratics, alvars (limestone areas covered by a very thin soil) and well-developed glacial and marine landforms. Limestone cliffs and shingle beaches abound with Silurian fossils and offer great opportunities to fossil collectors. The island is a prospective geopark. During the past few years, the geology of the island has become an intensely studied object of Estonian and Polish geologists.
“Dutchness” and the migrant “other”
Authors: Ghorashi Halleh 
Published: April 2010

Peter Jan Margry and Herman Roodenburg, eds., Reframing Dutch culture: Between otherness and authenticity. Aldershot: Ashgate, 2007, 291 pp., ISBN 978-0-754-64705-8 (hardcover).Ian Buruma, Murder in Amsterdam: Liberal Europe, Islam, and the limits of tolerance. New York: Penguin Books, 2006, 288 pp., ISBN 978-0-143-11236-5 (paperback).
Basal melting and freezing under the Amery Ice Shelf, East Antarctica
Authors: Wen Jiahong , Wang Yafeng , Wang Weili , Jezek K.C. , Liu Hongxing , Allison I. 
Published: April 2010

AbstractThe basal melting and freezing rates under the Amery Ice Shelf, East Antarctica, are evaluated, and their spatial distributions mapped. Ice velocity, surface elevation and accumulation rate datasets are employed in the analysis, along with a column-averaged ice density model. Our analysis shows that the total area of basal melting is 34 700 km2, with a total annual melt of 62.5 ± 9.3 Gt and an average melting rate of 1.8 ± 0.3 m a−1. Basal freezing mainly occurs in the northwestern part of the ice shelf, over a total area of 26 100 km2 and with a maximum freezing rate of 2.4 ± 0.4 m a−1. The total marine ice that accretes to the ice-shelf base is estimated to be 16.2 ± 2.4 Gt a−1. Using a redefined grounding line and geometry of the Amery Ice Shelf, we estimate the net melt over the ice-shelf base is about 46.4 ± 6.9 G ta−1, which is higher than previous modeling and oceanographic estimates. Net basal melting accounts for about half of the total ice-shelf mass loss, with the rest being from iceberg discharge. Our basal melting and freezing distribution map provides a scientific basis for quantitative analysis of ice–ocean interaction at the ice-shelf–ocean interface.
Flow of the Ross Ice Shelf, Antarctica, is modulated by the ocean tide
Authors: Brunt Kelly M. , King Matt A. , Fricker Helen Amanda , MacAyeal Douglas R. 
Published: April 2010

AbstractThe ice streams feeding the Ross Ice Shelf, Antarctica, have large tidally modulated (sinusoidal and stick–slip) flow, but the interaction with the ice shelf is poorly understood. We show that the flow of the Ross Ice Shelf front, up to ∼650 km from the ice streams, exhibits smooth, sinusoidal motions corresponding to tidal modulation. These observations suggest a possible linking of the ice shelf with the ice streams to form a unified system that responds to small perturbations in stresses associated with ocean tides. If this is the case, the presence of the sinusoidal motion but the absence of stick–slip motion suggests there is damping of very high-frequency signals. The dissimilar signatures of the motions observed in the ice streams and at the front of the ice shelf present challenges to model development aimed at understanding the dynamics of coupled ice-stream/ice-shelf flow and the movement of ice across grounding lines.
A new technique for firn grain-size measurement using SEM image analysis
Authors: Spaulding N.E. , Meese D.A. , Baker I. , Mayewski P.A. , Hamilton G.S. 
Published: April 2010

AbstractFirn microstructure is accurately characterized using images obtained from scanning electron microscopy (SEM). Visibly etched grain boundaries within images are used to create a skeleton outline of the microstructure. A pixel-counting utility is applied to the outline to determine grain area. Firn grain sizes calculated using the technique described here are compared to those calculated using the techniques of Gow (1969) and Gay and Weiss (1999) on samples of the same material, and are found to be substantially smaller. The differences in grain size between the techniques are attributed to sampling deficiencies (e.g. the inclusion of pore filler in the grain area) in earlier methods. The new technique offers the advantages of greater accuracy and the ability to determine individual components of the microstructure (grain and pore), which have important applications in ice-core analyses. The new method is validated by calculating activation energies of grain boundary diffusion using predicted values based on the ratio of grain-size measurements between the new and existing techniques. The resulting activation energy falls within the range of values previously reported for firn/ice.
Recording microscale variations in snowpack layering using near-infrared photography
Authors: Tape Ken D. , Rutter Nick , Marshall Hans-Peter , Essery Richard , Sturm Matthew 
Published: April 2010

AbstractDeposition of snow from precipitation and wind events creates layering within seasonal snowpacks. The thickness and horizontal continuity of layers within seasonal snowpacks can be highly variable, due to snow blowing around topography and vegetation, and this has important implications for hydrology, remote sensing and avalanche forecasting. In this paper, we present practical field and post-processing protocols for recording lateral variations in snow stratigraphy using near-infrared (NIR) photography. A Fuji S9100 digital camera, modified to be sensitive to NIR wavelengths, was mounted on a rail system that allowed for rapid imaging of a 10 m long snow trench excavated on the north side of Toolik Lake, Alaska (68°38′ N, 149°36′ W). Post-processing of the images included removal of lens distortion and vignetting. A tape measure running along the base of the trench provided known locations (control points) that permitted scaling and georeferencing. Snow layer heights estimated from the NIR images compared well with manual stratigraphic measurements made at 0.2 m intervals along the trench (n = 357, R2 = 0.97). Considerably greater stratigraphic detail was captured by the NIR images than in the manually recorded profiles. NIR imaging of snow trenches using the described protocols is an efficient tool for quantifying continuous microscale variations in snow layers and associated properties.
Une mise en forme de la compétence littéraire
Authors: Pamfil Alina 
Published: April 2010

L’article ouvre une double perspective – théorique et didactique – sur un modèle conceptuel possible de la compétence littéraire. L’approche théorique consiste dans la figuration du modèle sur un arrière-fond composé par les rôles potentiels des lecteurs et par les processus spécifiques à la lecture. De la sorte, sa structure est précisée en termes de savoirs et savoir-faire, et réunit des coordonnées textuelles et contextuelles. L’approche didactique reprend ces composantes, met en jeu trois binômes conceptuels (lecture première et relecture ; compréhension et interprétation ; contexte d’écriture et contexte de réception) et indique une succession de séquences et de techniques d’apprentissage, considérées appropriées et opérationnelles.
L'enseignement des langues et cultures d'origine : incertitudes de statut et ambigüité des missions
Authors: Bertucci Marie-Madeleine 
Published: April 2010

Entre 1973 et 2006, les ELCO passent d’un dispositif d’intégration pour les élèves migrants à un enseignement de langue vivante. Mais cette évolution instaure une inégalité de fait entre les langues car elle concerne principalement l’italien et le français. Les ELCO sont aussi affaiblis par de nombreux dysfonctionnements, soulignés par les instances compétentes : logique communautariste parfois, et inadaptation de l’enseignement aux enjeux de la politique d’intégration. L’avenir des ELCO parait donc incertain à moins de faire évoluer le dispositif en l’intégrant au milieu ordinaire. L’idéal serait de promouvoir une socialisation plurilingue et une didactique du plurilinguisme complémentaires de la didactique du français, dans le cadre d’une stratégie globale de l’enseignement des langues.