bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calculation of IBD probabilities with dense SNP or sequence data
Authors: Keith Jonathan M. , McRae Allan , Duffy David , Mengersen Kerrie , Visscher Peter M. 
Published: March 2008

AbstractThe probabilities that two individuals share 0, 1, or 2 alleles identical by descent (IBD) at a given genotyped marker locus are quantities of fundamental importance for disease gene and quantitative trait mapping and in family‐based tests of association. Until recently, genotyped markers were sufficiently sparse that founder haplotypes could be modelled as having been drawn from a population in linkage equilibrium for the purpose of estimating IBD probabilities. However, with the advent of high‐throughput single nucleotide polymorphism genotyping assays, this is no longer a reasonable assumption. Indeed, the imminent arrival of individual sequencing will enable high‐density single nucleotide polymorphism genotyping on a scale for which current algorithms are not equipped. In this paper, we present a simple new model in which founder haplotypes are modelled as a Markov chain. Another important innovation is that genotyping errors are explicitly incorporated into the model. We compare results obtained using the new model to those obtained using the popular genetic linkage analysis package Merlin, with and without using the cluster model of linkage disequilibrium that is incorporated into that program. We find that the new model results in accuracy approaching that of Merlin with haplotype blocks, but achieves this with orders of magnitude faster run times. Moreover, the new algorithm scales linearly with number of markers, irrespective of density, whereas Merlin scales supralinearly. We also confirm a previous finding that ignoring linkage disequilibrium in founder haplotypes can cause errors in the calculation of IBD probabilities. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.
Fragile X‐associated primary ovarian insufficiency: evidence for additional genetic contributions to severity
Authors: Hunter Jessica Ezzell , Epstein Michael P. , Tinker Stuart W. , Charen Krista H. , Sherman Stephanie L. 
Published: March 2008

AbstractThe fragile X mental retardation gene (FMR1) contains a CGG repeat sequence in its 5′ untranslated region that can become unstable and expand in length from generation to generation. Alleles with expanded repeats in the range of ∼55–199, termed premutation alleles, are associated with an increased risk for fragile‐X‐associated primary ovarian insufficiency (FXPOI). However, not all women who carry the premutation develop FXPOI. To determine if additional genes could explain variability in onset and severity, we used a random‐effects Cox proportional hazards model to analyze age at menopause on 680 women from 225 families who have a history of fragile X syndrome and 321 women from 219 families from the general population. We tested for the presence of a residual additive genetic effect after adjustment for FMR1 repeat length, race, smoking, body mass index, and method of ascertainment. Results showed significant familial aggregation of age at menopause with an estimated additive genetic variance of 0.55–0.96 depending on the parameterization of FMR1 repeat size and definition of age at menopause (P‐values ranging between 0.0002 and 0.0027). This is the first study to analyze familial aggregation of FXPOI. This result is important for proper counseling of women who carry FMR1 premutation alleles and for guidance of future studies to identify additional genes that influence ovarian insufficiency. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.
Synthesis, DNA‐Binding and Photocleavage Studies of the Ruthenium(II) Complexes [Ru(phen)2(ppd)]2+ and [Ru(phen)(ppd)2]2+ (ppd=Pteridino[6,7‐f] [1,10]phenanthroline‐11,13(10H,12H)‐dione, phen=1,10‐Phenanthroline)
Authors: Gao Feng , Chao Hui , Wei Yuan‐Fang , Yuan Yi‐Xian , Peng Bin , Chen Xin , Zheng Kang‐Cheng , Ji Liang‐Nian 
Published: March 2008

AbstractTwo new complexes, [Ru(phen)2(ppd)]2+ (1) and [Ru(phen)(ppd)2]2+ (2) (ppd=pteridino[6,7‐f] [1,10]phenanthroline‐11,13(10H,12H)‐dione, phen=1,10‐phenanthroline) were synthesized and characterized by ES‐MS, 1H‐NMR spectroscopy, and elemental analysis. The intercalative DNA‐binding properties of 1 and 2 were investigated by absorption‐spectroscopy titration, luminescence‐spectroscopy studies, thermal denaturation, and viscosity measurements. The theoretical aspects were further discussed by comparative studies of 1 and 2 by means of DFT calculations and molecular‐orbital theory. Photoactivated cleavage of pBR322 DNA by the two complexes were also studied, and 2 was found to be a much better photocleavage reagent than 1. The mechanism studies revealed that singlet oxygen and the excited‐states redox potentials of the complex may play an important role in the DNA photocleavage.
Unusual Nortriterpenoid Saponins from Stauntonia chinensis
Authors: Gao Hao , Wang Zhao , Yao Zhi‐Hong , Wu Ning , Dong Hua‐Jin , Li Jin , Wang Nai‐Li , Ye Wen‐Cai , Yao Xin‐Sheng 
Published: March 2008

AbstractFour new saponins, yemuosides YM17–YM20 (1–4, resp.), were isolated from the rattan of Stauntonia chinensis DC. (Lardizabalaceae) along with a known saponin, nipponoside D (5). Their structures were elucidated by spectroscopic analysis and chemical evidence as 20,30‐dihydroxy‐29‐noroleanolic acid 28‐O‐α‐L‐rhamnopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→6)‐β‐D‐glucopyranosyl ester (1), 20,29‐dihydroxy‐30‐noroleanolic acid 28‐O‐α‐L‐rhamnopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→6)‐β‐D‐glucopyranosyl ester (2), 29‐hydroxy‐30‐norolean‐20(21)‐enolic acid 28‐O‐α‐L‐rhamnopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→6)‐β‐D‐glucopyranosyl ester (3), 29‐hydroxyoleanolic acid 28‐O‐α‐L‐rhamnopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→6)‐β‐D‐glucopyranosyl ester (4), and 23,29‐dihydroxyoleanolic acid 28‐O‐α‐L‐rhamnopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→6)‐β‐D‐glucopyranosyl ester (5). Yemuoside YM17–YM19 (1–3, resp.) contain novel unusual nortriterpene aglycones.
Peat hydraulic conductivity in cold regions and its relation to pore size and geometry
Authors: Quinton William L. , Hayashi Masaki , Carey Sean K. 
Published: March 2008

AbstractSubsurface flow through peat plays a critical role in the hydrology of organic‐covered, permafrost terrains, which occupy a large part the continental arctic, sub‐arctic, and boreal regions. Hillslope drainage in these terrains occurs predominantly through the active flow zone between the relatively impermeable frost table and the water table above it. The hydraulic conductivity profile within this zone controls the subsurface drainage of snowmelt and storm water. Peat hydraulic conductivity profiles were examined at three sites in north‐western Canada, each representing a widely occurring organic‐covered, permafrost terrain type. Three independent measures of saturated hydraulic conductivity were used—tracer tests, constant‐head well‐permeameter tests, and laboratory measurements of undisturbed samples. At all three sites, the conductivity profiles contained very high values (10–1000 m d−1) within the top ca 0·1 m where the peat is only lightly decomposed, a large reduction with increasing depth below the ground surface in the transition zone, and relatively low values in a narrow range (0·5–5 m d−1) below ca 0·2 m depth, where the peat is in an advanced state of decomposition. Digital image analysis of resin‐impregnated peat samples showed that hydraulic conductivity is essentially controlled by pore hydraulic radius. The strong dependence of hydraulic conductivity on hydraulic radius implies that peat soils subjected to similar degrees of decomposition and compaction have a similar hydraulic conductivity regardless of the location. This explains the similarity of the depth‐conductivity profiles among all three terrain types. Copyright © 2008 John Wiley & Sons, Ltd.
Reverse transcriptase inhibitors induce cell differentiation and enhance the immunogenic phenotype in human renal clear‐cell carcinoma
Authors: Landriscina Matteo , Altamura Settimia Anna , Roca Leonarda , Gigante Margherita , Piscazzi Annamaria , Cavalcanti Elisabetta , Costantino Eleonora , Barone Carlo , Cignarelli Mauro , Gesualdo Loreto , Ranieri Elena 
Published: March 2008

AbstractReverse transcriptase (RT) inhibitors are emerging as a novel class of anticancer differentiating agents, active in several human tumor cell models, such as melanoma and prostate, thyroid and colon carcinoma. Indeed, much evidence suggests that they may act by inhibiting endogenous RT, a gene highly expressed in undifferentiated and transformed cells. We therefore evaluated whether endogenous RT may represent a new molecular target in the treatment of human renal clear‐cell carcinoma, a neoplasm with very low sensitivity to standard pharmacological therapies. Efavirenz and nevirapine, 2 non‐nucleosidic RT inhibitors commonly used in HIV patients, either induced a reversible downregulation of cell proliferation or enhanced cell differentiation in primary cultures of human renal carcinoma cells characterized by high levels of endogenous RT activity. Both agents upregulated the expression of the vitamin D receptor and calbindin 28k genes, which are constitutively expressed in renal tubular cells, and induced vitamin D signaling by enhancing the ability of tumor cells to upregulate the vitamin D‐dependent gene, CYP24. Furthermore, efavirenz‐ and nevirapine‐differentiated tumor cells exhibited an immunogenic phenotype with an increased expression of HLA‐I and CD40 antigens and an enhanced ability to elicit a specific T‐cell response in mixed lymphocyte/tumor‐cell cultures. Indeed, renal carcinoma cells exposed to efavirenz induced a CD8+CCR7‐CD45RA− effector memory T‐cell phenotype, whereas untreated RCC cells induced a CD8+CCR7+CD45RA− central memory T‐cell phenotype. These data suggest that RT inhibitors may be a novel tool in the treatment of human renal clear‐cell carcinoma, potentially able to enhance the immunogenic potential of tumor cell. © 2008 Wiley‐Liss, Inc.
Src kinase induces tumor formation in the c‐SRC C57BL/6 mouse
Authors: Kline Christina Leah B. , Jackson Rosalind , Engelman Robert , Pledger Warren Jack , Yeatman Timothy J. , Irby Rosalyn B. 
Published: March 2008

AbstractSrc kinase has been linked as a causative agent in the progression of a number of cancers including colon, breast, lung and melanoma. Src protein and activity levels are increased in colorectal cancer and liver metastases arising secondary to colon cancer. However, although Src protein is increased in colon cancer as early as the adenomatous polyp stage, a role for Src in carcinogenesis has not been established. We developed the c‐SRC transgenic mouse in the C57BL/6 strain to address the issue of carcinogenesis in cells with high levels of Src expression. The transgene was constructed with the human c‐SRC gene downstream of the mouse metallothionein promoter to create zinc inducible gene expression. In these C57BL/6 mice, Src protein was increased in a number of tissues both with and without zinc induction. No additional carcinogenic agent was administered. After 20 months, mice were assessed for tumor development in the liver and GI tract, as well as other organs. Of the mice with the transgene, 15% developed tumors in the liver while no tumors were detected in wild type C57BL/6 mice. A further study was conducted by crossing c‐SRC C57BL/6 mice with p21 nullizygous mice to determine the effect of oncogene expression combined with inactivation of the tumor suppressor gene, p21. Addition of the c‐SRC transgene to the p21−/− background increased tumor formation almost 3‐fold, while it increased metastasis 6‐fold. The data from our study show, for the first time, that Src kinase may play a role in carcinogenesis. © 2008 Wiley‐Liss, Inc.
Development of the treatment attitudes questionnaire in bipolar disorder
Authors: Johnson Sheri L. , Fulford Daniel 
Published: March 2008

AbstractDespite the success of pharmacotherapy in the management of bipolar disorder, as many as one‐half of those in treatment discontinue their medication over time. Currently, no self‐report measure is available that predicts treatment engagement in bipolar disorder. The goal of the current study was to develop a measure of awareness of symptoms and attitudes toward treatment among those with bipolar disorder. Sixty‐six participants diagnosed with bipolar I disorder on the SCID completed the Treatment Attitudes Questionnaire (TAQ) and were then followed for up to 2 years to assess symptom levels. Medication data were available for 37 participants. Analyses of the TAQ were conducted to examine reliability, predictors of subscales, and how well scores predicted medication and symptom levels over time. Results indicate that previous episodes of depression, but not episodes of mania, correlated with increased scores on the Insight and the Enjoyment of Mania subscales. Scores on the Nonbiological Attributions subscale predicted lower levels of lithium as well as increased depressive symptoms over time. Although the current study includes limited measurement of treatment engagement and a small sample size, this easily administered scale may help treatment planning for those with bipolar disorder. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64: 466–481, 2008.
Parent–child interactions in pediatric bipolar disorder
Authors: Schenkel Lindsay S. , West Amy E. , Harral Erin M. , Patel Nafisa B. , Pavuluri Mani N. 
Published: March 2008

AbstractParent–child relationships may have a significant effect on illness characteristics of children with pediatric bipolar disorder (PBD), and these relationships may, in turn, be affected by the child's illness. We characterized maternal reports of parent–child relationships using the five‐factor Parent–Child Relationship Questionnaire (PCRQ) in 60 families (30 PBD youth and 30 matched controls). Data on child proband and parental psychopathology were also obtained. Compared to controls, parent–child relationships in the PBD group were characterized by significantly less warmth, affection, and intimacy, and more quarreling and forceful punishment. Among PBD participants, elevated symptoms of mania, comorbid ADHD, an earlier age of illness onset, living in a single parent home, and the presence of a parental mood disorder were associated with greater parent–child relationship difficulties. These findings have implications for the development of interventions that focus on the quality of parent–child relationships, in addition to symptom management, in the treatment of PBD. © 2008, Wiley Periodicals, Inc. J Clin Psychol 64: 422–437, 2008.
Heme oxygenase‐1 mediates the anti‐inflammatory effect of Curcumin within LPS‐stimulated human monocytes
Authors: Hsu Hsien‐Yeh , Chu Li‐Chieh , Hua Kuo‐Feng , Chao Louis Kuoping 
Published: March 2008

AbstractCurcumin, a polyphenolic compound derived from plant, regulates heme oxygenase (HO‐1) expression within certain cell types; however, the Curcumin‐mediated signal transduction in the regulation of HO‐1 expression within human monocytes/macrophages is unclear. Herein, we show that Curcumin dose dependently induced HO‐1 expression and HO‐1 activity through the activation of PKCα, PKCδ/ERK1/2, p38α, and PI3‐kinase. In addition, H2O2 release is essential for Curcumin‐mediated ERK1/2 and p38 phosphorylation and HO‐1 expression. Further, Curcumin inhibited LPS‐induced IL‐1 and IL‐6 secretion and blockage of HO‐1 expression/activity by HO‐1 siRNA or HO‐1 inhibitor, SnPP reversed the inhibitory effects of Curcumin on cytokines secretion. HO‐1 over‐expression produced the same inhibitory effects of Curcumin on IL‐1 secretion. Collectively, our results suggest that Curcumin inhibits cytokines secretion within LPS‐stimulated monocytes through a mechanism that involves the action of HO‐1. J. Cell. Physiol. 215: 603–612, 2008. © 2008 Wiley‐Liss, Inc.
Holocene environmental change in the West African Sahel: sedimentological and mineral‐magnetic analyses of lake sediments from Jikariya Lake, northeastern Nigeria
Authors: Wang H. , Holmes J. A. , Street‐Perrott F. A. , Waller M. P. , Perrott R. A. 
Published: March 2008

AbstractPrevious studies have demonstrated long‐term changes in effective moisture in sub‐Saharan Africa. Here, we reconstruct Holocene environments using a ∼7 m lake‐sediment sequence recovered from the northeastern Nigerian Sahel and attempt to distinguish basin‐specific changes from regional climatic variations. The sequence was analysed for sedimentological properties, mineral magnetism and pollen, and dated by 137Cs, 210Pb excess and 14C. Extremely arid conditions of the terminal Pleistocene ended ca. 11 500 cal. BP (calendar years) when climate ameliorated and a lake developed until the occurrence of an arid event leading to lake desiccation at ∼11 200 cal. BP. Following this, climate ameliorated and a water body re‐emerged. Very wet conditions predominated 11 200–5600 cal. BP, followed by drought between 5600 and 5500 cal. BP and a return to moderate humidity from 5500 to 4000 cal. BP. After 4000 cal. BP, a marked deterioration occurred, culminating in lake desiccation at ca. 800 cal. BP. After this time the climate remained generally dry and the re‐emerging lake was shallow. Comparison of these results with other well‐dated sequences in the region demonstrates the importance of basin‐specific influences on the palaeolimnological records in addition to regional climatic controls. Disentangling these different controls, as well as the reconstruction of Holocene climate, therefore requires a multiple‐basin approach. Copyright © 2008 John Wiley & Sons, Ltd.
Local disappearance of bivalves in the Azores during the last glaciation
Authors: Ávila Sérgio P. , Madeira Patrícia , da Silva C. Marques , Cachão Mário , Landau Bernard , Quartau Rui , Martins A. M. de Frias 
Published: March 2008

AbstractThe Pleistocene (Eemian) outcrops of Lagoinhas and Prainha, located at Santa Maria Island (Azores), were investigated and their fossil mollusc content reported. These studies revealed that the last glaciation affected two groups of molluscs: the ‘warm‐guest’ gastropods with West African or Caribbean affinities (e.g. Conus spp., Cantharus variegatus, Bulla amygdala, Trachypollia nodulosa) and shallow bivalve species mainly associated with sandy habitats (Ensis minor, Lucinella divaricata, and probably Laevicardium crassum). In this paper we focus on this group of bivalves, which has since locally disappeared from the Azores. We relate the local disappearance of these bivalves in the Azores with the lack of sand in the shelf. The specific characteristics of the Santa Maria shelf combined with the sea‐level drop during the Weichselian prevented deposition of the lowstand deposits and permitted erosion of the previous ones, leaving the shelf without a sediment cover. Copyright © 2008 John Wiley & Sons, Ltd.
On the effect of ensemble size on the discrete and continuous ranked probability scores
Authors: Ferro Christopher A. T. , Richardson David S. , Weigel Andreas P. 
Published: March 2008

AbstractFour recent papers have investigated the effects of ensemble size on the Brier score (BS) and discrete ranked probability score (RPS) attained by ensemble‐based probabilistic forecasts. The connections between these papers are described and their results are generalized. In particular, expressions, explanations and estimators for the expected effect of ensemble size on the RPS and continuous ranked probability score (CRPS) are obtained. Copyright © 2008 Royal Meteorological Society
Doppler radar radial wind data in NWP model validation
Authors: Salonen Kirsti , Järvinen Heikki , Järvenoja Simo , Niemelä Sami , Eresmaa Reima 
Published: March 2008

AbstractValidation of mesoscale numerical weather prediction models calls for high‐resolution observations. Conventional data sources, such as radiosonde data, provide a reliable benchmark but their spatial resolution is insufficient for model validation in the kilometric scale. Doppler radar radial wind observations are used in this study as an alternative data source for model validation. Data assimilation system in general, and observation modelling in particular, are used as a toolbox for validation.Two versions of the High Resolution Limited Area Model (HIRLAM), which differ only in the formulation of the surface stress direction, are validated over a period of 1 month. The observation minus background (OmB) statistics advocate the merits of using high‐resolution radar data as model validation material. It is demonstrated that subtle differences in model versions due to different parameterization details can be distinguished with high statistical confidence. Copyright © 2008 Royal Meteorological Society
The extreme dependency score: a non‐vanishing measure for forecasts of rare events
Authors: Stephenson D. B. , Casati B. , Ferro C. A. T. , Wilson C. A. 
Published: March 2008

AbstractAccurate prediction of rare high‐impact events represents a major challenge for weather and climate forecasting. Assessment of the skill at forecasting such events is problematic because of the rarity of such events. Skill scores traditionally used to verify deterministic forecasts of rare binary events, such as the equitable threat score (ETS), have the disadvantage that they tend to zero for vanishingly rare events. This creates the misleading impression that rare events cannot be skilfully forecast no matter which forecasting system is used.This study presents a simple model for rare binary‐event forecasts and uses it to demonstrate the trivial non‐informative limit behaviour of several often‐used scores such as ETS. The extreme dependency score (EDS) is proposed as a more informative alternative for the assessment of skill in deterministic forecasts of rare events. The EDS has the advantage that it can converge to different values for different forecasting systems and furthermore it does not explicitly depend upon the bias of the forecasting system.The concepts and scores are demonstrated using an example of 6‐hourly precipitation total Met Office forecasts for Eskdalemuir in Scotland over the period 1998–2003. Copyright © 2008 Royal Meteorological Society; © Crown Copyright 2008. Reproduced with the permission of the Controller of HMSO. Published by John Wiley & Sons, Ltd
Searching for systematic location errors of quantitative precipitation forecasts over the Calabria region
Authors: Tartaglione Nazario , Mariani Stefano , Casaioli Marco , Accadia Christophe , Federico Stefano , Michaelides Silas Chr. 
Published: March 2008

AbstractThis article statistically analyses the location errors of the precipitation patterns forecast by three limited area models, namely the Fifth‐Generation NCAR/Penn State Mesoscale Model (MM5), the QUADRICS BOlogna Limited Area Model (QBOLAM) and the Regional Atmospheric Modelling System (RAMS), over the Calabria region (Italy) for the period October 2000–May 2002. Contiguous rain area (CRA) analysis is the diagnostic tool used to assess and quantify the position errors of the precipitation forecasts with respect to the observed precipitation patterns. Observation gridded analyses were obtained by means of the Barnes algorithm on the available rain gauge observations.Moreover, an approach to measure the quality of precipitation forecasts routinely by means of a global indicator called CRA Mean Shift (CMS) that summarizes the CRA verification outcomes is proposed. The CMS index would represent a statistical indicator of model quality in forecasting the correct positions of precipitation patterns.The model's tendency to misplace the forecast precipitation patterns towards a particular direction was tested by using a bootstrap procedure.All models seem to show statistically poor abilities in forecasting the correct precipitation pattern position over the verification domain considered. As far as the tendency towards a particular direction is concerned, only the RAMS model seems to show a systematic horizontal misplacement of precipitation patterns towards a particular direction. Copyright © 2008 Royal Meteorological Society