bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Marginal Likelihood Model for Family‐Based Data
Authors: Lo Shaw‐Hwa , Liu Xin , Shao Yongzhao 
Published: July 2003

SummaryThis paper presents a marginal likelihood model for family‐based data based upon the transmission of marker alleles from each heterozygous parent to his/her affected children. The proposed model, extending the maximum‐likelihood‐binomial (MLB) method and the disequilibrium maximum‐likelihood‐binomial (DMLB) method (Abel et al. 1998; Abel & Müller‐Myhsok, 1998; Huang & Jiang, 1999), is adaptive to linkage disequilibrium (LD) and linkage heterogeneity. Compared with other procedures, the likelihood ratio test (LRT) derived from the proposed model enjoys superior qualities. First, simulations indicate that the power of the LRT is greater than that of the TDT or DMLB in all of our studied scenarios. Second, when we applied the LRT and other tests to a Tourette Syndrome data, the result was data favorable to the use of the LRT. Therefore, we recommend the use of the LRT as an additional linkage test wherever applicable, especially when the amount of LD is uncertain.
Joining the Pillars of Hercules: mtDNA Sequences Show Multidirectional Gene Flow in the Western Mediterranean
Authors: Plaza S. , Calafell F. , Helal A. , Bouzerna N. , Lefranc G. , Bertranpetit J. , Comas D. 
Published: July 2003

SummaryPhylogenetic analysis of mitochondrial DNA (mtDNA) performed in Western Mediterranean populations has shown that both shores share a common set of mtDNA haplogroups already found in Europe and the Middle East. Principal co‐ordinates of genetic distances and principal components analyses based on the haplotype frequencies show that the main genetic difference is attributed to the higher frequency of sub‐Saharan L haplogroups in NW Africa, showing some gene flow across the Sahara desert, with a major impact in the southern populations of NW Africa. The AMOVA demonstrates that SW European populations are highly homogeneous whereas NW African populations display a more heterogeneous genetic pattern, due to an east‐west differentiation as a result of gene flow coming from the East. Despite the shared haplogroups found in both areas, the European V and the NW African U6 haplogroups reveal the traces of the Mediterranean Sea permeability to female migrations, and allowed for determination and quantification of the genetic contribution of both shores to the genetic landscape of the geographic area.Comparison of mtDNA data with autosomal markers and Y‐chromosome lineages, analysed in the same populations, shows a congruent pattern, although female‐mediated gene flow seems to have been more intense than male‐mediated gene flow.
miLD and booLD Programs for Calculation and Analysis of Corrected Linkage Disequilibrium
Authors: Aulchenko Y. S. , Axenovich T. I. , Mackay I. , Duijn C. M. van 
Published: July 2003

SummaryWe describe software which calculates a set of linkage disequilibrium statistics, including multiallelic D′ corrected by the bootstrap and permutation. The software also provides a tool for maximum likelihood and least squares estimation and testing of a set of hierarchical hypotheses formulated within the framework of the Malecot model of the decay of linkage disequilibrium with distance. Additionally, the bootstrap approach is used for estimation of the model parameter's confidence intervals and for hypothesis testing. The programs are available from http://www.geneticepi.com/Research/software/software.html
Y Chromosome and Mitochondrial DNA Characterization of Pasiegos, a Human Isolate from Cantabria (Spain)
Authors: Maca‐Meyer N. , Sánchez‐Velasco P. , Flores C. , Larruga J.‐M. , González A.‐M. , Oterino A. , Leyva‐Cobián F. 
Published: July 2003

SummaryMitochondrial DNA sequences and Y chromosome haplotypes were characterized in Pasiegos, a human isolate from Cantabria, and compared with those of other Cantabrian and neighbouring Northern Spain populations. Cantabria appears to be a genetically heterogeneous community. Whereas Lebaniegos do not differ from their eastern Basque and western Asturian and Galician neighbours, Pasiegos and other non‐Lebaniego Cantabrians show significant differences with all of them. Pasiegos are peculiar for their high frequencies of Y chromosomal markers (E‐M81) with North African assignation, and Y chromosomal (R‐SRY2627) and mtDNA (V, I, U5) markers related to northern European populations. This dual geographic contribution is more in agreement with the complex demographic history of this isolate, as opposed to recent drift effects. The high incidence in Cantabrians with pre‐V and V mtDNA haplotypes, considered as a signal of Postglacial recolonization in Europe from south‐western refugees, points to such refugees as a better candidate population than Basques for this expansion. However, this does not discount a conjoint recolonization.
A Reassessment of Genetic Diversity in Icelanders: Strong Evidence from Multiple Loci for Relative Homogeneity Caused by Genetic Drift
Authors: Helgason A. , Nicholson G. , Stefánsson K. , Donnelly P. 
Published: July 2003

SummaryThere has been some controversy in the literature concerning whether Icelanders are genetically homogenous or heterogeneous relative to other European populations. We reassess this question in the light of large data sets spanning 83 autosomal SNP loci, 14 serogenetic loci, 6622 Y‐chromosomes and 3214 sequences from mtDNA hypervariable segments 1 and 2 (HVS1 and HVS2). Our results strongly support the hypothesis that genetic drift, with a consequent loss of variation, has had a greater impact on Icelanders than most other Europeans. We also analyse 7245 HVS1 sequences from 25 European populations. In line with other studies, we observe a deficit of rare HVS1 haplotypes and an excess of intermediate frequency haplotypes in Icelanders compared to most European populations, with some measures of genetic diversity indicating relative heterogeneity and others indicating relative homogeneity of Icelanders. Simulations indicate that genetic drift, and not admixture (as proposed by Árnason, 2003) is the most likely cause of the atypical Icelandic HVS1 frequency spectrum. These simulations reveal that gene diversity (heterozygosity) and mean pairwise differences are largely insensitive to events in recent population history, while statistics based on the number of haplotypes or segregating sites are much more sensitive. Overall, our analyses strongly indicate that the Icelandic gene pool is less heterogeneous than those of most other European populations.
The Causal Element for the Lactase Persistence/ non‐persistence Polymorphism is Located in a 1 Mb Region of Linkage Disequilibrium in Europeans
Authors: Poulter M. , Hollox E. , Harvey C. B. , Mulcare C. , Peuhkuri K. , Kajander K. , Sarner M. , Korpela R. , Swallow D. M. 
Published: July 2003

SummaryExpression of lactase in the intestine persists into adult life in some people and not others, and this is due to a cis‐acting regulatory polymorphism. Previous data indicated that a mutation leading to lactase persistence had occurred on the background of a 60 kb 11‐site LCT haplotype known as A (Hollox et al. 2001). Recent studies reported a 100% correlation of lactase persistence with the presence of the T allele at a CT SNP at −14 kb from LCT, in individuals of Finnish origin, suggesting that this SNP may be causal of the lactase persistence polymorphism, and also reported a very tight association with a second SNP (GA –22 kb) (Enattah et al. 2002). Here we report the existence of a one megabase stretch of linkage disequilibrium in the region of LCT and show that the –14 kb T allele and the –22 kb A allele both occur on the background of a very extended A haplotype. In a series of Finnish individuals we found a strong correlation (40/41 people) with lactose digestion and the presence of the T allele. The T allele was present in all 36 lactase persistent individuals from the UK (phenotyped by enzyme assay) studied, 31/36 of whom were of Northern European ancestry, but not in 11 non‐persistent individuals who were mainly of non‐UK ancestry. However, the CT heterozygotes did not show intermediate lactase enzyme activity, unlike those previously phenotyped by determining allelic transcript expression. Furthermore the one lactase persistent homozygote identified by having equally high expression of A and B haplotype transcripts, was heterozygous for CT at the −14 kb site. SNP analysis across the 1 megabase region in this person showed no evidence of recombination on either chromosome between the –14 kb SNP and LCT. The combined data shows that although the –14 kb CT SNP is an excellent candidate for the cause of the lactase persistence polymorphism, linkage disequilibrium extends far beyond the region searched so far. In addition, the CT SNP does not, on its own, explain all the variation in expression of LCT, suggesting the possibility of genetic heterogeneity.
Microbial flora of technological interest in raw ovine milk during 6°C storage
Authors: Sanjuan Silvia , Rúa Javier , García‐Armesto María R 
Published: July 2003

Changes in the microbial flora of ovine milk of medium hygienic quality (initial mean total plate count 3.3 × 105 cfu/mL) were studied throughout refrigerated storage at 6°C. Total plate counts after 48 h of refrigerated storage (mean count 4.6 × 105 cfu/mL) were under the current standards in the European Union (EU) for raw ovine milk to be used for cheesemaking after heat treatment. However, after 96 h, mean total plate counts (1.6 × 107 cfu/mL) were above the standards. Lactococci were found at levels higher than Pseudomonas spp. in milk freshly drawn (54.5% and 3.5% of total plate count, respectively) and after 96 h at 6°C (47.9% and 33.9% of total plate count, respectively). Lactobacilli, enterococci, coliforms and thermodurics were found at values lower than lactococci and Pseudomonas spp., before and after refrigerated storage (≤ 0.08% of the total plate count). A significant growth (P < 0.001) was detected for mesophiles, Pseudomonas spp. and lactococci after 96 h of refrigeration at 6°C; however, thermodurics, coliforms, lactobacilli and enterococci, showed no significant increase (P > 0.05). Presumptive Escherichia coli (β‐glucuronidase‐positive) underwent a decrease throughout storage at 6°C.
Market segmentation of cheese consumers: an approach using consumer's attitudes, purchase behaviour and sociodemographic variables
Authors: Mesías Francisco J , Escribano Miguel , Rodríguez De Ledesma Antonio , Pulido Francisco 
Published: July 2003

Market segmentation, as a technique to split a market up into segments in which consumers are as homogeneous as possible, is of great importance for companies, as it allows objective markets to be chosen for the application of differentiated marketing policies. The aim of the present work is the segmentation of the cheese market in Extremadura (SW Spain), using cluster analysis.The data are taken from a survey of cheese consumers in Extremadura; the items of the survey are related to their cheese consumption habits, and their attitudes and preferences with respect to this product. The analysis distinguished four homogeneous consumer groups with respect to several sociodemographic and consumption behaviour variables that are of great interest for subsequent market interventions.
Textural and microstructural properties of urfa cheese (a white‐brined Turkish cheese)
Authors: Özer B H , Robinson R K , Grandison A S 
Published: July 2003

The texture and microstructure of white‐brined cheeses similar to urfa (a traditional Turkish cheese) were studied. One batch of cheeses was made in the traditional manner and one batch was made from ultrafiltered (UF) milk. Samples from each batch were either ripened in brine after production or scalded in whey for 3 min at 90°C prior to ripening. The results showed only marginal differences in the ripening profiles of both batches of unscalded cheeses, but scalding slowed down the extent of proteolysis in both batches. The scalded cheeses had a firmer texture than the unscalded ones, and the unscalded UF cheese had a more ‘springy’ body than the unscalded traditional cheese. Overall, scalding resulted in a more homogeneous structure, but the unscalded UF cheese had a close texture that resembled the scalded samples. It was concluded that, with respect to texture and structure, cheeses made with UF milk do not need to be scalded after production.
Some properties of set yoghurt made from caprine milk and bovine–caprine milk mixtures fortified by ultrafiltration or the addition of skim milk powder
Authors: Uysal Harun , Kilic Sevda , Kavas Gokhan , Akbulut Necati , Kesenkas Harun 
Published: July 2003

Set yoghurt was produced from caprine milk (A), 70% caprine‐30% bovine (B) and 50% caprine–50% bovine milk (C) mixtures, and stored for 14 days at ±4°C. Two methods of fortification, namely ultrafiltration (UF) and the addition of bovine skim milk powder (SMP), were applied to the milk mixtures. Some chemical, physical, microbiological and sensory properties of the six samples were analysed on the 1st, 7th and 14th days of storage. The effects of milk type, concentration method and storage period on the physicochemical and microbiological properties of the samples were investigated statistically.
Influence of different culturing conditions on kefir grain increase
Authors: Schoevers Anine , Britz Trevor J 
Published: July 2003

Kefir grains are the natural starter used during kefir production. Factors influencing grain increase—incubation temperature of 18, 22, 25 or 30°C, enrichment with combinations of tryptose (20 g/L) and yeast extract (20 g/L), and cultivation with and without agitation—were studied to develop a method for mass grain production. The highest grain increase (582%) was found with activated grains cultivated with agitation at 25°C in low‐fat milk containing tryptose and replacing the fermented milk daily. Full‐cream milk under the same conditions gave an increase of 522%. Cultivation without agitation resulted in 175% and 173% increases for low‐fat and full‐cream milk, respectively.
Dexamethasone treatment of a canine, but not human, tumour cell line increases chemoresistance independent of P‐glycoprotein and multidrug resistance‐related protein expression
Authors: Mealey K. L. , Bentjen S. A. , Gay J. M. , Hosick H. L. 
Published: July 2003

AbstractGlucocorticoids are often used in veterinary cancer patients because of their anti‐inflammatory actions, appetite‐stimulating effects, ability to decrease nausea and vomiting associated with some chemotherapy agents, and, in some instances, for their cytotoxic actions on susceptible tumour cells. Veterinary oncologists may not consider the possibility that the use of glucocorticoids may adversely affect response to chemotherapy. There is evidence that glucocorticoids can up‐regulate the expression of multidrug resistance genes in some tissues. Whether or not glucocorticoid‐induced expression of multidrug resistance proteins occurs in tumour cells is not presently known. The purpose of this study was to determine if dexamethasone induces P‐glycoprotein (P‐gp) or multidrug resistance‐related protein 1 (MRP1) in tumour cell lines. A canine osteosarcoma cell line (OS2.4) and a human myeloid leukaemia cell line 60 (HL60) were treated in culture with dexamethasone. The presence of a glucocorticoid receptor was confirmed in both cell lines by reverse‐transcriptase polymerase chain reaction. Western blots for P‐gp and MRP1 expression were performed on vehicle‐treated and dexamethasone‐treated cells. Sensitivity towards several chemotherapeutic drugs (cisplatin (cis‐diamminedichloroplatinum), doxorubicin, methotrexate and vincristine) was determined by 3‐(4,5‐dimthylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. While dexamethasone treatment of OS2.4 cells increased the resistance to cisplatin and methotrexate, an increase in P‐gp or MRP1 expression was not observed. Dexamethasone‐treated HL60 cells did not develop chemoresistance and did not show increased expression of P‐gp or MRP1.
Preclinical evaluation of 5‐aminolevulinic acid‐based photodynamic therapy for canine transitional cell carcinoma
Authors: Lucroy M. D. , Ridgway T. D. , Peavy G. M. , Krasieva T. B. , Higbee R. G. , Campbell G. A. , Blaik M. A. 
Published: July 2003

AbstractAs a prelude to photodynamic therapy, 5‐aminolevulinic acid (ALA) was given orally to healthy dogs. ALA‐induced protoporphyrin IX (PpIX) fluorescence significantly increased in the mucosa of the urinary bladder in an ALA dose‐dependent fashion. Vomiting occurred after ALA administration in 70% of the dogs but did not affect PpIX fluorescence. ALA‐based photodynamic therapy (PDT) of the urinary bladder in healthy dogs caused only submucosal oedema within the bladder wall. No haematologic or serum biochemistry abnormalities were observed after ALA administration. Microscopic haematuria was observed in all the dogs after PDT but was mild and self limiting. ALA‐based PDT was administered to six dogs with transitional cell carcinoma (TCC) of the lower urinary tract. ALA‐based PDT resulted in tumour progression‐free intervals from 4 to 34 weeks in five dogs; one dog with pre‐existing hydronephrosis died shortly after PDT. Dogs with TCC represent an outbred, spontaneous, tumour model for developing PDT protocols for humans with bladder cancer.
Intravenous administration of 9‐aminocamptothecin to dogs with lymphoma
Authors: Moore A. S. , Imondi A. R. , De Souza P. L. , Wood C. A. 
Published: July 2003

AbstractA colloidal dispersion formulation of 9‐aminocamptothecin (9‐AC) was administered intravenously to 10 dogs with previously untreated, spontaneously occurring, multicentric lymphoma. The dogs received a 72‐h infusion of 9‐AC at a rate of 46.5–51.25 µg m−2 h−1(total dose range 3.35–3.69 mg m−2). This dose range was associated with myelosuppression, consisting principally of neutropenia with a nadir at 7 days following the start of infusion. Neutropenia and thrombocytopenia were the most common toxicoses and are most likely to be dose‐limiting toxicities; low‐grade gastrointestinal signs were rarely seen. Concentrations of 9‐AC lactone, as well as clinical toxicities, compare favourably with those found in humans. Tumour responses were seen in all treated dogs. Response to other chemotherapy, following cessation of 9‐AC treatment, was not obviously compromised even in dogs clinically resistant to 9‐AC. 9‐AC is a novel treatment drug for canine lymphoma, which appears to show great promise.
Postoperative radiotherapy and mitoxantrone for anal sac adenocarcinoma in the dog: 15 cases (1991–2001)
Authors: Turek M. M. , Forrest L. J. , Adams W. M. , Helfand S. C. , Vail D. M. 
Published: July 2003

AbstractThe medical records of 15 dogs with anal sac adenocarcinoma (ASAC) treated with concurrent curative‐intent radiotherapy and mitoxantrone (MX) after surgical removal of the primary tumour were reviewed retrospectively. Radiation was prescribed at 15 daily fractions of 3.2 Gy for a total dose of 48 Gy. MX was given intravenously at a dosage of 5 mg m−2every 3 weeks for five treatment sessions. Twelve dogs received pelvic irradiation to include the regional lymph nodes (LNs) and three received radiation only to the perineum. At the time of diagnosis, four dogs were hypercalcaemic and seven dogs presented with regional LN metastasis. All the dogs with regional LN metastasis received pelvic irradiation, and in three cases, metastatic LNs were treated in the macroscopic disease setting. The median event‐free survival was 287 days, and the median overall survival was 956 days. Acute and chronic radiation complications were common and non‐life threatening, although chronic complications contributed to the decision to euthanize two dogs. The results observed in this retrospective analysis compare favourably with cases of ASAC in the literature related to treatment with surgery and/or chemotherapy.
Sarcoma development after radiotherapy in two dogs
Authors: Mellanby R. J. , Herrtage M. E. , Chantry J. , Dobson J. M. 
Published: July 2003

AbstractTwo dogs were treated with a hypofractionated course of radiotherapy following surgical excision of an intermediate grade mast cell tumour and a round cell tumour, respectively. Both dogs developed a sarcoma of the bone, within the irradiated site, several years after the initial radiotherapy treatment. Bone tumours arising within a previously irradiated area are well‐recognized late radiotherapy side‐effect in humans but have been reported infrequently in dogs. These are the first case reports to describe bone sarcomas in the appendicular skeleton at a site, which had been previously treated by a hypofractionated course of radiotherapy for an unrelated tumour.
Enhanced bioavailability of oral docetaxel by co‐administration of cyclosporin A in dogs and rats
Authors: McEntee M. , Silverman J. A. , Rassnick K. , Zgola M. , Chan A. O. , Tau P. T. , Page R. L. 
Published: July 2003

AbstractPharmacokinetic and pharmacodynamic endpoints of intravenously and orally administered docetaxel (DT) with or without oral cyclosporine were characterized in rats and dogs. Plasma samples were analysed for DT using liquid chromatography–mass spectrometry. DT area‐under‐the‐concentration–time curve, plasma clearance and maximum serum clearance were significantly affected by cyclosporine in rats (P ≤ 0.0005). Bioavailability of DT alone and DT combined with cyclosporine was 1.3 and 82%, respectively, in rats. In dogs, cyclosporine resulted in a 14–17‐fold increase in peak DT concentrations (P < 0.0005) and area‐under‐the‐curve (P < 0.0005), and a 17‐fold reduction in DT clearance (P < 0.005). Bioavailability of DT alone was 18 ± 16% and statistically exceeded 100% (251 ± 104%) when combined with cyclosporine in dogs. Two of the six dogs receiving DT plus cyclosporine developed neutropenia, and one of the six dogs experienced vomiting and diarrhoea. Cyclosporine significantly alters the disposition of oral DT in dogs and rats, such that clinically relevant serum concentrations are achievable.
The Scale of Successional Models and Restoration Objectives
Authors: Parker V. Thomas 
Published: July 2003

AbstractSuccessional models are used to predict how restoration projects will achieve their goals. These models have been developed on different spatial and temporal scales and consequently emphasize different types of dynamics. This paper focuses on the restoration goal of self‐sustainability, but only in the context of a long‐term goal. Because of the temporal scale of this goal, we must consider the impact of processes arising outside of the restoration site as of greater importance than restoration itself. Because ecological systems are open, restoration sites will be subjected to many external influential processes. Depending on the landscape context, the impact of these processes may not be noticeable, or, at the other extreme, they may prevent the achievement of restoration objectives. A second issue is to emphasize the nature of processes in the long term, that they are a complex of characteristics such as magnitude, frequency, and extent. Ecological systems are only adapted to a range of values in each of these characteristics. Restoration often combines goals that are of different scales. Models appropriate to these goals need consideration.