text:
Two-stage genome-wide association study identifies integrin beta 5 as having potential role in bull fertility
Fertility is one of the most critical factors controlling biological and financial performance of animal production systems and genetic improvement of lines. The objective of this study was to identify molecular defects in the sperm that are responsible for uncompensable fertility in Holstein bulls. We performed a comprehensive genome wide analysis of single nucleotide polymorphisms (SNP) for bull fertility followed by a second-stage replication in additional bulls for a restricted set of markers.
In the Phase I association study, we genotyped the genomic sperm DNA of 10 low-fertility and 10 high-fertility bulls using Bovine SNP Gene Chips containing approximately 10,000 random SNP markers. In these animals, 8,207 markers were found to be polymorphic, 97 of which were significantly associated with fertility (p < 0.01). In the Phase II study, we tested the four most significant SNP from the Phase I study in 101 low-fertility and 100 high-fertility bulls, with two SNPs (rs29024867 and rs41257187) significantly replicated. Rs29024867 corresponds to a nucleotide change of C → G 2,190 bp 3' of the collagen type I alpha 2 gene on chromosome 4, while the rs41257187 (C → T) is in the coding region of integrin beta 5 gene on chromosome 1. The SNP rs41257187 induces a synonymous (Proline → Proline), suggesting disequilibrium with the true causative locus (i), but we found that the incubation of bull spermatozoa with integrin beta 5 antibodies significantly decreased the ability to fertilize oocytes. Our findings suggest that the bovine sperm integrin beta 5 protein plays a role during fertilization and could serve as a positional or functional marker of bull fertility.
We have identified molecular markers associated with bull fertility and established that at least one of the genes harboring such variation has a role in fertility. The findings are important in understanding mechanisms of uncompensatory infertility in bulls, and in other male mammals. The findings set the stage for more hypothesis-driven research aimed at discovering the role of variation in the genome that affect fertility and that can be used to identify molecular mechanisms of development.
Fertilization is a critical event at the onset of mammalian development. The widespread use of artificial insemination has revealed great variation in fertility among sires
Uncompensable infertility defects may result from molecular defects caused by abnormalities in spermatozoal DNA, RNA, or proteins, which impair the ability of spermatozoa to interact with oocytes and induce embryonic development
Recent advances in animal genome sequencing and associated technologies are providing new insights into the genomics study of gametes and embryos
The objective of the present study was to use a high-throughput and a high-density SNP array to conduct a near-genome-wide association study of bull fertility. Spermatozoa DNA were isolated from well-characterized low fertility (n = 10) and high fertility (n = 10) bulls (Phase I study) and examined for approximately 10,000 SNPs, followed by the screening of the four most significant SNPs in a larger population (101 low- and 100 high-fertility bulls; Phase II study).
Bull selection
Pure Holstein bulls were selected based on their fertility as previously described by Peddinti et al.
Definition of low- and high-fertility bulls
The fertility of bulls (Holstein), drawn from a total population of 874 bulls, is based on an average of 788 breeding, ranging from 101 to 11,997. We used the model described by Zwald et al.
Table 1
Oligonucleotide probe sequences for single-nucleotide polymorphism (SNP) markers
Primers and detection probes
Forward primer: 5'-GTCTGGTATTCCCATCTCTTTCAGA-3'
Reverse primer: 5'-TTACTGATTGAAGGGCAACTGTGT-3'
Probe 1: 5'-6FAM-TTTTCCACAG
Probe 2: 5'-VIC-TTTTCCACAG
Forward primer: 5'-ACTCTGTCTCTGAGATTCGATTCAGT-3'
Reverse primer: 5'-CTGAAATCTTTCATTCCCTAGCTGATG-3'
Probe 1: 5'-6FAM-CTGAAAACTCT
Probe 2: 5'-VIC-CTGAAAACTCT
Forward primer: 5'-TGGAGGAGTTCTTTAATGCTTATAAATG-3'
Reverse primer: 5'-GGAGGCACAAAATAGTTAACAGACATC-3'
Probe 1: 5'-6FAM-CTAAAC
Probe 2: 5'-VIC-CTAAAC
Forward primer: 5'-CGAAATGGCTTCAAACCCTCTGTA-3'
Reverse primer: 5'-TGTTGAAGGTGAAATCCACAGTGT-3'
Probe 1: 5'-6FAM-CAGAAAGCC
Probe 2: 5'-VIC-AGAAAGCC
Isolation of pure sperm cells and DNA extraction
Alta Genetics Inc. (Watertown, WI) provided frozen semen straws of selected bulls. Thawed spermatozoa were then purified through a Percoll gradient, washed, counted, and pelleted for DNA isolation
SNP genotyping (Phase I study)
The 10 K SNP Bovine Gene Chip (Affymetrix/ParAllele GeneChip; Affymetrix Inc., Santa Clara, CA) was used to genotype DNA samples (250 ng/μl) of 10 low-fertility and 10 high-fertility bulls. The experiment was carried out at Baylor College of Medicine (Houston, TX), and assays utilized molecular inversion probe (MIP) technology, allowing the multiplex detection of single base variants using a 4-color array hybridization assay
Allelic discrimination analysis (Phase II study)
The allelic discrimination technique, based on the TaqMan technology (ABI Prism 7000 Sequence Detection System, Applied Biosystems, Foster City, CA) was performed by scientists at SeqWright, Inc. seqwright.com on DNA samples (4 ng/μl) of 101 low-fertility and 100 high-fertility bulls to validate the Phase I association study. Primer and probe sets were designed on a sequence of 501 nucleotides containing the SNP (250 nucleotides downstream and upstream of the SNP allele) using the Primer Express software (Applied Biosystems, Foster City, CA). The probes were designed and labeled with FAM (6-carboxy-fluorescein) or VIC fluorescent dyes (Applied Biosystems, Foster City, CA) to match perfectly either one of the alleles (Table
PCR reactions were carried out in a total volume of 25 μl as recommended by the manufacturer. Each reaction consisted of 5 μl of sperm DNA in 20 μl Master Mix solution (Applied Biosystems, TaqMan Universal PCR Master Mix) containing primers (900 nM) and probes (200 nM). DNA samples were amplified by 40 times (2 min-50°C, 10 min-95°C, 15 sec-92°C, and 1 min 60°C). For each PCR run, negative (no-template) and positive (oligos) controls were added, and each run was preceded or followed by 1-minute incubation at 60°C to determine the background, or final levels of fluorescence, in each reaction. The base calls were made by examining all samples on the allelic discrimination graph, and the Sequence Detection Software (Applied Biosystems, Foster City, CA) was used to determine the homozygosis or heterozygosis of alleles. All samples were run in triplicates for each SNP allele.
The major repository of SNP data in the National Center for Biotechnology Information (NCBI) database (dbSNP), combined with Entrez Genome (NCBI) as well as the Ensembl automatic analysis pipeline, were used to characterize and annotate the markers (SNPs and genes) based on the cattle genome assembly version 3.1. For each SNP, a sequence of 501 nucleotides consisting of the 250 nucleotides immediately upstream and downstream of the SNP allele, were extracted and the best hit in the Bovine 3.1 genome identified using BLASTN. We considered only the hits (i) found on the same chromosome as the query, (ii) with E-values equal or close to 0.00 and (iii) presenting at least 94% alignment with the full length of the query sequence. Furthermore, the same query sequences were used to search for putative transcription factor binding sites through the Transfac-blastX (TRANSFAC Database 7.0 for searching eukaryotic transcription factors).
Functional analysis of integrin beta 5 (ITGB5)
Sperm preparation and treatment
Thawed spermatozoa were purified through a Percoll gradient as previously reported
Oocyte maturation and in vitro fertilization
Bovine oocytes were purchased from Bomed Inc. (Madison, WI), and maturation took place during the transportation. These oocytes were washed and fertilized with treated and untreated spermatozoa at a final concentration of 106 spermatozoa/ml. After 18 hours of co-incubation, oocytes were collected, denuded, washed, fixed, and placed on slides for staining with 0.1% aceto-orcein on slides. The nuclear status of oocytes was observed under a microscope, and the fertilized oocytes (two extruded polar bodies and/or two pronuclei) were counted to assess the fertilization rates.
Statistical analysis
In the Phase I study, the 20 bulls of varied fertility were typed for 9,919 SNP using Affymetrix 10 K Xba 142 2.0 array. A total of 1,712 markers fixed for a single genotype in this sample were excluded from further analysis. Markers were tested for Hardy-Weinberg Equilibrium using a 1 degree of freedom chi-square test. Markers with a p value < 0.05 were flagged as potentially out of HWE, but were used for association analysis.
The fertility of the bulls was converted to Z-scores and used as the quantitative trait for the association analysis. Analysis was conducted only at the markers' positions; no attempt at interval mapping was made. At each marker, the mean fertility, scored as a Z-score, was compared between genotypes using single marker regression. If the n for a genotype was 1, the samples were collapsed into the heterozygote. Benjamini- Hochberg FDR was calculated at each marker, adjusting 8,207 tests. A p-value less than 0.01 was set as the threshold of a significant association between the SNP marker and bull fertility; this corresponds to an FDR of 84%. Similar analyses were conducted in Phase II data.
Results and discussion
The lack of methods to accurately predict sire fertility obliges the artificial insemination (AI) industry to keep and test hundreds of bulls. The selection of such bulls, whose fertility has been evaluated with progeny tests prior to their use in large-scale breeding programs, is costly and can take several years. Recent advances in cattle genome projects and molecular genetic technologies have increased the likelihood of identifying uncompensatory defects impairing the functions of spermatozoa. High-throughput technologies may help pinpoint relationships between a single DNA marker (i.e., SNP) and economically important traits in dairy cattle. Information about specific SNPs can enhance the efficiency of genetic selection, especially for traits that are (i) too difficult or expensive to measure in all animals and/or (ii) expressed after a long field trial (i.e., fertility).
Determination of bulls with uncompensatory infertility
The most fertile and the least fertile pure Holstein bulls were selected from a pool of 874 available bulls with at least 300 breeding records. These were defined as the representative outliers for their corresponding groups and the scaling of fertility as the deviation from the population average fertility. The average breeding and fertility rates of the 10 low- and 10 high-fertility bulls used in the Phase I association study were 1,974 and -9.2% versus 3,540 and 6.2%, respectively. In the Phase II study, these values were 904 and -4.2% for low-fertility (100), and 994 and 3.4%, for high (101) fertility bulls (Table
Table 2
Artificial insemination (A.I.) and fertility records of bulls
A.I. Services
Fertility data
Fertility status
(mean % ± sd)
SNP genotyping (Phase I study)
-9.2 ± 4.6
6.2 ± 1.9
Allelic discrimination (Phase II study)
-4.2 ± 1.9
3.4 ± 1.1
Identification of SNPs associated with fertility using DNA microarrays (Phase I study)
The recent progress in genomics and automation has rendered the SNP genotyping a promising technology for genetic studies of the cow genome, which contains approximately one SNP every 252 base pairs
Figure 1
The figure represents the fertility distribution of bulls used for SNP genotyping (mean ± SD)
The figure represents the fertility distribution of bulls used for SNP genotyping (mean ± SD). The scaling of fertility was defined as the deviation from the population average. The low-fertility bulls were scored below (negative data) the average conception rate while the high-fertility bulls scored above (positive data). The average difference between the two groups was 15.4%.
No significant difference was found between the average of SNP call rates in both groups (95.8% ± 4.8% versus 98.6% ± 0.7%, respectively; p-value = 0.15). The HWE test revealed an FDR of 61% corresponding to 790 SNP markers that failed the test (versus the 496 expected at random), but were used for QTL analysis as mentioned above (Statistical analysis section). A total of 1,712 SNP markers were excluded from analysis because they were not polymorphic. In the Phase I samples, the fertility (Z-score) of bulls was used as the quantitative trait for the association analysis of the remaining 8,207 markers. The p-value distribution of the 8,207 markers' test showed a slight deviation from the uniform to left end (near 0) of the distribution, indicating the presence of more putative fertility-associated SNP markers in the data (Figure
Additional File 1
Table S1.
Table S1. Mean fertility (in Z-score), standard deviation, minimum and maximum values for the four markers from the Phase II study.
Click here for file
Additional File 2
Table S2.
Table S2. List of 97 SNP markers associated with fertility (P < 0.01).
Click here for file
Figure 2
The figure represents the distribution of p-values of the 8,207 markers analyzed in the Phase I study
The figure represents the distribution of p-values of the 8,207 markers analyzed in the Phase I study. These p-values were used as guidance to select markers for Phase II.
High-throughput SNP arrays are powerful tools commonly used in humans to track population history and genes associated with diseases
The extent of linkage disequilibrium (LD) around the SNPs in the Holstein population is not clear yet, but we believe the LD may extend a good distance (≤ 0.5 Mb) around the markers due to the extensive inbreeding in the population
Genotyping of large numbers of bulls for the most significant SNP markers (Phase II study)
Large population sizes, often too large to be easily collected, are generally required for defining association between a given SNP and a trait with reasonable power. Thus, the use of several stages of analysis with progressively fewer markers typed in each replication population has become typical in human genome-wide association studies. The key reliability of a significant association result is replication in a second (or third) population. For example, a genome-wide-association (GWA) study of macular degeneration was successfully replicated when the initial study contained only 96 cases and 50 controls
Table 3
Highly informative SNP markers obtained in Phase 1 study.
SNP markers Id (rs#)
Association with fertility
Chromosome location
3.32 × 10-5
9.44 × 10-5
7.7 × 10-6 *
56 × 10-5
38 × 10-5
*Indicates an out of HWE test.
Table 4
Overall SNP call percentages and statistics obtained in Phase II study.
Allelic variation
SNP markers
85 (42%)
128 (64%)
0 (0%)
108 (54%)
25 (12%)
6 (3%)
18 (9%)
91 (45%)
66 (33%)
74 (37%)
156 (78%)
44 (22%)
Total of bulls
Test for HWE
P values
Asterix (*) indicates significant association.
Figure 3
The figure represents the fertility distribution of bulls used for allelic discrimination (mean ± SD)
The figure represents the fertility distribution of bulls used for allelic discrimination (mean ± SD). The scaling of fertility was defined as the deviation from the population average. The low-fertility bulls were scored below (negative data) the average conception rate while the high-fertility bulls scored above (positive data). The average difference between the two groups was 7.6%.
Bioinformatics on the four highly associated SNPs
Bioinformatics were restricted on the four highest significantly associated SNPs (rs29016875, rs29015574, rs29024867, and rs41257187). Only three SNPs gave valuable information (Table
Table 5
Bioinformatics on the four highly informative SNPs.
SNP markers
Gene candidates (NCBI-BLASTN)
Cytoplasmic dynein light chain
Rab3A-interacting molecule (NW_001495537)
Collagen I, alpha2
Integrin β5 (NW001493888)
9 × 10-122
4 × 10-32
Transcription factors (TRANSFAC-BLASTX)
No hits found
(Xl; T-01771)
(S.Cb; T-03376)
No hits found
(Mm; T-02439)
(Mm; T-01339)
S.Cb, Xl, and Mm stand for S. Caenorhabditis Briggsae, Xenopus laevis, and Mus musculus, respectively.
Irx, Ceh, and RAR stand for Iroquois homeobox, Caenorhabditis elegance homeodomain factor, and Retinoic acid receptor, respectively.
Putative binding sites for transcription factors with roles in embryogenesis were found within the nucleotide sequences flanking the SNPs rs29015574 (MEF-2D and Irx for, myocyte enhancer factor-2D and Iroquois homeobox, respectively) and rs29024867 (RAR β3 and Ceh-24 for, retinoic acid receptor and Caenorhabditis elegans-24, respectively). Hence, our findings suggest potential roles of the SNP mutations on regulation of gene expressions as already suggested in other studies
Taken together, our results provide novel loci candidates whose associations with the bull fertility have not previously been reported. Because of the great interest of the non-synonymous SNP rs41257187 associated with the ITGB5, we performed a Six Frame Translation of ITGB5 mRNA reference sequence reported on NCBI (NM_174679.2) using the Baylor College of Medicine's HGSC Search Launcher to find the reading frame leading to the amino acid change. We found that the complete ITGB5 protein could be obtained from two different reading frames (+3 or +1) when using the whole length of RNA sequence or the length from the start codon (ATG), respectively. Contrary to the NCBI report, we found that the SNP mutation site (C/T) induced a synonymous amino acid change of a Proline (CCC) to another Proline (CCT) at the position 778 (P778P). The same SNP (rs41257187) inducing a synonymous amino acid change (Proline to Proline) is also reported on the Ensembl database.
The interest of integrin beta 5 in our study resided in the role(s) played by the integrin family members during fertilization and embryogenesis. Integrins are known to be expressed in a variety of tissues, including reproductive tissues of mice, humans, pigs and cattle
Functional analysis of integrin beta 5
The biological function of the integrin beta 5 subunit is not clearly defined. We tested the potential involvement of ITGB5 isoform on sperm-egg interaction, and the results showed that the percentages of matured oocytes (metaphase II) undergoing a successful fertilization (1–2 PN) with spermatozoa pre-exposed to anti-integrin beta 5 antibody were decreased: 74, 60, and 47% normally fertilized oocytes in the presence of 0, 5, and 20 μg ITGB5/ml, respectively. This dose-dependent inhibition was not attributed to the antibody itself since the pre-exposure of spermatozoa to the non-mammalian protein (BIT) antibody had no effect on the ability of spermatozoa to fertilize the oocytes (Table
Table 6
Effect of masking spermatozoa ITGB5 protein during fertilization.
45 (13)a
242 (74)a
43 (13)a
106 (34)b
190 (60)ab
17 (5)a
116 (40)b
137 (47)b
40 (14)a
45 (17)a
190 (72)a
28 (11)a
*Bovine spermatozoa were exposed to antibodies (anti-ITGB5 and anti-BIT) for 2 h before being using to fertilize the oocytes.
"Fertilized oocytes" refers to oocytes observed with at least one pronucleus, while "Unfertilized oocytes" refers to those without any pronuclei, but containing a Germinal Vesicle or Metaphase-1 or -2 structures (with only one extruded polar body).
(%) Percentage expressed on total oocytes.
a, b Values with different superscripts within the same columns are significantly different (Student's test; p < 0.05).
We ruled out the likelihood of non-specific interactions of the anti-ITGB5 antibody and other integrin beta subunits. Indeed, the antibody is raised against a specific N-terminal epitope, which amino acid sequence is not found in other subunits of integrin beta protein. Therefore, our results contribute to the growing body of reports supporting the presence of αvβ integrins on sperm membranes
We have employed a high-density SNP genome association study to identify loci that may play a role in fertility in dairy cattle and significant results in two of four loci were replicated in a second population. Functional studies, including one for genes harboring a replicated locus, the ITGB5 gene, suggest that it may play a role in sperm-egg interaction. These results provide a foundation for more hypothesis-driven research in genome biology, evolution, QTL mapping, and discovering genes and genomic regions for selectable traits.
Authors' contributions
JMF carried out the sperm DNA isolation, performed the bioinformatics and functional analyses, and participated in the manuscript writing. AK and ET carried out the collection and analysis of fertility data and contributed to the study design and manuscript writing. GPP, LC, and TM participated in the design of the study and performed the statistical analysis, the SNP genotyping, and allelic discrimination data, and participated in manuscript writing. KH, LN, and RG performed the SNP genotyping and contributed to the manuscript writing. EM participated in the design of the study, coordinated the study and participated in manuscript writing.
This project was funded by the Mississippi Agricultural and Forestry Experiment Station of Mississippi State University (J-11262), and by Alta Genetics Inc.
High-fertility proteins enhance reproduction rates in Dairy cattle
The Relationship Between the Number of Spermatozoa Inseminated and the Reproductive Efficiency of Individual Dairy Bulls
The causes of reduced fertility with cryopreserved semen
Reproductive loss in high-producing dairy cattle: where will it end?
Sperm function tests and fertility
Invited Review: The Search is on: Finding Accurate Molecular Markers of Male Fertility
The sperm chromatin structure assay. Relationship with alternate tests of semen quality and heterospermic performance of bulls
The effect of semen quality on reproductive efficiency
Can spermatozoa with abnormal heads gain access to the ovum in artificially inseminated super- and single-ovulating cattle?
Relationship of semen quality to sperm transport, fertilization, and embryo quality in ruminants
Advances and applications of genomics and proteomics in gamete and embryo science
Mapping, Fine Mapping, and Molecular Dissection of Quantitative Trait Loci in Domestic Animals
BOARD-INVITED REVIEW: Applications of genomic information in livestock
Dynamics of global transcriptome in bovine matured oocytes and preimplantation embryos
Establishment of a high-resolution 2-D reference map of human spermatozoal proteins from 12 fertile sperm-bank donors
Proteomic identification of human sperm proteins
Spermatozoal RNA: why is it there and what does it do?
Applications of whole-genome high-density SNP genotyping
Genetic association studies of complex traits: design and analysis issues
SNP discovery in associating genetic variation with human disease phenotypes
Convergent adaptation of human lactase persistence in Africa and Europe
Polymorphism of the pig 2,4-dienoyl CoA reductase 1 gene (DECR1) and its association with carcass and meat quality traits
Nucleotide sequence polymorphism within exon 4 of the bovine prolactin gene and its associations with milk performance traits
Mapping and SNP analysis of bovine candidate genes for meat and carcass quality
Selection and use of SNP markers for animal identification and paternity analysis in U.S. beef cattle
Allelic variation in the erythropoietin receptor gene is associated with uterine capacity and litter size in swine
Single nucleotide polymorphisms in four functionally related immune response genes in the horse: CD14, TLR4, Cepsilon, andFcepsilon R1 alpha
Detection and characterization of SNPs useful for identity control and parentage testing in major European dairy breeds
The bovine fatty acid binding protein 4 gene is significantly associated with marbling and subcutaneous fat depth in Wagyu × Limousin F2 crosses
Identification of novel polymorphisms in the nuclear protein genes and their relationship with human sperm protamine deficiency and severe male infertility
Single nucleotide polymorphisms: discovery of the genetic causes of male infertility
Single nucleotide polymorphisms in the protamine-1 and -2 genes of fertile and infertile human male populations
No association of the A260G and A386G DAZL single nucleotide polymorphisms with male infertility in a Caucasian population
Comprehensive proteomic analysis of bovine spermatozoa of varying fertility rates and identification of biomarkers associated with fertility
Genetic Selection for Health Traits Using Producer-Recorded Data. I. Incidence Rates, Heritability Estimates, and Sire Breeding Values
Effects of trait definition on genetic parameter estimates and sire evaluation for clinical mastitis with threshold models
Multiplexed genotyping with sequence-tagged molecular inversion probes
Highly multiplexed molecular inversion probe genotyping: Over 10,000 targeted SNPs genotyped in a single tube assay
Developmental potential of bovine oocytes cultured in different maturation and culture conditions
Detection of Differences in Fertility
Extent of genome-wide linkage disequilibrium in Australian Holstein-Friesian cattle based on a high-density SNP panel
Population genetics for target identification
The human genome project and the discovery of genetic determinants of cancer susceptibility
An SNP in protamine 1: a possible genetic cause of male infertility?
A genome scan to detect quantitative trait loci for economically important traits in Holstein cattle using two methods and a dense single nucleotide polymorphism map
Extensive Genome-wide Linkage Disequilibrium in Cattle
Whole genome linkage disequilibrium maps in cattle
Genome-wide linkage disequilibrium in two Japanese beef cattle breeds
A primary assembly of a bovine haplotype block map based on a 15,036-single-nucleotide polymorphism panel genotyped in holstein-friesian cattle
Complement Factor H Polymorphism in Age-Related Macular Degeneration
Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man
A Common Allele on Chromosome 9 Associated with Coronary Heart Disease
Single-Nucleotide Polymorphisms and Mutation Analyses of the TNP1 and TNP2 Genes of Fertile and Infertile Human Male Populations
Allelic effects on gene regulation at the autoimmunity-predisposing CTLA4 locus: a re-evaluation of the 3[prime] +6230G>A polymorphism
Polymorphisms in the 5' Upstream Region of the CXCR1 Chemokine Receptor Gene, and Their Association with Somatic Cell Score in Holstein Cattle in Canada
Cis- and trans-acting gene regulation is associated with osteoarthritis
Influence of arginine-glycine-aspartic acid (RGD), integrins ([alpha]V and [alpha]5) and osteopontin on bovine sperm-egg binding, and fertilization in vitro
Integrins and adhesion mlecules: Cell adhesion molecules on the oocyte and preimplantation human embryo
Expression of cell adhesion molecules during human preimplantation embryo development
Timing of Gene Expression and Oolemma Localization of Mouse [alpha]6 and [beta]1 Integrin Subunits during Oogenesis
Molecular Basis of Mammalian Gamete Binding
Beta 1-integrins of spermatozoa: a flow cytophotometric analysis
Alpha6beta1 integrin expressed by sperm is determinant in mouse fertilization
Integrin cell adhesion molecules on human spermatozoa
Specific integrin subunits in bovine oocytes, including novel sequences for alpha 6 and beta 3 subunits


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Professor sets high goals in supporting urban and crop sustainability
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As a key player in sustainability science, professor Soe Myint uses his background in geospatial statistics and modeling to help policymakers and land users manage resources sustainably. This year alone, Myint was awarded three grants by the National Aeronautic and Space Administration (NASA), the National Science Foundation (NSF), and the National Oceanic and Atmospheric Administration (NOAA) – a notable accomplishment.
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Comparison Between C++ and C#
Visual Studio .NET 2003
The following table contains important comparisons between C++ and C# features. If you are a C++ programmer, this table will give you the most important differences between the two languages at a glance. For details, use the link to browse to the detailed topic.
Note C++ and C# projects are derived from different project models. For information on the differences between C++ and C# projects, see Item Management in Projects and Using Solution Explorer.
|Refer to the topic
|Inheritance: A class can inherit implementation from one base class only. Also a class or an interface can implement multiple interfaces.
|Arrays: The syntax of declaring C# arrays is different from that of C++ arrays. The tokens "[]" appear following the array type in C#.
|The bool type: There is no conversion between the bool type and other types (specifically int).
|The long type: In C#, the long data type is 64 bits, while in C++, it is 32 bits.
|The struct type: In C#, classes and structs are semantically different. A struct is a value type, while a class is a reference type.
|The switch statement: Unlike the C++ switch statement, C# does not support fall through from one case label to another.
|The delegate type: Delegates are roughly similar to function pointers in C++, but they are type-safe and secure.
|Calling the overridden base class members from derived classes.
See also the examples for override
|Using the new modifier to explicitly hide an inherited member.
|Declaring override methods requires the override keyword.
|Preprocessor directives are used for conditional compilation. No header files are used in C#.
|C# Preprocessor Directives
|Exception handling: Using the finally statement.
|C# operators: C# supports additional operators such as is and typeof. It also introduces different functionality of some logical operators.
|& Operator
|Use of the extern keyword.
|Use of the static keyword.
|An alternative way to the C++ initialization list in constructing the base class.
|See the examples for virtual
|The general structure of the C# program: namespaces, classes, structs, delegates, and enumerations.
|General Structure of a C# Program
|The Main method is declared differently from the main function in C++. Also, compare the usage of the command-line arguments for each language.
|Method parameters: C# supports ref and out parameters, which are used instead of pointers in passing parameters by reference.
|Pointers are allowed in C# but only in unsafe mode.
|Overloading operators is performed differently in C#.
|C# Operators
|Strings: C# strings are different from C++ strings.
|The foreach keyword allows you to iterate through arrays and collections.
|foreach, in
|No global methods or variables in C#: Methods and variables must be contained within a type declaration (such as class or struct).
|General Structure of a C# Program
|No header files or #include directives in C#: The using directive is used to reference types in other namespaces without fully qualifying the type names.
|Local variables in C# cannot be used before they are initialized.
|5. Variables
|Destructors: In C#, you don't have control over when a destructor is called because destructors are called automatically by the garbage collector.
|Constructors: Similar to C++, if you don't provide a class constructor in C#, a default constructor is automatically generated for you. The default constructor initializes all the fields to their default values.
|Instance Constructors
|C# does not support bit fields.
|C++ Bit Fields
|C# input/output services and formatting rely on the run-time library of the .NET Framework.
|C# Language Tour
|In C#, method parameters cannot have default values. Use method overloads if you want to achieve the same effect.
|Compiler Error CS0241
For comparisons between C# and other programming languages, see the Language Equivalents documentation.
See Also
C# Language Tour | Item Management in Projects | Using Solution Explorer


text:
World Mission
We are the worldwide distributor of "The Treasure" audio Bible and pledge to assist in the fulfillment of the Great Commission.
EIN: 383213457Muskegon, MI
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text:
Inter-Hotel Cositel, Coutances
- Free WiFi and free parking
Main amenities
- 55 guestrooms
- Restaurant and bar/lounge
- Breakfast available
- 24-hour front desk
- Garden
- Front desk safe
- Laundry service
- Conference space
For families
- Free cribs/infant beds
- Garden
- Flat-panel TV
- Dry cleaning/laundry service
- Free self parking
What's around
- Coutances Botanical Garden (1.3 mi / 2 km)
- Chateau de Gratot (1.3 mi / 2.2 km)
- Coutances Cathedral (1.4 mi / 2.3 km)
- Chateau Fort de Pirou (10.6 mi / 17.1 km)
- Centre Manche Golf (12.7 mi / 20.4 km)
Inter-Hotel Cositel, Coutances
Hotel Info: 866-539-8117from $56
- Suite
- Double Room Privilege
- Double Room
- Privilege Twin Room
- Comfort Twin Room
- Standard Double or Twin Room
- Double Room
- Comfort Quadruple Room
- Standard Double Room
- Comfort Triple Room
- Standard Triple Room
More great choices
At a glance
Key facts
Hotel size
- This hotel has 55 rooms
- This hotel is arranged over 2 floors
- Check-in time 6 PM-10 PM
- Check-out time is noon
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
- Pets allowed *
- Free WiFi in public areas
- Free WiFi in rooms
- Free self parking
Nearby Three Star Coutances hotels
In the hotel
- Buffet breakfast daily (surcharge)
- Restaurant
- Bar/lounge
- Room service (during limited hours)
- Golfing nearby
- Sailing nearby
- Conference space
- One meeting room
- 24-hour front desk
- Dry cleaning/laundry service
- Safe-deposit box at front desk
- Garden
- In-room accessibility
- Roll-in shower
In the room
- Shower only
- Hair dryer (on request)
- Flat-screen TV
- Desk
- Free WiFi
- Phone
Top Coutances hotels
Nearby hotels
Also popular with travelers from the USA
Inter-Hotel Cositel, Coutances's small print
Also known as
- INTER-HOTEL COSITEL Coutances
- INTER-HOTEL COSITEL Hotel
- INTER-HOTEL COSITEL Hotel Coutances
Mandatory fees
You'll be asked to pay the following charges at check in or check out:
- A tax is imposed by the city: EUR 0.70 per person, per night
Optional extras
Buffet breakfast is offered for an extra charge of EUR 10.50 per person (approximately)
Pets are allowed for an extra charge of EUR 6.50 per pet, per night
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.
What's around Inter-Hotel Cositel, Coutances
- Coutances Botanical Garden (1.3 mi / 2 km)
- Chateau de Gratot (1.3 mi / 2.2 km)
- Coutances Cathedral (1.4 mi / 2.3 km)
- Chateau Fort de Pirou (10.6 mi / 17.1 km)
- Centre Manche Golf (12.7 mi / 20.4 km)
Getting around
- Coutances Station 6-min drive
- Orval-Hyenville Station 7-min drive
- Carantilly-Marigny Station 18-min drive
- Free self parking
Recent reviews
Excellent 4.1 /5 from 54 reviews
Hotel rooms were acceptable but rather tired. No mini-fridge. No AC, but windows fronting garden opened to cool evening air. Might be stuffy on warm/calm nights. Staff were helpful. A little distant to in-town things to see and do.
Good size comfortable room with excellent en suite shower room. Breakfast of a reasonable choice although somewhat pricey.
The Hotel would benefit from tea and coffee facilities in the room and I didn't expect to have to ask for a hair dryer when it said one was provided. The breakfast which is extra was adequate and it was nice to have fresh fruit salad however the egg boiler needs replacing as even after eight minutes the eggs were still half raw.
My daughter and myself stayed at this Hotel about three years ago when it was in the Logis group and we found it very good. the food was excellent but not so good now
2-night stay whilst visiting Lessay Fair, about 15 miles away. Bedroom needed some refurbishment but was clean and comfortable. Staff friendly and helpful. Continental breakfast was self-service, plentiful and good quality. Quiet location, plenty of parking, good & free wi-fi. Would stay again.
Is the description of this hotel not correct? Tell us


text:
Pacific Capital Bancorp (PCBC) Video Chart for Thursday, December 16, 2010
PCBC is attempting to come off the bottom and has itself in a neutral position that is leaning towards turning bullish at this point. A financial play, it carries a bit more risk, but will be on radar for upward movement to break through resistance.
To view the video chart, visit the following link: http://www.qualitystocks.net/videocharts.php


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How Did You Sleep?
€ 16,99
Besorgung - Lieferbarkeit unbestimmt
Oktober 2000
BeschreibungPaul Glennon makes a commanding debut with a writing style that is both quirky and elusive. His stories -- strange, yet funny -- are about madmen, paranoiacs and the allegorically burdened. For the characters in these stories life is a board game to which we have lost, or perhaps never had, the instructions. Their predicaments are impossible, absurd but strangely genuine. A husband wonders if his wife has always been made of wood. A scientist suspects his left hand is plotting against him. A tourist visits a museum dedicated to his own failed romance. The world is trying to communicate something to these characters, but they cannot interpret it. These stories navigate an unusual course between science fiction, satire and psychology. It makes for a journey that is strange, disturbing and surreally comic.
InhaltsverzeichnisThe Museum of the Decay of Our Love My Babylon Cells How Did You Sleep? The Terror The Triangle Man The Bear Story One Hand Self-Loathing Stymies Council Reminiscence Chrome The Manikin Via Crucis: A Retrospective A History of My Mistakes Touched Icarus's Sister Save the Barbers An Anthology of Nestorian Literature Our Flotation on the Bourse The Secret Agent
PortraitPaul Glennon, born in England but resident in Ottawa since 1975, has been published in Descant, Matrix, Canadian Fiction Magazine, and the Blue Penny Quarterly. He has an MA from the University of Ottawa and currently works as a Human Factors specialist -- which means that he attempts to encourage software to work the way humans expect it to.
Pressestimmen'Glennon, however, is an inspired and skillful writer. His rhythm is nearly flawless, and I ended up wishing he had written these as prose poems. "Chrome" is one story that is beautifully realized: a man awakes to find that everything has a sheen of chrome. The narrator's fascination leads him inward and away from people, towards (ironically) the almost hyper-delicious nature of the visual and sensual. Sometimes the surface of things has its compensations.' -- Andrew Lesk Canadian Literature 'Paul Glennon is a rare bird. You would never guess it from his photo on the final page of this debut collection. He stands quite ordinarily under a snowy spruce tree in what could easily be Ottawa, his home since 1975. Contextually Canadianized, he squarely faces the camera, quietly earnest and unthreatening. It's a perfectly expected portrait of a fledgling Canuck writer -- and perfectly misleading. This bird's song is complex, refreshingly impudent and previously unknown.'In One Hand, a man tries to piece together the final weeks of a friend's life from the scribbled notes he has left in an edition of Leonardo da Vinci's notebooks. The friend, having by his own admission not 'an artistic bone in [his] body,' borrows da Vinci's technique of using left-hand, mirror-image writing, in hopes that the left-hand/right-brain neural connection might stimulate his creative side. As his left-hand notes produce involuntary palindromes, anagrams and increasingly mysterious poetry, his right-hand, analytical prose tries to make sense of the psychical Pandora's box he's opened. The final left-hand note offers two riddles that explain the friend's untimely death.'The Museum of the Decay of Our Love describes a scholar's visit to a Central American history museum. The tale hovers dreamlike between dry events and the inner sparks they ignite. The museum's inert displays, steeped in the mythology of conquest and revolution, become interior metaphors for the man's own failed ambition in love. What feels initially too schematic evolves into a subtle probing of how external things morph into symbols as they enter the mind. The award-winning title story offers a bracing and revealing reconception of a very mundane sort of domestic squabbling. Other tales amuse with their satirical quirks, or wrest attention with deft observation.'In Self-Loathing Stymies Council, we meet Mayor Nolan Plunge, a grandstanding windbag who bleats to council that self-loathing is "a Nessus's shirt" he wears daily. In Chrome, we're treated to a fluid metallic world evoked with keen imagination and riveting detail.'Glennon's charms have much to do with his originality, a willingness to veer from the safer formal path. Some stories feel overly glib or disappointingly contrived, and his repeated authorial winking is sometimes too obvious. But the eccentric and penetrating psyche at work here should not be missed.' -- Jim Bartley Globe and Mail 'In his first collection of short stories, How Did You Sleep? (Porcupine's Quill, 2000), Ottawa writer Paul Glennon eschews dirty realism and thinly-veiled autobiography for clever conceits and absurdly-extended metaphors. In one story, the president of a corporation is voted out of power by his executive board, which then votes unanimously to change him into a bear. In another, a man awakes to discover that his entire world appears to him as being made of chrome. Fiction which is funny and smart, without being either cloying or disposable, is a rare commodity in Canadian literature.' -- Nathan Whitlock Danforth Review
Untertitel: New. Sprache: Englisch.
Verlag: PORCUPINES QUILL
Erscheinungsdatum: Oktober 2000
Seitenanzahl: 155 Seiten
Format: kartoniert


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Sprint 4G Case for iPad review
Posted by Andru Edwards Categories: Accessories, Features, Handhelds, Hot Deals, Product Reviews
Update: Check out our Sprint 4G Case video review as well!
A few days ago, we applauded Sprint for the way they were promoting their 4G service in conjunction with the launch of the iPad with their Sprint 4G Case. Obviously marketed towards the iPad buyers to get them to choose using a Sprint Overdrive 4G device rather than AT&T's 3G plan, Sprint teamed up with Best Buy to give these cases away for free to anyone who'd purchase an Overdrive mobile hotspot at a participating Best Buy location.
Since we are in a 4G-enabled area, we figured we'd head on over to Best Buy to see if we couldn't finagle one of the Sprint 4G Cases from the store. We weren't going to be buying an Overdrive hotspot (we already have one,) but we were willing to just pay for one if that's what needed to happen. The first surprise came when Best Buy told us that we certainly could just buy one outright, and that it would cost us a full $0.01. A penny. For an iPad case! We gladly paid for it, and were on our way.
Now, I didn't recall exactly what the case that was advertised from Sprint looked like, but we did immediately think "Huh, this feels kinda cheap - I thought it would be better than this." When I got back, I took a look at the Sprint 4G Case promo again, and it was obvious - the case that Sprint is promoting on the site is not the same case that you will actually receive at Best Buy.
Update: Looks like a couple of people have tracked down the folio version of the case. We did some more calling around this morning to a total of 6 participating Best Buy locations, and none of them had a clue about the folio—however, they're out there somewhere. We recommend calling up your local Best Buy before heading over, to make sure they've got the one you want in stock!
Click to continue reading Sprint 4G Case for iPad review
Gallery: Sprint 4G Case for iPad review
Kick-Ass Pleased Fans, Underperformed at Box Office
Posted by Robin Paulson Categories: Movies, Reviews, Marvel Comics
UPDATE: According to THR, Kick-Ass did take the top rank at the box office, despite early Sunday estimates stating otherwise.
Matthew Vaughn's film adaptation of Kick-Ass contains plenty of good, geeky fun: nerds loving comics; Nicolas Cage channeling Adam West; and an adorable 12 year-old girl slicing and dicing grown men four times her size. Why did How to Train Your Dragon seriously beat this comic book movie down to second place at the box office?
Initially, I was ready to leave (without even finishing my popcorn, mind you!) the theater when I had seen how far the film strayed from the comic; however, I decided to give it a chance and left the theater quite pleased with my final decision. Despite all the alterations, the adaptation was a good time packed with Easter eggs that filled my nerdish heart's desire. Besides, everyone went nuts over this at last year's Comic-Con, right?
Click to continue reading Kick-Ass Pleased Fans, Underperformed at Box Office
Read More | The Wrap
Weekend Reading: Addams Family, Little Fuzzy, Danger Ace and Louisa May Alcott
Posted by Tom Mason Categories: Interviews
So your flight across the Atlantic was canceled due to volcano, and you're stuck at home with just your computer. Why not click a few links and find out how a New Yorker cartoonist kept a diary of sexual conquests, how John Scalzi is rebooting Little Fuzzy, and Shary Flenniken tackles Alcott?
The Addams Family Man: Charles Addams, creator of The Addams Family which began as a series of cartoons in The New Yorker, became a 1960s TV series, then a couple of movies, and now a critically-reviled Broadway musical, is the subject of a detailed biography. Cartoonist Edward Sorel has a review that also chronicles some of the hot chicks of the era who hooked up with the cartoonist, including Veronica Lake and JFK's wife. That's right, a cartoonist got to shag Veronica Lake, and even kept a diary entry about it.
Danger Ace: Yes, you could be reading Brightest Day or Nemesis right now, but you should really try the online comic from Chad Bowers and Carl Yonder.
Click to continue reading Weekend Reading: Addams Family, Little Fuzzy, Danger Ace and Louisa May Alcott
Bleeding Edge TV 344: Apple iPad review
Posted by Andru Edwards Categories: Full Episodes, Gizmatic, Apple, Features, Handhelds, Podcasts, Videocasts, Videos
So, we've already hit you with our in-depth iPad review when the device launched, but many asked for a video review as well, so here you are! In this episode of Bleeding Edge TV, we give you our thoughts on the iPad, we show you some of the new visual touches that you'll find on the device that aren't present on the iPhone or iPod touch, and we give you a look at a bunch of the iPad apps that we've been enjoying. Even better, we also show you Apple's official iPad case, and the iPad dock as well. Take a look at the video, and see what you think. Let us know if you have any iPad questions that you'd like us to address in the comments.
iPad review: An in-depth look at the Apple tablet
Posted by Andru Edwards Categories: Apple, Features, Handhelds, Product Reviews
When Apple finally revealed the iPad to the world back at their January 27th event, it was a long time coming for many an Apple fan. After almost three years with the iPhone around, everyone figured it was time for Apple to unleash a full-sized, proper tablet. However, time and time again the rumor mill was incorrect, as Apple Event after Apple Event came and went with nary a mention of a tablet device. So when the announcement finally came, and when pre-orders finally were being taken, many prepped to grab the iPad on day one. That day came on April 3 with the launch of the Wi-Fi iPad in the United States, which you can now purchase at the Apple Online Store.
The hype has been off the charts, so let's step back for a minute and examine this thing. The iPad sits somewhere between the iPhone juggernaut and the ridiculously popular MacBook. Many have said that it is simply a "big iPod touch" and nothing more. Apple has called it "magical and revolutionary." Who's right?
We bring you the answers in our review, so hit that read link and follow along as we delve into the iPad.
Click to continue reading iPad review: An in-depth look at the Apple tablet
Hands-On with Sony's PS3 3D Games
Posted by Alex Lifschitz Categories: Features, PlayStation 3, Reviews, Sony
3D was a fad that died a well-deserved death during the 90s. Of course, the flame was kept alive by evil, evil hipsters who swapped between polarized lenses and shutter shades for a while, but only recently has it come back in a big way (thanks to new glasses, new technology, and the ability for us as a culture to forgive transgressions for existing as fads before being properly implemented.)
Sony is apparently on board with the 3D revival, and they had a bunch of games and TVs showing off their 3D technology at the GDC. Hit the jump for our hands-on impressions.
Click to continue reading Hands-On with Sony's PS3 3D Games
Review: Marvel Comics Siege #2
Posted by David Torres Categories: Reviews, Marvel Comics
Rating: *** 1/2*
Marvel Comics' Siege continues this week with issue two of the four part mini-series. The issue returns to the scene of the battle in Oklahoma where Norman Osborn, HAMMER, and the Dark Avengers are battling it out with Thor and the citizens of Asgard. All look lost as Norman Osborn stands over a defeated Thor, but he's saved by Maria Hill using a bazooka, which blows Norman out of the way.
Ares discovers quickly that he's been duped by Norman into helping lead the invasion of Asgard. Ares decides to make good on his promise and rip Norman's head off when the Sentry comes in to protect Norman. They duke it out and in a shocking big splash page moment, the Sentry rips Ares in half. I knew someone was going to die in this issue and I had a feeling it would be Ares, but in no way did I see him meeting his end this way. Very cool!
Issue one left off with an angry Steve Rogers watching the footage of the invasion of Asgard. We pick up here with Steve gathering the New Avengers, the Young Avengers, and Nick Fury and his Secret Warriors so they can all head to Oklahoma to defeat Osborn once and for all. Also with this group is Bucky the new Captain America. He hands over the shield to Steve stating he believes if they are going to do this, it has to be done right and Steve must wield the shield once more.
Click to continue reading Review: Marvel Comics Siege #2
Weekend Reading: Plastic Man, iPads, Clowns, Jack Kirby & Top Cat
Posted by Tom Mason Categories: Editorials
Is everyone ready to read Bluewater's J.D. Salinger comic book on the iPad? Now that's a game-changer I can believe in! Let's see what I've got on my desktop this week:
Apple's iPad: Apparently Apple changed the game with some kind of game changer that's supposed to be the Jesus of print that'll save newspapers from their own stupidity and ineptitude and also change the way we read comics and make a BLT just the way I like it and find me a room at Comic Con International. Tom Spurgeon at The Comics Reporter coalesces his thoughts on the matter. Me? I'm waiting for the iPad with wings.
Plastic Man: There are other places that are dropping it, but my favorite is over at John Kricfalusi's blog. He's imbedded the 10-minute Plastic Man pilot that was created by Tom Kenny (the voice of Spongebob) and Stephen DeStefano (simply one of the great modern cartoonists, and co-creator/artist of the much-beloved 'Mazing Man). Says John: "It's a real cartoon and you can tell the creators like the audience. It sure stands out from most of what's out there." Go check it out.
Click to continue reading Weekend Reading: Plastic Man, iPads, Clowns, Jack Kirby & Top Cat
Review: DC Comics Adventure Comics #6
Posted by David Torres Categories: Reviews, DC Comics
Rating ****
Wow! That's all I have to say about Geoff Johns' final issue of Adventure Comics. It's too bad Geoff is leaving this book because in the short time he was been on this title, I've really come to like the character of Superboy. There is a genuineness to the character of Superboy aka Conner Kent aka Kon-El. Johns really writes this character as a teenage boy who like all teen boys can be insecure, have girl troubles, go to school, and have trouble with their families. Now none of us have the trouble he's going through, but no matter how old you are, you can definitely relate and feel for this kid. However, I think this issue is really more about the character of Lex Luthor than it is about Conner.
I think if I met someone who were new to comic books and wanted to know something about the character of Lex Luthor, I wouldn't send them to Wikipedia to read up on who Lex Luthor is - I would hand them this issue instead. In this issue alone, Johns shows you who Luthor really is and just how evil of man he is. The story picks up where we left off in the last issue where Superboy rescued a girl named Lori and brought her back home only to be find out that she is the niece of Lex Luthor, the man who cloned him from Superman and his greatest enemy. Luthor is here to recover his property (Superboy), but the revelation of who Lori and her mother are gets in the way of things.
Click to continue reading Review: DC Comics Adventure Comics #6
In Three Paragraphs: Bayonetta
Posted by Alex Lifschitz Categories: Action, SEGA, Xbox 360
Welcome to a new quickie feature for Playfeed, in which I attempt to distill a game review into a bite-size chunk for you to feed on demurely. At E3, I was singing nothing but praises about Bayonetta, and that was primarily from a one-level demo. Demos, of course, are either used to
- Sell a product by giving you the best of the best so you salivate like Pavlov's dogs when you pass the retail copy over
- Give you the only part of a game that is not festering, abject crap.
So now the retail copy has launched, and I am left to tell you what to expect, because I am forever carrying the cross of the game reviewer. Hit the jump for Bayonetta in 3 paragraphs.
NOTE: This is the Xbox 360 version of the game. The PS3 has been known to have some nasty framerate issues.
Click to continue reading In Three Paragraphs: Bayonetta
© Gear Live Inc. – User-posted content, unless source is quoted, is licensed under a Creative Commons Public Domain License. Gear Live graphics, logos, designs, page headers, button icons, videos, articles, blogs, forums, scripts and other service names are the trademarks of Gear Live Inc.


text:
It only takes a minute to get started. Fill out our simple sign up form and login to the site.
This step is elective but will drastically multiply your chances of having members look at your profile. Write about yourself, your interests and atach your nicest photo of yourself.
Use our website's cutting-edge search to find members who suit your needs. Or just flip through listings and find people that seem interesting.
Found someone who meets your criteria? Send an email to them or just a wink and let it develop from there. With a little luck you'll be on your way to discovering the love of your life.
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Interesting. A media outlet that actually gives both sides some talking points. I'd give the reporter some congratulations for some more or less "balanced" reporting.
Course you don't need us to cheerlead what some of the interviewed people already said!
I did think it was funny how they showed an old World War 2 Luger when they referred to "cheap" guns. haha


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Eighty Years of Book Cover Design
From Wikipedia, the free encyclopedia
Eighty Years of Book Cover Design is a 2009 book by Joseph Connolly published by Faber and Faber. It illustrates the distinctive cover designs used by Faber over the years.
External links[edit]
- Review in The Guardian
- "The art of book cover design" in The Independent
- Review in The Sunday Business Post
- Review in Soitu.es -- "Un magnífico libro"
|This article about a book on the media is a stub. You can help Wikipedia by expanding it.


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He's great with his family!
Justin Bieber & Selena Gomez are one of the most talented couples ever, and while they're both on their respective tours, we think it's important to step back and determine what truly matters: who is better in concert? They both have amazing voices and exciting stage shows, but today only one of them can win. So check out our pics and videos and tell us, HollywoodLifers — what superstar would YOU rather go see in concert?
Justin singing 'Eenie Meenie' with Sean Kingston:
Justin singing 'One Less Lonely Girl' in the Philippines:
Justin singing 'Never Say Never,' 'O.M.G.' & 'Baby' at the 2011 Grammys:
Justin singing 'Somebody To Love' & 'Baby' live on The X Factor:
Selena singing 'Naturally' live on a television show:
Selena singing 'A Year Without Rain' at a soundcheck:
Selena singing 'Love You Like A Love Song':
Selena singing 'Who Says' with an acoustic setup:
Lady in lace: A smoking hot Charlize Theron showed off a ton of leg in a black lace Christian Dior mini while hosting REACH: 24 portraits by Randall Slavin, an event which benefited the Charlize Theron Africa Outreach Programme.
Taylor Swift was the epitome of a southern belle in a pretty Tracy Reese striped dress and peep-toe pumps. She looked classy and sweet while promoting her fragrance, Wonderstruck, at Mayc's in NYC.
Royal Flush: Catherine, Duchess of Cambridge stepped out at a benefit for the Child Bereavement Charity, wearing a stunning red Beulah London gown. The princess looked absolutely radiant standing alongside her husband, Prince William.
Looking just as beautiful as ever, First Lady Michelle Obama proved why she's one of thee most stylish women to ever hit the White House when she wore a purple one-shoulder gown by Korean-American desiger Doo-Ri Chung to the state dinner with the President and First Lady of South Korea.
Amber Heard was truly a knockout at the red carpet premiere of 'The Rum Diary' at the Los Angeles County Museum of Art. She looked absolutely stunning in a beautiful red Elie Saab gown and nude Christian Louboutin peep-toe pumps.
We're not sure what exactly is going on with Sienna Miller in this coral, fringe infested, sequined Matthew Williamson Spring 2012 dress, but whatever the case she looks like she's having a good time in it! Besides, it's Sienna Miller, she looks pretty in everything!
Ciara attended the REACH: 24 portraits by Randall Slavin looking very foxy to say the least. The singer opted for a soft and pretty look, sporting a rose pink ruffled blouse and leather skirt, compliments of Valentino Pre-Fall 2011 collection.
Julianne Hough went for a sexy secretary look for her New York screening of 'Footloose.' Showing of plenty of those amazing legs, the dancer/actress wore a simple black Rachel Zoe 'Cameron' tuxedo jacket dress with black pointed-toe pumps and a black clutch to match.
Anna Kendrick looked fun and flirty at the red carpet premiere for '50/50′. Wearing a McQ Resort 2012 printed mini with black pointed-toe Christian Louboutin's, looked super hot and super fierce!
Pop Princess, Selena Gomez looked super cute at the LA premiere of 'The Thing'. The actress/singer showed off her long legs in black sequined shorts, paired with a sheer white blouse over a camisole and strapy heels. So edgy yet so elegant!
Taylor Swift looked chic and sweet in Tracy Reece, Selena Gomez was full of edge in sequins, while both Kate Middleton, (in Beulah London), and Amber Heard, (in Elie Saab), were radiant in red! Check out our picks of this week's best dressed and vote for your favorite look!
Kendall and Kylie Jenner's Second Limited-Edition Line, DropTwo…
Pretty Little Liars' Lucy Hale on Aria's Dark Turn: 'A Lot of…
Cannes Film Festival Boosts Security, Cancels Fireworks After…
Focus Features Acquires Lenny Abrahamson's 'The Little Stranger'…
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Divya accused the investigation agency of harassing her father. She has been quoted as saying, "I was allowed to meet him (Maderna) only for one minute on Wednesday and I found that he was seriously unwell as the CBI officials were harassing him during interrogation."
"My father is not keeping well. He has not slept and is under acute depression. But the CBI officials were asking unnecessary questions and forcing him to accept whatever they (officials) are asking," added Divya.
However, the CBI officials overruled all allegations hurled against them and claimed that they have been taking care of Maderna and have not done anything which can hamper his health condition.
Maderna was arrested on Dec 2 and later taken to Delhi for further interrogation by the Central Bureau of Investigation (CBI). The charge-sheet also been filed against three more accused - Shahbuddin, Sohanlal and Baldev for abducting Bhanwari on the behest of Maderna and Parasram Bishnoi, the brother of Congress MLA Malkhan Singh.
Bhanwari Devi had gone missing from Bilara area, Jodhpur since Sept 1. Mahipal Maderna was later sacked by Chief Minister Ashok Gehlot from the state cabinet on Oct 16. Earlier, the CBI had found some sex CDs, allegedly showing the former Water Resource Minister in a compromising position with the 36-year-old nurse.
OneIndia News


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Sports: The First Five Millennia
€ 26,49
Lieferbar innert 2 Wochen
April 2007
BeschreibungFrom ancient Egyptian archery and medieval Japanese football to contemporary American baseball, every sport has been shaped by--and in turn has helped shape--the culture of which it is part, Yet as Allen Guttmann shows in this far-ranging study, for all their differences sports have followed a similar historical trajectory from traditional to modern forms. In Sports: The First Five Millennia, Guttmann traces this evolution across continents, cultures, and historical epochs to construct a single comprehensive narrative of the world's sports.
PortraitALLEN GUTTMANN teaches at Amherst College. Among his many books on the history of sports are From Ritual to Record: The Nature of Modern Sports (1978), Women's Sports: A History (1991), Games and Empires (1994), and The Olympics: A History of the Modern Games (2002).
Untertitel: Empfohlen ab 22 Jahre. Sprache: Englisch.
Verlag: UNIV OF MASSACHUSETTS PR
Erscheinungsdatum: April 2007
Seitenanzahl: 448 Seiten
Format: kartoniert


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Latest content added for Digital Library Collection: Texas Fashion Collectionhttps://digital.library.unt.edu/explore/collections/TXFC/browse/?start=30&fq=str_location_country:United+States&fq=untl_decade:1940-19492015-02-05T21:59:29-06:00UNT LibrariesThis is a custom feed for browsing Digital Library Collection: Texas Fashion CollectionPetticoat2015-02-05T21:59:29-06:00https://digital.library.unt.edu/ark:/67531/metadc499008/

Petticoat of maroon taffeta with two tiers of 1-3/4" black horsehair braid. One inch waistband. Center back opening closed with hook & eyes. Two curved panels at hips are gathered at the hem. Unlined, with 3-1/2" band of black stiffened net at interior hem line. Combined designer/retailer label on inside seam: "Neiman-Marcus Dallas / Traina-Norell"
Daytime Dress2014-12-04T14:16:50-06:00https://digital.library.unt.edu/ark:/67531/metadc461828/

Daytime dress in modified shirtwaist/sheath style of black jersey wool. Sleeveless with padded shoulders and wide, notched collar. Street length. Center front opening with 6 large, clear, modified emerald cut rhinestone buttons and bound buttonholes. One-inch wide self fabric tie belt attached at sides. Small patch pockets at sides, below waist. Unlined. Combined retailer/designer's label at inside left seam near hem: "Neiman-Marcus dallas / Traina-Norell"
Cocktail Ensemble2014-12-04T14:16:50-06:00https://digital.library.unt.edu/ark:/67531/metadc461812/

Cocktail ensemble of heavy black silk faille, consisting of: A) Dress. Long dress, sleeveless, narrow straps, rounded neckline, higher in front. Slightly raised waist. Left side zipper. Very full skirt gathered into waist. Designer's label at inside skirt side seam: "Traina-Norell / New York" B) Jacket. Waist length jacket with rounded collar, short, highly puffed "pumpkin" sleeves which gather into shoulders. Center front opening with four black covered buttons. Flares from waist. Designer's label at inside back collar: "Traina-Norell / New York"
Cocktail Ensemble2014-12-04T14:16:50-06:00https://digital.library.unt.edu/ark:/67531/metadc461765/

Cocktail ensemble consisting of: A) Blouse of fuchsia wool jersey with long sleeves, banded neckline with placket down the center back, and 5 self-covered circular buttons. B) Skirt of black silk brocade, Dirndl style, below knee length, with center back opening having a zipper and 2 hook&eyes on waistband. Unlined. C) Belt of matching black silk brocade with matching fuchsia wool jersey on reverse. Square self-covered buckle. 2" wide. The blouse and belt with no labels or stamps. The skirt with combined Designer/Retailer label at side seam near hem: "Neiman-Marcus Dallas / Traina-Norell"
Day Dress2014-09-26T09:40:06-05:00https://digital.library.unt.edu/ark:/67531/metadc402484/

Daytime dress of navy blue silk crepe in modified shirtwaist style. Yoked shoulders with collar. Inner neckline has 7 small mother-of-pearl buttons for additional detachable collar to drape over existing collar. Center front opening with 6 large 1-1/4" mother of pearl buttons with vertical buttonholes. Long set-in sleeves with matching button at cuff. Evidence of smocking below waist seam, but threading is missing. Street length. Unlined. Designer's label at right seam near hem: "Traina-Norell / New York" b) Contour belt of navy leather. Wider at ends with rectangular buckle covered in same. Back stamped "14".
Hat2014-09-26T09:40:06-05:00https://digital.library.unt.edu/ark:/67531/metadc402466/

Hat of dark pink/mauve velvet. The low, domed crown is covered with large overlapping "petal" shapes of velvet arranged like scales, and has a large velvet rose/flower form at front of the same velvet petals. Lined in black fabric, and with black grosgrain ribbon inner hatband. Retailer's label sewn to inner hatband: "Sanger Bros / Dallas Texas"; and origin/size label: "New York / Creation / 22"
Hat2014-09-26T09:40:06-05:00https://digital.library.unt.edu/ark:/67531/metadc402481/

Dark orange velvet hat. The shaped crown is roughly square with low peak at top center, constructed of four triangular panels, creating slight "corners" at sides. No brim. Lined in black satin. Accompanied by two hatpins, the heads covered with matching velvet. Designer's label inside: "Original / Roberta Bernays"
Cocktail Dress2014-09-26T09:40:06-05:00https://digital.library.unt.edu/ark:/67531/metadc402569/

A) Cocktail dress of blue silk satin. Sleeveless with spaghetti straps of same. Set-in waist which scallops at bottom hem and attaches to panels of full skirt. Tea length. Left side zipper with hook & eye. Skirt lined in black tulle. Combined retailer/designer label at inside left seam near hem: "Neiman-Marcus dallas / Traina-Norell" B) Belt of same with rectangular, self covered buckle. 1/2 inch wide.
Hat2014-09-26T09:40:06-05:00https://digital.library.unt.edu/ark:/67531/metadc402570/

Hat of navy blue silk faille. Small brimless hat, formed with a very low domed crown. Lined in off-white organza(?), with deep edge of the faille extending up into the underside of the crown. With two small plastic combs to help secure it to wearer's head. No labels.
Hatlet2014-09-26T09:40:06-05:00https://digital.library.unt.edu/ark:/67531/metadc402517/

Hatlet of beaded hot pink satin. Brimless, the crown of the hat is shaped somewhat like a letter "K", the back of the K fitting across the head from ear to ear, while the arms extend to the back of the head. The whole is embellished with pink and gray/green beads, and with pink heart-shaped and teardrop shaped rhinestones. Lined in white and silver brocade, with small plastic comb affixed to center front inside edge to secure to wearer's head. Designer's label at center of inside crown: "Edna Mye / Dallas" Accompanied by two hatpins with heads covered in same hot pink satin.


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Over the years of designing and sewing and pattern making there has become quite a collection of patterns! I am the kind of sewer who tries a new thing every once in a while and then switches over to something different. Thus, there is so many different kinds of patterns- from dolls, plushies, mug rugs, baby quilts, big quilts, bags, pillows, applique and more! There is no stopping to the topic!
It would be over load if I shared all the patterns so today I am sticking with plushies. Hand Stitched Plushies to be exact. These patterns are 3.00 each or you can buy the full collection for $13.00 There are 9 different stuffed animals.
Let me tell you a little something about these– some have extras– like the acorn, removable wings, shell, etc. They are also perfect for you to teach hand stitching to younger kiddos. Shapes are simple. Stitches are simple- whipstitch and running stitch is all you will need to know!
Hand Stitched Plushie Patterns~
|Squirrel with acorn
|Rocket Ship with Alien and Astronaut
|Momma and Baby Snail
|Mr. Hedgehog
|Caterpillar & Butterfly – removable jacket
Do you think the collection should be added to? What animal would you suggest?
♥ Are you a member? Click here to login & access the exclusive content.
→ Not a member yet, but interested in our online quilt guild? Click here for more info and to sign up.


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Chapter 1. Introduction to Venture Capital. What is a VC?. (1) A VC is a financial intermediary , meaning that they take the investors' capital and invest it directly in portfolio companies .
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
Chapter 1
Introduction to Venture Capital
(1) A VC is a financial intermediary, meaning that they take the investors' capital and invest it directly in portfolio companies.
(2) A VC will only invest in private companies. This means that once the investments are made, the companies cannot be immediately traded on a public exchange.
(3) A VC takes an active role in monitoring and helping the companies in his portfolio.
(4) A VC's primary goal is to maximize his financial return by exiting investments through a sale or an initial public offering (IPO).
(5) VCs invest in order to fund the internal growth of companies.
Portfolio Companies
VC Funds
Managed by
General Partners
("VCs" or "GPs")
"Exits": Sale of
to public markets (IPOs)or to other companies
Limited Partners
(Investors or "LPs")
Private Equity
Hedge Funds
What Do VCs and Buyout Firms Do?
Chapter 2
The VC Players


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How to Make Money through Blogging?
Blogging started off as a way to express thoughts and opinions. However, blogging has now become an attractive and a popular way of earning some lucrative money. There are many expert bloggers who are making some decent money by the means of blogging.
We can categorize blogging into two main categories. The first kind of blogs is those that remain dedicated to their theme and do not aspire to earn money or monetary revenues. The second type of blogs is those that are created, or started, mainly with the aim of earning revenue. The first type of blogs contains serious and personalized opinions that are posted by those who feel vehemently about that theme or topic. Slowly and gradually, such blogs become akin to discussion forums and involve multiple opinions and responses.
There is a segment of web professionals who believe in making money from everything they do on the Internet, including blogging. Here in this article we would give them vital tips, ideas and suggestions that would enable them to earn money with their blogs.
There are multiple ways that can be used to make money from blogging. The main factors that will decide how much revenues can be earned from a blog are the theme or the topic of the blog; and its niche audience. It is also important to consider that while some particular themes of blogging earn money easily, some require more effort to attract revenue.
One popular revenue earning program that is very much preferred by bloggers is "AdSense". Those who set up an AdSense account on their blogs, give permission to Google for posting related ads over the blog that are relevant to its theme or topic. The blog owner, this way earns some amount every time that ad is clicked by the users. This way plenty of bloggers have charged up the content of their blogs to earn some lucrative money via Adsense.
Another way to enable a blog for earning money is associating it to sponsored posts. Those blogs that have product or service oriented theme are able to make some money via relevant sponsored posts that are in tandem with the featured services or products. In fact, several agencies have come into the scenario that acts as the mediators. They interact with brand owners and liaison them with bloggers for their respective benefits.
The brands' owners offer lucrative compensation / remuneration to some successful bloggers for appraising their products or services thus to help them in the enhancement of their business.
Another process that helps in earning money through blogging is affiliate marketing that is making big and impressive waves in the web world. Affiliate marketing is all about getting a monetary commission every time sale gets generated for any product or service. Once the affiliated services or products are mentioned over the successfully running blog, it might get purchased. And every time the affiliated services or products are sold, the bloggers get a neat commission from that generated sale.
Another effective way that can help aspiring and enterprising bloggers to earn money through their blogs is selling of ad space. If your blog is interesting, and inviting plenty of web traffic, due to the dint of its captivating content, they may contact a company that would feature their products or services as a banner ad over that blog. This method may involve plenty of hard work in publicizing the available ad space. Then there may be lots of discussions and negotiations involved in finalizing the rates. However, if paid relevant attention, this method may prove to be effective in long terms earning.
Here some more suggestions and tips to make your blog a consistent earning member –
- Maintain the quality of your content. As evident, content and only content would take your blog to the lofty heights of popularity and would fetch lucrative chances of earning good money.
- Conduct regular and meticulous research for relevant keywords so that your blog remains in vogue and SEO friendly.
- Do not write random content for your blog. Rather, follow a strategy so that content remains the strongest facet of your blog. The content can be posted over blog in multiple formats such as video or even audio, apart from the usual text content. Find such a format that would go hand in hand with the theme and topic or your blog and would heighten its relevance even further.
- Develop the habit of updating your blog regularly so that its content does not become redundant. A regularly updated blog is always more successful in earning web traffic in comparison to those that are seldom updated. And getting a good amount of traffic will ultimately lead towards attractive revenue.
- Finally, do not join any revenue earning program without thinking. First, think about the pros and cons about that program and then finalize the deal.
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4 Comments to "How to Make Money through Blogging?"
Thanks for the nice tips. I am actually a newbee and really struggling in this field . Till now my blog earning is zero . I was think of leaving it ,but your post really inspired me. I will try again.
firstname.lastname@example.com recently posted..How To Earn More Money Through Internet
This is really an inspiring post and will try to follow. We just few days back tarted a blogging site and we are very positive towards it. Will try to remember this tips
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