bluuebunny/crossref_metadata_2025 huggingface dataset:
Two loci for Tuberous Sclerosis: one on 9q34 and one on 16p13
Authors: POVEY S. , BURLEY M. W. , ATTWOOD J. , BENHAM F. , HUNT D. , JEREMIAH S. J. , FRANKLIN D. , GILLETT G. , MALAS S. , ROBSON E. B. , TIPPETT P. , EDWARDS J. H. , KWIATKOWSKI D. J. , SUPER M. , MUELLER R. , FRYER A. , CLARKE A. , WEBB D. , OSBORNE J.
Published: September 2007

32 families informative for the segregation of Tuberous sclerosis (TSC) have been examined for genetic markers on chromosomes 9, 11, 12 and 16. In one large family there was clear evidence of linkage to markers on chromosome 16p13.3 (lodscore with D16S291 of 4·7 at θ= 0) but other families were too small to give individually convincing lodscores. Combined results for all families gave positive results with ABO/DBH on chromosome 9 (max lod 2·63) and with D16S291 on chromosome 16 (max lod 3·98) at values of theta of 0·2 in each case. Further analysis showed strong evidence for heterogeneity with approximately half the families linked to a locus TSC1 on chromosome 9 between ASS and D9S298 and half to TSC2 on chromosome 16 close to D16S291. There was no definite support for a third locus although in many families this could not be excluded. In three families the segregation pattern of TSC remains unexplained. In two of these the family apparently segregates for TSC1 but in each case a single affected individual appeared to exclude the whole of the candidate region. Preliminary analysis of clinical features did not reveal any definite differences in incidence of mental handicap between individuals in different linkage groups or with different sex of the parent of origin. The frequencies of periungual fibromas and facial angiofibromas were also similar in both linkage groups. The difficulties of detecting linkage in small families where there is locus heterogeneity are discussed. The program ZZ was found to be helpful in this respect.
Bootstrapping in human genetic linkage
Authors: CHIANO M. N. , YATES J. R. W.
Published: September 2007

Linkage analysis of discrete Mendelian traits has made a major contribution to the mapping of the human genome. However, in more complex situations, particularly Mendelian disorders showing locus heterogeneity, linkage results have sometimes been misleading. The bootstrap confidence interval provides an assessment of the goodness of fit of the data to the genetic model and the presence of heterogeneity can inflate the confidence interval indicating that the fit is poor. The loss in statistical power and the potential unreliability of linkage analyses based on small samples or subsamples of pedigree material is explored and illustrated by using simulated data and also real data on 37 families affected by the heterogeneous disorder, tuberous sclerosis.
The distribution of Q: a powerful sibship test of association
Authors: SHAH S. , GREEN J. R.
Published: September 2007

Non‐random inheritance of the two parental haplotypes among siblings affected by certain diseases has long been used to provide evidence of the presence of disease susceptibility genes. The distribution of a powerful test, called Q, based on haplotype concordance and discordance, is derived under the null hypothesis of random inheritance of haplotypes by affected siblings. The presence of a disease gene possibly linked to one of the haplotypes causes a change in the distribution of these haplotypes in the affected siblings. This distribution is found to be that of the sum of two independent variates contributed by the two parents in all parental types except one where both parents are heterozygous for the disease allele; which is dealt with separately. For comparison, the tables showing the powers of the test along with those of another well‐known test, the N‐test of haplotype concordance, are given. This is because Q is a modification of N to deal with the case when information on unaffected siblings is also available.
DNA polymorphisms of the complement C6 and C7 genes
Authors: FERNIE B. A. , WÜRZNER R. , UNSWORTH D. J. , TUXWORTH R. I. , HOBART M. J.
Published: September 2007

The linked C6 and C7 loci are rich in genetic markers, both at the protein and DNA levels. There are now seven common DNA polymorphisms distributed over about 300 kbp of chromosome 5p12‐14. We report a new TaqI RFLP for C7 and a method for typing a C7 variant (T368S) hitherto known only from cDNA clones. We have re‐investigated the published RFLPs to provide information on their frequency in North European Caucasian (predominantly British and Irish) subjects and have revised some of the published parameters, especially the sizes of polymorphic restriction fragments. Their precise locations within the genes are also reported: the three markers for C6 are in exon 3, intron 3 and adjacent to exon 17 and the four markers for C7 are in introns 15 and 13 and in exons 13 and 9. The gene frequencies of the second commonest allele of all seven markers lie in the range 0·2 to 0·37, except C6 A/B in the Japanese, where the frequencies of both common alleles are about 0·45. We have estimated the gene frequencies for the DNA polymorphisms which correlate with C7 M/N phenotype and for the C6 A/B phenotype and find them to be the same as the phenotypic estimates in Caucasians and in the Japanese respectively. The markers provide the possibility of defining 128 haplotypes, many (28) of which have been observed. Allelic associations in these genes are generally surprisingly weak.
Complement component C6 and C7 haplotypes associated with deficiencies of C6
Authors: FERNIE B. A. , ORREN A. , WÜRZNER R. , JONES A. M. , POTTER P. C. , LACHMANN P. J. , HOBART M. J.
Published: September 2007

Both complete C6‐deficiency (C6*Q0) and subtotal C6‐deficiency (C6*SD) have been described as simple recessive traits and C6*SD has been described in combination with subtotal deficiency of the C7 coded at an adjacent locus. The trace of C6 protein found in both C6*SD traits is phenotypically indistinguishable, being smaller than normal C6 and having different isoelectric properties. A defect has been found in the C6 gene which plausibly explains the C6*SD phenotype, and this defect is also common to both C6*SD traits. We present data from seven DNA markers of the C6 and C7 genes which show that although at least four haplotypes are associated with C6*Q0, most South African C6*Q0 patients carry a common defective haplotype. The most common haplotype associated with C6*Q0 has been observed only once among unaffected haplotypes of relatives. In one family, the cases of C6*SD share a complete haplotype with both cases of combined deficiency and are probably heterozygous for this condition and complete deficiency of C6. In another family, the C6*SD is on a slightly different haplotype and C7 is normally expressed. Thus, the C6 defect is not sufficient on its own to explain the C7 deficiency in the combined deficient haplotype. The haplotype associated with the combined deficiency is found not only in normal control subjects, but also in one case of complete C6 deficiency. In this case the molecular defect seen in combined or C6*SD cases is absent.
Apolipoprotein E polymorphism in Italy investigated in native plasma by a simple polyacrylamide gel isoelectric focusing technique. Comparison with frequency data of other European populations
Authors: CORBO R. M. , SCACCHI R. , MUREDDU L. , MULAS G. , ALFANO G.
Published: September 2007

A new polyacrylamide gel isoelectric focusing (PAGIEF) technique has been developed that allows rapid and reliable identification of Apolipoprotein E (APOE) phenotypes directly from plasma or serum without any prior treatment.

This method was used to determine the APOE phenotypes in samples from Central and Southern Italy, Sicily, and Sardinia. The frequencies observed for the APOE*2, APOE*3, and AP0E*4 alleles in Central and Southern Italy (Sicily included) were similar (0·066, 0·851, 0·083 and 0·056, 0·858, 0·085 respectively) though lower APOE*4 frequencies were found in the more southern regions. The Sardinian population showed APOE gene frequencies (APOE*2= 0·050, APOE*3= 0·898, AP0E*4= 0·052) to be significantly different from those of the rest of Italy owing to the low AP0E*4 frequency, the lowest among Caucasian populations. The frequencies were compared with those found in other European populations. A clear cut North‐South decreasing cline was found for APOE*4 allele frequencies and an opposite trend was found for AP0E*3 frequencies. The overall dispersion of European populations as determined by the three APOE allele frequencies was graphically represented using coordinate analysis. The tendency of the APOE*4 frequency to decline with latitude both at the Italian and at the European level was discussed with reference to similar trends observed for dietary habits (saturated fat intake).
What stabilizes the sex ratio?
Authors: JAMES W. H.
Published: September 2007

It is suggested that the human sex ratio at birth is stabilized only to a minor extent by the direct processes of natural selection. Instead the major factors stabilizing sex ratio seem to be behavioural (coital rates) and psychological (parental perceptions of adult sex ratios). It is suggested that parental hormone levels are (a) a consequence of perceived adult sex ratios, and (b) a cause of sex ratio in the next generation, thus providing the basis for a negative feedback process stabilizing the sex ratio.
Structure of the human deoxyribonuclease I (DNase I) gene: identification of the nucleotide substitution that generates its classical genetic polymorphism
Authors: YASUDA T. , KISHI K. , YANAGAWA Y. , YOSHIDA A.
Published: September 2007

The objectives of this study were to elucidate the structural organization of the gene for human deoxyribonuclease I (DNase I) and to identify the mutation site underlying its classical genetic polymorphism. In order to determine the organization of this gene, we utilized a combination of direct polymerase chain reaction (PCR)‐amplification of human genomic DNA and isolation of the overlapping clones from a cosmid human genomic library. Restriction endonuclease mapping, Southern blotting and DNA sequencing showed that the DNase I gene was approximately 3·2 kilobases long, it comprised 9 (I‐IX) exons separated by eight introns and its complete sequence was determined. The first exon contained only the non‐translated sequences of mRNA. In addition to several putative regulatory elements, TATA‐like and CAAT‐like sequences were observed in the region upstream of the translation initiation codon. These results provide information that will help to understand the expression and regulation of DNase I. The isoelectric focusing patterns of human DNase I showed that it exhibits classical genetic polymorphism (Kishi et al. 1989, 1990). A comparison of the entire translated sequences of the DNase I gene from two pairs of individuals with common DNase I phenotypes 1 and 2 revealed only one nucleotide residue difference in exon VIII, A for phenotype 1 and G for phenotype 2, thus producing Gin and Arg amino acid substitutions respectively at position 222 from the NH2‐terminus of the mature enzyme. The predicted charge changes attributable to these amino acid substitutions are entirely consistent with the isoelectric focusing profiles of these two DNase I isozymes. We conclude that this substitution is solely responsible for the classical polymorphism of DNase I protein.
Posterior probability of linkage and maximal lod score
Authors: GÉNIN E. , MARTINEZ M. , CLERGET‐DARPOUX F.
Published: September 2007

To detect linkage between a trait and a marker, Morton (1955) proposed to calculate the lod score z(θ1) at a given value θ1 of the recombination fraction. If z(θ1) reaches +3 then linkage is concluded. However, in practice, lod scores are calculated for different values of the recombination fraction between 0 and 0·5 and the test is based on the maximum value of the lod score Zmax. The impact of this deviation of the test on the probability that in fact linkage does not exist, when linkage was concluded, is documented here. This posterior probability of no linkage can be derived by using Bayes' theorem. It is less than 5% when the lod score at a predetermined θ1 is used for the test. But, for a Zmax of +3, we showed that it can reach 16·4%. Thus, considering a composite alternative hypothesis instead of a single one decreases the reliability of the test. The reliability decreases rapidly when Zmax is less than + 3. Given a Zmax of +2·5, there is a 33% chance that linkage does not exist. Moreover, the posterior probability depends not only on the value of Zmax but also jointly on the family structures and on the genetic model. For a given Zmax, the chance that linkage exists may then vary.
Characterisation of a human chromosome 1 somatic cell hybrid mapping panel and regional assignment of 6 novel STS
Authors: ROBERTS T. , MEAD R. S. , COWELL J. K.
Published: September 2007

A somatic cell hybrid mapping panel has been constructed which allows subdivision of human chromosome 1 into 8 distinct subregions. All of the hybrids carry copies of chromosome 1 with specific deletions and the position of the breakpoints has been determined relative to the location of microsatellite markers in the genetic linkage map produced by Genethon. The majority of the breakpoints can be positioned between adjacent loci on the map. The usefulness of this hybrid panel for physical mapping has been demonstrated by the regional assignment of 6 novel STS markers made from Alu‐PCR clones generated from a hybrid which contains the short arm of chromosome 1.
Variants at the secretory phospholipase A2 (PLA2G2A) locus: analysis of associations with familial adenomatous polyposis and sporadic colorectal tumours
Authors: TOMLINSON I. P. M. , BECK N. E. , NEALE K. , BODMER W. F.
Published: September 2007

The Min mouse is a model for human familial adenomatous polyposis (FAP), an autosomal dominant disease characterised by multiple adenomatous gastrointestinal polyps. The severity of the Min phenotype is modified by a locus (Mom1) on mouse chromosome 4, at a position syntenic with human chromosome 1p35‐p36. The secretory phospholipase A2 (Pla2s) gene is a candidate for this modifier locus and there is evidence that a locus on human chromosome 1p35‐p36 acts to modify the severity of human duodenal FAP. We have analysed the human secretory phospholipase A2 locus (PLA2G2A) for variants that could directly influence the FAP phenotype. We found no PLA2G2A variants predicted to result in functional variation in the phospholipase A2 protein. Two PLA2G2A polymorphisms were, however, discovered, one a ‘silent’ base change in exon 3 and another in a non‐coding region. Three other variants (possible mutations) were found in non‐coding regions. In 70 FAP patients from 20 families, no associations were found between the severity of duodenal polyposis and any PLA2G2A variant. One allele at the exon 3 polymorphic site did, however, occur more often then expected in patients with relatively severe colonie FAP. Although of borderline statistical significance, this association, if genuine, is likely to result from linkage disequilibrium between the PLA2G2A alleles studied and undetected genetic variation at a closely linked locus. The frequency of the alleles at both polymorphic sites has also been determined in the germ line of patients with sporadic colorectal adenomas and carcinomas and in random controls, but no differences were found among these groups. Our results suggest that PLA2G2A variants do not influence inherited or sporadic colonie tumours. A linked locus may be a modifier of human FAP, but does not influence the risk of colorectal tumours in the general population.
Human sequences homologous to the gene for the cochlear protein Ocp‐II do not map to currently known non‐syndromic hearing loss loci
Authors: BROWN K. A. , LEEK J. P. , LENCH N. J. , MOYNIHAN L. M. , MARKHAM A. F. , MUELLER R. F.
Published: September 2007

The abundant and almost exclusive expression of OCP‐II protein in the mammalian cochlea has fuelled speculation that mutations in the OCP2 gene may result in inherited forms of hearing impairment. We have identified several human sequences related to OCP2 and sublocalised three of these OCP2 related loci to 4q12‐p14 or 4p16.2‐pter, 5q15‐q21.3 and 7p22‐q22 by PCR. 2 YACs with sequence consistent with the chromosome 7 locus were also used for FISH analysis and hybridised to chromosome 7q11. Our data suggest that the cytogenetic localisations of these OCP2 related sequences do not correlate with the precise chromosomal positions of deafness loci so far identified.
Geographic clustering of human Y‐chromosome haplotypes
Authors: LINARES A. RUIZ , NAYAR K. , GOLDSTEIN D. B. , HEBERT J. M. , SEIELSTAD M. T. , UNDERHILL P. A. , LIN A. A. , FELDMAN M. W. , SFORZA L. L. CAVALLI
Published: September 2007

Five polymorphic markers on the Y‐chromosome (mostly microsatellites) were typed in 121 individuals from 13 populations around the world. With these markers 78 different haplotypes were detected. Haplotypes present more than once tend to be shared by individuals from the same population or continent. A reconstruction of haplotype phylogeny also indicates significant geographic structure in the data. Based on the similarity of the haplotypes, population relationships were examined and found to be largely concordant with those obtained with other markers. Even though the sample size and the number of markers are small, there is very signficant clustering of the haplotypes by continent of origin.
Ancestry and interrelationships of the Indians and their relationship with other world populations: A study based on mitochondrial DNA polymorphisms*
Authors: BARNABAS S. , APTE R. V. , SURESH C. G.
Published: September 2007

Mitochondrial DNA variation was studied in 100 Indians using the same set of six restriction enzymes used in the study of other world ethnic groups in order to compare and discern possible relationships of the Indian populations. Twenty nine mtDNA types were found including the ones from an earlier study (Semino et al. 1991) and unweighted pair‐group method (UPGMA) and maximum parsimony trees were constructed using the mtDNA types. The nucleotide diversity values were calculated using the maximum likelihood method. From a study of the shared mitochondrial DNA types and the parsimony tree (Fig. 2) we came to the conclusion that the Indian population is closer to Caucasians and has an admixture with Asians. The North Indian population appears to have a recent admixture of the Caucasian mtDNA types which is absent in the south.
Genetic fitness in Huntington's Disease and Spinocerebellar Ataxia 1: a population genetics model for CAG repeat expansions
Authors: FRONTALI M. , SABBADINI G. , NOVELLETTO A. , JODICE C. , NASO F. , SPADARO M. , GIUNTI P. , JACOPINI A. G. , VENEZIANO L. , MANTUANO E. , MALASPPNA P. , ULIZZI L. , BRICE A. , DURR A. , TERRENATO L.
Published: September 2007

An analysis of genetic fitness was performed in Huntington's Disease (HD) and Spinocerebellar Ataxia 1 (SCA1) families. Two partially overlapping samples were used: clinically defined HD and SCA1 patients from families ascertained in definite geographical areas, and molecularly typed carriers of HD and SCA1 mutations (CAG trinucleotide expansions). In both cases, a control group of normal relatives was used. HD and SCA1 patients born before 1915–20 had more children than normal controls. Carriers of HD and SCA1 mutations, all in the low/medium expansion range (37–49 and 47–54 CAG repeats respectively), had a higher number of children than controls up to more recent times (1935–1950). The reproduction of heterozygotes for large expansions could be analysed only in subjects born after 1950 and provided indirect evidence of a lower than normal number of children. The above results fit a model based on a differential fitness according to the degree of expansion. Such a model predicts that 1) up to relatively recently the frequency of alleles in the low/medium range has been maintained or even increased by the increased fitness of their carriers, as well as by new mutations, and 2) the frequency of large expansions, part of which are lost at each generation, is maintained through further expansions of alleles in the low/medium expansion range. The implications of such a model on linkage disequilibrium and the possible spread of these diseases in future generations are discussed.
Genetic analysis of Sardinia: I. Data on 12 polymorphisms in 21 linguistic domains
Authors: CAPPELLO N. , RENDINE S. , GRIFFO R. , MAMELI G. E. , SUCCA V. , VONA G. , PIAZZA A.
Published: September 2007

(1) The microgeographic structure of Sardinia, well documented from a historical and linguistic point of view, further supported by archaeological evidence, can also be dissected at the genetic level: gene frequencies show heterogeneities which are statistically significant.

(2) Dendrogram analyses performed with different methods lead to the same result: even if gene frequencies cluster linguistically defined geographic domains in agreement with historical and archaeological evidence, no phylogenetic tree can be inferred, very likely because the assumptions which allow a phylogenetic tree to be a valid model of evolution (mainly constant evolutionary rates and independence between branches) do not apply to the genetic history of Sardinia.

(3) Evidence of a qualitative association between distribution of genes and distribution of languages or dialects seems to emerge also at the microgeographic level of our analysis. More linguistic and genetic data are planned to be considered.
Genetic relationship between the Canary Islanders and their African and Spanish ancestors inferred from mitochondrial DNA sequences
Authors: PINTO F. , GONZÁLEZ A. M. , HERNáNDEZ M. , LARRUGA J. M. , CABRERA V. M.
Published: September 2007

Nucleotide sequences of the hypervariable segment I of the control region of the mtDNA were determined in 101 individuals: 54 Canary Islanders, 18 North African Berbers, 18 Spanish mainlanders and 11 sub‐Saharan Guineans. In spite of the fact that only members of the Fang tribe were analysed, nucleotide diversity in Guineans (θ× 100 = 2·33)is one of the highest found in African populations.

Estimates of genetic contribution to the Canarians from their putative parental populations based on mtDNA (43·25 ± 1·38% Berbers, 35·54 ± 0·55% Spanish, 21·21 ± 1·92% Guineans) showed an important North African substrate. These mtDNA results, when compared with data based on nuclear markers, point to a strong male‐female asymmetry, 75% of the Spanish nuclear contribution was due to males and practically all the Berber and Guinean was due to females. These results are in agreement with the way that the Canary Islands were conquered.

Pairwise difference distributions in Guineans and Berbers are compatible with the model of populations in expansion. Departures from a Poisson distribution for the Canarians and Spanish can be explained by admixture and the way of sampling respectively.
Pairwise analysis of radiation hybrid mapping data
Authors: JONES H. B.
Published: September 2007

Two point lod scores are widely used in pedigree analysis as they provide a fast and efficient method of establishing linkage. Groups of markers that lie in close proximity to one another can be formed by admitting any locus that is linked to at least one existing member of the group with lod score greater than some predetermined value. It seems natural to extend this technique to Radiation Hybrid Mapping both for constructing groups of tightly linked loci that may then be analysed using more powerful statistics and as a method of ordering in its own right.

A general extension of two point analysis is derived and the problems associated with radiation hybrid data are discussed. In particular, the additional parameters representing the probabilities of different fragments being retained (which have no parallel in classical linkage analysis) lead to a range of estimators of the breakage probability, θ, which have equal and maximal likelihood. Ways of circumventing this problem are discussed along with the potential errors they introduce.

Importantly the ambiguity in estimation of θ is not carried through to the lod score as this depends only on the maximum value of the likelihood and not on the particular value of θ at which it occurs. Thus even though two point analysis fails to provide robust estimates of either breakage probabilities or the distance between loci, it represents a simple and effective method of constructing linkage groups that may be analysed with more powerful statistical methods. This is particularly important given the large number of microsatellites, ESTs and candidate genes currently being typed on radiation hybrids.
Apolipoprotein E genotype ε4/ε2 in the STANISLAS Cohort Study ‐ Dominance of the ε2 allele ?
Authors: BOHNET K. , REGIS‐BAILLY A. , VINCENT‐VIRY M. , SCHLENCK A. , GUEGUEN R. , SIEST G. , VISVIKIS S.
Published: September 2007

Apolipoprotein (apo) E has been discussed as a marker for cardiovascular risk, but information about lipid traits in healthy individuals having one of the rare apoE genotypes (ε4/ε2, ε2/ε2 or ε4/ε4) is scarce. Our work was designed to answer the following questions: 1. Are the allelic effects of ε2 and ε4 on lipid traits additive or dominant? 2. If there is additivity, do the allelic effects of ε2 and ε4 have the same magnitude? 3. Are the allelic effects neutralised in ε4/ε2 individuals who are under the influence of both rare alleles?

Allelic effects on apoB and apoE serum levels were codominant. Allelic models are thus not adequate to study the influence of apoE polymorphism on these traits. Allelic effects were additive for total cholesterol, LDL‐C, HDL‐C and apoAI, with ε2 having a greater impact than ε4. Serum levels differed significantly between ε4/ε2 and ε3/ε3 individuals only for apoE (p < 0ε001) and for apoB (p < 0ε05).
Ethanol Effects on Striatal Neuron Activity
Authors: Schoener Eugene P.
Published: September 2007

Cellular effects of ethanol were investigated in the rat neostriatum with local perfusion and extracellular, single unfl recording techniques. Neuronal activity was modulated specifically as a function of ethanol concentration over a wide test range. At extremely low doses (10‐9 and 10‐8 M), the neuronal responses to drug perfusion were exclusively excitatory. However, at the highest doses examined (10‐5 and 10‐4 M), the results were reversed. In the midrange, a number of apparently ineffective tests were obtained, along with bimodal (excitation followed by depression) responses. The unequivocal responsiveness to ethanol at very low concentrations raises the possibility of a physiological role for the endogenous substance.
The Relationship between Ethanol‐Induced Locomotor Activation and Narcosis in Long‐Sleep and Short‐Sleep Mice
Authors: Dudek Bruce C. , Abbott Michael E.
Published: September 2007

Mice selectively bred for marked response to hypnotic doses of ethanol (long‐sleep, LS) respond to subhypnotic doses of ethanol (ETOH) with less stimulation of locomotor activity than their short‐sleep (SS) counterparts. This assessment was made by comparing ETOH‐lnduced alterations in locomotor activity to an untreated baseline within individual subjects, and to a saline‐treated control group. A correlational study, using the same method in F, generation hybrids of the LS and SS Hnes, produced a negative correlation (‐.36) between locomotor stimulant effects of a subhypnotic dose of ETOH and length of loss of the righting reflex following a hypnotic dose. This relationship also appeared in a factor analysis of baseline locomotor activity, ETOH‐stimulated activity, and depressant response variables. The genetic selection for LS and SS mice appears to have differentiated tod that influence more than one type of behavioral response to ETOH, an example of pleiotropism.
Effects of Chronic Ethanol Ingestion on Male and Female Rat Liver Glycogen Phosphorylase Phosphatase
Authors: Winston Gary W. , Reitz Ronald C.
Published: September 2007

The effects of chronic ethanol ingestion on the interconversion of the active to the inactive form of glycogen phosphorylase by phosphorylase phosphatase was studied. Male and female rats also were compared. Chronic ethanol feeding decreased phosphorylase a and total phosphorylase activity in male rats. In females, no change was observed in phosphorylase a, whereas total phosphorylase activity was increased 73%. This was found to correlate with the relative activities of phosphorylase phosphatase. The data show differences between the two sexes with regard to the AMP inhibition of phosphorylase phosphatase and the caffeine stimulation of the phosphatase. Ethanol markedly enhanced the AMP inhibition of the phosphatase in males but had no effect in females. Further studies in females showed that ethanol completely obliterated the well documented stimulation of the phosphatase by caffeine; however, it did not alter the caffeine effect in males. These data suggest possible alterations in the tertiary structure of phosphorylase a.
An Improved Method for Collecting Breath for the Assay of Acetaldehyde
Authors: Phillips Michael , Hensley Preston , Baiter Richard A. , Cohan Stanley L.
Published: September 2007

An improved method is described for the collection of breath for the subsequent assay of acetaldehyde and other volatile components. Breath is collected in a Pyrex gas‐collecting tube sealed at both ends with Teflon taps. Prior to collection or assay of the samples, this tube is heated to 72oC; breath is sampled for assay by piercing a rubber septum on a sideport with the needle of a similarly heated gas‐tight syringe, and injected into a gas chromatograph (GC). The advantages of this system are: (1) Avoidance of the artefacts encountered in the assay of acetaldehyde in the blood; (2) suitability for sample collection at a site remote from the GC laboratory; (3) avoidance of sample loss by leakage, contamination, or partitioning into water condensed from breath; and (4) compatibility with a “nondedicated” GC lacking any special gas‐collecting circuitry. A typical study of a normal human volunteer is described, demonstrating the rise and fall of the concentration of acetaldehyde and ethanol in the breath following the ingestion of an oral dose of ethanol.
A Single Dose of Ethanol Suppresses Rat Embryo Development in Vivo
Authors: Pennington Sam N. , Taylor William A. , Cowan Diane H. , Kalmus Gerhard W.
Published: September 2007

In humans and animal models, maternal ethanol consumption during pregnancy results in a variety of fetal defects collectively termed the fetal alcohol syndrome (FAS). Limited follow‐up studies suggest that FAS children fail to achieve normal physical or mental development despite significant postnatal intervention. Although the complete FAS appears to result only when chronic, excessive alcohol consumption occurs throughout pregnancy, several investigators have suggested that ethanol consumption at intermediate levels may induce components of FAS. The defect most consistently observed in neonates exposed to ethanol is growth retardation. Even those children whose mothers consume limited amounts of ethanol during pregnancy have a significant incidence of fetal growth deficiency. We now report that a single dose of ethanol administered to female Holtzman rats within 8 hr after mating results in a dose‐dependent retardation of cell division in the fertilized ova. The growth retardation is sustained up to 42 hr after the dose and the embryos of young mothers are especially sensitive to ethanol. Animals with high blood alcohol levels (<150 mg/100 ml) show a significant increase in abnormal embryo morphology. These data suggest that maternal consumption of a single dose of ethanol near the time of conception retards embryonic growth and may be detrimental to the developing organism. Further, young female rats receiving a high dose of ethanol had significantly lower uterine weights and a lower number of corpora lutea per ovary, suggesting that a single dose of ethanol has a detrimental effect on maternal reproductive ability.
Arylsulfatase A Variants in Patients with Alcoholism
Authors: Hulyalkar Atul R. , Nora Rena , Manowitz Paul
Published: September 2007

Leukocytes from 200 mentally ill patients and 100 normal controls were analyzed for eiectrophoretic variants of arylsulfatase A. Four different variant forms were found in 15 subjects. There is a relatively high occurrence of the arylsulfatase A variants in patients with alcoholism. Twenty‐one per cent (12/56) of patients with alcoholism have a variant enzyme. Only one of the 100 normal controls has a variant enzyme. (This single subject was considered normal by the criteria of the study, namely, a self‐report of no current medical problem or psychiatric history. However, upon further testing, it was found that this subject has neurological and neuropsychological deficits.)

The hypothesis is presented that chronic alcohol intake and abnormal arylsulfatase A act in concert to elevate sulfatide levels which results in abnormalities of brain function. If this hypothesis is correct, persons in whom abnormal arylsulfatase A is expressed may be at risk to the neuropathological effects of alcohol.
A Prospective Study of Young Men at High Risk for Alcoholism: Neuropsychological Assessment
Authors: Drejer Kirsten , Theikjaard Alice , Teasdale Thomas W. , Schulsinger Fini , Goodwin Donald W.
Published: September 2007

As part of the first phase of a prospective longitudinal study on alcoholism, a battery of neuropsychological tests covering general intelligence, memory, attention, field‐dependence, categorizing ability, and organizing and planning, was administered to 204 18–19‐year‐old males. Of these, 134 subjects are the sons of alcoholic fathers and are thereby themselves at high risk for becoming alcoholic. The remaining 70 subjects comprise a control group matched for several social and familial variables. The high risk group was found to have a relatively poorer vocabulary and to perform worse on tests of categorizing ability and organization and planning. All of these findings concur with other results from this study. The anticipated future alcoholics from among the high risk subjects may prove to be those who differed most on these tests.
Symptomatology in Alcoholics at Various Stages of Abstinence
Authors: Soto Clinton B. De , O'Donnell William E. , Allred Linda J. , Lopes Cheryl E.
Published: September 2007

Evaluation of 312 abstinent alcoholic* (163 man and 149 women) with the Symptom Check‐List 90 revealed high levels of symptomatology for subjects in the early months of abstinence. Symptomatology decreased progressively with prolonged abstinence, approximating normal levels for subjects abstinent 10 years or more. The levels were similar for men and women. At aH stages, for both men and women, symptomatology was highest on the depression, interpersonal sensitivity, and obsessive‐compulsive symptom dimensions, with guilt a particularly persistent symptom. It is suggested that the findings depict a long‐term process of recovery from active alcoholism and are consistent with the concept of a protracted withdrawal syndrome, an intermediate (partially reversible) brain syndrome, and general psychosocial dysfunction and demoralization consequent to active alcoholism.
Measurement of Protein Synthetic Activity by Determination of Peptidyl[3H]puromycin Formation in Liver Slices after Ethanol Administration
Authors: Donohue Terrence M. , Sorrell James H. , Sorrell Michael F. , Tuma Dean J.
Published: September 2007

We investigated the utility of [3H]puromycin as an alternate and adjunct precursor to amino acids for measuring protein synthetic activity in rat liver slices. Slices were incubated in the presence of either [3H]puromycin or radiolabeled valine to compare the incorporation of these isotopic precursors into nascent hepatocellular proteins. Compared to liver slices from controls, comparable decreases in the incorporation of both [3H]puromycin and labeled valine were observed in experiments using slices from fasted rats and in slices preincubated with 25 mw ethanol. Radiolabeling of nascent polypeptides with either [3H]puromycin or labeled valine in liver slices from rats fed a liquid diet containing ethanol was also decreased compared to slices from pair‐fed control and chow‐fed animals. Our results demonstrated the validity of using [3H]puromycin to detect changes in protein synthetic activity under these conditions. The potential advantage of using [3H]puromycin for in vivo studies is discussed.
Genetic Variants of Enzymes of Alcohol and Aldehyde Metabolism
Authors: Holmes Roger S.
Published: September 2007

The distribution of genetic variants (or gene markers) for alcohol dehydrogenase, aldehyde dehydrogenase, aldehyde oxidase, and aldehyde reductase isozymes has been examined among 12 inbred strains of mice. Electrophoretic variants are described for the major liver and stomach alcohol dehydrogenase isozymes (ADH‐A2 and C2); liver, kidney, and stomach aldehyde dehydrogenase isozymes (AHD‐1; AHD‐2; AHD‐4); a liver‐specific aldehyde reductase (AHR‐A2); and a liver aldehyde oxidase isozyme (AOX‐2). Genetically determined activity variants were observed for a testis‐specific aldehyde dehydrogenase (AHD‐6); liver and kidney aldehyde reductase isozymes (AHR‐3 and AHR‐4); and the major aver AOX isozyme (AOX‐1). These variants may serve as useful gene markers in alcohol research involving animal model studies with inbred strains in mice.
Identification of glucocorticoid‐regulated genes that control cell proliferation during murine respiratory development
Authors: Bird Anthony D. , Tan Kheng H. , Olsson P. Fredrik , Zieba Malgorzata , Flecknoe Sharon J. , Liddicoat Douglas R. , Mollard Richard , Hooper Stuart B. , Cole Timothy J.
Published: September 2007

Glucocorticoids play a vital role in fetal respiratory development and act via the intracellular glucocorticoid receptor (GR) to regulate transcription of key target genes. GR‐null mice die at birth due to respiratory dysfunction associated with hypercellularity and atelectasis. To identify events associated with this lung phenotype we examined perinatal cellular proliferation rates and apoptotic indices. We demonstrate that compared to wild‐type controls, day 18.5 postcoitum (p.c.) GR‐null mouse lungs display significantly increased cell proliferation rates (1.8‐fold P < 0.05) and no change in apoptosis. To examine underlying molecular mechanisms, we compared whole genome expression profiles by microarray analysis at 18.5 days p.c. Pathways relating to cell proliferation, division and cell cycle were significantly down‐regulated while pathways relating to carbohydrate metabolism, kinase activities and immune responses were significantly up‐regulated. Differential levels of gene expression were verified by quantitative‐RT‐PCR and/or Northern analysis. Key regulators of proliferation differentially expressed in the lung of 18.5 p.c. GR‐null lungs included p21CIP1 (decreased 2.9‐fold, P < 0.05), a negative regulator of the cell cycle, and Mdk (increased 6.0‐fold, P < 0.05), a lung growth factor. The more under‐expressed genes in 18.5 p.c. GR‐null lungs included Chi3l3 (11‐fold, P < 0.05), a macrophage inflammatory response gene and Ela1 (9.4‐fold, P < 0.05), an extracellular matrix remodeling enzyme. Our results demonstrate that GR affects the transcriptional status of a number of regulatory processes during late fetal lung development. Amongst these processes is cell proliferation whereby GR induces expression of cell cycle repressors while suppressing induction of a well characterized cell cycle stimulator.
Effects of heat and cold stress on central vascular pressure relationships during orthostasis in humans
Authors: Wilson T. E. , Tollund C. , Yoshiga C. C. , Dawson E. A. , Nissen P. , Secher N. H. , Crandall C. G.
Published: September 2007

Central venous pressure (CVP) provides information regarding right ventricular filling pressure, but is often assumed to reflect left ventricular filling pressure. It remains unknown whether this assumption is correct during thermal challenges when CVP is elevated during skin‐surface cooling or reduced during whole‐body heating. The primary objective of this study was to test the hypothesis that changes in CVP reflect those in left ventricular filling pressure, as expressed by pulmonary capillary wedge pressure (PCWP), during lower‐body negative pressure (LBNP) while subjects are normothermic, during skin‐surface cooling, and during whole‐body heating. In 11 subjects, skin‐surface cooling was imposed by perfusing 16°C water through a water‐perfused suit worn by each subject, while heat stress was imposed by perfusing 47°C water through the suit sufficient to increase internal temperature 0.95 ± 0.07°C (mean ±s.e.m.). While normothermic, CVP was 6.3 ± 0.2 mmHg and PCWP was 9.5 ± 0.3 mmHg. These pressures increased during skin‐surface cooling (7.8 ± 0.2 and 11.1 ± 0.3 mmHg, respectively; P < 0.05) and decreased during whole‐body heating (3.6 ± 0.1 and 6.5 ± 0.2 mmHg, respectively; P < 0.05). The decrease in CVP with LBNP was correlated with the reduction in PCWP during normothermia (r= 0.93), skin‐surface cooling (r= 0.91), and whole‐body heating (r= 0.81; all P < 0.001). When these three thermal conditions were combined, the overall r value between CVP and PCWP was 0.92. These data suggest that in the assessed thermal conditions, CVP appropriately tracks left ventricular filling pressure as indexed by PCWP. The correlation between these values provides confidence for the use of CVP in studies assessing ventricular preload during thermal and combined thermal and orthostatic perturbations.
ON THE MONOTONICITY OF FLUCTUATION SPECTRA FOR THREE-STATE MARKOV PROCESSES
Authors: CHEN YONG
Published: September 2007

Explicit formulae for correlation functions and fluctuation spectra of the irreducible three-state Markov processes are presented. The necessary and sufficient conditions of existing nonmonotonic fluctuation spectra on [0, +∞) with respect to real functions are given, which reveals that the nonequilibrium flux must be strong enough to produce a peak in the fluctuation spectrum and the monotonicity of fluctuation spectra is related to the time scales of Markov processes.
EFFECTS OF CIRCUIT ELEMENTS AND HARMONIC OSCILLATION POWER ON FUNDAMENTAL PM NOISE POWER OF FET OSCILLATOR
Authors: ABO-ELNOR OSSAMA , ABOU-ELNOUR ALI
Published: September 2007

Analytical expressions for the PM noise in FET oscillators are derived in terms of the FET equivalent circuit elements and the passive circuitry. Efficient methods to reduce the PM noise in fundamental and in harmonic modes are suggested and implemented. The effects of the different FET equivalent circuit parameters on large-signal, small-signal, and noise behavior of FET oscillators are investigated. Finally, the effects of harmonic signal on the output noise power and on the phase noise at both fundamental and harmonic frequencies are determined.
PERFORMANCE LIMITS OF SIMULATION MODELS FOR NOISE CHARACTERIZATION OF MM WAVE DEVICES
Authors: ABOU-ELNOUR ALI
Published: September 2007

Based on Boltzmann transport equation, the drift-diffusion, hydrodynamic, and Monte-Carlo physical simulators are accurately developed. For each simulator, the model equations are self-consistently solved with Poisson equation, and with Schrödinger equation when quantization effects take place, in one and two-dimensions to characterize the operation and optimize the structure of mm-wave devices. The effects of the device dimensions, biasing conditions, and operating frequencies on the accuracy of results obtained from the simulators are thoroughly investigated. Based on physical understanding of the models, the simulation results are analyzed to fully determine the limits at which a certain device simulator can be accurately and efficiently used to characterize the noise behavior of mm-wave devices.
ANALYSIS OF FLUCTUATIONS IN WIND DEPENDENT SHALLOW WATER AMBIENT NOISE SPECTRUM
Authors: RAMJI S. , LATHA G. , RAMAKRISHANAN S.
Published: September 2007

In this work, the fluctuations in the spectrum level of shallow water ambient noise is analyzed for 3 different sea states. The shallow water ambient noise data were collected of Bay of Bengal using an omni directional hydrophone and a portable data acquisition system.100 sets of data were collected and organized according to the three different sea states using Beaufort scale. Fluctuations in noise spectrum level at different sea states were studied by dividing the spectral bandwidth of 12 kHz into low, mid and high frequency bands. Mean noise spectrum level for each sea state was calculated and the result shows the noise spectrum level increases with the sea state. Further it was found that the noise level was higher in lower frequency band and decreases in the higher frequency band. Also the correlation between the noise level and sea state was higher in the low frequency band and tend to decrease in the mid frequency band and there was no correlation in the higher frequency bands. The higher noise levels were associated with lower frequencies of the bandwidth whereas it is less in higher frequencies. The fluctuations were found to be higher in the lower frequency band than the mid and higher frequency band. In this paper the data collection, data processing and noise spectrum analysis are presented in detail. As the fluctuations in power spectrum level of the ambient noise is one of the primary factor which decides the signal to noise ratio of most of the acoustic instruments, these results seems to be significant.
CLOCK TIMING JITTER ANALYSIS AND COMPENSATION FOR BISTATIC SYNTHETIC APERTURE RADAR SYSTEMS
Authors: WANG WENQIN
Published: September 2007

Bistatic synthetic aperture radar (SAR) operates with distinct transmit and receive antennas that are mounted on separate platforms. Such a spatial separation has several operational advantages, which will increase the capability, reliability and flexibility of future SAR missions. However, this configuration results that there is no cancelation of low frequency oscillator noise as in the monostatic cases. As a consequence, high accurate time synchronization or clock timing jitter compensation must be provided. Literature search reveals little time synchronization work for bistatic SAR has been reported. As such, the use of a new range alignment algorithm to quantify and compensate clock timing jitter is proposed. The impact of clock timing jitter on bistatic SAR is analyzed, and the performance of the proposed algorithm is evaluated. Simulation results show that successful clock timing jitter compensation for bistatic SAR is achieved by using the proposed algorithm.
Application of Data Mining Techniques for Proper Design of Knowledge Repository
Authors: Anis M. Z. , Mukherjee A. , Roy B. K.
Published: September 2007

This paper reports a basic assessment of the usage of a knowledge repository called "XYZ Knowledge Repository", maintained by a company PQR for its client XYZ. Subsequently, a data mining method for finding sequential patterns in the web usage of the users was used. This captures the level of association between the web pages through two parameters, support and confidence. Depending upon the values of these two parameters, concepts of strong association, weak association and no association are realised. In case of strong association we recommended the pages be grouped together; while in the case of weak association, a link may be provided.
Engineering aspects of periglacial features in Britain
Authors: Higginbottom Ian Elliot , Fookes Peter George
Published: September 2007

The paper deals with ground effects resulting from snow and frost outside the margins of the ice sheets during the Quaternary ice ages. This environment, termed 'periglacial', is defined and the main classes of periglacial and related phenomena found fossil in Britain are classified and described, under the headings of superficial structural disturbances, mass movements, and periglacial deposits and their properties. The geotechnical aspects of each are described and illustrated with case histories. The paper concludes by reviewing, with examples, site investigation techniques appropriate to British periglacial problems.