On the distribution of the time required to remove white balls from an URN

Balls are removed one-at-a-time at equal time intervals from an urn initially containingw ₀ white balls and a large number b of black balls and each black or white ball is immediately replaced by a black ball. The distribution of the number of white balls remaining aftert iterations (under certain limiting operations) is taken from the literature. The problem is to use this result to find the time required to remove a fixed number of white ballsw ₁ from the urn. We then find the mean and variance of this distribution and also look at the special case whenw ₁ =w ₀.     

Experimental allergic encephalomyelitis mediated by cloned T cells specific for a synthetic peptide of myelin proteolipid protein. Fine specificity and T cell receptor V beta usage.

Proteolipid protein (PLP) is the major protein of central nervous system myelin. SJL (H-2s) mice immunized with a synthetic peptide corresponding to PLP residues 139-151 develop acute EAE. In this study, 6 IAs-restricted, CD4+, TCR alpha beta-bearing T cell clones were derived from SJL/J mice after immunization with this synthetic peptide. The clones responded in in vitro proliferative assays to the whole PLP molecule and to PLP peptide 139-151, but not to irrelevant Ag. They also responded to truncated and overlapping forms of the peptide but five distinct reactivity patterns were observed using these peptides. A panel of anti-TCR V beta mAb and TCR V beta-specific cDNA probes were used to determine the TCR V beta usage of the clones. Five clones were found to use four different V beta (V beta 2, V beta 6, V beta 10, or V beta 17a), whereas the V beta on the sixth clone could not be identified. Five of the clones induced EAE of varying severity upon adoptive transfer into naive syngeneic mice or mice pretreated with irradiation and pertussis and one clone was nonencephalitogenic. The Ag-specific proliferative response of all but the nonencephalitogenic clone could be blocked by an anti-CD4 mAb. Thus, the clones showed differences in their fine specifity, TCR V beta usage, sensitivity to antibody blocking, and encephalitogenic potency. These data demonstrate that the T cell response to the encephalitogenic PLP peptide 139-151 is heterogeneous.     

Malignant transformation and tumor promoter treatment increase levels of a transcript for a secreted glycoprotein.

The major excreted protein of transformed mouse fibroblasts, a secreted, mannose 6-phosphate-containing glycoprotein, is induced in nontransformed cells by a variety of transforming agents, by phorbol esters, and by platelet-derived growth factor. We report here the molecular cloning of the cDNA encoding this protein and demonstrate that its induction is a consequence of enhanced mRNA levels for major excreted protein in both tetradecanoyl phorbol acetate-treated 3T3 cells and 3T3 cells transformed by a variety of retroviruses or retroviral oncogenes. These results indicate that tumor promoters and retroviral transformation might share a common pathway of action in cultured cells and that major excreted protein is a molecular marker for the growth response of cells to these agents.     

Isolation and partial characterization of the entire human pro alpha 1(II) collagen gene.

Using a cDNA probe specific for the bovine Type II procollagen, a series of overlapping genomic clones containing 45 kb of contiguous human DNA have been isolated. Sequencing of a 54 bp exon, number 29, provided direct evidence that the recombinant clones bear human Type II collagen sequences. Localization of the 5' and 3' ends of the gene indicated that the human Type II collagen gene is 30 kb in size. This value is significantly higher than that of the homologous avian gene. The segregation of a polymorphic restriction site in informative families conclusively demonstrated that the Type II gene is found in a single copy in the human haploid genome. Finally, sequencing of a triple helical domain exon has confirmed that a rearrangement leading to the fusion of two exons occurred in the pro alpha 1(I) gene, following the divergence of the fibrillar collagens.     

Analysis of cDNA and genomic clones coding for the pro alpha 1 chain of calf type II collagen.

A bovine cDNA library constructed from fetal cartilage RNA was screened with a pro alpha 1(II) collagen specific chicken cDNA. A recombinant clone (Bc 7), with an insert of 1 kb, was identified and shown to contain sequences exhibiting 85% homology with the chicken pro alpha 1(II) collagen C-propeptide. Interspecies comparison strongly suggested that one potential glycosylation site present in the avian C-propeptide is not utilized, since this site is absent in the bovine chain. In addition, two overlapping genomic clones (Pal 3 and Pal 4) were isolated and partially characterized. These clones span 23 kb of DNA and contain approximately 17 kb of the pro alpha 1(II) calf gene. Sequencing of exon 1 has determined the length of the 3' untranslated region and the exact location of the polyadenylation attachment site.     

Localization of an Ataxia-Telangiectasia Gene to an −500-kb Interval on Chromosome 11q23.1: Linkage Analysis of 176 Families by an International Consortium

We describe a 20-point linkage analysis map of chromosome 11q22-23 that is based on genotyping 249 families (59 CEPH and 190 A-T). Monte Carlo linkage analyses of 176 ataxia-telangiectasia (A-T) families localizes the major A-T locus to the region between S1819(A4) and S1818(A2). When seven nonlinking families were excluded from subsequent analyses, a 2-lod support interval of ~500 kb was identified between S1819(A4) and S1294. No recombinants were observed between A-T and markers S384, B7, S535, or S1294. Only 17 of the international consortium families have been assigned to complementation groups. The available evidence favors either a cluster of A-T genes on chromosome 11 or intragenic defects in a single gene.     

Heterogeneity of amelogenin mRNA in the bovine tooth germ

The amelogenins are a complex mixture of hydrophobic proteins that are the major organic component of developing enamel. To study the molecular mechanisms underlying the heterogeneity of the amelogenins we isolated cDNA clones encoding these proteins. The clones were definitively identified by hybrid-selected translation experiments and by comparison of the DNA sequence with the protein-derived amino acid sequence. Southern hybridization of bovine genomic DNA indicated that amelogenin is a single copy gene. However, Northern hybridization experiments distinctly showed two major species of mRNA, each of which were sufficiently large enough to encode the highest known molecular weight species of amelogenin proteins. Furthermore, immunoprecipitation of hybrid-selected translation products using isolated amelogenin cDNA showed multiple, translated protein products. These data are supportive of a differential mRNA processing mechanism involved in generating a heterogeneous family of amelogenin matrix proteins from a single gene.