P53 mutations in human adrenocortical neoplasms

The mechanisms of tumorigenesis of adrenocortical neoplasms have not been elucidated as yet. However, loss of heterozygosity at chromosomal locus 17p has been consistently observed in adrenocortical cancer. p53 is a recessive tumor suppressor gene located on chromosome 17p. Mutations in the p53 gene play an important role in the tumorigenesis of diverse types of human neoplasms including breast and colon cancers. More than 90% of all mutations discovered in such tumors have been detected in 4 hot spot areas that lie between exons 5 and 8. In contrast to wild-type p53, mutant p53 accumulates intracellularly and can be easily detected by immunohistochemistry. We therefore investigated the frequency of p53 mutations in human adrenocortical neoplasms using molecular biology and immunohistochemistry techniques. Five patients with adrenocortical adenomas (5 female; ages 39-72 yr), 11 patients with adrenocortical carcinomas (8 female, 3 male; ages 15- 50 yr), and two adrenocortical tumor cell lines were studied. After DNA extraction from frozen tumor tissue or paraffin-embedded material, exons 5 through 8 were amplified using the polymerase chain reaction and directly sequenced by the dideoxy termination method. Immunohistochemistry was performed on paraffin-embedded tumor specimens obtained during adrenalectomy using a monoclonal antibody reacting with both wild-type and mutant p53. Prevalence of mutations was adenomas, 0/5, carcinomas, 3/11, and adrenocortical cell lines, 2/2. Single point mutations were detected in 3 cases (exons 5, 6, and 7, respectively), and rearrangements of exon 7/8 and 8 were found in 2 cases. Immunohistochemistry detected strong nuclear and/or cytoplasmic p53 immunoreactivity in all adrenocortical carcinomas with point mutations of the p53 gene but not in adenomas and carcinomas with the wild-type sequence or with deletion/rearrangement of the p53 gene. We conclude that p53 plays a role in the tumorigenesis of adrenocortical carcinomas but is of less importance to benign adenomas

The grinch who stole wisdom

Dr. Seuss is wise. How the Grinch Stole Christmas (Seuss, 1957) could serve as a parable for our time. It can also be seen as a roadmap for the development of contemplative wisdom. The abiding popularity of How the Grinch Stole Christmas additionally suggests that contemplative wisdom is more readily available to ordinary people, even children, than is normally thought. This matters because from the point of view of contemplatives in any of the world's philosophies or religions, people are confused about wisdom. The content of the nascent field of wisdom studies, they might say, is largely not wisdom at all but rather what it's like to live in a particular kind of prison cell, a well appointed cell perhaps, but not a place that makes possible either personal satisfaction or deep problem solving. I believe that what the contemplative traditions have to say is important; they offer a different orientation to what personal wisdom is, how to develop it, and how to use it in the world than is presently contained in either our popular culture or our sciences. In order to illustrate this I will examine, in some detail, one contemplative path within Buddhism. Buddhism is particularly useful in this respect because its practices are nontheistic and thus avoid many of the cultural landmines associated with the contemplative aspects of Western religions

Wavelet Packet Analysis of Amino Acid Chain Sequences in the Proteins of Mesophile and Thermophile Bacteria

In this project, proteins from mesophile and thermophile bacteria with similar functions are compared. Initially it is assumed that the differences between these two bacteria are substantial to be recognized in the amino acid sequences of their proteins. These differences would then lead to the creation of a statistical measure, which would allow the classification of a protein to its corresponding bacteria. By assigning hydrophobicity values from three well-known scales, a discrete numeric signal is produced for each protein, which is analyzed using wavelet packets. The result of this method indicates that the overall hydrophobic tendencies of these two bacteria’s proteins are very similar. As such, no identifying characteristic is readily apparent to classify a protein as belonging to specific bacteria

Neurodiversity and Disability: An Analysis of Social Movement Framing in Dialog Between Parents and Autistic Self-Advocates

Neurodiversity, the idea that people experience the world differently based on their neurological attributes, is emerging as an understanding of autism and other disabilities as well as the basis of a social movement. This is an idea not without controversy. Using disability studies as the conceptual anchor, this dissertation looks closely at an online dialog between two key stakeholders in the neurodiversity debate: parents of children with autism and autistic adult self-advocates. Using frame analysis as an analytic tool, it explores social movement frames and framing practices utilized in the dialog. Both the particular dimensions of autism/disability representations that emerged and the practices used by dialog participants to construct them have implications for educators, which are discussed

WAVELET ANALYSIS OF SHORT GLOBULAR HOMOLOGOUS PROTEINS IN MESOPHILE AND THERMOPHILE PROKARYOTES

This study looked to identify features related to thermal stability and function in the amino acid chains of short globular proteins from mesophile and thermophile species, within the constraint that the protein fold to perform a speci_c function. To do so 540 homologous pairs of proteins were studied. The amino acid chains were con-verted to hydrophobicity signals by assigning a hydropathy score to each residue in the polypeptide. The hydrophobicity signals were passed through a wavelet packet transform and the resulting spectra analyzed. Bootstrapping was used to gener-ate a control data set to determine if the true ordering of amino acids codes for a non-random uctuation in hydropathy along the length of the polypeptide. A method to relate the spectral characteristics to the function of a protein making use of gene ontologies was developed as a proof of concept. As a group, mesophile and thermophile proteins have very similar total power. However, on a protein-to-protein basis the thermophile contains a greater total power in 489 of the 540 pairs (90.56%). The hydrophobicity scale used in this study is strongly correlated with Gibbs free energy. The total power of a protein is also strongly correlated to the Gibbs free energy, so that the thermophile protein contains a greater free energy than its corresponding mesophile partner. It has been noted in the experimental literature that thermophile proteins are stabilized by increasing their Gibbs free en-ergy. The statistical measures skew and kurtosis were adapted so that a spectrum of skew and kurtosis values were generated for each protein. These values indicate that the uctuation in hydropathy is non random and position dependent. Thermophile proteins have larger power at frequency bands 21 through 31 (average intervals of 100 to 77 amino acids), and 44 to 56 (on average 46 to 19 amino acids), which may contribute to their having greater total power in 90.56% of the pairs. Increases to the uctuation in hydropathy within certain lengths throughout the total amino acid chain of a protein may be a means of raising the temperature at which a protein denatures

Little groups of irreps of O(3), SO(3), and the infinite axial subgroups

Little groups are enumerated for the irreps and their components in any basis of O(3) and SO(3) up to rank 9, and for all irreps of C$_{\infty}$, C$_{\infty h}$, C$_{\infty v}$, D$_{\infty}$ and D$_{\infty h}$. The results are obtained by a new chain criterion, which distinguishes massive (rotationally inequivalent) irrep basis functions and allows for multiple branching paths, and are verified by inspection. These results are relevant to the determination of the symmetry of a material from its linear and nonlinear optical properties and to the choices of order parameters for symmetry breaking in liquid crystals.Comment: 28 pages and 3 figure

Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC).

<p>Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC)</p

Experimental investigation of the initial regime in fingering electrodeposition: dispersion relation and velocity measurements

Recently a fingering morphology, resembling the hydrodynamic Saffman-Taylor instability, was identified in the quasi-two-dimensional electrodeposition of copper. We present here measurements of the dispersion relation of the growing front. The instability is accompanied by gravity-driven convection rolls at the electrodes, which are examined using particle image velocimetry. While at the anode the theory presented by Chazalviel et al. describes the convection roll, the flow field at the cathode is more complicated because of the growing deposit. In particular, the analysis of the orientation of the velocity vectors reveals some lag of the development of the convection roll compared to the finger envelope.Comment: 11 pages, 15 figures, REVTEX 4; reference adde

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia